[{"template":2,"link_id":"SSR00001","review_date":null,"drug_name":"Galexos (simeprevir)","safety_issue":"Assessing the Potential Risk of Severe Liver Problems","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1,"overview":"Health Canada carried out a safety review after Japan published a risk communication on severe liver problems and related death with the use of simeprevir. In patients with liver damage due to advanced chronic hepatitis C, increased levels of bilirubin in the blood can be a sign that the liver is not functioning properly. The use of simeprevir can further increase bilirubin levels in the blood; this risk is already included in the prescribing information.","use_canada":2,"findings":3,"conclusion":4,"additional":"
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - GALEXOS (simeprevir) - Assessing the Potential Risk of Severe Liver Problems","created_date":"2016-01-27","modified_date":null,"key_message_list":[{"field_id":1,"order_no":1,"bullet":"Galexos (simeprevir) is a drug used to treat chronic hepatitis C."},{"field_id":1,"order_no":2,"bullet":"A safety review was carried out by Health Canada after Japan published a risk communication on severe liver problems and related death with simeprevir use."},{"field_id":1,"order_no":3,"bullet":"The prescribing information for Galexos has been updated with warnings about the risk of severe liver problems and related death. It also reminds healthcare professionals to frequently monitor patients for liver problems when using this drug."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":2,"order_no":1,"bullet":"Simeprevir has been marketed in Canada under the brand name of Galexos since 2013."},{"field_id":2,"order_no":2,"bullet":"Simeprevir is a drug used for the treatment of chronic hepatitis C. It is taken as an oral tablet for 12 weeks in combination with other medicinal products such as peginterferon alfa and ribavirin or with sofosbuvir."},{"field_id":2,"order_no":3,"bullet":"Recently, the number of prescriptions in Canada for simeprevir has gone from 1700 prescriptions between July and September 2014, to 16 prescriptions between July and September 2015."}],"finding_list":[{"field_id":3,"order_no":1,"bullet":"At the time of the review, Health Canada had received 11 Canadian reports of severe liver problems, including 2 deaths, suspected of being linked with simeprevir. Upon review of these cases, no conclusions could be made regarding what role, if any, the drug may have played, due to limited information from these cases."},{"field_id":3,"order_no":2,"bullet":"In Japan, 8 cases of severe blood bilirubin levels and 3 deaths had been reported in association with simeprevir. Ethnic differences in susceptibility to liver problems exist, therefore the information from these cases needs to be interpreted with caution when considering the risk of simeprevir for other populations."},{"field_id":3,"order_no":3,"bullet":"Information was also received from the manufacturer about cases of severely abnormal bilirubin levels suspected of being linked with simeprevir. In some of these cases, the contribution of simeprivir to the side effect could not be ruled out."}],"conclusion_list":[{"field_id":4,"order_no":1,"bullet":"Based on all the information reviewed, Health Canada concluded that the prescribing information should be updated to reflect the level of evidence related to the risk of severe liver problems."},{"field_id":4,"order_no":2,"bullet":"The manufacturer of Galexos (simeprevir) has updated the prescribing information to:A Health Canada safety review was carried out as a follow-up assessment on the potential risk of retinal detachment with the use of oral fluoroquinolones. Health Canada's previous safety review examined the risk of retinal detachment with oral fluoroquinolones and had concluded that limited evidence was available to support a link at that time. Since Health Canada's initial review, many other studies have been conducted regarding the potential link between the use of oral fluoroquinolones and retinal detachment triggering this follow-up safety review.
Retinal detachment is a painless separation of the retina from the layer of support tissue and blood vessels at the back of the eye that provides the retina with oxygen and nourishment. Symptoms related to retinal detachment depend on the location and extent of the detachment, and may include the sudden appearance of debris in the field of vision (look like spots, hairs or strings and seem to float across one's vision -- floaters), the perception of flashes of light in the affected eye, the sensation that a shadow or curtain has come down over a portion of the visual field, or even sudden and complete loss of vision in the affected eye. Retinal detachment is considered a medical emergency and requires immediate attention to prevent permanent visual damage.
","use_canada":6,"findings":7,"conclusion":8,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":226,"footnotes":9,"title":"Summary Safety Review - Oral FLUOROQUINOLONES - Assessing the Potential Risk of Retinal Detachment","created_date":"2016-01-08","modified_date":null,"key_message_list":[{"field_id":5,"order_no":1,"bullet":"Oral fluoroquinolones are antibiotics used to treat bacterial infections."},{"field_id":5,"order_no":2,"bullet":"Health Canada's follow-up safety review on the link between the use of oral fluoroquinolones and retinal detachment was carried out to assess new evidence since the completion of Heath Canada's initial review on this issue in 2013."},{"field_id":5,"order_no":3,"bullet":"Health Canada's follow-up safety review concluded that a potential link between the use of oral fluoroquinolones and retinal detachment could not be ruled out at this time. Given that retinal detachment is a medical emergency, the recommendations of the Health Canada review were that the current labeling for oral fluoroquinolones be revised to highlight the urgency to consult a health care professional if patients experienced vision problems during or following oral fluoroquinolone's administration."}],"footnotes_list":[{"field_id":9,"order_no":1,"bullet":"Gatifloxacin was one of the oral fluoroquinolones identified in Etminan et al study and therefore was considered along with the other marketed FQs. However, oral gatifloxacin is no longer marketed in Canada (since June 29, 2006)."},{"field_id":9,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":9,"order_no":3,"bullet":"International reports were retrieved from the Eudravigilance database."},{"field_id":9,"order_no":4,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":226,"order_no":1,"bullet":"Etminan M, Forooghian F, Brophy JM, Bird ST and Maberley D, (2012), Oral fluoroquinolones and the risk of retinal detachment, JAMA 307:1414-1419."},{"field_id":226,"order_no":2,"bullet":"Chui CS, Man KK, Cheng CL, et al, (2014), An investigation of the potential association between retinal detachment and oral fluoroquinolones: a self-controlled case series study, J Antimicrob Chemother 69:2563-2567."},{"field_id":226,"order_no":3,"bullet":"Eftekhari K, Ghodasra DH, Haynes K, et al, (2014), Risk of retinal tear or detachment with oral fluoroquinolone use: a cohort study, Pharmacoepidemiol Drug Saf 23:745-752."},{"field_id":226,"order_no":4,"bullet":"Fife D, Zhu V, Voss E, Levy-Clarke G, Ryan P, (2014), Exposure to oral fluoroquinolones and the risk of retinal detachment: retrospective analyses of two large healthcare databases, Drug Saf 37:171-82."},{"field_id":226,"order_no":5,"bullet":"Kapoor KG, Hodge DO, St Sauver JL, Barkmeier AJ, (2014), Oral fluoroquinolones and the incidence of rhegmatogenous retinal detachment and symptomatic retinal breaks: A population-based study, Ophthalmology S0161-6420."},{"field_id":226,"order_no":6,"bullet":"Kuo SC, Chen YT, Lee YT, et al, (2014), Association between recent use of fluoroquinolones and rhegmatogenous retinal detachment: a population-based cohort study, Clin Infect Dis 58:197-203."},{"field_id":226,"order_no":7,"bullet":"Pasternak B, Svanström H, Melbye M, Hviid A, et al, (2013), Association between oral fluoroquinolone use and retinal detachment, JAMA 310:2184-2190."}],"use_canada_list":[{"field_id":6,"order_no":1,"bullet":"Oral fluoroquinolones are medicines widely used to treat bacterial infections (antibiotics), especially infections of the respiratory and the urogenital system (genitourinary tract)."},{"field_id":6,"order_no":2,"bullet":"There are five different oral fluoroquinolone drugs marketed in Canada by different companies: ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin a."}],"finding_list":[{"field_id":7,"order_no":1,"bullet":"At the time of the second Health Canada review, there were 3 reports of retinal detachment in Canada b that were linked to the use of oral fluoroquinolones. A causal relationship between the use of fluoroquinolones and the development of retinal detachment could not be established from these Canadian reports."},{"field_id":7,"order_no":2,"bullet":"At the time of the second Health Canada review, 22 reports c of retinal detachment linked with oral fluoroquinolones were reported internationally."},{"field_id":7,"order_no":3,"bullet":"Two publications (of four observational studies) found a modest link between the occurrence of retinal detachment and the use of fluoroquinolones (8 to 365 days after completion of treatment)."}],"conclusion_list":[{"field_id":8,"order_no":1,"bullet":"Health Canada's follow-up safety review concluded that a link between the use of fluoroquinolones and the occurrence of retinal detachment cannot be ruled out at the present time."},{"field_id":8,"order_no":2,"bullet":"Given that retinal detachment is a medical emergency, the recommendations of the review were that the current labeling for oral fluoroquinolones be revised to highlight the urgency to see a health care professional if patients experienced vision problems during or following oral fluoroquinolone administration."}]},{"template":2,"link_id":"SSR00003","review_date":null,"drug_name":"Avonex (interferon beta-1a)","safety_issue":"Assessing the Potential Risk of Clots in Small Blood Vessels (thrombotic microangiopathy)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":10,"overview":"Health Canada carried out a safety review to look into the potential risk of thrombotic microangiopathy with the use of Avonex. This issue was found during the review of new safety information given by the manufacturer.","use_canada":11,"findings":12,"conclusion":13,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - AVONEX (interferon beta-1a) - Assessing the Potential Risk of Kidney Damage (nephrotic syndrome)","created_date":"2015-12-23","modified_date":null,"key_message_list":[{"field_id":10,"order_no":1,"bullet":"Avonex is used to treat some forms of multiple sclerosis, a disease of the central nervous system."},{"field_id":10,"order_no":2,"bullet":"A safety review was triggered when Health Canada identified a possible risk of clots in small blood vessels (thrombotic microangiopathy) with Avonex treatment, during a routine review of information received from the manufacturer."},{"field_id":10,"order_no":3,"bullet":"Health Canada considers that after reviewing the totality of evidence available at this time, there is a potential risk of thrombotic microangiopathy with Avonex. Health Canada has therefore asked the manufacturer to update the Canadian prescribing information for Avonex to include this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":11,"order_no":1,"bullet":"Avonex is used to treat some forms of multiple sclerosis, to reduce damage to the central nervous system, and to slow down the worsening of the disease. Avonex is given by injection into the muscle at a dose of 30 micrograms once a week."},{"field_id":11,"order_no":2,"bullet":"Avonex has been marketed in Canada since December 2005. It is available by prescription only."}],"finding_list":[{"field_id":12,"order_no":1,"bullet":"Thrombotic microangiopathy is a group of serious life-threatening conditions involving the formation of clots in the small blood vessels. These clots can cause damage to organs and body systems by blocking proper blood flow."},{"field_id":12,"order_no":2,"bullet":"There are two forms of interferon beta sold in Canada to treat multiple sclerosis: Type 1a (Avonex and Rebif) and Type 1b (Betaseron and Extavia)."},{"field_id":12,"order_no":3,"bullet":"The manufacturer provided a report from the Avonex Global Safety Database, which had cases of thrombotic microangiopathy that were possibly caused by Avonex. The review of these cases was limited by many factors like other pre-existing diseases, other medications taken, and a possible confusion of thrombotic microangiopathy with other causes of organ damage. Nonetheless, a link between Avonex and the development of thrombotic microangiopathy could not be ruled out."},{"field_id":12,"order_no":4,"bullet":"At the time of the review, information regarding the risk of thrombotic microangiopathy was already included in the Canadian prescribing information for Rebif, but not for Avonex."}],"conclusion_list":[{"field_id":13,"order_no":1,"bullet":"Health Canada's safety review considers that there is a potential risk of thrombotic microangiopathy with Avonex, given the current evidence and reported cases."},{"field_id":13,"order_no":2,"bullet":"In addition, thrombotic microangiopathy has been linked to other interferon beta drugs and currently appears in the Canadian prescribing information for Rebif."},{"field_id":13,"order_no":3,"bullet":"Since there may be a possible link between Avonex and thrombotic microangiopathy, Health Canada requested that the manufacturer update the Canadian prescribing information to include this risk."},{"field_id":13,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving Avonex, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00004","review_date":null,"drug_name":"Finasteride","safety_issue":"Assessing the Potential Risk of Suicidal Thoughts and Behaviour (Suicidality)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":14,"overview":"This safety review was carried out as a follow-up assessment on the potential risk of suicidality with the use of finasteride. The issue was first identified through Health Canada's routine monitoring activities but there was not enough information to draw a conclusion about the potential risk.","use_canada":15,"findings":16,"conclusion":17,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Finasteride - Assessing the Potential Risk of Suicidal Thoughts and Behaviour (Suicidality)","created_date":"2015-12-17","modified_date":null,"key_message_list":[{"field_id":14,"order_no":1,"bullet":"Finasteride is a drug that is used to treat and control benign prostatic hyperplasia (non-cancerous enlargement of the prostate gland). At a lower dose, it is used to treat male pattern hair loss."},{"field_id":14,"order_no":2,"bullet":"The issue of suicidal thoughts and behaviours was first assessed in 2012 further to reports of depression and suicidality potentially linked with finasteride use. That safety review could not determine a link between finasteride and suicidality due to the limited information available. At that time, it was decided that Health Canada would carry out a re-assessment of the potential safety issue after 2 years."},{"field_id":14,"order_no":3,"bullet":"In this follow-up review, Health Canada examined new data, however evidence available for assessment was still considered to be too limited to determine whether or not a link between finasteride use and suicidality exists. Health Canada therefore continues to monitor this issue and encourages healthcare professionals to report any side-effects suspected of being linked to finasteride use."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":15,"order_no":1,"bullet":"Finasteride (5 mg) is used to treat and control benign prostatic hyperplasia. It can also be used at a lower dose (1 mg) to treat male pattern hair loss."},{"field_id":15,"order_no":2,"bullet":"There are currently 2 brand name finasteride products sold in Canada: PROSCAR (5 mg) and PROPECIA (1 mg). There are also some generic finasteride products sold in Canada."},{"field_id":15,"order_no":3,"bullet":"Proscar has been sold in Canada since 1992, and Propecia since 1998."}],"finding_list":[{"field_id":16,"order_no":1,"bullet":"From 1992 to the time of this review, Health Canada received 11 reports of suicidality that were suspected of being linked to the use of finasteride in Canada. Of these, 6 cases describe factors which appeared to be related to finasteride use, but 4 cases could not be assessed due to the limited information provided. One case was considered as unlikely related to finasteride use. Following the completion of this safety review, Health Canada received an additional report of suicidality with finasteride use. This case was assessed and it was determined that it may have been related to finasteride use."},{"field_id":16,"order_no":2,"bullet":"The World Health Organization's database contained 170 reports of suicidal thoughts and 56 reports of completed suicide with the use of finasteride at the time of the review. However, the data was not robust enough to definitively conclude on the strength of the link between finasteride and suicidality."},{"field_id":16,"order_no":3,"bullet":"Some literature reports have described a potential link between finasteride and suicidality, including studies describing side-effects such as depression, even when the patient stopped using finasteride. However, these few studies involving a small number of patients had limitations that could not confirm nor exclude a link between finasteride and suicidality."}],"conclusion_list":[{"field_id":17,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence was too limited to determine whether or not a link between finasteride and suicidality exists."},{"field_id":17,"order_no":2,"bullet":"Currently, the prescribing information for finasteride lists depression as a side-effect. Although it does not specifically list the risk of suicidality, it does advise patients to talk to their doctor or pharmacist promptly if they experience any known or unexpected symptoms."},{"field_id":17,"order_no":3,"bullet":"Health Canada will publish a Health Product InfoWatch article on finasteride and suicidality to inform Canadians about this safety review, and to encourage healthcare professionals to report any side-effects suspected of being linked with finasteride."},{"field_id":17,"order_no":4,"bullet":"Health Canada continues to monitor side effect information involving finasteride, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00005","review_date":null,"drug_name":"MELATONIN (N-acetyl-5-methoxytryptamine)","safety_issue":"Neurological side effects","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":18,"overview":"After becoming aware of international reports about neurological side effects, such as anxiety, panic reaction, visual hallucinations and seizures, possibly associated with melatonin use in children and adolescents ranging from newborn to 18 years old (pediatric population), Health Canada did a review of this safety issue in this age group. The review took into consideration the information on this patient population from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.","use_canada":19,"findings":20,"conclusion":21,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":22,"title":"Summary Safety Review - MELATONIN (N-acetyl-5-methoxytryptamine) - Review of the Safety of Melatonin in Children and Adolescents","created_date":"2015-12-11","modified_date":null,"key_message_list":[{"field_id":18,"order_no":1,"bullet":"Melatonin is used to help adults, adolescents and children with sleep problems as an over-the-counter natural health product in Canada."},{"field_id":18,"order_no":2,"bullet":"After becoming aware of international reports about serious neurological side effects possibly associated with the use of melatonin in children and adolescents, Health Canada did a review of this safety issue in this age group."},{"field_id":18,"order_no":3,"bullet":"At the time of this review, there was conflicting data of neurological side effects in children and adolescents. As a result of this review, Health Canada will request further safety information from the market authorization holder and will continue to monitor for information about this safety issue. Parents and caregivers are encouraged to consult a healthcare professional before giving melatonin to children and adolescents."}],"footnotes_list":[{"field_id":22,"order_no":1,"bullet":"More information about melatonin can be accessed through Health Canada's Listing of Monographs
"},{"field_id":22,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database
"}],"reference_list":[],"use_canada_list":[{"field_id":19,"order_no":1,"bullet":"Melatonin was first licensed in Canada in 2005 as a natural health product ingredient.a"},{"field_id":19,"order_no":2,"bullet":"In Canada, this naturally occurring hormone is used in adults to help re-set the body's sleep-wake cycle and to reduce the time to fall asleep. It is also used to improve the quality of sleep in adults who experience sleep problems because of shift-work or jet lag."},{"field_id":19,"order_no":3,"bullet":"Melatonin should not be used for more than four weeks without consulting a healthcare professional."},{"field_id":19,"order_no":4,"bullet":"Health Canada has licensed over 500 natural health products that include melatonin as an ingredient for use by adults. They are available over-the-counter as capsules, tablets placed under the tongue (sublingual), liquids and gums. Since 2011, 2 multi-ingredient natural health products containing melatonin have been licensed for use in Canada in children 12 years and older. At the time of this review, Health Canada has not authorised any melatonin-containing products for use in children 11 years and younger."}],"finding_list":[{"field_id":20,"order_no":1,"bullet":"At the time of the review, the Canada Vigilance Programb had received 18 Canadian reports of side effects associated with the use of natural health products containing melatonin in the pediatric population. The most frequently reported side effect was sleepiness. Although 5 cases were considered serious because they included symptoms of anxiety, panic reaction, visual hallucinations, and seizures, there was limited data to link these cases of side effects to the use of melatonin."},{"field_id":20,"order_no":2,"bullet":"A review of international data from the World Health Organization's database brought up 163 cases of side effects, of which 8 were from Canada, associated with the use of melatonin in the pediatric population. The most common side effects reported were general fatigue, aggression, abnormal dreams, and headache. Seventy-one cases were considered serious, but they could not be assessed further because the information contained in the reports was incomplete."},{"field_id":20,"order_no":3,"bullet":"The review found limited clinical data suggesting that melatonin shows benefits for treating sleep disorders when used for less than 4 months in those having disorders of brain function that affect emotion, learning, and memory (attention deficit hyperactivity disorder and autism spectrum disorders). The short term impact on the psychological development and the long term risk on growth in the pediatric population is still uncertain."}],"conclusion_list":[{"field_id":21,"order_no":1,"bullet":"As a result of the limited data about neurological side effects associated with the use of melatonin in the pediatric population, Health Canada is encouraging parents and caregivers to consult a healthcare professional before giving any natural health products containing melatonin to this age group, especially if they have serious medical conditions like hormonal, brain, heart, liver, or kidney diseases. Furthermore, healthcare professionals should be consulted if children are taking blood pressure, sedative, psychiatric, or immunosuppressive medications as there may be a risk of harmful interactions."},{"field_id":21,"order_no":2,"bullet":"Health Canada will continue to evaluate this safety issue by asking for information from the market authorization holder of the 2 melatonin natural health products used in children 12 years and older. In addition, Health Canada will proactively monitor for safety information related to the use of melatonin in the general pediatric population."}]},{"template":2,"link_id":"SSR00006","review_date":null,"drug_name":"Over-the-counter topical acne products containing either BENZOYL PEROXIDE or SALICYLIC ACID","safety_issue":"Assessing the potential risk of serious allergic reactions (serious hypersensitivity reactions)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":23,"overview":"A safety review was carried out to evaluate a potential link between serious allergic reactions (hypersensitivity reactions) and over-the-counter acne products containing either benzoyl peroxide or salicylic acid applied on skin (topical). As part of its routine health product monitoring, Health Canada carried out a safety review after the United States Food and Drug Administration identified that a risk of rare but serious hypersensitivity reactions may be linked to the use of these products (including some life-threatening allergic reactions known as anaphylactic reactions). Similar acne products are available in Canada. Symptoms of a serious hypersensitivity reaction, including anaphylaxis, may include itchy hives with swelling of the face, eyes, lips, mouth or throat; difficulty of breathing; throat tightness or hoarseness; and fainting. An anaphylactic reaction is a potentially life-threatening type of serious hypersensitivity reaction.","use_canada":24,"findings":25,"conclusion":26,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":27,"title":"Summary Safety Review - Over-the-counter topical acne products containing either BENZOYL PEROXIDE or SALICYLIC ACID - Assessing the potential risk of serious allergic reactions (serious hypersensitivity reactions)","created_date":"2015-12-10","modified_date":null,"key_message_list":[{"field_id":23,"order_no":1,"bullet":"Benzoyl peroxide and salicylic acid are medicinal ingredients in over-the-counter products that are applied to the skin (topical) to help treat acne."},{"field_id":23,"order_no":2,"bullet":"As part of its routine health product monitoring, Health Canada carried out a safety review after the United States Food and Drug Administration identified a risk of serious allergic reactions (serious hypersensitivity reactions), linked to the use of over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid."},{"field_id":23,"order_no":3,"bullet":"Health Canada's safety review concluded that there is evidence supporting a link between the use of over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid and serious hypersensitivity reactions, including anaphylactic reactions (which require emergency medical services). Health Canada will update the directions of use and warning sections of the Health Canada Acne Therapy Monograph for topical over-the-counter acne products containing either benzoyl peroxide or salicylic acid, and will issue an Information Update about these changes."}],"footnotes_list":[{"field_id":27,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":24,"order_no":1,"bullet":"Benzoyl peroxide and salicylic acid are medicinal ingredients applied to the skin to help treat acne."},{"field_id":24,"order_no":2,"bullet":"There are over 400 over-the-counter topical acne products marketed in Canada that contain either benzoyl peroxide or salicylic acid."},{"field_id":24,"order_no":3,"bullet":"These products generally contain 2.5% to 5% benzoyl peroxide or 0.5 to 2% salicylic acid, and are available in various forms, including soaps, creams, gels, and lotions."},{"field_id":24,"order_no":4,"bullet":"Irritation and dryness of the skin are known side effects linked with the use of either benzoyl peroxide or salicylic acid. Signs of irritation include redness, burning, peeling and mild swelling. These known side effects are already described on the package information of over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid that are available for sale in Canada."}],"finding_list":[{"field_id":25,"order_no":1,"bullet":"At the time of the review, Health Canadaa received 10 Canadian cases of serious hypersensitivity reactions linked to the use of over-the-counter benzoyl peroxide products. Of these cases, 5 were anaphylactic reactions. For over-the-counter salicylic acid products, 16 Canadian cases of serious hypersensitivity reactions were received. Of these cases, 4 were anaphylactic reactions. In 2 of the anaphylactic cases, both benzoyl peroxide and salicylic acid products were used together."},{"field_id":25,"order_no":2,"bullet":"131 reports of serious hypersensitivity reactions linked to the use of either benzoyl peroxide or salicylic acid products were identified by the United States Food and Drug Administration. Fifty of these reports involved anaphylactic reactions."}],"conclusion_list":[{"field_id":26,"order_no":1,"bullet":"Health Canada's safety review concluded that there is evidence supporting a link between the use of over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid and serious hypersensitivity reactions."},{"field_id":26,"order_no":2,"bullet":"As a result of the safety review findings, Health Canada will update the directions of use and warnings sections of the Health Canada Acne Therapy Monograph for over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid."},{"field_id":26,"order_no":3,"bullet":"Although localized skin irritation appears to be the most common side effect reported, some users of these products may develop more serious and life-threatening hypersensitivity reactions, including anaphylaxis."},{"field_id":26,"order_no":4,"bullet":"An Information Update will be published to inform healthcare professionals and consumers about the risk of serious hypersensitivity reactions and about changes to the product information of over-the-counter topical acne products containing either benzoyl peroxide or salicylic acid. The Information Update will also provide the following consumer advice in the event of an anaphylactic reaction: if you develop severe itching and hives, with swelling of the face, eyes, lips, mouth or throat; difficulty breathing, throat tightness or hoarseness; and /or fainting, please seek emergency medical services."}]},{"template":2,"link_id":"SSR00007","review_date":null,"drug_name":"Codeine prescription products indicated for cough","safety_issue":"Serious Breathing Problems in Children and Adolescents","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":28,"overview":"In 2013, Health Canada carried out a safety review to assess the risk of serious breathing problems, including death, which concluded that codeine is not recommended in children less than 12 years of age for any indication, including pain or cough. In 2015, the European Medicines Agency contraindicated the use of codeine for cough in children less than 12 years of age. Due to emerging new evidence, a new safety review was initiated in Canada to further assess the risk of serious breathing problems in children and adolescents treated with codeine prescription products for cough and to determine if additional restrictions were warranted to manage this risk.
Codeine is converted to morphine in the liver. Some people have genetic variations of liver enzymes which cause codeine to be converted to morphine faster and more completely than in other people. These people with genetic differences (ultra-rapid metabolizers) are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine can result in breathing difficulty, which may cause death. This information is included in the Canadian prescribing information for codeine products.
","use_canada":29,"findings":30,"conclusion":31,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - CODEINE PRESCRIPTION PRODUCTS Indicated for Cough - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents","created_date":"2015-12-09","modified_date":null,"key_message_list":[{"field_id":28,"order_no":1,"bullet":"Codeine-containing products are opiate drugs used to treat pain and to reduce coughing."},{"field_id":28,"order_no":2,"bullet":"In 2013, Health Canada carried out a safety review to assess the risk of serious breathing problems and death, which concluded that codeine-containing products are not recommended in children less than 12 years of age regardless of the indication."},{"field_id":28,"order_no":3,"bullet":"Following a new safety review in 2015 to further assess the risk of serious breathing problems in children and adolescents, Health Canada maintains its recommendation that codeine prescription products not be recommended in children less than 12 years of age. No modifications were recommended to the Canadian prescribing information."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":29,"order_no":1,"bullet":"Codeine-containing products are medicines approved for use in adults and children above 12 years of age to treat pain and reduce cough. Caution is advised regarding the use of codeine in patients with breathing conditions, including children."},{"field_id":29,"order_no":2,"bullet":"Codeine is available in Canada alone or in combination with acetaminophen or aspirin, and in some cough and cold medications. Some of these products are only available by prescription, while others are non-prescription."},{"field_id":29,"order_no":3,"bullet":"In recent years, the number of prescriptions in Canada for codeine products for pediatric use has decreased by more than 70% in children less than 12 years of age and by more than 30% in patients 13-18 years of age."}],"finding_list":[{"field_id":30,"order_no":1,"bullet":"At the time of the current review, no Canadian cases of breathing problems with codeine for the treatment of cough in children and adolescents were reported to Health Canada."},{"field_id":30,"order_no":2,"bullet":"Since Health Canada's 2013 review, one new international case was identified in the literature, which involved serious breathing problems with the use of codeine to reduce coughing. The case resulted in the death of a six year old patient. However, a direct role for codeine could not be established due to medication error and pre-existing breathing problems."},{"field_id":30,"order_no":3,"bullet":"Taken together, Health Canada's reviews identified a total of 16 published case reports in relation to serious side effects involving breathing problems with the use of codeine to reduce coughing. The ages of the children ranged from 17 days to 6 years. Out of these 16 cases, death was reported in 5 cases. In 13 of these 16 cases, there was a pre-existing respiratory disease described in addition to cough, such as respiratory tract infections."}],"conclusion_list":[{"field_id":31,"order_no":1,"bullet":"Health Canada maintains its warnings and recommendations to manage the risk of serious breathing problems and death, that codeine prescription products not be recommended in children less than 12 years of age. No modifications were recommended to the Canadian prescribing information."},{"field_id":31,"order_no":2,"bullet":"Health Canada will continue to monitor side effect information involving codeine, including non-prescription codeine products, as it does for all health products on the Canadian market, and will take additional actions, if warranted."}]},{"template":2,"link_id":"SSR00008","review_date":null,"drug_name":"Gardasil (Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine)","safety_issue":"Assessing General Safety with a Focus on Autoimmune and Cardiovascular Diseases","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":32,"overview":"The safety of all vaccines, including Gardasil, is under continuous monitoring by Health Canada and the Public Health Agency of Canada. The safety of Gardasil was reassessed as part of this monitoring and when cases of side effects after vaccination with Gardasil were reported in early 2015. These side effects included diseases where the body's own defence system attacks itself (autoimmune diseases), such as rheumatoid arthritis and multiple sclerosis, and diseases affecting the heart and blood vessels (cardiovascular diseases), such as low blood pressure and blood clots. Sources of information for this safety review included data from studies conducted before Gardasil came on the market, and side effects reported both to the Canada Vigilance program of Health Canada and the Canadian Adverse Event Following Immunization Surveillance System of the Public Health Agency of Canada by the provinces and territories. Also included was the most recent safety report received from the manufacturer, in addition to published studies on the safety of Gardasil after it was used in many countries.","use_canada":33,"findings":34,"conclusion":35,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":258,"title":"Summary Safety Review - GARDASIL (Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) - Assessing General Safety with a Focus on Autoimmune and Cardiovascular Diseases","created_date":"2015-12-09","modified_date":null,"key_message_list":[{"field_id":32,"order_no":1,"bullet":"Gardasil is a vaccine used to protect against four types of Human Papilloma Virus (HPV types 6, 11, 16, and 18), which cause 70% of cervical cancers, 90% of genital warts, and 80-90% of anal cancers."},{"field_id":32,"order_no":2,"bullet":"The safety of all vaccines, including Gardasil, is under continuous monitoring by Health Canada and the Public Health Agency of Canada. The safety of Gardasil was reassessed as part of this monitoring and when cases of side effects after vaccination with Gardasil were reported in early 2015. The side effects included diseases where the body's own defence system attacks itself (autoimmune diseases), such as rheumatoid arthritis and multiple sclerosis, and diseases affecting the heart and blood vessels (cardiovascular diseases), such as low blood pressure and blood clots."},{"field_id":32,"order_no":3,"bullet":"After reviewing all available information on its safety, Health Canada did not find any new safety issues for Gardasil. The benefits of Gardasil continue to be greater than the risks and existing prescribing information was considered appropriate. Health Canada will continue to monitor the safety of Gardasil."}],"footnotes_list":[{"field_id":258,"order_no":1,"bullet":"An update on the recommended Human Papillomavirus (HPV) vaccine immunization schedule is available on the Public Health Agency of Canada's Web site."}],"reference_list":[],"use_canada_list":[{"field_id":33,"order_no":1,"bullet":"Gardasil is a vaccine used to protect against four types of Human Papilloma Virus (HPV types 6, 11, 16, and 18), which cause 70% of cervical cancers, 90% of genital warts, and 80-90% of anal cancers."},{"field_id":33,"order_no":2,"bullet":"Gardasil is recommended for girls and women 9 to 45 years of age and in boys and men 9 to 26 years of age."},{"field_id":33,"order_no":3,"bullet":"Gardasil will not protect against diseases caused by other types of HPV or viruses, and works best when given before there has been any contact with the types of HPV included in the vaccine."},{"field_id":33,"order_no":4,"bullet":"Gardasil was authorized in Canada on July 10, 2006, and is approved in 133 countries around the world."},{"field_id":33,"order_no":5,"bullet":"Since 2006, more than 55 million patients have been vaccinated with Gardasil worldwide, and over 1 million in Canada."}],"finding_list":[{"field_id":34,"order_no":1,"bullet":"In studies received from the manufacturer before Gardasil was authorized for sale on the Canadian market, over 15,500 participants received Gardasil and over 13,500 participants received injections that did not contain Gardasil (placebo). Participants receiving Gardasil had more pain, swelling, and redness at the injection site and more mild fevers than those who did not receive Gardasil. The percentage of participants who developed autoimmune or cardiovascular diseases was similar in the two groups."},{"field_id":34,"order_no":2,"bullet":"Since its approval, more than 183,000 side effects following vaccination with Gardasil have been reported internationally, including over 4,000 in Canada. No new safety concerns were identified in the review of reports of side effects from Canada and in the most recent safety report from the manufacturer. The most commonly reported side effects were light-headedness, dizziness, nausea, headache, or fever, as well as pain, swelling or redness at the injection site. There were very few reports of autoimmune or cardiovascular diseases."},{"field_id":34,"order_no":3,"bullet":"Studies published in the scientific and medical literature on the safety of Gardasil after being used in the general population were conducted in the United States and several countries in Europe. More than a million girls and women received Gardasil in these studies. The studies compared the number of cases of autoimmune diseases, cardiovascular diseases, and diseases related to the brain or nervous system (neurologic) in those that received Gardasil with those that did not. No safety concerns consistently linked to Gardasil were found in these studies."}],"conclusion_list":[{"field_id":35,"order_no":1,"bullet":"Health Canada's review of the safety of Gardasil did not find any new safety issues after reviewing all available safety information. There were very few side effect reports of autoimmune or cardiovascular diseases, and in large safety studies, the frequency of autoimmune and cardiovascular diseases was not different between those who were vaccinated with Gardasil and those who were not."},{"field_id":35,"order_no":2,"bullet":"The most commonly reported side effects following vaccination with Gardasil are light-headedness, dizziness, nausea, headache, or fever; as well as pain, swelling or redness at the injection site. These side effects are already included in the Canadian prescribing information for Gardasil. The benefits of Gardasil continue to be greater than the risks and existing prescribing information was considered appropriate.a"},{"field_id":35,"order_no":3,"bullet":"An Information Update has been issued to inform Canadians about these findings."},{"field_id":35,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving Gardasil, as it does for all health products on the Canadian market, to find and study potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00009","review_date":null,"drug_name":"Votrient (pazopanib)","safety_issue":"Assessing the Potential Risk of Accumulation of Fluid Around the Heart (Pericardial Effusion)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":36,"overview":"A safety review was done to evaluate the potential risk of accumulation of fluid around the heart (pericardial effusion) in patients taking the anti-cancer drug Votrient (pazopanib). Pericardial effusion is a serious condition which can cause heart problems or lead to death. The safety review was triggered by an article in the World Health Organization (WHO) Pharmaceutical Newsletter which presented cases of this issue.","use_canada":37,"findings":38,"conclusion":39,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":40,"title":"Summary Safety Review - VOTRIENT (pazopanib) - Assessing the Potential Risk of Accumulation of Fluid Around the Heart (Pericardial Effusion)","created_date":"2015-11-30","modified_date":null,"key_message_list":[{"field_id":36,"order_no":1,"bullet":"Votrient (pazopanib) is a drug used to treat metastatic kidney and advanced soft tissue cancers."},{"field_id":36,"order_no":2,"bullet":"Health Canada's safety review on the possible accumulation of fluid around the heart (pericardial effusion) with Votrient use was triggered by an article in The World Health Organization (WHO) Pharmaceutical Newsletter which presented cases of this issue."},{"field_id":36,"order_no":3,"bullet":"The current safety review did not find enough information to support a link between the risk of pericardial effusion and the use of Votrient. Health Canada has requested the manufacturer to continue to provide information on this safety issue and will continue to monitor this potential risk."}],"footnotes_list":[{"field_id":40,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":37,"order_no":1,"bullet":"Votrient is an anti-cancer drug (a tyrosine kinase inhibitor)."},{"field_id":37,"order_no":2,"bullet":"Votrient is used to treat two rare and advanced types of cancers: metastatic kidney cancer and advanced soft tissue cancer. Metastatic kidney cancer (metastatic renal cell carcinoma) is a type of kidney cancer where cancer cells have spread from the kidney to other parts of the body. Advanced soft tissue cancer (soft tissue sarcoma) is a type of cancer that occurs in soft tissues like fat, muscle, tendon, nerves, blood vessels, etc."},{"field_id":37,"order_no":3,"bullet":"Although not commonly prescribed, Votrient use has been steadily increasing since its marketing in Canada in August 2010."}],"finding_list":[{"field_id":38,"order_no":1,"bullet":"At the time of the review, no cases of pericardial effusion linked with pazopanib were reported in Canadaa."},{"field_id":38,"order_no":2,"bullet":"Health Canada's review of the reported cases received from the manufacturer and /or found in the literature was limited in its ability to confirm and assess the potential role of Votrient and the risk of pericardial effusion based on factors such as the progression of the cancer."},{"field_id":38,"order_no":3,"bullet":"Limited information was found during the review of scientific literature on pericardial effusion with Votrient use."}],"conclusion_list":[{"field_id":39,"order_no":1,"bullet":"The safety review found limited evidence to support an increased risk of pericardial effusion with the use of the anti-cancer drug Votrient."},{"field_id":39,"order_no":2,"bullet":"Health Canada has asked the manufacturer to continue to provide information on this safety issue."},{"field_id":39,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Votrient, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00010","review_date":null,"drug_name":"Avastin (bevacizumab)","safety_issue":"Assessing the Potential Risk of Irreversible vocal cord damage (vocal cord necrosis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":41,"overview":"During routine monitoring, Health Canada identified a report of a woman who suffered from hoarseness due to vocal cord necrosis after using Avastin with another anti-cancer drug. As a result of this report, Health Canada undertook a review of this potential safety issue.","use_canada":42,"findings":43,"conclusion":44,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - AVASTIN (bevacizumab) - Assessing the Potential Risk of Irreversible Vocal Cord Damage (vocal cord necrosis)","created_date":"2015-11-30","modified_date":null,"key_message_list":[{"field_id":41,"order_no":1,"bullet":"In Canada, Avastin is used alone or with other drugs to treat cancers of the large bowel, lung or brain."},{"field_id":41,"order_no":2,"bullet":"During routine monitoring, Health Canada identified a report linking the use of Avastin to irreversible vocal cord damage (vocal cord necrosis). A safety review was done to further examine this potential issue."},{"field_id":41,"order_no":3,"bullet":"At the time of the review, Health Canada did not find enough evidence to link Avastin treatment with vocal cord necrosis. Health Canada will continue to monitor for information about this safety issue."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":42,"order_no":1,"bullet":"Avastin, when given in combination with other anti-cancer drugs, is used to treat patients with a specific type of lung cancer or patients with large bowel cancer that has spread."},{"field_id":42,"order_no":2,"bullet":"By itself, Avastin is used to treat patients with a specific type of aggressive brain cancer who have not improved enough with other treatments."},{"field_id":42,"order_no":3,"bullet":"Avastin has been sold in Canada since November 2005."}],"finding_list":[{"field_id":43,"order_no":1,"bullet":"There were no reports of vocal cord necrosis in patients using Avastin in Canada at the time of the review."},{"field_id":43,"order_no":2,"bullet":"Internationally, from 2000 to 2014, there were 14 reports of side effects affecting the vocal cords with 3 reports of vocal cord necrosis."},{"field_id":43,"order_no":3,"bullet":"Out of 26,420 patients in international clinical studies with Avastin, 11 reported possible vocal cord necrosis but the cause was not confirmed."},{"field_id":43,"order_no":4,"bullet":"An assessment of scientific and medical literature at the time of the review identified 16 international cases of damage to the vocal cords, 3 of which were confirmed cases of irreversible damage. There was incomplete information to confirm the other 13 cases."}],"conclusion_list":[{"field_id":44,"order_no":1,"bullet":"Health Canada's review found that there is not enough evidence to link Avastin treatment with an increased risk of vocal cord necrosis."},{"field_id":44,"order_no":2,"bullet":"The actual frequency of vocal cord necrosis in patients using Avastin is unknown because for most cases of side-effects to the vocal cords, procedures to confirm the exact condition were not performed."},{"field_id":44,"order_no":3,"bullet":"A very small number (0.04%) of patients enrolled in clinical studies with Avastin had symptoms of vocal cord necrosis that may have potentially been related to use of Avastin."},{"field_id":44,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving Avastin, as it does for all health products on the Canadian market, to identify and assess potential harms. Heath Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00011","review_date":null,"drug_name":"Abilify and Abilify Maintena (aripiprazole)","safety_issue":"Certain impulse control behaviours","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":45,"overview":"A safety review was conducted to evaluate the potential link between Abilify and Abilify Maintena (aripiprazole) and certain behaviours where individuals cannot control their urges (impulse control behaviours): uncontrollable gambling (pathological gambling) and sexual behaviours (hypersexuality).","use_canada":47,"findings":49,"conclusion":50,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":51,"title":"Summary Safety Review - ABILIFY and ABILIFY MAINTENA (aripiprazole) - Evaluating the Risk of Certain Impulse Control Behaviours","created_date":"2015-11-02","modified_date":null,"key_message_list":[{"field_id":45,"order_no":1,"bullet":"Abilify (aripiprazole) is a medicine taken by mouth, used to treat:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":56,"title":"Summary Safety Review - Strontium - Risk of Heart and Circulatory Side Effects","created_date":"2015-10-22","modified_date":null,"key_message_list":[{"field_id":52,"order_no":1,"bullet":"Strontium is a naturally occurring mineral available as an ingredient in over-the-counter (OTC) natural health products. It is sold in various salt forms and can be used to help support bone health."},{"field_id":52,"order_no":2,"bullet":"As a result of a European Medicines Agency's safety review (EMA) on the prescription dose of the ranelate form of strontium (strontium ranelate), Health Canada conducted a review of strontium. The EMA safety review found that the dose of 680 mg per day was beneficial for severe osteoporosis, but that it should not be used in patients who have pre-existing heart or circulatory problems."},{"field_id":52,"order_no":3,"bullet":"Health Canada's review did not find information available on cardiovascular risk with the strontium ranelate form at doses less than 680 mg strontium per day, or with other non-ranelate forms of strontium at any dose. While uncertainties remain, Health Canada is taking a precautionary approach and recommending updates to the labels of products containing strontium, including informing consumers not to use these products if they have pre-existing heart or circulatory problems, such as heart attack, stroke or blood clot."}],"footnotes_list":[{"field_id":56,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":53,"order_no":1,"bullet":"In Canada, strontium is a mineral and classified as a natural health product ingredient. It is found in licensed natural health products in various salt forms, including strontium citrate, strontium lactate, and strontium gluconate."},{"field_id":53,"order_no":2,"bullet":"At the time of the review, Health Canada had licensed 30 natural health products containing strontium (included in oral multi-ingredient products and in toothpastes). Of these, 16 provided daily doses of elemental strontium ranging from 4 mg up to 682 mg, in the forms of strontium citrate, strontium lactate, or strontium gluconate."}],"finding_list":[{"field_id":54,"order_no":1,"bullet":"There were no Canadiana or international reports of heart or circulatory side effects associated with the strontium salt forms licensed in Canada, including strontium citrate, strontium lactate, and strontium gluconate, at the time of the review."},{"field_id":54,"order_no":2,"bullet":"Health Canada's review determined that strontium is the only component of strontium salt combinations that plays an active role in the body, while the salt parts like ranelate, lactate, citrate, and gluconate help with absorption of the strontium. There is not enough information available to compare how the different strontium salt combinations are absorbed in the body or the safety risk of heart or circulatory side effects with low dose strontium."},{"field_id":54,"order_no":3,"bullet":"Health Canada's review did not find information available on cardiovascular risk with the strontium ranelate form at doses less than 680 mg/ day, or with other non-ranelate forms of strontium at any dose. While uncertainties remain, Health Canada is taking a precautionary approach and considers that strontium, regardless of the form it comes in, may have a potential risk of cardiovascular side effects in people who are already at risk."}],"conclusion_list":[{"field_id":55,"order_no":1,"bullet":"Although available evidence for heart and circulatory side effects involved strontium ranelate taken at 680 mg per day only, a risk at lower doses of strontium ranelate and with other strontium salt combinations could not be ruled out."},{"field_id":55,"order_no":2,"bullet":"While uncertainties remain, Health Canada is taking a precautionary approach and recommending that licence holders of those products providing adults with more than 4 mg of elemental strontium per day update the labelling to inform consumers not to use these products if they have, or are at high risk for heart disease, circulatory problems, or blood clots."},{"field_id":55,"order_no":3,"bullet":"Health Canada has issued an Information Update to inform Canadians about the label revisions and potential risk of cardiovascular side effects."},{"field_id":55,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving all salt forms of strontium, as it does for all health products on the Canadian market, and will take additional actions, if warranted."}]},{"template":2,"link_id":"SSR00013","review_date":null,"drug_name":"Sodium-glucose cotransporter-2 (SGLT2) inhibitors: Invokana (canagliflozin), Forxiga (dapagliflozin), Jardiance (empagliflozin)","safety_issue":"High levels of acids in the blood (diabetic ketoacidosis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":57,"overview":"Ketones are a type of waste product that the body creates when it breaks down fat to use for energy. If ketones begin to build up to toxic levels in the blood (a condition known as diabetic ketoacidosis) it can lead to symptoms such as difficulties in breathing, stomach pain, nausea and vomiting, confusion, tiredness, loss of appetite, and excessive thirst. It can lead to a coma in extreme cases. Diabetic ketoacidosis can happen to anyone with diabetes but it is more common in those with type 1 diabetes, and quite rare in people with type 2 diabetes.
A safety review was carried out by Health Canada to evaluate the risk of diabetic ketoacidosis in patients using SGLT2 inhibitors following the recent posting of a notice from the FDA about this side effect.
","use_canada":58,"findings":59,"conclusion":60,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":917,"title":"Summary Safety Review - SGLT2 Inhibitors (canagliflozin, dapagliflozin, empagliflozin) - Assessing the Risk of the Body Producing High Levels of Acids in the Blood (diabetic ketoacidosis)","created_date":"2016-05-16","modified_date":null,"key_message_list":[{"field_id":57,"order_no":1,"bullet":"SGLT2 inhibitors are drugs that can be used on their own with diet and exercise or with other products to decrease blood sugar levels in adults with type 2 diabetes."},{"field_id":57,"order_no":2,"bullet":"A safety review was triggered following the recent posting of a notice by the US Food and Drug Administration (FDA) about cases of acids building up in the blood, known as diabetic ketoacidosis (a potentially life-threatening event), in patients taking SGLT2 inhibitors."},{"field_id":57,"order_no":3,"bullet":"Health Canada's safety review concluded that SGLT2 inhibitors may increase the risk of experiencing diabetic ketoacidosis and recommended to update the product information to better explain the symptoms of diabetic ketoacidosis. "}],"footnotes_list":[{"field_id":917,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":58,"order_no":1,"bullet":"SGLT2 inhibitors are drugs designed to lower blood sugar in adults with type 2 diabetes by helping remove excess sugar from the body through the urine."},{"field_id":58,"order_no":2,"bullet":"SGLT2 inhibitors are used along with diet and exercise either alone or in combination with other specific agents that control blood sugar."},{"field_id":58,"order_no":3,"bullet":"Three SGLT2 inhibitors are currently available in Canada: Invokana (canagliflozin), Forxiga (dapagliflozin) and Jardiance (empagliflozin). Drugs of this type first entered the Canadian market in 2014."},{"field_id":58,"order_no":4,"bullet":"SGLT2 inhibitors should not be used (i.e. they are not indicated for use) in patients with type 1 diabetes."}],"finding_list":[{"field_id":59,"order_no":1,"bullet":"At the time of the review Health Canada had received 5 Canadian reports of diabetic ketoacidosisa (4 patients with type 2 diabetes and 1 patient with type 1 diabetes) all using Invokana.Each of these events was reported as serious and some patients were hospitalized."},{"field_id":59,"order_no":2,"bullet":"A total of 419 international cases (310 patients with type 2 diabetes and 119 patients with type 1 diabetes) of diabetic ketoacidosis were also found in patients taking any one of the SGLT2 inhibitors. The blood sugar of patients was generally observed to be normal or mildly elevated in reports that included this information. This observation is important because the side effects of diabetic ketoacidosis can occur regardless of the patient's blood sugar level."},{"field_id":59,"order_no":3,"bullet":"After reviewing a number of studies, it was found that type 2 diabetes patients taking SGLT2 inhibitors were more likely to experience diabetic ketoacidosis compared to those patients that were given a placebo or another type of drug that controls diabetes. In addition, in most type 2 diabetes patients, the SGLT2 inhibitors increased the levels of ketones in the blood but not enough that the patient would experience the side effects of diabetic ketoacidosis."},{"field_id":59,"order_no":4,"bullet":"The review also noted other conditions that further increased the likelihood of experiencing diabetic ketoacidosis. These included major surgeries, serious infections, sudden serious medical illnesses, having a diet low in carbohydrates, dehydration, high alcohol consumption or having low insulin levels."},{"field_id":59,"order_no":5,"bullet":"SGLT2 inhibitors are not indicated for use in patients with type 1 diabetes. Based on information from clinical trials, the use of SGLT2 inhibitors in these patients may further increase the risk of diabetic ketoacidosis."},{"field_id":59,"order_no":6,"bullet":"Despite the risk of diabetic ketoacidosis, the findings show that the benefits of these products still outweigh their risks, when used as authorized."}],"conclusion_list":[{"field_id":60,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence supported a link between the use of SGLT2 inhibitors and the risk of diabetic ketoacidosis."},{"field_id":60,"order_no":2,"bullet":"In order to raise awareness, Health Canada will work with manufacturers to update the product information so that it better explains the symptoms that may be signs of diabetic ketoacidosis: difficulty breathing, nausea, vomiting, stomach pain, confusion, loss of appetite, feeling very thirsty and feeling unusual tiredness. If these side effects occur, patients should stop taking the drug and call their doctor or pharmacist. Health care professionals should assess patients for diabetic ketoacidosis immediately if these symptoms occur, regardless of their blood sugar level, and the SGLT2 inhibitor treatment should be discontinued."},{"field_id":60,"order_no":3,"bullet":"A Health Product Risk Communication will also be issued to explain this side effect of using SGLT2 inhibitors."},{"field_id":60,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving SGLT2 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00014","review_date":null,"drug_name":"Octagam 5% and Octagam 10% (Immune Globulin Intravenous [Human])","safety_issue":"Lack of effectiveness and safety issues related to the manufacturing process","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":61,"overview":"","use_canada":62,"findings":63,"conclusion":64,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":65,"title":"Summary Safety Review - OCTAGAM 5% and OCTAGAM 10% (Immune Globulin Intravenous [Human]) - Assessing Lack of Effectiveness and Safety Issues Related To the Manufacturing Process","created_date":"2015-09-29","modified_date":null,"key_message_list":[{"field_id":61,"order_no":1,"bullet":"Octagam 5% is used to prevent infections in patients with immune system deficiencies. Octagam 10% is used to treat patients who have a blood disorder with decreased numbers of platelet cells, which are required for blood clotting."},{"field_id":61,"order_no":2,"bullet":"Health Canada conducted an in-depth safety review using additional information requested from the manufacturer of Octagam 5% and Octagam 10%. This was triggered after a routine Health Canada review of information provided by the manufacturer identified both a lack of effectiveness and safety issues related to the manufacturing process, such as allergic reactions (hypersensitivity) and abnormal blood clotting (thromboembolic events)."},{"field_id":61,"order_no":3,"bullet":"Health Canada's safety review found no evidence linking Octagam 5% or Octagam 10% to a lack of effectiveness or to an increase in allergic reactions and abnormal blood clotting. The risk of allergic reactions and abnormal blood clotting is known for these medicines and is already described in the Canadian prescribing information. Health Canada will continue to monitor safety information associated with Octagam 5% and Octagam 10%."}],"footnotes_list":[{"field_id":65,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":62,"order_no":1,"bullet":"Octagam 5% is authorized to help prevent infections in patients with immune system deficiencies. Although not sold in Canada, Octagam 5% was included as part of the safety review to help determine if there were safety issues."},{"field_id":62,"order_no":2,"bullet":"Octagam 10%, sold in Canada since 2013, is authorized to treat patients who have a blood disorder, which decreases their number of platelets (immune thrombocytopenic purpura). Patients with low numbers of platelets may experience increased bruising or bleeding. Octagam 10% can be used to decrease the high risk of bleeding or increase the number of platelets before surgery."},{"field_id":62,"order_no":3,"bullet":"Octagam 5% and Octagam 10% are reported to be used to treat other immune disorders that are not authorized by Health Canada."}],"finding_list":[{"field_id":63,"order_no":1,"bullet":"At the time of the review, no reports of Canadians experiencing a lack of effectiveness with Octagam 5% and Octagam 10% were received through the Canada Vigilance Programa. In addition, there were no reports linking the manufacturing process of these medicines to allergic reactions or abnormal blood clotting."},{"field_id":63,"order_no":2,"bullet":"In 2010, an increased number of reports of allergic reactions and blood clots were received by the manufacturer of Octagam 5% and Octagam 10%. The manufacturer determined that these safety issues were related to the manufacturing process and linked only to specific lots of Octagam 5% and Octagam 10%. These lots were never sold in Canada. The manufacturer recalled the affected lots and improved the manufacturing process to help prevent future occurrences of these side effects. Since the new manufacturing process was put in place, the frequency of reports of allergic reactions and blood clots has returned to normal."},{"field_id":63,"order_no":3,"bullet":"A review of Canadian and international case reports, clinical trial reports, and the scientific literature did not find information indicating a lack of effectiveness for these medicines or identify a change in the current safety profile of these products."}],"conclusion_list":[{"field_id":64,"order_no":1,"bullet":"Health Canada's review did not find information linking Octagam 5% and Octagam 10% to a lack of effectiveness. Health Canada also found no evidence that the safety issues related to the manufacturing process for Octagam 5% or Octagam 10% ever posed a health risk to Canadians."},{"field_id":64,"order_no":2,"bullet":"The risk of allergic reactions and abnormal blood clotting is known for these medicines and is already described in the Canadian prescribing information for Octagam 5% and Octagam 10%. Health Canada has also issued a notice to hospitals about the link between abnormal blood clotting and products like Octagam 5% and Octagam 10%."},{"field_id":64,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Octagam 5% and Octagam 10%, as it does for all health products on the Canadian market, to find and study potential harms. Health Canada will take the right and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00025","review_date":null,"drug_name":"Intravenous Methylprednisolone","safety_issue":"Liver injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":117,"overview":"A safety review was initiated following the identification of 28 published international cases of liver injury associated with intravenous methylprednisolone. Among these cases, four had a fatal outcome.","use_canada":118,"findings":119,"conclusion":120,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":121,"title":"Summary Safety Review - Intravenous Methylprednisolone - Liver Injury","created_date":"2015-06-18","modified_date":null,"key_message_list":[{"field_id":117,"order_no":1,"bullet":"Methylprednisolone is a corticosteroid drug typically used for its anti-inflammatory effects. Administration into a vein (intravenous) is generally only used for short periods in severe inflammatory conditions."},{"field_id":117,"order_no":2,"bullet":"A safety review was initiated following the identification of 28 published international cases of liver injury associated with intravenous methylprednisolone, some of which had a fatal outcome."},{"field_id":117,"order_no":3,"bullet":"The Canadian prescribing information for intravenous methylprednisolone products marketed under the brand names of SOLU-MEDROL and SOLU-MEDROL ACT-O-VIALS has been updated to include the risk of liver injury. Manufacturers of generic versions of this drug will be asked by Health Canada to update their product information."}],"footnotes_list":[{"field_id":121,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."},{"field_id":121,"order_no":2,"bullet":"As of January 2015, CARN has now become a monthly publication called Health Product InfoWatch"}],"reference_list":[],"use_canada_list":[{"field_id":118,"order_no":1,"bullet":"Intravenous methylprednisolone is marketed under the brand names of SOLU-MEDROL and SOLU-MEDROL ACT-O-VIALS. Generic versions of this drug are also available in Canada."},{"field_id":118,"order_no":2,"bullet":"Intravenous methylprednisolone is an anti-inflammatory steroid mainly used in hospitals for short periods to treat severe inflammatory conditions. Symptoms of inflammation are often seen with allergic reactions, intestinal disorders (ulcerative colitis), and organ transplants."}],"finding_list":[{"field_id":119,"order_no":1,"bullet":"Up until December 31, 2013, three Canadian reports were received through the Canada Vigilance Programa. Only one case of liver injury was possibly associated with intravenous methylprednisolone."},{"field_id":119,"order_no":2,"bullet":"Among the 28 cases identified in the literature, the time to onset of the liver injury varied from several days to several months. Of these cases, 27 were considered severe, and death was reported in 4 cases. Patients' signs and symptoms of liver injury improved when the treatment was stopped in 22 of these 28 cases. When intravenous methylprednisolone was restarted, liver injury reappeared in almost half of the cases."}],"conclusion_list":[{"field_id":120,"order_no":1,"bullet":"Evidence of an association between intravenous methylprednisolone with a variable time to onset and the occurrence of liver injury was found by Health Canada. The Canadian prescribing information for the products marketed under the brand names of SOLU-MEDROL and SOLU-MEDROL Act-O-VIALS have been updated to better reflect the available evidence regarding the risk of liver injury. Manufacturers of generic versions of this drug will also be asked by Health Canada to update their product information."},{"field_id":120,"order_no":2,"bullet":"Health Canada had published an article in the October 2014 Canadian Adverse Reaction Newsletter (CARN)b/sup> to communicate the risk of liver injury associated with intravenous methylprednisolone. This publication is intended to raise awareness among healthcare professionals and to encourage the reporting of similar adverse reactions."}]},{"template":2,"link_id":"SSR00015","review_date":null,"drug_name":"Remicade (infliximab)","safety_issue":"Blood cancers (lymphoma, hepatosplenic T-cell lymphoma, and leukemia)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":66,"overview":"","use_canada":67,"findings":68,"conclusion":69,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":70,"title":"Summary Safety Review - REMICADE (infliximab) - Evaluating for the Risk of Cancer (Lymphoma, Hepatosplenic T-Cell Lymphoma, and Leukemia)","created_date":"2015-09-29","modified_date":null,"key_message_list":[{"field_id":66,"order_no":1,"bullet":"Remicade treats inflammation that results from the body's own defence system attacking the skin, joints, intestines, or stomach (autoimmune disease)."},{"field_id":66,"order_no":2,"bullet":"Health Canada conducted a safety review to evaluate the risk of developing three types of cancers (lymphoma, hepatosplenic T-cell lymphoma, and leukemia) associated with the use of Remicade to treat an autoimmune disease of the skin (psoriasis) in adults."},{"field_id":66,"order_no":3,"bullet":"This issue was identified during Health Canada's review of safety information provided by the manufacturer."},{"field_id":66,"order_no":4,"bullet":"Health Canada's safety review did not find evidence of an association between lymphoma, hepatosplenic T-cell lymphoma, or leukemia, and the use of Remicade to treat psoriasis. Health Canada will continue to monitor this issue, including the assessment of medical and scientific literature and side effect reports."}],"footnotes_list":[{"field_id":70,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":67,"order_no":1,"bullet":"Remicade (infliximab) is a unique immune system protein (monoclonal antibody), which works by blocking a naturally occurring chemical TNF-α (Tumour Necrosis Factor-alpha) that causes inflammation."},{"field_id":67,"order_no":2,"bullet":"This medicine treats inflammation that results from the body's own defence system attacking the skin, joints, intestines, or stomach (autoimmune disease). Remicade is used for the treatment of autoimmune diseases including plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, adult and children's ulcerative colitis and Crohn's disease."},{"field_id":67,"order_no":3,"bullet":"Remicade has been marketed in Canada since 2001, and is available by prescription only."}],"finding_list":[{"field_id":68,"order_no":1,"bullet":"At the time of the review, the Canada Vigilance Programa received 77 reports of lymphoma, 5 reports of a type of lymphoma (Non-Hodgkin's Lymphoma) that also included cases of hepatosplenic T-cell lymphoma, and 8 reports of leukemia associated with the use of Remicade to treat autoimmune diseases. Health Canada's analysis of the reports found no association between these cancers with Remicade use for psoriasis."},{"field_id":68,"order_no":2,"bullet":"A review of international safety data provided by the manufacturer revealed cases of lymphoma and leukemia associated with Remicade treatment for psoriasis and psoriatic arthritis. No cases of hepatosplenic T-cell lymphoma were identified."},{"field_id":68,"order_no":3,"bullet":"A review of international data from the World Health Organization's database retrieved 413 reports of lymphoma, 73 reports of Non-Hodgkin's Lymphoma that included cases of hepatosplenic T-cell lymphoma, and 50 reports of leukemia associated with Remicade treatment of autoimmune diseases. Health Canada's evaluation of these reports did not indicate that these cancers were associated with Remicade treatment for psoriasis in particular."},{"field_id":68,"order_no":4,"bullet":"A review of the scientific and medical literature did not identify an association between lymphoma, hepatosplenic T-cell lymphoma, and leukemia and the use of Remicade for the treatment of psoriasis or psoriatic arthritis."},{"field_id":68,"order_no":5,"bullet":"Confirming and assessing these reports was limited by several factors, including an increased risk of cancer in patients having certain underlying diseases or having taken, or currently taking other medications."}],"conclusion_list":[{"field_id":69,"order_no":1,"bullet":"Health Canada's safety review did not find evidence of an association between lymphoma, hepatosplenic T-cell lymphoma, and leukemia and the use of Remicade for psoriasis."},{"field_id":69,"order_no":2,"bullet":"The Canadian prescribing information already includes the potential risk of developing hepatosplenic T-cell lymphoma in patients receiving Remicade for the treatment of autoimmune diseases. In 2004, Health Canada also issued a healthcare professional communication and a public communication about updated safety information addressing the risk of cancers linked to the use of Remicade."},{"field_id":69,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Remicade, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take right and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00016","review_date":null,"drug_name":"GILENYA (fingolimod)","safety_issue":"Abnormal tissue growth (Neoplasms)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":71,"overview":"A safety review was done to evaluate a potential link between Gilenya (fingolimod) and abnormal tissue growth (neoplasms). This issue was identified through a Health Canada review of safety information obtained by the manufacturer. When a neoplasm forms a mass, it can commonly be referred to as a tumour. Tumours can be further divided into those that are cancerous (malignant) and those that are non-cancerous (benign).","use_canada":72,"findings":73,"conclusion":74,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":75,"title":"Summary Safety Review - GILENYA (fingolimod) - Assessing the Risk of the Abnormal Tissue Growth (Cancer)","created_date":"2015-09-14","modified_date":null,"key_message_list":[{"field_id":71,"order_no":1,"bullet":"Gilenya (fingolimod) is used to treat multiple sclerosis, a condition that results in the damage of the nervous system, leading to physical and mental disability. It is specifically used in patients who have had a poor response to, or are unable to tolerate one or more therapies for multiple sclerosis."},{"field_id":71,"order_no":2,"bullet":"The potential link between the use of Gilenya and abnormal tissue growth (neoplasms) was identified during a Health Canada review of safety information obtained from the manufacturer."},{"field_id":71,"order_no":3,"bullet":"Health Canada's safety review showed evidence of a potential link between the use of Gilenya and an increased risk of lymphomas and other malignant cancers, particularly of the skin. The Canadian product monograph for Gilenya has been updated to include this information. Health Canada has requested additional safety information from the manufacturer and will continue to monitor this issue."}],"footnotes_list":[{"field_id":75,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":72,"order_no":1,"bullet":"Gilenya is a medicine used to treat multiple sclerosis, a condition that results in the damage of the nervous system. Gilenya reduces the frequency of signs and symptoms of multiple sclerosis by delaying the progression of physical disability. The most common type of multiple sclerosis is one where symptoms of an attack flare up and are then followed by a time of recovery (relapsing-remitting multiple sclerosis)."},{"field_id":72,"order_no":2,"bullet":"Gilenya is recommended in patients who have had a poor response to, or are unable to tolerate one or more therapies for multiple sclerosis."},{"field_id":72,"order_no":3,"bullet":"Gilenya was first marketed in Canada in March 2011."}],"finding_list":[{"field_id":73,"order_no":1,"bullet":"At the time of the review, the Canada Vigilancea program received 16 reports of neoplasms linked to Gilenya. There were no life-threatening events or deaths reported, and no more than two cases were reported for any particular type of cancer, including skin cancer and a type of blood cancer (lymphoma)."},{"field_id":73,"order_no":2,"bullet":"The World Health Organization's database presented 62 cases of skin cancer at the time of the review. Eight or fewer cases of each remaining non-skin cancer were reported, with the exception of breast cancer where there were 30 cases."},{"field_id":73,"order_no":3,"bullet":"A review of the scientific and medical literature identified two published patient medical reports (case reports), three medical research studies on human participants (clinical trials), and four safety reviews that describe cases of neoplasms in patients treated with Gilenya. In two of the clinical trials, participants receiving Gilenya had a higher occurrence of skin cancers than those who did not."},{"field_id":73,"order_no":4,"bullet":"Numerous patient medical reports received from the manufacturer link skin cancer to Gilenya since it was first approved for sale. In addition, reports of skin cancer have increased recently in patients treated with Gilenya."},{"field_id":73,"order_no":5,"bullet":"Patients receiving medicines that suppress the immune system, like Gilenya, are known to have an increased risk of lymphomas and other malignant cancers, particularly of the skin."},{"field_id":73,"order_no":6,"bullet":"At the time of the review, the Canadian product monograph already labeled for the risk of lymphoma with \"uncertain\" relationship to Gilenya, but it did not label for any other neoplasms."}],"conclusion_list":[{"field_id":74,"order_no":1,"bullet":"Health Canada's safety review showed evidence of a potential link between Gilenya and the increased risk of lymphomas and other malignant cancers, particularly of the skin."},{"field_id":74,"order_no":2,"bullet":"The Canadian product monograph for Gilenya has been updated to include the risk of lymphomas and other malignant cancers, particularly of the skin."},{"field_id":74,"order_no":3,"bullet":"Side effects like neoplasms are rare and could take a long time to develop or be detected. Therefore, additional safety information from the manufacturer of Gilenya about the risk of neoplasms has been requested by Health Canada. Furthermore, Health Canada will continue to monitor side effect information involving Gilenya, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00017","review_date":null,"drug_name":"Revolade (eltrombopag)","safety_issue":"Serious skin reactions","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":76,"overview":"A safety review was conducted to evaluate the potential link between serious skin reactions and the use of Revolade (eltrombopag). This issue was identified following new safety information that Health Canada asked from the manufacturer.","use_canada":78,"findings":79,"conclusion":81,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":82,"title":"Summary Safety Review - REVOLADE (eltrombopag) - Serious Skin Reactions","created_date":"2015-09-10","modified_date":null,"key_message_list":[{"field_id":76,"order_no":1,"bullet":"Revolade (eltrombopag) is a medicine used to treat patients with:A safety review was done to assess the potential association between flesh-eating disease and VELCADE (bortezomib). This issue was identified through a Health Canada review of safety information found in two published articles that described medical case reports of flesh-eating disease in two patients treated with bortezomib1,2
","use_canada":84,"findings":85,"conclusion":86,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":87,"footnotes":88,"title":"Summary Safety Review - Bortezomib (VELCADE and Generics) - Assessing a Potential Link with Flesh-Eating Disease (Necrotising Fasciitis)","created_date":"2015-09-03","modified_date":null,"key_message_list":[{"field_id":83,"order_no":1,"bullet":"VELCADE (bortezomib) is used to treat cancers of the bone marrow (multiple myeloma) and the lymphatic system that affects the white blood cells (mantle cell lymphoma)."},{"field_id":83,"order_no":2,"bullet":"This safety review was triggered by two published articles. These two articles described the potential association between treatment with bortezomib and flesh-eating disease (necrotising fasciitis), a rare infection of the deeper layers of skin and underlying tissues."},{"field_id":83,"order_no":3,"bullet":"At this time, there is limited evidence to make an association between bortezomib treatment and the risk of flesh-eating disease. Health Canada has requested additional safety information from the manufacturer to review and will continue to monitor VELCADE for the risk of flesh-eating disease."}],"footnotes_list":[{"field_id":88,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":88,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"},{"field_id":88,"order_no":3,"bullet":"Eudravigilance can be accessed through the Eudravigilance Online Database"}],"reference_list":[{"field_id":87,"order_no":1,"bullet":"Morita T, Ugai T, Tanimoto T, Matsue K. Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an elderly patient of Waldenstrom macroglobulinaemia. BMJ Case Reports. 26 Mar 2014;No. 203399."},{"field_id":87,"order_no":2,"bullet":"Rosser A, Swallow G, Swann RA, Chapman C. Salmonella enteritidis necrotising fasciitis in a multiple myeloma patient receiving bortezomib. Int J Hematol. 2010 Jan;91(1):149-5"}],"use_canada_list":[{"field_id":84,"order_no":1,"bullet":"VELCADE (bortezomib) is used to treat cancers of the bone marrow (multiple myeloma) and the lymphatic system that affects white blood cells (mantle cell lymphoma)."},{"field_id":84,"order_no":2,"bullet":"As of June 2015, less than 5,000 prescriptions have been issued each year in Canada. Bortezomib is mostly used in hospitalsa."}],"finding_list":[{"field_id":85,"order_no":1,"bullet":"At the time of the review, no cases of flesh-eating disease in association with bortezomib were reported in Canadab while 11 cases were reported in Europec."},{"field_id":85,"order_no":2,"bullet":"A review of the scientific and medical literature identified two additional medical case reports relevant to the topic of flesh-eating disease linked with the use of bortezomib."},{"field_id":85,"order_no":3,"bullet":"All reported cases reviewed by Health Canada may have been impacted by the use of two medications at the same time (co-medication: bortezomib and another medication) or other risk factors. The risk factors seen in these cases were diabetes, alcohol use, smoking and obesity, the decrease of a body's ability to fight a disease (immune suppression), chronic steroid use and blood circulation diseases affecting blood vessels. As such, these factors make it difficult to link the use of bortezomib alone and flesh-eating disease, at this time."}],"conclusion_list":[{"field_id":86,"order_no":1,"bullet":"At this time, the safety review found limited evidence to make a link between VELCADE (bortezomib) use and the risk of flesh-eating disease (necrotising fasciitis)."},{"field_id":86,"order_no":2,"bullet":"Health Canada has requested additional safety information from the manufacturer to review and will continue to monitor VELCADE (bortezomib) for the risk of flesh-eating disease."}]},{"template":2,"link_id":"SSR00019","review_date":null,"drug_name":"ENBREL (etanercept)","safety_issue":"Schizophrenia like symptoms","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":89,"overview":"Health Canada conducted a safety review to evaluate harmful effects (adverse reactions) related to symptoms resembling schizophrenia linked to the use of ENBREL. The safety review was triggered by a published case of a 54-year old woman taking ENBREL who developed symptoms similar to schizophrenia1. Symptoms of schizophrenia include disorganized thinking and speech, hearing or seeing things that are not there (hallucinations), suspiciousness, and false beliefs (delusions).
","use_canada":90,"findings":91,"conclusion":92,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":93,"footnotes":94,"title":"Summary Safety Review - ENBREL (etanercept) - Schizophrenia like symptoms","created_date":"2015-08-26","modified_date":null,"key_message_list":[{"field_id":89,"order_no":1,"bullet":"ENBREL is used to treat inflammation of joints and skin caused by the body's own defence system attacking its joints and skin, including certain forms of arthritis and psoriasis."},{"field_id":89,"order_no":2,"bullet":"Health Canada conducted a safety review after a report linking the use of ENBREL to the occurrence of symptoms resembling a form of mental illness (schizophrenia) was published in a scientific journal."},{"field_id":89,"order_no":3,"bullet":"The review did not find enough information to support an association between symptoms resembling schizophrenia and the use of ENBREL. Health Canada will continue to monitor this issue."}],"footnotes_list":[{"field_id":94,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[{"field_id":93,"order_no":1,"bullet":"Atigari OV, Healy D. Schizophrenia-like disorder associated with etanercept treatment. BMJ Case Rep. January 13, 2014."}],"use_canada_list":[{"field_id":90,"order_no":1,"bullet":"ENBREL is an immune system protein (monoclonal antibody) which works by blocking a chemical TNF-α (Tumour Necrosis Factor-alpha) that causes pain and swelling (inflammation)."},{"field_id":90,"order_no":2,"bullet":"This medicine treats inflammation that results from the body's own defence system attacking its joints and skin (autoimmune diseases). Examples of autoimmune joint and skin diseases include ankylosing spondylitis, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, and plaque psoriasis."},{"field_id":90,"order_no":3,"bullet":"ENBREL is given through an injection under the skin and is available by prescription only."},{"field_id":90,"order_no":4,"bullet":"ENBREL has been marketed in Canada since March 14, 2001."}],"finding_list":[{"field_id":91,"order_no":1,"bullet":"At the time of the review, 25 cases of mental health disorders (psychiatric disorders), including two cases where the patients were unable to recognize reality or relate to others (psychosis), were received through the Canada Vigilance Programa. No case of schizophrenia was reported. When Health Canada studied these 25 cases, no link between schizophrenia and the use of ENBREL was shown."},{"field_id":91,"order_no":2,"bullet":"A review of international data from the World Health Organization's database retrieved 209 cases of psychiatric disorders, including anxiety, depression, and psychosis. However, Health Canada's evaluation of the cases did not indicate that schizophrenia was linked to the use of ENBREL."},{"field_id":91,"order_no":3,"bullet":"Confirming and assessing these Canadian and international reports of psychiatric disorders was limited by many factors because the information in some reports was incomplete, patients had other diseases or a past history of psychiatric disorders, or patients were taking other medications at the same time as ENBREL."},{"field_id":91,"order_no":4,"bullet":"The risks of anxiety and depression are already included in the Canadian prescribing information for ENBREL."}],"conclusion_list":[{"field_id":92,"order_no":1,"bullet":"The current safety review by Health Canada does not support a link between a schizophrenia-like disorder and the use of ENBREL."},{"field_id":92,"order_no":2,"bullet":"The risks of anxiety and depression are already included in the Canadian prescribing information for ENBREL."},{"field_id":92,"order_no":3,"bullet":"Health Canada will continue to monitor adverse reaction information involving ENBREL, as it does with all health products on the Canadian market, to find and study potential harms. Health Canada will take appropriate and timely action, as appropriate, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00020","review_date":null,"drug_name":"XARELTO (rivaroxaban)","safety_issue":"Liver injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":95,"overview":"Health Canada completed a safety review to evaluate if using XARELTO is linked to a risk of liver injury. This issue was identified after two publications1,2 in the scientific literature described liver injury linked to the use of XARELTO in a total of 16 patients.","use_canada":97,"findings":98,"conclusion":99,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":100,"footnotes":101,"title":"Summary Safety Review - XARELTO (rivaroxaban) - Liver Injury","created_date":"2015-08-26","modified_date":null,"key_message_list":[{"field_id":95,"order_no":1,"bullet":"XARELTO (rivaroxaban) is used to:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":106,"footnotes":0,"title":"Summary Safety Review - Combined Hormonal Birth Control Products - Evaluating effectiveness when used by women who are obese","created_date":"2015-07-23","modified_date":null,"key_message_list":[{"field_id":102,"order_no":1,"bullet":"Combined hormonal birth control products containing forms of estrogen and progestin are used to prevent pregnancy."},{"field_id":102,"order_no":2,"bullet":"A safety review evaluated information about the potential for decreased effectiveness of combined hormonal birth control products when used by obese women. Obesity was calculated using a body mass index (BMI), a measure of fat based on a person's height and weight. Women were considered obese if they had a BMI of 30 kg/m2 or greater."},{"field_id":102,"order_no":3,"bullet":"The safety review did not find a higher risk of pregnancy in obese women compared to non-obese women when using combined hormonal birth control products. Health Canada will continue to monitor this issue."}],"footnotes_list":[],"reference_list":[{"field_id":106,"order_no":1,"bullet":"More information about Body Mass Index is available on Health Canada's Web site."},{"field_id":106,"order_no":2,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":106,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"use_canada_list":[{"field_id":103,"order_no":1,"bullet":"Combined hormonal birth control products are used to prevent pregnancy. These products are available as pills, skin patches and vaginal rings. The pill is the most common form."},{"field_id":103,"order_no":2,"bullet":"Combined hormonal birth control products are widely used in Canada. In 2014, they were among the top 100 most prescribed drugs in Canada2."}],"finding_list":[{"field_id":104,"order_no":1,"bullet":"Until May 31, 2014, Health Canada received 8 reports of pregnancy associated with combined hormonal birth control products with information to confirm obesity3. The review of these reports was limited by several factors, including not being able to confirm pre-pregnancy weight and compliance with the birth control product as directed. Therefore, these reports could not show an association between obesity and pregnancy occurring while taking combined hormonal birth control products."},{"field_id":104,"order_no":2,"bullet":"Some recent studies suggested that obese women may have lower blood levels of birth control hormones when compared to non-obese women. However, the studies did not demonstrate conclusive evidence that this leads to a decrease in effectiveness in obese women using combined hormonal birth control products. One study suggested that the patch form may be less effective in women with a body weight higher than 90 kg (198 pounds). This information is already found in the Canadian prescribing information for the patch."},{"field_id":104,"order_no":3,"bullet":"A majority of other studies on the effectiveness of combined hormonal birth control products also did not show conclusive evidence of a decreased effectiveness in obese women. Many of the studies had limitations of not being able to confirm the proper use of the pill and only included a small number of obese women in the studies."},{"field_id":104,"order_no":4,"bullet":"In 2007, the United States Food and Drug Administration's Advisory Committee for Reproductive Health Drugs recommended that the entry criteria of studies should include women with higher body mass indexes."}],"conclusion_list":[{"field_id":105,"order_no":1,"bullet":"The safety review found no conclusive evidence to show a higher risk of pregnancy in obese women compared to non-obese women when using combined hormonal birth control products."},{"field_id":105,"order_no":2,"bullet":"Health Canada is requiring that the labelling of newly marketed combined hormonal birth control products in Canada contain information regarding the weight of the people studied including BMI. This information is not required for older combined hormonal birth control products as it may not be available (for example, BMI may not have been collected during the clinical trials). This information is being added for specificity to provide further context on the parameters of the studies even though, at this time, the current safety review did not find a higher risk of pregnancy in obese women."},{"field_id":105,"order_no":3,"bullet":"Health Canada will continue to monitor this safety issue."}]},{"template":2,"link_id":"SSR00023","review_date":null,"drug_name":"FERAHEME (ferumoxytol)","safety_issue":"Serious allergic reactions (Hypersensitivity reactions)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":107,"overview":"Health Canada started a safety review following the identification of more than 20 Canadian reports of serious allergic reactions (hypersensitivity reactions) associated with FERAHEME injections. The review was done to determine if current strategies to minimize the risk were sufficient.","use_canada":108,"findings":109,"conclusion":110,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":111,"title":"Summary Safety Review - FERAHEME (ferumoxytol) - Serious allergic reactions (Hypersensitivity reactions)","created_date":"2015-07-03","modified_date":null,"key_message_list":[{"field_id":107,"order_no":1,"bullet":"FERAHEME is an injectable iron product used to treat low levels of iron in the blood (iron deficiency anemia) in adults with chronic kidney disease."},{"field_id":107,"order_no":2,"bullet":"A safety review was started following multiple reports of Canadian cases of serious allergic reactions (hypersensitivity reactions)."},{"field_id":107,"order_no":3,"bullet":"The Canadian prescribing information for FERAHEME has been updated with limitations for who should not be given FERAHEME, including patients with any known history of drug allergies, and with information on how it should be given to reduce the risk of serious hypersensitivity reactions."}],"footnotes_list":[{"field_id":111,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":108,"order_no":1,"bullet":"FERAHEME is an injectable iron product used to treat low levels of iron in the blood (iron deficiency anemia) in adults with chronic kidney disease."},{"field_id":108,"order_no":2,"bullet":"It was first marketed in Canada in May 2012."}],"finding_list":[{"field_id":109,"order_no":1,"bullet":"The risk of serious, potentially fatal, hypersensitivity reactions is known for FERAHEME and other injectable iron products."},{"field_id":109,"order_no":2,"bullet":"As of February 28, 2014, there were more than 20 Canadian reports of serious hypersensitivity reactions, including 2 deaths, received through the Canada Vigilance Programa. Over half were reported in a 6 month period."},{"field_id":109,"order_no":3,"bullet":"Many of the international cases of serious or fatal hypersensitivity reactions reported with FERAHEME documented patients as having allergies to other medicines as well."}],"conclusion_list":[{"field_id":110,"order_no":1,"bullet":"Although Health Canada's safety review determined that the Canadian prescribing information for FERAHEME contained warnings about the risk of serious hypersensitivity reactions, when considering the totality of the evidence an update was made to the prescribing information."},{"field_id":110,"order_no":2,"bullet":"The Canadian prescribing information for FERAHEME has been updated with the limitations for who should not be given FERAHEME and the information about how it should be given to reduce the risk of serious hypersensitivity reactions."},{"field_id":110,"order_no":3,"bullet":"Health Canada issued a healthcare professional communication and a public communication about new limitations for who should not be given FERAHEME, including patients with allergies to injectable iron products or with multiple drug allergies. Another healthcare professional communication was issued with information on how FERAHEME should be given to reduce the risk of serious hypersensitivity reactions. Additionally, the limitation information was updated to avoid giving FERAHEME to patients with any known history of drug allergy."},{"field_id":110,"order_no":4,"bullet":"Health Canada will continue to monitor adverse reaction information involving FERAHEME and other injectable iron products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00024","review_date":null,"drug_name":"Tecfidera (Dimethyl Fumarate)","safety_issue":"Serious allergic reactions including skin reactions and anaphylaxis","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":112,"overview":"A safety review evaluated information on potential hypersensitivity reactions associated with TECFIDERA. Hypersensitivity reactions occur when the body has a strong and undesirable immune system response toward a drug or an allergen. This review was triggered by published information associating TECFIDERA to the risks of swelling under the skin (angioedema) and life-threatening allergic reactions (anaphylaxis), two symptoms of hypersensitivity.","use_canada":113,"findings":114,"conclusion":115,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":116,"title":"Summary Safety Review - TECFIDERA (Dimethyl Fumarate) - Serious allergic reactions including skin reactions and anaphylaxis","created_date":"2015-06-26","modified_date":null,"key_message_list":[{"field_id":112,"order_no":1,"bullet":"TECFIDERA (dimethyl fumarate) is used to treat multiple sclerosis. It does not cure multiple sclerosis, but helps to reduce the number of flare-ups (relapses) that occur and slows the progression of physical disability."},{"field_id":112,"order_no":2,"bullet":"A safety review evaluated information on the potential risk of undesirable and strong immune reactions (hypersensitivity) with TECFIDERA. This review was triggered by published information associating TECFIDERA to the risks of swelling under the skin (angioedema) and life-threatening allergic reactions (anaphylaxis)."},{"field_id":112,"order_no":3,"bullet":"Health Canada determined that the overall benefits of TECFIDERA continue to outweigh the risks when used as recommended. However, an update to the Canadian prescribing information will now provide additional information on the risk of hypersensitivity."}],"footnotes_list":[{"field_id":116,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":113,"order_no":1,"bullet":"TECFIDERA is used to treat multiple sclerosis, a debilitating disease in which the immune system attacks the protective cover (myelin) of the nerves to disrupt communication between the brain and spinal cord with the rest of the body. Currently, there is no cure for multiple sclerosis."},{"field_id":113,"order_no":2,"bullet":"TECFIDERA helps to reduce the number of flare-ups (relapses) that occur and slows the progression of physical disability. It works by changing the way the body's immune system functions, helping to keep it from further damaging the brain and the spinal cord."},{"field_id":113,"order_no":3,"bullet":"TECFIDERA was first marketed in Canada on April 12, 2013."}],"finding_list":[{"field_id":114,"order_no":1,"bullet":"At the time of this review, Health Canada considered the evidence provided in both domestic and international reports, including those provided by the product manufacturer, of hypersensitivity associated with TECFIDERA."},{"field_id":114,"order_no":2,"bullet":"Up until June 30, 2014, the Canada Vigilance Program received 9 Canadian reports of hypersensitivity associated with TECFIDERA.a Of these cases, 4 were possibly or likely associated with TECFIDERA."},{"field_id":114,"order_no":3,"bullet":"Five international cases, which reported life-threatening anaphylactic events, were possibly or likely associated with TECFIDERA."},{"field_id":114,"order_no":4,"bullet":"Overall, the number of hypersensitivity reactions has been increasing for TECFIDERA with some reports being life-threatening. This increase may be due to a greater use of TECFIDERA."}],"conclusion_list":[{"field_id":115,"order_no":1,"bullet":"Health Canada concluded that the overall benefits of TECFIDERA continue to outweigh the risks when used as recommended."},{"field_id":115,"order_no":2,"bullet":"The Canadian prescribing information for TECFIDERA was updated to inform prescribers and patients of hypersensitivity reactions, including angioedema and anaphylaxis."},{"field_id":115,"order_no":3,"bullet":"During the safety review by Health Canada, the Canadian prescribing information was also updated to mention that the possibility of hypersensitivity or anaphylactic reactions should be considered in patients experiencing severe flushing reactions (e.g. flushing, hot flushes, warmth, redness, itching, and/or burning sensations). These symptoms may present similarities with hypersensitivity reactions."},{"field_id":115,"order_no":4,"bullet":"Health Canada will continue to monitor adverse reaction information involving TECFIDERA, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new information on this risk is identified."}]},{"template":2,"link_id":"SSR00026","review_date":null,"drug_name":"PROLIA (denosumab)","safety_issue":"Cardiovascular events","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":122,"overview":"A safety review was initiated to evaluate the potential risk of heart problems (cardiovascular adverse events) associated with the use of PROLIA (denosumab 60 mg). This issue was identified during a routine Health Canada review of safety information provided by the manufacturer.","use_canada":123,"findings":124,"conclusion":125,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":126,"title":"Summary Safety Review - PROLIA (denosumab) - Cardiovascular events","created_date":"2015-05-29","modified_date":null,"key_message_list":[{"field_id":122,"order_no":1,"bullet":"PROLIA (denosumab 60 mg) is a unique immune system protein (monoclonal antibody), which works by binding to and inhibiting specific cells that remove bone mass to slow bone loss and increase bone strength."},{"field_id":122,"order_no":2,"bullet":"A safety review was initiated to evaluate the potential risk of heart problems (cardiovascular adverse events) associated with the use of PROLIA and found no such association."},{"field_id":122,"order_no":3,"bullet":"The Canadian prescribing information for PROLIA already labels for low calcium levels in the blood (hypocalcemia), which can contribute to an increased risk of heart rhythm problems (cardiac arrhythmia)."}],"footnotes_list":[{"field_id":126,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":123,"order_no":1,"bullet":"Denosumab is marketed under the brand name PROLIA and has been available in Canada since 2010. Denosumab is also present in another medicine called XGEVA."},{"field_id":123,"order_no":2,"bullet":"PROLIA is a unique immune system protein (monoclonal antibody), which works by binding to and inhibiting specific cells that remove bone mass to slow bone loss and increase bone strength."},{"field_id":123,"order_no":3,"bullet":"It is used to treat postmenopausal women and men with weak and brittle bones (osteoporosis) at high risk of breaking their bones (fracture)."},{"field_id":123,"order_no":4,"bullet":"It is used to increase bone mass in men with prostate cancer that has not spread (nonmetastatic) and who are taking medicine to block the production of male hormones (androgen deprivation therapy)."},{"field_id":123,"order_no":5,"bullet":"It is used to increase bone mass in women with breast cancer that has not spread (nonmetastatic), who are taking medicine to block the production of female hormones (adjuvant aromatase inhibitor therapy)."}],"finding_list":[{"field_id":124,"order_no":1,"bullet":"In the safety review, the term \"cardiovascular adverse events\" was used to explain coronary artery disease, heart failure, and cardiac arrhythmia. Coronary artery disease occurs when plaques build up in the arteries of the heart, which could lead to a heart attack. Heart failure is a chronic condition in which the heart muscle is unable to pump enough blood to meet the body's needs for blood and oxygen. Cardiac arrhythmia refers to any change in the normal rhythm of the heart's electrical impulses."},{"field_id":124,"order_no":2,"bullet":"As of June 30, 2014, Health Canadaa identified three cases of heart rhythm problems (QT interval prolongation) as possibly related to low blood calcium (hypocalcemia) due to use of PROLIA. Because hypocalcemia is known to be associated with the use of PROLIA, the Canadian prescribing information already labels for this risk."},{"field_id":124,"order_no":3,"bullet":"In a review of international safety data provided by the manufacturer, the majority of the reports of the cases of cardiovascular adverse events occurred in patients who had other pre-existing risk factors or where information about the patients was incomplete. It was therefore difficult to determine whether the cardiovascular adverse events were caused by the use of PROLIA or were due to other reasons. Overall, the evidence did not suggest an increased risk of cardiovascular adverse events associated with the use of PROLIA."},{"field_id":124,"order_no":4,"bullet":"A review of the scientific and medical literature identified four research articles relevant to the topic of cardiovascular adverse events associated with the use of PROLIA. However, the frequency of cardiovascular adverse events associated with the use of PROLIA was comparable to placebo (sugar pill). As such, the link between the use of PROLIA and cardiovascular adverse events could not be concluded."}],"conclusion_list":[{"field_id":125,"order_no":1,"bullet":"At this time, the available evidence does not support an association between PROLIA and the risk of cardiovascular adverse events. In addition, the risk of low blood calcium and its effects on heart rhythm (e.g. QT interval prolongation) is already described in the Canadian prescribing information for PROLIA."},{"field_id":125,"order_no":2,"bullet":"Health Canada will continue to monitor adverse reaction information involving PROLIA, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00027","review_date":null,"drug_name":"NEXAVAR (sorafenib)","safety_issue":"Thyroid gland dysfunction","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":127,"overview":"A safety review studied the risk of drug-induced thyroid gland dysfunction associated with NEXAVAR. Thyroid gland dysfunction happens when the levels of the hormones that the thyroid gland makes are too high (hyperthyroidism) or too low (hypothyroidism). Thyroid gland dysfunction can impact metabolism as well as many other functions of the body. The safety review was triggered by a published fatal case of an elderly man who developed thyroid storm three weeks after he began treatment with NEXAVAR. Thyroid storm is a life-threatening form of hyperthyroidism.","use_canada":128,"findings":129,"conclusion":130,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":131,"title":"Summary Safety Review - NEXAVAR (sorafenib) - Thyroid Gland Dysfunction","created_date":"2015-05-28","modified_date":null,"key_message_list":[{"field_id":127,"order_no":1,"bullet":"NEXAVAR (sorafenib) is an anti-cancer drug from the multikinase inhibitor family of drugs used to treat specific types of liver, kidney, and thyroid cancers in adults."},{"field_id":127,"order_no":2,"bullet":"A safety review was done after a case of severe hyperthyroidism, called thyroid storm, associated with use of NEXAVAR was reported in a scientific journal. Hyperthyroidism is a type of thyroid gland dysfunction where excessive amounts of thyroid hormones are released into the blood that may cause fast heartbeat, tiredness, weight loss, nervousness and/or trembling."},{"field_id":127,"order_no":3,"bullet":"As a result of this safety review, the Canadian prescribing information for NEXAVAR has been updated to inform healthcare professionals, caregivers, and patients about the risks of thyroid gland dysfunction and the need to monitor thyroid function before and during use. The risk of thyroid gland dysfunction is already included in the Canadian prescribing information for other multikinase inhibitors."}],"footnotes_list":[{"field_id":131,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":128,"order_no":1,"bullet":"NEXAVAR is an anti-cancer drug from the multikinase inhibitor family of drugs used in adults. Although not widely used, it is for the treatment of specific types of relatively rare and advanced cancers, including liver, kidney, and thyroid cancers."},{"field_id":128,"order_no":2,"bullet":"NEXAVAR works by blocking the growth and spread of cancer cells."},{"field_id":128,"order_no":3,"bullet":"It was first marketed in Canada on July 31, 2006."}],"finding_list":[{"field_id":129,"order_no":1,"bullet":"Thyroid gland dysfunction may occur with NEXAVAR use, including, very rarely, thyroid storm."},{"field_id":129,"order_no":2,"bullet":"There were many case reports of thyroid gland dysfunction associated with the use of NEXAVAR in the scientific literature, manufacturer's database and the World Health Organization's database at the time of this safety review. The analysis of the cases showed evidence of thyroid disorders in association with NEXAVAR use. Up until January 31, 2015, there were no Canadian reports of thyroid gland dysfunction received through the Canada Vigilance Program.a"},{"field_id":129,"order_no":3,"bullet":"Canadian prescribing information for other multikinase inhibitors (e.g. Sunitinib, Pazopanib and Axitinib) already contains information on thyroid dysfunction."}],"conclusion_list":[{"field_id":130,"order_no":1,"bullet":"Health Canada's safety review showed evidence of thyroid gland disorders in association with NEXAVAR use."},{"field_id":130,"order_no":2,"bullet":"As a result of this safety review, Health Canada has updated the Canadian prescribing information for NEXAVAR (sorafenib) to inform healthcare professionals, caregivers, and patients about the risks of thyroid dysfunction. Thyroid function monitoring should be considered before and during NEXAVAR use."},{"field_id":130,"order_no":3,"bullet":"Health Canada will publish a safety information update in the May 2015 issue of the Health Product InfoWatch."}]},{"template":2,"link_id":"SSR00028","review_date":null,"drug_name":"Uloric (febuxostat)","safety_issue":"Agranulocytosis (severe reduction in the number of white blood cells)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":132,"overview":"A safety review was initiated following the identification of international cases of ULORIC-associated agranulocytosis. Agranulocytosis is a condition involving a severe reduction in the number of white blood cells. Patients with this condition are at increased risk of infectious diseases given that white blood cells protect the body against infections.","use_canada":133,"findings":134,"conclusion":135,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":136,"footnotes":0,"title":"Summary Safety Review - ULORIC (febuxostat) - Agranulocytosis (severe reduction in the number of white blood cells)","created_date":"2015-05-28","modified_date":null,"key_message_list":[{"field_id":132,"order_no":1,"bullet":"ULORIC is an oral medication used to lower uric acid levels in patients with gout (a painful form of arthritis)."},{"field_id":132,"order_no":2,"bullet":"A safety review was initiated following the identification of international cases of ULORIC-associated agranulocytosis."},{"field_id":132,"order_no":3,"bullet":"At the time of this review, there were no reported cases of agranulocytosis suspected of being associated with ULORIC in Canada."},{"field_id":132,"order_no":4,"bullet":"Health Canada has requested that the manufacturer submit information updates on the safety of ULORIC which Health Canada will monitor and assess."}],"footnotes_list":[],"reference_list":[{"field_id":136,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":136,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."},{"field_id":136,"order_no":3,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":136,"order_no":4,"bullet":"Kobayashi S, Ogura M, Hosoya T. Acute neutropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease. J Clin Pharm Ther 2013;38(3): 258-61."}],"use_canada_list":[{"field_id":133,"order_no":1,"bullet":"ULORIC is an oral medication used to lower uric acid levels in patients with gout (a painful inflammation of an articulation due to uric acid forming hard crystals in the joint)."},{"field_id":133,"order_no":2,"bullet":"It was first marketed in Canada on September 30, 2010."},{"field_id":133,"order_no":3,"bullet":"There were approximately 64,000 prescriptions for ULORIC in Canada in 2013, which increased to approximately 82,000 in 2014.1 In comparison, allopurinol, the most commonly used medication to treat gout accounted for 2,827,000 prescriptions in 2013, and 2,903,282 prescriptions in 2014.1 Therefore, for each ULORIC prescription in Canada, there were approximately 40 prescriptions for allopurinol."}],"finding_list":[{"field_id":134,"order_no":1,"bullet":"At the time of this review, there were no reported cases of agranulocytosis suspected of being associated with the use of ULORIC in Canada.2"},{"field_id":134,"order_no":2,"bullet":"The World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) contained 13 international cases of agranulocytosis suspected of being associated with the use of ULORIC.3"},{"field_id":134,"order_no":3,"bullet":"Two cases of ULORIC associated-neutropenia (an abnormally low number of neutrophils - a type of white blood cell) were published in the scientific literature.4 Although neutropenia can occur without agranulocytosis, it is an important component of agranulocytosis. In both cases, while the patients may have been exposed to other medications that could have contributed to this reaction, the use of ULORIC was considered the probable cause of the neutropenia."},{"field_id":134,"order_no":4,"bullet":"Agranulocytosis has also been reported in patients taking allopurinol, a drug which has been on the Canadian market for decades. The prescribing information for allopurinol mentions the risk of agranulocytosis."}],"conclusion_list":[{"field_id":135,"order_no":1,"bullet":"There are international cases of agranulocytosis that are associated with the use of ULORIC. It is important to note that Health Canada has not received any adverse reaction reports related to this issue."},{"field_id":135,"order_no":2,"bullet":"Health Canada has requested that the manufacturer submit information updates on the safety of ULORIC which Health Canada will monitor and assess."},{"field_id":135,"order_no":3,"bullet":"Health Canada will publish an article in the May 2015 issue of the Health Product InfoWatch to raise awareness and to encourage the reporting of related adverse reactions with ULORIC use."},{"field_id":135,"order_no":4,"bullet":"Health Canada will continue to monitor adverse reaction information involving all health products to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified."}]},{"template":2,"link_id":"SSR00029","review_date":null,"drug_name":"SEVORANE AF (sevoflurane) and generics","safety_issue":"Severe low heart rate in children with Down syndrome","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":137,"overview":"A safety review was initiated to evaluate the possible link between a severe lowering of the heart rate (a medical condition known as severe bradycardia) and the use of the general anaesthetic sevoflurane (SEVORANE AF and generics) in children with Down syndrome. This issue was identified by Health Canada during routine review of safety information provided by the manufacturer.","use_canada":138,"findings":139,"conclusion":140,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - SEVORANE AF (sevoflurane) - Severe low heart rate in children with Down syndrome","created_date":"2015-05-13","modified_date":null,"key_message_list":[{"field_id":137,"order_no":1,"bullet":"Sevoflurane is used as a general anaesthetic during surgery to make a patient unconscious and unable to feel pain."},{"field_id":137,"order_no":2,"bullet":"Health Canada noted differences between the sevoflurane prescribing information of different companies regarding the potential risk of severe lowering of the heart rate (severe bradycardia) in children with Down syndrome. Health Canada initiated a safety review to evaluate this issue further."},{"field_id":137,"order_no":3,"bullet":"The Canadian prescribing information for the product marketed under the brand name SEVORANE AF has been updated to highlight the occurrence of cases of bradycardia in pediatric patients with Down syndrome exposed to sevoflurane. Manufacturers of generic versions of this drug are in the process of updating their product information."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":138,"order_no":1,"bullet":"Sevoflurane is used as a general anaesthetic during surgery in adults and children to make them unconscious and unable to feel pain. It is used in hospitals and is administered only by persons trained in the administration of general anaesthesia."},{"field_id":138,"order_no":2,"bullet":"In Canada, sevoflurane is the most widely used inhalational general anaesthetic. Its use has remained constant over the last five years."},{"field_id":138,"order_no":3,"bullet":"Sevoflurane is administered through a vaporizer mask and is breathed into the lungs (inhalational)."},{"field_id":138,"order_no":4,"bullet":"It has been marketed in Canada since 1995."}],"finding_list":[{"field_id":139,"order_no":1,"bullet":"Bradycardia is defined as a heart rate below the lowest normal values which vary according to age group. If bradycardia is severe, slowing of the heart can occur to the point that the heart stops. Severe bradycardia can be treated with certain medications and interventions to restore normal heart rate. Complications of anaesthesia can occur in all patient populations. However some complications including bradycardia are more likely to occur in people with Down syndrome due to pre-existing heart defects and/or problems with the nervous system and muscles (neuromuscular problems)."},{"field_id":139,"order_no":2,"bullet":"At the time of the review, the Canadian prescribing information for sevoflurane products documented the incidence of bradycardia in children. Although the information available to prescribers did not directly address the risk of severe bradycardia in children with Down syndrome, it did address the risk in vulnerable children with and without additional medical conditions associated with neuromuscular problems which would include children with Down syndrome."},{"field_id":139,"order_no":3,"bullet":"At the time of the review, Health Canada had not received any reports of sevoflurane-associated bradycardia in children with Down syndrome. International reports of severe bradycardia in children with Down syndrome suspected to be associated with sevoflurane use were provided by the company that first marketed sevoflurane."},{"field_id":139,"order_no":4,"bullet":"A review of the scientific and medical literature identified a number of research articles relevant to the topic of bradycardia in children with Down syndrome associated with sevoflurane use. The information contained in these articles was limited in terms of both the number and quality of case reports. However, these articles highlighted the possibility of sevoflurane-induced bradycardia in children with Down syndrome. At the time of the review, the Canadian prescribing information was similar to the United States and European prescribing information with respect to the risk of bradycardia in vulnerable pediatric populations, especially those with problems with the nervous system and muscles (neuromuscular problems)."}],"conclusion_list":[{"field_id":140,"order_no":1,"bullet":"The risk of bradycardia (slowing of the heart rate) with sevoflurane should be considered for all children. The prescribing information for sevoflurane mentions the risk of bradycardia in healthy children and in children with neuromuscular problems. It is being updated to mention the occurrence of cases of bradycardia in children with Down syndrome."},{"field_id":140,"order_no":2,"bullet":"Health Canada will continue to monitor adverse reaction information involving sevoflurane, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new information on this risk is identified."}]},{"template":2,"link_id":"SSR00030","review_date":null,"drug_name":"Goldenseal (Hydrastis canadensis)","safety_issue":"Herb-Drug Interaction","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":141,"overview":"A safety review was initiated by Health Canada to evaluate the currently available information regarding the potential risk of herb-drug interactions associated with the herbal ingredient goldenseal. This review was prompted by an articlea published by the New Zealand Medicines and Medical Devices Safety Authority (MedSafe). This article mentioned goldenseal, among other herbal ingredients and food products, as having a potential risk for interaction with certain medications (through certain cytochrome P450 enzymes).","use_canada":489,"findings":143,"conclusion":144,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":145,"title":"Summary Safety Review - Goldenseal - Potential Herb-Drug Interaction","created_date":"2015-04-30","modified_date":null,"key_message_list":[{"field_id":141,"order_no":1,"bullet":"In Canada, goldenseal is a herbal ingredient traditionally used in herbal medicine to aid or alleviate a variety of digestive disorders."},{"field_id":141,"order_no":2,"bullet":"A safety review was initiated following the publication of an article by the New Zealand Medicines and Medical Devices Safety Authority (MedSafe). This article discussed herbal and food interactions, and included the potential risk of goldenseal and drug interactions (liver cytochrome P450 enzymes)."}],"footnotes_list":[{"field_id":145,"order_no":1,"bullet":"Medsafe. Drug Metabolism - The Importance of Cytochrome P450 3A4. Prescriber Update 2014;35(1):4-6."}],"reference_list":[],"use_canada_list":[{"field_id":489,"order_no":1,"bullet":"In Canada, goldenseal-containing oral health products are traditionally used in herbal medicine for aiding or alleviating a variety of digestive problems such as indigestion or heartburn, infectious and inflammatory conditions of the digestive tract such as inflammation of the lining of the stomach (gastritis), or to increase appetite. Health Canada has licensed several hundred natural health products (NHPs) that have goldenseal listed as a medicinal ingredient."}],"finding_list":[{"field_id":143,"order_no":1,"bullet":"There were no Canadian or international reports of adverse reactions assessed by Health Canada as having been associated with interactions between goldenseal-containing health products and other health products or medications. Side effects with all medications, and in particular NHPs, are known to be underreported."},{"field_id":143,"order_no":2,"bullet":"Some published studies have shown that goldenseal can slow down the activity of certain enzymes referred to as \"cytochrome P450 enzymes\" mainly in the liver. These enzymes are responsible for processing and eliminating many substances that are orally ingested, including medications (e.g., certain antidepressant drugs, anti-infective drugs, anti-anxiety drugs, cardiovascular drugs, cholesterol lowering drugs, etc.)."},{"field_id":143,"order_no":3,"bullet":"By slowing down the rate of these processing and eliminating enzymes, certain medications could remain in the body for longer than normal, potentially reaching toxic levels. In some cases, medications are given in their inactive form and require processing by these enzymes to become activated in the body."},{"field_id":143,"order_no":4,"bullet":"Health Canada has identified that many other factors can also affect the potential for any herb-drug interaction, including genetics, age and health status as well as the type, dose, timing and composition of health products being used together."}],"conclusion_list":[{"field_id":144,"order_no":1,"bullet":"The current available evidence suggests that use of oral goldenseal may contribute to herb-drug interactions, but the data is limited and no domestic or international cases of goldenseal-drug interactions are known to Health Canada."},{"field_id":144,"order_no":2,"bullet":"At this time, Health Canada will continue to monitor adverse reaction information for oral goldenseal-containing health products, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified."},{"field_id":144,"order_no":3,"bullet":"Health Canada will publish an article in the April 2015 issue of the Health Product InfoWatch to raise awareness and to encourage the reporting of related adverse reactions with goldenseal."}]},{"template":2,"link_id":"SSR00031","review_date":null,"drug_name":"Oral Ibuprofen (Non-steroidal Anti-inflammatory Drug; NSAID)","safety_issue":"Risk of serious heart and stroke adverse events at high doses","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":146,"overview":"A safety review was initiated by Health Canada to evaluate the possible link between heart and stroke related adverse events and the use of ibuprofen especially at high doses compared to other NSAIDs, including cyclo-oxygenase-2 (COX-2) selective inhibitors like celecoxib (Celebrex). This issue was identified by a published study, which found that ibuprofen at a daily dose of 2400 mg or more increased the risk of serious heart and stroke related adverse events. These findings were comparable to those associated with COX-2 inhibitors.","use_canada":147,"findings":148,"conclusion":149,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":150,"footnotes":624,"title":"Summary Safety Review - Prescription Oral Ibuprofen (Non-Steroidal Anti-inflammatory Drug) - Risk of Serious Heart and Stroke Adverse Events at High Doses","created_date":"2015-04-23","modified_date":"2016-02-01","key_message_list":[{"field_id":146,"order_no":1,"bullet":"Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain, reduce fever, and relieve inflammation."},{"field_id":146,"order_no":2,"bullet":"A safety review was initiated by Health Canada following the publication of a study, suggesting that ibuprofen at a daily dose of 2400 mg or higher increased the risk of serious heart and stroke related adverse events."},{"field_id":146,"order_no":3,"bullet":"Health Canada's safety review determined that the overall benefits of ibuprofen continue to outweigh the risk when used as recommended. No evidence of an increased cardiovascular risk has been found for over-the-counter oral ibuprofen at a maximum daily dose of 1200 mg or less when taken for a short duration of time (7 days or less)."},{"field_id":146,"order_no":4,"bullet":"Prescription oral ibuprofen at high doses (a daily dose of 2400 mg or more) has been found to be associated with an increased risk of heart attack and stroke, especially in patients having a history of, or risk factors for heart disease or stroke. This risk increases with dose and duration of use. The maximum recommended daily dose for prescription ibuprofen in Canada is 2400 mg"}],"footnotes_list":[{"field_id":624,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[{"field_id":150,"order_no":1,"bullet":"Bhala N, Emberson J, Merhi A, et al. Coxib and traditional NSAID trialist CNT Collaboration group: Vascular and upper gastrointestinal effects on non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.Lancet 2013;382:769-79."}],"use_canada_list":[{"field_id":147,"order_no":1,"bullet":"Most ibuprofen-containing products are sold as over-the-counter drugs for use by adults and children to treat pain, reduce fever, and relieve inflammation. These products contain 400 mg or less of ibuprofen, and the maximum recommended daily dose of ibuprofen for these products is 1200 mg."},{"field_id":147,"order_no":2,"bullet":"Products containing 600 mg of ibuprofen are available by prescription only for use by adults and children above 12 years to relieve the symptoms of arthritis (osteoarthritis and rheumatoid arthritis). The maximum recommended daily dose of ibuprofen for these prescription products is 2400 mg."},{"field_id":147,"order_no":3,"bullet":"Approximately 780 000 prescriptions for 600 mg strength oral ibuprofen have been issued each year in Canada over the last 5 years (2010-2014)."}],"finding_list":[{"field_id":148,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 26 Canadian case reportsa of serious heart and stroke related adverse events suspected of being associated with ibuprofen use. In the majority of these reports, the daily doses were unknown. Of these reports, 15 cases were further evaluated to determine whether the use of ibuprofen was the cause of the heart and stroke related adverse events. Ibuprofen was found to be a possible cause of these adverse events in 11 of these cases."},{"field_id":148,"order_no":2,"bullet":"Epidemiological data analyzed in the safety review suggested that there may be a slight increased risk of heart attack and stroke associated with ibuprofen at a daily dosage range between 1800 and 2400 mg, however additional studies would be needed to further assess this potential risk."},{"field_id":148,"order_no":3,"bullet":"The safety review found that patients who take oral ibuprofen at a prescription daily dose of 2400 mg or more have an increased risk of heart attack and stroke when compared to patients who do not use ibuprofen. The risk is comparable to patients who take COX-2 inhibitors, a subgroup of NSAIDS that includes celecoxib. The risk increases when ibuprofen is taken for a long duration and among patients having a history of, or risk factors for heart disease, stroke, or uncontrolled blood pressure."}],"conclusion_list":[{"field_id":149,"order_no":1,"bullet":"Health Canada concluded that there was evidence of an association between oral ibuprofen at a daily dose of 2400 mg or more and an increased risk of heart attack and stroke related adverse events. This is comparable to those associated with COX-2 inhibitors. The overall benefits of ibuprofen continue to outweigh the risks when used as recommended."},{"field_id":149,"order_no":2,"bullet":"Oral ibuprofen at a daily dose of 2400 mg should be avoided in patients with ischemic heart disease, cerebrovascular disease, congestive heart failure or with risk factors for cardiovascular disease."},{"field_id":149,"order_no":3,"bullet":"The Canadian prescribing information for ibuprofen-containing products will be updated to reflect this new information."},{"field_id":149,"order_no":4,"bullet":"The safety review did not find any evidence to show that ibuprofen presented an increased cardiovascular risk for over-the-counter use at the maximum daily dose of 1200 mg or less."},{"field_id":149,"order_no":5,"bullet":"Health Canada continues to monitor the risk of heart attack and stroke associated with oral ibuprofen at a daily dose range between 1800 mg and 2400 mg. As new studies become available, these will be assessed and regulatory actions taken as appropriate."},{"field_id":149,"order_no":6,"bullet":"Health Canada will continue to monitor adverse reaction information involving ibuprofen, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new information on this risk is identified."}]},{"template":2,"link_id":"SSR00032","review_date":null,"drug_name":"Methylphenidate","safety_issue":"Priapism","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":151,"overview":"A safety review was initiated to evaluate the available information regarding the potential risk of priapism associated with the use of methylphenidate products in the treatment of attention-deficit hyperactivity disorder (ADHD). Priapism is a prolonged and usually painful erection of the penis; it is considered a medical emergency. This review was prompted by actions by the United States Food and Drug Administration (FDA) indicating that all methylphenidate product labels and patient Medication Guides be updated to include information about the risk of priapism.","use_canada":152,"findings":153,"conclusion":154,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":155,"title":"Summary Safety Review - Methylphenidate - Priapism","created_date":"2015-04-21","modified_date":null,"key_message_list":[{"field_id":151,"order_no":1,"bullet":"Methylphenidate products are used for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and children 6 years of age and over."},{"field_id":151,"order_no":2,"bullet":"A safety review was initiated following the actions by the United States Food and Drug Administration (FDA) indicating that all methylphenidate product labels and patient Medication Guides be updated to include information about the risk of priapism. Priapism (prolonged and painful erection) is a rare but serious adverse reaction."},{"field_id":151,"order_no":3,"bullet":"The Canadian prescribing information for all brand name and generic methylphenidate products will be updated to include the risk of priapism."}],"footnotes_list":[{"field_id":155,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."},{"field_id":155,"order_no":2,"bullet":"Since the completion of the Safety Review, an additional case has been received by Health Canada."}],"reference_list":[],"use_canada_list":[{"field_id":152,"order_no":1,"bullet":"Methylphenidate is marketed under the brand names of BIPHENTIN, CONCERTA, RITALIN and RITALIN SR, and 16 generic methylphenidate products currently available in Canada."},{"field_id":152,"order_no":2,"bullet":"Methylphenidate products are used for the treatment of ADHD in adults and children 6 years of age and over."}],"finding_list":[{"field_id":153,"order_no":1,"bullet":"Priapism is rare. It is a serious medical condition that requires immediate medical attention to prevent possible long-term effects on the penis.Drugs are a known cause."},{"field_id":153,"order_no":2,"bullet":"At the time of this review, Health Canada had received one report of priapism associated with the use of methylphenidate.a b A description of this case was published in the Canadian Adverse Reaction Newsletter in July 2006"},{"field_id":153,"order_no":3,"bullet":"There were a small number of cases of priapism in association with methylphenidate products reported internationally and in the literature. In nearly half of these cases, methylphenidate products were found to be the probable cause of priapism."},{"field_id":153,"order_no":4,"bullet":"Priapism has been reported during treatment with methylphenidate products after increasing the dose or stopping the product even for a short period of time."}],"conclusion_list":[{"field_id":154,"order_no":1,"bullet":"Although there was only one report of priapism associated with methylphenidate in Canada, Health Canada's actions take into account the international experience with this rare, but serious adverse reaction."},{"field_id":154,"order_no":2,"bullet":"There is limited but good quality evidence of a possible association between priapism and the use of methylphenidate products."},{"field_id":154,"order_no":3,"bullet":"The Canadian prescribing information for all brand name and generic methylphenidate products will be updated to include the very rare risk of priapism."},{"field_id":154,"order_no":4,"bullet":"Health Canada issued a communication to inform healthcare professionals and patients about the possibility of priapism associated with the use of methylphenidate products."},{"field_id":154,"order_no":5,"bullet":"Health Canada will continue to monitor and evaluate the risk of priapism associated with the use of methylphenidate products. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified"}]},{"template":2,"link_id":"SSR00033","review_date":null,"drug_name":"Methylphenidate","safety_issue":"Suicidality","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":156,"overview":"A safety review was initiated to evaluate the available information regarding the potential risk of suicidal thoughts and behaviours, called suicidality, with the use of methylphenidate products used to treat attention-deficit hyperactivity disorder (ADHD). The findings of a recently completed review of amphetamines and the potential risk of suicidality raised the question of whether other stimulant drugs, like methylphenidate products, had a similar risk. This review was prompted by the reporting of suicidal adverse events associated with methylphenidate products to Health Canada.","use_canada":157,"findings":158,"conclusion":159,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":160,"title":"Summary Safety Review - Methylphenidate - Suicidal Thoughts and Behaviour (Suicidality)","created_date":"2015-03-30","modified_date":null,"key_message_list":[{"field_id":156,"order_no":1,"bullet":"Methylphenidate products are used for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and children 6 years of age and older."},{"field_id":156,"order_no":2,"bullet":"A safety review was initiated after Health Canada received reports of suicidality associated with methylphenidate products."},{"field_id":156,"order_no":3,"bullet":"The Canadian prescribing information for brand name and generic methylphenidate products will be updated to inform Canadians that rare cases of suicidality were reported in patients taking methylphenidate products. Although there is limited evidence showing that methylphenidate was the cause of suicidality, it is recommended that patients be monitored for signs of suicidality."}],"footnotes_list":[{"field_id":160,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":157,"order_no":1,"bullet":"Methylphenidate is marketed under the brand names of BIPHENTIN, CONCERTA, RITALIN and RITALIN SR. and 16 generic methylphenidate products in Canada, at the time of this review."},{"field_id":157,"order_no":2,"bullet":"Methylphenidate products are used for the treatment of ADHD in adults and children 6 years of age and older."}],"finding_list":[{"field_id":158,"order_no":1,"bullet":"Methylphenidate products are commonly used in children in Canada."},{"field_id":158,"order_no":2,"bullet":"Cases of suicidality have been reported with the use of methylphenidate for the treatment of ADHD in Canadaa and internationally."},{"field_id":158,"order_no":3,"bullet":"ADHD can be associated with other mental health conditions that may increase the risk of suicidal thoughts and behaviours."},{"field_id":158,"order_no":4,"bullet":"While most Canadian reports were about suicidal thoughts, a small number of suicide attempts and suicides were also reported. In general, the review of Canadian cases suggests that the use of methylphenidate products may contribute to suicidal thoughts or actions in some patients with ADHD, either alone or in association with other mental health conditions."}],"conclusion_list":[{"field_id":159,"order_no":1,"bullet":"Cases of suicidality have been reported with the use of methylphenidate products for the treatment of ADHD. However, there is limited evidence showing that methylphenidate products were the cause of suicidality."},{"field_id":159,"order_no":2,"bullet":"The Canadian prescribing information for brand name and generic methylphenidate products will be updated to inform Canadians that rare cases of suicidality were reported in patients taking methylphenidate products, recommend that patients be monitored for signs of suicidality, and encourage patients to report any distressing thoughts or feelings to their healthcare professional."},{"field_id":159,"order_no":3,"bullet":"Health Canada has issued a communication to inform Canadians about the risk of suicidality associated with the use of methylphenidate products."},{"field_id":159,"order_no":4,"bullet":"Health Canada will continue to monitor and evaluate the risk of suicidality associated with the use of methylphenidate products. It will keep Canadians informed and take action, as appropriate, if any new safety information is identified."}]},{"template":2,"link_id":"SSR00034","review_date":null,"drug_name":"Amphetamines","safety_issue":"Suicidality","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":161,"overview":"A safety review was initiated to evaluate the available information regarding the potential risk of suicidal thoughts and behaviours, called suicidality, with the use of amphetamine products used to treat attention-deficit hyperactivity disorder (ADHD). This review was prompted by the reporting of suicidal adverse events associated with amphetamine products to Health Canada.","use_canada":162,"findings":163,"conclusion":164,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":165,"title":"Summary Safety Review - Amphetamines - Suicidal Thoughts and Behaviours (Suicidality)","created_date":"2015-03-30","modified_date":null,"key_message_list":[{"field_id":161,"order_no":1,"bullet":"Amphetamine products (amphetamine, dextroamphetamine and lisdexamfetamine) are used for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and children 6 years of age and older."},{"field_id":161,"order_no":2,"bullet":"A safety review was initiated after Health Canada received reports of suicidality associated with amphetamine products."},{"field_id":161,"order_no":3,"bullet":"The Canadian prescribing information for all amphetamine products will be updated to inform Canadians that rare cases of suicidality were reported in patients taking amphetamine products. Although there is limited evidence showing that amphetamine was the cause of suicidality, it is recommended that patients be monitored for signs of suicidality."}],"footnotes_list":[{"field_id":165,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":162,"order_no":1,"bullet":"Amphetamine products are marketed under the brand names of DEXEDRINE (dextroamphetamine sulfate), ADDERALL XR (mixed salts amphetamine extended-release), and VYVANSE (lisdexamfetamine dimesylate)."},{"field_id":162,"order_no":2,"bullet":"Amphetamine products are used for the treatment of ADHD in adults and children 6 years of age and older."}],"finding_list":[{"field_id":163,"order_no":1,"bullet":"Amphetamine products are commonly used in children in Canada."},{"field_id":163,"order_no":2,"bullet":"Cases of suicidality have been reported with the use of amphetamine products for the treatment of ADHD in Canadaa and internationally."},{"field_id":163,"order_no":3,"bullet":"ADHD can be associated with other mental health conditions that may increase the risk of suicidal thoughts and behaviours."},{"field_id":163,"order_no":4,"bullet":"While most Canadian reports were about suicidal thoughts, a small number of suicide attempts and suicides were also reported. In general, the review of Canadian cases suggests that the use of amphetamine products may contribute to suicidal thoughts or actions in some patients with ADHD, either alone or in association with other mental conditions."},{"field_id":163,"order_no":5,"bullet":"At present, there is little information in the scientific literature to determine the role of amphetamine products in causing suicidality."}],"conclusion_list":[{"field_id":164,"order_no":1,"bullet":"Cases of suicidality have been reported with the use of amphetamine products for the treatment of ADHD. However, there is limited evidence showing that amphetamines were the cause of suicidality."},{"field_id":164,"order_no":2,"bullet":"The Canadian prescribing information for all amphetamine products will be updated to inform Canadians that rare cases of suicidality were reported in patients taking amphetamines, recommend that patients be monitored for signs of suicidality, and encourage patients to report any distressing thoughts or feelings to their healthcare professional."},{"field_id":164,"order_no":3,"bullet":"Health Canada has issued a communication to inform Canadians about the risk of suicidality associated with amphetamine products."},{"field_id":164,"order_no":4,"bullet":"Health Canada will continue to monitor and evaluate the risk of suicidality associated with the use of amphetamine products. It will keep Canadians informed and take action, as appropriate, if any new safety information is identified."}]},{"template":2,"link_id":"SSR00035","review_date":null,"drug_name":"Tumour necrosis factor (TNF) blockers","safety_issue":"Glioblastoma (brain tumour)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":166,"overview":"A safety review was initiated to evaluate the currently available information regarding the possibility of an increased risk of the cancerous (malignant) brain tumour called glioblastoma/glioblastoma multiforme following exposure to TNF blockers. This potential safety issue was identified as part of Health Canada's ongoing monitoring of safety information shared by other regulatory agencies.","use_canada":167,"findings":169,"conclusion":170,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":171,"title":"Summary Safety Review - Tumour necrosis factor (TNF) blockers - Glioblastoma (brain tumour)","created_date":"2015-03-18","modified_date":null,"key_message_list":[{"field_id":166,"order_no":1,"bullet":"TNF blockers are a class of drugs used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), and psoriasis."},{"field_id":166,"order_no":2,"bullet":"A safety review was initiated as part of Health Canada's ongoing monitoring of the safety of these products."},{"field_id":166,"order_no":3,"bullet":"Given the evidence available at the time of this review, no increased risk of glioblastoma after exposure to a TNF blocker was found."}],"footnotes_list":[{"field_id":171,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":167,"order_no":1,"bullet":"TNF blockers are used to treat specific inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g., Crohn's or ulcerative colitis), and psoriasis."},{"field_id":167,"order_no":2,"bullet":"At the time of the review, the following TNF blockers were marketed in Canada:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":176,"title":"Summary Safety Review - ZELBORAF (vemurafenib) - Pancreatitis","created_date":"2015-02-12","modified_date":null,"key_message_list":[{"field_id":172,"order_no":1,"bullet":"ZELBORAF is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma). It works by targeting proteins made from a mutated gene called \"BRAF\"."},{"field_id":172,"order_no":2,"bullet":"A safety review was initiated following the identification of cases of ZELBORAF-associated pancreatitis in ongoing clinical trials."},{"field_id":172,"order_no":3,"bullet":"The Canadian prescribing information for ZELBORAF has been updated to include the risk of pancreatitis. Health Canada has also issued a communication to inform patients and healthcare professionals of this risk."}],"footnotes_list":[{"field_id":176,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database."}],"reference_list":[],"use_canada_list":[{"field_id":173,"order_no":1,"bullet":"ZELBORAF slows down or stops the growth of cancer cells by targeting specific proteins."},{"field_id":173,"order_no":2,"bullet":"ZELBORAF is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma) that has a mutation in the BRAF gene and that cannot be removed by surgery or has spread to other parts of the body."},{"field_id":173,"order_no":3,"bullet":"It was first marketed in Canada on March 3, 2012."}],"finding_list":[{"field_id":174,"order_no":1,"bullet":"ZELBORAF may affect the multiplication and growth (proliferation) of tissue in the pancreas, which could potentially lead to obstructive pancreatitis."},{"field_id":174,"order_no":2,"bullet":"TAFINLAR, another BRAF-inhibitor, is labelled for pancreatitis."},{"field_id":174,"order_no":3,"bullet":"A total of 61 reports of pancreatitis associated with the use of ZELBORAF were retrieved from different sources (pre-clinical studies, scientific literature, manufacturer's clinical and safety databases, Health Canada's Canada Vigilance Program, the World Health Organization database and Health Canada's Office of Clinical Trials)a. Health Canada received 2 reports through the Canada Vigilance Program."},{"field_id":174,"order_no":4,"bullet":"In 10 of the 61 reports, ZELBORAF was deemed to have had a \"possible\" or \"probable\" connection in causing the pancreatitis."}],"conclusion_list":[{"field_id":175,"order_no":1,"bullet":"Evidence of an association between ZELBORAF and the occurrence of pancreatitis was found by Health Canada. This association may be due, in part, to the fact that the drug may stimulate the proliferation of cells leading to obstructive pancreatitis."},{"field_id":175,"order_no":2,"bullet":"The Canadian prescribing information for ZELBORAF has been updated to include the risk of pancreatitis."},{"field_id":175,"order_no":3,"bullet":"Health Canada has issued a communication to inform patients and healthcare professionals of the risk of pancreatitis associated with the use of ZELBORAF."}]},{"template":2,"link_id":"SSR00075","review_date":null,"drug_name":"Perjeta (pertuzumab)","safety_issue":"Stevens-Johnson Syndrome (serious condition of the skin and mucous membranes)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":555,"overview":"Health Canada carried out a safety review to look into the potential risk of Stevens-Johnson Syndrome with the use of Perjeta. This issue was found during a routine review of information received from the manufacturer. Stevens-Johnson Syndrome is a rare but serious and potentially life-threatening reaction. It involves blistering or peeling of large areas of skin and mucous linings.","use_canada":556,"findings":557,"conclusion":558,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - PERJETA (pertuzumab) - Assessing the Potential Risk of Stevens-Johnson Syndrome","created_date":"2016-04-04","modified_date":null,"key_message_list":[{"field_id":555,"order_no":2,"bullet":"Perjeta (pertuzumab), in combination with two other drugs, is used to treat breast cancer that has spread to other parts of the body."},{"field_id":555,"order_no":3,"bullet":"This safety review was triggered when Health Canada identified a possible risk of Stevens-Johnson Syndrome with Perjeta treatment, during the routine review of information received from the manufacturer."},{"field_id":555,"order_no":4,"bullet":"Health Canada's review concluded that the evidence was too limited to support a link between the use of Perjeta and the risk of Stevens-Johnson Syndrome. Health Canada has therefore asked the manufacturer to continue monitoring for this risk worldwide and to report new cases of this issue."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":556,"order_no":1,"bullet":"Perjeta, in combination with other treatments, is used to treat patients with breast cancer that has spread to other parts of the body."},{"field_id":556,"order_no":2,"bullet":"Perjeta has been sold in Canada since May 2013. It is available by prescription only."},{"field_id":556,"order_no":3,"bullet":"Perjeta is sold as an intravenous solution in a 30 mg/mL strength."}],"finding_list":[{"field_id":557,"order_no":1,"bullet":"At the time of the review, there were no Canadian reports of Stevens-Johnson Syndrome with the use of Perjeta."},{"field_id":557,"order_no":2,"bullet":"This safety review looked at 2 international reports of Stevens-Johnson Syndrome with the use of Perjeta that were submitted by the manufacturer. The review of these reports was limited by factors such as missing information and the possible role of other medications taken by the patient."},{"field_id":557,"order_no":3,"bullet":"A search of the scientific literature did not find any reports of Stevens-Johnson Syndrome with the use of Perjeta."},{"field_id":557,"order_no":4,"bullet":"Information regarding the risk of Stevens-Johnson Syndrome is already included in the Canadian prescribing information for one of the two other drugs that are used in combination with Perjeta."}],"conclusion_list":[{"field_id":558,"order_no":1,"bullet":"Health Canada's review concluded that the evidence was too limited to support a link between the use of Perjeta and the risk of Stevens-Johnson Syndrome."},{"field_id":558,"order_no":2,"bullet":"Health Canada has asked the manufacturer to continue to actively monitor for this risk worldwide and to report new cases of Stevens-Johnson Syndrome to Health Canada."},{"field_id":558,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Perjeta, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":1,"link_id":"SSR00037","review_date":null,"drug_name":"PRADAXA (dabigatran) and MULTAQ (dronedarone) or CORDARONE (amiodarone)","safety_issue":"Drug-Drug Interaction","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the available information on the interaction between PRADAXA (dabigatran), an anti-blood clotting drug, and MULTAQ (dronedarone) or CORDARONE (amiodarone), both used to control abnormal heart rates. This possible interaction can raise the blood level of dabigatran and potentially increase the bleeding risk associated with it. This review was prompted by cumulative evidence received by Health Canada, including evidence assessed by the European Medicines Agency, regarding the interaction between dronedarone and dabigatran.","background":"Dabigatran is used for the treatment and prevention of blood clots in the veins of legs and lungs, including in patients with knee or hip replacement surgery. It is also approved for the prevention of stroke or blood vessel blockage due to blood clotting in patients with an abnormal heart rhythm called atrial fibrillation.
Amiodarone is approved for the treatment of certain abnormal heart rhythms called ventricular arrhythmias. Dronedarone is approved for the treatment of certain abnormal heart rhythms called atrial fibrillation.
Generic amiodarone products are approved in Canada. There are no generics for dabigatran nor dronedarone.
Bleeding is a known risk of dabigatran. Bleeding of any type or severity may occur with the use of dabigatran, from minor bruising to major or severe bleeding in any part of the body. It is possible that amiodarone or dronedarone can block one of the mechanisms by which dabigatran is transported out of the body (P-glycoprotein) and eliminated. This may raise the blood level of dabigatran leading to an increased risk of bleeding.
To review the available evidence concerning the interaction between dabigatran and dronedarone or amiodarone. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data as well as what is known about the use of these products in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.
","objective":"To review the available evidence concerning the interaction between dabigatran and dronedarone or amiodarone. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data as well as what is known about the use of these products in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"Amiodarone, dabigatran and dronedarone were marketed in Canada in 1994, 2008 and 2009 respectively. Available information showed that the total number of dabigatran prescriptions was low from 2008 to 2010 and has increased from the year 2010 to 2012.
At the time of the review, Health Canada received 6 reports of bleeding in patients who were using dabigatran and dronedarone at the same time. Health Canada also received 19 reports of bleeding in patients who were using dabigatran and amiodarone at the same time. Some specific side effects that were mentioned in the reports included hemorrhage (heavy or uncontrollable bleeding) in the stomach and intestines, rectal bleeding and blood in the stools, hemorrhage in the lungs, pericardial effusion (too much fluid built up around the heart), increased International Normalised Ratio (increased blood clotting time) and decreased hemoglobin (decreased red blood cells).
Health Canada found that bleeding was possibly associated with the interaction between dabigatran and dronedarone in 4 cases, and possibly associated with the interaction between dabigatran and amiodarone in 7 cases.
The published scientific evidence on the interaction between dabigatran and amiodarone or dronedarone includes one clinical trial abstract (summary of a research study, Brunet et al, 2011) for the dabigatran and dronedarone interaction and 3 published case reports (one for the dabigatran and dronedarone interaction, and 2 for the dabigatran and amiodarone interaction).
The clinical trial (Brunet et al, 2011) was conducted on 16 healthy volunteers and suggested that dronedarone increased the body's exposure to dabigatran as well as patient blood clotting times.
In the published case report discussing an interaction between dronedarone and dabigatran, dabigatran was considered possibly associated with hemopericardium (a condition where blood leaks into the outer casing of the heart). In one of the two published case reports on the amiodarone and dabigatran interaction, the patient was bleeding in his digestive tract; this side effect was considered probably caused by the interaction between amiodarone and dabigatran. In the other case report, the patient had a stroke but no bleeding complications.
At the time of this review, the World Health Organization (WHO) VigiBase database contained 254 cases of bleeding related side effects reported in patients using both dabigatran and amiodarone. The database also had 199 cases of bleeding related side effects reported in patients using both dabigatran and dronedarone. Most of these cases were from the United States (175 suspecting the dabigatran-amiodarone interaction and 185 suspecting the dabigatran-dronedarone interaction). While a drug-drug interaction may be suspected in these bleeding events, other causes cannot be ruled out as detailed case reports were not available.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":441,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":621,"footnotes":622,"title":"Summary Safety Review - PRADAXA (dabigatran) and MULTAQ (dronedarone) or CORDARONE (amiodarone) - Drug-Drug Interaction","created_date":"2015-02-12","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":622,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc, An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":622,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."}],"reference_list":[{"field_id":621,"order_no":1,"bullet":"Assessment report - MULTAQ. London (UK): European Medicines Agency; 2012 September 20. (accessed 2014 November 28)."},{"field_id":621,"order_no":2,"bullet":"Brunet A, Hermabessiere S, Benain X. Pharmacokinetic and pharmacodynamic interaction of dronedarone and dabigatran in healthy subjects [abstract P3566]. Eur Heart J 2011;32(Suppl):618-9."},{"field_id":621,"order_no":3,"bullet":"Barton CA, McMillian WD, Raza SS, et al. Hemopericardium in a patient treated with dabigatran etexilate. Pharmacotherapy 2012;32(5):e103-7."},{"field_id":621,"order_no":4,"bullet":"Manso G, Jimeno FJ, Ordonez L, et al. Drug interactions of dabigatran: Report of one case [poster abstract P56]. Basic Clin Pharmacol Toxicol 2012;111(Suppl. s1):12-40."},{"field_id":621,"order_no":5,"bullet":"Neuffer EM, Tofade TS, Galpin LE, et al. Significant bleeding in elderly patient with atrial fibrillation due to probable interaction between dabigatran and amiodarone. J Pharm Technol 2012; 28(4):139-45."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":441,"order_no":1,"bullet":"At the time the safety review was completed, the available evidence supported that bleeding related side effects may be associated with the drug-drug interaction between dabigatran and dronedarone or amiodarone.
In order to address these safety concerns, Health Canada has reviewed the prescribing information for these drugs. The prescribing information for PRADAXA, MULTAQ and CORDARONE now includes information regarding this drug-drug interaction. The prescribing information for applicable generic amiodarone products is also being updated to include warnings regarding their possible interaction with dabigatran.
"}]},{"template":1,"link_id":"SSR00038","review_date":null,"drug_name":"Mycophenolates (CELLCEPT and MYFORTIC)","safety_issue":"Bronchiectasis (Damage to the Lung Airways) with or without Hypogammaglobulinemia (Low Levels of Immunoglobulins in the Blood)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was conducted to evaluate the risk of damage to the lung airways (bronchiectasis) in patients taking certain drugs (mycophenolates) which are used to prevent transplant rejection. The review also evaluated the risk of hypogammaglobulinemia (decreased quantity of immunoglobulins G or IgG, in the blood), which may occur together with bronchiectasis in patients taking mycophenolates. The assessment was prompted by an observation of a growing number of international reports and literature reports of bronchiectasis in transplant recipients treated with products containing mycophenolates.","background":"In Canada, products containing mycophenolates are currently marketed as CELLCEPT (mycophenolate mofetil) and MYFORTIC (mycophenolic acid), as well as their generic products. These products are used to prevent organ rejection in adults receiving kidney, heart or liver transplants, in combination with other organ rejection drugs (cyclosporine and corticosteroids). Some of these products are also used in children aged 2 to 18 years under certain conditions.
Bronchiectasis is a chronic, progressive lung disease characterized by damage to the structure of bronchial tubes (airways). It is associated with respiratory symptoms that include cough, daily sputum or mucus production, and fatigue.
Hypogammaglobulinemia means low levels of immunoglobulins G (IgG) in the blood; IgG are antibodies that are important in fighting infections and their decrease is often associated with infections. In transplant patients, hypogammaglobulinemia may increase the chances of having respiratory infections. The respiratory infections may trigger bronchiectasis. However, both diseases do not always occur together.
","objective":"To review the available evidence concerning the risk of developing bronchiectasis with or without hypogammaglobulinemia associated with products containing mycophenolates. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data as well as what is known about the use of these products in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"From 2009 to 2013, there has been a steady annual increase in the total number of prescriptions for mycophenolates in Canada. Over those 5 years, annual prescriptions have increased by 32% (from 154,781 in 2009 to 228,077 in 2013).
At the time of this review, Health Canada had not received any Canadian reports of bronchiectasis in transplant patients treated with mycophenolates.
Evidence from published medical and scientific literature suggests that bronchiectasis might be related to the use of mycophenolates as noted by the following:
Based on their own reviews, the manufacturers for CELLCEPT and MYFORTIC could not rule out a cause and effect relationship between these drugs and bronchiectasis and/or hypogammaglobulinemia.
At the time of the review, the World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) had 38 reports of bronchiectasis and 36 reports of hypogammaglobulinemia in patients treated with mycophenolates. Twenty-three of 38 reports of bronchiectasis also reported hypogammaglobulinemia.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":442,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":623,"footnotes":177,"title":"Summary Safety Review - Mycophenolates (CELLCEPT and MYFORTIC) - Bronchiectasis (Damage to the Lung Airways) with or without Hypogammaglobulinemia (Low Levels of Immunoglobulins in the Blood)","created_date":"2015-02-04","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":177,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":177,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":177,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":623,"order_no":1,"bullet":"Boddana P, Webb LH, Unsworth J, et al. Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil-treated renal transplant recipients: an emerging clinical phenomenon? Clin Transplant 2011;25(3):417-9."},{"field_id":623,"order_no":2,"bullet":"Rook M, Postma DS, van der Jagt EJ, et al. Mycophenolate mofetil and bronchiectasis in kidney transplant patients: a possible relationship. Transplantation 2006;81(2):287-9."},{"field_id":623,"order_no":3,"bullet":"Pijnenburg MW, Cransberg K, Wolff E, et al. Bronchiectasis in children after renal or liver transplantation: a report of five cases. Pediatr Transplant 2004;8(1);71-4."},{"field_id":623,"order_no":4,"bullet":"Merkus PJ, Pijnenburg M, Cransberg K. Mycophenolate mofetil and bronchiectasis in pediatric transplant patients. Transplantation 2006;82(10):1386."},{"field_id":623,"order_no":5,"bullet":"Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 2000;47(2-3):85-118."},{"field_id":623,"order_no":6,"bullet":"Allison AC, Eugui EM. Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection. Transplantation 2005;80(2 Suppl):S181-90."},{"field_id":623,"order_no":7,"bullet":"Smith KG, Isbel NM, Catton MG, et al. Suppression of the humoral immune response by mycophenolate mofetil. Nephrol Dial Transplant 1998;13(1):160-4."},{"field_id":623,"order_no":8,"bullet":"Corales R, Chua J, Mawhorter S, et al. Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon? Transpl Infect Dis 2000;2(3):133-9."},{"field_id":623,"order_no":9,"bullet":"Keven K, Sahin M, Kutlay S, et al. Immunoglobulin deficiency in kidney allograft recipients: comparative effects of mycophenolate mofetil and azathioprine. Transpl Infect Dis 2003;5(4):181-6."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":442,"order_no":1,"bullet":"The current evidence suggests that bronchiectasis with or without hypogammaglobulinemia may occur while taking products containing mycophenolates.
The prescribing information for CELLCEPT and MYFORTIC has been updated to include the possible risk of bronchiectasis and hypogammaglobulinemia. The prescribing information now also recommends that treating physicians further investigate patients with persistent lung symptoms and recurrent infections for the possibility of bronchiectasis and hypogammaglobulinemia, respectively. Manufacturers of generic versions of these drugs will also update their product information.
Health Canada will continue its ongoing monitoring of adverse reactions involving mycophenolates, in particular, the risk of bronchiectasis and/or hypogammaglobulinemia. Health Canada will keep Canadians informed and take action, as appropriate, if new safety information is identified.
"}]},{"template":1,"link_id":"SSR00039","review_date":null,"drug_name":"DOMPERIDONE","safety_issue":"Serious abnormal heart rhythms and sudden death (cardiac arrest)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was done to evaluate the risk of serious abnormal heart rhythms and sudden death (cardiac arrest) with domperidone for all uses. This review was prompted by the ongoing assessment of information regarding domperidone and heart events and from information shared by the European Medicines Agency (EMA).","background":"Domperidone was first marketed in Canada in 1985 under the name Motilium. Motilium is no longer marketed in Canada. It has been replaced by 13 generics or copies of Motilium.
Domperidone is used to treat symptoms of slowed stomach emptying seen in people with some gastrointestinal (GI) disorders (e.g., gastritis or inflammation of the GI tract). Domperidone is also used to reduce symptoms such as nausea and vomiting caused by some drugs used to treat Parkinson's disease.
Changes in the electrical activity of the heart, such as QT prolongation, can lead to an abnormal heart rhythm. An abnormal heart rhythm refers to the heart beating too fast, too slow or irregularly. In some rare cases, fast, irregular heartbeats can cause death.
","objective":"To assess the risk of a person developing serious abnormal heart rhythms and sudden death while taking domperidone. The evidence considered included Canadian and international adverse reaction reports, scientific and medical literature, international data, and what is known about the use of this product both in Canada and internationally.","key_findings":"Domperidone is widely used in Canada. There were about 2,000,000 prescriptions for domperidone in Canada in 2013.
At the time of this review, Health Canada had received 18 reports (no deaths) of serious adverse heart events with domperidone. Of these 18 reports, 12 reports were further evaluated to determine whether the use of domperidone was the cause of the heart events. Domperidone was found to be a possible cause for the development of heart events in most cases. However, it is difficult to determine to what extent domperidone contributes to heart events because other conditions known to cause electrical heart problems were also present in many cases.
Studies in patients have shown that domperidone may increase the risk of sudden death and serious abnormal heart rhythms. However, these studies had limitations, including small numbers of patients, and the possibility that factors other than domperidone could have led to the heart events. This risk may be higher in patients over 60 years of age, in patients using doses greater than 30 mg per day, and in patients taking domperidone together with drugs that can lead to increased blood levels of domperidone.
As part of this safety review, Health Canada received information from healthcare professional associations. Domperidone continues to be prescribed in Canada, sometimes at doses greater than 30 mg per day. However, some healthcare professionals consider measures to reduce the risk of heart effects such as requesting an electrical tracing of the heart (electrocardiogram or ECG) when prescribing domperidone to patients at higher risk of heart effects.
Cases supporting the association between domperidone and serious abnormal heart rhythms and sudden death have been reported worldwide. A search of the European Union innovator manufacturer's safety database found 342 reports of serious heart related events. In many of the reports, it was mentioned that patients had heart conditions or were taking other drugs that could cause abnormal heart rhythms. From 1982 to November 10, 2013, there were 137 reports of serious heart related events found in the World Health Organization database. These reports included serious abnormal heart rhythms, QT prolongation and sudden death.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":443,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":178,"footnotes":179,"title":"Summary Safety Review - DOMPERIDONE - Serious abnormal heart rhythms and sudden death (cardiac arrest)","created_date":"2015-01-27","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":179,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":179,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":179,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":178,"order_no":1,"bullet":"van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC. Domperidone and ventricular arrhythmia or sudden cardiac death: a population-based case-control study in the Netherlands. Drug Saf 2010;33(11):1003-14."},{"field_id":178,"order_no":2,"bullet":"Johannes CB, Varas-Lorenzo C, McQuay LJ, Midkiff KD, Fife D. Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study. Pharmacoepidemiol Drug Saf 2010;19(9):881-8."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":443,"order_no":1,"bullet":"There is evidence suggesting a link between the use of domperidone and the development of serious abnormal heart rhythms and sudden death. Risks are increased (i) in patients taking domperidone at doses greater than 30 mg a day, (ii) in patients over 60 years of age, and (iii) in patients taking domperidone together with drugs that can lead to increased domperidone blood levels or with drugs that are known to affect the electrical activity of the heart. This safety information applies to patients taking domperidone for any conditions.
Health Canada has previously communicated about abnormal heart rhythms with domperidone. In 2007, healthcare professionals were advised to watch for drug interactions and clinical risk factors that could result in changes to the electrical activity of the heart (QT prolongation) when using domperidone. In 2012, the prescribing information for domperidone was changed. It included advice to use the lowest possible dose of domperidone, and be cautious when prescribing domperidone to patients at high risk of developing abnormal heart rhythms. Health Canada, together with the Canadian manufacturers of domperidone, informed Canadians about these heart effects when taking domperidone.
At this time, to further reduce the risk of serious heart effects with domperidone, Health Canada has decided that additional measures are needed:
Health Canada will keep Canadians informed and take action, as appropriate, if any other new safety information is identified.
"}]},{"template":1,"link_id":"SSR00040","review_date":null,"drug_name":"PROLIA (denosumab)","safety_issue":"Risk of Malignancy (Cancer)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the current available information on the potential risk of cancer associated with PROLIA (denosumab). This review was prompted by a safety report of cases of death submitted to Health Canada from the manufacturer as part of regular regulatory requirements. In that report, Health Canada noted cases of cancer. Therefore, Health Canada requested that the manufacturer submit a summary report on all cases of cancer associated with the use of PROLIA for further evaluation.","background":"PROLIA is used to treat osteoporosis (thinning and weakening of the bone) in women after menopause who have an increased risk of fractures. It is also used in some men with osteoporosis. PROLIA is also used to increase bone mass in men with prostate cancer and women with breast cancer who are receiving cancer treatment.
Malignancy is a cancerous tumour which is able to grow and invade nearby tissues and spread to other parts of the body. Cancer cells that spread to other parts of the body are called metastases.
","objective":"To assess the available evidence regarding the possible risk or chance of developing all types of cancer in patients taking PROLIA. Specifically, Health Canada assessed new cases of cancer after treatment with PROLIA was started. If the patient had cancer before, or if a previous cancer reoccurred, this was not considered to be caused by PROLIA. The evidence that was considered included Canadian patient reports, reports from the manufacturer, scientific literature reports and what is known about the use of this medicine both in Canada and internationally.","key_findings":"Upon further analysis of both the Canadian and international case reports, only 16 cases of cancer out of a possible 1,140 were identified as potentially related to the use of PROLIA. The current PROLIA prescribing information contains statements explaining that the rates of cancer observed in clinical trials were similar in patients who received PROLIA compared to those who received the placebo.
Based on the information provided in this review, Health Canada concluded that there is not enough evidence at this time to suggest an association between the use of PROLIA and cancer.
Health Canada will continue its monitoring of adverse reaction information involving PROLIA, as it does for all health products, to assess and identify potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00041","review_date":null,"drug_name":"Atypical Antipsychotics","safety_issue":"Liver failure","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the potential risk of liver failure associated with atypical antipsychotics, a class of drugs that are mainly used to treat schizophrenia, bipolar disorder and depression. This review was prompted by information from the scientific literature that linked one of these drugs (quetiapine) with the risk of liver failure.","background":"Atypical antipsychotics marketed in Canada include: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone. These products have different approved uses, but generally, atypical antipsychotics are used for the treatment of schizophrenia, bipolar disorder and, in some cases, depression.
Liver failure occurs when the liver has been severely damaged and becomes unable to perform its normal functions. Symptoms of liver failure can include jaundice (yellowing of the skin and the whites of eyes), nausea and vomiting, a general sense of feeling unwell, an accumulation of fluid within the abdomen (ascites), a tendency to bruise and bleed easily and mental disorientation or confusion.
","objective":"To assess the available evidence concerning the potential risk of liver failure associated with the use of atypical antipsychotics. This review considered Canadian adverse reaction reports, scientific and medical literature, and international safety data, as well as what is known about the use of these products both in Canada and internationally.","key_findings":"Atypical antipsychotics are frequently prescribed drugs. Quetiapine is the most prescribed atypical antipsychotic, with 7,054,492 prescriptions dispensed in 2012. The number of prescriptions dispensed for all atypical antipsychotics has increased from 10,311,586 in 2008 to 14,786,633 in 2012.
At the time of this review, Health Canada had received several reports of liver failure suspected of being associated with atypical antipsychotics (aripiprazole = 2; asenapine = 0; clozapine = 16; lurasidone = 0; olanzapine = 3; paliperidone = 0; quetiapine = 3; risperidone = 2; and ziprasidone = 0). Some of these cases involved a rapid loss of liver function (acute liver failure). Most of the reports did not provide enough information for a thorough analysis.
This review was first prompted by 4 literature reports describing cases of liver failure associated with quetiapine (Al Mutairi et al, 2012; El Hajj et al, 2004; Li et al, 2010; Naharci et al, 2011).
Three published cases (two international and one Canadian) suggested a probable association between quetiapine and acute liver failure. Two of these cases resulted in patient death.
Overall, the published evidence linking liver failure with the use of other atypical antipsychotics was limited, with the exception of clozapine and olanzapine, where the risk of liver failure is recognized and included in their prescribing information.
At the time of this review, the World Health Organization (WHO) Global Individual Case Safety Reports Database System (Vigibase) contained a number of reports involving atypical antipsychotics and liver failures (aripiprazole = 15; asenapine = 4; clozapine = 85; lurasidone = 0; olanzapine = 70; paliperidone = 15; quetiapine = 54; risperidone = 34; and ziprasidone = 15).
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":445,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":182,"footnotes":183,"title":"Summary Safety Review - Atypical Antipsychotics - Liver failure","created_date":"2015-01-22","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":183,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":183,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":183,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":182,"order_no":1,"bullet":"Al Mutairi F, Dwivedi G, Al Ameel T. Fulminant hepatic failure in association with quetiapine: A case report. J Med Case Rep 2012;6(1):418."},{"field_id":182,"order_no":2,"bullet":"Bawolak MT. Quetiapine and acute liver failure. Can Advers Reaction Newsl2014;24(2):1-2."},{"field_id":182,"order_no":3,"bullet":"El Hajj I, Sharara AI, Rockey DC. Subfulminant liver failure associated with quetiapine.Eur J Gastroenterol Hepatol 2004;16(12):1415-8."},{"field_id":182,"order_no":4,"bullet":"Li J, Zhu X, Liu F, et al. Cytokine and autoantibody patterns in acute liver failure. J Immunotoxicol 2010;7(3):157-64."},{"field_id":182,"order_no":5,"bullet":"Naharci MI, Karadurmus N, Demir O, et al. Fatal hepatotoxicity in an elderly patient receiving low-dose quetiapine. Am J Psychiatry 2011;168(2):212-3."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":445,"order_no":1,"bullet":"Atypical antipsychotics are very widely used. A relatively small number of cases of liver failure have been reported in association with these drugs, although cases were serious and sometimes resulted in death. The risk of liver failure is currently included in the prescribing information for clozapine and olanzapine-containing products. With regard to the other atypical antipsychotics, most of the evidence gathered involved quetiapine.
Health Canada has determined that the overall benefits of quetiapine continue to outweigh the risks, when used as recommended but Health Canada has taken the following actions to minimize the risk of liver failure associated with quetiapine:
Evidence linking the other 6 atypical antipsychotics (aripiprazole, asenapine, lurasidone, paliperidone, risperidone and ziprasidone) was limited. Health Canada will continue its ongoing monitoring of adverse reaction information involving all other atypical antipsychotics, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00042","review_date":null,"drug_name":"ARICEPT (donepezil)","safety_issue":"Risk of Rhabdomyolysis and Neuroleptic Malignant Syndrome","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was conducted to evaluate the available information on the potential risk of rhabdomyolysis (muscle breakdown) and/or Neuroleptic Malignant Syndrome (NMS), a life-threatening neurological disorder associated with donepezil. The review was prompted by a case of rhabdomyolysis reported to Health Canada.","background":"Donepezil is used to treat the symptoms of Alzheimer's disease. Donepezil has been marketed in Canada under the brand names ARICEPT® since 1997 and ARICEPT® Rapidly Disintegrating Tablet (RDT) since 2006. As of November 2014, 16 companies have also received authorizations to sell generic donepezil in Canada.
Rhabdomyolysis is a condition that results in the breakdown of muscle tissue. Typical clinical symptoms can include muscle pain, fever, weakness, nausea, and dark urine. Rhabdomyolysis can lead to life-threatening abnormal heart rhythms and kidney failure. Rhabdomyolysis can be drug-induced, but can also happen due to chemicals causing muscular damage, physical overexertion or other causes.
NMS is a rare life-threatening condition with changes in the nervous, muscular and cardiovascular systems. Symptoms of NMS include fever, mental changes, agitation, delirium, and muscle rigidity that can potentially lead to rhabdomyolysis. NMS is most often associated with the use of antipsychotics and dopamine enhancing drugs. It is believed that NMS is caused by an imbalance in brain cell chemicals.
","objective":"To assess the available evidence concerning the risk of developing rhabdomyolysis and/or NMS with the use of donepezil. The evidence considered included Canadian adverse reaction reports, scientific and medical literature, as well as what is known about the use of this medicine in Canada and internationally. The review evaluated the risks and suggested ways to minimize it. Since there is overlap in clinical symptoms of rhabdomyolysis and NMS relating to muscle pain/rigidity, and in several of the cases, both medical conditions were reported, the risks of rhabdomyolysis and NMS were reviewed together.","key_findings":"The number of donepezil prescriptions filled in community pharmacies in Canada has been increasing at a rate of approximately 10% annually since 2008. It is estimated that 2,041,755 prescriptions of donepezil, both brand name and generic were dispensed in Canada in 2013.
As of June 30th 2014, Health Canada received one Canadian report of rhabdomyolysis with donepezil. The report described an incident in a patient taking donepezil among other medications. The patient recovered. The event of rhabdomyolysis was found to be possibly related to donepezil. As of 30-Jun-2014, there have been no Canadian cases of NMS reported with donepezil.
Health Canada asked the brand name manufacturer of donepezil products to submit their case reports of rhabdomyolysis and NMS. A total of 88 international cases of rhabdomyolysis and 67 international cases of NMS with donepezil were received and reviewed. Most cases of rhabdomyolysis or NMS occurred alone but some cases presented both conditions. There were 3 fatal cases associated with rhabdomyolysis, and 9 fatal cases with NMS. The majority of fatalities occurred in Japan. The prescribing information for health care professionals in other countries (i.e. Europe, Australia, and Japan) includes the risk of rhabdomyolysis resulting from NMS.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":446,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":184,"footnotes":185,"title":"Summary Safety Review - ARICEPT (donepezil) - Risk of Rhabdomyolysis and Neuroleptic Malignant Syndrome","created_date":"2015-01-21","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":185,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc, An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":185,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":184,"order_no":1,"bullet":"Sahin OZ, Ayaz T, Yuce S, et al. A Rare Case of Acute Renal Failure Secondary to Rhabdomyolysis Probably Induced by Donepezil. Case Rep Nephrol 2014;2014:214359."},{"field_id":184,"order_no":2,"bullet":"Sahin OZ, Ayaz T, Yuce S, et al. A Rare Case of Acute Renal Failure Secondary to Rhabdomyolysis Probably Induced by Donepezil. Case Rep Nephrol 2014;2014:214359."},{"field_id":184,"order_no":3,"bullet":"Warwick TC, Moningi V, Jami P, et al. Neuroleptic malignant syndrome variant in a patient receiving donepezil and olanzapine Nat Clin Pract Neurol 2008; 4(3):170-4."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":446,"order_no":1,"bullet":"The available evidence suggests that rhabdomyolysis and/or NMS may occur with donepezil use. The prescribing information for ARICEPT® and ARICEPT® RDT has been updated to include the possible risks of rhabdomyolysis and NMS. Manufacturers of generic products will also update their product information. It is important for healthcare professionals and patients to be aware of the possibility of these rare serious reactions, and for steps to be taken for early detection of rhabdomyolysis and/or NMS. Health Canada has issued an Information Update to inform health care professionals and Canadians of the risks of rhabdomyolysis and/or NMS for donepezil. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00043","review_date":null,"drug_name":"Metoclopramide","safety_issue":"Abnormal Involuntary Movements of the Body (Extrapyramidal Symptoms) in Children","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the possible risk of abnormal involuntary movements of the body, known as extrapyramidal symptoms (EPS), in children taking the recommended daily dose of metoclopramide. This review was prompted by a report published by the European Medicines Agency which found that the development of EPS was common in children taking metoclopramide at the recommended daily dose. Prior to this report, the possibility of EPS in children was believed to mostly occur at doses greater than recommended.","background":"Metoclopramide has been on the Canadian market for decades. It was introduced under the brand name MAXERAN in 1974. At the time of this review, it was sold by 5 generic companies.a
In Canada, metoclopramide is approved for the treatment of conditions such as slowed stomach emptying and for medical procedures like inserting a tube into the small intestine (called small bowel intubation). The recommended daily dose for children (0.5 mg/kg/day) is provided in the prescribing information for metoclopramide. At the time of the review, the prescribing information for metoclopramide included warnings on the risk of EPS in children taking more than the recommended daily dose. They contained limited information on the risk of EPS in children taking the recommended daily dose.
EPS refer to a variety of abnormal involuntary movements caused by a malfunctioning of the part of the brain responsible for the movements of the body. Although they are mostly reversible, EPS also include a condition called tardive dyskinesia (TD), which is serious and may be permanent. TD is a repetitive, involuntary movement which affects mainly the face, tongue, arms and legs. TD is rare in children.
","objective":"To assess the available evidence concerning the possible risk of EPS in children treated with metoclopramide at the recommended daily dose. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data, as well as what is known about the use of these products both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"Metoclopramide is not widely used to treat children in Canada. In 2011-2012, major reasons for prescribing metoclopramide in children included the treatment of inflammation of the esophagus (esophagitis), headache, nausea and vomiting. In 2012, metoclopramide use in children represented 3% of 419,000 prescriptions for metoclopramide in Canada.
At the time of this review, Health Canada had identified 8 reports of EPS suspected of being associated with metoclopramide in children receiving the recommended daily dose.
There is limited information on the safety of metoclopramide in children in the scientific literature. Most articles described studies on the effect of metoclopramide (called efficacy studies).
A review of the available scientific information on EPS and the use of metoclopramide in children showed that EPS can occur in children taking recommended daily doses of metoclopramide. Children younger than one year of age appear to be at higher risk of EPS.
A review of the European data found many cases of EPS in children less than 18 years of age treated with metoclopramide. Most cases occurred when recommended doses were used.
At the time of this review, several other countries had restricted the use of metoclopramide in children.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":447,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":186,"footnotes":187,"title":"Summary Safety Review - Metoclopramide - Abnormal Involuntary Movements of the Body (Extrapyramidal Symptoms) in Children","created_date":"2015-01-15","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":187,"order_no":1,"bullet":"Metoclopramide is currently sold by 4 generic companies."},{"field_id":187,"order_no":2,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":187,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":186,"order_no":1,"bullet":"European Medicines Agency. Rapporteur's Public Paediatric Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended; 2010."},{"field_id":186,"order_no":2,"bullet":"Council of International Organizations of Medical Sciences (CIOMS). Reporting adverse drug reactions: definition of terms and criteria for their use; 1999."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":447,"order_no":1,"bullet":"The safety review showed that EPS can occur in children treated with metoclopramide at the recommended daily dose (0.5 mg/kg/day). It also showed that metoclopramide should not be used in children less than one year of age. Finally, the risk of EPS should be considered with the expected benefits of metoclopramide use in children older than one year of age.
In order to reduce the risks associated with metoclopramide use in children, Health Canada has worked with the manufacturers of metoclopramide to incorporate the following information in their prescribing information:
Health Canada has also issued a communication to inform healthcare professionals and patients about the risk of EPS at recommended doses of metoclopramide and changes to the prescribing information.
"}]},{"template":1,"link_id":"SSR00044","review_date":null,"drug_name":"Vascular Endothelial Growth Factor Receptor Inhibitors","safety_issue":"Thrombotic Microangiopathy","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the possible risk of blood clots in small vessels, called thrombotic microangiopathy (TMA) associated with the use of vascular endothelial growth factor (VEGF) receptor inhibitors. This review was prompted by information submitted by one of the manufacturers of this class of drugs. VEGF inhibitors developed from living sources, known as biologic drugs, were not included in this review. A safety summary review of biologic drugs was published in September 2014.
","background":"VEGF receptor inhibitors are used for treating various types of cancer. The type of cancer treated varies with each specific VEGF receptor inhibitor used. VEGF receptor inhibitors work by slowing down the growth and spread of cancer cells by cutting off the blood supply that keeps cancer cells growing. The VEGF receptor inhibitors included in this review are: SUTENT (sunitinib); NEXAVAR (sorafenib); VOTRIENT (pazopanib); CAPRELSA (vandetanib); INLYTA (axitinib); and STIVARGA (regorafenib).
Thrombotic microangiopathy, or blood clots in small vessels, refers to a group of disorders that involve the occurrence of blood clots in small blood vessels which can damage organs. Signs and symptoms of these disorders may include increased bruising, bleeding, fewer numbers of platelets and red blood cells, high blood pressure, and extreme weakness. Other organs and body systems that can be affected include the kidneys and the nervous system.
Information on the risk of TMA is included in the prescribing information of certain VEGF inhibitors, specifically SUTENT and VOTRIENT.
","objective":"To assess the available evidence concerning VEGF receptor inhibitors and the risk of TMA and whether the risk of TMA is associated with all VEGF receptor inhibitors. This review considered Canadian adverse reaction reports, scientific literature, and international data, as well as what is known about the use of these products both in Canada and internationally.","key_findings":"At the time of this review, Health Canada had not received any reports of TMA suspected of being associated with any of the VEGF receptor inhibitors considered.
Eleven cases of TMA involving SUTENT were published in the scientific literature. In some of these cases, TMA resolved or improved when treatment with SUTENT was stopped. At the time of the review, no cases of TMA were published for the other VEGF receptor inhibitors (NEXAVAR, CAPRELSA, INLYTA, STIVARGA and VOTRIENT).
The exact reason behind a possible association between TMA and VEFG receptor inhibitors is not known.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":448,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":188,"footnotes":189,"title":"Summary Safety Review - Vascular Endothelial Growth Factor Receptor Inhibitors - Thrombotic Microangiopathy","created_date":"2015-01-14","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":189,"order_no":1,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":188,"order_no":1,"bullet":"Moreira IS, Fernandes PA, Ramos MJ. Vascular endothelial growth factor (VEGF) inhibition-a critical review. Anticancer Agents Med Chem 2007;7(2):223-45."},{"field_id":188,"order_no":2,"bullet":"Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thrombotic microangiopathy with targeted cancer agents. Clin Cancer Res 2011;17(18):5858-66."},{"field_id":188,"order_no":3,"bullet":"Levey SA, Bajwa RS, Picken MM, et al. Thrombotic microangiopathy associated with sunitinib, a VEGF inhibitor, in a patient with factor V Leiden mutation. NDT Plus 2008;1(3):154-6."},{"field_id":188,"order_no":4,"bullet":"Kapiteijn E, Brand A, Kroep J, et al. Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome. Ann Oncol 2007;18(10):1745-7."},{"field_id":188,"order_no":5,"bullet":"Bollée G, Patey N, Cazajous G, et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant 2009;24(2):682-5."},{"field_id":188,"order_no":6,"bullet":"Frangié C, Lefaucheur C, Medioni J, et al. Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 2007;8(2):177-8."},{"field_id":188,"order_no":7,"bullet":"Talebi TN, Stefanovic A, Merchan J, et al. Sunitinib-induced microangiopathic hemolytic anemia with fatal outcome. Am J Ther 2012;19(4):143-5."},{"field_id":188,"order_no":8,"bullet":"Choi MK, Hong JY, Jang JH, et al. TTP-HUS associated with sunitinib. Cancer Res Treat 2008;40(4):211-3."},{"field_id":188,"order_no":9,"bullet":"Feldman DR, Baum MS, Ginsberg MS, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27(9):1432-9."},{"field_id":188,"order_no":10,"bullet":"Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008;358(11):1129-36."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":448,"order_no":1,"bullet":"TMA is a rare but serious adverse reaction. Several cases of TMA involving SUTENT have been published in the literature. Although the risk of TMA is recognized for certain VEGF receptor inhibitors (SUTENT and VOTRIENT), based on the information reviewed, there is not sufficient information, at this time, for updating the prescribing information for all VEGF receptor inhibitors.
Health Canada will continue to monitor adverse reaction information involving VEGF receptor inhibitors to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00045","review_date":null,"drug_name":"Hydroxyethyl Starch Solutions","safety_issue":"Risk of Kidney Injury and Death","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the possible increased risk of kidney injury and death associated with hydroxyethyl starch (HES) solutions when compared to alternative treatments. This review was prompted by the publication of three studies (Perner et al, 2012; Brunkhorst et al, 2008; Myburgh et al, 2012) whose results indicated an increased risk of kidney injury and death associated with HES solutions.","background":"HES solutions are used for treating low blood volume. They work by increasing the amount of fluid in circulating blood. At the time of this review, 3 HES solutions were marketed in Canada: VOLUVEN, VOLULYTE, and PENTASPAN. HEXTEND, another HES product, was approved at the time of this review but it was no longer being marketed.a
Kidney injury refers to a decrease or loss of kidney function, which can lead to a number of complications. In advanced cases, kidney replacement therapy, such as dialysis to filter the blood, may be needed to replace certain functions typically performed by a healthy kidney.
This review also assessed evidence regarding the possibility of death (for any reason), as an overall measure of safety.
","objective":"To assess the available evidence concerning the increased safety risks associated with the use of HES solutions in comparison to alternative treatments. This review considered Canadian adverse reaction reports, scientific and medical literature, and international safety data, as well as what is known about the use of these products both in Canada and internationally.","key_findings":"HES solutions are used in hospitals and in other emergency settings where treatment for low blood volume may be required.
At the time of this review, Health Canada had received 28 reports of adverse reactions suspected of being associated with HES solutions. In general, reports lacked important details regarding the health of the patient at the time the HES solution was given, as well as the amount of HES that was administered. The most commonly reported side effect was a blood clotting disorder (coagulopathy). This is a well-known side effect which is described in the prescribing information for these products. Among the 28 reports, there was one case of kidney failure and one case of death involving a blood clotting disorder.
Data from 3 published studies showed an increased risk of kidney injury or death requiring kidney replacement therapy in patients receiving HES solutions in comparison to alternative treatments. These studies involved critically ill patients, including patients with a severe blood infection called sepsis. These findings were supported by 3 additional published analyses (Haase et al, 2013; Perel et al, 2013; Zarychanski et al, 2013) that took into consideration a large volume of related literature on this subject (meta-analyses).
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":449,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":190,"footnotes":191,"title":"Summary Safety Review - Hydroxyethyl Starch Solutions - Risk of Kidney Injury and Death","created_date":"2014-12-03","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":191,"order_no":1,"bullet":"HEXTEND and PENTASPAN were discontinued in Canada, as of July 12, 2013 and November 8, 2013, respectively."},{"field_id":191,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":190,"order_no":1,"bullet":"Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012;367(2):124-34."},{"field_id":190,"order_no":2,"bullet":"Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358(2):125-39."},{"field_id":190,"order_no":3,"bullet":"Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367(20):1901-11."},{"field_id":190,"order_no":4,"bullet":"Haase N, Perner A, Hennings LI, et al. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 2013;346:f839."},{"field_id":190,"order_no":5,"bullet":"Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;2:CD000567."},{"field_id":190,"order_no":6,"bullet":"Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013;309(7):678-88."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":449,"order_no":1,"bullet":"Health Canada has completed its review of the available safety information and has found that there is an increased risk of kidney injury and death in critically ill patients, including patients with a severe blood infection (sepsis), who are treated with HES solutions.
Health Canada actions:
YERVOY is a prescription medicine used to treat melanoma (a kind of skin cancer) that has spread or cannot be removed by surgery. It is administered into a vein (intravenous infusion) for the treatment of melanoma in adults.
Posterior reversible encephalopathy syndrome (PRES) is characterized by seizures, mental status changes, visual disturbances, severe headache, nausea, vomiting, and/or difficulties in communicating. This condition usually starts rapidly. It is reversible if identified and treated appropriately. However, if undetected, PRES may lead to permanent neurologic damage or death.
","objective":"To assess the risk of a person developing PRES while taking YERVOY. The evidence considered included Canadian adverse reaction reports, scientific and medical literature, international safety data, and what is known about the use of this product both in Canada and internationally.","key_findings":"YERVOY was introduced on the Canadian market in March 2012. It is given in a hospital or clinic under medical supervision.
No Canadian cases of PRES had been reported in association with YERVOY at the time of this review.
A 2012 publication identified a possible case of PRES in the medical literature (Maur et al, 2012). It occurred in a 58 year-old woman treated with YERVOY for melanoma. The patient also had renal failure and hypertension.
At the time of this review, the World Health Organization (WHO) Database (VigiBase) contained a single case of PRES following YERVOY exposure in a 50 year-old man. The potential risk of PRES with the use of YERVOY is also being investigated by other regulators.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":450,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":192,"footnotes":193,"title":"Summary Safety Review - YERVOY (ipilimumab) - Posterior Reversible Encephalopathy Syndrome (PRES)","created_date":"2014-12-01","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":193,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":193,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":193,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":192,"order_no":1,"bullet":"Maur M, Tomasello C, Frassoldati A, et al. Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma. J Clin Oncol 2012;30(6):e76-8."},{"field_id":192,"order_no":2,"bullet":"Pharmacovigilance Risk Assessment Committee (PRAC). Pharmacovigilance Risk Assessment Committee (PRAC) - Minutes of the meeting on 10-13 June 2014. London (UK): European Medicines Agency, 2014. (accessed 2014 October 9)."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":450,"order_no":1,"bullet":"PRES is a disorder that is not yet fully understood. In addition, there is no clear explanation of how YERVOY may cause PRES. Given that this product is new to the Canadian market, there is limited information concerning this possible risk. It has been determined that information is too limited to accurately assess the risk of PRES with the use of YERVOY.
Therefore, Health Canada has asked the manufacturer of YERVOY to perform continued surveillance of this adverse event with Periodic Safety Update Reports (or PSURs), which provide an update of the worldwide safety experience of a health product.
Health Canada will also continue its ongoing monitoring of adverse reaction information involving YERVOY, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00047","review_date":null,"drug_name":"Stelara (ustekinumab)","safety_issue":"Serious Skin Disorders (Exfoliative Dermatitis and Erythrodermic Psoriasis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the possible link between serious skin disorders called exfoliative dermatitis and erythrodermic psoriasis and the drug STELARA. The review concluded that it was necessary to closely monitor this risk. Health Canada subsequently received additional information from the European Medicines Agency which confirmed the possible link between this risk and STELARA use.","background":"STELARA, also known as ustekinumab, is a drug used to treat adults with moderate to severe psoriasis (a persistent inflammatory skin condition) and psoriatic arthritis, a variation of psoriasis that is associated with inflammation of the joints. STELARA is given as an injection under the skin.
Exfoliative dermatitis and erythrodermic psoriasis are serious, yet rare skin conditions characterized by extreme reddening and inflammation of the skin resulting in peeling of the skin over large areas of the body.
","objective":"To review the available evidence concerning the risk of developing exfoliative dermatitis and erythrodermic psoriasis, while taking STELARA for psoriasis. The evidence considered included safety information prepared by the manufacturer of the product as requested by Health Canada, medical and scientific literature, and what is known about the use of STELARA in Canada and internationally. The current strategies to minimize the risk were also considered, including a review of the product information available to health professionals and to patients.","key_findings":"The number of STELARA prescriptions in Canada has been increasing on average by 1% annually, since 2010. It is estimated that approximately 15,094 prescriptions in total were dispensed in 2013.
By the time of this review, Health Canada had received 5 reports of skin exfoliation (2 serious and 3 non-serious) and 1 non-serious report of exfoliative dermatitis. None of the reports contained enough information to determine whether or not the drug caused the cutaneous skin reaction.
Very few skin-related side effects have been reported for STELARA and even fewer of these can be categorised as exfoliative dermatitis and erythrodermic psoriasis.
Internationally, 20 cases of exfoliative dermatitis and erythrodermic psoriasis have been reported in association with the use of STELARA. In 12 of the 20 cases, the reaction occurred shortly after the individual started the medication and in 4 of these, the affected patient had a similar reaction when given the medication again. However, it is difficult to determine to what extent STELARA contributed to the exfoliative dermatitis and erythrodermic psoriasis or if the patient's underlying psoriasis could also have contributed.
Additional information was recently obtained from a larger patient population in the European Union which consisted of 46 additional cases. In 15 of these cases, STELARA was considered to have a role in the development of exfoliative dermatitis and erythrodermic psoriasis.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":451,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":194,"title":"Summary Safety Review - STELARA (ustekinumab) - Serious Skin Disorders (Exfoliative Dermatitis and Erythrodermic Psoriasis)","created_date":"2014-11-24","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":194,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":194,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."}],"reference_list":[],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":451,"order_no":1,"bullet":"Health Canada will continue its ongoing monitoring of adverse reaction information involving STELARA, as it does for all health products on the Canadian market, to identify and assess potential harms.
The new data from the larger population in Europe as well as foreign regulatory actions have prompted Health Canada to consider changes to the product information and to inform healthcare professionals and the public about the risk of exfoliative dermatitis and erythrodermic psoriasis with STELARA.
Health Canada will keep Canadians informed and take action, as appropriate, if any new information is identified
"}]},{"template":1,"link_id":"SSR00048","review_date":null,"drug_name":"Imovane (zopiclone)","safety_issue":"Next-Day Impairment","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the risk of next-day impairment, including altered driving skills leading to car accidents, after exposure to IMOVANE and generic zopiclone products. The review was prompted by the results of recent studies that reported driving impairment the morning following bedtime use of hypnotics, especially at the higher recommended doses.","background":"IMOVANE and generic zopiclone products are approved for short-term use (up to 7 to 10 consecutive days) by adult patients with insomnia characterized by difficulties falling asleep, nighttime awakenings and/or early morning awakenings causing impaired daytime functioning.
Zopiclone products are currently marketed in Canada as 5 mg and 7.5 mg tablets. The 7.5 mg tablet can be split in half to achieve a lower dose (i.e., 3.75 mg). Zopiclone is taken at bedtime.
Next-day impairment with the use of hypnotics such as zopiclone is generally recognized as a decreased ability to be alert the next day after taking the medicine. It can include symptoms such as daytime sleepiness, impaired hand eye coordination, decreased mental sharpness and related motor functions. Some patients may have zopiclone blood levels in the morning that are high enough to produce psychological and motor impairment.
","objective":"To assess the available evidence concerning the risk of next-day impairment associated with the use of zopiclone. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data, as well as what is known about the use of zopiclone products both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"From 2008 to 2013, Canadian pharmacies dispensed more than 28 million prescriptions of zopiclone products, mostly in the 7.5 mg tablet strength. It is unclear what percentage of these prescriptions was written for use as one half of a 7.5 mg tablet. Zopiclone is generally prescribed to adults (more than 18 years of age). More than one third of all patients receiving zopiclone in Canada are 65 years of age or older.
At the time of this review, Health Canada had received 5 reports of next-day impairment suspected of being associated with zopiclone use. None of these cases resulted in an accident. In one case, excessive daytime drowsiness and fatigue were considered probably related to zopiclone therapy. In the remaining 4 cases, the reaction (e.g., confusion, fatigue, sleepiness, or drowsiness) could also be explained by other factors.
Evidence from studies has shown that healthy individuals taking zopiclone 7.5 mg at bedtime may have a decreased ability for vehicle control the morning after. The subjects are generally not aware of the possibility for this impairment.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":452,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":195,"footnotes":196,"title":"Summary Safety Review - IMOVANE (zopiclone) - Next-Day Impairment","created_date":"2014-11-21","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":196,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":196,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":195,"order_no":1,"bullet":"Verster JC, Spence DW, Shahid A, et al. Zopiclone as positive control in studies examining the residual effects of hypnotic drugs on driving ability. Current Drug Safety 2011;6(4):209-18."},{"field_id":195,"order_no":2,"bullet":"Leufkens TR, Ramaekers JG, de Weerd AW, et al. Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study. Psychopharmacology (Berl). 2014;231(14):2785-98."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":452,"order_no":1,"bullet":"The current available evidence suggests that next-day impairment may occur in patients the morning following bedtime zopiclone use, including altered driving skills which could lead to accidents.
Health Canada actions:
Sulfamethoxazole (SMX) and trimethoprim (TMP) are different antibiotics that can be used alone or in combination. When used separately, these antibiotics only stop the growth of bacteria. However, when combined together, these antibiotics kill the bacteria. It can lead to a better outcome for the patient. SMX-TMP containing products are used for the treatment of various infections such as bladder, lung, and ear infections. These products have been on the Canadian market since 1973.
Thrombocytopenia is a reduced number of platelets in the blood. Platelets are blood cells that play an important role in blood clotting. Severe bleeding may happen when the blood contains a low number of platelets. Drugs can cause thrombocytopenia by different mechanisms. For example, thrombocytopenia can be due to an allergic reaction to the drug, called hypersensitivity reaction. SMX-TMP use can trigger the immune system to produce antibodies that will destroy the platelets. This is called drug-induced immune thrombocytopenia.
","objective":"To review the available evidence concerning the risk of developing drug-induced immune thrombocytopenia while taking SMX-TMP containing medications. The evidence considered included Canadian patient reports of thrombocytopenia while taking SMX-TMP, medical and scientific literature, and what is known about the use of SMX-TMP containing products both in Canada and internationally. The current strategies to minimize the risk were also considered, including a review of the product information available to health care professionals and patients.","key_findings":"SMX-TMP containing products are widely used in Canada. At the time of the review, Health Canada estimated the number of prescriptions for these drugs at about 1,000,000 per year for the past 6 years.
At the time of the review, Health Canada had received 130 adverse reaction reports of thrombocytopenia with the use of SMX-TMP containing products. More than half of these reported thrombocytopenia without any other blood disorder. A fatal outcome was reported for 12 of these cases.
A number of case reports of thrombocytopenia associated with SMX-TMP have been published over the years. A search of the medical literature identified three population studies. The analysis of these studies showed an increased risk of thrombocytopenia with the use of SMX-TMP. The risk appears to be increased in some patients such as those who have the Acquired Immune Deficiency Syndrome (AIDS).
Taking into account the studies and case reports, it is possible that SMX/TMP can contribute to the development of drug-induced immune thrombocytopenia in some patients. Overall, the incidence of this reaction appears to be very low.
The U.S. prescribing information includes a warning on the risk of immune thrombocytopenia and a contraindication in patients allergic to SMX-TMP or with a history of drug-induced thrombocytopenia.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":453,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":197,"footnotes":198,"title":"Summary Safety Review - Sulfamethoxazole-Trimethoprim - Risk of Drug-induced Immune Thrombocytopenia","created_date":"2014-11-18","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":198,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":198,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":197,"order_no":1,"bullet":"Garbe E, Andersohn F, Bronder E, et al. Drug-induced immune thrombocytopaenia: results from the Berlin Case-Control Surveillance Study. Eur J Clin Pharmacol 2012;68(5):821-32."},{"field_id":197,"order_no":2,"bullet":"Ten Berg MJ, Huisman A, Souverein PC, et al. Drug-induced thrombocytopenia: a population study. Drug Saf 2006;29(8):713-21."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":453,"order_no":1,"bullet":"Considering the evidence regarding the risk of thrombocytopenia, the possible mechanism of SMX-TMP induced immune thrombocytopenia, and widespread use of these products in Canada, Health Canada is currently working with the manufacturers to update the prescribing information for SMX-TMP containing products. This will inform health professionals and patients of the potential risk of drug-induced immune thrombocytopenia with SMX-TMP containing products. The prescribing information will include a new contraindication indicating that SMX-TMP containing products should not be used in patients with a known hypersensitivity including a history of drug-induced immune thrombocytopenia.
"}]},{"template":1,"link_id":"SSR00050","review_date":null,"drug_name":"Azithromycin","safety_issue":"Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the possible link between a medical condition called DRESS which stands for Drug Reaction/Rash with Eosinophilia and Systemic Symptoms, and the antibiotic azithromycin (Zithromax®, Zmax® and its generics). This review was prompted from an adverse reaction report submitted to Health Canada.","background":"Azithromycin belongs to a group of antibiotics called macrolides. It is approved by Health Canada to treat mild to moderate infections in adults or children depending on the type of infection (e.g., pneumonia, influenza and sinus infections). Azithromycin is available as an oral liquid, a tablet and an injectable product.
DRESS describes a group of rare but serious and potentially life-threatening adverse reactions to medications. These reactions usually occur two weeks to two months after starting a medication. Patients may experience symptoms such as a fever, a severe skin rash with swollen face or peeling of the skin over large areas of the body. Abnormal changes in blood cells or organ function such as the liver and kidney may also occur. The reasons why DRESS can occur with some medications are unknown.
","objective":"To review the available evidence concerning the risk of DRESS associated with the use of azithromycin. The evidence that was considered included Canadian patient reports, scientific and medical literature on the use of azithromycin both in Canada and internationally.","key_findings":"Azithromycin was prescribed approximately 2 million times a year in Canada from 2008 to 2012. The group that received the greatest number of prescriptions for azithromycin was patients aged 19 years and younger with an average of 500 000 prescriptions a year from 2008 to 2012.
At the time of the review, Health Canada had received 1 report of DRESS associated with the use of azithromycin in Canada.
Four cases of DRESS involving azithromycin have been reported in the literature. However, as of the time of this review, no clinical or larger scale population studies have been published on the association of DRESS and azithromycin.
At the time of the review, the WHO Adverse Reaction Database, also known as Vigibase, contained 14 cases of DRESS associated with the use of azithromycin.
After review of all of the Canadian and foreign cases, the development of DRESS was found to be possibly associated with azithromycin in 3 of the cases, including the Canadian case and 2 foreign pediatric cases. Three of the 14 foreign cases resulted in death.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":454,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":199,"footnotes":200,"title":"Summary Safety Review - Azithromycin - Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2014-10-21","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":200,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":200,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogenous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."}],"reference_list":[{"field_id":199,"order_no":1,"bullet":"Walsh S, Diaz-Cano S, Higgins E, et al. Drug reaction with eosinophilia and systemic symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases. Br J Dermatol 2013;168(2):391-401."},{"field_id":199,"order_no":2,"bullet":"Criado PR, Avancini J, Santi CG, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a complex interaction of drugs, viruses and the immune system. Isr Med Assoc J 2012;14(9):577-82."},{"field_id":199,"order_no":3,"bullet":"Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 1996;15(4):250-7."},{"field_id":199,"order_no":4,"bullet":"Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 2013;169(5):1071-80."},{"field_id":199,"order_no":5,"bullet":"Shiohara T, Iijima M, Ikezawa Z, et al. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 2007;156(5):1083-4."},{"field_id":199,"order_no":6,"bullet":"Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol 2003;24(7):376-9."},{"field_id":199,"order_no":7,"bullet":"Kelemen JJ, III, Cioffi WG, McManus WF, et al. Burn center care for patients with toxic epidermal necrolysis. J Am Coll Surg 1995;180(3):273-8."},{"field_id":199,"order_no":8,"bullet":"Halebian PH, Corder VJ, Madden MR, et al. Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg 1986;204(5):503-12."},{"field_id":199,"order_no":9,"bullet":"Bauer KA, Brimhall AK, Chang TT. Drug reaction with eosinophilia and systemic symptoms (DRESS) associated with azithromycin in acute Epstein-Barr virus infection. Pediatr Dermatol 2011;28(6):741-3."},{"field_id":199,"order_no":10,"bullet":"Cascaval RI, Lancaster DJ. Hypersensitivity syndrome associated with azithromycin. Am J Med 2001;110(4):330-1."},{"field_id":199,"order_no":11,"bullet":"Pursnani A, Yee H, Slater W, et al. Hypersensitivity myocarditis associated with azithromycin exposure. Ann Intern Med 2009;150(3):225-6."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":454,"order_no":1,"bullet":"The current available evidence suggests the possibility that DRESS may occur with azithromycin use. Furthermore, DRESS is a known risk for a similar antibiotic, clarithromycin. Other serious, rare, allergic skin reactions such as Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are described in the prescribing information for azithromycin. Common features between all three conditions may make it more difficult for early diagnosis.
The prescribing information for Zithromax® and Zmax® has been updated to include the possible risk of DRESS. Manufacturers of generic versions of these drugs will also update their product information.
It is important for healthcare professionals and patients to be aware of the possibility of these rare serious reactions, and for steps to be taken for early detection of DRESS due to the fact that the treatment of TEN and SJS is different from DRESS. Health Canada has previously communicated with health professionals to raise awareness about this possible risk.
"}]},{"template":1,"link_id":"SSR00051","review_date":null,"drug_name":"Immunoglobulins","safety_issue":"Risk of Blood Clots (Thrombosis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to examine the information in the Canadian product monograph on the risk of blood clots (thrombotic events) for all non-hyperimmune immunoglobulin products (referred to as immunoglobulins for the purpose of this summary). The review was prompted by the ongoing assessment of information regarding these products and this adverse event, including data provided by manufacturers, two scientific and medical publications as well as regulatory actions by the United States Food and Drug Administration (US-FDA).","background":"Immunoglobulin products contain human antibodies which are also present in blood. Antibodies help the body to fight infections. While there are different strengths and ways to administer them, immunoglobulins are generally used in patients who do not have enough antibodies in their blood and tend to get frequent infections (called Primary and Secondary Immune Deficiency). In addition, some products are used to treat specific conditions that affect the nervous system, conditions that can cause the immune system to attack the body (autoimmunity), blood cancers (leukemia), and a severe decline in the number of blood clotting cells (platelets) called immune thrombocytopenic purpura (ITP).
Thrombosis (or blood clot) is a condition that results in a partial or complete blockage of blood flow, and can arise in a wide variety of ways and in any location in the body, including in the legs (deep vein thrombosis), the lungs (pulmonary embolism), the heart (myocardial infarction), and the brain (stroke). In many cases, thrombotic events may be life threatening.
The risk of thrombosis has been a known issue with some immunoglobulin products, and can occur regardless of immunoglobulin dose or route of administration (injection into a muscle, vein, or under the skin).
","objective":"To assess available information regarding the risk of thrombosis (blood clots) for all immunoglobulin products, and to determine the need for updating the Canadian product information for all immunoglobulin products. The evidence considered Canadian and international adverse reaction reports, scientific and medical literature, as well as what is known about the use of these products both in Canada and internationally.","key_findings":"The immunoglobulins are a large and diverse group of products derived from human blood and their use in clinical settings varies widely from region to region. Immunoglobulins are issued to hospitals in Canada by the Canadian Blood Services and Héma-Québec.
The following immunoglobulins are authorized for sale in Canada: Gammagard Liquid and Gammagard S/D; GamaSTAN; Gamunex; Hizentra; IGIVnex; Immune Serum Globulin (human); Octagam (5% and 10%); and Privigen.
At the time of this review, 19 cases in Canada were reported, all involving intravenous (injected into the vein) immunoglobulin products. Various thrombotic events were reported but there was no pattern in the type of thrombotic event.
Two separate publications in 2012 and 2013 detailed the findings of the review of a large database. In both studies, it was found that the risk of thrombosis appeared to span all products and routes of administration. Although both studies had limitations, there was enough evidence to suggest the need for a closer examination of the Canadian product information for all immunoglobulin products.
Furthermore, additional data submitted by the manufacturers in Canada, as part of regular periodic review, was analyzed and also justified the need for updating the product information, for consistency.
In addition, as part of Health Canada's monitoring of international events, it was learned that in 2013, the US-FDA issued a Safety Communication that was based on the emergence of post-marketing reports as well as the review of the database. The US-FDA stated that thrombosis risks applied to all routes of administration. The proposed new labelling for these products would include strong warnings and specific information regarding the types of events that could occur and risk factors.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":455,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":201,"footnotes":202,"title":"Summary Safety Review - Immunoglobulins - Risk of Blood Clots (Thrombosis)","created_date":"2014-10-09","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":202,"order_no":1,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":201,"order_no":1,"bullet":"FDA Drug Safety Communication: FDA Safety Communication: New boxed warning for thrombosis related to human immune globulin products. Silver Spring (MD): US Food and Drug Administration; 2013 Nov 14. (accessed 2013 Nov 14)."},{"field_id":201,"order_no":2,"bullet":"Daniel GW, Menis M, Sridhar G, et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010. Transfusion 2012;52(10):2113-21."},{"field_id":201,"order_no":3,"bullet":"Menis M, Sridhar G, Selvam N, et al. Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011. Am J Hematol 2013;88(12):1035-40."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":455,"order_no":1,"bullet":"Based on information reviewed, it was determined that there is enough evidence for updating the information for all immunoglobulin products.
The following actions have been undertaken by Health Canada:
Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00052","review_date":null,"drug_name":"Diclofenac","safety_issue":"Risk of Major Heart and Stroke Related Adverse Events","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was conducted to evaluate the currently available information regarding the potential heart and stroke related risks with diclofenac-containing products in tablet and suppository forms (VOLTAREN and VOLTAREN SR, VOLTAREN RAPIDE, or ARTHROTEC and generic equivalents). The review was prompted by the results of a study published in the scientific journal, The Lancet (Bhala et al, 2013). This study indicated that diclofenac increases heart and stroke related adverse events more than other non-steroidal anti-inflammatory drugs (NSAIDs) and comparably to cyclooxygenase 2 (COX-2) inhibitors, a subgroup of NSAIDs which includes celecoxib.","background":"Diclofenac is used for relieving pain and inflammation in conditions such as arthritis. Diclofenac is also used for the short-term treatment of pain and inflammation related to muscle, bone or soft tissue trauma, including sprains and pain following dental extractions. It belongs to a group of drugs called NSAIDs. Diclofenac was first marketed in Canada on December 31, 1989.
Serious heart and stroke related adverse events are rare, but are known potential side effects associated with the use of diclofenac and other NSAIDs. The risk of heart attack or stroke is higher in patients with a history of heart attack or stroke, or other risk factors for heart disease or stroke, including, angina, congestive heart failure, high blood pressure, high levels of fats in the blood, diabetes, and smoking. The risk of serious heart and stroke related adverse events is outlined in the product information available to the public.
","objective":"To assess the available evidence concerning the association of diclofenac with an increased risk of serious heart and stroke related adverse events, especially in patients with a history of, or risk factors for heart disease or stroke. This review considered scientific and medical literature, Canadian patient reports and what is known about the use of this drug both in Canada and internationally.","key_findings":"From 2008 to 2012, over 2 million prescriptions for oral diclofenac-containing products and around 30,000 prescriptions for rectal diclofenac-containing products were dispensed annually by pharmacies in Canada.
From January 1, 2008 to December 31, 2012, Health Canada received 39 reports of serious heart and stroke related adverse events potentially associated with diclofenac use. One of these cases had a fatal outcome. Although some of the reports did not provide sufficient information for thorough analysis, a number of cases did suggest a possible role for diclofenac in causing the serious heart and stroke related adverse event.
In 2008, Health Canada completed a safety review for diclofenac and found that diclofenac, especially at high doses (150 mg per day or more), is associated with an increased risk of serious heart and stroke adverse events. Information on the increased risk associated with the higher doses was included in the prescribing information for diclofenac-containing products. The current review investigated the more recent evidence published since 2008. The evidence confirmed the risk of serious heart and stroke adverse events in patients taking diclofenac for all indications, particularly at high doses (150 mg per day). Several large scale studies confirmed that users of diclofenac were at higher risk of heart and stroke related side effects than non-users as well as users of other NSAIDs.
Additionally, evidence suggests that diclofenac, particularly at higher doses (150 mg per day or more), is associated with an increased risk of heart and stroke related adverse events that is comparable to COX-2 inhibitors. The risk may increase with the dose and duration of use. Patients with a history of, or risk factors for heart disease, stroke or uncontrolled high blood pressure may be at greater risk.
At the time of this review, the World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) contained 1740 heart and stroke related adverse events associated with diclofenac use. These heart and stroke related reports come from over 50 different countries.
The European Medicines Agency (EMA) also commissioned a review of the current evidence and issued a safety communication regarding the increased risk of serious heart and stroke related adverse events with diclofenac use which is comparable to the use of COX-2 inhibitors.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":456,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":203,"footnotes":204,"title":"Summary Safety Review - Diclofenac - Risk of Major Heart and Stroke Related Adverse Events","created_date":"2014-10-06","modified_date":"2014-10-14","key_message_list":[],"footnotes_list":[{"field_id":204,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":204,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":204,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":203,"order_no":1,"bullet":"Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects on non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894):769-79."},{"field_id":203,"order_no":2,"bullet":"PRAC recommends the same cardiovascular precautions for diclofenac as for selective COX-2 inhibitors. London (UK): European Medicines Agency; 2013 June 14. (accessed 2014 Aug 28)."},{"field_id":203,"order_no":3,"bullet":"Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin Pharmacol Ther 2009;85(2):190-7."},{"field_id":203,"order_no":4,"bullet":"McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med 2011; 8(9):e1001098."},{"field_id":203,"order_no":5,"bullet":"Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342:c7086."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":456,"order_no":1,"bullet":"Health Canada's review of the safety of diclofenac has found that diclofenac is associated with an increased risk of heart and stroke related adverse events that is comparable to COX-2 inhibitors, and that this risk should be considered when prescribing or taking diclofenac.
In order to further reduce the risks associated with diclofenac, additional information is being added to the prescribing information for diclofenac-containing products, which includes:
The update to the prescribing information does not refer to topical formulations of diclofenac, such as gel or eye drops.
Health Canada has also issued a communication to inform healthcare professionals and patients about this risk and the changes to the Canadian prescribing information.
Health Canada has determined that the overall benefits of diclofenac continue to outweigh the risks, when used as recommended. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00060","review_date":null,"drug_name":"Diane 35 (Cyproterone Acetate and Ethinyl Estradiol)","safety_issue":"Venous Thromboembolism (blood clot)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"As part of Health Canada's efforts to minimize health risk factors to Canadians, a safety review was initiated to evaluate the currently available information regarding the potential risk of blood clots with DIANE-35. The review was prompted by a French medicines regulatory agency announcement on January 30th, 2013 indicating its intention to suspend the marketing authorizations for DIANE-35 and its generics for acne treatment in France within 3 months. The French decision was triggered by reports of deaths caused by blood clots associated with the use of DIANE-35 in France.a The Health Canada review includes the consideration of strategies that would minimize potential risks to Canadians with the use of DIANE-35.","background":"DIANE-35 and its generics are approved in Canada for the treatment of severe acne with accompanying symptoms of androgenisation (male characteristics) including excessively oily skin as well as facial and body hair growth, after topical therapy or systemic antibiotic treatments have failed. It is to be used only after other acne treatments have not worked. In discussion with a woman's health care provider, the use of these medicines should be discontinued when signs of acne have cleared.
Blood clots are a rare but well-known side effect associated with the use of DIANE-35 and other hormonal products containing progestins and estrogens. The risk of blood clot formation is less common in young, healthy, non-pregnant women than in those on hormonal products. Other issues that may increase a woman's chance of developing a clot include older age, smoking, obesity and periods of immobility such as those associated with long-distance travel or hospitalization. Some evidence indicates that the chance of developing clots may be higher during the first year of use with hormonal products. The risk of blood clots is outlined in the product information available to the public.
","objective":"To assess the available evidence that dealt with a woman's chance of developing a blood clot while taking DIANE-35. The evidence considered Canadian patient reports, scientific and medical literature, and what is known about the use of this medicine both in Canada and internationally. The currently existing strategies to minimize this risk were also considered, including a review of the product information available to health care professionals and patients.","key_findings":"Health Canada estimates the number of prescriptions for DIANE-35 and generics to be stable over the last five years at approximately 450,000 prescriptions per year, which corresponds to about 40,000 women using this drug each year in Canada. The major reason for prescribing this medicine is for the treatment of severe acne, but the data also indicates its usage as a means of birth control (estimated at 35-40% of prescriptions given by general practitioners and obstetrician/gynecologists), which is considered an unapproved use of this drug. However, due to the relatively low number of overall prescriptions for DIANE-35 in Canada, these figures on use as a means of birth control can only be used as guidance for estimation.
The Canada Vigilance database was searched for reports that implicated both cyproterone acetate and ethinyl estradiol products and a blood clot-related incident or any report of death. Reports from the point of DIANE-35 becoming available in Canada, in 1998, up to May 1, 2013, were collected. The search retrieved 95 unique reports. A total of 12 reports of death were identified and were further investigated. In 10 out of the 12 cases, the likelihood of the drug causing the death was considered to be at least "possible," with the other two reports containing not enough information to determine whether or not the drug caused the death. However, in nine out of these possible 10 cases, the patients had additional risk factors that would predispose or make it possible for them to have blood clots, such as obesity, smoking, previous trauma and decreased mobility. The case reports do not indicate a change in the known safety profile of DIANE-35 for blood clots in Canada.
The review considered the scientific and medical literature. Several scientific studies addressed the risk of blood clots with different types of hormonal products such as DIANE-35 and birth control pills. The risk of blood clots with these products was compared to the risk of blood clots in women that do not use these products. It was found that the occurrence of blood clots in users of DIANE-35 was higher than non-users but similar to some of the hormonal birth control products currently available on the Canadian market. It was concluded that this information does not point to a higher risk of blood clots than what is already known about DIANE-35 and outlined in the product information.
It was important to determine how DIANE-35 was being used in other countries to better understand the French medicines regulatory agency's decision. At that time, the approved use of the drug in France was for treating acne, potentially exposing a greater number of French patients to the risk of blood clots than in Canada. In comparison, the approved use in the United Kingdom is similar to Canada: for treatment of moderate to severe acne and after used topical therapy or systemic antibiotic treatments have failed.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":464,"additional":"Suggested Prescriber/Counselling Checklist for DIANE-35 (cyproterone acetate/ethinylestradiol) and its generics ","full_review":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":219,"footnotes":220,"title":"Summary Safety Review - DIANE 35 (Cyproterone Acetate and Ethinyl Estradiol) - Venous Thromboembolism (blood clot)","created_date":"2014-04-08","modified_date":"2014-11-17","key_message_list":[],"footnotes_list":[{"field_id":220,"order_no":1,"bullet":"DIANE-35 was re-instated in France in January 2014."}],"reference_list":[{"field_id":219,"order_no":1,"bullet":"Bayer Inc. Official Canadian Product Monograph for DIANE-35 (dated June 17, 2010)"},{"field_id":219,"order_no":2,"bullet":"Bird ST, et al. (2013) Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. CMAJ 185(2):E115-E120"},{"field_id":219,"order_no":3,"bullet":"Hansson PO, Sorbo J and Eriksson H. (2000) Recurrent venous thromboembolism after deep vein thrombosis: Incidence and risk factors. Arch Intern Med;160:769-774."},{"field_id":219,"order_no":4,"bullet":"Heinemann LAJ and Dinger JC. (2007) Range of published estimates of venous thromboembolism incidence in young women. Contraception 75:328-36."},{"field_id":219,"order_no":5,"bullet":"Heit JA, et al. (2005). Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 143:697-706."},{"field_id":219,"order_no":6,"bullet":"Johnson JV, et al. (2008) Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial. Obstet Gynecol 111:278-84."},{"field_id":219,"order_no":7,"bullet":"Lidegaard O, et al. (2011) Risk of venous thromboembolism from use of oral contraceptives containing different progestogenes and oestrogen doses: Danish cohort study, 2001-2009. BMJ. 343:d6423."},{"field_id":219,"order_no":8,"bullet":"Lidegaard O, et al. (2009) Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ; 339:b2890"},{"field_id":219,"order_no":9,"bullet":"Lidegaard O, et al. (2002) Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception 65:187-196."},{"field_id":219,"order_no":10,"bullet":"Middeldorp S, et al. (2000) Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a crossover study. Thromb Haemost 84:4-8."},{"field_id":219,"order_no":11,"bullet":"Nast A, et al. (2012) European Evidence-Based (S3) Guidelines for the Treatment of Acne. J Eur Acad Dermatol Venereol 26(S1):1-29."},{"field_id":219,"order_no":12,"bullet":"Rosendaal FR. (1999) Venous thrombosis: a multicausal disease. Lancet 353:1167-73."},{"field_id":219,"order_no":13,"bullet":"Seaman HE, et al. (2004) Venous thromboembolism associated with cyproterone acetate in combination with ethinyloestradiol (Dianette®): observational studies using the UK General Practice Research Database. Pharmacoepidemiol Drug Saf 13:427-436."},{"field_id":219,"order_no":14,"bullet":"Silverstein MD, et al. (1998) Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population- based study. Arch Intern Med 158:585-593."},{"field_id":219,"order_no":15,"bullet":"Tans G, et al. (2000) A randomized cross-over study on the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulant pathways. Thromb Haemost 84:15-21."},{"field_id":219,"order_no":16,"bullet":"Tchaikovski SN and Rosing J. (2010) Mechanisms of estrogen-induced venous thromboembolism. Thromb Res 126:5-11."},{"field_id":219,"order_no":17,"bullet":"Thiboutot D, et al. (2009) New insights into the management of acne: An update from the Global Alliance to improve outcomes in acne group. J Am Acad of Dermatol 60(5) S1:pp.S1-S50."},{"field_id":219,"order_no":18,"bullet":"UK Summary of Product Characteristics for Dianette updated 19 March 2012 http://www.medicines.org.uk/emc/medicine/1814/SPC"},{"field_id":219,"order_no":19,"bullet":"van Hylckama Vlieg A, et al. (2009) The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 339:b2921."},{"field_id":219,"order_no":20,"bullet":"Vasilakis-Scaramozza C and Jick H. (2001) Risk of venous thromboembolism with cyproterone or levonorgestrel contraceptives. Lancet 358:1427-29."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":464,"order_no":1,"bullet":"The current prescribing information for DIANE-35 already contained warnings about the risk of blood clots. This information is supported by evidence from key scientific studies. Considering the current evidence and discussions that have taken place internationally, Health Canada is adopting a precautionary approach and has updated the prescribing information to provide further clarity regarding this rare but known risk. The completion of the review was communicated in the form of an advisory, to inform the public and health care professionals about the safe use of this product in the appropriate patient population. Health Canada's review of the safety of the anti-acne medication DIANE-35 has found that the drug's benefits continue to outweigh the risks, when used as authorized."}]},{"template":1,"link_id":"SSR00053","review_date":null,"drug_name":"Imuran (azathioprine)","safety_issue":"Serious Brain Infection (Progressive Multifocal Leukoencephalopathy)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was conducted to evaluate the available information regarding the potential risk of developing a serious brain infection called progressive multifocal leukoencephalopathy or PML with azathioprine. This review was conducted because several cases of PML had been reported worldwide in patients who had received azathioprine.","background":"Azathioprine has been on the market in Canada since 1966 under the name Imuran. Since then, generics of Imuran have also been made available on the Canadian market. Azathioprine is an immunosuppressant. It lowers the body's defenses by reducing the strength of the immune system. The drug is indicated for people with kidney transplants and with rheumatoid arthritis (RA). The prescribing information (Canadian Product Monograph or CPM) includes information concerning the possibility of infection but does not specifically mention PML.
PML is a rare, serious infection of the brain caused by the John Cunningham (JC) virus. PML develops most commonly in people whose body defense mechanisms are very low; the virus does not cause PML in healthy individuals. Some people with Acquired Immunodeficiency Syndrome (AIDS), certain cancers, tuberculosis or organ transplantation may be at higher risk of having PML. It may also develop when people are taking certain drugs such as other immunosuppressants. PML, if severe, may cause death.
People with PML may have paralysis on one side of the body, unsteady gait, abnormal behaviour, seizures, and coma. Diagnosis of PML is based on radiological testing such as magnetic resonance imaging (MRI) and laboratory tests that detect the virus in the brain and spinal fluid. However, the best test for PML is a brain biopsy. There is no specific drug to treat PML. The main goal of treatment is to support the body's defense mechanisms.
","objective":"To assess the risk of a person developing PML while taking azathioprine. The evidence considered included Canadian adverse reaction reports, scientific and medical literature, international safety data, and what is known about the use of this product both in Canada and internationally.","key_findings":"Prescription data over approximately a 5 year period suggest that the use of azathioprine in Canada is on the rise in the community, whereas its use in hospitals is on the decline.
At the time of this review, no Canadian cases had been reported suggesting PML in association with azathioprine.
At the time of this review, 56 cases of PML associated with azathioprine had been identified worldwide. Of these cases, 24 had sufficient information to be further reviewed by Health Canada. Azathioprine was found to be a possible cause for the development of PML in all 24 cases. However, it is difficult to determine to what extent azathioprine contributes to PML because azathioprine is usually given in combination with other drugs that can cause PML. In addition, the disease being treated with azathioprine can also cause PML.
There was no evidence to suggest that the dose of azathioprine taken had an effect on the development of PML. However, people may get better when the dose of azathioprine is decreased or the drug is stopped.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":457,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":205,"footnotes":206,"title":"Summary Safety Review - Imuran (azathioprine) - Serious Brain Infection (Progressive Multifocal Leukoencephalopathy)","created_date":"2014-09-30","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":206,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":206,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":206,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":205,"order_no":1,"bullet":"Imuran® (azathioprine) Canadian Product Monograph, January 31, 2013."},{"field_id":205,"order_no":2,"bullet":"Chihara D, Takeoka T, Shirase T, et al. Progressive multifocal leukoencephalopathy in myelodysplastic syndrome involving pure red cell aplasia. Intern Med 2010; 49:2347-52."},{"field_id":205,"order_no":3,"bullet":"Schmedt N, Andersohn F, Garbe E. Signals of progressive multifocal leukoencephalopathy for immunosuppressants: a disproportionality analysis of spontaneous reports within the US Adverse Event Reporting System (AERS). Pharmacoepidemiol Drug Saf 2012; 21(11):1216-20."},{"field_id":205,"order_no":4,"bullet":"Keene DL, Légaré C, Taylor E, et al. Monoclonal antibodies and progressive multifocal leukoencephalopathy. Can J Neurol Sci 2011; 38(4):565-571."},{"field_id":205,"order_no":5,"bullet":"Koralnik IJ. Progressive multifocal leukoencephalopathy revisited: has the disease outgrown its name? Ann Neurol 2006; 60(2):162-73."},{"field_id":205,"order_no":6,"bullet":"Palazzo E, Yahia SA. Progressive multifocal leukoencephalopathy in autoimmune diseases. Joint Bone Spine 2012; 79(4):351-5."},{"field_id":205,"order_no":7,"bullet":"Carson KR, Focosi D, Major EO, et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncology 2009;10(8):816-24."},{"field_id":205,"order_no":8,"bullet":"Piccinni C, Sacripanti C, Poluzzi E, et al. Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents. Eur J Clin Pharmacol 2010; 66(2):199-206."},{"field_id":205,"order_no":9,"bullet":"Mentzer D, Prestel J, Adams O, et al. Case definition for progressive multifocal leukoencephalopathy following treatment with monoclonal antibodies. J Neurol Neurosurg Psychiatry 2012; 83(9):927-933."},{"field_id":205,"order_no":10,"bullet":"Calabrese L. A rational approach to PML for the clinician. Cleve Clin J Med 2011; 78(Suppl 2):S38-41."},{"field_id":205,"order_no":11,"bullet":"Brew BJ, Davies NW, Cinque P, et al. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat Rev Neurol 2010; 6(12):667-79."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":457,"order_no":1,"bullet":"There is evidence that suggests a link between azathioprine and PML, a rare and serious brain infection. It is difficult to determine to what extent azathioprine contributes to PML. However, healthcare professionals and patients should be aware of the possibility for PML to develop with azathioprine.
Health Canada is working with manufacturers to update the CPM for Imuran and generics and the risk of PML.
Health Canada will keep Canadians informed and take action, as appropriate, if any other new safety information is identified.
"}]},{"template":1,"link_id":"SSR00054","review_date":null,"drug_name":"Avastin (bevacizumab) and Lucentis (ranibizumab)","safety_issue":"Thrombotic Microangiopathy","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the possible risk of thrombotic microangiopathy (TMA), a blood clotting disorder affecting small blood vessels, associated with the use of AVASTIN (bevacizumab) and LUCENTIS (ranibizumab). AVASTIN and LUCENTIS are biologic drugs (products developed from living sources) called vascular endothelial growth factor (VEGF) inhibitors. These drugs help to stop the abnormal growth of blood vessels that surround tumours and in the eye. This review was a continuation of Health Canada's review activities of the large class of VEGF inhibitors. At the time, TMA was a known safety issue for AVASTIN, but not LUCENTIS.","background":"AVASTIN is used in combination with chemotherapy to treat colon, rectal, or lung cancers. It is also conditionally approved to be used to treat a particular type of brain cancer called glioblastoma. AVASTIN is given through a needle placed in a vein (intravenously).
LUCENTIS is used to treat damage to the light-sensitive back part of the eye, known as the retina, in various diseases of the eye, such as wet age-related macular degeneration. LUCENTIS is given as an injection into the eye (intravitreally).
Thrombotic microangiopathy refers to a group of disorders that involve the occurrence of blood clots in small blood vessels and can end in organ damage. Signs and symptoms of these disorders may include increased bruising, bleeding, fewer numbers of platelets and red blood cells, high blood pressure, and extreme weakness. Other organs and body systems that can be affected include the kidneys and the nervous system. TMA in the kidneys can result in excess proteins in the urine (proteinuria), which is an early sign of kidney damage. The risk of TMA in the kidneys, including proteinuria, is described in the Canadian product monograph (CPM) for AVASTIN. The association of TMA with VEGF inhibitors, including AVASTIN, has previously been communicated by Health Canada in 2008 and 2014.
","objective":"To assess the latest evidence for AVASTIN regarding the risk of TMA to determine if current risk minimization measures continue to be appropriate. Safety data for LUCENTIS was also assessed to determine if TMA is a new risk that needs to be minimized for this product. This review considered information from Canadian and international adverse reaction reports, scientific and medical literature, as well as what is known about the use of these products both in Canada and internationally.","key_findings":"Health Canada estimates the number of prescriptions dispensed by pharmacies for AVASTIN between 2009 and 2013 to be 24,504.
The number of prescriptions dispensed by pharmacies for LUCENTIS between 2009 and 2013 is estimated to be 338,889.
At the time of this review, Health Canada had received 7 reports of TMA suspected of being associated with AVASTIN. These reports involved patients being treated with AVASTIN for various types of cancer. Health Canada also received 27 reports of proteinuria suspected of being associated with AVASTIN. Proteinuria is an important sign of kidney damage which may have occurred as a result of TMA. Overall, reports of TMA or proteinuria in Canada suspected of being associated with AVASTIN are estimated to be rare.
There were no reports of TMA and one report of proteinuria suspected of being associated with LUCENTIS. Overall, reports of TMA or proteinuria in Canada suspected of being associated with LUCENTIS are estimated to be very rare.
Cases of TMA and proteinuria occurring after exposure to AVASTIN have been published in the literature. In some cases, kidney function and proteinuria improved when the drug was discontinued, suggesting the adverse reaction was at least partially reversible.
There is limited information on TMA in connection with LUCENTIS in the literature. One report was retrieved in which the drug was discontinued after the occurrence of TMA, and the patient was treated and fully recovered.
The literature suggests that the risk of TMA is applicable to the entire class of VEGF inhibitors (i.e., biologic and pharmaceutical drugs). The kidney is affected in most cases of TMA; however, cases of TMA affecting all parts of the body have also been observed. The scientific literature does not clearly explain how VEGF inhibitors can cause TMA.
There are international cases of TMA associated with AVASTIN and LUCENTIS. A review of the product information for AVASTIN and LUCENTIS in the United States, Australia, and Europe was done. It confirmed that product information in Canada regarding TMA and proteinuria is consistent with international product information.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":458,"additional":"For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":207,"footnotes":208,"title":"Summary Safety Review - AVASTIN (bevacizumab) and LUCENTIS (ranibizumab) - Thrombotic Microangiopathy","created_date":"2014-09-29","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":208,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":208,"order_no":2,"bullet":"It should be noted that the number of prescriptions or units dispensed does not reflect the number of patients receiving the product."},{"field_id":208,"order_no":3,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":208,"order_no":4,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":207,"order_no":1,"bullet":"Bollée G, Patey N, Cazajous G, et al.Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant 2009;24(2):682-5."},{"field_id":207,"order_no":2,"bullet":"Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008;358(11):1129-36."},{"field_id":207,"order_no":3,"bullet":"Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9(6):669-76."},{"field_id":207,"order_no":4,"bullet":"Frangié C, Lefaucheur C, Medioni J, et al. Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 2007;8(2):177-8."},{"field_id":207,"order_no":5,"bullet":"Hayman SR, Leung N, Grande JP, et al. VEGF inhibition, hypertension, and renal toxicity. Curr Oncol Rep 2012;14(4):285-94."},{"field_id":207,"order_no":6,"bullet":"Kremer Hovinga JA, Vesely SK, Terrell DR, et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010;115(8):1500-11."},{"field_id":207,"order_no":7,"bullet":"Moake JL. Thrombotic microangiopathies. NEngl JMed 2002;347(8):589-600."},{"field_id":207,"order_no":8,"bullet":"Neufield G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999;13(1):9-22."},{"field_id":207,"order_no":9,"bullet":"Pellé G, Shweke N, Duong Van Huyen JP, et al. Systemic and kidney toxicity of intraocular administration of vascular endothelial growth factor inhibitors. Am J Kidney Dis 2011;57(5):756-9."},{"field_id":207,"order_no":10,"bullet":"Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012;158(3):323-35."},{"field_id":207,"order_no":11,"bullet":"Stokes MB, Erazo MC, D'Agati VD. Glomerular disease related to anti-VEGF therapy. Kidney Int 2008;74(11):1487-91."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":458,"order_no":1,"bullet":"The current CPM for AVASTIN already contains warnings about the risk of TMA in the kidney and associated proteinuria, which is based on evidence from clinical studies and real-world use.
Given the evidence available at the time of this review, TMA is not considered to be a risk for LUCENTIS.
Health Canada decided to continue its ongoing monitoring of adverse reaction information involving AVASTIN and LUCENTIS, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00055","review_date":null,"drug_name":"Interferon-beta Products","safety_issue":"Thrombotic Microangiopathy","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the possible risk of thrombotic microangiopathy (TMA), a blood clotting disorder affecting small blood vessels, with the use of interferon-beta products. This review was prompted by a drug safety update issued in 2013 by the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) regarding several reports of TMA involving interferon-beta products.","background":"Four interferon-beta products are available in Canada: AVONEX (interferon beta-1a, first marketed in Canada in 2005); BETASERON (interferon beta-1b, first marketed in Canada in 1995); EXTAVIA (interferon beta-1b, first marketed in Canada in 2010); and REBIF (interferon beta-1a, first marketed in Canada in 1998). All four products are indicated for use in the treatment of multiple sclerosis.
In 2009, the Canadian product label for REBIF was updated to include information on the possible risk of TMA.
Thrombotic microangiopathy refers to a group of disorders that involve the occurrence of blood clots in small blood vessels which can end in organ damage. Signs and symptoms of these disorders may include increased bruising, bleeding, reduced numbers of platelets and red blood cells, high blood pressure, and extreme weakness. Other organs and body systems that can be affected include the kidneys, eyes and the nervous system.
","objective":"To assess the available evidence concerning the risk of developing TMA following exposure to any interferon-beta product. This review considered Canadian adverse reaction reports, scientific and medical literature, and international safety data, as well as what is known about the use of these products both in Canada and internationally, and evaluated the possible risk of TMA.","key_findings":"The total number of units purchased per product from January 2009 to March 2014 was as follows: 227,100 units of AVONEX; 123,466 units of BETASERON; 75,957 units of EXTAVIA; and 2,435,321 units of REBIF.
As of February 28, 2014, Health Canada received 3 reports of TMA following exposure to REBIF. No cases of TMA were reported for AVONEX, BETASERON or EXTAVIA.
A literature review identified 8 articles related to TMA involving interferon-beta products. A total of 11 cases were reported in these 8 articles. With the exception of one case, the interferon-beta product was used to treat a relapsing form of multiple sclerosis. The average time between starting the interferon-beta product and the diagnosis of TMA was approximately 4.4 years (range: 44 days to 10 years). All the cases were associated with kidney failure and the diagnosis was confirmed by kidney biopsy. In the majority of cases, the name of the interferon-beta product used was not provided. In one case, the use of BETAFERON (called BETASERON in Canada) was reported.
As of March 2014, the World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) contained 48 reports of TMA suspected of being associated with interferon-beta products (AVONEX = 6, BETASERON = 3, EXTAVIA = 0, REBIF = 39). The WHO data suggested that a cluster of reports involving REBIF occurred in 2011 (10 reports) and 2013 (17 reports). These two time periods accounted for two thirds of all reported cases of TMA following exposure to REBIF and approximately half of all reported cases of TMA involving any of the 4 interferon-beta products.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":459,"additional":"","full_review":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":209,"footnotes":210,"title":"Summary Safety Review - Interferon-beta Products - Thrombotic Microangiopathy","created_date":"2014-08-22","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":210,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":210,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the health product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."},{"field_id":210,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":209,"order_no":1,"bullet":"Broughton A, Cosyns JP, Jadoul M. Thrombotic microangiopathy induced by long-term interferon-ß therapy for multiple sclerosis: a case report. Clin Nephrol 2011;76(5):396-400."},{"field_id":209,"order_no":2,"bullet":"Nerrant E, Charif M, Ramay AS, et al. Hemolytic uremic syndrome: an unusual complication of interferon-ß treatment in a MS patient. J Neurol 2013;260(7):1915-6."},{"field_id":209,"order_no":3,"bullet":"Olea T, Díaz-Mancebo R, Picazo ML, et al. Thrombotic microangiopathy associated with use of interferon-beta. Int J Nephrol Renovasc Dis 2012;5:97-100."},{"field_id":209,"order_no":4,"bullet":"Cavoli GL, Passantino R, Tortorici C, et al. Comment on thrombotic microangiopathy induced by interferon-ß therapy. Clin Nephrol 2012;78(6):506-7."},{"field_id":209,"order_no":5,"bullet":"Orvain C, Augusto JF, Besson V, et al. Thrombotic microangiopathy due to acquired ADAMTS13 deficiency in a patient receiving interferon-beta treatment for multiple sclerosis. Int Urol Nephrol 2014;46(1):239-42."},{"field_id":209,"order_no":6,"bullet":"Mahe J, Meurette A, Moreau A, et al. Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis. Drug Des Devel Ther 2013;7:723-8."},{"field_id":209,"order_no":7,"bullet":"Hunt D, Kavanagh D, Drummond I, et al. Thrombotic microangiopathy associated with interferon beta. N Engl J Med 2014;370(13):1270-1."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":459,"order_no":1,"bullet":"A small number of cases of TMA after exposure to interferon-beta products have been reported in Canada and internationally. Several cases were suspected of being associated with REBIF. The current Canadian product label for REBIF currently addresses this risk. The scientific literature does not clearly explain why interferon-beta products can cause TMA.
Given the limited information available at the time of this review, Health Canada decided to continue its ongoing monitoring of adverse reaction information involving interferon-beta products, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00056","review_date":null,"drug_name":"Neupogen (filgrastim) and Neulasta (pegfilgrastim)","safety_issue":"Capillary Leak Syndrome","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the potential risk of capillary leak syndrome with NEUPOGEN (filgrastim) and NEULASTA (pegfilgrastim). The review was prompted from information shared by the European Medicines Agency (EMA). To follow up, Health Canada asked the manufacturer to provide their reports of capillary leak syndrome.","background":"NEUPOGEN and NEULASTA are used in Canada to treat neutropenia. Neutropenia is a condition where the body makes too few neutrophils, a type of white blood cell. Neutropenia can increase the chances of getting an infection and prevents the body from fighting it.
NEUPOGEN and NEULASTA have a similar effect.
NEUPOGEN has been marketed in Canada since 2002 and NEULASTA since 2004.
Cases of capillary leak syndrome have been reported internationally as an adverse reaction in persons receiving NEUPOGEN and NEULASTA. Capillary leak syndrome is a rare disorder characterized by massive leakage of fluid from the small blood vessels, also called capillaries, into surrounding tissues and body cavities. The leakage is caused by a sudden, unexplained change in the walls of the capillaries. This leakage results in a sharp drop in blood pressure which can lead to destruction of body tissues and death.
Symptoms of capillary leak syndrome include swelling or puffiness, which may be associated with passing water less frequently, difficulty breathing, abdominal swelling, a feeling of fullness and a general feeling of tiredness. These symptoms generally develop rapidly. Episodes vary in severity and frequency and may be fatal.
","objective":"To assess the association between the use of NEUPOGEN and NEULASTA and the occurrence of capillary leak syndrome. The evidence considered included Canadian adverse reaction reports, scientific and medical literature, as well as what is known about the use of this medicine in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"NEUPOGEN and NEULASTA are products that are more commonly used in the hospital setting, but can also be dispensed from non-hospital based pharmacies. The number of NEUPOGEN and NEULASTA prescriptions filled in non-hospital based pharmacies in Canada has been increasing at approximately 13% annually since 2009. It was estimated that approximately 83,363 prescriptions were dispensed in 2013.
As of January 2014, Health Canada did not receive any reports of capillary leak syndrome associated with NEUPOGEN and NEULASTA.
It is not clear from the scientific and medical literature why capillary leak syndrome occurs after exposure to NEUPOGEN and NEULASTA. However, it has been suggested in the literature that these drugs could have a direct effect on capillary walls, or cause an inflammatory response which may lead to tissue damage. The syndrome does appear to be more common in persons with overwhelming infections, in persons who had a bone marrow transplant, and in persons who had received anti-cancer drugs.
A search of the manufacturer's safety database retrieved 38 international cases of capillary leak syndrome following exposure to NEUPOGEN and 5 cases following exposure to NEULASTA. All the cases were reported to have also involved an anti-cancer therapy. Twenty-seven cases occurred after receiving the first dose of NEUPOGEN. Ten deaths were reported to have occurred following exposure to NEUPOGEN and 2 deaths occurred after exposure to NEULASTA. None of these cases were reported in Canada.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":460,"additional":"","full_review":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":211,"footnotes":212,"title":"Summary Safety Review - NEUPOGEN (filgrastim) and NEULASTA (pegfilgrastim) - Capillary Leak Syndrome","created_date":"2014-07-29","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":212,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc, An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":212,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":211,"order_no":1,"bullet":"Druey KM, Greipp PR. Narrative review: the systemic capillary leak syndrome. Ann Intern Med 2010;153(2):90-98."},{"field_id":211,"order_no":2,"bullet":"Kawabe S, Saeki T, Yamazaki H et al. Systemic capillary syndrome. Internal Med 2002;41:211-5."},{"field_id":211,"order_no":3,"bullet":"Nagao Y, Harada H, Yamanaka H, et al. Possible mediators for systemic capillary leak syndrome. Am J Med 2011;124(1):e7-9."},{"field_id":211,"order_no":4,"bullet":"Rechner I, Brito-Babapulle F, Fielden J. Systemic capillary leak syndrome after granulocyte colony-stimulating factor (G-CSF). Hematol J 2003;4:54-56."},{"field_id":211,"order_no":5,"bullet":"Shinohara K. Systemic capillary leak syndrome caused by granulocyte colony-stimulating factor. Intern Med 2011;50:2259."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":460,"order_no":1,"bullet":"Based on the information provided in this review, Health Canada concluded that there is sufficient evidence to support the association between the use of NEUPOGEN and NEULASTA and the occurrence of capillary leak syndrome.
The following actions have been undertaken by the manufacturer and Health Canada to minimize this risk:
Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00057","review_date":null,"drug_name":"Topical Antiseptic Products","safety_issue":"Risk of Infection","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"A safety review was initiated to evaluate the currently available information regarding the possible risk of infection associated with the use of topical antiseptic products intended for skin preparation before an operation (preoperative) or before an injection (preinjection). This review was prompted by a United States (U.S.) Food and Drug Administration (FDA) safety alert1 issued on November 13, 2013. The alert informed consumers of the ongoing evaluation of infrequent but continuing reports of infection resulting from antiseptic products used to clean the skin during preoperative preparation or preinjection preparation.","background":"Topical antiseptics are antimicrobial substances used to destroy or reduce harmful microorganisms such as bacteria or fungi on the skin. These products are used by both consumers and health care professionals. In Canada, there are several types of topical antiseptics. The current review focusses only on preoperative and preinjection topical antiseptic skin preparations.
There are a variety of topical antiseptic products licensed by Health Canada for preoperative or preinjection skin preparation. These products often contain ethyl alcohol, isopropyl alcohol, povidone-iodine, and chlorhexidine gluconate. They may be packaged in single-use forms such as individual swabs, wipes, pads, or sponges, or multiple-use forms such as a multi-use container. Antiseptics that are sterile will be labelled as such, with the word sterile appearing on the label. Health Canada has developed a document used as referencing standards for topical antiseptic products: Human-Use Antiseptic Drugs Guidance Document. This document outlines the requirements of antiseptic products including specific labelling.
When used properly, antiseptic products are safe and effective in reducing the number of microorganisms on the skin prior to surgery or injections. If they become contaminated from improper handling, storage or use; however, harm can occur. Cases of infection associated with contaminated antiseptic products from improper handling, storage or use have been reported in the U.S.
Microorganisms in the contaminated antiseptic product can be transferred into the body and may cause infections. Infections can occur at the injection or the operation site, such as at the skin (cellulitis), the joints (septic arthritis), or the intravenous (IV) site (phlebitis). Other infections may involve the blood (bacteremia) and other organs in the body (sepsis). Some of these complications are considered serious and can be fatal. Complications from the use of contaminated antiseptics can affect both healthy persons and those with chronic illnesses. Patients who have recently had surgery, or require regular skin disinfection for daily injections (such as persons with diabetes), intravenous treatments (such as persons receiving chemotherapy), blood transfusions, and/or dialysis, are more likely to be vulnerable to complications arising from infections.
","objective":"To summarize the available evidence concerning the risk of infection from contaminated antiseptic products intended for preoperative or preinjection skin preparation. This review considered Canadian adverse reaction reports, scientific and medical literature, and what is known about the use of these products both in Canada and internationally. Existing strategies currently available to minimize this risk were also considered, including a review of safety information available to consumers and health care professionals.","key_findings":"As of July 31, 2013, Health Canada received 4 reports involving topical antiseptic products intended for preoperative or preinjection skin preparation and symptoms related to infection. All 4 reports were considered serious. Three of these reports involved antiseptic products that were possibly contaminated during their manufacturing and were not related to improper handling, storage or use by users. These products were recalled in 2011 in Canada and the U.S. In the fourth Canadian report, there was not enough information to link the cause of the infection to the use of a contaminated antiseptic product. Overall, Health Canada could not confirm any reports of infections associated with improper handling, storage or use of topical antiseptic products. Literature specific to Canada on the use of these products is not available.
In the scientific and medical literature, there are several reports of infection associated with the use of topical antiseptic products intended for preoperative or preinjection skin preparation that have been contaminated from improper handling, storage or use. Many of these reports are hospital-based and from the U.S. Examples of improper handling, storage or use include: diluting the antiseptic product with contaminated water, failing to use a clean (sterile) technique during its use or preparation, using dirty containers to prepare solutions, storing solutions with cotton gauze and storing products without a lid.
According to the safety alert issued by the FDA, there were 88 reported cases of infection associated with the use of contaminated topical antiseptic products intended for preoperative or preinjection skin preparation, including 4 deaths. To decrease the risk of infection, the FDA recommended that health care professionals and patients follow all directions on product labels. They also recommended that manufacturers of these products voluntarily revise their labels and package these products in single-use containers.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":461,"additional":"","full_review":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":213,"footnotes":214,"title":"Summary Safety Review - Topical Antiseptic Products - Risk of Infection","created_date":"2014-07-25","modified_date":null,"key_message_list":[{"field_id":0,"order_no":9,"bullet":""}],"footnotes_list":[{"field_id":214,"order_no":1,"bullet":"FDA Drug Safety Communication: FDA requests label changes and single-use packaging for some over-the-counter topical antiseptic products to decrease risk of infection. Silver Spring (MD): US Food and Drug Administration; 2013 Nov 13. (accessed 2014 Jul 11)."},{"field_id":214,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":213,"order_no":1,"bullet":"Guidance Document - Human-Use Antiseptic Drugs. Ottawa (ON): Health Canada; 2009. (accessed 2014 Jul 11)."},{"field_id":213,"order_no":2,"bullet":"Weber DJ, Rutala WA, Sickbert-Bennett EE. Outbreaks associated with contaminated antiseptics and disinfectants. Antimicrob Agents Chemother 2007;51(12):4217-24."},{"field_id":213,"order_no":3,"bullet":"Triad group issues a voluntary nationwide recall of all lots of alcohol prep pads, alcohol swabs, and alcohol swabsticks due to potential microbial contamination. Silver Spring (MD): US Food and Drug Administration; 2011 Jan 5. (accessed 2014 Jul 11)."},{"field_id":213,"order_no":4,"bullet":"FDA Drug Safety Communication: FDA requests label changes and single-use packaging for some over-the-counter topical antiseptic products to decrease risk of infection. Silver Spring (MD): US Food and Drug Administration; 2013 Nov 13. (accessed 2014 Jul 11)."},{"field_id":213,"order_no":5,"bullet":"Chang CY, Furlong LA. Microbial stowaways in topical antiseptic products. N Engl J Med 2012;367(23):2170-3."},{"field_id":213,"order_no":6,"bullet":" Notes from the field: Contamination of alcohol prep pads with Bacillus cereus group and Bacillus species ― Colorado, 2010. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep 2011;60(11):347."},{"field_id":213,"order_no":7,"bullet":" Allergy injection-associated Mycobacterium abscessus outbreak ― Texas, 2009. Arlington (VA): Infectious Diseases Society of America; 2010 Oct 22. (accessed 2014 Jul 11)."},{"field_id":213,"order_no":8,"bullet":"Arjunwadkar VP, Bal AM, Joshi SA, et al. Contaminated antiseptics ― an unnecessary hospital hazard. Indian J Med Sci 2001;55(7):393-8."}],"use_canada_list":[{"field_id":0,"order_no":9,"bullet":""}],"finding_list":[{"field_id":0,"order_no":9,"bullet":""}],"conclusion_list":[{"field_id":461,"order_no":1,"bullet":"Topical antiseptic products for preoperative or preinjection skin preparation are safe and effective; however, if proper care is not taken when using them, they can become contaminated and cause serious, subsequent infections. Although Health Canada could not confirm any Canadian reports of infection associated with improper handling, storage or use of topical antiseptic products, proactive measures are being taken due to the availability of products in Canada similar to those in the U.S., where cases of infection associated with improper handling, storage or use of topical antiseptic products have been reported.
Health Canada actions:
In Canada, there are 12 testosterone-containing products that are currently marketed for use as testosterone replacement therapy: ANDRIOL, ANDRODERM, ANDROGEL, AXIRON, DELATESTRYL, DEPO-TESTOSTERONE, TESTIM and their equivalent generics. These products are approved for use in adult males who are experiencing medical conditions because their body cannot make enough testosterone. Testosterone replacement products should not be used in men for non-specific symptoms if laboratory tests have not been done to confirm a low testosterone level, and if other possible causes of symptoms have not been excluded.
Cardiovascular risk refers to the risk of a group of heart and blood vessel problems that can include, but is not limited to, heart attacks, strokes, blood clots in the lungs or legs, and an irregular heart rate. It is known that testosterone replacement therapy may cause an increase in blood pressure and fluid retention/swelling. In addition to these risks, testosterone replacement products may also cause blood vessel narrowing by promoting the build-up of fats and other materials in the inner walls of blood vessels. This narrowing of blood vessels makes it harder for blood to flow through, and if a blood clot forms and blocks the flow of blood, it may cause a heart attack or stroke. Testosterone replacement products may also cause blood clots in the lungs or legs by affecting blood clotting processes.
At the time of this review, the Canadian product label for testosterone replacement products identified the risk of high blood pressure, as well as fluid retention/swelling (particularly in persons with underlying heart problems).
","objective":"To assess the available evidence concerning the cardiovascular risk, beyond the known risks of high blood pressure and fluid retention/swelling, which may be linked to testosterone replacement products. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data, as well as what is known about the use of these products both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"Similar to the trend in other countries, prescriptions for testosterone replacement products in Canada have been increasing. Testosterone was most commonly prescribed to men aged 40-59 years. The elderly population (65 years old and over) is the second most prescribed age group.
As of Aug. 31, 2013, Health Canada received 35 reports of cardiovascular problems involving testosterone replacement products. Some of these reports described the problem as disappearing after the patient stopped using the product or as re-appearing when the patient re-started the product after having temporarily stopped it. This may support a possible link between cardiovascular risk and testosterone replacement products. Some of the reports also described patients with current, or a history of, conditions (e.g., diabetes and high blood pressure) that may also be associated with the reported cardiovascular problems. In 11 of the 35 reports, heart attack, blood clots in the lungs, or irregular heart rate were considered possibly related to testosterone therapy.
Several studies conducted after marketing suggest an increased risk of serious cardiovascular problems (e.g., heart attack and stroke) that may be linked to testosterone replacement products. Although these studies have limitations, they provide evidence in support of this possible association when considered as a whole.
Additional cases of cardiovascular problems, such as blood clots in the lungs and legs, have also been reported in the literature, as well as in other countries. Some of these cases also described the problem as disappearing after the patient stopped using the product or as re-appearing after the patient re-started the product after having temporarily stopped it.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":462,"additional":"","full_review":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":215,"footnotes":216,"title":"Summary Safety Review - Testosterone Replacement Products - Cardiovascular Risk","created_date":"2014-07-15","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":216,"order_no":1,"bullet":"Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310(17):1829-36."},{"field_id":216,"order_no":2,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":216,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":215,"order_no":1,"bullet":"Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310(17):1829-36."},{"field_id":215,"order_no":2,"bullet":"Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95(6):2536-59."},{"field_id":215,"order_no":3,"bullet":"Dohle GR, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism. European Association of Urology 2012; Feb:1-28."},{"field_id":215,"order_no":4,"bullet":"Ajayi AAL, Mathur R, Halushka PV. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses. Circulation 1995;91(11):2742-7."},{"field_id":215,"order_no":5,"bullet":"Death AK, McGrath KCY, Sader MA, et al. Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway. Endocrinology 2004;145(4):1889-97."},{"field_id":215,"order_no":6,"bullet":"McCrohon JA, Jessup W, Handelsman DJ, et al. Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1. Circulation 1999;99(17):2317-22."},{"field_id":215,"order_no":7,"bullet":"Sandset PM, Høibraaten E, Eilertsen AL, et al. Mechanisms of thrombosis related to hormone therapy. Thromb Res 2009;123, Suppl 2:S70-3."},{"field_id":215,"order_no":8,"bullet":"Swerdloff RS, Wang C, Cunningham G, et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85(12):4500-10."},{"field_id":215,"order_no":9,"bullet":"Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363(2):109-22."},{"field_id":215,"order_no":10,"bullet":"Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 2014;9(1):e85805."},{"field_id":215,"order_no":11,"bullet":"Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 2013;11:108."},{"field_id":215,"order_no":12,"bullet":"Glueck CJ, Goldenberg N, Budhani S, et al. Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. Transl Res 2011;158(4):225-34."},{"field_id":215,"order_no":13,"bullet":"Glueck CJ, Richardson-Royer C, Schultz R, et al. Testosterone, thrombophilia, and thrombosis. Clin Appl Thromb Hemost 2014;20(1):22-30."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":462,"order_no":1,"bullet":"The current available evidence suggests the possibility that cardiovascular problems, other than those already identified, may occur with the use of testosterone replacement products. The use of these products in Canada (and internationally) has been increasing and findings from a Canadian study raise additional concerns that these products may not always be used within the approved patient population.
Health Canada actions:
Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
"}]},{"template":1,"link_id":"SSR00059","review_date":null,"drug_name":"Serotonin blocking drugs (serotonin antagonists) ALOXI® (palonosetron), ANZEMET® (dolasetron), KYTRIL®(granisetron) and generics, and ZOFRAN® (ondansetron) and generics","safety_issue":"Serotonin Syndrome","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"Health Canada has completed a safety review of the serotonin blocking drugs (serotonin antagonists) dolasetron (was sold under the brand name ANZEMET® and was recently withdrawn from the market by the manufacturer), granisetron (KYTRIL®1 and generics), ondansetron (ZOFRAN®2 and generics) and palonosetron (ALOXI®3). These drugs are used for treating nausea and vomiting due to cancer therapy. This review identified a potential risk of serotonin syndrome.4 Serotonin syndrome occurs when serotonin accumulates to high levels in the body.
A 2012 article in the World Health Organization (WHO) Pharmaceuticals Newsletter prompted the review. The publication indicated that ondansetron used together with other drugs that affect serotonin levels (serotonergic drugs) may contribute to the development of serotonin syndrome in susceptible patients.5
","background":"These drugs are indicated for the treatment of nausea and vomiting associated with cancer therapy in adults. However, individual drugs in this class have specific indications (please refer to the drug specific Canadian Product Monograph1, 2, 3 for details).
Cells which are part of the intestine store about 90% of the body's serotonin.6 Cancer therapy can damage the intestine and trigger the release of serotonin.7 The released serotonin can cause nausea and vomiting. Serotonin blocking drugs (5-HT3 receptor antagonists) help prevent nausea and vomiting by blocking the effect of serotonin.
Serotonin syndrome occurs when serotonin, a chemical normally found in the body, accumulates to high levels. This usually happens with combinations of certain drugs that affect serotonin levels, but may also occur with a single drug.
It is very important to diagnose serotonin syndrome early as it can be fatal if not treated. Symptoms of serotonin syndrome may include any combination of confusion, agitation, restlessness, muscle twitching or stiffness, fever, increased sweating and heart rate, blood pressure fluctuations, pupil dilatation, nausea and/or vomiting, loss of consciousness and coma.8, 9 Neuroleptic malignant syndrome is a life-threatening condition with changes in the nervous, muscular and cardiovascular system. Neuroleptic malignant syndrome is associated with the use of antipsychotics and dopamine enhancing drugs10, 11 and it presents with clinical features similar to serotonin syndrome. Dopamine is another chemical normally found in the body. The way neuroleptic malignant syndrome occurs in the body is different to how serotonin syndrome occurs in the body. However, these two syndromes raise a diagnostic problem to the treating healthcare professional. As the treating healthcare professional could misdiagnose serotonin syndrome, it is important that patients who experience any of these symptoms talk to a healthcare professional immediately.
","objective":"To assess the available evidence concerning the risk of developing serotonin syndrome associated with serotonin blocking drugs used to treat nausea and vomiting. The evidence considered Canadian patient reports, scientific and medical literature, and other publically available information about the use of these drugs both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.","key_findings":"Full review reports are available upon request to Marketed Health Products Directorate. These reports are subject to redactions of personal and confidential information.
","references":217,"footnotes":218,"title":"Summary Safety Review - Serotonin blocking drugs (serotonin antagonists) ALOXI® (palonosetron), ANZEMET® (dolasetron), KYTRIL® (granisetron) and generics, and ZOFRAN® (ondansetron) and generics - Serotonin Syndrome","created_date":"2014-05-14","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":218,"order_no":1,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."}],"reference_list":[{"field_id":217,"order_no":1,"bullet":"Hoffman-La Roche Ltd. Canadian Product Monograph for KYTRIL® (dated December 13, 2013)."},{"field_id":217,"order_no":2,"bullet":"GlaxoSmithKline Inc. Canadian Product Monograph for ZOFRAN® and ZOFRAN® ODT (dated September 13, 2013)."},{"field_id":217,"order_no":3,"bullet":"Eisai Ltd. Canadian Product Monograph for ALOXI® (dated November 25, 2013)."},{"field_id":217,"order_no":4,"bullet":"Boyer EW, Shannon M. Current concepts: The serotonin syndrome. N Engl J Med. 2005; 352(11):1112-1120."},{"field_id":217,"order_no":5,"bullet":"WHO Pharmaceuticals Newsletter. Ondansetron and serotonin syndrome. 2012; 3:16-21."},{"field_id":217,"order_no":6,"bullet":"Kovac AL. Prophylaxis of postoperative nausea and vomiting: Controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists. J Clin Anesth. 2006; 18(4):304-318."},{"field_id":217,"order_no":7,"bullet":"Feyer P, Jordan K. Update and new trends in antiemetic therapy: The continuing need for novel therapies. Ann Oncol. 2011; 22(1):30-38."},{"field_id":217,"order_no":8,"bullet":"Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004; 42(3):277-285."},{"field_id":217,"order_no":9,"bullet":"Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: Review. J Clin Psychopharmacol. 1997;17(3):208-221."},{"field_id":217,"order_no":10,"bullet":"Moscovich M, Nóvak FTM, Fernandes AF, Bruch T, Tomelin T, Nóvak EM, et al. Neuroleptic malignant syndrome. Arq Neuropsiquiatr. 2011; 69(5):751-755."},{"field_id":217,"order_no":11,"bullet":"Perry PJ, Wilborn CA. Serotonin syndrome vs neuroleptic malignant syndrome: A contrast of causes, diagnoses, and management. Ann Clin Psychiat. 2012; 24(2):155-162."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":463,"order_no":1,"bullet":"The Health Canada review noted that when used as indicated, serotonin blocking drugs used to treat nausea and vomiting alone are unlikely to cause serotonin syndrome. However, when these drugs are used in combination with other drugs that affect serotonin levels, the way they work together in the body could explain how serotonin syndrome can occur.
Health Canada has requested that manufacturers incorporate the risk of serotonin syndrome into the Warnings and Precautions section and the Consumer Information section of the Canadian Product Monograph for these drugs. The Canadian Product Monographs for ALOXI®, KYTRIL®, and ZOFRAN® now contain this new safety information. ANZEMET® has recently been discontinued by the manufacturer in Canada. Manufacturers of generic versions of these drugs will also update their Product Monographs. On May 14, 2014 Health Canada also issued an Information Update to the public communicating the risk of serotonin syndrome with serotonin blocking drugs used to treat nausea and vomiting.
"}]},{"template":2,"link_id":"SSR00061","review_date":null,"drug_name":"Essure Permanent Birth Control System manufactured by Bayer Healthcare LLC","safety_issue":"Complications including allergic reactions, abnormal bleeding/menstrual changes and the need for device removal","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":491,"overview":"Health Canada carried out a safety review due to concerns regarding complications associated with the Essure device after it is inserted into the fallopian tubes. In certain cases, the symptoms have led patients to have the Essure device removed, which requires surgical intervention and may include removal of the uterus (hysterectomy).","use_canada":492,"findings":493,"conclusion":494,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":495,"footnotes":0,"title":"Summary Safety Review - ESSURE Permanent Birth Control System - Assessing the Risk of Complications Including Allergic Reactions, Abnormal Bleeding/Menstrual Changes and the Potential Need for Device Removal","created_date":"2016-05-25","modified_date":null,"key_message_list":[{"field_id":491,"order_no":1,"bullet":"Essure is a medical device for women who are interested in permanent birth control."},{"field_id":491,"order_no":2,"bullet":"Health Canada carried out a safety review after becoming aware of a large patient study1 and reports regarding safety concerns with the Essure device."},{"field_id":491,"order_no":3,"bullet":"As a result of this safety review, Health Canada has recommended increased monitoring of the safety of the Essure system and will work with the manufacturer to issue a risk communication to help clarify information about the device and associated safety concerns. Health Canada will also work with the manufacturer to strengthen the product labelling for Essure regarding these safety concerns."}],"footnotes_list":[],"reference_list":[{"field_id":495,"order_no":1,"bullet":"Mao J, Pfeifer S, Schlegel P, Sedrakyan A. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: an observational cohort study. BMJ. 2015; 351:h5162."}],"use_canada_list":[{"field_id":492,"order_no":1,"bullet":"The Essure system is an option for permanent birth control (sterilization) in women (without the need for incisions or general anesthesia, and the device does not contain or release any hormones. The device is permanently inserted into the fallopian tubes of a woman's uterus in order to block sperm from reaching her eggs."},{"field_id":492,"order_no":2,"bullet":"The system includes two small, spring-shaped inserts (the device), and the disposable delivery tools that assist the medical professional to implant the device."},{"field_id":492,"order_no":3,"bullet":"Essure has been marketed in Canada since 2002 and over 8,000 units have been sold from 2002-2014. This figure amounts to approximately 1% of the units sold worldwide over the same period of time."}],"finding_list":[{"field_id":493,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 18 reports associated with Essure, with half of those reports received in 2015 alone. The most commonly reported complaints were pain, followed by changes in menstrual bleeding and allergic (immune or hypersensitivity) reactions. Of these 18 reports, at least 10 mentioned surgery to remove the device as a treatment for these complications."},{"field_id":493,"order_no":2,"bullet":"The review of the scientific and medical literature also found that up to one-third of women reported changes in their menstrual periods within months to years after receiving the Essure device. The women described that the bleeding was either heavier than usual or was irregular such as bleeding in the middle of a cycle. The causes of the changes in menstrual bleeding may be due to a variety of factors because large community-based surveys of adult women, in general, note similar proportions of individuals that have changes in menstrual patterns over time."},{"field_id":493,"order_no":3,"bullet":"Some women have reported symptoms including fatigue, depression, mood swings, bloating, nausea, weight gain, headaches and hair loss. Some of these symptoms have been related to an inflammation or immune-type reaction after having the Essure device inserted. However, such symptoms are not rare in the general population and may be associated with other physiologic and disease states. There is also a lack of studies directly comparing individuals that have the Essure device with those that have chosen another method of permanent birth control (e.g. tubal ligation, often referred to as \"having your tubes tied\"). It is therefore difficult to determine if the Essure device itself is the cause of these symptoms. In rare cases, true allergic reactions have been reported which may be related to one of the materials used in the Essure device (e.g. nickel)."},{"field_id":493,"order_no":4,"bullet":"Although several articles with guidelines have been published, there is no standard way of removing the Essure device after the first 3 months of it being inserted (the initial embedment period). The decision is made based on a discussion between the healthcare professional and their patient. Available information suggests that Essure removals often involve removing the woman's uterus (hysterectomy) as well. In many (but not all) cases, device removal has led to resolution or improvement in symptoms."},{"field_id":493,"order_no":5,"bullet":"Health Canada's safety review included a review of the Essure Instructions for Use(IFU) and consultation with the Society of Obstetricians and Gynaecologists of Canada (SOGC). Taken together, the discussion suggested the need for more detailed safety warnings in the device's instructions for use (product labelling) and improved availability of information about possible complications associated with Essure so that women can make more informed decisions."}],"conclusion_list":[{"field_id":494,"order_no":1,"bullet":"This safety review found that there are risks associated with the use of Essure that need to be better communicated and further monitored."},{"field_id":494,"order_no":2,"bullet":"Health Canada is working with the manufacturer to issue a risk communication that includes a general discussion of the Essure device, the types of adverse events reported in Canada and internationally, a summary of Health Canada's safety review activities and recommendations to healthcare professionals and their patients to help better understand the risks associated with Essure."},{"field_id":494,"order_no":3,"bullet":"Health Canada will also work with the manufacturer to update the product labelling for Essure so that both healthcare professionals and patients have a better understanding of the risks involved."},{"field_id":494,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Essure, to identify and assess potential harms. In addition, the manufacturer will be asked to submit to Health Canada the results of an upcoming study on Essure as required by the United States Food and Drug Administration, once it is completed. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00062","review_date":null,"drug_name":"Sodium-glucose cotransporter-2 (SGLT2) inhibitors: Invokana (canagliflozin), Forxiga (dapagliflozin)","safety_issue":"Acute kidney injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":501,"overview":"A safety review was done to evaluate the potential risk of acute kidney injury and the use of two SGLT2 inhibitors, Invokana (canagliflozin) or Forxiga (dapagliflozin). This issue was identified following new safety information received from the manufacturer of Invokana following the marketing of this product.","use_canada":502,"findings":503,"conclusion":504,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors INVOKANA (canagliflozin) and FORXIGA (dapagliflozin) - Evaluation of a Potential Risk of Acute Kidney Injury","created_date":"2015-10-16","modified_date":null,"key_message_list":[{"field_id":501,"order_no":1,"bullet":"Invokana and Forxiga are SGLT2 inhibitors, which are drugs that can be used on their own with diet and exercise or with other products to decrease blood sugar levels in adults with type 2 diabetes."},{"field_id":501,"order_no":2,"bullet":"This safety review of Invokana and Forxiga on acute kidney injury was triggered by new safety information received from the manufacturer of Invokana following the marketing of this product."},{"field_id":501,"order_no":3,"bullet":"Health Canada's safety review found a link between events of acute kidney injury and the use of Invokana and Forxiga. Health Canada is working with the manufacturers on an update to the Canadian prescribing information of Invokana and Forxiga to strengthen the wording relating to kidney injury to reflect this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":502,"order_no":1,"bullet":"The SGLT2 inhibitors are medicines used to treat type 2 diabetes by reducing high blood sugar levels. Type 2 diabetes is a disease where the pancreas does not produce enough insulin leading to an inability to control blood sugar levels."},{"field_id":502,"order_no":2,"bullet":"Type 2 diabetes may lead to several health problems, such as eye disorders (diabetic retinopathy), kidney disorders (diabetic nephropathy), nervous system disorders (diabetic neuropathy) and cardiovascular disorders (such as heart attacks)."},{"field_id":502,"order_no":3,"bullet":"The review focused on Invokana and Forxiga, marketed since June 2014 and January 2015, respectively. Invokana and Forxiga use has been steadily increasing since the time of their marketing in Canada."},{"field_id":502,"order_no":4,"bullet":"A third SGLT2 inhibitor, Jardiance (empagliflozin) was marketed in August 2015. This product was not included in the review due to its recent approval; however, it already contains wording in its labelling for acute kidney failure (acute renal failure)."}],"finding_list":[{"field_id":503,"order_no":1,"bullet":"This safety review considered serious reports of acute kidney injury, acute renal failure and renal failure (severe renal impairment). These kidney problems occur when the kidneys suddenly become unable to filter waste products from the blood."},{"field_id":503,"order_no":2,"bullet":"At the time of the review, Health Canada had received two reports of acute kidney injury in Invokana users."},{"field_id":503,"order_no":3,"bullet":"Additional international reports of kidney injury suspected to be linked with either Invokana or Forxiga were provided by their Canadian manufacturers. The review of these cases showed that there was a link between events of acute kidney injury and the use of these SGLT2 inhibitors."},{"field_id":503,"order_no":4,"bullet":"A review of the scientific literature linking Invokana or Forxiga to acute kidney injury provided limited evidence on this topic, although their renal effects were noted as a potential problem."},{"field_id":503,"order_no":5,"bullet":"At the time of the review, the product information for both Invokana and Forxiga already included some warnings on the use of these products in patients who have severe kidney problems or are on dialysis. The product labeling also reports the occurrence of decreased kidney function in patients treated with SGLT2 inhibitors."}],"conclusion_list":[{"field_id":504,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence supported the existence of a link between the use of SGLT2 inhibitors and the risk of acute kidney injury."},{"field_id":504,"order_no":2,"bullet":"Health Canada is working with the manufacturers on an update to the Canadian prescribing information of Invokana and Forxiga to reflect the risk of acute kidney injury and will notify Canadians when changes have occurred. Currently, the product labeling reports the occurrence of decreased kidney function in patients treated with SGLT2 inhibitors."},{"field_id":504,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving SGLT2 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00065","review_date":null,"drug_name":"Topical antiseptic non-prescription chlorhexidine products","safety_issue":"Serious allergic reactions (hypersensitivity reactions)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":511,"overview":"This safety review was carried out to look at the potential link between non-prescription topical antiseptic chlorhexidine products and serious allergic reactions, and to determine if there is a need for additional labelling requirements. This issue came to light when Health Canada found published cases of serious allergic reactions linked with the use of topical chlorhexidine, during routine health product monitoring. Symptoms of a serious allergic reaction, including anaphylaxis, may include itchy hives with swelling of the face, eyes, lips, mouth or throat; difficulty breathing; throat tightness or hoarseness; and fainting. An anaphylactic reaction is a serious and potentially life-threatening hypersensitivity reaction.","use_canada":512,"findings":513,"conclusion":514,"additional":"Additional Information The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Topical Antiseptic Non-Prescription Chlorhexidine Products - Assessing the Potential Risk of Serious Allergic Reactions (hypersensitivity reactions)","created_date":"2016-05-13","modified_date":null,"key_message_list":[{"field_id":511,"order_no":1,"bullet":"Chlorhexidine is used in non-prescription topical antiseptic products to kill harmful bacteria on the skin and to reduce the risk of infection."},{"field_id":511,"order_no":2,"bullet":"This safety review was triggered when Health Canada identified published cases of serious allergic reactions, including anaphylaxis, linked with the use of topical chlorhexidine, during routine health product monitoring."},{"field_id":511,"order_no":3,"bullet":"Health Canada's safety review determined that topical chlorhexidine may cause serious allergic anaphylactic reactions in certain conditions when used in the mouth, on open wounds, or immediately before or during surgery. Health Canada's Antiseptic Skin Cleansers monograph already requires that the labelling for chlorhexidine-containing hand cleansers include warnings against using the product on persons who are allergic to the ingredients. Health Canada will work to update the product information with these new findings."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":512,"order_no":1,"bullet":"Non-prescription chlorhexidine products are applied to the skin (topically) as an antiseptic in order to reduce the risk of bacterial infection."},{"field_id":512,"order_no":2,"bullet":"There are over 50 non-prescription topical chlorhexidine products for human use in Canada."},{"field_id":512,"order_no":3,"bullet":"In Canada, chlorhexidine may be sold as a non-prescription drug for topical use at concentrations of 2-4%, and these products are available in forms such as creams, liquids, gels and sprays. Chlorhexidine products used in the mouth (orally), such as mouthwashes, are available by prescription only."}],"finding_list":[{"field_id":513,"order_no":1,"bullet":"At the time of this review, Health Canada had received 53 reports of serious allergic reactions with the use of non-prescription topical chlorhexidine products. Of these, 3 were anaphylactic reactions."},{"field_id":513,"order_no":2,"bullet":"There are also published case reports of serious allergic reactions, including anaphylaxis, with non-prescription topical chlorhexidine products."},{"field_id":513,"order_no":3,"bullet":"Allergic reactions, including anaphylaxis, are a known risk with prescription oral chlorhexidine products and are already included in the Canadian prescribing information."},{"field_id":513,"order_no":4,"bullet":"Serious allergic anaphylactic reactions to non-prescription topical chlorhexidine products are not common. Health Canada's safety review determined that topical chlorhexidine may cause serious allergic anaphylactic reactions in certain conditions when used in the mouth, on open wounds, or immediately before or during surgery."}],"conclusion_list":[{"field_id":514,"order_no":1,"bullet":"Health Canada's safety review determined that topical antiseptic chlorhexidine products may cause serious allergic reactions. These findings suggest that some conditions may increase the risk of anaphylaxis, such as using chlorhexidine in the mouth, on open wounds, or immediately before or during surgery."},{"field_id":514,"order_no":2,"bullet":"Health Canada's Antiseptic Skin Cleansers monograph already requires that the labelling for non-prescription topical chlorhexidine products include a warning statement to minimize the risk of allergic reactions. Health Canada will work to update the product information with these new findings."},{"field_id":514,"order_no":3,"bullet":"Health Canada continues to monitor side effect information involving chlorhexidine, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00067","review_date":null,"drug_name":"Eylea (aflibercept)","safety_issue":"Possible risk of side effects outside the eye","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":519,"overview":"A safety review was carried out by Health Canada to evaluate the risk of harmful side effects in areas of the body other than the eye (systemic toxicity) associated with Eylea. The review was triggered by 3 scientific studies which observed that following injection into the eye, Eylea is removed from the body's bloodstream slower than alternative products, and this could possibly lead to systemic toxicity.1,2,3 The rare side effects of these medications include stroke, heart disease, high blood pressure, bleeding and signs of harm to the kidneys such as passing protein in the urine.","use_canada":520,"findings":521,"conclusion":522,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what are known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":523,"footnotes":741,"title":"Summary Safety Review - EYLEA (aflibercept) - Assessing the Risk of Side Effects Outside the Eye (systemic side effects)","created_date":"2016-05-10","modified_date":null,"key_message_list":[{"field_id":519,"order_no":1,"bullet":"Eylea is a medicine that is injected into the eye to treat vision impairment caused by diseases that affect the blood vessels in the sensory layer at the back of the eye (the retina)."},{"field_id":519,"order_no":2,"bullet":"Health Canada carried out a safety review after new published literature suggested that the body takes a longer time to remove Eylea from the circulating blood (prolonged systemic exposure) compared to a similar product used for the same condition, which may put patients at greater risk of side effects in areas outside the eye."},{"field_id":519,"order_no":3,"bullet":"Health Canada's safety review concluded that despite the presence of low levels of Eylea in the rest of the body, the risk of experiencing side effects was not different from that of the similar product.Health Canada continues to monitor the safety of Eylea and encourages health care professionals to report any side effects related to the use of this health product."}],"footnotes_list":[{"field_id":741,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":741,"order_no":2,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review."}],"reference_list":[{"field_id":523,"order_no":1,"bullet":"Avary RL et al. systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br J Ophthalmology. 2014; 98 (12): 1636-1641."},{"field_id":523,"order_no":2,"bullet":"Wang X et al. Serum and plasma vascular endothelial growth factor concentrations before and after intravitreal injection of aflibercept or ranituzumab for age-related macular degeneration. AM J Ophthalmology. 2014; 158 (4): 738-744 e 1."},{"field_id":523,"order_no":3,"bullet":"Yoshida I et al. Evaluation of plasma endothelial growth factor levels after intravitreal injection of ranituzumab and aflibercept for exudative age-related macular degeneration. AM J of Ophthalmology. 2014; 252 (9):1483-1489."}],"use_canada_list":[{"field_id":520,"order_no":1,"bullet":"Eylea (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor. It is a type of biologic medicine (recombinant fusion protein) which blocks the effects of VEGF which is normally produced in the body to help in the growth or repair of blood vessels."},{"field_id":520,"order_no":2,"bullet":"Eylea is in a formulation that is directly injectable into the eye (intravitreal injection) and acts to prevent the formation of new blood vessels that could damage the sensory layer at the back of the eye (the retina). Eylea is used to treat diseases of the retina including \"wet\" age-related macular degeneration, diabetic macular edema or macular edema resulting from retinal blood vessel occlusion."},{"field_id":520,"order_no":3,"bullet":"Eylea has been marketed in Canada since late 2013."}],"finding_list":[{"field_id":521,"order_no":1,"bullet":"At the time of the review Health Canada received 4 Canadian reportsa of systemic side effects that were all related to bleeding. However, the reports either involved cases of bleeding at the injection site (hemorrhage into the eye) or did not contain enough information to conclude that Eylea itself was the cause of bleeding in another part of the body."},{"field_id":521,"order_no":2,"bullet":"The published studies showed that Eylea (mainly in its inactive form) is removed from the body slower than a similar product used for the same purpose."},{"field_id":521,"order_no":3,"bullet":"However, the review of the published studies and safety data from international reports found that, overall, the occurrence and severity of systemic side effects was comparable between the 2 products."}],"conclusion_list":[{"field_id":522,"order_no":1,"bullet":"Health Canada's review found that there was not enough evidence to conclude that Eylea is associated with a greater risk of systemic side effects. The potential for experiencing some side effects in areas of the body other than the eye is already mentioned in the Canadian product safety information for Eylea."},{"field_id":522,"order_no":2,"bullet":"Health Canada will continue to monitor safety information associated with the use of Eylea as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified."}]},{"template":2,"link_id":"SSR00069","review_date":null,"drug_name":"Proton pump inhibitors","safety_issue":"Clostridium difficile infection","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":529,"overview":"This safety review was carried out to look at new information in the scientific literature that has emerged since the completion of a previous review in 2012 about the risk of Clostridium difficile infection with proton pump inhibitor use. Clostridium difficile infection ranges from mild diarrhea to life-threatening multi-organ failure, especially in elderly patients with other pre-existing conditions. This safety issue has been monitored by Health Canada since 2009, and in 2010, the prescribing information documents for all proton pump inhibitors were updated to inform Canadians about the potential role of these drugs as a risk factor for Clostridium difficile infection. In 2012, Health Canada carried out a follow-up assessment and posted an Advisory to inform Canadians of the potential contribution of proton pump inhibitors to the overall risk of Clostridium difficile infection.","use_canada":530,"findings":531,"conclusion":532,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally. The Canadian Agency for Drugs and Technologies in Health carried out a review in 2014-2015 to look at the link between proton pump inhibitor use and Clostridium difficile infection. The findings of this review were similar to those from Health Canada's safety review on this issue. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Proton Pump Inhibitors - Assessing the Potential Risk of Clostridium difficile Infection","created_date":"2016-05-06","modified_date":null,"key_message_list":[{"field_id":529,"order_no":1,"bullet":"Proton pump inhibitors are drugs that are used to reduce stomach acid to treat heartburn and ulcers on the lining of the stomach/intestines."},{"field_id":529,"order_no":2,"bullet":"Health Canada's review on the potential risk of Clostridium difficile infection with proton pump inhibitor use was carried out to assess new evidence since completion of the previous review in 2012. Following the 2012 review, Health Canada issued an Advisory to inform Canadians of the potential contribution of proton pump inhibitors to the overall risk of Clostridium difficile infection."},{"field_id":529,"order_no":3,"bullet":"The current Health Canada review concluded that the evidence is limited to establish that proton pump inhibitors cause Clostridium difficile infection. The Canadian prescribing information for all proton pump inhibitors already reflects the observation that patients using these drugs are slightly more likely to develop Clostridium difficile infections. It will be updated to include additional details on the risk of Clostridium difficile infection and to encourage optimal use of proton pump inhibitors."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":530,"order_no":1,"bullet":"Proton pump inhibitors are drugs that are used to reduce stomach acid in the treatment of heartburn and stomach/intestinal ulcers."},{"field_id":530,"order_no":2,"bullet":"There are six proton pump inhibitors available in Canada: omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet) and dexlansoprazole (Dexilant). There are also some generic versions of these drugs sold in Canada."},{"field_id":530,"order_no":3,"bullet":"Most proton pump inhibitors are available by prescription only, however some omeprazole products are available without a prescription (e.g., Olex)."}],"finding_list":[{"field_id":531,"order_no":1,"bullet":"At the time of this review, Health Canada had received a total of 10 reports of Clostridium difficile infection in patients who were using proton pump inhibitors. Of these reports, 2 were received since the previous review in 2012."},{"field_id":531,"order_no":2,"bullet":"A search in the World Health Organization's database at the time of this review found 233 reports of Clostridium difficile infection in patients who were using proton pump inhibitors."},{"field_id":531,"order_no":3,"bullet":"Given the widespread use of these drugs in Canada and internationally, the number of reports is considered to be low."},{"field_id":531,"order_no":4,"bullet":"Scientific literature reports have described a potential link between proton pump inhibitor use and Clostridium difficile infection and/or recurrence. However, patients included in these studies had other known risk factors that could have contributed to the development of Clostridium difficile infection."}],"conclusion_list":[{"field_id":532,"order_no":1,"bullet":"Health Canada's safety reviews concluded that the evidence was too limited to establish that the use of proton pump inhibitors causes Clostridium difficile infection."},{"field_id":532,"order_no":2,"bullet":"Currently, the prescribing information for proton pump inhibitors reflects the observation that patients using proton pump inhibitors are slightly more likely to develop Clostridium difficile infections. Since the potential link has not been ruled out, the prescribing information will be updated to provide more information on various risk factors."},{"field_id":532,"order_no":3,"bullet":"The prescribing information for proton pump inhibitors will also be updated to remind healthcare professionals and patients that these drugs should be used at the lowest dose and for the shortest duration appropriate to the condition being treated. "},{"field_id":532,"order_no":4,"bullet":"Health Canada continues to monitor side effect information involving proton pump inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00071","review_date":null,"drug_name":"Yervoy (ipilimumab)","safety_issue":"Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":537,"overview":"Health Canada carried out a safety review to look into the potential risk of DRESS with the use of Yervoy. This issue was found during the review of published case reports. The review also looked at new safety information that was requested from the manufacturer.
DRESS describes a group of rare but serious and potentially life-threatening adverse reactions to medications, such as fever, severe skin rash with swollen face or peeling of the skin over large areas of the body, etc. These reactions usually occur two weeks to two months after starting a medication.
","use_canada":538,"findings":539,"conclusion":540,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - YERVOY (ipilimumab) - Assessing the Potential Risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2016-04-22","modified_date":null,"key_message_list":[{"field_id":537,"order_no":1,"bullet":"Yervoy is a drug that is used to treat malignant melanoma (a type of skin cancer) that has spread or that cannot be removed by surgery."},{"field_id":537,"order_no":2,"bullet":"This safety review was triggered when Health Canada identified a possible risk of DRESS with Yervoy treatment, during the routine review of published case reports."},{"field_id":537,"order_no":3,"bullet":"Health Canada's safety review concluded that there is a potential risk of DRESS with Yervoy. Therefore, Health Canada worked with the manufacturer to update the Canadian prescribing information for Yervoy to include more details about this potential safety issue."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":538,"order_no":1,"bullet":"Yervoy is used to treat adult patients with malignant melanoma that has spread or that cannot be removed by surgery."},{"field_id":538,"order_no":2,"bullet":"Yervoy has been sold in Canada since 2012. It is available by prescription only."},{"field_id":538,"order_no":3,"bullet":"Yervoy is sold as a liquid in a 5 mg/mL strength and is given intravenously in a hospital or clinic under medical supervision."}],"finding_list":[{"field_id":539,"order_no":1,"bullet":"At the time of the review, there were no Canadian case reports of DRESS with the use of Yervoy."},{"field_id":539,"order_no":2,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found 3 reports of DRESS with the use of Yervoy."},{"field_id":539,"order_no":3,"bullet":"The manufacturer shared a report from the Global Safety Database which contained cases of DRESS that were possibly caused by Yervoy. As the review of these cases was complicated by various factors, a link between Yervoy and DRESS could not be established or ruled out."}],"conclusion_list":[{"field_id":540,"order_no":1,"bullet":"Based on the information reviewed, Health Canada concluded that there may be a link between Yervoy and DRESS. Yervoy affects the immune system of the patient in a way which may increase the chances for DRESS to develop."},{"field_id":540,"order_no":2,"bullet":"The Canadian prescribing information for Yervoy has been updated to include this potential risk."},{"field_id":540,"order_no":3,"bullet":"Health Canada continues to monitor side effect information involving Yervoy, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00073","review_date":null,"drug_name":"Celecoxib (Celebrex and generics)","safety_issue":"Risk of serious heart and stroke side effects at high doses relative to other non-steroidal anti-inflammatory drugs (NSAIDs)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":545,"overview":"Health Canada carried out a safety review of all the available evidence to evaluate the risk of side effects related to heart and stroke linked with celecoxib, in comparison to other NSAIDs (diclofenac, ibuprofen, naproxen).","use_canada":546,"findings":547,"conclusion":548,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what are known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":549,"footnotes":0,"title":"Summary Safety Review - Celecoxib (CELEBREX and generics) - Assessing the Risk of Serious Heart and Stroke Side Effects at High Doses Relative to Other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)","created_date":"2016-04-11","modified_date":null,"key_message_list":[{"field_id":545,"order_no":1,"bullet":"Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used for relief of pain and inflammation from diseases affecting the joints such as osteoarthritis, adult rheumatoid arthritis and ankylosing spondylitis."},{"field_id":545,"order_no":2,"bullet":"Health Canada carried out a safety review following the publication of a studya. The study indicated that celecoxib (at doses of higher than 200 mg per day) may be linked with an increased risk of serious heart and stroke related side effects and this risk is similar to the risks linked with the use of high doses of diclofenac (≥150 mg per day) or ibuprofen (≥2400 mg per day)."},{"field_id":545,"order_no":3,"bullet":"Health Canada's safety review found that celecoxib's overall benefits continue to be greater than its risks, when used as recommended. However, celecoxib at doses higher than 200 mg per day may be linked with an increased risk of serious side effects related to heart and stroke, especially in patients with pre-existing factors for heart disease or those taking the drug for longer than 18 months."}],"footnotes_list":[],"reference_list":[{"field_id":549,"order_no":1,"bullet":"Bhala N, Emberson J, Merhi A, et al. Coxib and traditional NSAID trialist CNT Collaboration group: Vascular and upper gastrointestinal effects on non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382:769-79."}],"use_canada_list":[{"field_id":546,"order_no":1,"bullet":"Celecoxib is indicated for relief of symptoms linked with:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":567,"title":"Summary Safety Review - ULORIC (febuxostat) - Assessing the Potential Risk of Heart Failure","created_date":"2016-04-01","modified_date":null,"key_message_list":[{"field_id":563,"order_no":1,"bullet":"Uloric (febuxostat) is a drug used to treat gout, a painful form of arthritis."},{"field_id":563,"order_no":2,"bullet":"During routine monitoring of information received from the manufacturer, several international cases of heart failure suspected of being linked with the use of febuxostat were found. A safety review was carried out by Health Canada to further assess the issue."},{"field_id":563,"order_no":3,"bullet":"Health Canada has asked the manufacturer to update the Canadian prescribing information for febuxostat to include the risk of heart failure in patients that have cardiovascular disease and/or other risk factors."}],"footnotes_list":[{"field_id":567,"order_no":1,"bullet":"World Health Otranization (WHO) adverse reaction information provided by: The WHO collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."}],"reference_list":[],"use_canada_list":[{"field_id":564,"order_no":1,"bullet":"Febuxostat has been marketed in Canada under the brand name Uloric since 2010."},{"field_id":564,"order_no":2,"bullet":"Febuxostat is an oral medication used for the treatment of gout (a painful inflammation of joints caused when uric acid forms hard crystals in the joint) to lower uric acid levels in the blood."},{"field_id":564,"order_no":3,"bullet":"At the time of the review, there were approximately 82,000 prescriptions each year for Uloric in Canada."}],"finding_list":[{"field_id":565,"order_no":1,"bullet":"At the time of the review, no cases of heart failure linked with febuxostat use were reported in Canada."},{"field_id":565,"order_no":2,"bullet":"As of March 01, 2015, there were 32 Individual Case Safety Reports of heart failure suspected of being linked with febuxostat use in the World Health Organization (WHO) Global Individual Case Safety Reports Database System, of which 8 were linked with deaths.a"},{"field_id":565,"order_no":3,"bullet":"Scientific literature reports that hyperuricemia (high levels of uric acid in the blood) and gout are linked with an increased risk of cardiovascular disease which affects the interpretation of cardiovascular side effects in this population. Researchers also mentioned that a contribution from febuxostat causing or worsening heart failure could not be ruled out."}],"conclusion_list":[{"field_id":566,"order_no":1,"bullet":"Based on all of the information reviewed, Health Canada has asked the manufacturer of Uloric (febuxostat) to include a statement regarding the potential increased risk of heart failure in patients with pre-existing cardiovascular disease and/or risk factors in the Canadian prescribing information document."},{"field_id":566,"order_no":2,"bullet":"Health Canada will continue to monitor side effect information for febuxostat, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00079","review_date":null,"drug_name":"Imatinib mesylate (Gleevec and generics)","safety_issue":"Assessing the Risk of Decline in Kidney Function During Long-Term Treatment","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":573,"overview":"Health Canada carried out a safety review after receiving Canadian and international reports of tendon disorders in patients treated with Gleevec.
Tendon disorders are medical conditions that result in the tendons not functioning normally. A tendon is a flexible but non-elastic piece of tissue in the body that attaches a muscle to a bone.
","use_canada":574,"findings":575,"conclusion":576,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":577,"title":"Summary Safety Review - Imatinib Mesylate (GLEEVEC and generics) - Assessing the Risk of Decline in Kidney Function During Long-Term Treatment","created_date":"2016-03-07","modified_date":"2018-06-08","key_message_list":[{"field_id":573,"order_no":1,"bullet":"Imatinib is a drug authorized for sale in Canada to treat cancer (chemotherapy). It is used to treat several solid tumours or blood cancers."},{"field_id":573,"order_no":2,"bullet":"Health Canada reviewed the potential risk of tendon disorders with the use of imatinib after receiving Canadian and international reports of tendon disorders in patients treated with Gleevec"},{"field_id":573,"order_no":3,"bullet":"Health Canada's review of the available information did not find a link between the use of imatinib and the risk of tendon disorders. Health Canada will continue to monitor the safety of products containing imatinib. "}],"footnotes_list":[{"field_id":577,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":574,"order_no":1,"bullet":"Imatinib belongs to a class of cancer drugs called tyrosine kinase inhibitors. It is used to treat several solid tumours such as certain tumours of the gastrointestinal tract, or blood cancers such as chronic myeloid leukemia."},{"field_id":574,"order_no":2,"bullet":"Imatinib has been marketed in Canada since 2001 under the brand name Gleevec. It is available as tablets taken by mouth."},{"field_id":574,"order_no":3,"bullet":"Generic versions of imatinib are also available."}],"finding_list":[{"field_id":575,"order_no":1,"bullet":"The review identified 6 Canadiana and 36 international reports of tendon disorders in patients treated with Gleevec that had enough information for assessment. The review of these reports could not conclude whether the tendon disorders were caused by imatinib. Other reasons could have explained the events that were observed, such as accidents, the presence of other diseases (e.g., diabetes), and the use of other medication (e.g., quinolone antibiotics) known to cause tendon disorders."},{"field_id":575,"order_no":2,"bullet":"A search for published information found 1 long-term safety study that reported 3 serious cases of tendon injury among 832 patients treated with imatinib for more than 2 years. However, there was not enough information to further assess these cases."},{"field_id":575,"order_no":3,"bullet":"At the time of the review, there have been no international regulatory actions taken with respect to this issue."}],"conclusion_list":[{"field_id":576,"order_no":1,"bullet":"Health Canada's review of the available information did not find a link between the use of imatinib and the risk of tendon disorders."},{"field_id":576,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":576,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving imatinib to identify and assess potential harms, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00081","review_date":null,"drug_name":"Bcr-Abl tyrosine kinase inhibitors (Gleevec [and its generics], Sprycel, Tasigna, and Bosulif)","safety_issue":"Assessing the Potential Harm to the Fetus","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":583,"overview":"Based on additional safety information received from the manufacturers, Health Canada carried out this safety review to further assess the risk of fetal harm when Bcr-Abl tyrosine kinase inhibitors are used by either parent (father or mother) in order to determine if there is a need for additional warnings in the prescribing information. The potential for these drugs to cause harm to the fetus (i.e., birth defects and miscarriage) is known and is mentioned in the Canadian label. The label further tells women to use effective birth control during treatment.","use_canada":584,"findings":585,"conclusion":586,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Bcr-Abl Tyrosine Kinase Inhibitors - Assessing the Potential Harm to the Fetus","created_date":"2016-03-02","modified_date":null,"key_message_list":[{"field_id":583,"order_no":2,"bullet":"Bcr-Abl tyrosine kinase inhibitors are used to treat blood cancers. The potential for these drugs to cause harm to the fetus is known and is included in the Canadian label. The label further tells women to use effective birth control during treatment."},{"field_id":583,"order_no":3,"bullet":"Based on additional safety information received from the manufacturers, Health Canada carried out a safety review to further assess the risk of fetal harm with Bcr-Abl tyrosine kinase inhibitors."},{"field_id":583,"order_no":4,"bullet":"Following the completion of the safety review, the manufacturer has updated the prescribing information for Gleevec to tell doctors to confirm by pregnancy test that female patients are not pregnant before starting treatment."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":584,"order_no":1,"bullet":"There are currently four brand name Bcr-Abl tyrosine kinase inhibitors sold in Canada: Gleevec (imatinib), Sprycel (dasatinib), Tasigna (nilotinib), and Bosulif (bosutinib). Generic versions of imatinib are also available in Canada."},{"field_id":584,"order_no":2,"bullet":"These drugs are taken orally to treat blood cancers. Gleevec is also used to treat some solid tumours."},{"field_id":584,"order_no":3,"bullet":"Gleevec has been sold in Canada since September 2001, Sprycel since April 2007, Tasigna since September 2008, and Bosulif since April 2014."}],"finding_list":[{"field_id":585,"order_no":1,"bullet":"No Canadian cases of harm to the fetus have been received through the Canada Vigilance program with any Bcr-Abl tyrosine kinase inhibitors."},{"field_id":585,"order_no":2,"bullet":"At the time of the review, a total of 27 published international studies and case reports of pregnant women treated with Gleevec were found in the scientific literature. After review of these studies and according to the outcomes reported by the authors, overall healthy babies were the most reported outcomes (50.2%), followed by elective abortions (30.7%), miscarriages (10.6%) and birth defects (8.4%)."},{"field_id":585,"order_no":3,"bullet":"Based on the information reviewed, including the scientific literature, there were no new findings on the effects of Sprycel (dasatinib), Tasigna (nilotinib) and Bosulif (bosutinib) on pregnancy outcome."}],"conclusion_list":[{"field_id":586,"order_no":1,"bullet":"At the time of the review, the prescribing information for Bcr-Abl tyrosine kinase inhibitors included wording regarding the potential harm to a fetus, including birth defects and miscarriage. Women are also told to use effective birth control during treatment."},{"field_id":586,"order_no":2,"bullet":"Further to this safety review, the manufacturer has updated the prescribing information for Gleevec to tell doctors to confirm by pregnancy test that female patients are not pregnant before starting treatment. No modifications were recommended for the prescribing information of the other tyrosine kinase inhibitors, at this point in time based on the lack of evidence of increased fetal harm and because of differences in the mechanism of action of these medications."},{"field_id":586,"order_no":3,"bullet":"The review did not find additional safety concerns for the unborn child when Bcr-Abl tyrosine kinase inhibitors are used by the father. Health Canada has determined that there is no need to modify the warnings already included in the Canadian prescribing information regarding this particular risk when these drugs are used by the father."},{"field_id":586,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving Bcr-Abl tyrosine kinase inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00087","review_date":null,"drug_name":"Cisplatin","safety_issue":"Assessing the Potential Risk of Blood Clots in the Veins (venous thromboembolism)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":611,"overview":"Health Canada carried out a safety review to look into the potential increased risk of venous thromboembolism with the use of cisplatinFootnote 1. This issue was found during a routine review of new safety information published by a foreign regulatory agency (Japan)Footnote 2.","use_canada":612,"findings":613,"conclusion":614,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":615,"title":"Summary Safety Review - Cisplatin - Assessing the Potential Risk of Blood Clots in the Veins (venous thromboembolism)","created_date":"2016-02-12","modified_date":null,"key_message_list":[{"field_id":611,"order_no":1,"bullet":"Cisplatin, in combination with other treatments, is used to treat advanced bladder, testicular and ovarian cancers."},{"field_id":611,"order_no":2,"bullet":"This safety review was triggered when Health Canada identified a possible risk of blood clots in the veins (venous thromboembolism) with cisplatin treatment, during the routine review of updated prescribing information published by a foreign regulatory agency (Japan)."},{"field_id":611,"order_no":3,"bullet":"Health Canada's review concluded that cisplatin is linked to a higher risk of venous thromboembolism when used to treat patients with advanced bladder, testicular and ovarian cancers. Health Canada has therefore asked manufacturers of cisplatin products to update their prescribing information to include warnings about this increased risk."}],"footnotes_list":[{"field_id":615,"order_no":1,"bullet":"Briplatin injection 10 mg, 25 mg, 50 mg (Bristol Myers K.K.), Randa Inj. 10 mg/20 mL, 25 mg/50 mL, 50 mg/100 mL (Nippon Kayaku Co., Ltd.) and the others."},{"field_id":615,"order_no":2,"bullet":"Pharmaceuticals and Medical Devices Safety Information No. 307 November 2013 - Early Notification September 26, 2013."},{"field_id":615,"order_no":3,"bullet":"Seng S, Liu, Z, Chiu, SK, Proverbs-Singh T, Sonpavde G, Choueiri, TK, Tsao CK, Yu M, Han NM , Oh WK, Glasky MD. A systematic review and meta-analysis. Journal of Clinical Oncology 30. 35, 4416-26, 2012."}],"reference_list":[],"use_canada_list":[{"field_id":612,"order_no":1,"bullet":"Cisplatin, in combination with other treatments, is used to treat patients with some forms of advanced bladder, testicular and ovarian cancers."},{"field_id":612,"order_no":2,"bullet":"Cisplatin has been sold in Canada since 1979. It is available by prescription only."},{"field_id":612,"order_no":3,"bullet":"There are 5 generic cisplatin products on the Canadian market, sold as intravenous injections in a 1 mg/mL strength, in 10 mL, 50 mL and 100 mL sizes."}],"finding_list":[{"field_id":613,"order_no":1,"bullet":"At the time of the review, Health Canada had received 18 reports of venous thromboembolism with the use of cisplatin. All cases were determined to be possibly related to the drug. Among the reported cases, 5 had a reported fatal outcome, but no conclusions could be made regarding the cause of death based on the information provided in the adverse event reports. Cancer patients have a higher risk of venous thromboembolism and related fatal complications."},{"field_id":613,"order_no":2,"bullet":"The World Health Organization's database had 520 cases of venous thromboembolism linked with cisplatin at the time of this review."},{"field_id":613,"order_no":3,"bullet":"A published study3 looked at how often venous thromboembolism occurs in patients receiving cancer treatment. It concluded that there is a greater risk of venous thromboembolism with cisplatin treatment, compared to non-cisplatin treatment, when used in patients with solid tumours."}],"conclusion_list":[{"field_id":614,"order_no":1,"bullet":"Health Canada's safety review considers that there is an increased risk of venous thromboembolism with the use of cisplatin in the treatment of advanced bladder, testicular and ovarian cancers."},{"field_id":614,"order_no":2,"bullet":"Health Canada has recommended that the prescribing information for cisplatin products be updated by all manufacturers of cisplatin in Canada to include warnings about the increased risk of venous thromboembolism."},{"field_id":614,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving cisplatin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00083","review_date":null,"drug_name":"Piperacillin containing products (alone or in combination with tazobactam)","safety_issue":"Assessing the Potential Risk of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":591,"overview":"Health Canada carried out a safety review to evaluate the potential link between the antibiotic drug combination piperacillin and tazobactam or piperacillin alone and DRESS following published cases of DRESS associated with the drug combination. DRESS describes a group of rare but serious and potentially life-threatening adverse reactions to medications, such as fever, severe skin rash with swollen face or peeling of the skin over large areas of the body, etc. These reactions usually occur two weeks to two months after starting a medication.","use_canada":592,"findings":593,"conclusion":594,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug combination both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":0,"footnotes":595,"title":"Summary Safety Review - Piperacillin Containing Products (alone or in combination with tazobactam) - Assessing the Potential Risk of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2016-02-24","modified_date":null,"key_message_list":[{"field_id":591,"order_no":1,"bullet":"Piperacillin is an antibiotic that is available alone or in combination with a product that enhances piperacillin activity (tazobactam). Both products are administered into a vein (intravenously) or in a muscle (intramuscularly) and are used to treat different types of infections."},{"field_id":591,"order_no":2,"bullet":"Following published cases of DRESS with the drug combination piperacillin and tazobactam, Health Canada carried out a safety review for all piperacillin containing products."},{"field_id":591,"order_no":3,"bullet":"Health Canada's safety review concluded that there is evidence of a link between the drug combination piperacillin and tazobactam and DRESS. Additionally, a contributing role for piperacillin alone and DRESS could not be ruled out. Health Canada has begun updating the Canadian prescribing information for the drug combination piperacillin-tazobactam to include a warning statement for the risk of DRESS, and as a potential side effect for piperacillin alone. Also, Health Canada will issue a Health Product InfoWatch article about these changes."}],"footnotes_list":[{"field_id":595,"order_no":1,"bullet":"This data was provided by IMS Health Canada Inc. and is copyright protected. Prior to reproduction or other use of this data, it is necessary to seek the authorization of IMS Health Canada Inc."},{"field_id":595,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":592,"order_no":1,"bullet":"Piperacillin is an antibiotic that is available alone or in combination with a product that enhances piperacillin activity (tazobactam). They are both administered into a vein (intravenously) or in a muscle (intramuscularly) and are used to treat infections in different parts of the body."},{"field_id":592,"order_no":2,"bullet":"The drug combination piperacillin and tazobactam has been marketed in Canada since 1993. Piperacillin alone has been marketed in Canada since 1982. In 2014, the drug combination piperacillin and tazobactam was used approximately 100 times more often than piperacillin alonea."}],"finding_list":[{"field_id":593,"order_no":1,"bullet":"At the time of Health Canada’s review, two cases of DRESS suspected of being linked with the drug combination piperacillin and tazobactam were reported in Canadab. Upon further review, both cases of DRESS were considered linked with piperacillin-tazobactam drug combination."},{"field_id":593,"order_no":2,"bullet":"A Health Canada review of the published scientific and medical literature identified 17 published cases of DRESS linked with the drug combination piperacillin and tazobactam. One case out of 17 resulted in death; however a direct role for the drug combination could not be established due to pre-existing health problems. In 10 cases, the patients recovered after stopping the combination treatment with or without additional treatment reported. The six remaining cases could not be assessed further because the information contained in the reports was incomplete."},{"field_id":593,"order_no":3,"bullet":"Additional investigation of a subset of the 17 cases, suggests that the role played by piperacillin alone could not be excluded."}],"conclusion_list":[{"field_id":594,"order_no":1,"bullet":"Health Canada's safety review concluded that there is evidence of a link between the drug combination piperacillin and tazobactam and DRESS. Additionally, a contributing role for piperacillin alone and DRESS could not be ruled out."},{"field_id":594,"order_no":2,"bullet":"After reviewing the available evidence, Health Canada has begun updating the Canadian prescribing information for the drug combination of piperacillin and tazobactam with a warning statement for the risk for DRESS and the inclusion of DRESS as a potential side effect to piperacillin alone."},{"field_id":594,"order_no":3,"bullet":"Health Canada will publish an article in the Health Product InfoWatch to communicate the update of labelling associated with drug combination \"piperacillin and tazobactam\" and piperacillin alone. This publication is intended to raise awareness among health care professionals and to encourage the reporting of similar adverse reactions."},{"field_id":594,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving piperacillin and tazobactam, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00085","review_date":null,"drug_name":"Over-the-counter products containing pseudoephedrine","safety_issue":"Assessing the Potential Risk of Inflammation and Injury of the Large Intestine due to Insufficient Blood Supply (ischemic colitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":601,"overview":"A safety review was carried out to evaluate the potential link between the use of pseudoephedrine and ischemic colitis. This issue was identified after a serious foreign case report was published in the scientific literature linking ischemic colitis with the use of pseudoephedrineFootnote 1. Ischemic colitis is an inflammation and injury of the large intestine (colon) due to reduced blood flow. Although uncommon in the general population, ischemic colitis occurs with greater frequency in the elderly (age-related reduction in blood flow). This condition may also be linked with other blood vessel problems (hardening of blood vessels, low blood pressure, blood clots), or other conditions that may reduce blood flow to the colon (i.e., blockage, surgery, intense exercise, use of pharmaceutical agents or medications).","use_canada":602,"findings":603,"conclusion":604,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.","full_review":"","references":605,"footnotes":0,"title":"Summary Safety Review - Over-the-Counter Products Containing Pseudoephedrine - Assessing the Potential Risk of Inflammation and Injury of the Large Intestine due to Insufficient Blood Supply (ischemic colitis)","created_date":"2016-02-24","modified_date":null,"key_message_list":[{"field_id":601,"order_no":1,"bullet":"Pseudoephedrine is a medicinal ingredient in over-the-counter products that is used to treat the blockage of nasal passages due to excess fluid or mucus (nasal congestion)."},{"field_id":601,"order_no":2,"bullet":"Health Canada carried out a safety review on the potential link between ischemic colitis and the use of pseudoephedrine after a foreign serious case report of ischemic colitis was published in the scientific literature."},{"field_id":601,"order_no":3,"bullet":"Health Canada's safety review concluded that there is very limited evidence of ischemic colitis with the occasional use of pseudoephedrine in Canada at recommended dose and duration, in the absence of other risk factors. No cases have been reported in Canada. An article will be published in the Health Product InfoWatch regarding this issue to raise awareness and to encourage reporting of ischemic colitis with health products, including pseudoephedrine and other over-the-counter products."}],"footnotes_list":[],"reference_list":[{"field_id":605,"order_no":1,"bullet":"Sherid M, Samo S, Husein H, Sulaiman S, Vainder JA. Pseudoephedrine-induced ischemic colitis: Case report and literature review. Journal of Digestive Diseases.2014; 15: 276-280."}],"use_canada_list":[{"field_id":602,"order_no":1,"bullet":"Pseudoephedrine is a medicinal ingredient in over-the-counter products that is used to treat the blockage of nasal passages due to excess fluid or mucus (nasal congestion)."},{"field_id":602,"order_no":2,"bullet":"These products are generally intended for short-term use. A healthcare practitioner should be consulted for use beyond seven days."},{"field_id":602,"order_no":3,"bullet":"Pseudoephedrine is one of the most commonly used ingredients in over-the-counter oral nasal decongestants, and can be found either as a single ingredient natural health product, or as a non-prescription combination drug product with other ingredients such as antihistamines, analgesics, or antitussive agents."},{"field_id":602,"order_no":4,"bullet":"There are more than 200 over-the-counter products containing pseudoephedrine that have been licensed by Health Canada."}],"finding_list":[{"field_id":603,"order_no":1,"bullet":"At the time of the review, no Canadian cases of ischemic colitis were reported with the use of pseudoephedrine."},{"field_id":603,"order_no":2,"bullet":"A review of international data from the World Health Organization's case report database identified 24 cases of ischemic colitis, 7 of which involved the use of single ingredient pseudoephedrine. These 24 cases could not be assessed due to limited information provided."},{"field_id":603,"order_no":3,"bullet":"A review of the scientific and medical literature identified 9 cases of ischemic colitis associated with the use of pseudoephedrine, 2 cases of which could not be assessed due to limited information."},{"field_id":603,"order_no":4,"bullet":"Of the remaining 7 published cases, 6 were found to have other contributing risk factors (use of other drugs, pre-existing health conditions, excessive use of pseudoephedrine). Only in 1 recent case report1, it was determined by the authors that pseudoephedrine alone was the probable cause of ischemic colitis."}],"conclusion_list":[{"field_id":604,"order_no":1,"bullet":"Health Canada's safety review concluded that there is very limited evidence of ischemic colitis linked with the occasional use of pseudoephedrine at recommended dose and duration, in the absence of other risk factors. Pseudoephedrine and several other types of medications are known to cause narrowing of blood vessels (vasoconstriction), so a risk of ischemic colitis cannot be ruled out entirely in susceptible people (e.g. those with other underlying conditions, etc.)."},{"field_id":604,"order_no":2,"bullet":"Health Canada will publish an article in the Health Product InfoWatch to raise awareness and to encourage healthcare practitioners to ask their patients about the use of health products containing pseudoephedrine."},{"field_id":604,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving pseudoephedrine, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00089","review_date":null,"drug_name":"Alpha lipoic acid-containing natural health products.","safety_issue":"Low blood sugar (hypoglycemic episodes)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":621,"overview":"This safety review was carried out by Health Canada after the publication of case reports of IAS (insulin autoimmune syndrome) causing hypoglycemic episodes linked with the use of oral alpha lipoic acid products in individuals with a genetic variation which causes the body's own defence system to attack insulin (insulin autoimmune syndrome).","use_canada":622,"findings":623,"conclusion":624,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Alpha Lipoic Acid - Assessing the Potential Risk of Low Blood Sugar (Hypoglycemic Episodes)","created_date":"2016-06-30","modified_date":null,"key_message_list":[{"field_id":621,"order_no":1,"bullet":"Alpha lipoic acid is an ingredient in some natural health products and is used as an antioxidant for the maintenance of good health and/or to promote the healthy breakdown of glucose."},{"field_id":621,"order_no":2,"bullet":"Health Canada carried out a safety review with case reports of hypoglycemic episodes linked with the use of alpha lipoic acid that were published in the scientific literature."},{"field_id":621,"order_no":3,"bullet":"Health Canada's review concluded that alpha lipoic acid may cause a condition known as IAS (insulin autoimmune syndrome), which can result in low blood sugar (hypoglycemia) in individuals with a specific genetic variation. The cases of hypoglycemia resolved once the alpha lipoic acid was stopped."},{"field_id":621,"order_no":4,"bullet":"Health Canada is therefore considering updates to the labelling standard for alpha lipoic acid to inform consumers to stop using it and consult a healthcare professional if they experience symptoms of low blood sugar such as sweating, paleness, chills, headache, dizziness and/or confusion. In addition, Health Canada will publish a Health Product InfoWatch article to raise awareness of this potential risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":622,"order_no":1,"bullet":"Alpha lipoic acid is a medicinal ingredient in some natural health products and is used as an antioxidant for the maintenance of good health and/or to help promote the healthy breakdown of glucose. It is also used as a preservative (non-medicinal ingredient) in some natural health products."},{"field_id":622,"order_no":2,"bullet":"At the time of the review, Health Canada had licensed over 800 natural health products containing alpha lipoic acid, also known as thioctic acid, as a medicinal ingredient for human use."}],"finding_list":[{"field_id":623,"order_no":1,"bullet":"At the time of the review, there were no Canadian reports of hypoglycemic episodes reported with the use of alpha lipoic acid."},{"field_id":623,"order_no":2,"bullet":"There are several published international case reports of hypoglycemic episodes in individuals with IAS (insulin autoimmune syndrome) which may have been triggered by the use of oral products containing alpha lipoic acid. The cases of hypoglycemia resolved once the alpha lipoic acid was stopped."},{"field_id":623,"order_no":3,"bullet":"There is scientific evidence linking a genetic predisposition for IAS (insulin autoimmune syndrome) with the risk for developing hypoglycemic episodes with the use of oral alpha lipoic acid."},{"field_id":623,"order_no":4,"bullet":"Although most of these cases originate from Asia where these genetic variations are more common, cases have recently been reported in Europe as well. It is not known how common this specific genetic variation is within the Canadian population, which is multi-cultural and genetically varied."}],"conclusion_list":[{"field_id":624,"order_no":1,"bullet":"Health Canada's safety review concluded that alpha lipoic acid may cause a condition known as IAS (insulin autoimmune syndrome), which can result in low blood sugar (hypoglycemia). This side effect seems to be rare and the reported cases happened in individuals with a specific genetic variation. The cases of hypoglycemia resolved once the alpha lipoic acid was stopped."},{"field_id":624,"order_no":2,"bullet":"Consumers may not be aware of the risk until they are exposed to alpha lipoic acid, therefore Health Canada is considering updates to the labelling standard for alpha lipoic acid to inform consumers to stop using the product and to consult a healthcare professional if they experience symptoms of low blood sugar such as sweating, paleness, chills, headache, dizziness and/or confusion."},{"field_id":624,"order_no":3,"bullet":"In addition, Health Canada will publish a Health Product InfoWatch article to raise awareness of this potential risk."},{"field_id":624,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving alpha lipoic acid, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00090","review_date":null,"drug_name":"Avonex (interferon beta-1a)","safety_issue":"Kidney damage (nephrotic syndrome)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":629,"overview":"Health Canada carried out a safety review to look into the potential risk of nephrotic syndrome with the use of Avonex. This issue was raised when the European Medicines Agency requested that the risk of nephrotic syndrome be included on the label for all interferon beta products.
Nephrotic syndrome includes symptoms of kidney damage, such as protein in the urine, low levels of protein in the blood, high cholesterol levels, and swelling.
","use_canada":630,"findings":631,"conclusion":632,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - AVONEX (interferon beta-1a) - Assessing the Potential Risk of Kidney Damage (nephrotic syndrome)","created_date":"2016-06-30","modified_date":null,"key_message_list":[{"field_id":629,"order_no":1,"bullet":"Avonex is used to treat some forms of multiple sclerosis, a disease affecting the central nervous system. "},{"field_id":629,"order_no":2,"bullet":"This safety review was carried out by Health Canada after the European Medicines Agency requested that all interferon beta manufacturers include the risk of nephrotic syndrome in the prescribing information for these products."},{"field_id":629,"order_no":3,"bullet":"Health Canada's safety review concluded that there is a potential risk of nephrotic syndrome with the use of Avonex. Health Canada has therefore asked the manufacturer to update the Canadian prescribing information for Avonex to include this risk. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":630,"order_no":1,"bullet":"Avonex is used to treat some forms of multiple sclerosis, to reduce damage to the central nervous system, and to slow down the worsening of the disease. Avonex is given by injection into the muscle at a dose of 30 micrograms once a week."},{"field_id":630,"order_no":2,"bullet":"Avonex has been marketed in Canada since December 2005. It is available by prescription only."}],"finding_list":[{"field_id":631,"order_no":1,"bullet":"At the time of the review, there was only 1 Canadian case of nephrotic syndrome reported in a multiple sclerosis patient using Avonex."},{"field_id":631,"order_no":2,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found 10 cases of nephrotic syndrome reported in multiple sclerosis patients treated with interferon beta products."},{"field_id":631,"order_no":3,"bullet":"In the scientific and medical literature, there were 7 cases of nephrotic syndrome found with the use of interferon beta products."},{"field_id":631,"order_no":4,"bullet":"In addition, the manufacturer shared a report from the Global Safety Database which contained 9 cases of nephrotic syndrome with Avonex. Upon review of these cases, they were considered to be possibly related to the use of Avonex."},{"field_id":631,"order_no":5,"bullet":"Information regarding the risk of nephrotic syndrome is already included in the prescribing information for all other interferon beta products in Canada (i.e., Betaseron, Rebif, and Extavia). Information on the risk of nephrotic syndrome appears in the European product labelling for all interferon beta drugs."}],"conclusion_list":[{"field_id":632,"order_no":1,"bullet":"Health Canada's safety review concluded that there is a potential risk of nephrotic syndrome with the use of Avonex for the following reasons:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":641,"footnotes":642,"title":"Summary Safety Review - ULORIC (febuxostat) - Assessing a Possible Risk of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2016-06-13","modified_date":null,"key_message_list":[{"field_id":637,"order_no":1,"bullet":"Uloric (febuxostat) is used to lower blood uric acid levels in patients with gout (a painful inflammation of a joint due to uric acid forming hard crystals)."},{"field_id":637,"order_no":2,"bullet":"A safety review was started after finding international cases of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS) suspected of being linked with the use of febuxostat."},{"field_id":637,"order_no":3,"bullet":"Health Canada has reviewed all the information available and concluded that the data, though limited, suggested a possible link between DRESS and febuxostat. The Canadian prescribing information for Uloric has been updated to include the risk of DRESS. Health Canada has also published an article in the Health Product InfoWatch to raise awareness and encourage reporting by patients and healthcare professionals."}],"footnotes_list":[{"field_id":642,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":642,"order_no":2,"bullet":"World Health Organization (WHO) adverse reaction information provided by: The WHO collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO."}],"reference_list":[{"field_id":641,"order_no":1,"bullet":"Doré M, Frenette AJ, Mansour AM, et al. Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels. Ann Pharmacother 2014;48(5):648-51."}],"use_canada_list":[{"field_id":638,"order_no":1,"bullet":"Febuxostat is an oral medication used to lower uric acid levels in patients with gout (a painful inflammation of a joint due to uric acid forming hard crystals)."},{"field_id":638,"order_no":2,"bullet":"Febuxostat has been marketed in Canada under the brand name Uloric since 2010."},{"field_id":638,"order_no":3,"bullet":"At the time of review, there were approximately 82,000 prescriptions per year for Uloric in Canada. In comparison, the most commonly used medication to treat gout, allopurinol, had 2,903,282 prescriptions in the same timeframe. Allopurinol has been available on the Canadian market for decades."}],"finding_list":[{"field_id":639,"order_no":1,"bullet":"At the time of this review, Health Canada had received 1 Canadian report of DRESS in a patient taking febuxostat.a This case was also published in the scientific literature.1"},{"field_id":639,"order_no":2,"bullet":"Three additional international cases of DRESS in association with febuxostat therapy were reported in the scientific literature."},{"field_id":639,"order_no":3,"bullet":"The World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) had received 13 international cases of DRESS suspected of being associated with the use of febuxostat.b"},{"field_id":639,"order_no":4,"bullet":"Ten cases of DRESS suspected of being associated with the use of febuxostat worldwide had been reported to Health Canada by the manufacturer, 2 of which were also published in the scientific literature."},{"field_id":639,"order_no":5,"bullet":"Allopurinol is also known to be associated with serious skin reactions including DRESS. Many of the patients that have reported serious skin and hypersensitivity reactions with febuxostat had also reported previous skin reactions to allopurinol."}],"conclusion_list":[{"field_id":640,"order_no":1,"bullet":"Health Canada has reviewed all the information available and concluded that the data, though limited, suggested a possible link between DRESS and febuxostat."},{"field_id":640,"order_no":2,"bullet":"Health Canada has asked the manufacturer of Uloric (febuxostat) to include DRESS in the Canadian prescribing information. The risk of DRESS has been added to the list of serious skin and hypersensitivity reactions."},{"field_id":640,"order_no":3,"bullet":"The Canadian prescribing information for Uloric (febuxostat) also mentions that many of the patients who have had serious skin reactions with this product also reported similar skin reactions while using allopurinol. Febuxostat should be used with caution in patients who have experienced previous skin reactions to allopurinol."},{"field_id":640,"order_no":4,"bullet":"Health Canada also published an article in the May 2015 edition of the Health Product InfoWatch to inform patients and healthcare professionals of this risk."},{"field_id":640,"order_no":5,"bullet":"Health Canada will continue to monitor side effect information for febuxostat, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00092","review_date":null,"drug_name":"Hydroxyzine (Atarax and generics)","safety_issue":"Abnormal heart rhythm (QT interval prolongation)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":649,"overview":"A safety review was undertaken soon after the European Medicines Agency notified Health Canada of the possibility that the use of hydroxyzine products could be associated with abnormal changes in the electrical activity of the heart, such as QT interval prolongation. These changes can lead to an abnormal heart rhythm (such as what is known as torsades de pointes). An abnormal heart rhythm refers to the heart beating too fast, too slow or irregularly. In some rare cases, abnormal heart rhythm can cause death.","use_canada":650,"findings":651,"conclusion":652,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":653,"title":"Summary Safety Review - Hydroxyzine (ATARAX and generics) - Assessing the Potential Risk of Abnormal Heart Rhythm","created_date":"2016-06-06","modified_date":null,"key_message_list":[{"field_id":649,"order_no":1,"bullet":"Hydroxyzine is a first-generation antihistamine used as part of treatment of anxiety; for itching (pruritus) due to allergic skin reactions; as a pre-surgical medication, such as for dental procedures; and for nausea and vomiting."},{"field_id":649,"order_no":2,"bullet":"Health Canada carried out a safety review following an action taken by the European Medicines Agency to limit the use of this medicine, partly by reducing the dose. This was brought on because slight changes in the heart rhythm were seen in a study of patients using this medicine."},{"field_id":649,"order_no":3,"bullet":"Health Canada is working with the manufacturers of Atarax to update the product information to better reflect the risk of changes in the heart rhythm, especially in patients with factors that would increase the risk of this side effect. Manufacturers of generic hydroxyzine products will also update their product information."}],"footnotes_list":[{"field_id":653,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":650,"order_no":1,"bullet":"Hydroxyzine has been marketed in Canada since 1956."},{"field_id":650,"order_no":2,"bullet":"Hydroxyzine is an anti-histamine that works in the skin to alleviate allergic reactions (e.g. swelling, itching) and in the brain to cause a sedative effect."},{"field_id":650,"order_no":3,"bullet":"With approximately 750,000 prescriptions and refills in Canada for 2013, 9 out of every 10 were written for adult patients - primarily to treat allergic reactions."},{"field_id":650,"order_no":4,"bullet":"Hydroxyzine is available in 3 different formulations: tablets, syrup, and as an injection into a muscle. These medicines are available only by prescription. It is known under the brand name Atarax and generic products are available."}],"finding_list":[{"field_id":651,"order_no":1,"bullet":"At the time of Health Canada's review, cases of QT interval prolongation or torsades de pointes (QTP/TdP) associated with the use of hydroxyzine were reported in 35 CanadianFootnote a and 26 international patients since the products were introduced to the market. In the majority of those cases, the patients had additional characteristics that would place them at a higher risk of experiencing these side effects. These factors included taking additional medicines known to be associated with QTP/TdP, having an imbalanced body chemistry (electrolyte imbalance), family history (such as congenital long QT syndrome), consuming daily doses of hydoxyzine that are over 100 mg, and/or using drugs that prevent the breakdown of hydroxyzine in the body."},{"field_id":651,"order_no":2,"bullet":"Of these reports, only three cases (all international) provided enough information for a more detailed medical review. Hydroxyzine was found to have had a \"possible\" or \"probable\" contribution to QTP/TdP. It was observed in these reports that at least one of the risk factors above could also have played a role in the adverse events. No cases of QTP/TdP without risk factors were identified by the medical evaluator. This made it difficult to conclude that hydroxyzine was the sole cause of the effects on the heart."},{"field_id":651,"order_no":3,"bullet":"During a review of the published medical literature, a slight QT interval prolongation was observed after a single 100 mg dose of hydroxyzine in a recent clinical study, and with even higher doses in older clinical studies."},{"field_id":651,"order_no":4,"bullet":"Studies in animals and human cells have showed that the doses of hydroxyzine typically used in therapy can cause QT interval prolongation. The size of the effect depended on the dose."}],"conclusion_list":[{"field_id":652,"order_no":1,"bullet":"Health Canada's safety review concluded that there is evidence that hydroxyzine may contribute, along with other risk factors, to changes in the electrical activity of the heart and adversely affect heart rhythm."},{"field_id":652,"order_no":2,"bullet":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is currently known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":663,"title":"Summary Safety Review - Denosumab (Prolia and Xgeva) - Hearing loss and deafness","created_date":"2016-06-06","modified_date":null,"key_message_list":[{"field_id":659,"order_no":1,"bullet":"Prolia (denosumab 60 mg) and Xgeva (denosumab 120 mg) are two strengths of a unique immune system protein (monoclonal antibody) that are used to slow bone loss and increase bone strength."},{"field_id":659,"order_no":1,"bullet":"Health Canada carried out a safety review after receiving a report from the European Medicines Agency of cases of hearing loss and deafness linked with the use of denosumab (Prolia or Xgeva). Health Canada's review concluded that the information currently available is not sufficient to confirm any additional link between denosumab and hearing loss or deafness at this time."},{"field_id":659,"order_no":2,"bullet":"Hearing problems are already listed in the Canadian prescribing information for Xgeva where it is listed as a less common side effect for people with advanced bone cancer, but not for Prolia."}],"footnotes_list":[{"field_id":663,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":660,"order_no":1,"bullet":"Prolia is used to treat weak and brittle bones (osteoporosis) in men and postmenopausal women who have high risk of bone breakage (fracture). It may also be used to slow bone loss and increase bone strength in women and men with a high risk of bone fracture due to treatments for certain types of cancer (breast cancer or prostate cancer)."},{"field_id":660,"order_no":2,"bullet":"Xgeva is used to prevent bone fractures and other bone (skeletal) conditions in people with tumors (except multiple myeloma) that have spread to bones; or to treat giant cell tumor of bone in adults and some adolescents."},{"field_id":660,"order_no":3,"bullet":"Denosumab is marketed in Canada under the brand names Prolia (denosumab 60 mg) available since 2010, and Xgeva (denosumab 120 mg) available since 2011."}],"finding_list":[{"field_id":661,"order_no":1,"bullet":"At the time of the review, Health Canada had received 16 Canadian reports of hearing loss associated with denosumab use, from the manufacturer.Footnote a Due to limited information from these cases, no conclusions could be made regarding what role, if any, the drug may have played."},{"field_id":661,"order_no":2,"bullet":"Worldwide, 89 reports of hearing loss had been reported in patients using denosumab, at the time of this review. However, the rate of hearing loss related to use of denosumab is not different from the rate of hearing loss in the general public."},{"field_id":661,"order_no":3,"bullet":"It is difficult to link hearing loss and deafness to denosumab use because patients using denosumab may have additional risk factors for hearing loss such as age, and having other diseases or taking other medications at the same time."}],"conclusion_list":[{"field_id":662,"order_no":1,"bullet":"Health Canada's review concluded that the current findings were not sufficient to confirm any additional link between denosumab (Prolia or Xgeva) and hearing loss or deafness at this time."},{"field_id":662,"order_no":2,"bullet":"Health Canada has asked the manufacturer of Prolia and Xgeva to actively monitor the risk of hearing loss and deafness in patients worldwide and to report these to Health Canada."},{"field_id":662,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information for Prolia and Xgeva, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00235","review_date":null,"drug_name":"Propyl-Thyracil (propylthiouracil)","safety_issue":"Birth defects","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2068,"overview":"Health Canada reviewed the potential risk of birth defects in babies whose mothers used PTU during pregnancy after becoming aware of international reports that suggested that such a link existed.
","use_canada":2069,"findings":2070,"conclusion":2071,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of PTU during pregnancy both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2072,"title":"Summary Safety Review - Propyl-Thyracil (propylthiouracil): Assessing the Potential Risk of Birth Defects","created_date":"2020-04-03","modified_date":null,"key_message_list":[{"field_id":2068,"order_no":1,"bullet":"Propyl-Thyracil (propylthiouracil) is a prescription drug authorized for sale in Canada to treat various conditions where too much thyroid hormone is produced."},{"field_id":2068,"order_no":2,"bullet":"Health Canada reviewed the potential risk of birth defects in babies whose mothers were treated with propylthiouracil (PTU) during pregnancy. This review was triggered by international reports of birth defects linked with PTU use in pregnant women."},{"field_id":2068,"order_no":3,"bullet":"Health Canada's review of the available information could not confirm or exclude a link between the risk of birth defects in babies and use of PTU in women during pregnancy."},{"field_id":2068,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the Canadian product safety information for PTU products to inform health care professionals and patients about this potential risk."}],"footnotes_list":[{"field_id":2072,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2069,"order_no":1,"bullet":"Propyl-Thyracil (propylthiouracil) is a prescription drug authorized for sale in Canada to:The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - TYSABRI (natalizumab) - Assessing the Potential Risk of Hemolytic Anemia","created_date":"2016-06-06","modified_date":null,"key_message_list":[{"field_id":669,"order_no":1,"bullet":"Tysabri (natalizumab) is used to treat patients with the relapsing-remitting form of multiple sclerosis (MS)."},{"field_id":669,"order_no":2,"bullet":"This safety review was triggered by a safety signal from a foreign regulator and published reports from the literature."},{"field_id":669,"order_no":3,"bullet":"Health Canada's review concluded that the evidence was too limited to confirm an increased risk of the hemolytic type of anemia in MS patients treated with Tysabri. However, post-market cases suggest that anemia is a potential consequence of Tysabri treatment. Following the completion of the safety review, the manufacturer has updated the prescribing information for Tysabri to better reflect the risk of anemia."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":670,"order_no":1,"bullet":"Tysabri is used for the treatment of patients with the relapsing-remitting form of MS. It is generally recommended for MS patients who have not responded well to other treatments or who are unable to tolerate them."},{"field_id":670,"order_no":2,"bullet":"Tysabri is a unique immune system protein, which prevents the active immune cells from reaching the brain. It is used for decreasing the inflammation in the brain and therefore reduces nerve damage caused by MS."},{"field_id":670,"order_no":3,"bullet":"Tysabri has been marketed in Canada since November 2006."},{"field_id":670,"order_no":4,"bullet":"Tysabri is administered into a vein (intravenously) over time (an infusion) by a healthcare professional. The recommended dose of Tysabri is 300 mg every 4 weeks."}],"finding_list":[{"field_id":671,"order_no":1,"bullet":"This safety review considered Canadian and international post-market cases of anemia that were reported on MS patients treated with Tysabri. Most case reports lacked detailed information, including information to determine if the cases of anemia were of the hemolytic type."},{"field_id":671,"order_no":2,"bullet":"The published articles reviewed cases that reported possible hemolytic anemia and anemia."},{"field_id":671,"order_no":3,"bullet":"Overall, the evidence was too limited to support a direct link between the use of Tysabri and the risk of hemolytic anemia. However, post-market cases of anemia which were mainly \"characterised by temporary decreases in hemoglobin levels\", were reported in MS patients treated with Tysabri for which a possible role of the drug could not be ruled out."},{"field_id":671,"order_no":4,"bullet":"Anemia is a rare but potentially serious side effect in MS treatment. It is therefore important to monitor anemia during treatment with Tysabri."}],"conclusion_list":[{"field_id":672,"order_no":1,"bullet":"Health Canada's review concluded that there is currently insufficient evidence to support a direct link between the use of Tysabri and hemolytic anemia. However, post-market cases of anemia in MS patients treated with Tysabri were reported."},{"field_id":672,"order_no":2,"bullet":"Health Canada requested that the manufacturer update the prescribing information to better reflect the risk of anemia."},{"field_id":672,"order_no":3,"bullet":"Following the completion of this safety review, the manufacturer has updated the Canadian Product Monograph for Tysabri with new information about the risk of anemia."},{"field_id":672,"order_no":4,"bullet":"Health Canada will continue to monitor side effect information involving Tysabri, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00096","review_date":null,"drug_name":"Codeine-containing products","safety_issue":"Serious breathing problems (respiratory depression) in children and adolescents.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":677,"overview":"In 2013 and 2015, Health Canada carried out safety reviews on codeine-containing products as they relate to the risk of potentially life-threatening breathing problems. At the time, it was recommended that codeine-containing products no longer be used in children under 12 years of age. New safety reviews were carried out to further assess the risk of serious breathing problems in children and adolescents treated with codeine to decide if more should be done to manage this risk in this age group.
Codeine is changed into morphine by the liver; both drugs belong to the family of opioids. It is known that opioids can slow the pace of breathing. Having too much of an opioid can slow down breathing enough to be life-threatening. Some people are ultra-rapid metabolizers, which means that they convert codeine into morphine more quickly and completely. They are more likely to have greater than expected amounts of morphine in their blood after taking codeine-containing products, which can be more dangerous.
","use_canada":678,"findings":733,"conclusion":679,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":680,"title":"Summary Safety Review - Codeine-containing products - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents","created_date":"2016-07-28","modified_date":null,"key_message_list":[{"field_id":677,"order_no":1,"bullet":"Codeine-containing products are opiate medications used to treat pain and reduce coughing."},{"field_id":677,"order_no":2,"bullet":"Health Canada continues to recommend that prescription and non-prescription codeine should not be used in children under 12 years of age."},{"field_id":677,"order_no":3,"bullet":"Health Canada is working with manufacturers to update the safety information for prescription products so that they are no longer recommended for use after surgery to remove tonsils or adenoids in patients under 18 years of age."}],"footnotes_list":[{"field_id":680,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[],"use_canada_list":[{"field_id":678,"order_no":1,"bullet":"Codeine-containing medicines are used to treat pain and reduce cough."},{"field_id":678,"order_no":2,"bullet":"Codeine is available either alone or in combination with other medications. Some codeine-containing products are only available by prescription while others are non-prescription. For non-prescription codeine-containing products, consumers must have a discussion with a pharmacist before they can purchase it."},{"field_id":678,"order_no":3,"bullet":"The safety information for codeine-containing products warns against using them if you have conditions that would make breathing difficult, such as asthma, chronic lung disease or other breathing problems."}],"finding_list":[{"field_id":733,"order_no":1,"bullet":"Prescription codeine
Non-prescription codeine
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this treatment both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":689,"title":"Summary Safety Review - ENBREL (etanercept) - Assessing the potential harm to the developing babies of mothers treated with ENBREL","created_date":"2016-08-04","modified_date":null,"key_message_list":[{"field_id":685,"order_no":1,"bullet":"Enbrel is used to treat inflammation of joints and skin which occurs when the body's own defence system attacks the joints and/or the skin, including certain forms of arthritis and psoriasis. The product information for Enbrel does not recommend use during pregnancy."},{"field_id":685,"order_no":2,"bullet":"Health Canada carried out a safety review after receiving information from a study of a long-term pregnancy registry. In this study, Enbrel use during pregnancy was associated with fewer reports of miscarriages but a slightly increased chance of having a baby with a birth defect, compared to pregnant women who did not take Enbrel."},{"field_id":685,"order_no":3,"bullet":"Health Canada will work with the manufacturer to update the product safety information for Enbrel to share information regarding what is known about the potential harm to a developing baby when mothers are treated with this medicine during pregnancy."}],"footnotes_list":[{"field_id":689,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":686,"order_no":1,"bullet":"Enbrel is a medicine which works by blocking a chemical produced in the body that causes pain and swelling (inflammation)."},{"field_id":686,"order_no":2,"bullet":"This medicine treats inflammation that results from the body's own defence system attacking its joints and skin (autoimmune diseases). Examples of autoimmune joint and skin diseases include ankylosing spondylitis, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, and plaque psoriasis."},{"field_id":686,"order_no":3,"bullet":"Enbrel is given through an injection under the skin and is available by prescription only."},{"field_id":686,"order_no":4,"bullet":"Enbrel has been marketed in Canada since March 14, 2001."}],"finding_list":[{"field_id":687,"order_no":1,"bullet":"At the time of the review, Health Canada had received 7 Canadian reportsa of birth defects in the newborn babies of mothers treated with Enbrel. The babies had one of many kinds of abnormalities in parts of the body including the heart, skull and jawbone. Some reports noted that Enbrel crossed the placenta from the mother to the baby (in general, many medicines typically do). However, many of the women were also taking other medications, making it difficult to determine if Enbrel caused the birth defects."},{"field_id":687,"order_no":2,"bullet":"The review of the pregnancy registry study, found that women treated with Enbrel had less miscarriages compared to those women not treated with Enbrel. The study also found slightly more reports of major and minor birth defects in children born to pregnant mothers treated with Enbrel than in children born to women not treated with Enbrel. There was no pattern or unique kinds of birth defects."},{"field_id":687,"order_no":3,"bullet":"It was not possible to determine whether Enbrel itself caused birth defects because many of the women that were represented in the pregnancy registry took other medications while taking Enbrel."}],"conclusion_list":[{"field_id":688,"order_no":1,"bullet":"Health Canada's review noted that taking Enbrel during pregnancy was associated with a lesser risk of experiencing a miscarriage but a potential risk of carrying to full term a newborn with a birth defect. The review could not conclude that Enbrel by itself was the cause of birth defects."},{"field_id":688,"order_no":2,"bullet":"Health Canada is working with the manufacturer to update the product safety information for Enbrel to share information regarding what is known about the potential harm to a developing baby when mothers are treated with this medicine during pregnancy."},{"field_id":688,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Enbrel, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new information on this risk is identified."}]},{"template":2,"link_id":"SSR00100","review_date":null,"drug_name":"Hydrocodone-containing products","safety_issue":"Serious breathing problems (respiratory depression) in children and adolescents","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":705,"overview":"It is known that hydrocodone can slow breathing when too much is taken. The labelling for these drugs already warns of this risk and it applies to all ages, including children. Health Canada's safety review activities on hydrocodone further studied the risk of serious breathing problems in children and adolescents and stems from review work with codeine (another opioid drug) to determine if more safety measures were needed.","use_canada":706,"findings":707,"conclusion":708,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":709,"title":"Summary Safety Review - Hydrocodone-containing products - Assessing the Risk of Serious Breathing Problems (respiratory depression) in Children and Adolescents","created_date":"2016-07-28","modified_date":null,"key_message_list":[{"field_id":705,"order_no":1,"bullet":"Hydrocodone is an opioid prescription drug used to treat exhausting, dry (non-productive) cough."},{"field_id":705,"order_no":2,"bullet":"Following a safety review by Health Canada looking at codeine use and the risk of serious breathing problems in children, it was decided that a similar review should be carried out for hydrocodone."},{"field_id":705,"order_no":3,"bullet":"This safety review identified cases of serious breathing problems with hydrocodone mainly when used in children under 6 years of age. Health Canada will work with manufacturers to update the product information for hydrocodone so that it is no longer recommended for use in this age group."}],"footnotes_list":[{"field_id":709,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":706,"order_no":1,"bullet":"Hydrocodone is a prescription opioid drug used to reduce exhausting, dry (non-productive) cough and has been marketed in Canada since the late 1950s."},{"field_id":706,"order_no":2,"bullet":"In Canada, some hydrocodone-containing products are recommended for use in children under 6 years of age. However, in recent years, the number of prescriptions (new and refills) of hydrocodone in children and adolescents has declined from 42,000 in 2010 to 28,000 in 2014."}],"finding_list":[{"field_id":707,"order_no":1,"bullet":"At the time of the review Health Canada assessed a total of 7 reports, in children and adolescents, of hydrocodone use related to serious breathing problems or related to hydrocodone overdosea. Two reports involved children that were 7 and 15 years old; one was considered related to the hydrocodone use but there was not enough information provided in the other report to assess it. There were five reports in children under 6 years of age and upon further analysis three were considered related to the hydrocodone use. Death was reported in 2 of these (involving a 2 year-old and 5 year-old); one was considered related to the hydrocodone use but there was not enough information provided in the other report to determine if the death was due to hydrocodone use."},{"field_id":707,"order_no":2,"bullet":"A review of the published literature identified one international case of a 3-year old child that experienced serious breathing difficulties after use of hydrocodone and later died. Upon further review, the event was considered to be due to hydrocodone use."},{"field_id":707,"order_no":3,"bullet":"In the majority of the cases, including the fatal cases, the children received more hydrocodone than recommended for their age."},{"field_id":707,"order_no":4,"bullet":"At this time, the evidence available in the side effect reports of hydrocodone does not present enough information to conclude that the rate in which it is broken down (metabolized) causes breathing difficulties as is the case for codeine."}],"conclusion_list":[{"field_id":708,"order_no":1,"bullet":"The majority of cases of serious breathing problems identified in the safety review involved children under 6 years of age and usually involving higher-than-recommended doses."},{"field_id":708,"order_no":2,"bullet":"Health Canada will work with manufacturers to update the product information for hydrocodone to inform that its use in children under 6 years of age is no longer recommended. Health Canada will also issue an Information Update regarding the risk of serious breathing problems."},{"field_id":708,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving hydrocodone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00102","review_date":null,"drug_name":"Yondelis (trabectedin)","safety_issue":"Fluid leakage from small blood vessels (capillary leak syndrome)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":725,"overview":"Health Canada carried out a safety review to look into the potential risk of capillary leak syndrome with the use of Yondelis. During routine monitoring, Health Canada became aware of international reports of capillary leak syndrome in patients who were treated with Yondelis.
Capillary leak syndrome is a rare but potentially life-threatening condition which involves the leakage of fluid from the small blood vessels into various parts of the body. This can cause sudden swelling, shortness of breath, passing less urine, and a drop in blood pressure. Patients with capillary leak syndrome require timely treatment to replace fluid in the body with saline based fluids through the veins, and manage their symptoms in order to improve their condition.
","use_canada":726,"findings":727,"conclusion":728,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - YONDELIS (trabectedin) - Assessing the Potential Risk of Fluid Leakage from Small Blood Vessels (capillary leak syndrome)","created_date":"2016-08-04","modified_date":null,"key_message_list":[{"field_id":725,"order_no":1,"bullet":"Yondelis is used alone to treat some advanced soft tissue cancers, or together with another drug to treat ovarian cancer, when other treatments did not work."},{"field_id":725,"order_no":2,"bullet":"This safety review was triggered by international reports of fluid leakage from small blood vessels (a rare but serious condition called capillary leak syndrome) in patients who used Yondelis. Health Canada carried out the review to look at the possible link between Yondelis and capillary leak syndrome, and to determine whether steps need to be taken to minimize the risk."},{"field_id":725,"order_no":3,"bullet":"Health Canada's safety review concluded that there is a potential risk of capillary leak syndrome with the use of Yondelis. Health Canada is therefore recommending updates to the Canadian product information for Yondelis to include this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":726,"order_no":1,"bullet":"Yondelis is used alone to treat some advanced cancers, such as those from fat cells (liposarcoma) or from smooth muscles (leiomyosarcoma). It can also be used together with another drug to treat ovarian cancer. Yondelis is usually used when other treatments have not worked."},{"field_id":726,"order_no":2,"bullet":"Yondelis has been sold in Canada since August 2010. It is not widely used in Canada."},{"field_id":726,"order_no":3,"bullet":"Yondelis is usually prescribed by cancer specialists. It is given by injection into a large vein once every 3 weeks. The dose is calculated using the patient's height and weight."}],"finding_list":[{"field_id":727,"order_no":1,"bullet":"At the time of the review, there were no Canadian cases of capillary leak syndrome reported with the use of Yondelis."},{"field_id":727,"order_no":2,"bullet":"A search was carried out on published scientific and medical literature. It did not find strong evidence of a link between capillary leak syndrome and the use of Yondelis."},{"field_id":727,"order_no":3,"bullet":"There were international cases of capillary leak syndrome reported with the use of Yondelis. Health Canada reviewed 26 international case reports. The review showed that Yondelis played a possible role in 20 cases of capillary leak syndrome. It was difficult to determine how much of a role Yondelis played in the reported cases of capillary leak syndrome because other health conditions could have explained some of the reported medical problems."},{"field_id":727,"order_no":4,"bullet":"The literature review showed that capillary leak syndrome has been reported with other drugs, some of them being used to treat various cancers. Some of these cancer drugs are labelled for capillary leak syndrome in their product information. Capillary leak syndrome is listed in the European product information for Yondelis."}],"conclusion_list":[{"field_id":728,"order_no":1,"bullet":"Health Canada's safety review concluded that there is a potential risk of capillary leak syndrome with the use of Yondelis."},{"field_id":728,"order_no":2,"bullet":"Health Canada is recommending updates to the Canadian product information to include the potential risk of capillary leak syndrome with the use of Yondelis."},{"field_id":728,"order_no":3,"bullet":"Health Canada continues to monitor side effect information involving Yondelis, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00103","review_date":null,"drug_name":"Gabapentin","safety_issue":"Further Assessing the Risk of Serious breathing problems (respiratory depression)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":743,"overview":"In 2014, the product information for gabapentin products was updated to warn about the risk of serious breathing problems (respiratory depression) when it is used with an opioid. While reviewing safety information given by the manufacturer for this change, Health Canada found cases of respiratory depression in patients treated with gabapentin alone. Therefore, this current safety review was carried out to assess the possibility of the same concerns in patients using gabapentin alone (when not taken with opioids) and to find out if more safety measures were needed.","use_canada":744,"findings":745,"conclusion":746,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":747,"footnotes":748,"title":"Summary Safety Review - Gabapentin - Assessing the Potential Risk of Serious Breathing Problems","created_date":"2016-09-16","modified_date":null,"key_message_list":[{"field_id":743,"order_no":1,"bullet":"Gabapentin belongs to the family of medicines called antiepileptic drugs and is used for treating epilepsy (seizures)."},{"field_id":743,"order_no":2,"bullet":"While reviewing information provided by the manufacturer, Health Canada found cases of serious breathing problems in patients treated with gabapentin."},{"field_id":743,"order_no":3,"bullet":"Health Canada's review concluded that there is evidence supporting a risk of serious breathing problems when gabapentin is used. Health Canada recommended updates to the product information for gabapentin to warn about this risk."}],"footnotes_list":[{"field_id":748,"order_no":1,"bullet":"a Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[],"use_canada_list":[{"field_id":744,"order_no":1,"bullet":"Gabapentin belongs to the family of medicines called antiepileptic drugs and is used for treating epilepsy (seizures) when other treatments have not worked."},{"field_id":744,"order_no":2,"bullet":"Gabapentin has been marketed in Canada since 1994 under the brand name Neurontin and generic products are also available. It is available by prescription only. In 2015, approximately 3.9 million prescriptions (new and refills) were filled."}],"finding_list":[{"field_id":745,"order_no":1,"bullet":"At the time of the review, Health Canada received 1 Canadian report a where gabapentin use was considered related to respiratory depression."},{"field_id":745,"order_no":2,"bullet":"Health Canada is aware that in other countries gabapentin has approved uses other than for the treatment of epilepsy."},{"field_id":745,"order_no":3,"bullet":"The review gathered an additional 20 international reports related to serious breathing problems associated with gabapentin use from the scientific and medical literature as well as information received from drug manufacturers. In these reports, the drug was used in some patients for treating epilepsy and in other patients for other uses including pain management. Some reports described that when the patient stopped using gabapentin the breathing problems went away and when the medication was restarted the breathing problems reappeared. This finding supports that gabapentin use may have contributed to the side effects."},{"field_id":745,"order_no":4,"bullet":"The review also found that patients having lung, kidney or nervous system diseases that impact breathing, as well as those that are elderly, or using other drugs that can affect breathing are at higher risk of serious breathing problems."}],"conclusion_list":[{"field_id":746,"order_no":1,"bullet":"Health Canada's safety review concluded that there is evidence of a link between the use of gabapentin, in general, and the risk of serious breathing problems."},{"field_id":746,"order_no":2,"bullet":"Health Canada will work with manufacturers to update the product information to further warn about the risk of serious breathing problems. Health Canada will also issue a notice in the Health Product InfoWatch when the product information is updated."},{"field_id":746,"order_no":3,"bullet":"Health Canada continues to monitor safety information involving gabapentin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00104","review_date":null,"drug_name":"Soliris and Bexsero","safety_issue":"Increased risk of hemolysis and low hemoglobin when patients receiving Soliris were vaccinated with Bexsero","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":755,"overview":"The safety of all vaccines, including Bexsero, is under continuous monitoring by Health Canada and the Public Health Agency of Canada. Health Canada carried out a safety review of Bexsero after 1 year on the market. By studying cases reported to the Canada Vigilance program, more reports of serious side effects were found in patients that were also treated with Soliris than in other patients. Health Canada conducted a follow up review of Soliris to find out why there were more reports.","use_canada":756,"findings":757,"conclusion":758,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of Soliris and Bexsero in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":759,"footnotes":760,"title":"Summary Safety Review - SOLIRIS (eculizumab) and BEXSERO (Multicomponent Meningococcal B Vaccine [recombinant, adsorbed]) - Assessing the Potential Risk of Hemolysis and Low Hemoglobin in Patients Treated with Soliris and Vaccinated with Bexsero","created_date":"2016-09-16","modified_date":null,"key_message_list":[{"field_id":755,"order_no":1,"bullet":"Soliris is a prescription drug used to treat patients with Paroxysmal Nocturnal Hemoglobinuria (PNH), or atypical Haemolytic Uremic Syndrome (aHUS). Patients receiving Soliris are at increased risk of meningitis (an inflammation of the lining of the brain) and should be vaccinated for meningitis before, or when, they start treatment with Soliris. "},{"field_id":755,"order_no":2,"bullet":"Bexsero is a vaccine used to protect against Neisseria meningitidis serogroup B, a germ (bacterium) that causes meningitis. Bexsero has been marketed in Canada since 2014, which is 5 years after Soliris began to be sold. "},{"field_id":755,"order_no":3,"bullet":"A Health Canada safety review of patients treated with Soliris concluded that there was an increased risk of anemia or the destruction of red blood cells (hemolysis) when patients already receiving Soliris were vaccinated with Bexsero. The risk was highest when patients already being treated with Soliris received a dose of Soliris within 2 weeks after being vaccinated with Bexsero."},{"field_id":755,"order_no":4,"bullet":"The manufacturer has updated the Canadian product information for Soliris to include the risk of hemolysis with vaccines against Neisseria meningitidis serogroup B. To minimize the risk of hemolysis, the manufacturer recommends that patients who are already being treated with Soliris should only be vaccinated when their disease is controlled and the Soliris concentration in the blood is high. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":756,"order_no":1,"bullet":"Soliris is a prescription drug that is used to treat patients with a rare disease called Paroxysmal Nocturnal Hemoglobinuria (PNH), in which the immune system breaks down the patient's red blood cells (hemolysis). Soliris is also used to treat patients with a rare disease called atypical Haemolytic Uremic Syndrome (aHUS), in which activation of the immune system causes blood clots (thrombi) in small blood vessels throughout the body and kidney failure."},{"field_id":756,"order_no":2,"bullet":"Soliris blocks part of the immune system called terminal complement in these patients, which makes them more likely to get life-threatening, sometimes deadly infections, including meningitis. The manufacturer recommends that patients taking Soliris should be vaccinated for meningitis before, or when they start treatment with Soliris. Patients vaccinated less than 2 weeks prior to starting Soliris therapy must receive antibiotics until 2 weeks after vaccination."},{"field_id":756,"order_no":3,"bullet":"Soliris has been marketed in Canada since May 2009, and at that time, there was no vaccine against the Neisseria meningitidis group B bacteria available."},{"field_id":756,"order_no":4,"bullet":"Bexsero is a vaccine used for the prevention of disease caused by the Neisseria meningitidis group B bacteria (germs). These germs can cause serious, and sometimes life threatening, infections of the lining of the brain and spine (meningitis) and blood poisoning (sepsis)."},{"field_id":756,"order_no":5,"bullet":"Bexsero has been marketed in Canada since February 2014, and is authorized for use in children aged 2 months to 17 years."}],"finding_list":[{"field_id":757,"order_no":1,"bullet":"Health Canada's safety review of Bexsero found that low hemoglobin was a common side effect in patients treated with Soliris, but not in other patients vaccinated with Bexsero."},{"field_id":757,"order_no":2,"bullet":"A review of reports of low hemoglobin in patients treated with Soliris and vaccinated with Bexsero found that the reporting rate for low hemoglobin was 1 case per month in the year before vaccination, 16 per month in the 30 days following vaccination, and less than 1 per month more than 30 days after vaccination. The risk was highest when patients already being treated with Soliris received a dose of Soliris within 2 weeks after being vaccinated with Bexsero."}],"conclusion_list":[{"field_id":758,"order_no":1,"bullet":"A review of the reports for patients treated with Soliris concluded that there was an increased risk of anemia or the destruction of red blood cells (hemolysis) when patients already receiving Soliris were vaccinated with Bexsero."},{"field_id":758,"order_no":2,"bullet":"The manufacturer has updated the Canadian product information for Soliris to include the risk of hemolysis with vaccines against Neisseria meningitidis serogroup B. To minimize the risk of hemolysis, the manufacturer recommends that patients who are already being treated with Soliris should only be vaccinated when their disease is controlled and the Soliris concentration in the blood is high."},{"field_id":758,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Soliris and Bexsero, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00105","review_date":null,"drug_name":"Viscous Lidocaine 2%","safety_issue":"Severe side effects in infants and young children","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":767,"overview":"Health Canada carried out a safety review to assess the potential risk of severe side effects in infants and young children with the use of viscous lidocaine. The issue was triggered after the United States Food and Drug Administration issued a safety announcement that viscous lidocaine should not be used for teething pain in infants and children. In addition, the Food and Drug Administration required that labels describe the risk of severe side effects in this age group. The severe side effects reported in the United States have not been seen in Canada, but they have been reported in the international medical literature. The current Canadian product information does not recommend the use of viscous lidocaine for teething pain in infants and young children.
In addition, the Canadian Paediatric Society, an association that represents professionals who work with and care for children, have developed teething guidelines a that do not support the use of these products.
","use_canada":768,"findings":769,"conclusion":770,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":771,"footnotes":772,"title":"Summary Safety Review - Viscous Lidocaine 2% - Assessing the Potential Risk of Severe Side Effects in Infants and Young Children","created_date":"2016-08-29","modified_date":null,"key_message_list":[{"field_id":767,"order_no":1,"bullet":"Viscous lidocaine 2% is used to reduce pain and discomfort in the mouth or to numb an area in the mouth before a medical exam or procedure. "},{"field_id":767,"order_no":2,"bullet":"A safety review was carried out by Health Canada after the United States Food and Drug Administration issued a safety announcement that this product should not be used in infants and children for teething pain, and that the labels must describe the risk of severe side effects such as seizures, severe brain injury, heart problems and death which have been reported in patients from 5 months to 4 years of age in the United States. No similar cases were reported in Canada."},{"field_id":767,"order_no":3,"bullet":"Health Canada's safety review concluded that there is a link between the use of viscous lidocaine 2% and severe side effects in infants and young children. Health Canada is working with the manufacturers of viscous lidocaine 2% products to update the Canadian product information to include these severe side effects. "}],"footnotes_list":[{"field_id":772,"order_no":1,"bullet":"a The Canadian Paediatric Society. Caring for Kids: Healthy Teeth for Children."}],"reference_list":[],"use_canada_list":[{"field_id":768,"order_no":1,"bullet":"Viscous lidocaine 2% is used to reduce pain and discomfort in the mouth or to numb an area in the mouth before a medical exam or procedure in the mouth area."},{"field_id":768,"order_no":2,"bullet":"There are 4 non-prescription viscous lidocaine 2% products sold in Canada. They can be obtained without a prescription from a pharmacist."}],"finding_list":[{"field_id":769,"order_no":1,"bullet":"At the time of the review, there were no Canadian cases of serious side effects reported with the use of viscous lidocaine 2% products."},{"field_id":769,"order_no":2,"bullet":"The review of the international medical literature showed 13 reported cases of serious side effects with the use of viscous lidocaine 2% products in infants and young children."},{"field_id":769,"order_no":3,"bullet":"Although the Canadian product information does not recommend using viscous lidocaine 2% for teething pain, the product labelling and dosing instructions for some products do not specify about how much time should be left between doses. This could lead to high levels of lidocaine in the patient, resulting in the severe side effects reported in infants and young children."}],"conclusion_list":[{"field_id":770,"order_no":1,"bullet":"Health Canada's safety review concluded that there is a link between viscous lidocaine 2% and severe side effects (seizures, severe brain injury, heart problems, and death) in infants and young children from 5 months to 4 years of age."},{"field_id":770,"order_no":2,"bullet":"Health Canada is working with the manufacturers of viscous lidocaine 2% products to update the product information with warnings about the risk of severe side effects in infants and young children and clarify directions for approved uses."},{"field_id":770,"order_no":3,"bullet":"Health Canada continues to monitor side effect information involving viscous lidocaine 2%, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00106","review_date":null,"drug_name":"Bortezomib (Velcade and generics)","safety_issue":"Flesh-eating disease (necrotizing fasciitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":779,"overview":"This safety review was done as a follow-up assessment on the possible risk of flesh-eating disease with the use of bortezomib. Health Canada originally published a summary of that safety review on September 3, 2015 At that time, insufficient data was available to make a conclusion about this possible risk. Health Canada asked for additional safety information from the manufacturer and has now completed a follow-up safety review, looking at the new safety information received.","use_canada":780,"findings":781,"conclusion":782,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":783,"footnotes":784,"title":"Summary Safety Review - Bortezomib (VELCADE and generics) - Assessing the Potential Risk of Flesh-Eating Disease (Necrotizing Fasciitis) - UPDATE","created_date":"2016-08-26","modified_date":null,"key_message_list":[{"field_id":779,"order_no":1,"bullet":"Bortezomib (Velcade and generics) is used to treat cancers of the bone marrow (multiple myeloma) and of the lymphatic system (mantle cell lymphoma) affecting the white blood cells."},{"field_id":779,"order_no":2,"bullet":"A summary safety review was published on September 3, 2015, following Health Canada's assessment of a possible link between treatment with bortezomib and flesh-eating disease. That safety review recommended that Health Canada continue to monitor bortezomib for the risk of flesh-eating disease and request additional safety information from the manufacturer."},{"field_id":779,"order_no":3,"bullet":"In a follow-up safety review, Health Canada assessed the additional safety information received from the manufacturer. At the time of the updated review, there was insufficient evidence to make a link between bortezomib treatment and the risk of flesh-eating disease. Health Canada will continue to monitor this issue. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":780,"order_no":1,"bullet":"VELCADE (bortezomib) is used to treat cancers of the bone marrow (multiple myeloma) and the lymphatic system that affects white blood cells (mantle cell lymphoma)."},{"field_id":780,"order_no":2,"bullet":"Bortezomib is used for the treatment of adult patients who have cancers of the bone marrow called Multiple Myeloma (MM) or of the blood called Mantle Cell Lymphoma (MCL) affecting the white blood cells."},{"field_id":780,"order_no":3,"bullet":"The number of Canadian prescriptions for bortezomib is relatively low (about 5000 prescriptions per year). Bortezomib is mostly used in hospitals."}],"finding_list":[{"field_id":781,"order_no":1,"bullet":"At the time of the updated review, which was based on the safety information received from the manufacturer, there were no cases of flesh-eating disease linked with the use of bortezomib in Canada."},{"field_id":781,"order_no":2,"bullet":"A search of the manufacturer's safety database for Velcade (bortezomib) found 11 international cases of flesh-eating disease. Health Canada reviewed these international cases and found that 8 cases were possibly linked and 3 cases were unlikely to be linked to the use of bortezomib. All 11 cases may have been impacted by the use of other medicines at the same time as bortezomib (concomitant medications), underlying diseases or other risk factors which could also have played a role in the development of flesh-eating disease."},{"field_id":781,"order_no":3,"bullet":"Risk factors for flesh-eating disease include diabetes, alcohol use, smoking, obesity, the decrease of a body's ability to fight a disease (immune suppression), chronic steroid use, and blood circulation diseases affecting blood vessels (peripheral vascular disease). In addition, transplant and cancer patients are more likely to get infections in general, including being infected by germs that cause flesh-eating disease, due to their weakened immune system."}],"conclusion_list":[{"field_id":782,"order_no":1,"bullet":"Health Canada's follow-up safety review concluded that there was insufficient evidence at this time to make a link between bortezomib and flesh-eating disease."},{"field_id":782,"order_no":2,"bullet":"Health Canada will continue to monitor side effect information for bortezomib (Velcade and generics), as it does for all health products on the Canadian market, to identify and assess possible harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00107","review_date":null,"drug_name":"Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, (Digoxin)","safety_issue":"Increased risk of death in patients with irregular heart rhythm (atrial fibrillation) and patients with heart failure taking digoxin compared to patients with the same health issues but not using digoxin.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":791,"overview":"Health Canada completed a safety review to evaluate if using digoxin was linked to a higher risk of death compared to patients not using digoxin. The issue was triggered by two publications in the scientific literature 1, 2 which investigated the link between digoxin and death. Results of the studies suggested that digoxin use may be linked with a higher risk of death when compared to patients not using digoxin, especially among patients diagnosed with an irregular heart rhythm.","use_canada":792,"findings":793,"conclusion":794,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":795,"footnotes":796,"title":"Summary Safety Review - Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, (Digoxin) - Assessing the Potential Higher Risk of Death Compared to Patients not Using Digoxin","created_date":"2016-08-23","modified_date":null,"key_message_list":[{"field_id":791,"order_no":1,"bullet":"Digoxin is marketed in Canada for the treatment of mild to moderate heart failure and to control the heart rate in patients with chronic irregular heart rhythm."},{"field_id":791,"order_no":2,"bullet":"This safety review was carried out by Health Canada after two published studies suggested that digoxin use may be linked with an increased risk of death, particularly in patients with irregular heart rhythm. "},{"field_id":791,"order_no":3,"bullet":"Health Canada concluded that a link between digoxin use and a higher risk of death when compared to those not using digoxin could not be established. Health Canada will continue monitoring the issue and will re-evaluate it when new information becomes available "}],"footnotes_list":[{"field_id":796,"order_no":1,"bullet":"a Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":795,"order_no":1,"bullet":"1 Vamos,M., Erath,J.W., & Hohnloser,S.H. Digoxin-associated mortality: a systematic review and meta-analysis of the literature Eur. Heart J. 36, 1831-1838 (2015)"},{"field_id":795,"order_no":2,"bullet":"2 Freeman,J.V. et al. Digoxin and risk of death in adults with atrial fibrillation: The ATRIA-CVRN study. Circ. Arrhythm electrophysiol. 8, 49-58 (2015)"}],"use_canada_list":[{"field_id":792,"order_no":1,"bullet":"Digoxin has been marketed in Canada since 1936. It is currently marketed under the following brand names: Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, and Digoxin Injection C.S.D."},{"field_id":792,"order_no":2,"bullet":"Digoxin is used to treat mild to moderate heart failure by improving heart pumping activity and improving the symptoms of heart failure. It is also used to control heart rate in patients with irregular heart rhythm."},{"field_id":792,"order_no":3,"bullet":"At the time of review, the estimated number of prescriptions (including refills) for digoxin in Canada was 1.68 million per year."},{"field_id":792,"order_no":4,"bullet":"The product information for Digoxin in Canada explains that digoxin is not to be used in patients with the condition where the lower chambers of the heart contract rapidly and uncoordinatedly so the heart pumps little or no blood (ventricular fibrillation)."}],"finding_list":[{"field_id":793,"order_no":1,"bullet":"At the time of the review, Health Canada had received 39 Canadian cases of death a. Of the 39 cases, 22 were due to intentional overdoses (suicide) or accidental overdoses (medication errors). The remaining 16 Canadian reports (1 was reported twice) did not have a clear relationship between digoxin use and the corresponding reported deaths because the patients had other medical conditions which could have been linked to their death."},{"field_id":793,"order_no":2,"bullet":"The World Health Organization's database showed that there were 1086 reports of death linked with digoxin use. However, only 15 of the reports contained enough information to allow for a meaningful assessment. A clear link between digoxin and death could not be made for these 15 cases because the medical conditions digoxin treats already carries the risk of death. There are also differences in local treatment guidelines and allowed uses for digoxin worldwide."},{"field_id":793,"order_no":3,"bullet":"The review of the scientific and medical literature, including the 2 studies that triggered the safety review, showed that study outcomes were conflicting and the results of the respective studies depended on the specific study methods and design. As a result, the reviewed studies could not provide enough evidence of a link for digoxin and a higher risk of death."}],"conclusion_list":[{"field_id":794,"order_no":1,"bullet":"Based on its review of the current scientific literature and medical literature, Health Canada did not find evidence supporting a link between the use of digoxin and a higher risk of death."},{"field_id":794,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving digoxin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action when any new health risks are identified."}]},{"template":2,"link_id":"SSR00108","review_date":null,"drug_name":"Gilenya (fingolimod)","safety_issue":"Rare brain infection (progressive multifocal leukoencephalopathy)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":803,"overview":"Health Canada's safety review was carried out as a result of an international report of a suspected progressive multifocal leukoencephalopathy (a rare brain infection) in a patient taking Gilenya for multiple sclerosis. This patient had no previous treatment with other multiple sclerosis drugs known to increase the risk of this brain infection. Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system).
During Health Canada's safety review, the manufacturer updated the product information to reflect the risk of progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy is a rare brain infection caused by a virus (John Cunningham Virus). This infection can happen as a result of a weakened immune system, and is often fatal.
","use_canada":804,"findings":805,"conclusion":806,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":807,"footnotes":808,"title":"Summary Safety Review - GILENYA (fingolimod) - Assessing the Potential Risk of a Rare Brain Infection (Progressive Multifocal Leukoencephalopathy)","created_date":"2016-08-19","modified_date":null,"key_message_list":[{"field_id":803,"order_no":1,"bullet":"Gilenya (fingolimod) is used to treat multiple sclerosis, a disease of the nervous system. It is used in adult patients with a specific type of multiple sclerosis (relapsing-remitting) who do not respond well, or are unable to tolerate other (one or more) therapies for multiple sclerosis."},{"field_id":803,"order_no":2,"bullet":"Health Canada carried out a safety review as a result of an international report of a rare brain infection (progressive multifocal leukoencephalopathy), in a patient taking Gilenya (fingolimod). This patient had no previous treatment with other multiple sclerosis drugs known to increase the risk of this brain infection."},{"field_id":803,"order_no":3,"bullet":"Health Canada's review concluded that from the available evidence, there was a possible link between progressive multifocal leukoencephalopathy and Gilenya (fingolimod).While this review was being carried out, the product information for Gilenya (fingolimod) was updated by the manufacturer to warn about this potential risk. Health Canada has requested the manufacturer to continue to monitor for this potential risk and provide Health Canada with any new information it becomes aware of on this safety issue. "}],"footnotes_list":[{"field_id":808,"order_no":1,"bullet":"a Health Canada. Information Update - Multiple sclerosis drug Gilenya (fingolimod): Safety information on the risk of skin cancer and a rare brain infection. September 30, 2015. Accessed 2016-02-02."},{"field_id":808,"order_no":2,"bullet":"b Health Canada. Health Product InfoWatch October, 2015. Accessed 2016-02-02."}],"reference_list":[],"use_canada_list":[{"field_id":804,"order_no":1,"bullet":"Gilenya (fingolimod) is used for the treatment of adult patients with a specific type of multiple sclerosis (relapsing-remitting multiple sclerosis) who do not respond well, or are unable tolerate other (one or more) multiple sclerosis therapies."},{"field_id":804,"order_no":2,"bullet":"Gilenya (fingolimod) has been marketed in Canada since 2011, but to date it is not widely used in Canada."}],"finding_list":[{"field_id":805,"order_no":1,"bullet":"At the time of the review, there were 4 international case reports of suspected progressive multifocal leukoencephalopathy linked to fingolimod use that happened to patients who had not used other multiple sclerosis drugs known to increase the risk of this brain infection before. There were no Canadian case reports."},{"field_id":805,"order_no":2,"bullet":"Health Canada's review showed a possible link between progressive multifocal leukoencephalopathy and Gilenya (fingolimod). However, some of the patients had other medical conditions or used drugs, which could also be linked with progressive multifocal leukoencephalopathy."},{"field_id":805,"order_no":3,"bullet":"A search of the literature found some evidence of a link between progressive multifocal leukoencephalopathy and fingolimod use. However, more evidence was found on the risk of progressive multifocal leukoencephalopathy with other drugs used to treat multiple sclerosis."},{"field_id":805,"order_no":4,"bullet":"The product information was updated by the manufacturer on September 15, 2015 to include new warnings of the potential risk of progressive multifocal leukoencephalopathy with Gilenya (fingolimod). Health Canada's safety review did not identify any new safety concerns."}],"conclusion_list":[{"field_id":806,"order_no":1,"bullet":"The safety review did not identify the need for further updates to the product information on the known potential risk of progressive multifocal leukoencephalopathy. The product information for Gilenya already warns of the potential risk of progressive multifocal leukoencephalopathy."},{"field_id":806,"order_no":2,"bullet":"Health Canada has already shared information with Canadians on the potential risks of progressive multifocal leukoencephalopathy with Gilenya, and the changes to the product information.a b"},{"field_id":806,"order_no":3,"bullet":"Health Canada has requested the manufacturer to continue to provide information on this safety issue."},{"field_id":806,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Gilenya (fingolimod), as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00110","review_date":null,"drug_name":"Atypical antipsychotics","safety_issue":"Breaks in breathing or shallow breaths while sleeping (Sleep apnoea)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":827,"overview":"Health Canada carried out a safety review to look into the risk of sleep apnoea with the use of atypical antipsychotics. Sleep apnoea is a disorder that causes breaks in breathing or shallow breaths during sleep. This review was triggered by the submission of new safety information from the manufacturer of quetiapine (Seroquel) that included cases of sleep apnoea in patients using quetiapine. Health Canada decided to review the evidence linking sleep apnoea to all atypical antipsychotics available in Canada.","use_canada":828,"findings":829,"conclusion":830,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":831,"footnotes":832,"title":"Summary Safety Review - Atypical antipsychotics - Assessing the Potential Risk of Sleep Apnoea","created_date":"2016-08-16","modified_date":null,"key_message_list":[{"field_id":827,"order_no":1,"bullet":"Atypical antipsychotics are medications used to treat mental disorders including schizophrenia, bipolar disorder and, in some cases, depression."},{"field_id":827,"order_no":2,"bullet":"The safety review of atypical antipsychotics was triggered by new safety information regarding sleep apnoea (a disorder that causes breaks in breathing or shallow breaths while sleeping) that was received from the manufacturer of quetiapine (Seroquel)."},{"field_id":827,"order_no":3,"bullet":"Health Canada found a link between the use of atypical antipsychotics and sleep apnoea, and recommended to update the safety information for these products to highlight this side effect."}],"footnotes_list":[{"field_id":832,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":828,"order_no":1,"bullet":"Atypical antipsychotics are used to treat psychiatric disorders such as schizophrenia, bipolar disorder, and for a few products, depression. Risperidone is also used to treat and manage the symptoms of violent behaviours and psychotic symptoms in severe Alzheimer type dementia."},{"field_id":828,"order_no":2,"bullet":"Nine different atypical antipsychotic medications have been marketed in Canada since 1991: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone."},{"field_id":828,"order_no":3,"bullet":"In 2014, there were over 16 million prescriptions for atypical antipsychotics. The most commonly prescribed was quetiapine with about 8 million prescriptions alone."},{"field_id":828,"order_no":4,"bullet":"Sleep apnoea is currently labelled in the product information for paliperidone (Invega), paliperidone prolonged-released (Sustenna), risperidone (Risperdal) and quetiapine (Seroquel)."}],"finding_list":[{"field_id":829,"order_no":1,"bullet":"A review of the scientific literature showed that atypical antipsychotics are linked to sleep apnoea. Three studies supported this link, even though patients had other medical conditions (obesity) and used other medications, which may play a role in the development of sleep apnoea."},{"field_id":829,"order_no":2,"bullet":"At the time of the review, Health Canada had received a total of 80 Canadian casesa of sleep apnoea that were linked to the use of atypical antipsychotics. It could not be determined that these drugs caused sleep apnoea given other factors in the reports such as obesity or the use of other medications. However, the link between the use of atypical antipsychotics and the risk of experiencing sleep apnoea could not be ruled out."},{"field_id":829,"order_no":3,"bullet":"At the time of the review, there were 490 international cases of sleep apnoea linked to atypical antipsychotics. Information from these cases suggests that there is a relationship between quetiapine, olanzapine, ziprasidone, clozapine, aripiprazole, and risperidone and sleep apnoea."}],"conclusion_list":[{"field_id":830,"order_no":1,"bullet":"Health Canada recommended to update the current labeling for aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone to highlight the risk of sleep apnoea"},{"field_id":830,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving atypical antipsychotics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."},{"field_id":830,"order_no":4,"bullet":"Health Canada has reviewed all the scientific literature available and concluded that the data suggested a possible link between the use of aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone and sleep apnoea."}]},{"template":2,"link_id":"SSR00123","review_date":null,"drug_name":"DPP-4 inhibitors (gliptins)","safety_issue":"Gastrointestinal blockage (gastrointestinal obstruction)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":969,"overview":"A safety review was carried out by Health Canada to evaluate the potential risk of gastrointestinal obstruction with the use of DPP-4 inhibitors after international reports of gastrointestinal obstruction were found in patients who used a gliptin called sitagliptin.","use_canada":970,"findings":971,"conclusion":972,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":973,"title":"Summary Safety Review - DPP-4 inhibitors (gliptins) - Assessing the Potential Risk of Gastrointestinal Blockage (Gastrointestinal Obstruction)","created_date":"2016-11-14","modified_date":null,"key_message_list":[{"field_id":969,"order_no":1,"bullet":"DPP-4 inhibitors, known as gliptins, are prescription drugs used to treat type 2 diabetes."},{"field_id":969,"order_no":2,"bullet":"This review was initially triggered by international reports of gastrointestinal obstruction in patients who used the drug sitagliptin. The review was then extended to include all gliptins available in Canada."},{"field_id":969,"order_no":3,"bullet":"Health Canada's safety review concluded that there is not enough information available at this time to confirm a link between gliptin use and gastrointestinal obstruction. Health Canada will continue to monitor the safety of gliptins."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":970,"order_no":1,"bullet":"In addition to diet and exercise, DPP-4 inhibitors, known as gliptins, are used alone or with other anti-diabetic drugs, to help improve blood sugar control in adult patients with type 2 diabetes. There are currently 4 different gliptins on the Canadian market: sitagliptin, saxagliptin, linagliptin and alogliptin. These drugs are also available in products that combine them with other drugs that treat type 2 diabetes."},{"field_id":970,"order_no":2,"bullet":"Sitagliptin was the first gliptin sold in Canada in 2008. In 2015, about 3 million prescriptions of sitagliptin were filled in Canada."}],"finding_list":[{"field_id":971,"order_no":1,"bullet":"At the time of the review, 39 international and 1 Canadian reports of gastrointestinal obstruction in patients who used a gliptin were assessed. Of the 40 reports, the gliptin was found to be possibly linked to the gastrointestinal obstruction in 11 international reports (6 with sitagliptin, 3 with alogliptin and 2 with linagliptin). However, with these 11 cases, there were other potential causes of gastrointestinal obstruction which made it difficult to conclude that the obstruction was caused by gliptins alone."},{"field_id":971,"order_no":2,"bullet":"The review of the literature did not show enough information to support a link between gliptin use and gastrointestinal obstruction."}],"conclusion_list":[{"field_id":972,"order_no":1,"bullet":"Health Canada's review concluded that the evidence does not support a link between gliptin use and gastrointestinal obstruction."},{"field_id":972,"order_no":2,"bullet":"Health Canada will continue to monitor side effect information involving gliptins, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00111","review_date":null,"drug_name":"Intuniv XR (guanfacine hydrochloride extended-release tablets)","safety_issue":"Raynaud's phenomenon","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":839,"overview":"A safety review was carried out to evaluate the potential risk of Raynaud's phenomenon in patients taking Intuniv XR. Raynaud's phenomenon is a disorder of the blood vessels, mainly in the fingers and toes, where they episodically do not receive enough blood and oxygen. The resulting lack of blood and oxygen causes numbness and the skin will turn a pale or bluish colour. Most episodes of this phenomenon last about 15 minutes but in severe cases this can cause damage to the skin and muscle (through oxygen deprivation and tissue death). Health Canada started a review because other drugs used to treat ADHD contain warnings in their product safety information about the risk of Raynaud's phenomenon. The review aimed to determine whether there was enough evidence to include a similar stronger warning for Intuniv XR.","use_canada":840,"findings":841,"conclusion":842,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":843,"footnotes":844,"title":"Summary Safety Review - INTUNIV XR (guanfacine hydrochloride) - Assessing the Potential Risk of Raynaud's Phenomenon","created_date":"2016-08-15","modified_date":null,"key_message_list":[{"field_id":839,"order_no":1,"bullet":"Intuniv XR is used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents 6 to 17 years."},{"field_id":839,"order_no":2,"bullet":"Health Canada reviewed the use of Intuniv XR and the risk of Raynaud's phenomenon, a disorder of the blood circulation in fingers and toes that causes the skin to turn pale or blue."},{"field_id":839,"order_no":3,"bullet":"Health Canada's safety review did not find sufficient evidence to support strengthening the product safety information that already exists for this side effect. Health Canada will continue to monitor the safety of this medicine."}],"footnotes_list":[],"reference_list":[{"field_id":843,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"use_canada_list":[{"field_id":840,"order_no":1,"bullet":"Intuniv XR is used for the treatment of ADHD in children and adolescents aged 6 to 17 years."},{"field_id":840,"order_no":2,"bullet":"Intuniv XR is a once-a-day, extended-release tablet that is available in 1 mg, 2 mg, 3 mg and 4 mg doses."},{"field_id":840,"order_no":3,"bullet":"Although not commonly prescribed, Intuniv XR use has been increasing since it entered the Canadian market in August 2013."}],"finding_list":[{"field_id":841,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian report1 of Raynaud's phenomenon with the use of Intuniv XR. Although the case report lacked detailed information, the review found that it was possible that Intuniv XR caused the Raynaud's phenomenon."},{"field_id":841,"order_no":2,"bullet":"Health Canada's review of the 30 reports received from the manufacturer was limited in its ability to confirm and assess the potential role of Intuniv XR. In general, the reports lacked details, including information to determine if the patient was actually experiencing Raynaud's phenomenon."},{"field_id":841,"order_no":3,"bullet":"There was no direct evidence in the literature to support the risk of Raynaud's phenomenon with the use of Intuniv XR and other guanfacine-containing products used in other countries."},{"field_id":841,"order_no":4,"bullet":"The product safety information of Intuniv XR lists Raynaud's phenomenon as a \"less frequent\" and \"possibly guanfacine-related\" event."}],"conclusion_list":[{"field_id":842,"order_no":1,"bullet":"Health Canada's safety review findings did not support strengthening the existing product safety information for Intuniv XR on the risk of Reynaud's phenomenon."},{"field_id":842,"order_no":2,"bullet":"Health Canada will continue to monitor side effect information involving Intuniv XR, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00112","review_date":null,"drug_name":"Trifecta heart valve manufactured by St. Jude Medical","safety_issue":"Early wear (structural valve deterioration)","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":851,"overview":"After reviewing an article about the wearing out of the Trifecta heart valve 34 months after it was implanted in a patient1, Health Canada carried out a safety review of related patient reports both in Canada and internationally. When a heart valve implant does not function properly it can place stress on the heart and a patient typically has to undergo surgery or an invasive procedure to have the valve repaired or replaced.","use_canada":852,"findings":853,"conclusion":854,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":855,"footnotes":856,"title":"Summary Safety Review - Trifecta Heart Valve - Assessing the Potential Risk of Early Wear","created_date":"2016-08-15","modified_date":null,"key_message_list":[{"field_id":851,"order_no":1,"bullet":"Trifecta is an artificial valve that is placed in the heart (an implanted device) when patients require replacement of a diseased, damaged, or malfunctioning aortic heart valve."},{"field_id":851,"order_no":2,"bullet":"Health Canada's safety review was triggered by a published report that described the wearing out (structural valve deterioration) of a patient's Trifecta valve approximately 3 years after it was placed in the heart, which is earlier than expected."},{"field_id":851,"order_no":3,"bullet":"In carrying out this safety review, Health Canada determined that there was not enough long-term evidence available to make changes to the product information at this time. Health Canada will continue to monitor safety information including the manufacturer's 10-year long patient studies and other patient safety reports on an annual basis regarding the Trifecta heart valve."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":852,"order_no":1,"bullet":"The Trifecta heart valve is an artificial aortic heart valve (pericardial aortic, supra annular, stented tissue valve) that has been designed to closely resemble the same valve in a human. It is made, in part, from pig and cow heart tissue that has been prepared for human use."},{"field_id":852,"order_no":2,"bullet":"This device is meant to be a replacement for a diseased, damaged, or malfunctioning aortic heart valve or as a replacement for a previously implanted aortic prosthetic heart valve."},{"field_id":852,"order_no":3,"bullet":"The Trifecta valve was first licensed in Canada in October 2010 and is manufactured by St. Jude Medical. From January 2010 to August 2015, over 125,000 of these valves were sold worldwide and 3,500 of these were sold in Canada."}],"finding_list":[{"field_id":853,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 13 case reports related to the wearing out (structural valve deterioration) of the Trifecta valve. The reports describe patients that had the device implanted in their heart for 1.5 to 6 years. Information received from the manufacturer describes 117 cases of potential structural valve deterioration of this device from January 2010 to August 2015, world-wide. The number of complaints of early wear for the Trifecta valve (about 1 report for every 1,000 valves implanted) is comparable to valves of the same type."},{"field_id":853,"order_no":2,"bullet":"The scientific literature explains that, when implanted in patients older than 65 years, artificial heart valves made of animal tissues are generally expected to last approximately 10 to 15 years.23"},{"field_id":853,"order_no":3,"bullet":"There is limited information about the long-term durability of the Trifecta valve because the product has only been on the market in Canada since 2010. The manufacturer started two long-term studies to monitor the safety of this valve in a group of patients. The \"Trifecta Durability Study\" has been ongoing since 2011 and will conclude in 2021 and the \"Long Term Follow-up Study of the St. Jude Medical Trifecta Valve\" started in 2012 and will conclude in 2020. The studies will monitor patients for ten years to determine how frequently structural valve deterioration occurs."},{"field_id":853,"order_no":4,"bullet":"The current Canadian product information for the Trifecta valve mentions the potential for \"structural deterioration\". The Warnings section of this document provides a list of factors that may place patients at greater risk of having their Trifecta valve wear down because of calcium build-up (calcific degeneration)."},{"field_id":853,"order_no":5,"bullet":"At the time of the review, the product information did not include specific guidelines for when or how healthcare professionals should follow-up with patients, and did not state how long the device should last. The American Heart Association/American College of Cardiology Guideline for the Management of Patients with Valvular Heart Disease provides recommendations4 for following up with patients that have prosthetic heart valve implants."}],"conclusion_list":[{"field_id":854,"order_no":1,"bullet":"As a result of a safety review, Health Canada considered updating the product information for the Trifecta valve regarding the potential of early wear. However, given longer-term studies are ongoing Health Canada will await these results before finalizing any updates to the product information."},{"field_id":854,"order_no":2,"bullet":"Health Canada will monitor safety information regarding the durability of the Trifecta heart valve as it becomes available, including the manufacturer's 10-year long patient studies and other patient safety reports on an annual basis. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00113","review_date":null,"drug_name":"Antidepressants","safety_issue":"Angle-closure glaucoma","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":863,"overview":"Health Canada carried out this safety review when it became aware that the FDA was investigating the risk of angle-closure glaucoma linked to antidepressant use. Angle-closure glaucoma is a serious eye disorder where eye fluid drainage is blocked, leading to a sudden increase in the pressure in the eye and causing pain and blurred vision. If not treated immediately, angle-closure glaucoma can lead to permanent vision loss.
The safety review was carried out to determine whether the information available on angle-closure glaucoma included in the Canadian product information for antidepressants was accurate and in agreement with the current scientific evidence.
","use_canada":864,"findings":865,"conclusion":866,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":867,"footnotes":868,"title":"Summary Safety Review - Antidepressants - Assessing the Potential Risk of Serious Eye Disorder (Angle-Closure Glaucoma)","created_date":"2016-08-12","modified_date":null,"key_message_list":[{"field_id":863,"order_no":1,"bullet":"Antidepressants are drugs used for the treatment of depression, anxiety, obsessive compulsive disorder, insomnia, and post-traumatic stress disorder, among many other conditions."},{"field_id":863,"order_no":2,"bullet":"Health Canada carried out a safety review when it became aware that the U.S. Food and Drug Administration (FDA) was investigating the risk of angle-closure glaucoma linked to antidepressant use."},{"field_id":863,"order_no":3,"bullet":"Health Canada's review found a link between antidepressant use and the occurrence of angle-closure glaucoma. Health Canada is therefore working with manufacturers of antidepressant products to update the Canadian product information to include a warning of the potential risk for angle-closure glaucoma with the use of antidepressants."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":864,"order_no":1,"bullet":"Antidepressants are widely used drugs that have been available on the Canadian market since the 1950s for the treatment of depression, anxiety, obsessive compulsive disorder, insomnia, and post-traumatic stress disorder, among many other conditions."},{"field_id":864,"order_no":2,"bullet":"The safety review focused on the following 23 antidepressant medications available in Canada: desipramine, imipramine, clomipramine, doxepin, trimipramine, amitriptyline, nortriptyline, maprotiline, mirtazapine, phenelzine, moclobemide, tranylcypromine, fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram, venlafaxine, duloxetine, desvenlafaxine, trazodone, and bupropion."},{"field_id":864,"order_no":3,"bullet":"Prescriptions for antidepressants in Canada have been increasing since 2009 at an average rate of 5.6% per year. An estimated 40.5 million prescriptions of antidepressants were dispensed in 2013."}],"finding_list":[{"field_id":865,"order_no":1,"bullet":"At the time of the review, there were 163 reports of angle-closure glaucoma linked with the use of antidepressants from different sources. Health Canada received 2 of these reports through the Canada Vigilance Program."},{"field_id":865,"order_no":2,"bullet":"At the time of the review, there were 2226 reports of pupil dilation linked with the use of antidepressants from different sources. Health Canada received 130 of these reports through the Canada Vigilance Program. Pupil dilation is a well-known risk factor that may lead to angle-closure glaucoma in certain patients (patients who have narrow eye fluid channels)."},{"field_id":865,"order_no":3,"bullet":"Based on the review finding that there was no difference in the level of risk for angle-closure glaucoma among the different antidepressants reviewed, it was recommended that the potential risk of angle-closure glaucoma be listed in the product information for all antidepressants."}],"conclusion_list":[{"field_id":866,"order_no":1,"bullet":"Health Canada's review found a link between antidepressant use and the occurrence of angle-closure glaucoma."},{"field_id":866,"order_no":2,"bullet":"Health Canada is working with manufacturers of antidepressant products to update the Canadian product information to include a warning of the potential risk for angle-closure glaucoma with antidepressant use."},{"field_id":866,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving antidepressants, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00114","review_date":null,"drug_name":"Hormone replacement therapy (estrogenic and progestogenic agents) and selective estrogen receptor modulators (SERMs)","safety_issue":"Ovarian cancer in menopausal women","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":875,"overview":"Based on a publication of a study suggesting that the risk of ovarian cancer may be increased in women undergoing HRT for less than 5 years, Health Canada carried out a safety review to further assess this risk and to determine if additional changes to the product information are needed. As of 2008, the Canadian product information for HRT products includes warning statements about the risk of ovarian cancer during treatment, especially after 5 years of treatment or more. Although SERMs (raloxifene, bazedoxifene) were not included in that study, Health Canada also assessed the risk of ovarian cancer with this class of drugs since they may have similar effects in the body.","use_canada":876,"findings":877,"conclusion":878,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":879,"footnotes":880,"title":"Summary Safety Review - Hormone Replacement Therapy (Estrogenic and Progestogenic Agents) and Selective Estrogen Receptor Modulators (SERMs) - Assessing the Potential Risk of Ovarian Cancer","created_date":"2016-08-09","modified_date":null,"key_message_list":[{"field_id":875,"order_no":1,"bullet":"Hormone replacement therapy (HRT) products containing estrogens and/or progestogens are used to treat symptoms of menopause and in some cases, to prevent weakening of bones (osteoporosis). Some selective estrogen receptor modulators (SERMs) (raloxifene, bazedoxifene) are also used for these same purposes."},{"field_id":875,"order_no":2,"bullet":"This safety review was triggered following the publication of a study showing a potential for increased risk of ovarian cancer in women undergoing HRT for less than 5 years."},{"field_id":875,"order_no":3,"bullet":"As of 2008, the Canadian product information for HRT products includes warning statements about the risk of ovarian cancer during treatment, especially after 5 years of treatment or more."},{"field_id":875,"order_no":4,"bullet":"Health Canada's safety review did not identify any changes in the known risk of ovarian cancer in women undergoing HRT. The review did not find evidence for a link between SERMs (raloxifene, bazedoxifene) and ovarian cancer."}],"footnotes_list":[{"field_id":880,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":880,"order_no":2,"bullet":"Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. The Lancet. 2015; Volume 385, Issue 9980, Pages 1835-1842."}],"reference_list":[],"use_canada_list":[{"field_id":876,"order_no":1,"bullet":"HRT products containing estrogens and/or progestogens are used to treat menopausal symptoms such as hot flashes, night sweats, and vaginal dryness. Some HRT products are also used to prevent weakening of bones (osteoporosis). Selective estrogen receptor modulators (SERMs) (raloxifene, bazedoxifene) are also used for preventing and treating osteoporosis and some symptoms of menopause."},{"field_id":876,"order_no":2,"bullet":"There are 37 HRT products (containing estrogen and/or progesterone) and 7 SERMs products (containing raloxifene or bazedoxifene) approved for use in postmenopausal women in Canada."}],"finding_list":[{"field_id":877,"order_no":1,"bullet":"At the time of the review, there was 1 Canadian case of ovarian cancer reported in a patient undergoing HRT, but there was not enough information to determine a link between HRT and ovarian cancera. There were no Canadian cases of ovarian cancer reported with the use of SERMs (raloxifene, bazedoxifene) for symptoms of menopause."},{"field_id":877,"order_no":2,"bullet":"A published studyb showed the potential for a higher risk of ovarian cancer in women undergoing HRT for less than 5 years. Health Canada's safety review found limitations, which questioned the conclusions of the study. Most studies, showing a link between HRT and ovarian cancer, are related to undergoing HRT for 5 years or more."},{"field_id":877,"order_no":3,"bullet":"The review did not find published studies looking at the link between ovarian cancer and SERM use in menopausal women."}],"conclusion_list":[{"field_id":878,"order_no":1,"bullet":"At this time, Health Canada's safety review did not find enough information to confirm that the risk of ovarian cancer is increased in women undergoing HRT for less than 5 years. The current Canadian product information for HRT products warns about the risk of ovarian cancer during treatment, especially after 5 years of treatment or more."},{"field_id":878,"order_no":2,"bullet":"The safety review did not find evidence for a link between SERMs (raloxifene, bazedoxifene) and ovarian cancer."},{"field_id":878,"order_no":3,"bullet":"Based on the review findings, no changes will be made to the product information for HRT or SERMs at this time. Health Canada will continue to monitor side effect information involving HRT and SERMs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00115","review_date":null,"drug_name":"Propecia (finasteride 1 mg), Proscar (finasteride 5 mg), and generics","safety_issue":"Seizures","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":887,"overview":"Health Canada carried out a safety review to look at the potential risk of seizures in patients taking finasteride after cases of seizures were published in the WHO Pharmaceuticals Newslettera.","use_canada":888,"findings":889,"conclusion":890,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":891,"footnotes":892,"title":"Summary Safety Review - Propecia (finasteride 1 mg) and Proscar (finasteride 5 mg) - Assessing the Potential Risk of Seizures","created_date":"2016-08-05","modified_date":null,"key_message_list":[{"field_id":887,"order_no":1,"bullet":"Propecia (finasteride 1 mg) and generics are used to treat hair loss in men (androgenetic alopecia). Proscar (finasteride 5 mg) and generics are used to treat prostate gland enlargement (benign prostatic hyperplasia)."},{"field_id":887,"order_no":2,"bullet":"A safety review was carried out by Health Canada after cases of seizures with finasteride use were published in the WHO Pharmaceuticals Newslettera."},{"field_id":887,"order_no":3,"bullet":"The Health Canada safety review findings did not support a link between seizures and finasteride. Health Canada will continue to monitor the safety of finasteride products."}],"footnotes_list":[{"field_id":892,"order_no":1,"bullet":"WHO Pharmaceuticals Newsletter, No. 4, 2014."}],"reference_list":[],"use_canada_list":[{"field_id":888,"order_no":1,"bullet":"Propecia (finasteride 1 mg) is used to treat hair loss in men (androgenetic alopecia). Proscar (finasteride 5 mg) is used to treat prostate gland enlargement (benign prostatic hyperplasia). There are generic finasteride products (1 mg and 5 mg) available in Canada that are also used to treat these respective conditions."},{"field_id":888,"order_no":2,"bullet":"While finasteride is not indicated for use in women, Health Canada is aware that it has been used in women for the treatment of conditions such as hair loss."},{"field_id":888,"order_no":3,"bullet":"Proscar has been sold in Canada since 1992 and Propecia since 1998. About1.2 million prescriptions (new and refills) for finasteride-containing products were dispensed in Canada in 2014. Most were given for the treatment of prostate gland enlargement."}],"finding_list":[{"field_id":889,"order_no":1,"bullet":"At the time of the review, 95 unique cases of seizures associated with finasteride use were found worldwide. Of these, 45 were relevant for this review and further assessed. Ten of the 45 cases were Canadian cases. No female cases were reported in Canada. Upon review of these cases, no conclusions could be made on whether finasteride played a role in seizures because the information contained in the reports was limited and some patients had other conditions that could cause seizures."},{"field_id":889,"order_no":2,"bullet":"The scientific literature showed that studies in animals with seizures indicated an increased risk of seizures with finasteride. However, it did not find enough evidence to support an increased risk of seizures in people treated with finasteride."}],"conclusion_list":[{"field_id":890,"order_no":1,"bullet":"Health Canada's safety review findings did not support a link between an increased risk of seizures in patients treated with finasteride."},{"field_id":890,"order_no":2,"bullet":"Health Canada has asked the manufacturers of Propecia and Proscar to continue to provide information on this safety issue."},{"field_id":890,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving finasteride products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00116","review_date":null,"drug_name":"Kogenate FS/Helixate FS (Antihemophilic Factor [Recombinant])","safety_issue":"Potential changes in the known risk of the development of inhibitors (inhibitory antibodies) in previously untreated patients (PUPs) with severe hemophilia A","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":899,"overview":"Inhibitor antibodies (IA) development is a known concern in hemophilia A patients treated with antihemophilic factors. IA are a result of the immune system reacting to the treatment. IA development may cause the treatment to fail to prevent or stop a bleeding episode. This is especially concerning in young children with severe hemophilia A during their first years of treatment and any patient who has had limited previous treatment with factor VIII products (also known as 'previously untreated patients' or 'PUPs'). Some published studies suggested that Kogenate FS/Helixate FS may be linked to a greater risk of development of IA in PUPs compared to similar factor VIII products. The safety review by Health Canada was carried out to determine if the risk of inhibitor development was greater with Kogenate FS/Helixate FS use in PUPs compared to similar medicines and whether more actions were needed to manage this risk.","use_canada":901,"findings":903,"conclusion":905,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this product both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":907,"footnotes":909,"title":"Summary Safety Review - KOGENATE FS/HELIXATE FS (Antihemophilic Factor [Recombinant]) - Assessing the Potential Changes in the Known Risk of Inhibitors (Inhibitory Antibody - IA) Development in Previously Untreated Patients with Severe Hemophilia A","created_date":"2016-07-26","modified_date":null,"key_message_list":[{"field_id":899,"order_no":1,"bullet":"Kogenate FS and Helixate FS are used for the treatment of classical hemophilia A, a disease that prevents the blood from clotting properly."},{"field_id":899,"order_no":2,"bullet":"Health Canada carried out a safety review based on recent published studies that suggested an increased risk of developing inhibitors (inhibitory antibodies) to Kogenate FS/Helixate FS compared to similar medicines. The result is that the treatment may fail to prevent or stop episodes of bleeding."},{"field_id":899,"order_no":3,"bullet":"Health Canada's safety review concluded that the recent evidence does not present a new safety concern and the Kogenate FS/Helixate FS product information already warns of this potential event. Health Canada will continue to monitor the issue of IA development when these products are used."}],"footnotes_list":[{"field_id":909,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[{"field_id":907,"order_no":1,"bullet":"Calvez T, Chambost H, Claeyssens-Donadel S, et al. Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood 2014; 124:3398-408."},{"field_id":907,"order_no":2,"bullet":"Collins PW, Palmer BP, Chalmers EA, et al. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe haemophilia A, 2000-2011. Blood 2014; 124:3389-97."},{"field_id":907,"order_no":3,"bullet":"Gouw SC, van der Bom JG, Ljung R, et al. PedNet and RODIN Study Group. Factor VIII Products and Inhibitor Development in Severe Hemophilia A.N Engl J Med 2013; 368: 231-9."}],"use_canada_list":[{"field_id":901,"order_no":1,"bullet":"Kogenate FS and Helixate FS are identical blood clotting factor VIII products. They are very similar to the factor VIII that is made naturally in human blood. These products have been marketed in Canada since 2000 and 2008, respectively."},{"field_id":901,"order_no":2,"bullet":"They are both used for the treatment of adults and children with classical hemophilia A as a replacement for the missing clotting factor. In these patients, the products help to prevent bleeding episodes or stop a bleeding episode that has already begun. They can manage bleeding during emergency or scheduled surgery and can also help prevent joint damage in children."}],"finding_list":[{"field_id":903,"order_no":1,"bullet":"Health Canada had received reports related to IA development associated with the use of Kogenate FS/Helixate FS, or instances where these products were not working. The reports represented 31 Canadian patientsa with hemophilia and included both children and adults. Overall, these Canadian reports did not provide enough information to conclude that there is a greater risk of IA development when Kogenate FS/Helixate FS is used in PUPs as compared to similar products."},{"field_id":903,"order_no":2,"bullet":"The review also looked into recent published studies1 2 3 of hemophilia A patients treated with factor VIII products. While the studies suggested there is a potential increased risk of IA development in PUPs treated with Kogenate FS/Helixate FS, there were concerns with how the studies were designed and analyzed. As a result, this information could not show that the use of Kogenate FS/Helixate FS carries a greater risk of the development of IA in PUPs with severe hemophilia A as compared to similar products."}],"conclusion_list":[{"field_id":905,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence does not suggest any additional concerns regarding the risk of inhibitors (IA) development toward Kogenate FS/Helixate FS, and the Canadian labels for these products have warnings regarding the risk of inhibitor development."},{"field_id":905,"order_no":2,"bullet":"Health Canada has requested that the manufacturers continue to share any new information related to this risk, as it becomes available."},{"field_id":905,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Kogenate FS/Helixate FS, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":1,"link_id":"SSR00117","review_date":null,"drug_name":"Diclectin (doxylamine and pyridoxine combination)","safety_issue":"","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"Diclectin is a drug authorized in Canada to treat nausea and vomiting in pregnancy (i.e. morning sickness). It is a fixed dose-combination product of doxylamine (an antihistamine) and pyridoxine (a form of vitamin B6). The doxylamine/pyridoxine containing products have been used in Canada since 1957. Health Canada has been monitoring the safety of Diclectin and updating the prescribing information as necessary, as it does for all products on the Canadian market.
The safety of Diclectin was recently reviewed by Health Canada as part of its routine health product monitoring. Public interest was also raised by recent media reports on Diclectin.
","background":"Health Canada regulates drugs and other health products available to Canadians. Before a therapeutic product is authorized for sale in Canada, the manufacturer must provide evidence of its safety, efficacy and quality, as defined by regulations. Health Canada reviews the evidence to determine whether the risks associated with the product are acceptable in light of its potential benefits. If they are, and if the product has been shown to be effective under specified conditions, it is authorised for sale in Canada.
Authorized use of Diclectin
Diclectin is a drug used to treat nausea and vomiting in pregnancy, which is a very common condition affecting 50%-90% of pregnant women with varying severity and durationa. Diclectin is currently the only prescription drug authorized in Canada for the treatment of nausea and vomiting in pregnancy.
The current Guidelines issued by the Society of Obstetricians and Gynaecologists of Canada (SOGCa recommend Diclectin as a treatment for nausea and vomiting in pregnant women when other measures such as dietary and lifestyle changes have not been effective. According to the SOGC website, the current clinical practice guidelines on the management of nausea and vomiting in pregnancy are being reviewedb.
Canadian and international regulatory history
In 1975, Diclectin was authorized in Canada as a generic form of Bendectin, a 3-component product: doxylamine, dicyclomine and pyridoxine, which had been marketed in Canada since 1957. Dicyclomine, which decreases muscle spasms in the digestive system, was later excluded from the drug formulation since it was not found to help in treating nausea and vomiting in pregnancy. Since the 1960s, Bendectin was suspected of causing congenital malformations; however, accumulated safety data failed to show an association. Nevertheless, the manufacturer of Bendectin discontinued the product worldwide in 1983 reportedly due to increasing costs from lawsuits. In Canada, the generic product, Diclectin (pyridoxine (B6)/doxylamine), remained available.
In 1989, the then Minister of Health and Welfare Canada requested an independent review of the safety of Diclectin/Bendectin products by an external expert panel. The expert panel confirmed the positive benefit-risk profile for Diclectin and noted that it should continue to be available to Canadian women.
In 1999, the US Food and Drug Administration (FDA) conducted its own review to confirm why Bendectin was removed from the market in 1983. The FDA determined that Bendectin was not discontinued for safety or effectiveness reasons.
In 2013, the US FDA authorized Diclegis (US equivalent to Diclectin) for the treatment of nausea and vomiting in pregnant women as a "Category A drug" (the safest for use in pregnant women). This drug approval was supported by historical and recent data.
","objective":"The objective of this review was to assess available evidence on Diclectin since the 1989 Expert Advisory Panel. The evidence considered Canadian patient reports, scientific and medical literature, and what is known about the use of this medicine both in Canada and internationally. The current strategies to minimize this risk were also considered, including a review of the product information available to health care professionals and patients.
","key_findings":"Use of Diclectin in Canada
Health Canada estimates the number of prescriptions for Diclectin to be stable over the last five years at approximately 180,000 new prescriptions per yearc. During a pregnancy, a woman may require more than one prescription for Diclectin depending on the duration of use. Of note, the number of births in Canada for 2015 is expected to be around 388,000 according to the Statistics Canada websited.
Canadian reports of birth defects/congenital malformations associated with Diclectin use
The Canada Vigilance database was searched for all reports that listed Diclectin since 1975 and found 75 Canadian cases of side effects associated with Diclectin use. Of these, 29 unique cases were considered to be related to the safety review and were further investigated. These included cases reported in infants or neonates as well as cases with events of interest (e.g. spontaneous abortion, congenital impairment, fetal death). Seven cases were assessed as 'possibly associated'e with Diclectin use while the remaining 22 were classified as unlikely to be associated with Diclectin use or un-assessable (the reports did not have enough information to determine if there was a causal relationship to the drug or whether it was related to natural occurrence). The number of cases reported in Diclectin users is considered to be within the expected incidence (natural occurrence) of major birth defects (3-5%) in newborn babiesf. No pattern of malformation types or group of malformations was identified in these case reports. The summary of these findings do not indicate a change in the current benefit/risk profile of the product.
Scientific reports
The safety review considered the scientific and medical literature published up to May 20, 2015. The potential association between doxylamine/pyridoxine and the risk of birth defects has been extensively studied in numerous types of clinical trials (observational studies, meta-analyses and systematic reviews). Five separate meta-analyses, which combine numerous individual studies, concluded that doxylamine/pyridoxine was not associated with increased risk of birth defectg.
While some individual studies reported possible links between doxylamine/pyridoxine use by pregnant women and the occurrence of various birth defects, the majority of the studies did not find a link. There are no identified malformation types or group of malformations that have consistently been reported in the scientific literature to be increased in the populations exposed to doxylamine/pyridoxine combination.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":911,"additional":"On June 2, 2016, a Scientific Advisory Panel on Diclectin met to consider whether specific study information on Diclectin may be useful to healthcare professionals or patient decision making about the use of the drug. In summary, the panel recommended that no changes to the indicated use of Diclectin are warranted based on the latest available information.
","full_review":"The full review report for Diclectin is available upon request to the Marketed Health Products Directorate. As with all safety reviews, these reports are subject to redactions of personal and confidential information.
","references":913,"footnotes":915,"title":"Summary Safety Review - DICLECTIN (doxylamine and pyridoxine combination) - Assessing Safety in pregnancy","created_date":"2016-07-15","modified_date":"2016-07-19","key_message_list":[],"footnotes_list":[{"field_id":915,"order_no":1,"bullet":"Arsenault M-Y, Lane CA. The management of nausea and vomiting of pregnancy. SOGC Clinical Practice Guideline. J Obstet Gynaecol Can 2002;24:817-23. Also available at: http://sogc.org/guidelines/the-management-of-nausea-vomiting-of-pregnancy/ (Accessed on 2016-06-06)."},{"field_id":915,"order_no":2,"bullet":"http://sogc.org/clinical-practice-guidelines/(Accessed on 2016-06-06)."},{"field_id":915,"order_no":3,"bullet":"The IMS data in this report must not be used or cited by stakeholders external to Health Canada. An external party cannot refer to nor use IMS data, which have been presented by Health Canada, without a Third Party Agreement in place."},{"field_id":915,"order_no":4,"bullet":"Births, estimates, by province and territory. Available at: http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo04a-eng.htm (Accessed on 2016-06-06)."},{"field_id":915,"order_no":5,"bullet":"A clinical event is deemed 'possible' when there is a reasonable time sequence to administration of the drug, but it could also be explained by other factors/conditions."},{"field_id":915,"order_no":6,"bullet":"Public Health Agency of Canada. Congenital Anomalies in Canada 2013: A Perinatal Health Surveillance Report. Ottawa, 2013. Available at http://publications.gc.ca/pub?id=9.697790&sl=0 (Accessed on 2016-06-06)."},{"field_id":915,"order_no":7,"bullet":"Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiological studies. Drug Intell Clin Pharm 1988;22:813-24.
McKeigue PM, Lamm SH, Linn S, Kutcher JS. BENDECTIN and birth defects: I. A meta-analysis of the epidemiologic studies. Teratology 1994;50:27-37.
Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis. American Journal of Perinatology 1997;14(3):119-24.
Mazzotta P, Magee LA. A risk-benefit assessment of pharmacological and non-pharmacological treatments for nausea and vomiting of pregnancy. Drugs 2000;59:781-800.
Chin JWS, Gregor S, Persaud N. Re-analysis of safety data supporting doxylamine use for nausea and vomiting of pregnancy. American Journal of Perinatology 2013; Vol. eFirst 9 December 2013.
Health Canada has found that Diclectin's benefits continue to outweigh its risks, when used as authorized. The safety information reviewed on Diclectin and birth defects (fetal adverse events) showed no change in the safety profile of Diclectin in pregnant women. The review also concluded that the evidence continues to support Diclectin's safe and effective use for the treatment of nausea and vomiting during pregnancy.
The most recent prescribing information for Diclectin (dated March 2016) continues to reflect the overall knowledge on the safe and effective use of the drug in pregnant women.
Health Canada has shared information on Diclectin externally with third parties, and will continue to make relevant information available as applicable.
Health Canada will continue to monitor the safety of Diclectin as it does for all health products on the Canadian market and will take appropriate and timely action if new health risks are identified. Health Canada will communicate emerging safety information, as necessary, resulting from its post-marketing surveillance program, to health care professionals and consumers, so they can make timely decisions on the risks and benefits.
"}]},{"template":1,"link_id":"SSR00120","review_date":null,"drug_name":"Acetaminophen","safety_issue":"Liver Injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"Acetaminophen has been widely used for over 50 years in Canada to treat pain and fever and, when taken as directed, is a safe and effective medicine. Despite its established safety profile, acetaminophen is the leading cause of acute liver failure in Canada. Incidents of serious liver injury associated with acetaminophen continue to be reported in Canada and internationally. The effects of acetaminophen on the liver have been recognized for many years and, over the past 10 years, Health Canada has taken a number of measures to act on information related to the safety of acetaminophen.
In 2009, an initial safety review was conducted by Health Canada in response to a request for stronger label warnings to reduce the occurrence of unintentional acetaminophen overdoses. Following this review, a guidance document, the Acetaminophen Labelling Standard, was released in 2009 to update labelling language for non-prescription acetaminophen products. The new standard included increased warnings for potentially serious and possibly fatal liver injury in the event of an acetaminophen overdose associated with these products.
As part of Health Canada's efforts to minimize health risk factors to Canadians, a more in-depth scientific review was undertaken to evaluate additional evidence and evaluate the situation in Canada. Acetaminophen Overdose and Liver Injury in the Canadian Context (2014) (henceforth referred to as the Acetaminophen Report) contains key findings and recommends options for consideration to further reduce the risk of liver injury to Canadians using acetaminophen.
","background":"All medications, including acetaminophen, carry risks. Canada and a number of other countries around the world have taken steps in the past to enable the safe use of acetaminophen and continue to work to address this complex problem. Health Canada has identified options to reduce the risk of liver injury related to acetaminophen in the Acetaminophen Report, and continues to assess the feasibility of which options would be most beneficial in the Canadian context.
Prescription and non-prescription acetaminophen products have a long history of treating pain and fever, and their use in Canada dates back to 1961. Acetaminophen is available as a single-ingredient product or in combination with other ingredients, such as in cold and cough medications or narcotic pain relievers (e.g., in combination with codeine). More than 475 different acetaminophen products are authorized for marketing, the majority being non-prescription. Currently, 4 g of acetaminophen per day is the maximum recommended daily dose in Canada and many other countries, while the maximum recommended duration of use is 5 days for pain relief and 3 days for fever.
Although generally considered to be a safe medicine when taken as directed, taking too much acetaminophen (i.e., more than indicated on the label), either intentionally or unintentionally (both called an overdose), can cause serious liver injury, including acute liver failure. Acute liver failure is a medical emergency and hospitalization is needed right away. It may also result in the need for liver transplantation, or in the most serious of cases, death.
It is generally recognized that doses above 10 g per day in adults (or 150 mg acetaminophen per kg body weight per day) are damaging to the liver. However, there have also been rare reports of liver injury in adults at doses below the maximum recommended dose, mostly in patients with conditions affecting their liver. There is evidence suggesting that the risk of liver injury with acetaminophen use may be increased in certain situations, such as alcoholism, malnutrition, some liver diseases, or use of acetaminophen for more than the recommended length of time.
Health Canada has taken a number of steps to investigate and reduce the risk of liver injury associated with acetaminophen. Two advisories regarding the safe use of acetaminophen have been issued by Health Canada; one in February 2003 and the other in January 2011. In addition, an initial safety review on acetaminophen-induced liver injury was completed in 2009. Health Canada published the Acetaminophen Labelling Standard1 in November 2009, which included improved warnings for the potential for serious and possibly fatal liver injury in the event of an overdose, as well as weight and age-based dosing guidelines for pediatric use. The 2009 safety review also recommended the creation of a Health Canada inter-directorate working group to further study the risk of acetaminophen-induced liver injury. These activities are in line with work done by other countries worldwide.
","objective":"The objective of the Acetaminophen Report was to assess the risk of acetaminophen-related liver injury in Canada. Evidence from several sources was considered, including published scientific and medical literature, regulatory-specific documents, case reports of adverse drug reactions sent to Health Canada, data from Canadian hospitals and coroners' offices, and consumer information polls. This information was used to better understand the Canadian context and propose ways to further reduce liver injuries.
","key_findings":"The Acetaminophen Report found that there are more than 4,000 hospitalizations in Canada each year for acetaminophen overdose. Approximately 1 in 5 cases are due to people exceeding the recommended dose unintentionally. An important finding was that the number of hospitalizations for unintentional overdoses is rising in Canada.
Adolescents and young adults were the most likely age group to overdose (both intentionally and unintentionally) with acetaminophen products. It also found overdoses to be more common in females compared to males. The number of cases of overdose leading to liver injury is higher with prescription combination products (i.e., acetaminophen with narcotics) because of their tendency to be used for prolonged periods of time or misused/abused.
Acetaminophen is the leading cause of all serious liver injury, including acute liver failure, in many countries, such as Canada, the United States, the United Kingdom and Australia. The Acetaminophen Report found that out of the more than 250 cases of serious liver injury per year in Canada related to acetaminophen, over half were associated with unintentional overdoses. This implies that the likelihood of severe liver injuries is more common with unintentional overdoses than intentional overdoses. Most of these cases involved single-ingredient acetaminophen products or prescription combination products containing narcotics.
Moreover, up to 1 in 5 of acetaminophen-related liver injuries reported to Canada Vigilance mentioned doses within the recommended range (i.e., less than 4 g per day - which is equivalent to 8 tablets of extra-strength acetaminophen 500 mg). In many of these cases, patients had identifiable risk factors for acetaminophen liver injury, such as alcoholism or viral liver disease.
","key_messages":0,"overview":"","use_canada":0,"findings":0,"conclusion":943,"additional":"For a copy of the Executive Summary of the 2014 Acetaminophen Report, or for additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":944,"footnotes":945,"title":"Summary Safety Review - Acetaminophen - Liver Injury","created_date":"2015-07-09","modified_date":null,"key_message_list":[],"footnotes_list":[{"field_id":945,"order_no":1,"bullet":"A non-prescription drug labelling standard was developed for acetaminophen and outlines the permissible conditions of use and labelling requirements, such as dose, intended use, directions, warnings, active ingredients and combinations thereof for the entire class of products."},{"field_id":945,"order_no":2,"bullet":"IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place."},{"field_id":945,"order_no":3,"bullet":"This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the Acetaminophen Summary Report."}],"reference_list":[{"field_id":944,"order_no":1,"bullet":"Bond GR, Ho M, Woodward RW. Trends in hepatic injury associated with unintentional overdose of paracetamol (Acetaminophen) in products with and without opioid: an analysis using the National Poison Data System of the American Association of Poison Control Centers, 2000-7. Drug Saf 2012;35(2):149-57."},{"field_id":944,"order_no":1,"bullet":"Hornsby LB, Przybylowicz J, Andrus M, Starr J. Survey of physician knowledge and counseling practices regarding acetaminophen. J Patient Saf 2010;6(4):216-20."},{"field_id":944,"order_no":2,"bullet":"Morgan O, Griffiths C, Majeed A. Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study. J Public Health (Oxf) 2005;27(1):19-24."},{"field_id":944,"order_no":3,"bullet":"Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005;42(6):1364-72."},{"field_id":944,"order_no":4,"bullet":"Abdel-Qader DH, Harper L, Cantrill JA,Tully MP. Pharmacists' interventions in prescribing errors at hospital discharge: an observational study in the context of an electronic prescribing system in a UK teaching hospital. Drug Saf 2010;33:1027-44."},{"field_id":944,"order_no":5,"bullet":"Nguyen NT, Vierling JM. Acute liver failure. Curr Opin Organ Transplant2011;16(3):289-96."},{"field_id":944,"order_no":6,"bullet":"Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin North Am2008;92(4):761-94, viii."},{"field_id":944,"order_no":7,"bullet":"Bretherick AD, Craig DG, Masterton G, et al. Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and outcome. QJM 2011;104(11):945-56."},{"field_id":944,"order_no":8,"bullet":"Mort JR, Shiyanbola OO, Ndehi LN, Xu Y, Stacy JN. Opioid-paracetamol prescription patterns and liver dysfunction: a retrospective cohort study in a population served by a US health benefits organization. Drug Saf 2011;34(11):1079-88."},{"field_id":944,"order_no":9,"bullet":"Lee WM. Acetaminophen Toxicity: Changing Perceptions on a Social/Medical Issue. Hepatology 2007;46(4):966-70."},{"field_id":944,"order_no":10,"bullet":"Schilling A, Corey R, Leonard M, Eghtesad B. Acetaminophen: old drug, new warnings. Cleve Clin J Med 2010;77(1):19-27."}],"use_canada_list":[],"finding_list":[],"conclusion_list":[{"field_id":943,"order_no":1,"bullet":"Although acetaminophen remains a safe and effective medicine, there are risks of serious liver injury when it is not used as directed, such as exceeding the recommended dose or duration of use. Increasing awareness about the presence of acetaminophen in certain medicines and the risk of liver injury when acetaminophen is not used as directed on product labels may help to decrease the occurrence of unintentional overdoses that may cause serious liver injury.
The 2014 Acetaminophen Report proposes several options for consideration that may reduce the occurrence of acetaminophen-related liver injury, particularly in the context of unintentional overdoses. They include limiting the overall availability of acetaminophen to consumers; lowering the maximum recommended daily dose; decreasing the amount of acetaminophen contained in some products; decreasing the quantity available in a package of acetaminophen; and re-evaluating the role of products that combine both acetaminophen and narcotics. Specific measures for enhancing the safe use in children are also recommended, such as requiring that accurate dosing devices come with all children's liquid products.
In July 2014, Health Canada held a technical discussion on the Acetaminophen Report and the recommended risk minimization options with various stakeholders, including patient safety groups, pharmacists, retail pharmacies, and industry associations. As a result of this discussion, a steering committee of Health Canada and stakeholder representatives was tasked with developing and implementing an education approach to promote the safe use of acetaminophen. This collaboration has led to the development of key educational messages, which will be shared by stakeholders with the public through various communication channels beginning in Summer 2015. Health Canada will also be using use social media to disseminate these key messages, and a Web page on acetaminophen safety has already been posted on the Healthy Canadians Web site to inform the public. In addition, Health Canada has issued an Information Update to help educate and remind Canadians about the safe use of acetaminophen.
In October 2014, Health Canada formed an internal group to assess which of the remaining options were most feasible, and will seek external input on those. Health systems, policy, regulatory, and international perspectives were considered to determine the feasibility of the risk minimization options. New information that has appeared since the Acetaminophen Report was completed, along with the actions of other international regulators, predominately those of the United States Food and Drug Administration, have been taken into account during discussions. To reflect these developments, the Acetaminophen Labelling Standard is being revised to help educate consumers about the possible risks associated with the use of acetaminophen.
Health Canada is working collaboratively with its stakeholders as the feasibility and anticipated effectiveness of the remaining risk minimization options from the Acetaminophen Report are further analyzed. Decreasing the maximum recommended daily dose for all oral and rectal forms of acetaminophen containing products is being considered, as is decreasing the unit dose for some products. The improvement of product labelling and packaging, including the requirement that all children's liquid products be sold with an accurate dosing device in the package, is also being examined. Once the Acetaminophen Labelling Standard has been updated, it will be Web posted in Summer 2015 to receive stakeholders' comments before being finalized.
A technical discussion with stakeholders is planned for Fall 2015 to consider the feasibility of the proposed risk minimization options as recommended by the internal group following further analysis. In addition, Health Canada will continue to collaborate with stakeholders to further develop the acetaminophen education approach.
"}]},{"template":2,"link_id":"SSR00121","review_date":null,"drug_name":"Atypical antipsychotics","safety_issue":"Difficulty urinating or inability to completely empty the bladder (urinary retention)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":949,"overview":"Health Canada carried out a safety review to look into the use of atypical antipsychotics and the potential risk of having difficulty urinating or not being able to fully empty the bladder (urinary retention). This can be an emergency that requires medical attention. This review was triggered by new safety information received from the manufacturer of Seroquel (quetiapine) that included reports of urinary retention in patients using quetiapine. Health Canada reviewed evidence that may have also linked this side effect to other atypical antipsychotics available in Canada.","use_canada":950,"findings":951,"conclusion":952,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":953,"title":"Summary Safety Review - Atypical antipsychotics - Assessing the Potential Risk of Urinary Retention","created_date":"2016-10-21","modified_date":null,"key_message_list":[{"field_id":949,"order_no":1,"bullet":"Atypical antipsychotics are used to treat mental disorders including schizophrenia, bipolar disorder and, in some cases, depression."},{"field_id":949,"order_no":2,"bullet":"The safety review of atypical antipsychotics and urinary retention was triggered by new safety information received from the manufacturer of Seroquel (quetiapine)."},{"field_id":949,"order_no":3,"bullet":"Health Canada's safety review found a potential link between the use of atypical antipsychotics and urinary retention. Health Canada is working with the manufacturer of olanzapine to update the safety information to increase the strength of the warning of the potential risk of urinary retention. Currently labelling for this risk is adequate in other antipsychotics in the Canadian market."}],"footnotes_list":[{"field_id":953,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[],"use_canada_list":[{"field_id":950,"order_no":1,"bullet":"Atypical antipsychotics are used to treat psychiatric disorders such as schizophrenia, bipolar disorder, and in some cases, depression. Risperidone is also used for the short-term symptomatic management of aggressive behaviour and psychotic symptoms in severe Alzheimer-type dementia."},{"field_id":950,"order_no":2,"bullet":"Nine different atypical antipsychotic medications have been marketed in Canada since 1991, available by prescription only: Abilify (aripiprazole), Saphris (asenapine), Clozaril (clozapine), Latuda (lurasidone), Zyprexa (olanzapine), Invega (paliperidone), Seroquel (quetiapine), Risperdal (risperidone) and Zeldox (ziprasidone). Some of these medications are available as generic versions."}],"finding_list":[{"field_id":951,"order_no":1,"bullet":"At the time of the review, Health Canada had received 38 Canadian reportsa related to urinary retention and the use of atypical antipsychotics (none with lurasidone use)."},{"field_id":951,"order_no":2,"bullet":"The reports above, as well as those from published literature, noted that most patients recovered or were recovering from the side effects after stopping the antipsychotic medication. In some cases, urinary retention re-occurred after the drug was taken again, further supporting a potential link between the atypical antipsychotic and urinary retention."},{"field_id":951,"order_no":3,"bullet":"At the time of the review, there were 1254 international reports of urinary retention with the use of any of the atypical antipsychotics."},{"field_id":951,"order_no":4,"bullet":"The risk of urinary retention is mentioned in the product safety information for most of the atypical antipsychotics. However, the wording used to explain the risk of urinary retention for the approved drug olanzapine was not consistent with the evidence reviewed."}],"conclusion_list":[{"field_id":952,"order_no":1,"bullet":"Health Canada's safety review found evidence supporting a potential link between the use of atypical antipsychotics and the occurrence of urinary retention."},{"field_id":952,"order_no":2,"bullet":"Health Canada will be updating the information for olanzapine to highlight what is currently known about the risk of urinary retention when this drug is taken. The update will be consistent with the safety information provided for the other products, which is considered at this time to be sufficient to remind about the risk of urinary retention."},{"field_id":952,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving atypical antipsychotics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00122","review_date":null,"drug_name":"Cervarix (Human Papillomavirus vaccine Types 16 and 18 [Recombinant, AS04 adjuvanted])","safety_issue":"A condition in which the body's defense system (immune system) damages nerves (Guillain-Barré Syndrome)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":959,"overview":"Health Canada and the Public Health Agency of Canada continuously monitor the safety of all vaccines, including Cervarix. Health Canada reviewed the potential link between Cervarix and a rare disorder in which the body's own defense system (immune system) damages nerves, causing muscle weakness, and sometimes paralysis (Guillain-Barré Syndrome). This review was started after a study by France's \"Agence nationale de sécurité du médicament et des produits de santé (ANSM)\" reported a slight increased risk of Guillain-Barré Syndrome (GBS)a after vaccination with Cervarix. Health Canada assessed the risk of GBS with Cervarix using information provided by the manufacturer, cases of GBS reported to the Canada Vigilance Programb and to Canadian Adverse Events Following Immunization Surveillance System (CAEFISS), as well as studies published in the literature.","use_canada":960,"findings":961,"conclusion":962,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":963,"title":"Summary Safety Review - Cervarix (Human Papillomavirus vaccine Types 16 and 18 [Recombinant, AS04 adjuvanted]) - Assessing the Potential Risk of a Condition in which the body's defense system damages nerves (Guillain-Barré Syndrome)","created_date":"2016-10-27","modified_date":null,"key_message_list":[{"field_id":959,"order_no":1,"bullet":"Cervarix is a vaccine used to protect against infection by the human papillomavirus (HPV) types 16 and 18 that cause cervical and anal cancer."},{"field_id":959,"order_no":2,"bullet":"Health Canada reviewed the risk of a rare disorder in which the body's own defense system (immune system) damages nerves, causing muscle weakness, and sometimes paralysis (Guillain-Barré Syndrome). This review was started after a study by France's \"Agence nationale de sécurité du médicament et des produits de santé (ANSM)\" reported a slight increased risk of Guillain-Barré Syndrome (GBS)a after vaccination with Cervarix."},{"field_id":959,"order_no":3,"bullet":"Health Canada's review of all of the available information did not find an increased risk of GBS following vaccination with Cervarix. Health Canada will continue to monitor the safety of Cervarix."}],"footnotes_list":[{"field_id":963,"order_no":1,"bullet":"Agence nationale de sécurité du médicament et des produits de santé (ANSM). Vaccins anti-HPV et risque de maladies auto-immunes : étude pharmaco-épidémiologique. Rapport final. Septembre 2015."},{"field_id":963,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":960,"order_no":1,"bullet":"Cervarix is a vaccine used to protect against infection by the human papillomavirus (HPV) types 16 and 18 that cause cervical and anal cancer."},{"field_id":960,"order_no":2,"bullet":"Cervarix has been sold in Canada since February 2010."},{"field_id":960,"order_no":3,"bullet":"Approximately 30,000 people in Canada were vaccinated with Cervarix between May 2007 and November 2015."}],"finding_list":[{"field_id":961,"order_no":1,"bullet":"At the time of the review, there were no Canadian cases of GBS reported following vaccination with Cervarix."},{"field_id":961,"order_no":2,"bullet":"No cases of GBS were reported in clinical trials before the marketing of Cervarix. After marketing, the manufacturer received 45 reports worldwide of GBS from May 2007 until November 2015. Only 10 of these reports had the signs and symptoms of GBS. However, it was not possible to determine if there was a link between Cervarix and GBS in these cases because not enough information was available for assessment, or there were other possible causes of GBS."},{"field_id":961,"order_no":3,"bullet":"The review did find that the number of cases of GBS reported following vaccination with Cervarix is much lower than the number expected in the general population."},{"field_id":961,"order_no":4,"bullet":"In the French study,a there were only 2 cases of GBS reported following vaccination with Cervarix. There was not enough clinical information to confirm that the cases were GBS."},{"field_id":961,"order_no":5,"bullet":"There was no evidence of an increased risk of GBS with Cervarix reported in other studies."}],"conclusion_list":[{"field_id":962,"order_no":1,"bullet":"Health Canada's review of all of the available information did not find an increased risk of GBS following vaccination with Cervarix."},{"field_id":962,"order_no":2,"bullet":"Health Canada will continue to monitor the side effect information involving Cervarix, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00124","review_date":null,"drug_name":"Enlite Glucose Sensor manufactured by Medtronic MiniMed","safety_issue":"Improper glucose (sugar) management","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":979,"overview":"Health Canada carried out a safety review of information related to the use of the Enlite Glucose Sensor after receiving reports that describe potentially inaccurate readings as compared to methods that measure blood sugar levels. If a person manages their diabetes based on inaccurate readings, they could experience potentially dangerous side effects from low blood sugar or high blood sugar (hypoglycemia or hyperglycemia).","use_canada":980,"findings":981,"conclusion":982,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Enlite Glucose Sensor- Assessing the Potential Risk of Improper Glucose Management","created_date":"2016-11-14","modified_date":null,"key_message_list":[{"field_id":979,"order_no":1,"bullet":"The Enlite Glucose Sensor is a single-use, disposable device that is intended to continuously monitor sugar levels in the fluid surrounding the body's tissues (interstitial glucose levels) for up to 6 days in persons with diabetes."},{"field_id":979,"order_no":2,"bullet":"Health Canada's safety review was triggered by reports that describe potentially inaccurate readings by the Enlite Glucose Sensor as compared to traditional blood sugar readings measured with the manual fingerstick method."},{"field_id":979,"order_no":3,"bullet":"As a result of this safety review, Health Canada concluded that the evidence does not suggest that there is a new safety risk. Health Canada will continue to monitor safety information regarding the Enlite Glucose Sensor and improper sugar management."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":980,"order_no":1,"bullet":"The Enlite Glucose Sensor is a single-use, disposable device that is intended to continuously monitor sugar in the fluid surrounding the body's tissues (interstitial glucose levels) for up to 6 days in persons with diabetes."},{"field_id":980,"order_no":2,"bullet":"A sensor on the device is inserted under the patient's skin and the device sends information wirelessly to an insulin pump or other display or recording device. These systems notify the patient about trends in the rise and fall of their sugar levels."},{"field_id":980,"order_no":3,"bullet":"It is expected that readings from the Enlite Glucose Sensor may differ slightly from the blood sugar levels. Therapy decisions should not be based on readings from the sensor alone. Fingerstick testing (to prick a finger with a small, needle-like lancet) of blood sugar levels is required to confirm if a patient needs treatment for high or low blood sugar."},{"field_id":980,"order_no":4,"bullet":"The Enlite Glucose Sensor was first licensed in Canada in February 2013 and is manufactured by Medtronic MiniMed."}],"finding_list":[{"field_id":981,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 33 reports describing a potential difference between measured blood sugar and the interstitial sugar reading provided by the Enlite Glucose Sensor. The report that triggered the review described that a user fainted after giving themselves too much insulin, based on readings from an Enlite Glucose Sensor. The report lacked additional information as to whether or not they were using their Enlite Glucose Sensor, fingerstick tests and insulin properly. The majority of the remaining reports described high or low blood sugar values with no resulting health consequences."},{"field_id":981,"order_no":2,"bullet":"The number of reports received by Health Canada related to potentially inaccurate readings is considered to be within the manufacturer's expected performance for the Enlite Glucose Sensor. The available scientific literature generally indicates that some inaccuracy of the Enlite Glucose Sensor device (in terms of reflecting blood sugar values) is expected and can vary depending on the individual, time of day, state of the sugar level (high or low) and age of the device."},{"field_id":981,"order_no":3,"bullet":"The Canadian Enlite Glucose Sensor \"Step by Step Guide\" specifies that interstitial sugar is measured by the sensor and highlights that a fingerstick test to confirm the blood sugar level is required prior to taking action to manage blood sugar, if needed."},{"field_id":981,"order_no":4,"bullet":"Based on Canadian and American diabetes association publications, a device like the Enlite Glucose Sensor is considered a useful addition to the self-monitoring of blood sugar, but it should not be used by itself for decision-making to manage blood sugar levels."}],"conclusion_list":[{"field_id":982,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence does not suggest that there is a new safety risk associated with the Enlite Glucose Sensor at this time."},{"field_id":982,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving the Enlite Glucose Sensor, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00125","review_date":null,"drug_name":"Havrix (hepatitis A vaccine, inactivated)","safety_issue":"Decreased amounts of platelets (cell fragments in blood involved with clotting)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":987,"overview":"Health Canada and the Public Health Agency of Canada continuously monitor the safety of all vaccines, including Havrix. After receiving a report of a patient developing a low platelet count following vaccination with Havrix, Health Canada reviewed a potential link between vaccination with Havrix and the development of thrombocytopenia. As a part of this review, Health Canada evaluated cases of thrombocytopenia provided by the manufacturer, cases reported to the Canada Vigilance Programa and to the Canadian Adverse Events Following Immunization Surveillance System (CAEFISS), and case reports published in the literature.","use_canada":988,"findings":989,"conclusion":990,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this vaccine both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":991,"title":"Summary Safety Review - Havrix (hepatitis A vaccine, inactivated) - Assessing the Potential Risk of Decreased Amounts of Blood Platelets (thrombocytopenia)","created_date":"2016-10-27","modified_date":null,"key_message_list":[{"field_id":987,"order_no":1,"bullet":"Havrix is a vaccine used to protect against hepatitis A virus infection."},{"field_id":987,"order_no":2,"bullet":"Health Canada reviewed a potential link between vaccination with Havrix and the development of thrombocytopenia after receiving a report of a patient developing a low platelet count following vaccination with Havrix."},{"field_id":987,"order_no":3,"bullet":"The review did not find an increased risk of thrombocytopenia with Havrix. Health Canada will continue to monitor the safety of Havrix."}],"footnotes_list":[{"field_id":991,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":988,"order_no":1,"bullet":"Havrix is a vaccine used to protect against hepatitis A virus infection in people at risk of coming into contact with the hepatitis A virus."},{"field_id":988,"order_no":2,"bullet":"Havrix has been sold in Canada since 1994, and is currently approved in 108 countries."},{"field_id":988,"order_no":3,"bullet":"An estimated 2.8 to 5.7 million Canadians have been vaccinated, and approximately 160 to 320 million people have been vaccinated world-wide."}],"finding_list":[{"field_id":989,"order_no":1,"bullet":"At the time of the review, only 1 case of thrombocytopenia following vaccination with Havrix had been reported to the Canada Vigilance Programa. Three other cases were also reported to the Canadian Adverse Events Following Immunization Surveillance System (CAEFISS)."},{"field_id":989,"order_no":2,"bullet":"No confirmed cases of thrombocytopenia were reported in clinical trials before the marketing of Havrix. From 1992 until 2015, the manufacturer received 99 international reports of thrombocytopenia. It was not possible to determine if there was a link between Havrix and thrombocytopenia for either the Canadian or international cases because the cases were either not confirmed as thrombocytopenia, there were other possible causes of thrombocytopenia, or there was not enough information provided for assessment."},{"field_id":989,"order_no":3,"bullet":"The number of cases of thrombocytopenia following vaccination with Havrix reported internationally and in Canada, is much lower than the number expected in the general population."},{"field_id":989,"order_no":4,"bullet":"No association between the hepatitis A vaccine and thrombocytopenia has been reported in the literature."}],"conclusion_list":[{"field_id":990,"order_no":1,"bullet":"Health Canada's review did not identify a link between vaccination with Havrix and thrombocytopenia following a review of the available data."},{"field_id":990,"order_no":2,"bullet":"Health Canada will continue to monitor the side effect information involving Havrix, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00126","review_date":null,"drug_name":"Incretin-based therapies: sitagliptin, saxagliptin, linagliptin, alogliptin (alone or in combination with metformin) and exenatide.","safety_issue":"Pancreatic cancer","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":997,"overview":"During the last few years, a small number of studies have found a possible link between the use of incretin-based therapies and an increased risk of pancreatic cancer. Worldwide, the number of case reports of pancreatic cancer potentially linked to the use of incretin-based therapies has been increasing steadily. This new evidence led Health Canada to assess the risk of pancreatic cancer linked to the use of incretin-based therapies. Pancreatic cancer is one of the deadliest forms of cancer with a low survival rate 5 years after diagnosis (6%). Risk factors for pancreatic cancer include smoking, obesity, a family history of pancreatic cancer, chronic pancreatitis and diabetes.","use_canada":998,"findings":999,"conclusion":1000,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1001,"footnotes":0,"title":"Summary Safety Review - Incretin-Based Therapies - Assessing the Potential Risk of Pancreatic Cancer","created_date":"2016-10-21","modified_date":null,"key_message_list":[{"field_id":997,"order_no":1,"bullet":"Incretin-based therapies are prescription drugs that are used with or without other anti-diabetic drugs along with diet and exercise to improve blood sugar levels in adult patients with type 2 diabetes."},{"field_id":997,"order_no":2,"bullet":"This review was triggered by studies that suggested a potential link between the use of incretin-based therapies and an increased risk of pancreatic cancer."},{"field_id":997,"order_no":3,"bullet":"Health Canada's safety review concluded that there is not enough evidence at this time to confirm this link. Health Canada will continue to monitor the safety of incretin-based therapies, and encourages healthcare professionals to report side effects that may be linked to the use of incretin-based therapies."}],"footnotes_list":[],"reference_list":[{"field_id":1001,"order_no":1,"bullet":"Azoulay L, Filion KB, Platt RW et al, (2016), Incretin-based drugs and the risk of pancreatic cancer: An international multi-centre cohort study, BMJ on-line publication. http://dx.doi.org/10.1136/bmj.i581"},{"field_id":1001,"order_no":2,"bullet":"Knapen LM, van Dalem J, Keulemans YC, et al, (2016), Use of incretin agents and risk of pancreatic cancer: A population-based cohort study, Diabetes, Obesity and Metabolism 18:258-265."},{"field_id":1001,"order_no":3,"bullet":"Tseng C-H, (2016), Sitagliptin and pancreatic cancer risk in patients with type 2 diabetes, Eur J Clin Invest 46:70-79."}],"use_canada_list":[{"field_id":998,"order_no":1,"bullet":"Incretin-based therapies are prescription drugs that are used with diet and exercise, and with other drugs, to improve blood sugar levels in adults with type 2 diabetes. They work by improving the secretion of insulin by the pancreas by either increasing the level of incretins in the blood or by acting like incretins."},{"field_id":998,"order_no":2,"bullet":"There are currently 9 pharmaceutical incretin-based therapies marketed in Canada. These products are either (1) DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin and alogliptin), used alone or in combination with metformin, or (2) incretin-like molecules (exenatide), approved only for use with other anti-diabetic agents."},{"field_id":998,"order_no":3,"bullet":"Sitagliptin was the first incretin-based therapy sold in Canada starting in 2008 and alogliptin was the latest in 2014."},{"field_id":998,"order_no":4,"bullet":"Incretin-based therapies are widely used in Canada, with close to 16 million prescriptions being filled in Canada since they have been marketed."}],"finding_list":[{"field_id":999,"order_no":1,"bullet":"At the time of the review, going back to the introduction of incretin-based therapies in Canada (2008), 15 cases of pancreatic cancer have been reported to Health Canada that may have been linked to the use of incretin-based therapies."},{"field_id":999,"order_no":2,"bullet":"In February 2014, the United States Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) published a scientific article that concluded that a link between incretin-based therapies and pancreatitis/pancreatic cancer could not be made based on data at hand. Both groups continue to look into this safety issue."},{"field_id":999,"order_no":3,"bullet":"Although some non-clinical studies using animal or human models have suggested that the use of incretin-based therapies may be linked to an increased risk of pancreatic cancer, results from clinical trials and many studies looking at the patterns, causes, and effects of health and disease conditions in people, do not support this link."},{"field_id":999,"order_no":4,"bullet":"Lately, two studies12 concluded that incretin-based therapies were not linked to pancreatic cancer. A third study3 reported an increased risk of pancreatic cancer only for patients who had taken sitagliptin non-stop for close to 1 year. It is possible that this observation was due to patients that already had pancreatic cancer that has not been diagnosed before being treated with sitagliptin."}],"conclusion_list":[{"field_id":1000,"order_no":1,"bullet":"Health Canada's review concluded that there is not enough evidence at this time to confirm a link between incretin-based therapies and pancreatic cancer."},{"field_id":1000,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving incretin-based therapies, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00127","review_date":null,"drug_name":"Interferon beta-1a (Avonex and Rebif) and interferon beta-1b (Betaseron and Extavia)","safety_issue":"Risk of high blood pressure in the arteries which carry blood from the heart to the lungs (pulmonary arterial hypertension)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1007,"overview":"Health Canada carried out a safety review regarding the risk of pulmonary arterial hypertension associated with the use of interferon beta products after a report from the European Medicines Agency found a possible link between them. Pulmonary arterial hypertension is potentially life-threatening if untreated. Cases of pulmonary arterial hypertension in patients treated with interferon beta therapies to treat multiple sclerosis have been reported in safety reports received from the manufacturers and in published case reports.","use_canada":1008,"findings":1009,"conclusion":1010,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what are known about the use of this product both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1011,"footnotes":1012,"title":"Summary Safety Review - Interferon beta products - Assessing the Potential Risk of Pulmonary Arterial Hypertension","created_date":"2016-11-02","modified_date":"2016-11-30","key_message_list":[{"field_id":1007,"order_no":1,"bullet":"Interferon beta products are used to treat some forms of multiple sclerosis, a disease of the central nervous system."},{"field_id":1007,"order_no":2,"bullet":"Health Canada carried out a safety review, after the European Medicines Agency found a possible link between the use of interferon beta products for treating multiple sclerosis and the risk of high blood pressure in the arteries which carry blood from the heart to the lungs (pulmonary arterial hypertension)."},{"field_id":1007,"order_no":3,"bullet":"Health Canada's safety review concluded that there was a possible link between the use of interferon beta products for multiple sclerosis and the risk of developing pulmonary arterial hypertension. The Canadian product safety information for interferon beta products has been updated to include the risk of this side effect."}],"footnotes_list":[{"field_id":1012,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1011,"order_no":1,"bullet":"Gibbons E, et al. Reversible pulmonary arterial hypertension associated with interféron-beta treatment for multiple sclerosis. Can Resp J. 2015;22(5):263-265. (Cas canadien)"}],"use_canada_list":[{"field_id":1008,"order_no":1,"bullet":"Interferon beta products are used to treat multiple sclerosis."},{"field_id":1008,"order_no":2,"bullet":"Two types of interferon beta products are authorized for sale, by prescription only, in Canada: type 1a (Avonex and Rebif) and type 1b (Betaseron and Extavia)."},{"field_id":1008,"order_no":3,"bullet":"The first of these (Avonex) was marketed in Canada in 2005."}],"finding_list":[{"field_id":1009,"order_no":1,"bullet":"At the time of the review, there were 2 Canadian cases of pulmonary arterial hypertension that were possibly related to interferon beta use, and in both cases, the patients improved with treatment of the pulmonary arterial hypertension, and stopping interferon beta use.1a"},{"field_id":1009,"order_no":2,"bullet":"Worldwide, there were 136 case reports of pulmonary arterial hypertension in patients that were using interferon beta (which includes the 2 Canadian cases). In 14 cases, the pulmonary arterial hypertension may have been related to interferon beta use. In the remaining cases, the information available was too limited to make any conclusions."},{"field_id":1009,"order_no":3,"bullet":"At the time of the review, information regarding the risk of pulmonary arterial hypertension was not included in the Canadian product safety information for any of the interferon beta products."}],"conclusion_list":[{"field_id":1010,"order_no":1,"bullet":"Health Canada's safety review concluded that pulmonary arterial hypertension is a very rare side effect of interferon beta use. Given the potentially life-threatening effects of pulmonary arterial hypertension, healthcare professionals and patients should be made aware of this risk."},{"field_id":1010,"order_no":2,"bullet":"Health Canada has worked with the manufacturers to include the risk of pulmonary arterial hypertension in the Canadian product safety information for interferon beta products."},{"field_id":1010,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving interferon beta products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00128","review_date":null,"drug_name":"Levetiracetam and methotrexate","safety_issue":"Drug-drug interaction","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1019,"overview":"Health Canada carried out a safety review after learning that the European Medicines Agency was looking into a potential interaction between levetiracetam and methotrexate. The interaction between the two drugs may lead to higher amount of methotrexate in the blood, which may cause serious side effects. The side effects, which can be fatal, include sudden (acute) kidney failure.","use_canada":1020,"findings":1021,"conclusion":1022,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1023,"footnotes":0,"title":"Summary Safety Review - Levetiracetam and Methotrexate - Assessing the Potential Risk of Drug-Drug Interaction","created_date":"2016-10-24","modified_date":null,"key_message_list":[{"field_id":1019,"order_no":1,"bullet":"Levetiracetam is used to help epilepsy treatment be more effective. Methotrexate is used to treat cancer or to treat arthritis."},{"field_id":1019,"order_no":2,"bullet":"A safety review was carried out after a scientific article1 was published regarding the potential interaction between levetiracetam and methotrexate, as well as the issue being reviewed by the European Medicines Agency."},{"field_id":1019,"order_no":3,"bullet":"Health Canada's review concluded that there are risks of serious side effects when these drugs are taken together and recommended that the product information for levetiracetam and methotrexate products be updated to inform about this drug interaction. Product labelling now recommends that the amounts of levetiracetam and methotrexate be carefully monitored in the blood when patients are treated with the two drugs at the same time."}],"footnotes_list":[],"reference_list":[{"field_id":1023,"order_no":1,"bullet":"Bain E, Birhiray RE, Reeves DJ. Drug-drug interaction between methotrexate and levetiracetam resulting in delayed methotrexate elimination. Ann Pharmacother. 2014;48(2):292-6."}],"use_canada_list":[{"field_id":1020,"order_no":1,"bullet":"Levetiracetam is a drug used to help epilepsy treatment be more effective. Levetiracetam is available in Canada as oral tablets. It has been marketed under the brand name Keppra since 2003. Generic versions are also available."},{"field_id":1020,"order_no":2,"bullet":"Methotrexate is a drug used to treat cancer and also arthritis at a lower dose. Methotrexate is available in Canada as oral tablets and as an injectable liquid. It has been marketed since 1955 under various brand names and generic versions are also available."},{"field_id":1020,"order_no":3,"bullet":"Given its potential serious side effects, methotrexate is used to treat life-threatening stages of cancers, and in patients with disease in the joints (arthritis) severe enough to cause disability, and when standard treatments have failed."}],"finding_list":[{"field_id":1021,"order_no":1,"bullet":"At the time of the review, there were no reported cases, in the Canada Vigilance Database, of patients who had received levetiracetam and methotrexate at the same time."},{"field_id":1021,"order_no":2,"bullet":"The manufacturer of levetiracetam provided 13 international reports of a potential interaction between levetiracetam and methotrexate. The review of these reports was limited by many factors such as pre-existing diseases, other medications taken, and lack of laboratory data (e.g. blood levels of methotrexate)."},{"field_id":1021,"order_no":3,"bullet":"Of these 13 reports, 5 reports noted that patients who were taking both levetiracetam and methotrexate at the same time had greater amounts of methotrexate in their blood."},{"field_id":1021,"order_no":4,"bullet":"Some of these 13 reports noted side effects to the kidneys when levetiracetam and methotrexate were taken together. Kidney damage and a sudden failure of the kidneys is a known potential side effect when taking methotrexate; this risk is mentioned in the product safety information."}],"conclusion_list":[{"field_id":1022,"order_no":1,"bullet":"Health Canada's safety review found that there is a potentially greater risk of side effects when levetiracetam and methotrexate are taken together."},{"field_id":1022,"order_no":2,"bullet":"The assessment recommended that the product information for levetiracetam and methotrexate products be updated to inform about this drug interaction. Product labelling now recommends that blood methotrexate and levetiracetam levels should be carefully monitored in patients treated with the two drugs at the same time."},{"field_id":1022,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving levetiracetam and methotrexate, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00129","review_date":null,"drug_name":"Loratadine","safety_issue":"Abnormal heart rhythm (QT interval prolongation)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1029,"overview":"Health Canada carried out a safety review to investigate the potential risk of developing an abnormal heart rhythm (QT interval prolongation) with the use of over-the-counter (OTC) drug products containing loratadine. This safety review was triggered by a publication, in the World Health Organization (WHO) Pharmaceuticals Newsletter1, describing cases of an abnormal heart rhythm (QT interval prolongation) possibly associated with the use of loratadine and desloratadine.","use_canada":1030,"findings":1031,"conclusion":1032,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1033,"footnotes":0,"title":"Summary Safety Review - Loratadine - Abnormal heart rhythm (QT interval prolongation)","created_date":"2016-11-09","modified_date":null,"key_message_list":[{"field_id":1029,"order_no":1,"bullet":"Loratadine is available as an ingredient in some over-the-counter (OTC) products used for the relief of symptoms of allergy."},{"field_id":1029,"order_no":2,"bullet":"Health Canada carried out a safety review following international reports of abnormal heart rhythm (QT interval prolongation) suspected of being associated with the use of loratadine."},{"field_id":1029,"order_no":3,"bullet":"After review of available data, a link between the use of loratadine and the abnormal heart rhythm could not be established. Health Canada will continue to monitor the safety of loratadine containing products."}],"footnotes_list":[],"reference_list":[{"field_id":1033,"order_no":1,"bullet":"World Health Organization. (2015). Desloratadine and QT Prolongation. WHO Pharmaceuticals Newsletter, 23-27."}],"use_canada_list":[{"field_id":1030,"order_no":1,"bullet":"In Canada, loratadine is an ingredient found in some OTC drug products that relieve symptoms of seasonal allergy or allergy caused by pollen or dust (hay fever) such as sneezing, runny or itchy nose, itchy watery burning eyes, as well as allergic skin conditions."},{"field_id":1030,"order_no":2,"bullet":"Loratadine has been marketed in Canada since 1988 under the brand name Claritin. Generic versions are also available. It is available in tablets or syrup."}],"finding_list":[{"field_id":1031,"order_no":1,"bullet":"At the time of the review, Health Canada had received 21 Canadian reports of abnormal heart rhythm (QT interval prolongation) suspected to be associated with loratadine use. Of these, 4 cases were further assessed. The review of these 4 cases could not conclude whether loratadine played a role in the abnormal heart rhythm. The information contained in the reports was limited, and some patients may have had other underlying heart conditions or were taking greater than the recommended dose of loratadine."},{"field_id":1031,"order_no":2,"bullet":"In addition, Health Canada reviewed 81 international reports, of abnormal heart rhythm with the use of loratadine, that were provided by the manufacturer. A link between these cases and the abnormal heart rhythm could not be established, due to other risk factors which may have played a role, or there was not enough information in the reports to draw conclusions."},{"field_id":1031,"order_no":3,"bullet":"Also, a search in the World Health Organization's Adverse Drug Reaction Database (VigiBase) found 101 cases of abnormal heart rhythm suspected to be associated with loratadine use. A link between the use of loratadine and the abnormal heart rhythm could not be established, because there was not enough information in the reports to draw conclusions."},{"field_id":1031,"order_no":4,"bullet":"Scientific studies have shown that loratadine was not associated with abnormal heart rhythm in humans"}],"conclusion_list":[{"field_id":1032,"order_no":1,"bullet":"After review of available data, a link between the use of loratadine and the abnormal heart rhythm (QT interval prolongation) could not be established."},{"field_id":1032,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving loratadine, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00131","review_date":null,"drug_name":"Rivastigmine (Exelon and generics)","safety_issue":"Increased risk of death","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1051,"overview":"As part of the routine monitoring of side effects for rivastigmine, Health Canada evaluated whether there was an increase in the number of patients that died over the past few years while using the Exelon patch (which is the only transdermal formulation currently available in Canada) compared to patients taking rivastigmine pills or liquid (oral formulations). A safety review was carried out to assess the risk of death with Exelon in all formulations to find out if further actions were needed to manage this issue.","use_canada":1052,"findings":1053,"conclusion":1054,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1055,"footnotes":1056,"title":"Summary Safety Review - Rivastigmine (Exelon and generics) - Assessing the Potential Increased Risk of Death","created_date":"2016-11-09","modified_date":null,"key_message_list":[{"field_id":1051,"order_no":1,"bullet":"Rivastigmine is used to treat dementia in patients with Alzheimer's or Parkinson's diseases."},{"field_id":1051,"order_no":2,"bullet":"As part of the review of information provided by the manufacturer, Health Canada assessed whether there was an increased risk of death in patients using rivastigmine by patch, compared to pill or liquid."},{"field_id":1051,"order_no":3,"bullet":"Health Canada's safety review did not find an increased risk of death in patients taking rivastigmine regardless of formulation used. Health Canada will continue to monitor side effects for this drug and has requested the manufacturer of Exelon to continue to provide information on the use of this product."}],"footnotes_list":[{"field_id":1056,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1055,"order_no":1,"bullet":"Ganguli, M., et al. 2005. Alzheimer disease and mortality, a 15 year epidemiological study. Archives of Neurology, 62: 779-784."}],"use_canada_list":[{"field_id":1052,"order_no":1,"bullet":"Rivastigmine is used to treat dementia symptoms in patients with Alzheimer's or Parkinson's diseases."},{"field_id":1052,"order_no":2,"bullet":"Rivastigmine is mainly used in elderly patients since the risk of Alzheimer's and Parkinson's diseases increases with age. In Canada, almost 10 million total units of rivastigmine (pills, patches or milliliters of liquid) are sold each year."},{"field_id":1052,"order_no":3,"bullet":"Exelon has been sold in Canada since 2000. Exelon as patch formulations has been sold in Canada since 2007. The use of the patches has increased over time. In 2014, the patch was the form used by about half of all patients treated with rivastigmine."}],"finding_list":[{"field_id":1053,"order_no":1,"bullet":"At the time of the review, Health Canada had received 194 reportsa of death in patients taking rivastigmine. The patch was used in 39 of these reports, oral formulations (pills or liquid) were used in 113 reports; the remaining reports did not have information on the type of formulation. It is difficult to link an increased risk of death to rivastigmine use, regardless the formulation, because patients using rivastigmine may have additional risk factors for death such as advanced age, having other diseases, or taking other medications at the same time."},{"field_id":1053,"order_no":2,"bullet":"Based on the information reviewed, the number of deaths reported in patients treated with rivastigmine regardless of formulations remained low and stable between 2011 and 2015."},{"field_id":1053,"order_no":3,"bullet":"The number of deaths reported among patients treated with rivastigmine was lower than expected in an elderly population with Alzheimer's disease.1"},{"field_id":1053,"order_no":4,"bullet":"In the literature, there was no evidence of increased risk of death with rivastigmine use."}],"conclusion_list":[{"field_id":1054,"order_no":1,"bullet":"Health Canada's safety review did not find an increased risk of death in patients taking rivastigmine regardless of the formulation used."},{"field_id":1054,"order_no":2,"bullet":"Health Canada has asked the manufacturers of Exelon to continue to provide information on the use of this product."},{"field_id":1054,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Exelon and its generics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00139","review_date":null,"drug_name":"Zelboraf (vemurafenib)","safety_issue":"Bone marrow side effects (bone marrow toxicity or suppression)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1139,"overview":"A safety review was carried out after receiving a report from the manufacturer regarding the potential for side effects related to the destruction (toxicity) or decreased production (suppression) of bone marrow cells in patients treated with Zelboraf.
","use_canada":1140,"findings":1141,"conclusion":1142,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Zelboraf (vemurafenib) - Assessing the Potential Risk of Bone Marrow Side Effects (Bone Marrow Toxicity or Suppression)","created_date":"2016-11-14","modified_date":null,"key_message_list":[{"field_id":1139,"order_no":1,"bullet":"Zelboraf is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma). It works by targeting proteins made from a mutated gene called \"BRAF\"."},{"field_id":1139,"order_no":2,"bullet":"Health Canada carried out a safety review after receiving a report from the manufacturer regarding the safety of Zelboraf."},{"field_id":1139,"order_no":3,"bullet":"Health Canada concluded that the evidence did not support a link between Zelboraf use and bone marrow side effects. Health Canada will continue to monitor safety information involving Zelboraf."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1140,"order_no":1,"bullet":"Zelboraf (vemurafenib) slows down or stops the growth of cancer cells by targeting specific proteins (proteins from the BRAF gene)."},{"field_id":1140,"order_no":2,"bullet":"Zelboraf is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma) that has a mutation in the BRAF gene and cannot be removed by surgery or has spread to other parts of the body."},{"field_id":1140,"order_no":3,"bullet":"Zelboraf has been marketed in Canada since March 2012."}],"finding_list":[{"field_id":1141,"order_no":1,"bullet":"The bone marrow related side effects investigated during this safety review included very low levels of at least two types of blood cells, either red or white blood cells or platelets (bicytopenia or pancytopenia)."},{"field_id":1141,"order_no":2,"bullet":"At the time of review, Health Canada had not received any Canadian reports of bone marrow related side effects in patients using Zelboraf."},{"field_id":1141,"order_no":3,"bullet":"The World Health Organization's Adverse Drug Reaction Database (VigiBase) had received 6 reports of side effects describing bone-marrow cell suppression (pancytopenia) suspected of being linked with the use of Zelboraf. The 6 reported cases were either incomplete or did not have enough information for further assessment."},{"field_id":1141,"order_no":4,"bullet":"A review of the scientific and medical literature did not find any articles or studies describing the development of bone marrow toxicity or suppression with Zelboraf."},{"field_id":1141,"order_no":5,"bullet":"Bone marrow side effects (toxicity or suppression) can occur in advanced metastatic melanoma patients from the use of other/previous chemotherapy treatments."},{"field_id":1141,"order_no":6,"bullet":"Although the report submitted to Health Canada by the manufacturer showed a potential for side effects related to bone marrow toxicity/suppression with Zelboraf use, further review by the manufacturer concluded that a link could not be established."}],"conclusion_list":[{"field_id":1142,"order_no":1,"bullet":"Health Canada's safety review concluded that the current evidence available does not support a link between Zelboraf use and bone marrow toxicity or suppression."},{"field_id":1142,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving Zelboraf, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely actions when any new health risks are identified."}]},{"template":2,"link_id":"SSR00132","review_date":null,"drug_name":"Sodium-glucose cotransporter-2 (SGLT2) inhibitors: Invokana (canagliflozin), Forxiga (dapagliflozin), Jardiance (empagliflozin)","safety_issue":"Loss of bone minerals with a risk of brittle or broken bones","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1063,"overview":"The minerals stored within the bones help provide strength. Bones that have fewer minerals (less bone mineral density) are more likely to become brittle and break (fracture). A safety review was carried out by Health Canada to evaluate the risk of bone-related side effects of using SGLT2 inhibitors. The review was triggered by a notice about international reports of bone-related side effects experienced in patients taking the SGLT2 inhibitor canagliflozin.","use_canada":1064,"findings":1065,"conclusion":1066,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of these drugs and their associated risks in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1067,"footnotes":1068,"title":"Summary Safety Review - SGLT2 Inhibitors (canagliflozin, dapagliflozin, empagliflozin) - Assessing the Potential Risk of Bone-Related Side Effects","created_date":"2016-11-14","modified_date":null,"key_message_list":[{"field_id":1063,"order_no":1,"bullet":"SGLT2 inhibitors are drugs used to treat adults with type 2 diabetes."},{"field_id":1063,"order_no":2,"bullet":"This safety review was triggered following international reports about the increased risk of losing bone minerals or suffering broken bones in patients taking canagliflozin."},{"field_id":1063,"order_no":3,"bullet":"Health Canada's safety review found a link between bone-related side effects and the use of canagliflozin. Health Canada is working with the manufacturer to update the safety information of canagliflozin to reflect these risks. For dapagliflozin, these risks were only identified in patients who had kidney problems and this is already explained in the safety information. No evidence of bone-related side effects was found to date with the use of empagliflozin."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1064,"order_no":1,"bullet":"SGLT2 inhibitors are drugs designed to lower blood sugar in adults with type 2 diabetes by helping remove excess sugar from the body through the urine."},{"field_id":1064,"order_no":2,"bullet":"SGLT2 inhibitors are used along with diet and exercise either alone or in combination with other specific agents that control blood sugar."},{"field_id":1064,"order_no":3,"bullet":"Three SGLT2 inhibitors are currently available in Canada: Invokana (canagliflozin), Forxiga (dapagliflozin) and Jardiance (empagliflozin). Drugs of this type have been available in Canada since 2014."}],"finding_list":[{"field_id":1065,"order_no":1,"bullet":"At the time of the review Health Canada had not received any Canadian reports of loss of bone mineral density or broken bones related to the use of SGLT2 inhibitors."},{"field_id":1065,"order_no":2,"bullet":"Recent medical studies have found an increased risk of losing bone mineral density and an increased risk of bone fracture occurring as early as 12 weeks of being on treatment with canagliflozin, but these side effects are still rare. An increased risk of bone fracture associated with the use of dapagliflozin was also noted in patients with kidney problems (moderate renal impairment). No evidence of bone-related side effects was found to date with the use of empagliflozin."},{"field_id":1065,"order_no":3,"bullet":"Based on how SGLT2 inhibitors work in the body, they may affect the way the body takes in minerals to strengthen the bones. The evidence from scientific literature showed that this may contribute to the side effects."},{"field_id":1065,"order_no":4,"bullet":"At the time of the review, the product safety information for canagliflozin and dapagliflozin already included some information on the risk of bone fracture."}],"conclusion_list":[{"field_id":1066,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence supported a link between the risks of bone fracture and loss of bone mineral density with the use of canagliflozin. With use of dapagliflozin, these risks were only identified in patients who had kidney problems.No evidence of bone-related side effects was found to date with the use of empagliflozin."},{"field_id":1066,"order_no":2,"bullet":"Health Canada is working with the manufacturer to update the safety information for canagliflozin to reflect these risks. The dapagliflozin product safety information already mentions the risks, so no updates were recommended from this review."},{"field_id":1066,"order_no":3,"bullet":"Health Canada will mention the update in the Health Product InfoWatch, to inform physicians about the potential risk of bone-related side effects in patients treated with canagliflozin, and to consider factors that contribute to the fracture risk."},{"field_id":1066,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving SGLT2 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00135","review_date":null,"drug_name":"Zofran (ondansetron)","safety_issue":"Harm to the fetus","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1099,"overview":"Health Canada carried out a safety review to assess the risk of birth defects with the use of ondansetron, as part of routine health product monitoring and because this drug is not authorized for sale in Canada to treat nausea and vomiting during pregnancy. The use of ondansetron during pregnancy is not recommended because its safety has not been established in pregnant women.
","use_canada":1100,"findings":1101,"conclusion":1102,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1104,"title":"Summary Safety Review - ZOFRAN (ondansetron) - Assessing the Potential Harm to the Fetus","created_date":"2016-11-16","modified_date":null,"key_message_list":[{"field_id":1099,"order_no":1,"bullet":"Ondansetron is a prescription drug which is authorized for sale in Canada to manage nausea and vomiting associated with cancer treatment or surgery. Health Canada is aware that ondansetron is prescribed by some clinicians for the treatment of nausea and vomiting related to other conditions, including pregnancy."},{"field_id":1099,"order_no":2,"bullet":"As part of routine monitoring of ondansetron and because this drug is not authorized for sale in Canada to treat nausea and vomiting during pregnancy, Health Canada carried out a safety review to assess the risk of birth defects."},{"field_id":1099,"order_no":3,"bullet":"After review of available data, there was not enough information to establish a link between the use of ondansetron during pregnancy and the risk of birth defects. Health Canada will continue to monitor the safety information involving the use of ondansetron during pregnancy."}],"footnotes_list":[{"field_id":1104,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1100,"order_no":1,"bullet":"Ondansetron is a prescription drug which is authorized for sale in Canada to manage nausea and vomiting associated with cancer treatment or surgery. Health Canada is aware that ondansetron is prescribed by some clinicians for the treatment of nausea and vomiting related to other conditions, including pregnancy."},{"field_id":1100,"order_no":2,"bullet":"Ondansetron has been marketed in Canada since 1991 under the brand name Zofran. Generic versions of ondansetron are also available. Ondansetron is available for oral and intravenous administration."}],"finding_list":[{"field_id":1101,"order_no":1,"bullet":"At the time of the review, Health Canada had received 14 reportsa of birth defects in the newborn babies of mothers treated with ondansetron. In 4 of these reports, there was not enough information to know at what stage of the pregnancy ondansetron was given. In 2 other reports, ondansetron was given after the organs of the fetus were already developed. In the remaining 8 reports, ondansetron was given to the mother at the stage the organs were developing."},{"field_id":1101,"order_no":2,"bullet":"In these 8 reports, a link between birth defects and ondansetron could not be ruled out. It was not possible to come to a conclusion whether ondansetron itself caused birth defects because many of the reports lacked information regarding how much and for how long ondansetron was taken. Information about the medical history of the mother, including additional medications she may have been taking, was also lacking. There was no pattern of birth defects."},{"field_id":1101,"order_no":3,"bullet":"Findings from published scientific studies were not consistent. Moreover, there were concerns with how the studies were designed. The majority of these studies had a number of limitations (e.g., concomitant medications, study design) and conclusions could not be made about the safety of ondansetron use in pregnancy."},{"field_id":1101,"order_no":4,"bullet":"The findings from animal studies have not established that ondansetron can cause birth defects."}],"conclusion_list":[{"field_id":1102,"order_no":1,"bullet":"After review of available data, there was not enough information to establish a link between the use of ondansetron during pregnancy and the risk of birth defects. Ondansetron is not authorized for sale in Canada to treat nausea and vomiting in pregnant women, as its safety in that population has not been evaluated."},{"field_id":1102,"order_no":2,"bullet":"Health Canada is working with the Drug Safety and Effectiveness Network to further investigate the extent of ondansetron use during pregnancy and the risk to the fetus. Health Canada has requested that manufacturers submit information they may have regarding birth defects and use of ondansetron during pregnancy."},{"field_id":1102,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving the use of ondansetron as it does for all health products on the Canadian market, to find and study potential harms. Health Canada will take the right and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00136","review_date":null,"drug_name":"Phenylephrine and acetaminophen","safety_issue":"Drug-drug interaction","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1111,"overview":"Health Canada initiated a safety review following a report by the European Medicines Agency about the potential drug-drug interaction between phenylephrine and acetaminophen. These drugs are often found together in over-the-counter health products including those for treating cold, flu and allergies. People who have high blood pressure or heart disease may be more vulnerable to the side effects of phenylephrine if both of these drugs are taken together as there appears to be an interaction between them that leads to an increase of phenylephrine in the body (increased bioavailability).
","use_canada":1112,"findings":1113,"conclusion":1114,"additional":"Canadian and international adverse reaction reports and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1115,"footnotes":1116,"title":"Summary Safety Review - Phenylephrine and acetaminophen - Drug-drug interaction","created_date":"2016-11-23","modified_date":null,"key_message_list":[{"field_id":1111,"order_no":1,"bullet":"Phenylephrine and acetaminophen are drugs often found together in non-prescription health products used to relieve symptoms from the common cold, flu and allergies."},{"field_id":1111,"order_no":2,"bullet":"This safety review was triggered by a report from the European Medicines Agency about the potential risk of an interaction between phenylephrine and acetaminophen and potential side effects when these two drugs are taken together."},{"field_id":1111,"order_no":3,"bullet":"Health Canada's safety review concluded that the evidence shows a drug-drug interaction between acetaminophen and phenylephrine which may lead to an increased amount of phenylephrine in the body; however, there is no evidence at this time to show that this is a significant risk to healthy consumers. Certain people may be at a greater risk of phenylephrine's side effects due to pre-existing health conditions, but this caution is already required to be on the labels of these products."},{"field_id":1111,"order_no":4,"bullet":"Health Canada will continue to monitor this safety issue and will publish a Health Product InfoWatch article to help raise awareness of the interaction among healthcare professionals and consumers."}],"footnotes_list":[{"field_id":1116,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[{"field_id":1115,"order_no":1,"bullet":"Tark BE, Messe SR, Balucani C, Levine SR. Intracerebral hemorrhage associated with oral phenylephrine use: A case report and review of the literature. J Stroke Cerebrovas Dis. 2014; 23(9): 2296-300."}],"use_canada_list":[{"field_id":1112,"order_no":1,"bullet":"At the time of the review there were 66 non-prescription products on the Canadian market that combined both phenylephrine to treat congestion and acetaminophen for pain and fever relief due to the common cold, flu and allergies. All of these products are for use in adults and children 12 years and older only."},{"field_id":1112,"order_no":2,"bullet":"In Canada, all non-prescription, phenylephrine-containing products must include a warning statement to \"ask a doctor before use if you have heart disease, high blood pressure, thyroid disease or diabetes.\""}],"finding_list":[{"field_id":1113,"order_no":1,"bullet":"At the time of the review there was 1 Canadian reporta of increased blood pressure due to a possible drug interaction between phenylephrine and acetaminophen, which was further assessed. The individual had been taking an acetaminophen-phenylephrine combination product and was also taking another medication to treat his pre-existing high blood pressure. However, after adjustment of the blood pressure medication the blood pressure returned back to normal and he did not experience any further blood-pressure related side effects."},{"field_id":1113,"order_no":2,"bullet":"There is one published report in the scientific literature1 of a bleed in the brain (intracerebral hemorrhage) in a person taking multiple cough and cold medicines containing phenylephrine over a 30-day period. However, it could not be confirmed that this event was due to an interaction between phenylephrine and acetaminophen, given that there were multiple ingredients in the product, and the person had used multiple cough and cold medicines. Overall, the safety data reviewed by Health Canada were all lacking relevant information to determine if these side effects were due to a drug-drug interaction between phenylephrine and acetaminophen."},{"field_id":1113,"order_no":3,"bullet":"People who have high blood pressure or heart disease may be more vulnerable to the side effects of phenylephrine if both of these drugs are taken together as there appears to be an interaction between them that leads to an increase of phenylephrine in the body."}],"conclusion_list":[{"field_id":1114,"order_no":1,"bullet":"Health Canada's safety review concluded that the evidence shows a drug-drug interaction between phenylephrine and acetaminophen which may lead to an increased amount of phenylephrine in the body; however, there is no evidence at this time to show that this is a significant risk to healthy consumers. Certain people may be at a greater risk of phenylephrine's side effects due to pre-existing health conditions, but this caution is already required to be on the labels of these products."},{"field_id":1114,"order_no":2,"bullet":"Health Canada will publish a Health Product InfoWatch article to help raise awareness of this drug interaction among healthcare professionals and consumers."},{"field_id":1114,"order_no":3,"bullet":"Health Canada continues to monitor the safety of non-prescription phenylephrine and acetaminophen combination products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00142","review_date":null,"drug_name":"Keppra (levetiracetam) and generics","safety_issue":"Acute kidney injury (acute renal failure/interstitial nephritis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1165,"overview":"Health Canada reviewed the potential risk of acute kidney injury with the use of levetiracetam, because of an article that was published by the WHO suggesting this risk. Health Canada assessed the risk of acute kidney injury, which is defined as a sudden loss of kidney function, including kidney failure and interstitial nephritis. Interstitial nephritis is the inflammation of the kidneys and is one of the conditions that may lead to kidney failure.
","use_canada":1166,"findings":1167,"conclusion":1168,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - KEPPRA (levetiracetam) - Assessing the Potential Risk of Acute Kidney Injury (Acute renal failure/Interstitial nephritis)","created_date":"2017-01-06","modified_date":null,"key_message_list":[{"field_id":1165,"order_no":1,"bullet":"Levetiracetam is authorized for sale in Canada, to help reduce the number of seizures when taken together with other seizure medicines. "},{"field_id":1165,"order_no":2,"bullet":"Health Canada reviewed the potential risk of acute kidney injury with the use of levetiracetam, because of an article that was published by the World Health Organization (WHO) suggesting this risk. "},{"field_id":1165,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of levetiracetam and the risk of acute kidney injury. The current product information for Keppra informs that cases of acute kidney injury have been reported in patients treated with levetiracetam. Health Canada has requested that the other manufacturers of levetiracetam-containing products also update their product information with the same wording."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1166,"order_no":1,"bullet":"Levetiracetam is a prescription drug authorized for sale in Canada, to help reduce the number of seizures when taken together with other seizure medicines."},{"field_id":1166,"order_no":2,"bullet":"Levetiracetam is available in Canada as oral tablets. It has been marketed under the brand name Keppra since 2003. Generic products are also available."},{"field_id":1166,"order_no":3,"bullet":"There were about 583 000 prescriptions of levetiracetam-containing products filled in 2015."}],"finding_list":[{"field_id":1167,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of acute kidney injury related to levetiracetam use."},{"field_id":1167,"order_no":2,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database (Vigibase) found more than 150 international reports of acute kidney injury with the use of levetiracetam. The WHO reviewed 39 of these 150 reports in depth and concluded that levetiracetam had possibly caused acute kidney injury."},{"field_id":1167,"order_no":3,"bullet":"In addition, there were 6 cases of acute kidney injury linked to the use of levetiracetam, published in the scientific literature. While the cases noted other factors such as pre-existing diseases, other medications taken at the same time, or other additional medical conditions, a link between the use of levetiracetam and acute kidney injury could not be ruled out."}],"conclusion_list":[{"field_id":1168,"order_no":1,"bullet":"Health Canada's review found a possible link between the use of levitiracetam and the risk of acute kidney injury."},{"field_id":1168,"order_no":2,"bullet":"The current product information for Keppra informs that cases of acute kidney injury have been reported in patients treated with levetiracetam. Health Canada has requested that the other manufacturers of levetiracetam-containing products also update their product information with the same wording."},{"field_id":1168,"order_no":3,"bullet":"Health Canada will continue to monitor side effects information involving levetiracetam, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00137","review_date":null,"drug_name":"Oral and injectable bisphosphonates (alendronate, clodronate, etidronate, pamidronate, risedronate and zoledronate)","safety_issue":"Jaw bone loss (osteonecrosis of the jaw)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1123,"overview":"Health Canada reviewed the potential risk factors that may play a role in osteonecrosis of the jaw (jaw bone loss) with bisphosphonate use in light of updates to the European product safety information for injectable bisphosphonates. Osteonecrosis of the jaw is a condition where bones of the jaw begin to weaken and die. There are many factors that may place a person at greater risk for jaw bone loss such as radiation therapy, use of certain medications, dental conditions and procedures, and other medical conditions (diabetes, low red blood cells count, and weakened immune systems). The risk of jaw bone loss with the use of bisphosphonates is well-known and described in the Canadian product safety information.
","use_canada":1124,"findings":1125,"conclusion":1126,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Bisphosphonates - Assessing the Risk of Jaw Bone Loss (osteonecrosis of the jaw)","created_date":"2016-11-25","modified_date":null,"key_message_list":[{"field_id":1123,"order_no":1,"bullet":"Bisphosphonates are prescription drugs used to strengthen bones and to treat a variety of bone-related diseases. "},{"field_id":1123,"order_no":2,"bullet":"Health Canada's safety review of bisphosphonate use and the known risk of jaw bone loss was triggered by the European Medical Agency's (EMA) review of a side effect report where zoledronate was used. "},{"field_id":1123,"order_no":3,"bullet":"Health Canada's review confirmed the known risk of jaw bone loss with bisphosphonate product use, and further concluded that this risk is higher with intravenous bisphosphonate products, especially in cancer patients. "},{"field_id":1123,"order_no":4,"bullet":"Health Canada is working with manufacturers to update safety information of the intravenous bisphosphonates products to reflect this risk, and to mention the additional factors that may play a role in jaw bone loss for all bisphosphonate products."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1124,"order_no":1,"bullet":"Bisphosphonates are used to strengthen bones in a variety of bone-related diseases such as:Health Canada carried out this safety review after becoming aware of reports of HBV reactivation in patients infected with both HBV and HCV treated with DAAs. Reactivation refers to the return of an active infection and, in the case of HBV, it can lead to serious complications such as liver disease (hepatitis).
","use_canada":1132,"findings":1133,"conclusion":1134,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Direct-acting antivirals - Assessing the Potential Risk of Hepatitis B Virus Reactivation","created_date":"2016-12-01","modified_date":null,"key_message_list":[{"field_id":1131,"order_no":1,"bullet":"Direct-acting antivirals (DAAs) are drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection, a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) and liver cancer. "},{"field_id":1131,"order_no":2,"bullet":"Health Canada carried out a review of the potential risk of hepatitis B virus (HBV) reactivation with the use of DAAs. The review was triggered by reports that patients infected with both HBV and HCV may experience a reactivation of their HBV infection if DAAs are used to treat their HCV infection. These reports were identified by the European Medicines Agency (EMA)."},{"field_id":1131,"order_no":3,"bullet":"Health Canada's review concluded that there is a potential risk of HBV reactivation in patients co-infected with both HBV and HCV, and the use of DAAs. Health Canada has recommended that the safety information for all DAAs be updated to inform about this potential risk. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1132,"order_no":1,"bullet":"DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection in adult patients."},{"field_id":1132,"order_no":2,"bullet":"This review included the following products available in Canada and they contain either a single DAA or multiple DAAs together: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Holkira Pak (dasabuvir, paritaprevir, ombitasvir, ritonavir), Technivie (paritaprevir, ombitasvir, ritonavir), Galexos (simeprevir), Sunvepra (asunaprevir), and Zepatier (grazoprevir, elbasvir)."},{"field_id":1132,"order_no":3,"bullet":"The first DAA available in Canada was Galexos (simeprevir), introduced in 2013."}],"finding_list":[{"field_id":1133,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of HBV reactivation related to DAA use in patients infected with both HBV and HCV."},{"field_id":1133,"order_no":2,"bullet":"A total of 13 international reports of HBV reactivation were retrieved from different sources. Of these, 12 reports were considered to be possibly related to the use of these DAAs: 11 reports where sofosbuvir or sofosbuvir with ledipasvir was used and one report where daclatasvir was used. The remaining report (with sofosbuvir use) could not be reviewed further because it did not provide enough information. Of the reports, 3 described symptoms of moderate HBV reactivation. One of the cases reported severe HBV reactivation resulting in liver failure and the patient needed a liver transplant."},{"field_id":1133,"order_no":3,"bullet":"Potential processes have been proposed in the scientific literature to explain how HBV infection could become reactivated in patients that are being treated for their HCV infection."},{"field_id":1133,"order_no":4,"bullet":"Two studies of the use of DAAs in patients infected with both HCV and HBV reported an increase in viral genes (HBV DNA) in some of the patients. This could lead to a reactivation of the HBV infection."}],"conclusion_list":[{"field_id":1134,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the risk of HBV reactivation in patients infected with both HBV and HCV that have been treated with certain DAAs."},{"field_id":1134,"order_no":2,"bullet":"Health Canada has recommended that the safety information for all DAAs be updated to inform about this risk, as a precaution. In addition, an Information Update will be published to further inform Canadians and health care professionals."},{"field_id":1134,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving DAAs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00140","review_date":null,"drug_name":"Tumour necrosis factor (TNF) alpha blockers (Simponi and Cimzia)","safety_issue":"Inflammation of the liver (Autoimmune Hepatitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1147,"overview":"Health Canada reviewed the link between TNF alpha blockers and liver inflammation following publication of 2 serious cases in the scientific literature, in which patients were treated with the TNF alpha blockers, Humira and Remicade. The Canadian product information for Humira, Remicade and Enbrel already stated liver inflammation as a very rare event that may lead to liver failure, but not for Simponi and Cimzia. Therefore, Health Canada assessed the risk of liver inflammation associated with use of all TNF alpha blockers using information provided by the manufacturer, cases published in scientific literature and cases of liver inflammation reported to the Canada Vigilance Database.
","use_canada":1148,"findings":1149,"conclusion":1150,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Tumour Necrosis Factor (TNF) alpha blockers (SIMPONI and CIMZIA) - Assessing the Potential Risk of Liver Inflammation (Autoimmune Hepatitis)","created_date":"2016-10-25","modified_date":null,"key_message_list":[{"field_id":1147,"order_no":1,"bullet":"Tumour Necrosis Factor (TNF) alpha blockers are a class of drugs used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) and psoriasis."},{"field_id":1147,"order_no":2,"bullet":"Health Canada reviewed the risk of liver inflammation after 2 cases of serious liver inflammation linked with treatments using TNF alpha blockers were reported in a scientific publication. Health Canada's review concluded that there may be a link between liver inflammation and treatment with TNF alpha blockers."},{"field_id":1147,"order_no":3,"bullet":"The Canadian product information for Simponi and Cimzia has been updated to better reflect the available evidence regarding the risk of inflammation of the liver. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1148,"order_no":1,"bullet":"TNF alpha blockers are immune system proteins (monoclonal antibodies) that block a specific protein (TNF alpha), resulting in a decrease of inflammation."},{"field_id":1148,"order_no":2,"bullet":"At the time of this review, five TNF alpha blockers were marketed in Canada:A safety review was completed to look into a potential link between Gilenya (fingolimod) and abnormal tissue growth (cancer). When a cancer forms a mass, it can commonly be referred to as a tumor. Tumors can be further divided into those that are cancerous (malignant) and those that are non-cancerous (benign).
This follow-up safety review assessed the data provided by the manufacturer in response to Health Canada’s request following the first safety review conducted in 2014.
","use_canada":1156,"findings":1157,"conclusion":1158,"additional":"There have been a Summary Safety Reviewa and 2 risk communications related to skin cancer issued by Health Canada: an Information Updateb and an Info Watch article in the Health product Infowatchc.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1159,"footnotes":0,"title":"Summary Safety Review - GILENYA (fingolimod) - Assessing the Risk of the Abnormal Tissue Growth (Cancer)","created_date":"2016-10-19","modified_date":null,"key_message_list":[{"field_id":1155,"order_no":1,"bullet":"Gilenya (fingolimod) is used to treat multiple sclerosis, a condition that leads to the damage of the nervous system, causing physical disability. It is specifically used in patients who have had a poor response to, or are unable to tolerate one or more other therapies for multiple sclerosis."},{"field_id":1155,"order_no":2,"bullet":"Health Canada first carried out a safety review in 2014, to assess the risk of abnormal tissue growth, and requested more information from the manufacturer. This review is a follow-up assessment of the data provided by the manufacturer. "},{"field_id":1155,"order_no":3,"bullet":"The current review concluded that the current product labelling appropriately describes the risks linked with the use of Gilenya and that Health Canada should continue to conduct annual assessments of abnormal tissue growth (cancer), particularly those related to skin as associated with Gilenya (fingolimod)."}],"footnotes_list":[],"reference_list":[{"field_id":1159,"order_no":1,"bullet":""},{"field_id":1159,"order_no":2,"bullet":""},{"field_id":1159,"order_no":3,"bullet":"Health Product InfoWatch - October 2015
"}],"use_canada_list":[{"field_id":1156,"order_no":1,"bullet":"Gilenya is a medicine used to treat multiple sclerosis to reduce the frequency of signs and symptoms of multiple sclerosis and delay the progression of physical disability."},{"field_id":1156,"order_no":2,"bullet":"Gilenya is recommended in patients who have had a poor response to, or are unable to tolerate one or more other therapies for multiple sclerosis."},{"field_id":1156,"order_no":3,"bullet":"Gilenya was first marketed in Canada in March 2011."}],"finding_list":[{"field_id":1157,"order_no":1,"bullet":"The updated data reviewed indicated that there has been some additional cases of skin cancer reported but at this point the frequency does not appear to be increased. This has been previously observed and included in the product label."},{"field_id":1157,"order_no":2,"bullet":"Patients receiving medicines that suppress the immune system, like Gilenya, are known to have increased risk for the development of abnormal tissue growth (cancer). Product information for these drugs typically mentions this risk."},{"field_id":1157,"order_no":3,"bullet":"Product information for Gilenya includes information about the risk of cancer, especially skin cancers. It also recommends to check for suspicious skin lesions before starting treatment and regularly during treatment with Gilenya, and to promptly evaluate any such lesions. This information can be found in the Warnings and Precautions, Adverse Reactions and Consumer Information sections of the product information for Gilenya."}],"conclusion_list":[{"field_id":1158,"order_no":1,"bullet":"Health Canada's current safety review concluded that the previous actions including labelling changes and annual assessments of information pertaining to abnormal tissue growth (cancer) associated with the use of Gilenya remains appropriate given the information reviewed."},{"field_id":1158,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving Gilenya, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00143","review_date":null,"drug_name":"Oral retinoid products (isotretinoin, tretinoin, alitretinoin and acitretin)","safety_issue":"Impotence (erectile dysfunction)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1173,"overview":"Health Canada reviewed the potential risk of impotence (erectile dysfunction) with the use of oral retinoids because of a publication from the Netherlands that linked isotretinoin use with this side effect.1 Health Canada also reviewed the related evidence regarding all oral retinoids available in Canada. Impotence is when a man cannot achieve or maintain an erect penis for sexual activity.
","use_canada":1174,"findings":1175,"conclusion":1176,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1177,"footnotes":1178,"title":"Summary Safety Review - Oral Retinoid Products - Assessing the Potential Risk of Impotence (erectile dysfunction)","created_date":"2017-01-10","modified_date":null,"key_message_list":[{"field_id":1173,"order_no":1,"bullet":"Oral retinoids are a group of prescription drugs authorized for sale in Canada to treat various skin conditions like severe acne, chronic eczema and psoriasis. Tretinoin is also used to treat a type of blood cancer. "},{"field_id":1173,"order_no":2,"bullet":"Health Canada reviewed the potential risk of impotence because of an article in the scientific literature suggesting that treatment with isotretinoin can cause this side effect. "},{"field_id":1173,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of oral isotretinoin products and the risk of impotence, but could not draw the same conclusion for the other drugs in the class. Health Canada recommended that the product information for all isotretinoin products be made consistent by listing impotence as a side effect."}],"footnotes_list":[{"field_id":1178,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1177,"order_no":1,"bullet":"Netherlands Pharmacovigilance Centre Lareb report. Isotretinoin and erectile dysfunction (May 15, 2015)."}],"use_canada_list":[{"field_id":1174,"order_no":1,"bullet":"Oral retinoids (in capsules taken by mouth) are prescription drugs authorized for sale in Canada to treat various skin conditions like severe acne, chronic eczema and psoriasis. Tretinoin is also authorized for sale in Canada to treat a type of cancer of the blood (acute promyelocytic leukemia)."},{"field_id":1174,"order_no":2,"bullet":"At the time of the review, there were 3 oral isotretinoin-containing products marketed in Canada: Accutane, Clarus, Epuris. The other oral retinoid products include Toctino (alitretinoin), Vesanoid (tretinoin) and Soriatane (acitretin). Oral retinoid products first entered the Canadian market in 1983."},{"field_id":1174,"order_no":3,"bullet":"In 2015 there were over 300 000 prescriptions (new and refills) for oral retinoids in Canada. The most commonly prescribed was isotretinoin with approximately 265 000 prescriptions."}],"finding_list":[{"field_id":1175,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 9 unique Canadian reportsa of impotence with oral isotretinoin use. There were no relevant Canadian reports for the other oral retinoid products. There were no instances that showed with certainty that the use of isotretinoin caused impotence because there were other factors that may have played a role, such as depression."},{"field_id":1175,"order_no":2,"bullet":"The review found 215 international reports of erectile dysfunction where retinoids were used. There were also published cases of oral isotretinoin use leading to impotence."},{"field_id":1175,"order_no":3,"bullet":"A review of the scientific literature showed that there were several animal studies which reported that retinoids may have an effect on the male sex organs (testes). One theory proposed in the scientific literature is that retinoids may have an effect on testes leading to a decrease in testosterone and a decrease in sexual function."},{"field_id":1175,"order_no":4,"bullet":"At the time of the review, erectile dysfunction was specifically mentioned in the product information for Epuris (isotretinoin) and Soriatane (acitretin)."},{"field_id":1175,"order_no":5,"bullet":"All oral retinoids mention depression as a side effect in their product information. Depression may contribute to impotence."}],"conclusion_list":[{"field_id":1176,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of oral isotretinoin products and the risk of impotence, but could not draw the same conclusion for the other drugs in the class."},{"field_id":1176,"order_no":2,"bullet":"Health Canada recommended that the product information for all isotretinoin products be made consistent to include this risk by adding erectile dysfunction as a side effect in the product information for Accutane and Clarus, as it already appears in the product information for Epuris."},{"field_id":1176,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving oral retinoid products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00144","review_date":null,"drug_name":"Selective serotonin reuptake inhibitors (SSRIs)","safety_issue":"Autism spectrum disorders (autism)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1184,"overview":"Health Canada reviewed this issue because a published study found a link between SSRI exposure during pregnancy and an increased risk of autism in children. Autism is a developmental disability with lifelong impact. It affects a child's ability to communicate and interact with others.
","use_canada":1185,"findings":1186,"conclusion":1187,"additional":"The analysis that contributed to this safety review included scientific and medical literature, guidelines for managing mental illness during pregnancy, and what is known about the use of SSRIs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1188,"title":"Summary Safety Review - Selective Serotonin Reuptake Inhibitors (SSRIs) - Assessing the Potential Risk of Autism","created_date":"2017-01-06","modified_date":null,"key_message_list":[{"field_id":1184,"order_no":1,"bullet":"Selective Serotonin Reuptake Inhibitors (SSRIs) are prescription drugs authorized for sale in Canada to treat depression. Some are also authorized to treat anxiety disorders."},{"field_id":1184,"order_no":2,"bullet":"Health Canada reviewed the risk of autism in children whose mothers used SSRIs during pregnancy, because of a published study on this topic. "},{"field_id":1184,"order_no":3,"bullet":"While some studies have found associations (links) between SSRI use during pregnancy and development of autism in children, others have not. Overall, Health Canada's review found that the available evidence is not strong enough to conclude that SSRI use during pregnancy can cause autism in exposed children."}],"footnotes_list":[{"field_id":1188,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1185,"order_no":1,"bullet":"SSRIs are prescription drugs authorized for sale in Canada to treat depression. Some are also authorized to treat anxiety disorders."},{"field_id":1185,"order_no":2,"bullet":"SSRIs have been marketed in Canada for many years under the brand names Celexa (citalopram), Cipralex (escitalopram), Prozac (fluoxetine), Luvox (fluvoxamine), Paxil (paroxetine) and Zoloft (sertraline). Generic versions of all of these drugs are also available."},{"field_id":1185,"order_no":3,"bullet":"During 2011, approximately 16 million SSRI prescriptions were filled in Canada. Available prescription data do not show how many SSRI prescriptions were filled by pregnant women."},{"field_id":1185,"order_no":4,"bullet":"The Canadian product information for SSRIs recommends that they only be used in pregnancy if the potential benefit to the mother outweighs the potential risk to the unborn baby."}],"finding_list":[{"field_id":1186,"order_no":1,"bullet":"The literature review showed that the causes of autism are not yet well understood. Both genetics (inherited traits) and the environment that a person is exposed to in their daily life may be involved. While animal and human studies suggest that the chemical made in the body known as serotonin is important in brain development, it is hard to predict the effects of SSRI exposure on autism risk."},{"field_id":1186,"order_no":2,"bullet":"Health Canada reviewed 11 studies that looked at the potential link between SSRI use during pregnancy and the development of autism in exposed children. Some studies found a link while others did not. It was difficult to draw conclusions from these studies. For example, it was difficult to separate the effects of mothers' mental illness from the effects of medications used to treat them. In other words, the links seen in certain studies may not be due to a direct effect of using SSRIs."},{"field_id":1186,"order_no":3,"bullet":"At the time of the review, Health Canada had received 2 Canadian reports of autism in children after SSRI use during pregnancy.a Since the causes of autism are not well understood and since there are many factors that may add to the overall risk, it was not possible to determine the role of SSRIs in the individual cases."}],"conclusion_list":[{"field_id":1187,"order_no":1,"bullet":"Health Canada's review found that the available evidence is not strong enough to conclude that SSRI use during pregnancy can cause autism in exposed children."},{"field_id":1187,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving SSRIs, as it does for all health products on the Canadian market, in order to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00145","review_date":null,"drug_name":"Amiodarone (intravenous)","safety_issue":"Side effects in fetuses and newborns","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1194,"overview":"Health Canada reviewed the potential risk of side effects in fetuses and newborns with intravenous amiodarone, because of a product label update in the United States which included warnings about the potential for effects on the heart, nervous system, development and growth of fetuses and newborns. Health Canada reviewed the available evidence regarding side effects on the heart, hypothyroidism (less than normal levels of thyroid hormone) in newborns and developmental delays occurring in fetuses and newborns exposed to amiodarone.
","use_canada":1195,"findings":1196,"conclusion":1197,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1198,"footnotes":1199,"title":"Summary Safety Review - Amiodarone (intravenous) - Assessing the potential risk of side effects in fetuses and newborns","created_date":"2017-01-06","modified_date":null,"key_message_list":[{"field_id":1194,"order_no":1,"bullet":"Amiodarone is a prescription drug authorized for sale in Canada to treat life-threatening abnormal heart rhythms (arrhythmias) in adults. Health Canada is aware that amiodarone is prescribed by some doctors during pregnancy, to treat the mother or fetus, or to treat newborns."},{"field_id":1194,"order_no":2,"bullet":"Health Canada reviewed the risk of side effects in fetuses and newborns exposed to intravenous amiodarone, because of a product information update in the United States."},{"field_id":1194,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between amiodarone use during pregnancy or in newborns and the risk of side effects on the heart. Health Canada has requested that manufacturers update the product information for intravenous amiodarone products to inform healthcare professionals about this risk."}],"footnotes_list":[{"field_id":1199,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1198,"order_no":1,"bullet":"Saul JP, et al. Intravenous amiodarone for incessant tachyarrhythmia in children. A randomized, double-blind, antiarrhythmic drug trial. Circulation 2005;112:3470-3477."}],"use_canada_list":[{"field_id":1195,"order_no":1,"bullet":"Amiodarone is a prescription drug authorized for sale in Canada to treat life-threatening abnormal heart rhythms (arrhythmias) in adults."},{"field_id":1195,"order_no":2,"bullet":"Amiodarone is available as an oral medication or as an intravenous injection. Intravenous amiodarone has been marketed in Canada since 2000. These products are available by prescription only."},{"field_id":1195,"order_no":3,"bullet":"Health Canada is aware that amiodarone is prescribed by some doctors for the treatment of life-threatening arrhythmias in fetuses and newborns when other medications have not worked."},{"field_id":1195,"order_no":4,"bullet":"Use of amiodarone to treat pregnant women is uncommon and its use is considered only if the potential benefit to the mother outweighs the risk to the fetus."}],"finding_list":[{"field_id":1196,"order_no":1,"bullet":"At the time of the review, Health Canada received 3 Canadian reportsa and retrieved 12 additional reports from published literature about serious side effects on the heart including potentially fatal heart attacks in newborns who received amiodarone for life-threatening abnormal heart rhythms. In 13 of the 15 reports reviewed it was determined that amiodarone may have played a role in the side effects."},{"field_id":1196,"order_no":2,"bullet":"A published study of amiodarone use in children1 suggested that the risk of low blood pressure (hypotension), slow heartbeat (bradycardia) and problems with the electrical activity of the heart (atrioventricular block) may be greater than in adults exposed to amiodarone."},{"field_id":1196,"order_no":3,"bullet":"Having less than normal levels of thyroid hormone (hypothyroidism) can be caused by amiodarone exposure in utero and is a known cause of developmental delays (such as in learning, speech and movement) if untreated. However, some children have had developmental delays following amiodarone exposure despite having normal levels of thyroid hormone."},{"field_id":1196,"order_no":4,"bullet":"Abnormal heart rhythm is a risk factor for heart attack, death, developmental delays, premature birth, even in the absence of amiodarone."}],"conclusion_list":[{"field_id":1197,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the use of amiodarone during pregnancy and the risk of developmental delays in newborns but did find a possible link to side effects on the heart."},{"field_id":1197,"order_no":2,"bullet":"Health Canada requested that the manufacturers update the product information for intravenous amiodarone products with regard to heart risks in newborns. Although this information is already included regarding adult patients, it is important that health care professionals recognize that there are potential risks when using this drug in newborns and infants."},{"field_id":1197,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving amiodarone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00146","review_date":null,"drug_name":"Low-molecular-weight heparins","safety_issue":"Spinal/epidural hematoma","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1206,"overview":"Health Canada reviewed information related to the known, rare risk of bleeding in or around the spinal cord (spinal/epidural hematoma) in patients receiving LMWH to prevent blood clots while undergoing spinal/epidural anaesthesia or spinal puncture. The review was initiated because of an update to the United States product safety information for LMWH related to this risk.
","use_canada":1207,"findings":1208,"conclusion":1209,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1210,"title":"Summary Safety Review - Low-Molecular-Weight Heparins - Assessing the potential risk of bleeding in or around the spinal cord (Spinal/Epidural Hematoma)","created_date":"2017-02-08","modified_date":null,"key_message_list":[{"field_id":1206,"order_no":1,"bullet":"Low-molecular-weight heparins (LMWH) are prescription drugs which are authorized for sale in Canada to treat or prevent blood clots. "},{"field_id":1206,"order_no":2,"bullet":"Health Canada reviewed information related to the known, rare risk of bleeding in or around the spinal cord (spinal/epidural hematoma) in patients receiving LMWH to prevent blood clots while undergoing spinal/epidural anaesthesia or spinal puncture. The review was initiated because of an update by the United States Food and Drug Administration (FDA) to the safety information for LMWH related to this risk."},{"field_id":1206,"order_no":3,"bullet":"Health Canada's review concluded that the risk of bleeding may increase if the spinal procedure is carried out soon after injection of LWMH. Health Canada requested that the manufacturers of LMWH update the Canadian safety information to include information on the recommended length of time between LMWH injection and spinal/epidural anaesthesia or spinal puncture. This length of time can vary, but should be determined by the prescriber in accordance with recommendations in the Canadian safety information."}],"footnotes_list":[{"field_id":1210,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1207,"order_no":1,"bullet":"LMWH are prescription drugs which are authorized for sale in Canada to treat or prevent blood clots."},{"field_id":1207,"order_no":2,"bullet":"LMWH have been marketed in Canada since 1993 and are currently sold under the brand names Fragmin, Fraxiparine/Fraxiparine Forte, Innohep and Lovenox/Lovenox HP. LMWH products are available for intravenous and/or subcutaneous injection."}],"finding_list":[{"field_id":1208,"order_no":1,"bullet":"At the time of the review, Health Canada had received 2 Canadian casesa of bleeding in or around the spinal cord in patients receiving LMWH and undergoing spinal/epidural anaesthesia or spinal puncture. In these 2 reports, there was not enough information to determine what may have played a role in the bleeding that occurred."},{"field_id":1208,"order_no":2,"bullet":"This safety review looked at 153 international reports of bleeding in or around the spinal cord in patients receiving LMWH while undergoing spinal/epidural anaesthesia or spinal puncture. In these 153 reports, it was found that a short length of time between LWMH use and the spinal procedure may have increased the risk of bleeding."}],"conclusion_list":[{"field_id":1209,"order_no":1,"bullet":"Health Canada's review concluded that the risk of bleeding may increase if the spinal procedure is carried out soon after injection of LWMH."},{"field_id":1209,"order_no":2,"bullet":"Health Canada requested that the manufacturers of LMWH update the Canadian safety information to include information on the recommended length of time between LMWH injection and spinal/epidural anaesthesia or spinal puncture. This length of time can vary, but should be determined by the prescriber in accordance with recommendations in the Canadian safety information."},{"field_id":1209,"order_no":3,"bullet":"Health Canada will continue to monitor safety information for LMWH, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00147","review_date":null,"drug_name":"Over-the-counter topical pain relievers containing menthol, methyl salicylate or capsaicin","safety_issue":"Risk of serious skin burns","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1216,"overview":"In 2013, Health Canada carried out a safety review on the risk of rare but serious skin burns associated with the use of topical pain relievers containing menthol, methyl salicylate or capsaicin. Health Canada requested additional safety information from certain manufacturers of these products. This follow-up safety review assessed the information that was provided by these manufacturers, as well as additional information that Health Canada has gathered on this safety issue.
","use_canada":1217,"findings":1218,"conclusion":1219,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Over-the-Counter Topical Pain Relievers Containing Menthol, Methyl Salicylate or Capsaicin - Assessing the Risk of Serious Skin Burns","created_date":"2017-02-13","modified_date":null,"key_message_list":[{"field_id":1216,"order_no":1,"bullet":"Over-the-counter (OTC) topical pain relievers are authorized for sale in Canada to relieve pain in muscles or joints, when applied on the skin."},{"field_id":1216,"order_no":2,"bullet":"Health Canada first carried out a safety review in 2013 to assess the risk of rare but serious skin burns with the use of OTC topical pain relievers containing menthol, methyl salicylate or capsaicin. Its conclusion and action was to request additional safety information from certain manufacturers of select OTC topical pain relievers containing these ingredients. This review is a follow-up assessment on the safety issue and includes new data provided by the manufacturers."},{"field_id":1216,"order_no":3,"bullet":"Health Canada's current review of the available information has established a link between the use of topical pain relievers containing menthol and the risk of rare but serious skin burns; however, there was not enough information to draw the same conclusions for the products containing methyl salicylate or capsaicin alone. Health Canada is updating the labelling standard for OTC topical pain relievers containing menthol alone or in combination, to inform about this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1217,"order_no":1,"bullet":"OTC topical pain relievers are authorized for sale in Canada to relieve pain in muscles or joints, when applied on the skin. These products, which may contain menthol, methyl salicylate or capsaicin, either alone or in combination, relieve pain by slightly irritating the skin surface. This irritation reduces the feeling of pain in the underlying joints and muscles."},{"field_id":1217,"order_no":2,"bullet":"There are over 400 OTC topical pain relievers available for sale in Canada that contain menthol, methyl salicylate or capsaicin, either alone or in combination. These products are available in various forms including creams, gels, liquids, and patches."},{"field_id":1217,"order_no":3,"bullet":"Some of these products already include safety information related to the risk of rare but serious skin burns."}],"finding_list":[{"field_id":1218,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 29 unique Canadian reports of serious skin burns related to the use of OTC topical pain relievers containing menthol, methyl salicylate or capsaicin. The products were used as directed in 28 reports; in some reports, other factors may have played a role in the development of burns. In the remaining report, the product was not used as directed. Of these 29 reports, there were 7 reports involving products containing only menthol, 2 reports involving products containing only methyl salicylate, and 1 report involving a product containing only capsaicin. There were 19 reports involving products containing multiple ingredients, and most of these contained menthol and methyl salicylate together."},{"field_id":1218,"order_no":2,"bullet":"The review of the safety information provided by manufacturers identified over 100 additional international reports of serious burns linked to the use of topical pain relievers. The majority of these cases contained menthol, alone or in combination with methyl salicylate. There were no cases of serious burns linked to the use of topical muscle and joint pain relievers containing methyl salicylate or capsaicin alone."},{"field_id":1218,"order_no":3,"bullet":"In the medical literature, there is only one case of serious skin burns linked to the use of a topical pain reliever product containing menthol and methyl salicylate; however, the product was used inappropriately."}],"conclusion_list":[{"field_id":1219,"order_no":1,"bullet":"Health Canada's current review of the available information has established a link between the use of topical pain relievers containing menthol and the risk of rare but serious skin burns; however, there was not enough information to draw the same conclusions for the products containing methyl salicylate or capsaicin alone."},{"field_id":1219,"order_no":2,"bullet":"Health Canada is updating the labelling standard for all topical pain relievers containing menthol alone or in combination, to inform consumers about this potential risk, and that they should stop use of the product and get medical help right away if they experience severe skin reactions such as pain, swelling or blistering."},{"field_id":1219,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving topical pain relievers containing menthol, methyl salicylate or capsaicin, as it does for all health products on the Canadian market, to identify and assess possible harms. Health Canada will take appropriate and timely action, if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00148","review_date":null,"drug_name":"Bisphosphonates [Fosamax and Fosavance (alendronate); Clasteon and Bonefos (clodronate); Actonel, Actonel DR and Actonel Plus Calcium (risedronate); Didronel and Didrocal (etidronate)]","safety_issue":"Severe bone damage (osteonecrosis), beyond the area of the jawbone","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1224,"overview":"Health Canada reviewed the potential risk of severe bone damage (osteonecrosis) with bisphosphonate use because of product information updates in Europe that warn about the risk of severe bone damage in the outer part of the ear canal. Previously, Health Canada completed a safety review of the risk of severe jawbone damage associated with bisphosphonate use. Therefore, the current safety review focused on severe bone damage other than to the jawbone.
In Canada, the labels for some bisphosphonate-containing products already warn about the risk of severe bone damage of the outer ear canal and/or other areas of the body and include:
Therefore a safety review was carried out for the following products:
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1228,"title":"Summary Safety Review - Bisphosphonates - Assessing the Potential Risk of Severe Bone Damage (osteonecrosis)","created_date":"2017-02-21","modified_date":null,"key_message_list":[{"field_id":1224,"order_no":1,"bullet":"Bisphosphonates are prescription drugs that are authorized for sale in Canada to strengthen the bones and to treat a variety of bone-related diseases. They are known to be associated with a risk of severe jawbone damage (osteonecrosis of the jaw). "},{"field_id":1224,"order_no":2,"bullet":"Health Canada reviewed the risk of severe bone damage other than to the jaw from bisphosphonate use. This was due to product information updates in Europe that warn about the risk of bone damage in the outer part of the ear canal."},{"field_id":1224,"order_no":3,"bullet":"In Canada, the labels for some of the bisphosphonate-containing products already include warnings about the risk of bone damage in the outer ear canal and/or other bones of the body. The current review was to determine if such warning statements should apply for all bisphosphonate-containing products."},{"field_id":1224,"order_no":4,"bullet":"Health Canada's review of the available information did not establish a link between the use of these other bisphosphonates and the risk of severe bone damage (osteonecrosis) of the external ear canal or other parts of the body other than the jaw. Health Canada will continue to monitor the safety of bisphosphonates."}],"footnotes_list":[{"field_id":1228,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":1228,"order_no":2,"bullet":"These findings do not include reports of osteonecrosis of the jaw associated with bisphosphonate use as they were already addressed in a prior safety review."}],"reference_list":[],"use_canada_list":[{"field_id":1225,"order_no":1,"bullet":"Bisphosphonates are prescription drugs which are authorized for sale in Canada to treat bone-related diseases such as:The product information for tramadol warns of the risk of serious breathing problems when too much is taken. Health Canada's safety review on codeine (another opioid drug) to study the risk of serious breathing problems in children and adolescents triggered this review for tramadol. Tramadol is an opioid drug authorized in Canada for the treatment of moderate to moderately severe pain but is not recommended for use in patients under 18 years of age. However, Health Canada is aware that this drug is being used in children and adolescents (known as off-label use).
Some people convert tramadol into its active drug form more quickly and completely than others. The use of tramadol in these patients, called \"ultra-rapid metabolizers\", may lead to unexpectedly high levels of active drug, and increase the risk of serious breathing problems.
","use_canada":1235,"findings":1236,"conclusion":1237,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Tramadol-containing Products - Assessing the Potential Risk of Serious Breathing Problems (Respiratory Depression) in Children and Adolescents","created_date":"2017-02-22","modified_date":null,"key_message_list":[{"field_id":1234,"order_no":1,"bullet":"Tramadol is an opioid prescription drug authorized for sale in Canada to treat moderate to moderately severe pain in adults. "},{"field_id":1234,"order_no":2,"bullet":"After a safety review by Health Canada to further study codeine and the risk of serious breathing problems in children, it was decided that a similar review would be carried out for tramadol. "},{"field_id":1234,"order_no":3,"bullet":"There was also evidence to show that the way in which certain people metabolize this drug may increase the risk of serious breathing problems. Health Canada's safety review found limited information regarding serious breathing problems with the use of tramadol in children. "},{"field_id":1234,"order_no":4,"bullet":"The product information for tramadol-containing products has been updated to further manage the risk of serious breathing problems based on this evidence. A Health Product InfoWatch notice will give Canadians more details on this risk."},{"field_id":1234,"order_no":5,"bullet":"Health Canada reminds Canadians that tramadol is not recommended for use in patients under 18 years of age."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1235,"order_no":1,"bullet":"Tramadol is an opioid prescription drug authorized for sale in Canada to treat moderate to moderately severe pain in adults. It is not recommended for use in patients under 18 years of age because it has not been studied in this age group."},{"field_id":1235,"order_no":2,"bullet":"Tramadol has been marketed in Canada since 2005 and is available alone or together with acetaminophen. It is available by prescription only."}],"finding_list":[{"field_id":1236,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of serious breathing problems related to the use of tramadol in children and adolescents."},{"field_id":1236,"order_no":2,"bullet":"This safety review found 1 international report of respiratory depression in the published literature, linked to the use of tramadol in a 5-year old child. The child was an ultra-rapid metabolizer and this may have played a role."},{"field_id":1236,"order_no":3,"bullet":"Many studies suggest that differences in how the liver works could affect the risk of side effects experienced by patients using tramadol. These studies help confirm that ultra-rapid metabolizer patients may be more at risk of developing respiratory depression with the use of tramadol."}],"conclusion_list":[{"field_id":1237,"order_no":1,"bullet":"The product information for tramadol-containing products has been updated to further highlight the risk of serious breathing problems based on the evidence found in the safety review. This has included the addition of warnings that some patients treated with tramadol may be \"ultra-rapid metabolizers\" which can lead them to convert tramadol more quickly and completely than normal. This may result in an increased risk of serious breathing problems."},{"field_id":1237,"order_no":2,"bullet":"In addition, Health Canada will publish a Health Product InfoWatch notice to inform Canadians and healthcare professionals of label changes related to this risk."},{"field_id":1237,"order_no":3,"bullet":"Health Canada reminds Canadians that tramadol is not recommended for use in patients under 18 years of age."},{"field_id":1237,"order_no":4,"bullet":"Health Canada continues to monitor side effect information involving tramadol, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00150","review_date":null,"drug_name":"Colorectal stents used with Avastin (bevacizumab)","safety_issue":"Increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1242,"overview":"Health Canada carried out this safety review because of published studies1 that reported a potential increased risk of bowel rupture in patients that received a colorectal stent and bevacizumab treatment at the same time. Bowel rupture is when a break or hole is formed in the wall of the intestine. It is a serious medical event which may be fatal if not found and treated in time. In most cases a patient has to undergo surgery or an invasive procedure to repair the rupture. Bowel rupture is a known risk associated with the use of either colorectal stents or bevacizumab individually, and is also mentioned in the safety information for these products.
","use_canada":1243,"findings":1244,"conclusion":1245,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1246,"footnotes":1247,"title":"Summary Safety Review - Colorectal Stents Used with AVASTIN (bevacizumab) - Assessing the potential increased risk of bowel rupture (intestinal perforation)","created_date":"2017-02-22","modified_date":null,"key_message_list":[{"field_id":1242,"order_no":1,"bullet":"Colorectal stents are medical devices licensed for sale in Canada to treat parts of the bowel that may become unusually narrowed (intestinal strictures). Avastin (bevacizumab) is a prescription health product authorized for sale in Canada as part of the treatment of certain cancers including those in the bowel."},{"field_id":1242,"order_no":2,"bullet":"Health Canada reviewed the risk of bowel rupture from colorectal stents used with bevacizumab because of published studies that reported an increased risk of bowel rupture in patients that received both treatments at the same time."},{"field_id":1242,"order_no":3,"bullet":"Health Canada's review concluded that there is limited evidence suggesting an increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients. "},{"field_id":1242,"order_no":4,"bullet":"Health Canada will issue a Health Product InfoWatch article to raise awareness of this potential safety issue and will continue to monitor the safety of both colorectal stents and bevacizumab."}],"footnotes_list":[{"field_id":1247,"order_no":1,"bullet":"Incident reports as retrieved from the Health Canada Medical Device System."},{"field_id":1247,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1246,"order_no":1,"bullet":"van Halsema EE, van Hooft JE, Small AJ, et al. Perforation in colorectal stenting: a meta-analysis and a search for risk factors. Gastrointest Endosc. 2014; 79:970-982 e7."},{"field_id":1246,"order_no":2,"bullet":"Manes G, de Bellis M, Fuccio L, et al. Endoscopic palliation in patients with incurable malignant colorectal obstruction by means of self-expanding metal stent: analysis of results and predictors of outcomes in a large multicenter series. Arch Surg. 2011; 146:1157-1162."},{"field_id":1246,"order_no":3,"bullet":"Small AJ, Coelho-Prabhu N and Baron TH. Endoscopic placement of self-expandable metal stents for malignant colorectal obstruction: long-term outcomes and complication factors. Gastrointest Endosc. 2010; 71:560-572."},{"field_id":1246,"order_no":4,"bullet":"Imbulgoda A, MacLean A, Heine J, et al. Colorectal perforation with intraluminal stents and bevacizumab in advanced colorectal cancer: retrospective case series and literature review. Can J Surg.2015; 58:167-171."},{"field_id":1246,"order_no":5,"bullet":"van Hooft JE, van Halsema EE, Vanbiervliet G, et al. Self-expandable metal stents for obstructing colorectal and extracolorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline, Endoscopy 2014; 46(11): 990-1002."}],"use_canada_list":[{"field_id":1243,"order_no":1,"bullet":"Colorectal stents are part of a group of devices known as self-expandable metallic stents and are licensed for sale in Canada to treat intestinal strictures. A stent is put into the unusually narrow part of the bowel (the intestinal stricture) and it expands as a tube-shaped frame to keep the bowel passage opened."},{"field_id":1243,"order_no":2,"bullet":"Bevacizumab (marketed under the brand name Avastin) is a health product authorized for sale in Canada as part of the treatment, along with a specific type of chemotherapy, for certain cancers including those in the bowel. It is available as a solution for injection"}],"finding_list":[{"field_id":1244,"order_no":1,"bullet":"At the time of the review, Health Canada received 6 unique Canadian reportsa of bowel rupture related to the use of colorectal stents and 83 unique Canadian reportsb of bowel rupture related to the use of bevacizumab. Only three of these reports mentioned that the two products were used together."},{"field_id":1244,"order_no":2,"bullet":"A number of published studies1,2,3 including a recent Canadian study4 reported an increased risk of bowel rupture in patients treated with colorectal stents and bevacizumab-based chemotherapy, as compared to patients receiving colorectal stents and chemotherapy without bevacizumab for the treatment of bowel cancer. It was difficult to make conclusions about the extent of the increased risk because of other factors that could also have played a role in the bowel rupture, including the type of cancer itself and how much the cancer had grown or developed."},{"field_id":1244,"order_no":3,"bullet":"Bowel rupture can happen when colorectal stents and bevacizumab-based treatments are used together because the wall of the bowel can become weak from the treatment killing the cancer cells (tumors) that are growing in the bowel wall. Very small ruptures can form in a blocked or narrowed bowel. Bevacizumab works to slow down the growth of new blood vessels. This action may weaken the bowel wall and it could rupture from the expanded colorectal stent. Given this increased risk, some publications for healthcare professionals5 have indicated that treatment using colorectal stents along with bevacizumab should be carefully considered, and avoided if possible."}],"conclusion_list":[{"field_id":1245,"order_no":1,"bullet":"Health Canada's review concluded that there is limited evidence at this time suggesting an increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients."},{"field_id":1245,"order_no":2,"bullet":"Health Canada will issue a Health Product InfoWatch article to raise awareness of this potential safety issue. Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products."},{"field_id":1245,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving colorectal stents and bevacizumab, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00151","review_date":null,"drug_name":"Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin, Norfloxacin and Ofloxacin)","safety_issue":"Persistent (prolonged) and disabling side effects including tendonitis/tendinopathy (tendon inflammation or disorder), peripheral neuropathy (damage to or disorder affecting the nerves outside the spinal cord and brain) and central nervous system disorders (related to disorders of the brain).","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1254,"overview":"Health Canada started a safety review following a review done by the FDA on systemic (taken by mouth or by injection) fluoroquinolone drugs. The FDA review showed that there were persistent (lasting 30 days or longer after stopping use of fluoroquinolones) and disabling side effects linked to the use of fluoroquinolone products. The Health Canada safety review focussed on serious known side effects that included: tendonitis/tendinopathy (tendon inflammation), peripheral neuropathy (damage to or disorder affecting the nerves), worsening of myasthenia gravis (a chronic autoimmune disease), hypersensitivity and serious skin reactions, mental disorders, depression and suicide/self-injury, convulsions (seizure), cardiovascular disorders, phototoxicity (light sensitivity) and vision disorders.
","use_canada":1255,"findings":1256,"conclusion":1257,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1258,"title":"Summary Safety Review - Fluoroquinolones - Assessing the potential risk of persistent and disabling side effects","created_date":"2017-01-23","modified_date":null,"key_message_list":[{"field_id":1254,"order_no":1,"bullet":"Fluoroquinolones are antibacterial (antibiotics) prescription drugs which are authorized for sale in Canada to treat many types of bacterial infections including urinary tract and respiratory infections."},{"field_id":1254,"order_no":2,"bullet":"Health Canada carried out a review of the potential risk of persistent and disabling side effects linked to the use of fluoroquinolones. The review was triggered by a benefit and safety review done by the United States Food and Drug Administration (FDA) on systemic (taken by mouth or by injection) fluoroquinolone drugs."},{"field_id":1254,"order_no":3,"bullet":"Health Canada's review concluded that some of the known side effects (tendonitis/tendinopathy, peripheral neuropathy and central nervous system disorders) linked to the use of fluoroquinolones may be persistent and disablinga in rare cases. Health Canada is working with the manufacturers to update the safety information for all fluoroquinolones to inform about this potential risk."}],"footnotes_list":[{"field_id":1258,"order_no":1,"bullet":"Disability is defined as a significant, persistent, or permanent change, impairment, damage or disruption in [the] body's function/structure, physical activities or quality of life. A disability is considered to be persistent when it lasts for at least 30 days after discontinuation of fluoroquinolone treatment."},{"field_id":1258,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1255,"order_no":1,"bullet":"Fluoroquinolones (taken by mouth or by injection) are authorized for sale in Canada for the treatment of many types of bacterial infections, including urinary and respiratory tract infections."},{"field_id":1255,"order_no":2,"bullet":"Fluoroquinolones have been marketed in Canada since 1986. There are several oral and injectable fluoroquinolones available in Canada, as generics and brand names:Health Canada reviewed the risk of serious infections with Zydelig because of clinical trial reports of increased rates of serious infections (sometimes leading to death) amongst those treated with Zydelig, compared to those who were not.
In March 2016, Health Canada reported that clinical trials involving Zydelig, in Canada and internationally, were being stopped due to serious side effects. In May 2016, Health Canada reported that serious side effects seen in clinical trials included infections with Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV). These clinical trials were testing new uses of Zydelig: earlier treatment and different drug combinations than authorized by Health Canada.
","use_canada":1265,"findings":1266,"conclusion":1267,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
The most recent update of the Canadian product information includes recommendations to use antibiotics against PJP and watch for CMV infection during treatment with Zydelig. It is also recommended that patients being treated with Zydelig should stop treatment if they develop either PJP or CMV infections. Zydelig is not authorized for use in first-line chronic lymphocytic leukemia and early-line indolent non-Hodgkin lymphoma outside of a clinical trial.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Zydelig (idelalisib) - Assessing the potential risk of serious infections","created_date":"2017-03-03","modified_date":null,"key_message_list":[{"field_id":1264,"order_no":1,"bullet":"Zydelig is authorized for sale in Canada to treat 2 types of blood cancer: relapsed chronic lymphocytic leukemia, and follicular lymphoma in patients who have received at least two other types of treatment that no longer work for them. "},{"field_id":1264,"order_no":2,"bullet":"Health Canada reviewed the risk of serious infections with Zydelig because of clinical trial reports of an increased rate of serious infections (sometimes leading to death) amongst those treated with Zydelig, compared to patients who were not. These clinical trials were testing new uses of Zydelig: earlier treatment and different drug combinations than currently authorized by Health Canada. "},{"field_id":1264,"order_no":3,"bullet":"Health Canada's review of the available information concluded there was a risk of serious infections (sometimes leading to death) associated with Zydelig use. As such, the product information was updated to warn about the increased risk of infections."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1265,"order_no":1,"bullet":"Zydelig is a prescription drug authorized for sale in Canada to treat 2 types of blood cancers: relapsed chronic lymphocytic leukemia and follicular lymphoma. Zydelig belongs to a group of medicines called antineoplastic agents that acts by changing the growth of cancerous white blood cells, causing them to die. The drug is used together with rituximab (another anti-cancer drug) for the treatment of chronic lymphocytic leukemia, a type of blood cancer, in patients previously treated with other drugs. Zydelig is also used alone for the treatment of follicular lymphoma, a type of blood cancer, in patients who have received at least two other types of treatment that no longer work for them."},{"field_id":1265,"order_no":2,"bullet":"Idelalisib has been marketed in Canada since April 2015 under the brand name Zydelig. It is available as a tablet that is taken by mouth."}],"finding_list":[{"field_id":1266,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 23 Canadian reports of death associated with Zydelig use (6 from clinical trials and 17 from after being on the market). In these reports, there was 1 death reported with a PJP infection, and none with CMV infection. These reports did not provide strong evidence that Zydelig alone was the cause of death, since the disease itself or other patient risk factors may also be associated with these infections. These cases all occurred in patients with other risk factors for PJP."},{"field_id":1266,"order_no":2,"bullet":"A search of the scientific literature found cases describing serious infections in patients treated with Zydelig."},{"field_id":1266,"order_no":3,"bullet":"Patients with chronic lymphocytic leukemia and follicular lymphoma are at an increased risk of infections such as PJP and CMV due to the disease itself as well as possible complications linked with disease treatments."}],"conclusion_list":[{"field_id":1267,"order_no":1,"bullet":"Health Canada's review of the available information concluded there was a risk of serious infections, which may lead to death, associated with Zydelig use."},{"field_id":1267,"order_no":2,"bullet":"The Canadian product information was updated to warn about the increased risk of infections."},{"field_id":1267,"order_no":3,"bullet":"Health Canada has requested the manufacturer to provide any new information on this safety issue."},{"field_id":1267,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Zydelig, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00153","review_date":null,"drug_name":"Esophageal Stents","safety_issue":"Damage to the esophagus and nearby major blood vessels","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1272,"overview":"Health Canada reviewed the potential risk of damage to the esophagus and nearby major blood vessels after receiving a Canadian report in which an esophageal stent placed in a patient had worn through the esophagus and damaged the aorta (a large blood vessel connected to the heart), causing death.
","use_canada":1273,"findings":1274,"conclusion":1275,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Esophageal Stents - Assessing the potential risk of damage to the esophagus and nearby major blood vessels","created_date":"2017-03-29","modified_date":null,"key_message_list":[{"field_id":1272,"order_no":1,"bullet":"Esophageal stents are medical devices authorized for sale in Canada that help allow for the proper passage of food and drink through the esophagus (from the mouth to the stomach). They are metal or plastic hollow tubes that are placed inside the esophagus to widen areas that have become narrow due to cancer or scarring, or to seal off leaks in the esophagus."},{"field_id":1272,"order_no":2,"bullet":"Health Canada reviewed the potential risk of damage to the esophagus and nearby major blood vessels after receiving a Canadian report in which an esophageal stent placed in a patient had worn through the esophagus and damaged the aorta (a large blood vessel connected to the heart), causing death."},{"field_id":1272,"order_no":3,"bullet":"Health Canada's review of the available information has confirmed the potential risk of esophageal stents to damage the esophagus and nearby major blood vessels. Health Canada will work with device manufacturers to update the safety information for all esophageal stents to include details about this potential risk and potential factors that may increase this risk. "},{"field_id":1272,"order_no":4,"bullet":"In addition, Health Canada will issue an article in the Health Product InfoWatch to raise awareness of this safety issue and will continue to monitor the safety of esophageal stents."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1273,"order_no":1,"bullet":"Esophageal stents are medical devices authorized for sale in Canada to allow for proper passage of food and drink from the mouth to the stomach. They are hollow tubes placed inside the esophagus to widen areas that have become narrow because of cancer or scarring, or to seal off leaks in the esophagus."},{"field_id":1273,"order_no":2,"bullet":"Esophageal stents have been marketed in Canada since 1999. There are multiple esophageal stent systems currently sold in Canada by 5 different companies. They are made of metal or plastic."}],"finding_list":[{"field_id":1274,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 14 unique Canadian reports related to esophageal stents. Only 1 of these cases was related to damage (erosion) of the esophagus and damage (perforation) of a nearby blood vessel. In this report, a patient had a stent placed in their esophagus to seal off a leak. Just over two weeks later, the patient began coughing up large amounts of blood and later died. The autopsy showed that the stent had worn through the esophagus and perforated the aorta."},{"field_id":1274,"order_no":2,"bullet":"A review of the scientific and medical literature found 18 other cases of these stents damaging the esophagus and nearby major blood vessels. Out of these 18 reports, 11 were fatal. Most of the events occurred from 1 to 2 months after stent placement, but some events happened after the stent had been in place for about 12 to 18 months."},{"field_id":1274,"order_no":3,"bullet":"Factors that may increase the risk of damaging the esophagus and nearby major blood vessels include a history of radiation treatment or chemotherapy, recent chest or heart infection, patients with uncommon blood vessel location, and specific characteristics of the stent used."}],"conclusion_list":[{"field_id":1275,"order_no":1,"bullet":"Health Canada's review of the available information has confirmed the potential risk of esophageal stents to damage the esophagus and nearby major blood vessels."},{"field_id":1275,"order_no":2,"bullet":"The current safety information for esophageal stents does not specifically describe this risk. Therefore, Health Canada will work with device manufacturers to update the safety information for all esophageal stents to include details about this potential risk and potential factors that may increase this risk. In addition, Health Canada will issue an article in the Health Product InfoWatch to raise awareness of this safety issue."},{"field_id":1275,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving esophageal stents, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00154","review_date":null,"drug_name":"Avastin (bevacizumab)","safety_issue":"Damage in bones other than the jawbone (non-mandibular osteonecrosis) in adult cancer patients","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1280,"overview":"Health Canada reviewed the risk of damage in bones other than the jawbone (non-mandibular osteonecrosis) in adult cancer patients treated with Avastin (bevacizumab) following the publication of 2 reports1 in the literature of this side effect. Damage in the jawbone (mandibular osteonecrosis) is a known risk and is reflected in details on the Canadian product safety information for Avastin. Therefore, this safety review focused on non-mandibular osteonecrosis. This type of bone damage is serious because it causes severe pain and the affected bone can become deformed or can fracture.
","use_canada":1281,"findings":1282,"conclusion":1283,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this health product both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1284,"footnotes":1285,"title":"Summary Safety Review - Avastin (bevacizumab) - Assessing the Potential Risk of Damage in Bones other than the Jawbone in Adult Cancer Patients","created_date":"2017-04-05","modified_date":null,"key_message_list":[{"field_id":1280,"order_no":1,"bullet":"Avastin (bevacizumab) is a prescription health product authorized for sale in Canada, when used alone or with chemotherapy to treat certain types of cancer."},{"field_id":1280,"order_no":2,"bullet":"Health Canada reviewed the risk of damage in bones other than the jawbone (non-mandibular osteonecrosis) in adult cancer patients treated with Avastin (bevacizumab) following the publication of 2 reports1 of this side effect."},{"field_id":1280,"order_no":3,"bullet":"After reviewing the available data, it was determined that there was not enough information to establish a definitive link between the use of Avastin and the risk of non-mandibular osteonecrosis in adults. However, Health Canada has recommended that the manufacturer update the product safety information to include information on reports of non-mandibular osteonecrosis in adult cancer patients treated with Avastin."}],"footnotes_list":[{"field_id":1285,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1284,"order_no":1,"bullet":"Reactions Weekly Bevacizumab Osteonecrosis: 2 case reports October 2015, Volume 1573, Issue 1, pp 51-51"}],"use_canada_list":[{"field_id":1281,"order_no":1,"bullet":"Avastin is a prescription health product authorized for sale in Canada, to treat a certain type of brain cancer (glioblastoma), when used alone. It can also be used with chemotherapy to treat certain types of cancer of the large bowel, lung, female reproductive system and the lining of the abdominal cavity."},{"field_id":1281,"order_no":2,"bullet":"Avastin has been marketed in Canada since 2005. It is available as a solution for injection."}],"finding_list":[{"field_id":1282,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian reporta of non-mandibular osteonecrosis related to Avastin use. In that report, there was not enough information to conclude that Avastin use alone had caused this condition, although a link could not be ruled out."},{"field_id":1282,"order_no":2,"bullet":"This safety review also looked at information on 67 international reports of non-mandibular osteonecrosis related to the use of Avastin, including the 2 cases1 that triggered Health Canada's safety review. In 26 of these reports, a link between Avastin and non-mandibular osteonecrosis could not be definitively ruled out. In the remaining 41 reports, there was either not enough information to establish a link, or there were other factors that could have explained the condition such as other medical conditions of the bones or being on treatments that are known to cause bone damage."}],"conclusion_list":[{"field_id":1283,"order_no":1,"bullet":"After review of available data, it was determined that there was not enough information to establish a definitive link between the use of Avastin and non-mandibular osteonecrosis in adult cancer patients. However, Health Canada has recommended that the manufacturer update the product safety information to include information of the reports of non-mandibular osteonecrosis in adult cancer patients treated with Avastin. The current Canadian safety information only mentions this risk in children treated with Avastin, not in adults."},{"field_id":1283,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving Avastin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00155","review_date":null,"drug_name":"Hospital beds","safety_issue":"Patient entrapment","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1292,"overview":"Hospital beds are used in a wide range of locations, including hospitals, long-term care facilities, nursing homes and private residences.
Patient entrapment is when a patient or a resident becomes caught, trapped or entangled in the bed rails, mattress or frame. Health Canada has closely monitored the issue of patient entrapment in hospital beds for over 20 years and has taken actions to raise awareness of the risk. This included an article in 2015 and a notice to hospitals, nursing homes and long-term care facilities in 2012. Several incidents have been reported in Canada over the last years and Health Canada continues to monitor this risk.
","use_canada":1293,"findings":1294,"conclusion":1295,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of these devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Hospital Beds - Assessing the Potential Risk of Patient Entrapment","created_date":"2017-04-10","modified_date":null,"key_message_list":[{"field_id":1292,"order_no":1,"bullet":"Health Canada has closely monitored the issue of patient entrapment in hospital beds for over 20 years and has taken actions to raise awareness of the risk and to ensure safety of patients. "},{"field_id":1292,"order_no":2,"bullet":"Health Canada's recent review concluded that it is possible to improve the safety of hospital beds by increasing the awareness of the risk of patient entrapment. "},{"field_id":1292,"order_no":3,"bullet":"Health Canada will work with manufacturers to help ensure that hospital beds continue to meet safety standards. Health Canada will continue to monitor the issue of patient entrapment and will publish a Health Product Risk Communication to remind healthcare professionals about the importance of this issue and to outline identified risks for entrapment and specific mitigation measures."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1293,"order_no":1,"bullet":"Hospital beds are designed for hospitalized patients, long-term care facility or nursing home residents or for any individual receiving care."},{"field_id":1293,"order_no":2,"bullet":"Bed rails can be used to help a patient change positions and can reduce the risk of falling from the bed."}],"finding_list":[{"field_id":1294,"order_no":1,"bullet":"At the time of the review, Health Canada had received 44 reports of patient entrapment in hospital beds that occurred over the last three years (from July 2013 to June 2016):Health Canada reviewed the potential risk of hypothyroidism with the use of ICM because one of the manufacturers proposed to include this risk in the safety information for their product after updates were made to all product labels in the United States. There are concerns about hypothyroidism, especially in infants, as they may be more likely to experience this side effect and it can affect their development.
","use_canada":1301,"findings":1302,"conclusion":1303,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1304,"footnotes":0,"title":"Summary Safety Review - Iodinated Contrast Medium - Assessing the Potential Risk of Decreased Thyroid Hormone Production (Hypothyroidism)","created_date":"2017-04-24","modified_date":null,"key_message_list":[{"field_id":1300,"order_no":1,"bullet":"Iodinated contrast medium (ICM) products are medical imaging dyes authorized for sale in Canada for viewing the insides of different body parts."},{"field_id":1300,"order_no":2,"bullet":"Health Canada reviewed the potential risk of transient or permanent hypothyroidism with the use of ICM because one of the manufacturers proposed to include this risk in the safety information for their product. "},{"field_id":1300,"order_no":3,"bullet":"Health Canada's review concluded that there is a rare potential risk of hypothyroidism with the use of ICM in certain patients, mostly infants. Health Canada is working with the manufacturers to update the safety information for all ICM products to inform about this potential risk. "},{"field_id":1300,"order_no":4,"bullet":"A Health Product Risk Communication will be published to further inform healthcare professionals about this safety information and recommendations to monitor thyroid function following ICM use in infants."}],"footnotes_list":[],"reference_list":[{"field_id":1304,"order_no":1,"bullet":"Ahmet A., Lawson, M. L., Babyn, P. et al. Hypothyroidism in neonates post-iodinated contrast media: a systematic review. Acta Paediatr. 2009; 98:1568-1574."},{"field_id":1304,"order_no":2,"bullet":"l'Allemand, D., Gruters, A., Beyer, P. & Weber, B. Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care. Horm. Res. 1987; 28:42-49."},{"field_id":1304,"order_no":3,"bullet":"Barr, M. L. et al. Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media. J. Clin. Endocrinol. Metab. 2016; 101:2366-2370."},{"field_id":1304,"order_no":4,"bullet":"Van Vliet, G. Neonatal hypothyroidism: treatment and outcome. Thyroid 1999; 9:79-84."},{"field_id":1304,"order_no":5,"bullet":"Oerbeck, B., Sundet, K., Kase, B. F. & Heyerdahl, S. Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults. Pediatrics 2003; 112, 923-930."},{"field_id":1304,"order_no":6,"bullet":"Dimitropoulos, A. et al. Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment. Pediatr. Res. 2009; 65:242-248."}],"use_canada_list":[{"field_id":1301,"order_no":1,"bullet":"ICM products are medical imaging dyes authorized for sale in Canada for viewing the insides of various body parts."},{"field_id":1301,"order_no":2,"bullet":"The review included the following products available in Canada: Gastrografin, Ultravist, Sinografin, Isovue, Cholografin, Meglumine, Telebrix, Optiray, Conray, Visipaque and Omnipaque."},{"field_id":1301,"order_no":3,"bullet":"The first ICM marketed in Canada was Gastrografin, introduced in 1978."}],"finding_list":[{"field_id":1302,"order_no":1,"bullet":"At the time of review, Health Canada had not received any Canadian reports of ICM and hypothyroidism."},{"field_id":1302,"order_no":2,"bullet":"This safety review looked at 23 international side effect reports of hypothyroidism with the use of ICM. Of these, 10 were considered to be related to the use of ICM. Of these 10 reports, in 3 reports the patients recovered, in 2 reports the patients did not recover and in the remaining 5 reports there was no information provided on whether or not the patient had recovered. The remaining 13 reports did not contain enough information to determine if the ICM product played a role in the onset of hypothyroidism. While the reports represented patients from all age groups, 6 of the 10 reports related to ICM use involved infants (less than 1 year of age)."},{"field_id":1302,"order_no":3,"bullet":"The review also looked into the published scientific literature and found a link between ICM use and the potential risk of hypothyroidism.1, 2, 3 Most of the reports involved infants but adults also experienced this side effect. The scientific literature explains how ICM exposure might lead to hypothyroidism in sensitive populations (e.g. infants, the elderly and those with underlying thyroid disease). The iodine in the ICM may affect the production of thyroid hormone, which also contains iodine."},{"field_id":1302,"order_no":4,"bullet":"Studies have reported that untreated hypothyroidism following ICM injection in infants may result in life-long negative effects including severe delays in growth and development (including mental development).4, 5, 6"}],"conclusion_list":[{"field_id":1303,"order_no":1,"bullet":"Health Canada's review concluded that there is a rare potential risk of hypothyroidism with the use of ICM in certain patients, mostly infants."},{"field_id":1303,"order_no":2,"bullet":"Health Canada is working with the manufacturers to update the safety information for all ICM products to inform about this risk. In addition, a Health Product Risk Communication will be published to inform healthcare professionals about this safety information and recommendations to monitor thyroid function following ICM use in infants."},{"field_id":1303,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving ICM products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00157","review_date":null,"drug_name":"Direct-acting antivirals (DAAs)","safety_issue":"Liver cancer recurrence","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1310,"overview":"Health Canada reviewed the potential risk of liver cancer recurrence with the use of DAAs, following the publication of a study1 suggesting this potential risk.
","use_canada":1311,"findings":1312,"conclusion":1313,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these health products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1314,"footnotes":0,"title":"Summary Safety Review - Direct-Acting Antivirals - Assessing the Potential Risk of Liver Cancer Recurrence","created_date":"2017-04-27","modified_date":null,"key_message_list":[{"field_id":1310,"order_no":1,"bullet":"Direct-acting antivirals (DAAs) are prescription drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection in adult patients, which is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) or liver cancer."},{"field_id":1310,"order_no":2,"bullet":"Health Canada reviewed the potential risk of liver cancer coming back (recurrence) with the use of DAAs, following the publication of a study1 suggesting this potential risk. "},{"field_id":1310,"order_no":3,"bullet":"Health Canada's review concluded that there was not enough information to establish a link between DAAs and liver cancer recurrence. Health Canada has requested additional safety information from some manufacturers of DAAs."}],"footnotes_list":[],"reference_list":[{"field_id":1314,"order_no":1,"bullet":"Reig M, Marino Z, Perello C, Inarrairaegui M, Ribeiro A, Lens S, et al. Unexpected early tumor recurrence in patients with hepatitis C virus -related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol 2016."},{"field_id":1314,"order_no":2,"bullet":"Burak KW, Sherman M; Hepatocellular carcinoma: Consensus, controversies and future directions. A report from the Canadian Association for the Study of the Liver Hepatocellular Carcinoma Meeting, Can J Gastroenterol Hepatol; 2015 May;29(4):178-84."}],"use_canada_list":[{"field_id":1311,"order_no":1,"bullet":"DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection in adult patients, which is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) or liver cancer."},{"field_id":1311,"order_no":2,"bullet":"The review included the following products available in Canada which contain either a single DAA or multiple DAAs together: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Holkira Pak (dasabuvir, paritaprevir, ombitasvir, ritonavir), Technivie (paritaprevir, ombitasvir, ritonavir), Galexos (simeprevir), Sunvepra (asunaprevir), and Zepatier (grazoprevir, elbasvir)."},{"field_id":1311,"order_no":3,"bullet":"The first DAA available in Canada was Galexos (simeprevir), introduced in 2013."}],"finding_list":[{"field_id":1312,"order_no":1,"bullet":"At the time of the review, Health Canada had received 3 unique Canadian reports of liver cancer recurrence related to DAAs use (2 with Sovaldi and 1 with Holkira Pak). All 3 reports were considered to be related to the use of DAAs. However, other factors present in the cases may have played a role in the liver cancer recurrence, such as serious scarring of the liver (cirrhosis), previous history of liver cancer and other treatments known to be associated with a higher risk of liver cancer recurrence, including surgery and a cancer treatment using radio waves (radiofrequency ablation)."},{"field_id":1312,"order_no":2,"bullet":"This safety review also looked at information from 14 international reports of liver cancer recurrence related to DAAs use: 9 reports involved Sovaldi, 4 reports involved Harvoni and 1 report involved Holkira Pak. All 14 reports were considered to be related to DAAs use. However, factors known to be associated with a higher risk of liver cancer recurrence may have played a role."},{"field_id":1312,"order_no":3,"bullet":"A search of the scientific literature identified 7 relevant studies describing the recurrence of liver cancer related to DAA use. The safety review could not conclude whether the use of DAAs played a role because the lengths of time the patients were monitored were different between the studies. The patients also had a variety of risk factors for liver cancer, including HCV infection, cirrhosis, previous history of liver cancer and advanced age."},{"field_id":1312,"order_no":4,"bullet":"Some studies have found that liver cancer recurrence was more likely to happen in patients who underwent surgery or radiofrequency ablation compared to those patients that received a liver transplant2."}],"conclusion_list":[{"field_id":1313,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough information to establish a link between DAAs and liver cancer recurrence. Health Canada has also requested additional safety information from manufacturers of DAAs regarding this risk as it becomes available."},{"field_id":1313,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving DAAs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00158","review_date":null,"drug_name":"Dipeptidylpeptidase-4 (DPP-4) inhibitors","safety_issue":"Severe joint pain (arthralgia)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1320,"overview":"Health Canada reviewed the potential risk of severe joint pain (arthralgia) with the use of DPP-4 inhibitors because of side effect reports received by the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database and seen in the published literature.1, 2, 3","use_canada":1321,"findings":1322,"conclusion":1323,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1324,"footnotes":1325,"title":"Summary Safety Review - Dipeptidylpeptidase-4 (DPP-4) inhibitors - Assessing the risk of joint pain (arthralgia)","created_date":"2017-04-27","modified_date":null,"key_message_list":[{"field_id":1320,"order_no":1,"bullet":"DPP-4 inhibitors, also known as gliptins, are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults."},{"field_id":1320,"order_no":2,"bullet":"Health Canada reviewed the risk of developing severe joint pain with DPP-4 inhibitor use because of international reports from the United States and seen in the published literature regarding this side effect. "},{"field_id":1320,"order_no":3,"bullet":"Health Canada's review concluded there is a potential link between the use of DPP-4 inhibitors and the development of severe joint pain. Health Canada is working with manufacturers to update the product safety information for all DPP-4 inhibitors to communicate the risk of developing severe and disabling joint pain with the use of these drugs. "}],"footnotes_list":[{"field_id":1325,"order_no":1,"bullet":"The products Oseni, Glyxambi and Qtern were not yet marketed in Canada at the time of the safety review."},{"field_id":1325,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1324,"order_no":1,"bullet":"FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. August 28, 2015. Accessed February 28, 2017. http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm."},{"field_id":1324,"order_no":2,"bullet":"Tarapues M, Cereza G, and Figueras A. (2013), Association of musculoskeletal complaints and gliptin use: Review of spontaneous reports. Pharmacoepidemiol Drug Saf;22:1115-1118."},{"field_id":1324,"order_no":3,"bullet":"Mascolo A, Rafaniello C, Sportiello L, et al., (2016), Dipeptidyl peptidase (DPP)-4 inhibitor-induced Arthritis/Arthralgia: A review of clinical cases. Drug Saf 39(5): 401-407."}],"use_canada_list":[{"field_id":1321,"order_no":1,"bullet":"DPP-4 inhibitors are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults. They are used along with an appropriate diet and exercise to control blood sugar. In some cases, they are used with another anti-diabetic drug."},{"field_id":1321,"order_no":2,"bullet":"There are currently 11 products marketed in Canada that contain a DPP-4 inhibitor: Nesina (alogliptin), Kazano (alogliptin-metformin), Osenia (alogliptin-pioglitazone), Trajenta (linagliptin), Jentadueto (linagliptin-metformin), Glyxambia (linagliptin-empagliflozin), Onglyza (saxagliptin), Komboglyze (saxagliptin-metformin), Qterna (saxagliptin-dapagliflozin), Januvia (sitagliptin), and Janumet/Janumet XR (sitagliptin-metformin)."}],"finding_list":[{"field_id":1322,"order_no":1,"bullet":"At the time of the review, Health Canada received 10 Canadian reportsb of severe joint pain associated with the use of a DPP-4 inhibitor (saxagliptin, sitagliptin or linagliptin). Health Canada also received another 20 international reports from the manufacturers regarding severe joint pain with the use of any DPP-4 inhibitor."},{"field_id":1322,"order_no":2,"bullet":"The reports provided evidence that the use of DPP-4 inhibitors contributed to severe (disabling or incapacitating) joint pain. Of all the reports, 17 noted that the patient developed joint pain within the first 30 days of taking the DPP-4 inhibitor. The majority of patients either improved or recovered from their joint pain after the treatment was stopped."},{"field_id":1322,"order_no":3,"bullet":"Some of the cases have also reported medical conditions that may have contributed to the joint pain including gout, pre-existing rheumatoid arthritis, Crohn's disease and obesity."},{"field_id":1322,"order_no":4,"bullet":"This safety review also considered information from the United States Food and Drug Administration which included 33 reports of severe joint pain with the use of DPP-4 inhibitors. Two other publications have noted reports of joint pain with the use of these drugs. 1, 2, 3"},{"field_id":1322,"order_no":5,"bullet":"At the time of the review, the Canadian safety information for saxagliptin-containing products had a warning for the risk of severe and disabling joint pain. This warning was not included in the safety information of the other DPP-4 inhibitor-containing products marketed in Canada."}],"conclusion_list":[{"field_id":1323,"order_no":1,"bullet":"Health Canada's review of the available information concluded there is a potential link between the use of DPP-4 inhibitors and the development of severe joint pain."},{"field_id":1323,"order_no":2,"bullet":"Health Canada is working with manufacturers to update the product safety information for all DPP-4 inhibitors to inform healthcare professionals and patients about the risk of developing joint pain when DPP-4 inhibitors are used."},{"field_id":1323,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving DPP-4 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00159","review_date":null,"drug_name":"Infrared thermometers","safety_issue":"Inaccuracy in children under 2 years old","safetyissue_title":"Potential safety issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1332,"overview":"Health Canada reviewed the risk of IR thermometers being inaccurate when checking the temperature of children under 2 years old because of new information that became available. At the time of the review, IR thermometers were not recommended to be used in children under 2 years old. Note that there was not enough information gathered in this review for non-contact forehead thermometers, so the recommendations from this review apply to only contact forehead and ear IR thermometers.
","use_canada":1333,"findings":1334,"conclusion":1335,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Ear and Forehead (contact) Infrared Thermometers (various brands) - Assessing the potential risk of inaccuracy in children under 2 years old","created_date":"2017-05-03","modified_date":null,"key_message_list":[{"field_id":1332,"order_no":1,"bullet":"Infrared (IR) thermometers are widely available in drug stores across Canada. These products are often used at home to measure temperature in children."},{"field_id":1332,"order_no":2,"bullet":"Health Canada reviewed the risk of these thermometers giving inaccurate temperatures of children under 2 years old because of new information that became available. Previously, in 2009, Health Canada published a Notice stating that infrared thermometers should not be used in children under 2 years old."},{"field_id":1332,"order_no":3,"bullet":"Health Canada's review concluded that there is new information (literature and clinical guidance) to show that ear and forehead contact IR thermometers are appropriate for use in children under 2 years old. Health Canada will now consider requests from these manufacturers to recommend use in this age group on labels. However, information is still lacking for non-contact IR thermometers, so this type is not recommended for use in children under 2 years old."},{"field_id":1332,"order_no":4,"bullet":"Health Canada will continue to monitor scientific literature and clinical information about the accuracy of IR thermometers in children under 2 years old."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1333,"order_no":1,"bullet":"IR thermometers are used in the ear or on the forehead to measure a person's body temperature."},{"field_id":1333,"order_no":2,"bullet":"IR-sensing ear canal thermometers detect heat (IR energy) coming from the ear canal and ear drum (tympanic membrane)."},{"field_id":1333,"order_no":3,"bullet":"There are 2 types of forehead (temporal artery) IR sensing skin surface thermometers: contact and non-contact. Forehead contact thermometers measure the highest temperature while the thermometer is being moved across the skin. Forehead non-contact thermometers are held near the skin to measure the highest temperature from the forehead."}],"finding_list":[{"field_id":1334,"order_no":1,"bullet":"At the time of the review, Health Canada received 2 reports (1 in 1999 and 1 in 2005) related to mistaken (lower) temperature readings, both reports involved IR ear thermometers. In the 1999 report, the parents of a 2-month old infant were not able to detect what they thought may have been a fever. The parents waited until the next morning to go to the hospital. By that time, the infant's fever was very high and the child went into septic shock. The infant recovered after receiving fluids and antibiotics. In the 2005 report, there were no ill effects described."},{"field_id":1334,"order_no":2,"bullet":"There has only been 1 recall of IR thermometers in the past 10 years related to mistakes in the temperature display where temperatures being shown on the thermometer were lower than real body temperatures. There were no ill effects related to this recall reported to Health Canada."},{"field_id":1334,"order_no":3,"bullet":"Recent literature suggests that IR ear thermometer measurements are accurate when used in children under 1 year old. Both forehead contact and ear IR measurements were found to be accurate in feverish children. The measurements from forehead contact thermometers were the most similar to the measurements from rectal thermometers, which are thought to be the most accurate way to measure the temperature in young children. Literature suggests that ear IR thermometer measurement may be appropriate in hospitals for screening children."},{"field_id":1334,"order_no":4,"bullet":"This review concluded that the overall benefits of using forehead contact IR thermometers outweigh the risks, especially when the use of other types of thermometers may be more difficult (for example, the use of rectal thermometers) in young children."}],"conclusion_list":[{"field_id":1335,"order_no":1,"bullet":"Health Canada's review concluded that there is new information (literature and clinical guidance) to show that ear and forehead contact IR thermometers are appropriate for use in children under 2 years old. Health Canada will now consider requests from these manufacturers to recommend use in this age group on labels. However, information is still lacking for non-contact IR thermometers, so this type is not recommended for use in children under 2 years old."},{"field_id":1335,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to inaccurate temperature readings from the use of these devices."},{"field_id":1335,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving temperature inaccuracies with IR thermometers, as it does for all medical devices on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00160","review_date":null,"drug_name":"Xalkori (crizotinib)","safety_issue":"Increased risk of developing a hole in the bowel (gastrointestinal perforation)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1340,"overview":"Health Canada reviewed the potential risk of developing a hole in the bowel (gastrointestinal perforation) with the use of crizotinib because of side effect reports received by the manufacturer as part of their annual review of safety. Gastrointestinal perforation is when a break or hole is formed in the wall of the esophagus, stomach or intestine and may allow food or digested contents to leak out. It is a serious medical event which may be fatal if not found and treated in time. In most cases a patient has to undergo surgery or an invasive procedure to repair the hole. Gastrointestinal perforation is a known risk, associated with the use of some other products in the same class as crizotinib (e.g. sorafenib, regorafenib and axitinib) and it is also mentioned in the safety information for these products.
","use_canada":1341,"findings":1342,"conclusion":1343,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - XALKORI (crizotinib) - Assessing the potential risk of developing a hole in the bowel (gastrointestinal perforation)","created_date":"2017-05-04","modified_date":null,"key_message_list":[{"field_id":1340,"order_no":1,"bullet":"Xalkori (crizotinib) is a prescription drug authorized for sale in Canada to treat specific types of advanced lung cancers."},{"field_id":1340,"order_no":2,"bullet":"Health Canada reviewed the potential risk of developing a hole in the bowel (gastrointestinal perforation) with the use of crizotinib because of reports received by the manufacturer. "},{"field_id":1340,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of crizotinib and the risk of developing a hole in the bowel. Health Canada will continue to monitor the safety of crizotinib."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1341,"order_no":1,"bullet":"Crizotinib is a prescription drug authorized for sale in Canada to treat specific types of advanced lung cancer."},{"field_id":1341,"order_no":2,"bullet":"Crizotinib has been marketed in Canada since 2012 under the brand name Xalkori and is available as capsules taken by mouth."},{"field_id":1341,"order_no":3,"bullet":"About half of the product sold in Canada each year is used by patients in hospitals."}],"finding_list":[{"field_id":1342,"order_no":1,"bullet":"At the time of the review, Health Canada did not receive any Canadian reports of the development of a hole in the bowel related to crizotinib use."},{"field_id":1342,"order_no":2,"bullet":"This safety review looked at information collected by the manufacturer. Included were 32 international reports of the development of a hole in the bowel with the use of crizotinib. In general, the reports did not contain enough information to determine if crizotinib use caused the side effect. The advanced lung cancer itself may have also played a role."},{"field_id":1342,"order_no":3,"bullet":"While some other products in the same class as crizotinib have been linked to gastrointestinal perforation (e.g. sorafenib, regorafenib and axitinib), Health Canada's search of the published literature did not find any studies or patient reports of this side effect with the use of crizotinib."}],"conclusion_list":[{"field_id":1343,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the use of Xalkori (crizotinib) and developing holes in the bowel."},{"field_id":1343,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1343,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving crizotinib, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00161","review_date":null,"drug_name":"Mefloquine","safety_issue":"Rare long-lasting and permanent adverse events related to the brain and nervous system (neurological) and mental health (psychiatric)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1348,"overview":"Health Canada reviewed the potential risk of rare long-lasting and permanent neurological and psychiatric adverse events with the use of mefloquine because it has been an ongoing concern in Canada and internationally. The current Canadian product information for mefloquine warns about neuropsychiatric adverse events including depression, tinnitus (a persistent noise or \"ringing\" in the ears), dizziness or vertigo (the sensation of motion of self or one's surroundings). These adverse events may last for months or years after stopping the medication. Patients should consult a healthcare professional if these adverse events happen and in order to be prescribed another medication to prevent malaria. Mefloquine should not be prescribed to patients who have or have had serious psychiatric disorders.
The safety review focused on all the evidence available to date to determine whether there was a potential link between the use of mefloquine (for malaria prevention) and rare long-lasting or permanent neurological and psychiatric adverse events, as well as how often these adverse events happen and how serious they are. Another goal of the review was to identify factors that may put certain groups of individuals at increased risk and ways to manage these risks. In this review, a \"long-lasting\" adverse event was considered to be one that lasted 90 days or more after stopping the use of mefloquine.
","use_canada":1349,"findings":1350,"conclusion":1351,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.
Health Canada is aware that the Department of National Defence has completed its own review of mefloquine to help protect the health and safety of members of our Canadian Armed Forces. Health Canada's review focused on the potential long-term neurological and psychiatric adverse events associated with mefloquine in all populations. The Department of National Defence's review focused on treatment options for malaria prevention (including mefloquine) and impact on ability to perform occupational tasks. Although the two reviews were different in scope, Health Canada considered the Department of National Defence's findings before finalizing its review. Please contact the Department of National Defence for information on their findings.
","full_review":"","references":0,"footnotes":1352,"title":"Summary Safety Review - Mefloquine - Assessing the potential risk of rare long-lasting and permanent adverse events related to the brain and nervous system (neurological) and mental health (psychiatric)","created_date":"2017-06-01","modified_date":null,"key_message_list":[{"field_id":1348,"order_no":1,"bullet":"Mefloquine is a prescription drug authorized for sale in Canada to prevent and treat malaria. Malaria is a serious infectious disease that is spread by mosquitoes in certain parts of the world."},{"field_id":1348,"order_no":2,"bullet":"Because of ongoing concerns, Health Canada reviewed available evidence on the risk of long-lasting and permanent neurological and psychiatric adverse events with the use of mefloquine."},{"field_id":1348,"order_no":3,"bullet":"Health Canada's safety review found limited evidence supporting that long-lasting and permanent neurological and psychiatric adverse events are caused by the use of mefloquine. It also concluded that the current product information for mefloquine describes the potential for long-lasting neurological and psychiatric adverse events which aligns with the review findings. However, the risk of rare permanent vestibular damage could be more clearly explained in the Patient Medication Information section."},{"field_id":1348,"order_no":4,"bullet":"Health Canada will be working with the manufacturer to update the Patient Medication Information section of the product information for mefloquine to better reflect the findings of the safety review. The review also found that some individuals were prescribed mefloquine even though they had past or ongoing neurological or psychiatric conditions, which are reasons not to use mefloquine (contraindications). Therefore, to assist healthcare professionals in deciding whether to prescribe mefloquine to individual patients, a checklist will be developed."}],"footnotes_list":[{"field_id":1352,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1349,"order_no":1,"bullet":"Mefloquine is a prescription drug authorized for sale in Canada to prevent and treat malaria. It is one of a small number of medication options to prevent malaria"},{"field_id":1349,"order_no":2,"bullet":"Mefloquine has been marketed in Canada since 1993 under the brand name Lariam but only a generic version is available now. Mefloquine is available in a tablet form."},{"field_id":1349,"order_no":3,"bullet":"The use of mefloquine has been declining in Canada. The available data estimates that, in 2000, the number of prescriptions filled (new and refills) through retail pharmacies was about 60,000 and, in 2016, about 31,000 prescriptions were filled."}],"finding_list":[{"field_id":1350,"order_no":1,"bullet":"From the time mefloquine entered the Canadian market in 1993 to September 30, 2016, Health Canada had received 27 Canadian reportsa of adverse events that met Health Canada's criteria for being categorized as long-lasting or potentially long-lasting. There were 17 reports of long-lasting adverse events related to mefloquine use (lasting for 90 days or more) and 10 of potentially long-lasting (lasting between 30 and 90 days and the patient was reported as having not yet recovered). In addition, 37 international reports (from databases and published literature) of adverse events lasting for 90 days or more, including 5 reports of permanent damage to the vestibular system, were identified for further review."},{"field_id":1350,"order_no":2,"bullet":"The vast majority of the reports (61 out of 64) were deemed to have a possible link between the use of mefloquine and the long-lasting or permanent adverse events. However, the information provided in the reports was not enough to conclude that mefloquine use was responsible for the adverse event(s) reported."},{"field_id":1350,"order_no":3,"bullet":"When the prescription information is considered along with the number of reports deemed possible between the years 2000 and 2016, there were about 1.5 reports of long-lasting neurological or psychiatric adverse events for every 100,000 prescriptions filled in Canada."},{"field_id":1350,"order_no":4,"bullet":"The review also found that some patients were prescribed mefloquine even though they had past or ongoing neurological or psychiatric conditions, which are reasons not to use mefloquine (contraindications)."},{"field_id":1350,"order_no":5,"bullet":"No additional factors that may put certain individuals or groups of individuals at increased risk of experiencing these long-term adverse events were identified."},{"field_id":1350,"order_no":6,"bullet":"The review of the literature did not identify a clear process (biological mechanism) to explain how mefloquine could cause rare long-lasting or permanent neurological and psychiatric adverse events."},{"field_id":1350,"order_no":7,"bullet":"Published studies conducted in cells and animals provided little evidence supporting the permanent nature of mefloquine-associated neurological adverse events. A small number of human studies, of which most were based on surveys of patients who had taken mefloquine, suggested that psychiatric adverse events could be long-lasting."},{"field_id":1350,"order_no":8,"bullet":"The current product information for mefloquine describes the potential for long-lasting neurological and psychiatric adverse events that aligns with the review findings. However, the risk of rare permanent vestibular damage could be more clearly explained in the Patient Medication Information section."}],"conclusion_list":[{"field_id":1351,"order_no":1,"bullet":"Health Canada's safety review found limited evidence supporting that long-lasting and permanent neurological and psychiatric adverse events are caused by the use of mefloquine. The review also found that some individuals were prescribed mefloquine even though they had past or ongoing neurological or psychiatric conditions which are reasons not to use mefloquine."},{"field_id":1351,"order_no":2,"bullet":"Health Canada will be working with the manufacturer to update the Patient Medication Information section of the product information for mefloquine to better reflect the findings of the safety review. A notice will be issued in the Health Product InfoWatch to inform healthcare professionals and the public once the updates are completed."},{"field_id":1351,"order_no":3,"bullet":"In addition, a checklist will be developed to assist healthcare professionals in deciding whether to prescribe mefloquine to individual patients."},{"field_id":1351,"order_no":4,"bullet":"Health Canada will continue to monitor the safety information involving mefloquine, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00162","review_date":null,"drug_name":"Tecfidera (dimethyl fumarate)","safety_issue":"Kidney injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1358,"overview":"Health Canada reviewed the risk of kidney injury with Tecfidera after finding international cases of this risk in patients treated with Tecfidera. These cases were found during routine review of information received from the manufacturer. In Canada, the product information for Tecfidera has details about possible kidney effects that were seen in animal studies, in addition to changes in urine test results seen in human studies. Based on this, monitoring of kidney function is recommended on the product information as a precaution. Potential causes of kidney injury can include not having enough fluids in the body (dehydration) resulting from nausea and vomiting, which were common in human studies with Tecfidera.
","use_canada":1359,"findings":1360,"conclusion":1361,"additional":"For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1362,"title":"Summary Safety Review - TECFIDERA - Assessing the Potential Risk of Kidney Injury","created_date":"2017-06-15","modified_date":"2017-06-30","key_message_list":[{"field_id":1358,"order_no":1,"bullet":"Tecfidera is a prescription drug authorized for sale in Canada to treat a form of multiple sclerosis in which symptoms intensify and then decrease over a certain period of time (relapsing remitting multiple sclerosis). Tecfidera helps to reduce the number of flare-ups (relapses) that occur and to slow the build-up of physical problems due to multiple sclerosis."},{"field_id":1358,"order_no":2,"bullet":"Health Canada reviewed the risk of kidney injury with Tecfidera after finding international cases of this risk in patients treated with Tecfidera. These cases were found during routine review of information received from the manufacturer."},{"field_id":1358,"order_no":3,"bullet":"Health Canada's review concluded that there is little evidence at this time suggesting kidney injury was caused by the use of Tecfidera. The findings of this review are already reflected in the product information. Health Canada will continue to monitor the safety of Tecfidera."}],"footnotes_list":[{"field_id":1362,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1359,"order_no":1,"bullet":"Tecfidera is a prescription drug authorized for sale in Canada to treat relapsing remitting multiple sclerosis. Tecfidera helps to reduce the number of flare-ups (relapses) that happen and to slow the build-up of physical problems due to multiple sclerosis."},{"field_id":1359,"order_no":2,"bullet":"Multiple sclerosis is a deteriorating disease in which the immune system attacks the protective cover (myelin) of the nerves to interrupt communication between the brain and spinal cord with the rest of the body."},{"field_id":1359,"order_no":3,"bullet":"Tecfidera has been marketed in Canada since April 2013 and is available as a capsule that is taken by mouth."}],"finding_list":[{"field_id":1360,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 5 Canadiana reports of potential serious kidney injury from any cause (such as dehydration or damage to the kidney itself) with Tecfidera use. Three reports did not have enough information to confirm kidney injury. The remaining 2 reports, with one reporting death, were further assessed. While a possible link between Tecfidera and kidney injury was found in these 2 reports, other risk factors could have explained the condition, including other medication used at the same time and dehydration."},{"field_id":1360,"order_no":2,"bullet":"The safety review of 41 international reports of serious kidney injury with Tecfidera use focused on those suggesting damage to the kidney itself or those without other drugs or conditions that may cause kidney injury. As such, 40 of the 41 international reports identified were excluded from further review. The remaining report described damage to the kidney confirmed by biopsy. While a possible link was found between Tecfidera and kidney damage, another drug being used at the same time could have explained the condition."},{"field_id":1360,"order_no":3,"bullet":"A search of the scientific literature found no cases describing kidney injury in patients treated with Tecfidera."}],"conclusion_list":[{"field_id":1361,"order_no":1,"bullet":"Health Canada's safety review concluded that there is limited evidence at this time suggesting kidney injury with Tecfidera. The findings of this review are already reflected in the product information. Health Canada has asked the manufacturer to provide additional safety information on this risk as it becomes available."},{"field_id":1361,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Tecfidera."},{"field_id":1361,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Tecfidera, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00163","review_date":null,"drug_name":"DPP-4 inhibitors (gliptins): alogliptin, saxagliptin, sitagliptin and linagliptin","safety_issue":"Heart failure","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1368,"overview":"A safety review was carried out by Health Canada to evaluate the increased risk of heart failure with the use of DPP-4 inhibitors as a follow-up to a risk communication released by the U.S. FDA stating that saxagliptin and alogliptin might increase the risk of heart failure, in particular in patients who have other risk factors for heart failure. The product safety information in the U.S. and Canada were recently updated to include this risk.
In Canada, the product safety information for the 4 different gliptins on the Canadian market (sitagliptin, saxagliptin, alogliptin and linagliptin) currently discusses the risks of using these products in patients with a history of congestive heart failure.
","use_canada":1369,"findings":1370,"conclusion":1371,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of DPP-4 inhibitors both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1372,"title":"Summary Safety Review - Dipeptidylpeptidase-4 (DPP-4) Inhibitors - Assessing the Potential Risk of Heart Failure","created_date":"2017-06-15","modified_date":null,"key_message_list":[{"field_id":1368,"order_no":1,"bullet":"DPP-4 inhibitors, also known as gliptins, are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults."},{"field_id":1368,"order_no":2,"bullet":"Health Canada reviewed the increased potential risk of heart failure with the use of these products as a follow-up to a risk communication released by the United States Food and Drug Administration (U.S. FDA) stating that saxagliptin and alogliptin might increase the risk of heart failure, in particular in patients who have other risk factors for heart failure. Health Canada's review included all DPP-4 inhibitors available in Canada."},{"field_id":1368,"order_no":3,"bullet":"While Health Canada was carrying out the review, the manufacturers of DPP-4 inhibitors updated the product safety information to include information regarding the potential risk of heart failure. Health Canada's review of the available information concluded that the recently updated product safety information for DPP-4 inhibitors accurately describes the potential risk of heart failure when using these products. Health Canada will continue to monitor the safety of DPP-4 inhibitors."}],"footnotes_list":[{"field_id":1372,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1369,"order_no":1,"bullet":"DPP-4 inhibitors, also known as gliptins, are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults. They are used along with an appropriate diet and exercise to control blood sugar. In some cases, they are used with another anti-diabetic drug."},{"field_id":1369,"order_no":2,"bullet":"There are currently 4 different gliptins on the Canadian market: sitagliptin, saxagliptin, linagliptin and alogliptin. These drugs are also available in products that combine them with other drugs that treat type 2 diabetes."},{"field_id":1369,"order_no":3,"bullet":"Sitagliptin was the first gliptin sold in Canada in 2008. There were around 4.8 million prescriptions for DPP-4 inhibitors in 2015."}],"finding_list":[{"field_id":1370,"order_no":1,"bullet":"At the time of the review, Health Canada received 9 Canadian reportsa of heart failure where DPP-4 inhibitors were used, and in 8 of these reports, there was a possible link between the use of a DPP-4 inhibitor and heart failure (5 with sitagliptin, 2 with saxagliptin and 1 with linagliptin). However, these 8 reports included other factors that may have contributed to heart failure. This made it difficult to know the role of DPP-4 inhibitors in these reports of heart failure, especially since heart failure happens more often in diabetics than in people who are not diabetic."},{"field_id":1370,"order_no":2,"bullet":"In 2008, the U.S. FDA asked the manufacturers of all antidiabetic drugs (including DPP-4 inhibitors) to do more safety studies to assess the risks linked to problems of the heart and blood vessels (cardiovascular events). Studies for 3 DPP-4 inhibitors (sitagliptin, saxagliptin and alogliptin) have been completed and reviewed by Health Canada, while the studies for linagliptin will be completed in 2019. The results of the 3 completed safety studies do not agree with each other on the increased risk of hospitalization due to heart failure in patients treated with DPP-4 inhibitors. Some studies found a link while others did not. The results from these 3 completed safety studies have been added to the product safety information for sitagliptin (October 2016), saxagliptin (August 2016) and alogliptin (April 2016)."},{"field_id":1370,"order_no":3,"bullet":"Health Canada reviewed 7 publications that combine the results of many studies (meta-analyses) that looked at the increased risk of heart failure in patients treated with DPP-4 inhibitors. Some authors found a link, while others did not. Most of the clinical trials did not, or could not, separate the risk associated with each DPP-4 inhibitor, so it is not possible to tell if there is a difference in the risk between the different DPP-4 inhibitors."}],"conclusion_list":[{"field_id":1371,"order_no":1,"bullet":"While Health Canada was carrying out the review, the manufacturers of DPP-4 inhibitors updated the product safety information to include information regarding the potential risk of heart failure. Health Canada's review of the available information concluded that the recently updated product safety information for DPP-4 inhibitors accurately describes the potential risk of heart failure when using these products."},{"field_id":1371,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products."},{"field_id":1371,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving DPP-4 inhibitors, as it does for all health products on the Canadian market, in order to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00164","review_date":null,"drug_name":"Finasteride (Propecia, Proscar and generic products)","safety_issue":"Serious muscle-related side effects","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1378,"overview":"Health Canada reviewed the risk of potential serious muscle-related side effects with finasteride use because of reports in which these events were seen in patients treated with Propecia and Proscar. The safety review focussed on potential risks of serious muscle-related adverse events such as rhabdomyolysis (pain in muscles with breakdown of muscle tissue and an increase in certain muscle proteins known as creatine kinase [CK] enzymes, myopathy (disease of muscles with pain and an increase in CK enzymes) and muscle disorders such as pain, weakness, atrophy (wasting) or stiffness.
","use_canada":1379,"findings":1380,"conclusion":1381,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Finasteride - Assessing the Potential Risk of Serious Muscle-Related Side Effects","created_date":"2017-06-22","modified_date":null,"key_message_list":[{"field_id":1378,"order_no":1,"bullet":"Finasteride is a prescription drug that is authorized for sale in Canada to treat and control non-cancerous enlargement of the gland that makes semen in males (prostate gland) and, improves symptoms associated with this medical condition. At a lower dose, it is authorized for sale to treat hair loss in men."},{"field_id":1378,"order_no":2,"bullet":"Health Canada reviewed the risk of potential serious muscle-related side effects with finasteride use because of reports in which these side effects were seen in patients treated with Propecia and Proscar."},{"field_id":1378,"order_no":3,"bullet":"Health Canada's review of the available information concluded that the risk of serious muscle-related side effects with the use of finasteride could not be ruled out. Currently, the product information for finasteride does not include the potential risk of serious muscle-related side effects. Health Canada has recommended that the manufacturers update the product information of finasteride-containing products to inform about this potential risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1379,"order_no":1,"bullet":"Finasteride at a dose of 5mg is a prescription drug that is authorized for sale in Canada to treat and control non-cancerous enlargement of the prostate gland (benign prostatic hyperplasia) and improves symptoms related to this condition. Finasteride at a dose of 1mg is authorized for sale in Canada to treat hair loss in men (androgenic alopecia)."},{"field_id":1379,"order_no":2,"bullet":"Finasteride (5mg) has been marketed in Canada since 1992 under the brand name Proscar, and finasteride (1mg) since 1998 under the brand name Propecia. Generic versions of finasteride are also available."}],"finding_list":[{"field_id":1380,"order_no":1,"bullet":"At the time of this review, Health Canada had received 11 Canadian reports of serious muscle-related side effects suspected of being linked to finasteride use. Of these, 4 cases were further assessed:Health Canada conducted a review of the potential risk of blood abnormalities in newborns whose mothers were treated with Tysabri during pregnancy. The review included reports provided by the manufacturer and from published literature. Blood (hematological) abnormalities have been reported in adult patients treated with Tysabri and this was already written in the product information.
","use_canada":1387,"findings":1388,"conclusion":1389,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this product both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - TYSABRI (natalizumab) - Blood (hematological) Abnormalities in Newborns whose Mothers were treated with Tysabri During Pregnancy","created_date":"2017-06-22","modified_date":null,"key_message_list":[{"field_id":1386,"order_no":1,"bullet":"Tysabri (natalizumab) is authorized for sale in Canada to treat patients with the relapsing-remitting form of multiple sclerosis (MS)."},{"field_id":1386,"order_no":2,"bullet":"Health Canada reviewed the potential risk of blood abnormalities in newborns whose mothers were treated with Tysabri during pregnancy following the publication of reports of newborns having lower numbers of red blood cells (anemia) and platelets (thrombocytopenia) and higher numbers of white blood cells (leukocytosis)."},{"field_id":1386,"order_no":3,"bullet":"Health Canada's safety review concluded that there is a potential for blood abnormalities in newborns whose mothers were treated with Tysabri during pregnancy. Since the completion of this review, the Canadian product information for Tysabri has been updated to reflect this potential risk in newborns."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1387,"order_no":1,"bullet":"Tysabri (natalizumab) is authorized for sale in Canada to treat patients with the relapsing-remitting form of multiple sclerosis (MS). Tysabri is generally recommended for MS patients who have not responded well to other treatments or who are unable to tolerate them."},{"field_id":1387,"order_no":2,"bullet":"Tysabri belongs to a family of medicines called monoclonal antibodies. It prevents active immune cells from reaching the brain where they can cause the inflammation and the nerve damage seen in MS."},{"field_id":1387,"order_no":3,"bullet":"Tysabri has been marketed in Canada since 2006. Tysabri is given into a vein (intravenously) and is available by prescription only."},{"field_id":1387,"order_no":4,"bullet":"At the time of this review, the Canadian product information for Tysabri included the risk of blood abnormalities in adult patients."}],"finding_list":[{"field_id":1388,"order_no":1,"bullet":"At the time of the review, Health Canada had received, from the manufacturer, 15 reports of blood abnormalities in newborns whose mothers were treated with Tysabri during pregnancy. None of the reports were from mothers treated in Canada."},{"field_id":1388,"order_no":2,"bullet":"It was determined that in 14 of the 15 reports the abnormalities in the newborns' blood was potentially related to the Tysabri treatment, while the remaining 1 case could not be assessed due to missing information. The blood abnormalities included having lower numbers of red blood cells (anemia) and platelets (thrombocytopenia) and higher numbers of white blood cells (leukocytosis)."},{"field_id":1388,"order_no":3,"bullet":"In 3 of the 15 cases it was reported that the newborns' umbilical cord blood was found to contain Tysabri. This suggests that Tysabri can cross from the mother's blood into the fetus and may contribute to a blood abnormality in the newborn."}],"conclusion_list":[{"field_id":1389,"order_no":1,"bullet":"Health Canada's safety review concluded that there is a potential for blood abnormalities to happen in newborns whose mothers were treated with Tysabri during pregnancy."},{"field_id":1389,"order_no":2,"bullet":"Since the completion of the review, the Canadian product information has been updated to reflect this potential risk."},{"field_id":1389,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Tysabri, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00166","review_date":null,"drug_name":"Brilinta (ticagrelor)","safety_issue":"Severe skin side effects (Severe cutaneous adverse reactions, SCAR) which include: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1394,"overview":"Health Canada reviewed the potential risk of SCAR associated with the use of Brilinta because there was an increase in the number of reports severe skin reactions, which require hospitalization and can be sometimes be fatal.
","use_canada":1395,"findings":1396,"conclusion":1397,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - BRILINTA (ticagrelor) - Assessing the Potential Risk of Severe Skin Side Effects","created_date":"2017-06-26","modified_date":null,"key_message_list":[{"field_id":1394,"order_no":1,"bullet":"Brilinta is a prescription drug that is authorized for sale in Canada and used with low-dose aspirin (acetylsalicylic acid) to reduce the risk of having a stroke, having another heart attack or dying from a disease related to the heart or blood vessels."},{"field_id":1394,"order_no":2,"bullet":"Health Canada reviewed the risk of severe skin side effects (SCAR) after an increase in the number of SCAR reports was seen in the safety information provided by the manufacturer. "},{"field_id":1394,"order_no":3,"bullet":"Health Canada's review concluded that there was not enough information available to confirm a link between the risk of SCAR and the use of Brilinta. Health Canada will continue to monitor this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1395,"order_no":1,"bullet":"Brilinta is a prescription drug that is authorized for sale in Canada and used with low-dose aspirin (acetylsalicylic acid) to reduce the risk of having a stroke, having another heart attack or dying from a disease related to the heart or blood vessels."},{"field_id":1395,"order_no":2,"bullet":"Brilinta is available as a tablet."},{"field_id":1395,"order_no":3,"bullet":"Although not commonly prescribed, Brilinta use has steadily increased since it became available on the Canadian market in June 2011."}],"finding_list":[{"field_id":1396,"order_no":1,"bullet":"At the time of the review, Health Canada had received 2 Canadian reports of SCAR associated with the use of Brilinta. Of these 2 reports, 1 was found to show a possible link between SCAR and the use of Brilinta, which means that the drug was 1 reason among others that could explain why SCAR happened. The second report was left out because it did not present symptoms of SCAR."},{"field_id":1396,"order_no":2,"bullet":"The safety review also looked at 40 international reports of SCAR associated with the use of BRILINTA. In 4 of the 40 reports, there was considered to be a possible link between SCAR and the use of Brilinta."},{"field_id":1396,"order_no":3,"bullet":"In the literature reviewed, there was no evidence of increased risk of SCAR with the use of Brilinta."},{"field_id":1396,"order_no":4,"bullet":"The product label for Brilinta does not mention a risk of SCAR. However, less severe skin reactions such as rashes are included in the product label."}],"conclusion_list":[{"field_id":1397,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough information available to confirm that there is a link between the risk of SCAR and the use of Brilinta."},{"field_id":1397,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1397,"order_no":3,"bullet":"Health Canada will continue to monitor side effects involving Brilinta, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00167","review_date":null,"drug_name":"AUBAGIO (teriflunomide)","safety_issue":"Inflammation of the colon (colitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1402,"overview":"Health Canada reviewed the potential risk of colitis with Aubagio use after finding reports (since being marketed) of colitis as part of routine review of information received from the manufacturer. Also, the product safety information of a closely-related drug, Arava (leflunomide) was updated to include a new warning for colitis. In Canada, the product safety information for Aubagio does not mention the risk of colitis.
","use_canada":1403,"findings":1404,"conclusion":1405,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - AUBAGIO (teriflunomide) - Assessing the potential risk of inflammation of the colon (colitis)","created_date":"2017-06-28","modified_date":null,"key_message_list":[{"field_id":1402,"order_no":1,"bullet":"Aubagio (teriflunomide) is a prescription drug authorised for sale in Canada to treat patients with multiple sclerosis. Aubagio helps to reduce the number of flare-ups (relapses) that happen and slow the worsening of physical problems and other symptoms due to multiple sclerosis."},{"field_id":1402,"order_no":2,"bullet":"Health Canada reviewed the risk of inflammation of the colon (colitis) with the use of teriflunomide after finding reports of colitis (since being marketed) as part of routine review of information received from the manufacturer. Also, the product safety information of a closely-related drug, Arava (leflunomide) was updated to include a new warning for colitis."},{"field_id":1402,"order_no":3,"bullet":"Health Canada's review of the available information concluded that a link between Aubagio use and colitis could not be confirmed at this time. However, Health Canada will work with the manufacturer to update the product safety information to note that reports of colitis with Aubagio use have been received."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1403,"order_no":1,"bullet":"Aubagio (teriflunomide) is a prescription drug authorised for sale in Canada to help reduce the number of flare-ups (relapses) and to slow the worsening of physical problems and other symptoms in patients with the relapsing remitting form of multiple sclerosis."},{"field_id":1403,"order_no":2,"bullet":"Aubagio (teriflunomide) has been marketed in Canada since 2013 and is available as a capsule that is taken by mouth."}],"finding_list":[{"field_id":1404,"order_no":1,"bullet":"At the time of the review, Health Canada had received 3 reports of colitis related to Aubagio use. Upon analysis of these reports, Health Canada concluded that 2 of the 3 reports were possibly related to the use of Aubagio. There was not enough information included in the third report to support a possible link."},{"field_id":1404,"order_no":2,"bullet":"Nine additional reports of colitis (3 Canadian and 6 international), reported to Health Canada by the Canadian manufacturer of Aubagio were also assessed. Health Canada concluded that all 9 reports were possibly related to the use of Aubagio."},{"field_id":1404,"order_no":3,"bullet":"A search of the scientific literature found 1 report of colitis in a patient using Aubagio. However, there was not enough information in this report to assess the link between colitis and the use of Aubagio."},{"field_id":1404,"order_no":4,"bullet":"To date, there is no suggested way to explain how Aubagio could cause colitis."},{"field_id":1404,"order_no":5,"bullet":"While some reports of colitis assessed above were found to be possibly linked to Aubagio use, other factors may have also contributed to this risk. These factors included the disease being treated (multiple sclerosis), the use of other medications at the same time or other health problems (for example, bowel inflammation)."}],"conclusion_list":[{"field_id":1405,"order_no":1,"bullet":"Health Canada's review of the available information concluded that a link between Aubagio use and colitis could not be confirmed at this time. However, Health Canada will work with the manufacturer to update the product safety information to note that reports of colitis with Aubagio use have been received."},{"field_id":1405,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1405,"order_no":3,"bullet":"Health Canada will continue to monitor side effect information involving Aubagio, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00168","review_date":null,"drug_name":"Hydroxyethyl starch (Voluven and Volulyte)","safety_issue":"Acute Kidney Injury (AKI) in non-critically ill patients","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1410,"overview":"In 2013, Health Canada reviewed the risk of kidney injury and death associated with hydroxyethyl starch products when used in critically ill patients and found an increased risk in these patients. This finding led to updates to the hydroxyethyl starch product information to include warnings about the risk of kidney injury and death in patients with low blood volume needing intensive or emergency care. At the time of that review, it was unclear if the risk of kidney injury and death also applied to non-critically ill patients, such as those with non-life threatening injuries or having a planned surgery. Health Canada had asked the manufacturer of hydroxyethyl starch products to provide all available safety information of these products when used in non-critically ill patients. This review is a follow-up assessment of all the available data on this risk.
","use_canada":1411,"findings":1412,"conclusion":1413,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Hydroxyethyl starch (voluven and volulyte) - Assessing the Potential Risk of Acute Kidney Injury in Non-Critically Ill Patients","created_date":"2017-06-30","modified_date":null,"key_message_list":[{"field_id":1410,"order_no":1,"bullet":"Hydroxyethyl starch is a drug authorized for sale in Canada to treat low blood volume (not enough fluid in the blood)."},{"field_id":1410,"order_no":2,"bullet":"Health Canada first carried out a safety review in 2013 that found a higher risk of AKI and death when hydroxyethyl starch products are used in critically ill patients. This current review evaluated all available safety information on the risk of AKI in non-critically ill patients with the use of these products to see if this risk was present in this population of patients."},{"field_id":1410,"order_no":3,"bullet":"Health Canada's review concluded that there was not enough information to establish a link between the use of hydroxyethyl starch products in non-critically ill patients and the risk of AKI. Health Canada has requested additional safety information from the manufacturer and will continue to monitor safety information of hydroxyethyl starch products as it becomes available."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1411,"order_no":1,"bullet":"Hydroxyethyl starch is a drug authorized for sale in Canada to treat low blood volume."},{"field_id":1411,"order_no":2,"bullet":"Hydroxyethyl starch has been marketed in Canada since 2006 under the brand name Voluven and since 2011 under the brand name Volulyte. It is available as an intravenous solution."},{"field_id":1411,"order_no":3,"bullet":"Approximately 500,000 patients have been treated with Voluven or Volulyte in Canada since they were first marketed."}],"finding_list":[{"field_id":1412,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of AKI associated with the use of hydroxyethyl starch products in non-critically ill patients."},{"field_id":1412,"order_no":2,"bullet":"This safety review looked at information from 7 international reports of AKI where hydroxyethyl starch products have been used in non-critically ill patients. In these reports, there was not enough information to establish a link between hydroxyethyl starch products and AKI, although a link could not be ruled out. Other risk factors, such as low blood volume, could have caused the condition."},{"field_id":1412,"order_no":3,"bullet":"Health Canada reviewed 13 published articles related to AKI with the use of hydroxyethyl starch products in non-critically ill patients. These articles included the results of studies and clinical trials. In 10 of the 13 studies and trials looked at, the methods used were not suitable to test for a link between Voluven or Volulyte and AKI in non-critically ill patients. The remaining 3 studies did not suggest hydroxyethyl starches were associated with an increased risk of AKI in non-critically ill patients."}],"conclusion_list":[{"field_id":1413,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough information to establish a link between the use of hydroxyethyl starch products in non-critically ill patients and the risk of AKI. Health Canada has requested additional safety information from the manufacturer as it becomes available."},{"field_id":1413,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1413,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving hydroxyethyl starch products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00182","review_date":null,"drug_name":"Proton pump inhibitors (PPIs)","safety_issue":"A type of skin reaction known as subacute cutaneous lupus erythematosus (SCLE)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1532,"overview":"Health Canada reviewed the potential risk of a type of skin reaction known as subacute cutaneous lupus erythematosus (SCLE) with the use of PPIs after a published article1 that found these drugs may contribute to the reaction.
","use_canada":1533,"findings":1534,"conclusion":1535,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1536,"footnotes":1537,"title":"Summary Safety Review - Proton Pump Inhibitors (PPIs) - Assessing the risk of a type of skin reaction [Subacute Cutaneous Lupus Erythematosus (SCLE)]","created_date":"2017-12-07","modified_date":null,"key_message_list":[{"field_id":1532,"order_no":1,"bullet":"Proton pump inhibitors (PPIs) are medications used to reduce stomach acid, and treat heartburn and sores on the lining of the stomach. They are available with a prescription and over-the-counter."},{"field_id":1532,"order_no":2,"bullet":"A published article suggested that PPIs may contribute to a type of skin reaction known as subacute cutaneous lupus erythematosus (SCLE). Health Canada reviewed this potential risk, and concluded there is a rare risk of SCLE with the use of PPIs. "},{"field_id":1532,"order_no":3,"bullet":"Health Canada is working with manufacturers to update the safety information for all PPI products to inform healthcare professionals and patients. In addition, Health Canada will issue a notice in the Health Product InfoWatch to raise awareness of this potential safety issue."}],"footnotes_list":[{"field_id":1537,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1536,"order_no":1,"bullet":"Aggarwal, N. Drug-Induced Subacute Cutaneous Lupus Erythematosus Associated with Proton Pump Inhibitors. Drugs Real. World Outcomes. 2016:3;145-154."}],"use_canada_list":[{"field_id":1533,"order_no":1,"bullet":"PPIs are drugs authorized for sale in Canada to reduce stomach acid, and to treat heartburn (i.e., gastroesophageal reflux disease) and sores on the lining of the stomach (i.e., peptic ulcers)."},{"field_id":1533,"order_no":2,"bullet":"There are six PPIs available in Canada: omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet) and dexlansoprazole (Dexilant). There are also some generic versions of these drugs sold in Canada."},{"field_id":1533,"order_no":3,"bullet":"Most PPIs are available by prescription only. However, some omeprazole products are available without a prescription (e.g., Olex)."},{"field_id":1533,"order_no":4,"bullet":"PPIs are widely used in Canada, with over 33 million prescriptions dispensed in 2016."}],"finding_list":[{"field_id":1534,"order_no":1,"bullet":"The safety review was triggered by a published article1 that looked at reports in the United States Food and Drug Administration Adverse Event Reporting System. The authors noted that, over a two-year period between 2013 and 2015, there were 120 reports which involved the use of PPIs that were thought to have caused the skin reaction.1"},{"field_id":1534,"order_no":2,"bullet":"As of September 30, 2016, Health Canada had received two Canadian reportsa of potential SCLE with PPI use, but there was not enough information in these reports to show that the patients had all the symptoms of SCLE or to conclude that the PPI caused the skin reaction."},{"field_id":1534,"order_no":3,"bullet":"Health Canada reviewed another 18 patient international reports in the published literature of potential SCLE with PPI use (5 with pantoprazole, 6 with omeprazole, 6 with lansoprazole and 1 with esomeprazole). Other factors may have contributed to the skin reaction, e.g., other drugs were taken at the same time as the PPI, or the patient had experienced SCLE at some time before taking the PPI. It was noted that, of these patients, 16 recovered when they stopped taking the PPI."},{"field_id":1534,"order_no":4,"bullet":"SCLE cases have not been reported for all PPIs. However, given these drugs share many similarities, it is expected that they could potentially all lead to the development of SCLE in some individuals."}],"conclusion_list":[{"field_id":1535,"order_no":1,"bullet":"Health Canada concluded that there is a rare risk of SCLE associated with PPI use."},{"field_id":1535,"order_no":2,"bullet":"Health Canada is working with manufacturers to update the safety information for all PPI-containing products to inform healthcare professionals and patients. In addition, Health Canada will issue a notice in the Health Product InfoWatch to raise awareness of this potential safety issue."},{"field_id":1535,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving PPI products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00169","review_date":null,"drug_name":"Amino-acid solutions for parenteral (intravenous) nutrition","safety_issue":"Deaths in premature infants when the solutions are not protected from light","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1418,"overview":"Health Canada reviewed the risk of death in premature infants when fed with amino-acid solutions for PN that are not protected from light because of published studies that suggested greater risk of harm with these conditions. The studies discuss the possibility that light exposure can cause harmful chemicals (including toxic peroxides) to be made within the PN solution that the infant's body would not be able to process. Oxygen therapy, receiving blood (blood transfusions) and infections both in the infant and the mother may also play a role in the production of these harmful chemicals.
","use_canada":1419,"findings":1420,"conclusion":1421,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1422,"footnotes":1423,"title":"Summary Safety Review - Amino-acid solutions for parenteral nutrition - Assessing the potential risk of death in premature infants when the solutions are not protected from light","created_date":"2017-07-06","modified_date":null,"key_message_list":[{"field_id":1418,"order_no":1,"bullet":"Amino-acid solutions for parenteral (intravenous) nutrition (PN) are authorized for sale in Canada to provide nutrition through a vein. Some of these are used to feed premature infants."},{"field_id":1418,"order_no":2,"bullet":"Health Canada reviewed the risk of death in premature infants when fed with amino-acid solutions for PN that are not protected from light while being used because of published studies that suggested light exposure increases the risk of harm."},{"field_id":1418,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the risk of death in premature infants and the use of amino-acid solutions for PN that have not been protected from light while being used. Health Canada will continue to monitor the safety of these products and encourages healthcare professionals to report side effects that may be linked to the use of these products."}],"footnotes_list":[{"field_id":1423,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1422,"order_no":1,"bullet":"Chessex P, Laborie S, Nasef N, et al. Shielding parenteral nutrition from light improves survival rate in premature infants. JPEN J Parenter Enteral Nutr 2017; 41:378-383."},{"field_id":1422,"order_no":2,"bullet":"Sherlock R, Chessex P. Shielding parenteral nutrition from light: does the available evidence support a randomized, controlled trial? Pediatrics. 2009; 123:1529-1533."}],"use_canada_list":[{"field_id":1419,"order_no":1,"bullet":"Amino-acid solutions for parenteral nutrition (PN) are authorized for sale in Canada to provide nutrition through a vein (intravenous). Premature infants are not developed enough to digest food in their gut and PN can help meet their feeding needs."},{"field_id":1419,"order_no":2,"bullet":"Amino-acid solutions for PN that are available in Canada include the following products: Primene, Prosol, Clinimix, Olimel, Travasol, Smofkabiven and Aminosyn."},{"field_id":1419,"order_no":3,"bullet":"Other than Primene, these products are not specifically authorized to be used in infants or children."},{"field_id":1419,"order_no":4,"bullet":"The product information for the above amino-acid solutions (except for Olimel and Smofkabiven) state that they should be protected from light during storage, but do not mention about protection from light when the solutions are being used."}],"finding_list":[{"field_id":1420,"order_no":1,"bullet":"At the time of the review, Health Canada received 5 Canadian reportsa of deaths in premature infants, suspected to be related to the use of PN. All of these reports involved Primene. None of the reports included information on whether or not the solutions were protected from light while being used."},{"field_id":1420,"order_no":2,"bullet":"In addition, 13 international reports that involved premature infants were received from manufacturers. All of these reports involved Primene. None of the reports included information on whether or not the solutions were protected from light."},{"field_id":1420,"order_no":3,"bullet":"In the review of the 18 reports, 10 reports showed that the cause of death was not due to the light exposure of the PN solutions as these infants died from common causes of death associated with being born prematurely. In the remaining 8 reports, it was not possible to assess the link between the deaths and light exposure of the PN solutions because not enough information was provided."},{"field_id":1420,"order_no":4,"bullet":"A published article1 assessed 4 individual studies together (a meta-analysis) regarding premature infants being fed with amino-acid solutions for PN and concluded that there is a greater risk of death associated with the use of PN solutions that are not protected from light. However, there were differences noted in each study. The quality of the amino-acid solutions, the number of days the infants were given PN, the health outcomes of interest (e.g. diseases that premature infants are likely to get) and medical practices (e.g. oxygen therapy or receiving blood) varied among the studies. In addition, there was limited or no information on other risk factors such as infections, the age of the infants at the time of death, medications and therapy that may have been used at the same time, and the causes of death."},{"field_id":1420,"order_no":5,"bullet":"Another article2 was reviewed which assessed information from the Canadian Neonatal Network about premature infants receiving PN. It concluded that protecting the amino-acid solutions for PN from light does not lessen the risk of side effects or death."}],"conclusion_list":[{"field_id":1421,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the risk of death in premature infants and the use of amino-acid solutions for PN that have not been protected from light."},{"field_id":1421,"order_no":2,"bullet":"Health Canada encourages healthcare professionals to report side effects related to the use of these health products."},{"field_id":1421,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving parenteral nutrition solutions, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00170","review_date":null,"drug_name":"Intraocular lenses","safety_issue":"Development of glistening","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1430,"overview":"As part of Health Canada's ongoing monitoring of glistening development in IOLs, Health Canada reviewed the available safety information related to this issue. Health Canada has been actively monitoring reports of IOL glistening since 2012, with additional safety reviews completed in May 2015 and the current review. The findings from Health Canada's 2012 review were published in Health Canada's Canadian Adverse Reaction Newsletter (CARN) to raise awareness about this potential side effect and to encourage reporting of glistening associated with IOLs.
","use_canada":1431,"findings":1432,"conclusion":1433,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of these devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Intraocular lenses - Assessing the potential risk of developing small pockets of liquid in intraocular lenses (glistening)","created_date":"2017-07-26","modified_date":null,"key_message_list":[{"field_id":1430,"order_no":1,"bullet":"An intraocular lens (IOL) is a medical device licensed for sale in Canada to replace a cloudy lens in the eye of a cataract patient. Glistening is when very small pockets of liquid collect inside the IOL, which may change the quality of a person's vision by increasing glare and/or making things blurry. "},{"field_id":1430,"order_no":2,"bullet":"As part of Health Canada's ongoing monitoring of glistening development in IOLs, Health Canada reviewed the available safety information about how and why glistening develops, and if glistening changes the quality of a person's vision. "},{"field_id":1430,"order_no":3,"bullet":"Overall, Health Canada's review found that the available evidence is not strong enough to determine how or why glistening develops, or if glistening changes the quality of a person's vision. Health Canada will continue to monitor the safety of IOLs and will take appropriate action, if and when new information becomes available."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1431,"order_no":1,"bullet":"An intraocular lens (IOL) is a medical device licensed for sale in Canada to replace a cloudy lens in a cataract patient's eye."},{"field_id":1431,"order_no":2,"bullet":"A cataract is a cloudiness in the normally clear lens of the eye. The cloudiness can decrease the quality of a person's vision, and may lead to blindness unless the lens is replaced."}],"finding_list":[{"field_id":1432,"order_no":1,"bullet":"When the current review was started, Health Canada had received a total of 180 reports of the development of glistening in people with IOLs, of which 26 were reported to Health Canada between May 2015 and December 2015. From January to August 2016, Health Canada received 1 report of glistening in IOLs."},{"field_id":1432,"order_no":2,"bullet":"Many of the Canadian reports of glistening also noted that there was a change in the quality of a person's vision, by increasing glare and/or making things blurry. This possible association could not be confirmed because the lenses were not returned to the manufacturer for more testing."},{"field_id":1432,"order_no":3,"bullet":"There was not enough detailed information in the reports received by Health Canada to confirm if the glistening was responsible for the changes in the person's vision, or if the changes were due to a different eye problem, or if there were any follow-up actions taken (for example, whether the IOL was replaced)."},{"field_id":1432,"order_no":4,"bullet":"In the literature, there are reports of glistening development in IOLs associated with different types of IOLs made by different manufacturers. So far, all of the glistening reports received by Health Canada have been for IOLs made by a single manufacturer, Alcon Laboratories. In 2012, Alcon Laboratories introduced changes to how their IOLs are made in order to decrease the likelihood of glistening development."},{"field_id":1432,"order_no":5,"bullet":"In the literature, some studies have found links between glistening and a change in the quality of a person's vision while others have not. There are many factors that can affect the risk of glistening development including: what the IOL is made of, how the IOL is made, how the IOL is packaged and changes in IOL temperature. Further studies are needed to find out how or why glistening develops in IOLs and its potential effect on the quality of a person's vision."}],"conclusion_list":[{"field_id":1433,"order_no":1,"bullet":"Overall, Health Canada's review found that the available evidence is not strong enough to determine how or why glistening develops, and if it changes the quality of a person's vision."},{"field_id":1433,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any cases of glistening development in IOLs."},{"field_id":1433,"order_no":3,"bullet":"Furthermore, in patients who have developed glistening in their IOL(s), if the lens is surgically removed, doctors should return the defective devices to the manufacturer for further study."},{"field_id":1433,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving IOLs, as it does for all medical devices on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00171","review_date":null,"drug_name":"Aubagio (teriflunomide)","safety_issue":"Sudden onset of kidney injury (acute renal injury) or formation of kidney stones (nephrolithiasis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1438,"overview":"Health Canada reviewed the potential risk of sudden onset of kidney injury or formation of kidney stones with the use of teriflunomide because of safety information received from the manufacturer. Patients with MS, in general, may be at a greater risk of experiencing problems with their kidneys than healthy people.
","use_canada":1439,"findings":1440,"conclusion":1441,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1442,"title":"Summary Safety Review - Aubagio (teriflunomide) - Assessing the potential risk of sudden kidney injury or kidney stones","created_date":"2017-08-04","modified_date":null,"key_message_list":[{"field_id":1438,"order_no":1,"bullet":"Aubagio (teriflunomide) is a prescription drug authorized for sale in Canada to treat patients with multiple sclerosis (MS). Aubagio helps to reduce the number of flare-ups (relapses) and slows the worsening of physical problems and other symptoms associated with MS."},{"field_id":1438,"order_no":2,"bullet":"Following the receipt of new safety information from the manufacturer, Health Canada reviewed the potential risk of sudden onset of kidney injury or formation of kidney stones with the use of teriflunomide."},{"field_id":1438,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of teriflunomide and a risk of sudden onset of kidney injury or formation of kidney stones. Health Canada will continue to monitor the safety of teriflunomide."}],"footnotes_list":[{"field_id":1442,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[],"use_canada_list":[{"field_id":1439,"order_no":1,"bullet":"Aubagio (teriflunomide) is a prescription drug authorized for sale in Canada to treat patients with MS. Aubagio helps to reduce the number of flare-ups (relapses) that happen and slows the worsening of physical problems and other symptoms associated with MS."},{"field_id":1439,"order_no":2,"bullet":"Teriflunomide has been marketed in Canada since 2013, under the brand name Aubagio. It is available as a tablet that is taken by mouth."}],"finding_list":[{"field_id":1440,"order_no":1,"bullet":"At the time of the review, Health Canada received, from the manufacturer's worldwide database, 55 reports (all were international) of suspected sudden onset of kidney injury and 135 reports (8 of these were Canadian) of suspected kidney stones with teriflunomide use.a No additional reports were found in Health Canada's Canada Vigilance database."},{"field_id":1440,"order_no":2,"bullet":"Upon review of the above information, only 2 reports of patients with sudden onset of kidney injury were considered to be possibly related to the use of teriflunomide. The review of reports of kidney stones did not show a link related to the use of teriflunomide. In these reports, other factors could have played a role, such as the MS itself or problems with the bladder. There was also limited information in the reports that described the health of the patient's kidneys before taking teriflunomide."},{"field_id":1440,"order_no":3,"bullet":"In the published scientific literature, there were no reports or studies related to the possible association of sudden onset of kidney injury or formation of kidney stones with the use of teriflunomide."},{"field_id":1440,"order_no":4,"bullet":"There was limited evidence to suggest that MS patients may be at greater risk of kidney injury or forming kidney stones when taking teriflunomide."}],"conclusion_list":[{"field_id":1441,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the use of teriflunomide and a risk of sudden onset of kidney injury or formation of kidney stones."},{"field_id":1441,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this/these health product(s)."},{"field_id":1441,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving teriflunomide, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00172","review_date":null,"drug_name":"Desloratadine (Aerius and generics)","safety_issue":"Abnormal heart rhythm (QT interval prolongation)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1448,"overview":"Health Canada carried out a safety review to look at the potential risk of abnormal heart rhythm (QT interval prolongation) with the use of over-the-counter (OTC) desloratadine-containing products. This safety review was triggered by a publication, in the World Health Organization (WHO) Pharmaceuticals Newsletter1, describing cases of abnormal heart rhythm suspected to be associated with the use of loratadine and desloratadine. Health Canada already carried out a safety review for loratadine in 2016. This safety review focused on desloratadine.
","use_canada":1449,"findings":1450,"conclusion":1451,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this health product in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1452,"footnotes":0,"title":"Summary Safety Review - Desloratadine - Assessing the potential risk of abnormal heart rhythm (QT interval prolongation)","created_date":"2017-08-10","modified_date":null,"key_message_list":[{"field_id":1448,"order_no":1,"bullet":"Desloratadine is available as an ingredient in some over-the-counter (OTC) products (marketed as Aerius and generics) used for the relief of allergy symptoms."},{"field_id":1448,"order_no":2,"bullet":"Health Canada carried out a safety review following international cases of abnormal heart rhythm (QT interval prolongation) suspected of being associated with the use of desloratadine."},{"field_id":1448,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of desloratadine and abnormal heart rhythm. Health Canada will continue to monitor the safety of desloratadine-containing products."}],"footnotes_list":[],"reference_list":[{"field_id":1452,"order_no":1,"bullet":"WHO. (2015). Desloratadine and QT Prolongation. WHO Pharmaceuticals Newsletter, Issue 2, pp: 23-27Health Canada reviewed the potential risk of liver injury with green tea extract-containing natural health products because of ongoing reports of serious liver injury worldwide, including a recent report in Canada. More information regarding this recent case was published in Health Canada's Health Product InfoWatch in 2016. Health Canada's Green Tea Extracts monograph published in 2008 includes the following risk information:
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of green tea extract both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1462,"title":"Summary Safety Review - Green tea extract-containing natural health products - Assessing the potential risk of liver injury (hepatotoxicity)","created_date":"2017-11-15","modified_date":"2017-12-12","key_message_list":[{"field_id":1458,"order_no":1,"bullet":"Green tea extract-containing natural health products are authorized for sale in Canada for a variety of uses, including to help in weight management (along with diet and exercise) and as a source of antioxidants for the maintenance of good health. The vast majority of those who consume green tea, in any form, do so without harm."},{"field_id":1458,"order_no":2,"bullet":"Health Canada reviewed the potential risk of liver injury (hepatotoxicity) associated with green tea extract because of ongoing reports of serious liver injury worldwide, including a recent report in Canada."},{"field_id":1458,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of green tea extract and a risk of rare and unpredictable liver injury. While this risk is already identified in Health Canada's Green Tea Extracts monograph, Health Canada's review found that cases of liver injury continue to be reported in Canada and worldwide, and that Canadian safety information could be stronger."},{"field_id":1458,"order_no":4,"bullet":"As a result, Health Canada will strengthen the current cautionary risk statement in Health Canada's Green Tea Extracts monograph to include the following:Health Canada reviewed the potential risk of SCAR with the use of Effient because cases were reported by the manufacturer. The product safety information for Effient does not mention the risk of SCAR but includes less severe skin reactions such as rashes.
","use_canada":1469,"findings":1470,"conclusion":1471,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - EFFIENT (prasugrel) - Assessing the Potential Risk of Severe Skin Side Effects","created_date":"2017-08-28","modified_date":null,"key_message_list":[{"field_id":1468,"order_no":1,"bullet":" Effient (prasugrel) is a prescription drug that is authorized for sale in Canada and used with low-dose acetylsalicylic acid, such as aspirin, to decrease the risk of having a stroke, having another heart attack or dying from a disease related to the heart or blood vessels."},{"field_id":1468,"order_no":2,"bullet":" Health Canada reviewed the risk of severe skin side effects (SCAR) after cases of this risk were reported by the manufacturer."},{"field_id":1468,"order_no":3,"bullet":"Health Canada's review concluded that there was not enough information available to establish a link between the risk of SCAR and the use of Effient. Health Canada will continue to monitor this risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1469,"order_no":1,"bullet":"Effient is a prescription drug that is authorized for sale in Canada and used with low-dose acetylsalicylic acid, such as aspirin, to reduce the risk of having a stroke, having another heart attack or dying from a disease related to the heart or blood vessels."},{"field_id":1469,"order_no":2,"bullet":"Effient was first marketed in Canada in 2010 and is available as a tablet."},{"field_id":1469,"order_no":3,"bullet":"In 2016, approximately 28,000 prescriptions were filled in Canada."}],"finding_list":[{"field_id":1470,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of SCAR linked to the use of Effient."},{"field_id":1470,"order_no":2,"bullet":"The safety review looked at 11 international reports of SCAR in patients treated with Effient. In 7 of the 11 reports, the link between SCAR and the use of Effient was considered to be possible; however other factors such as the advanced age of the patients and the use of other medications at the same time may have played a role. For the remaining 4 reports, the condition was considered unlikely linked to Effient use or there was not enough information to assess the link."},{"field_id":1470,"order_no":3,"bullet":"In the literature reviewed, there was no evidence of increased risk of SCAR with the use of Effient."}],"conclusion_list":[{"field_id":1471,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough information available to establish a link between the risk of SCAR and the use of Effient."},{"field_id":1471,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1471,"order_no":3,"bullet":"Health Canada will continue to monitor side effects involving Effient, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00175","review_date":null,"drug_name":"Paradigm insulin infusion pump manufactured by Medtronic MiniMed","safety_issue":"Risk of device malfunctions: loose drive support cap, keypad issues and blank screens","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1476,"overview":"In 2015, Health Canada reviewed the risk of problems with the Paradigm insulin infusion pump following reports involving the drive support cap as well as the keypad. In 2017, Health Canada wrote another review to assess the effectiveness of changes to the pump and identified additional issues to monitor. The 2017 review assessed complaints reported between 2015 and 2016.
","use_canada":1477,"findings":1478,"conclusion":1479,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information, and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Paradigm insulin infusion pump - Assessing the potential risk of malfunctions with the device","created_date":"2017-10-23","modified_date":null,"key_message_list":[{"field_id":1476,"order_no":1,"bullet":"The Paradigm insulin infusion pump is a medical device licensed for sale in Canada to give insulin and help diabetic patients manage their blood sugar levels."},{"field_id":1476,"order_no":2,"bullet":"Health Canada performed a review to assess the effectiveness of changes to the pump following recommendations from a previous review in 2015. "},{"field_id":1476,"order_no":3,"bullet":"The current review identified additional issues relating to loose drive support caps, keypad problems and blank screens. These malfunctions may lead to the patient's blood sugar becoming too high or too low."},{"field_id":1476,"order_no":4,"bullet":"Health Canada will monitor and reassess these issues in 2 years as the manufacturer is making additional changes to the pump to address current issues."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1477,"order_no":1,"bullet":"The Paradigm insulin infusion pump is a medical device licensed for sale in Canada to give insulin and help diabetic patients manage their blood sugar levels."},{"field_id":1477,"order_no":2,"bullet":"Some of the issues are due to user errors. Patientsare reminded to carefully read the pump's instructions to ensure that they are using the device correctly and not to expose the pump to water during activities like swimming, showering or bathing, as the pump is not waterproof."},{"field_id":1477,"order_no":3,"bullet":"The pump has been licensed in Canada since May 2002. Between 2011 and 2016, approximately 38,300 pumps were distributed in Canada. The life-span of the pump is 4 years."}],"finding_list":[{"field_id":1478,"order_no":1,"bullet":"Loose drive support capHealth Canada reviewed the potential risk of SW and SRED with the use of atypical antipsychotics, following the publication of a case report describing these events in a patient treated with ziprasidone. Sleep walking is a sleep disorder that causes people to get up and walk or do other complex actions while asleep. Sleep-related eating disorder is a variant of SW in which people get up frequently to eat and drink while asleep. As a consequence, the person may have dangerous behaviors such as cooking food while asleep, which may lead to injuries.
","use_canada":1477,"findings":1478,"conclusion":1479,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1480,"title":"Summary Safety Review - Atypical antipsychotics - Assessing the potential risk of sleep walking and sleep-related eating disorder","created_date":"2017-09-21","modified_date":null,"key_message_list":[{"field_id":1476,"order_no":1,"bullet":"Atypical antipsychotics are authorized for sale in Canada to treat mental disorders including schizophrenia, bipolar disorder and depression."},{"field_id":1476,"order_no":2,"bullet":"Health Canada reviewed the potential risk of sleep walking (SW) and sleep-related eating disorder (SRED) with the use of atypical antipsychotics, following the publication of a case report describing these events in a patient treated with ziprasidone."},{"field_id":1476,"order_no":3,"bullet":"Health Canada's safety review has found a link between SW and SRED and the use of atypical antipsychotics. Health Canada has recommended to update the product safety information for all atypical antipsychotics to include these side effects."}],"footnotes_list":[{"field_id":1480,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[],"use_canada_list":[{"field_id":1477,"order_no":1,"bullet":"Atypical antipsychotics are authorized for sale in Canada to treat mental disorders such as schizophrenia, bipolar disorder and depression."},{"field_id":1477,"order_no":2,"bullet":"There are 9 different atypical antipsychotics marketed in Canada since 1991: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. Some of these medications are available as generic versions."},{"field_id":1477,"order_no":3,"bullet":"Sleep walking is currently mentioned in the product safety information for aripiprazole, lurasidone, paliperidone, quetiapine, and risperidone. Sleep-related eating disorder is only mentioned in the product safety information for lurasidone, paliperidone, quetiapine, and risperidone."},{"field_id":1477,"order_no":4,"bullet":"In 2016, there were approximately 18 million prescriptions for atypical antipsychotics filled in Canada."}],"finding_list":[{"field_id":1478,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 13 unique Canadian reportsa of SW and SRED suspected to be linked to the use of atypical antipsychotics. The review of these 13 reports suggested that in 2 cases the sleep disorders were likely linked to the use of atypical antipsychotics. The patients recovered when they stopped the treatment. Six (6) reports, out of 13, were found to have a possible link. Other risk factors such as pre-existing conditions, history of these sleep disorders or use of other medications, could have contributed to the events; however, a link could not be ruled out. The 5 remaining reports could not be assessed because there was not enough information."},{"field_id":1478,"order_no":2,"bullet":"This safety review looked at information from 413 international reports of SW and SRED associated with the use of atypical antipsychotics, but these reports provided limited additional information."},{"field_id":1478,"order_no":3,"bullet":"In addition, Health Canada found 23 published case reports of SW and SRED associated with the use of atypical antipsychotics. In the majority of these reports, patients recovered when they stopped the treatment and in some cases, the events returned when patients resumed the treatment. The drug was taken as recommended and the events appeared to happen more often with higher doses. Overall, the review of these case reports suggested a link between the use of atypical antipsychotics and SW and SRED."}],"conclusion_list":[{"field_id":1479,"order_no":1,"bullet":"Health Canada's safety review has found a link between SW and SRED and the use of atypical antipsychotics. Health Canada has recommended to update the product safety information for all atypical antipsychotics to include these side effects."},{"field_id":1479,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products."},{"field_id":1479,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving atypical antipsychotics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00177","review_date":null,"drug_name":"Birth control hormone (levonorgestrel, LNG)-releasing systems that are placed into the uterus (intrauterine systems, IUS) - Mirena, Jaydess and Kyleena","safety_issue":"Decreased breast milk production (suppressed lactation)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1486,"overview":"Health Canada reviewed the risk of decreased breast milk production with the use of LNG-IUS products because of Canadian reports in women using Mirena. The current Canadian product information for LNG-IUS mentions that these methods of birth control do not seem to affect the amount and quality of breast milk.
","use_canada":1487,"findings":1488,"conclusion":1489,"additional":"The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports, as well as what is known about the use of these health products in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1490,"title":"Summary Safety Review - Birth control hormone systems (intrauterine) - Assessing the potential risk of less breast milk production","created_date":"2017-09-21","modified_date":null,"key_message_list":[{"field_id":1486,"order_no":1,"bullet":"LNG-IUS products (Mirena, Jaydess and Kyleena) are prescription drug-releasing devices authorized for sale in Canada for birth control. Mirena is also authorized for the treatment of heavy periods (menstrual bleeding) without a known cause."},{"field_id":1486,"order_no":2,"bullet":"Health Canada reviewed the risk of decreased breast milk production with the use of LNG-IUS products because of Canadian reports regarding women using Mirena."},{"field_id":1486,"order_no":3,"bullet":"Health Canada's review concluded that there is currently limited evidence to suggest a link between LNG-IUS products and the risk of decreased breast milk production. Health Canada is considering updating the LNG-IUS product information to mention that cases of decreased breast milk production in women using LNG-IUS have been reported."}],"footnotes_list":[{"field_id":1490,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1487,"order_no":1,"bullet":"LNG-IUS products (Mirena, Jaydess and Kyleena) release the birth control hormone levonorgestrel. These products are placed into a woman's uterus to provide birth control for up to 3 to 5 years depending on the product."},{"field_id":1487,"order_no":2,"bullet":"Mirena, Jaydess and Kyleena have been marketed in Canada since 2001, 2013 and 2017, respectively."},{"field_id":1487,"order_no":3,"bullet":"In 2016, most of the prescriptions filled for LNG-IUS products were for Mirena."}],"finding_list":[{"field_id":1488,"order_no":1,"bullet":"24 published studies about women who were breastfeeding and using LNG-IUS products were reviewed. The studies concluded that the use of LNG-IUS provides highly effective birth control and that these products do not affect breastfeeding."},{"field_id":1488,"order_no":2,"bullet":"At the time of the review, Health Canada had received 19 Canadian reportsa of decreased breast milk production in breastfeeding women using LNG-IUS. All the reports were for Mirena. For 13 reports, it was considered that the use of LNG-IUS may have played a role in breastfeeding difficulties. For 3 of these reports, it was considered that the LNG-IUS was probably associated with breastfeeding difficulties, as breast milk production returned to normal when the LNG-IUS was removed. The remaining 3 reports did not have enough information to conclude that the LNG-IUS affected breast milk production."}],"conclusion_list":[{"field_id":1489,"order_no":1,"bullet":"Health Canada's review concluded that there is currently limited evidence to suggest a link between LNG-IUS products and the risk of decreased breast milk production."},{"field_id":1489,"order_no":2,"bullet":"Health Canada is considering updating the product information for these products to mention that cases of decreased breast milk production in women using LNG-IUS have been reported."},{"field_id":1489,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving LNG-IUS products as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00178","review_date":null,"drug_name":"Non-prescription (oral, 150 mg) fluconazole products","safety_issue":"Unwanted effects in pregnancy including pregnancy loss and birth defects","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1496,"overview":"Health Canada reviewed the potential risk of unwanted effects in pregnancy including loss of the developing fetus (i.e., miscarriage or stillbirth), or birth defects (i.e., major congenital malformations) with the use of non-prescription fluconazole products in part because a recently published pregnancy registry study from Denmark1 suggested that such a risk may exist. In a pregnancy registry study, information is collected from pregnant women taking certain medications to study the health of their pregnancies.
In Canada, the product information for consumers on oral non-prescription fluconazole currently does not recommend using the product during pregnancy; however, the risk information for healthcare professionals currently does not include the most recent information from published studies about use in pregnant patients. Currently, both the Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada's practice guidelines recommend that only creams applied directly to the skin and vagina (i.e., topical antifungal therapies) be used for the treatment of vaginal yeast infections during pregnancy. They also advise that fluconazole products taken by mouth (i.e., orally) should be avoided in pregnancy, and that the safety of these products in the later stages of pregnancy (i.e. the second and third trimesters) has not been studied.
","use_canada":1497,"findings":1498,"conclusion":1499,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1500,"footnotes":1501,"title":"Summary Safety Review - Non-prescription fluconazole - Assessing potential risks to pregnancy outcomes","created_date":"2017-11-09","modified_date":null,"key_message_list":[{"field_id":1496,"order_no":1,"bullet":"Non-prescription (oral, 150 mg) fluconazole products are authorized for sale in Canada to treat vaginal yeast infections (i.e., vaginal candidiasis). The consumer information for these products recommends not to use them during pregnancy."},{"field_id":1496,"order_no":2,"bullet":"Health Canada reviewed the potential risk of unwanted effects in pregnancy, including pregnancy loss (i.e., miscarriage or stillbirth) or birth defects (i.e., major congenital malformations) with non-prescription fluconazole use, in part because a recently published study1 suggested that such a risk may exist."},{"field_id":1496,"order_no":3,"bullet":"Health Canada's review found that a link between the use of non-prescription fluconazole and the risk of unwanted effects in pregnancy cannot be made at this time based on the currently available information."},{"field_id":1496,"order_no":4,"bullet":"Recently, the manufacturer of Diflucan ONE voluntarily updated the Canadian product safety information about the potential risk of pregnancy loss and birth defects. Diflucan ONE is known as the Canadian Reference Product and, as such, all the other non-prescription fluconazole products in Canada must have the same safety information. Health Canada concluded that the proposed update for Diflucan ONE is suitable and has recommended that the Canadian product information for all other non-prescription fluconazole products be updated in the same way, in order to give Canadians the most complete and up-to-date information available."},{"field_id":1496,"order_no":5,"bullet":"The updated safety information for these products will make clear that they are also not recommended for use by women who are trying to become pregnant."}],"footnotes_list":[{"field_id":1501,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1500,"order_no":1,"bullet":"Molgaard-Nielsen,D., Svanstrom,H., Melbye,M., Hviid,A., & Pasternak,B. Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth. JAMA 315, 58-67 (2016)"}],"use_canada_list":[{"field_id":1497,"order_no":1,"bullet":"Non-prescription (oral, 150 mg) fluconazole products are authorized for sale in Canada to treat vaginal yeast infections (i.e., vaginal candidiasis) in a single dose taken by mouth. Some combination packs are available, containing the single-dose, oral fluconazole capsules along with a topical antifungal cream (e.g. clotrimazole or miconazole)."},{"field_id":1497,"order_no":2,"bullet":"Non-prescription fluconazole products have been marketed in Canada since 2010. There are currently 20 such products including the brand names Diflucan ONE, Canesoral, and Monicure, as well as generic versions."}],"finding_list":[{"field_id":1498,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian reporta and 3 international reports of miscarriage that were possibly related to non-prescription fluconazole use. Five international cases were identified in the information received from the manufacturers describing birth defects that were possibly associated with non-prescription fluconazole use; however there was not enough information in any of these reports to conclude that the fluconazole product itself caused the birth defects"},{"field_id":1498,"order_no":1,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found 360 cases including pregnancy loss or birth defects, reported in patients treated with fluconazole. There was not enough information in these reports to conclude that fluconazole caused these outcomes or to determine whether the women were taking low dose fluconazole (150 mg or less) or higher doses. Higher dose fluconazole products, available by prescription only, are known to have pregnancy-related risks and these are communicated in the product safety information."},{"field_id":1498,"order_no":2,"bullet":"In the pregnancy registry study1 that suggested a link between fluconazole use and unwanted effects in pregnancy, there was not enough information to conclude whether or not the fluconazole product itself was the cause. This is partly because it was not possible to know the dose of fluconazole that was used, whether it was prescription or non-prescription, the reasons for taking the drug, how long the drug was taken, and how drug exposure was measured. In general, studies on this issue are scarce, due to the ethical and safety concerns of testing drugs in pregnant women"}],"conclusion_list":[{"field_id":1499,"order_no":1,"bullet":"Health Canada's review found that a link between the use of non-prescription fluconazole and the risk of unwanted effects in pregnancy cannot be made at this time based on the currently available information. Given the potential risk and the fact that there are other products to treat vaginal yeast infection during pregnancy, this risk information would still be useful to healthcare professionals."},{"field_id":1499,"order_no":2,"bullet":"While Health Canada was carrying out the review, the manufacturer of Diflucan ONE voluntarily updated their Canadian product safety information to communicate this potential risk, as well as to clarify that women who are trying to become pregnant should avoid using the product as well. Diflucan ONE is known as the Canadian Reference Product and, as such, all the other non-prescription fluconazole products in Canada must have the same safety information."},{"field_id":1499,"order_no":3,"bullet":"Health Canada concluded that the proposed update for Diflucan ONE is suitable and has recommended that the Canadian product safety information for all non-prescription fluconazole products be updated in the same way with this additional risk information. Women continue to be advised to avoid use of non-prescription fluconazole products while pregnant."}]},{"template":2,"link_id":"SSR00179","review_date":null,"drug_name":"Breast implants","safety_issue":"Breast implant associated-anaplastic large cell lymphoma (BIA-ALCL)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1508,"overview":"Health Canada has completed a safety review on the potential risk of BIA-ALCL, following an increase in the number of cases reported internationally. The review analysed the available information on the Canadian rate of BIA-ACL (the number of confirmed cases of BIA-ALCL reported in relation to the number of implants sold in Canada over the past 10 years). The review also looked at the literature on BIA-ALCL to better understand the characteristics of this condition.
As defined by the World Health Organisation (WHO), BIA-ALCL is a rare type of non-Hodgkin lymphoma. Non-Hodgkin lymphoma is a cancer that originates from lymphatic cells, which are part of the immune system (the system that fights infections). It is not a cancer of the breast tissue. It is usually in the form of a seroma (a clear fluid which develops in a place where tissue has been removed, for example after a surgery) between the implant itself and the surrounding tissue.
","use_canada":1509,"findings":1510,"conclusion":1511,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse event reports and what is known about BIA-ALCL both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Breast Implants - Assessing the potential risk of cancer (Breast implant associated-anaplastic large cell lymphoma)","created_date":"2017-11-24","modified_date":null,"key_message_list":[{"field_id":1508,"order_no":1,"bullet":"Breast implants are medical devices licensed for sale in Canada, used to increase breast size, replace a previous implant, correct breast unevenness, or rebuild breast tissue following surgery. Breast implants are made of a smooth or textured silicone shell and are usually filled with silicone gel or sterile salt water."},{"field_id":1508,"order_no":2,"bullet":"Health Canada has completed a safety review on the potential risk of BIA-ALCL, following an increase in the number of cases reported internationally. The review analysed the available information on the Canadian rate of BIA-ALCL. The review also looked at the literature on BIA-ALCL to better understand the characteristics of this condition."},{"field_id":1508,"order_no":3,"bullet":"Health Canada's safety review found that the Canadian rate of BIA-ALCL is low. Nearly all of the cases were associated with implants that have a textured surface, similar to what was found in other countries. "},{"field_id":1508,"order_no":4,"bullet":"Health Canada will:Health Canada reviewed the potential risk of compression of the heart due to fluid buildup around it (i.e., cardiac tamponade) after receiving Canadian reports associated with the use of TactiCath Quartz. This risk is known and labelled in the current Instructions for Use for TactiCath Quartz.
","use_canada":1517,"findings":1518,"conclusion":1519,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - TactiCath Quartz - Assessing the potential risk of compression of the heart (cardiac tamponade)","created_date":"2017-11-23","modified_date":null,"key_message_list":[{"field_id":1516,"order_no":1,"bullet":"TactiCath Quartz is a medical device authorized for sale in Canada. It is used in heart procedures to treat patients with unusual heartbeats (i.e., arrhythmias). "},{"field_id":1516,"order_no":2,"bullet":"Health Canada reviewed the potential risk of compression of the heart due to fluid buildup around it (i.e., cardiac tamponade) after receiving Canadian reports associated with the use of TactiCath Quartz. "},{"field_id":1516,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there is a potential link between the use of TactiCath Quartz and the development of cardiac tamponade. However, the risk is known and is not specific to the device itself, as it is also associated with the heart procedure. The current Instructions for Use for TactiCath Quartz does mention this risk. "},{"field_id":1516,"order_no":4,"bullet":"Health Canada encourages healthcare professionals to follow the Instructions for Use given by the manufacturer when using this device, and to report any side effects associated with its use. "},{"field_id":1516,"order_no":5,"bullet":"Health Canada will continue to monitor this safety issue and reassess if new information becomes available."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1517,"order_no":1,"bullet":"TactiCath Quartz is a medical device authorized for sale in Canada to treat patients with unusual heartbeats (i.e., arrhythmias) when drugs have not helped. It is used only by qualified heart specialists (i.e., cardiologists) in hospital or clinical settings. It is a flexible tube (catheter) put into the heart to deliver heat to treat the tissues in the heart that cause the unusual heartbeats."},{"field_id":1517,"order_no":2,"bullet":"TactiCath Quartz has been marketed in Canada since 2015."}],"finding_list":[{"field_id":1518,"order_no":1,"bullet":"At the time of the review, Health Canada had received a total of 16 unique Canadian reports of fluid buildup around the heart (i.e., pericardial effusion) associated with the use of TactiCath Quartz either during or shortly after the procedure. Of the 16 cases, 3 led to cardiac tamponade due to excess fluid around the heart. In 12 of the 16 patients, the fluid needed to be drained, while the remaining 4 patients required no treatment."},{"field_id":1518,"order_no":2,"bullet":"A review of the published literature indicated that fluid buildup around the heart leading to cardiac tamponade can happen during or shortly after these kinds of heart procedures. The risk is known, but it is not specific to any particular catheter device or manufacturer. It is believed that less than 1 in 100 patients have experienced these issues when TactiCath Quartz was used. This amount is comparable to patients having these heart procedures with other brands of devices."},{"field_id":1518,"order_no":3,"bullet":"Factors that can add to the risk of cardiac tamponade may include, but are not limited to:Health Canada reviewed the potential link between thrombocytopenia and Gilenya following annual reports that were received from the manufacturer. Thrombocytopenia is a condition where there are not enough platelets (cells in the blood involved in clotting), which may cause too much bleeding. The impact of thrombocytopenia may be worse in patients with multiple sclerosis because of their difficulty in walking which may lead to a greater risk of falls and bleeding.
","use_canada":1525,"findings":1526,"conclusion":1527,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - GILENYA (fingolimod) - Assessing the potential risk of decreased amounts of blood platelets (thrombocytopenia)","created_date":"2017-12-06","modified_date":null,"key_message_list":[{"field_id":1524,"order_no":1,"bullet":"Gilenya (fingolimod) is authorized for sale in Canada to treat multiple sclerosis, a condition that leads to damage of the nervous system, causing physical disability. It is used in patients who have had a poor response to, or are unable to tolerate one or more other therapies for multiple sclerosis."},{"field_id":1524,"order_no":2,"bullet":"Health Canada reviewed the potential link between thrombocytopenia and the use of Gilenya following annual reports that were received from the manufacturer."},{"field_id":1524,"order_no":3,"bullet":"Health Canada's safety review concluded that there was a potential link between the use of fingolimod and thrombocytopenia. The product safety information for Gilenya has been updated to inform about this potential safety issue."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1525,"order_no":1,"bullet":"Gilenya is authorized for sale in Canada to treat multiple sclerosis, a condition that leads to damage of the nervous system, causing physical disability. Gilenya reduces the frequency of signs and symptoms of multiple sclerosis and delays the progression of physical disability."},{"field_id":1525,"order_no":2,"bullet":"Gilenya is recommended for patients who have had a poor response to, or are unable to tolerate one or more other therapies for multiple sclerosis."},{"field_id":1525,"order_no":3,"bullet":"Gilenya was first marketed in Canada in March 2011."}],"finding_list":[{"field_id":1526,"order_no":1,"bullet":"At the time of the review, Health Canada had received 11 unique Canadian reports of thrombocytopenia suspected to be linked to the use of Gilenya. Eight (8) reports were excluded from further review mainly because there was not enough information. A possible link between Gilenya and thrombocytopenia was found in the remaining 3 reports."},{"field_id":1526,"order_no":2,"bullet":"This safety review also looked at information from 56 international reports and 1 literature report (from the manufacturer) of thrombocytopenia associated with the use of Gilenya. Forty (40) reports were excluded from further review mainly because there was not enough information. Of the remaining 17 reports, 14 suggested a possible link between Gilenya and thrombocytopenia, and in 3 cases, thrombocytopenia was most likely due to other causes such as infection or another medication."},{"field_id":1526,"order_no":3,"bullet":"A search of the literature found some evidence of a potential link between thrombocytopenia and Gilenya use."}],"conclusion_list":[{"field_id":1527,"order_no":1,"bullet":"Health Canada's safety review established a potential link between the use of Gilenya and thrombocytopenia."},{"field_id":1527,"order_no":2,"bullet":"The product safety information for Gilenya has been updated to inform about this potential safety issue."},{"field_id":1527,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1527,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Gilenya, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00183","review_date":null,"drug_name":"Zydelig (idelalisib)","safety_issue":"Rare brain infection (progressive multifocal leukoencephalopathy [PML])","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1544,"overview":"Health Canada reviewed the potential risk of a rare brain infection known as PML with the use of Zydelig following the publication of reports of PML in patients taking Zydelig. In 2016, the product safety information for Zydelig was updated to include a warning about the risk of serious infections; however, the potential risk of PML was not identified at that time.
","use_canada":1545,"findings":1546,"conclusion":1547,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - ZYDELIG (idelalisib) - Assessing the potential risk of a rare brain infection (progressive multifocal leukoencephalopathy)","created_date":"2017-12-15","modified_date":null,"key_message_list":[{"field_id":1544,"order_no":1,"bullet":"Zydelig (idelalisib) is a prescription drug authorized for sale in Canada to treat certain types of blood cancer."},{"field_id":1544,"order_no":2,"bullet":"Health Canada reviewed the potential risk of progressive multifocal leukoencephalopathy (PML) with the use of Zydelig, following the publication of reports of PML in patients taking Zydelig. "},{"field_id":1544,"order_no":3,"bullet":"Health Canada's review concluded that there was a possible link between Zydelig and PML. Health Canada is working with the manufacturer to update the product safety information with a warning about the risk of this rare brain infection."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1545,"order_no":1,"bullet":"Zydelig (idelalisib) is a prescription drug authorized for sale in Canada to treat 2 types of cancers:Health Canada carried out a safety review to assess the potential for negative effects on the development of children's brains (i.e., neurodevelopmental disorders) with specific sedative and anesthetic drugs (propofol, ketamine, sevoflurane, desflurane and isoflurane) used in early childhood or in pregnant women (exposure of the fetus). Health Canada initiated this review to determine if there were concerns in Canada about the negative effects on the development of children's brains with the use of certain benzodiazepines and barbiturates, after concerns wereraised by the United States Food and Drug Administration (U.S. FDA) . In December 2016, the U.S. FDA added warning statements in the product information for several sedative and anesthetic drugs regarding this risk. The risk of neurodevelopmental disorders with the use of other sedative and anesthetic drugs (lorazepam, midazolam, phenobarbital and thiopental) in early childhood or in pregnant women is assessed in a separate review.
The product safety information for propofol and ketamine warn that they should not be used during pregnancy. The product safety information for sevoflurane, desflurane and isoflurane warns that healthcare professionals should use these drugs to treat pregnant patients only if they think that the benefits outweigh the risks. Also, restrictions for use in children vary from one drug to another.
Neurodevelopmental disorders affect the functioning of the brain that may include, for example, intellectual disabilities, learning disabilities or problems with communication and movement. Many factors (e.g., genetic, social, economic and environmental) may play a role in these disorders.
","use_canada":1553,"findings":1554,"conclusion":1555,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of the sedative and anesthetic drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1556,"title":"Summary Safety Review - Sedative and anesthetic drugs (DIPRIVAN [propofol], KETALAR [ketamine], SEVORANE [sevoflurane], SUPRANE [desflurane], FORANE/ISOFLURANE USP [isoflurane] - Assessing the potential risk of negative effects on the development of children's brains (neurodevelopmental disorders)","created_date":"2017-12-22","modified_date":null,"key_message_list":[{"field_id":1552,"order_no":1,"bullet":"Sedative and anesthetic drugs are used by healthcare professionals during surgeries or medical procedures in children and adults."},{"field_id":1552,"order_no":2,"bullet":"Health Canada reviewed the potential risk of negative effects on the development of children's brains with the use of specific sedative and anesthetic drugs in early childhood or in pregnant women (exposure of the fetus)."},{"field_id":1552,"order_no":3,"bullet":"Health Canada initiated this review to determine if there were concerns in Canada about the negative effects on the development of children's brains with the use of certain benzodiazepines and barbiturates, after concerns were raised by the United States Food and Drug Administration."},{"field_id":1552,"order_no":4,"bullet":"Health Canada's review concluded that these drugs, when used repeatedly or for a lengthy period of time (more than 3 hours) during the third trimester of pregnancy or in children up to approximately 3 years of age, may potentially lead to neurodevelopmental disorders in children. However, more studies are needed to better understand the effects of these drugs on the development of children's brains."},{"field_id":1552,"order_no":5,"bullet":"Pregnant women, parents and caregivers should discuss any questions or concerns about the safety of sedative and anesthetic drugs, and the necessity of a procedure requiring these drugs with their healthcare professional."},{"field_id":1552,"order_no":6,"bullet":"Health Canada will work with the manufacturers to update the Canadian product information of these drugs with warnings about this potential risk. The Department will post an Information Update to raise awareness about this issue to parents and healthcare professionals."}],"footnotes_list":[{"field_id":1556,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1553,"order_no":1,"bullet":"Sedative and anesthetic drugs are used by healthcare professionals during surgeries and medical procedures in children and adults."},{"field_id":1553,"order_no":2,"bullet":"Propofol, ketamine, sevoflurane, desflurane and isoflurane are currently authorized for use on the Canadian market."}],"finding_list":[{"field_id":1554,"order_no":1,"bullet":"At the time of the review, Health Canada did a search for Canadiana and international reports of potential negative effects on the development of children's brains related to the use of sedative and anesthetic drugs in pregnant women or young children. In the reports that were found(39 Canadian and 38 international), 2 reports of international patients were of interest but there was not enough information to further assess these reports."},{"field_id":1554,"order_no":2,"bullet":"Published studies in animals suggest that repeated or lengthy exposure (more than 3 hours) to sedative and anesthetic drugs during the third trimester of pregnancy or in young animals can cause neurodevelopmental issues, such as problems with learning and memory. In contrast, neurodevelopmental issues were not seen when animals were treated for a shorter period of time (3 hours)."},{"field_id":1554,"order_no":3,"bullet":"Published studies, mostly in children up to 3 years of age, were also found. In these studies, some found no link between the use of these drugs and neurodevelopmental disorders while others found similar results as those seen in the animal studies. However, in studies on children, it was not clear whether the neurodevelopmental disorder was due to the drug or other factors such as illness or the surgery itself."}],"conclusion_list":[{"field_id":1555,"order_no":1,"bullet":"Health Canada's review concluded that repeated or lengthy use (more than 3 hours) of these sedative and anesthetic drugs in the third trimester of pregnancy and in children up to approximately 3 years of age may potentially lead to neurodevelopmental disorders in children."},{"field_id":1555,"order_no":2,"bullet":"Health Canada will work with the manufacturers to update the Canadian product information of these drugs with warnings about this potential risk. In addition, the Department will issue an Information Update to raise awareness about this issue to parents and healthcare professionals."},{"field_id":1555,"order_no":3,"bullet":"Health Canada will look into working with the Drug Safety and Effectiveness Network (DSEN) to further study this issue to better understand the effects that sedative and anesthetic drugs have on the development of children's brains."},{"field_id":1555,"order_no":4,"bullet":"Pregnant women, parents and caregivers should discuss any questions or concerns about the safety of sedative and anesthetic drugs and the necessity of a procedure requiring these drugs with their healthcare professional."},{"field_id":1555,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving sedative and anesthetic drugs as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00185","review_date":null,"drug_name":"Ativan (lorazepam) and midazolam (benzodiazepines); phenobarbital and thiopental (barbiturates)","safety_issue":"Negative effects on the development of children's brains (neurodevelopmental disorders)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1562,"overview":"Health Canada carried out a safety review to assess the potential fornegative effects on the development of children's brains (i.e. neurodevelopmental disorders) with specific sedative and anesthetic drugs (lorazepam, midazolam, phenobarbital and thiopental) used in early childhood (up to and including 5 years of age) or in pregnant women (exposure of the fetus). Health Canada initiated this review to determine if there were concerns in Canada, about the negative effects on the development of children's brains with the use of certain benzodiazepines and barbiturates, as these concerns were raised by the United States Food and Drug Administration (U.S. FDA),through a communication issued in December 2016.
The Canadian product safety information for lorazepam and midazolam warn that they should not be used during pregnancy. The Canadian product safety information for phenobarbital warns that during pregnancy the drug's benefit should be weighed against its risk. Also, restrictions for use in children vary from one drug to another.
The risk of neurodevelopmental disorders with the use of sedative and anesthetic drugs other than benzodiazepines and barbiturates (propofol, ketamine, sevoflurane, desflurane and isoflurane) in early childhood or pregnant women is assessed in a separate review.
Neurodevelopmental disorders affect the functioning of the brain that may include, for example, intellectual disabilities, learning disabilities or problems with communication and movement. Many factors (e.g., genetic, social, economic and environmental) may play a role in these.
","use_canada":1563,"findings":1564,"conclusion":1565,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these sedative and anesthetic drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1566,"title":"Summary Safety Review - Benzodiazepines and barbiturates - Assessing the potential risk of negative effects on the development of children's brains (neurodevelopmental disorders)","created_date":"2017-12-22","modified_date":null,"key_message_list":[{"field_id":1562,"order_no":1,"bullet":"Benzodiazepines and barbiturates are sedative and anesthetic drugs often required during surgeries and medical procedures in children and adults."},{"field_id":1562,"order_no":2,"bullet":"Health Canada reviewed the potential risk of negative effects on the development of children's brains with the use of specific sedative and anesthetic drugs in early childhood or in pregnant women (exposure of the fetus)."},{"field_id":1562,"order_no":3,"bullet":"Health Canada initiated this review to determine if there were concerns in Canada about the negative effects on the development of children's brains with the use of certain benzodiazepines and barbiturates, after concerns were raised by the United States Food and Drug Administration."},{"field_id":1562,"order_no":4,"bullet":"Health Canada's review concluded that there is limited evidence suggesting a link between the use of these sedative or anesthetic drugs and potential negative effects on the development of children's brains."},{"field_id":1562,"order_no":5,"bullet":"Pregnant women, parents and caregivers should discuss any questions or concerns about the safety of sedative and anesthetic drugs, and the necessity of a procedure requiring these drugs, with their healthcare professional."},{"field_id":1562,"order_no":6,"bullet":"Health Canada will continue to monitor this risk and will post an Information Update to raise awareness about this issue to parents and healthcare professionals."}],"footnotes_list":[{"field_id":1566,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1563,"order_no":1,"bullet":"Benzodiazepines and barbiturates are sedative and anesthetic drugs often required during surgeries and procedures in children and adults."},{"field_id":1563,"order_no":2,"bullet":"Phenobarbital, midazolam and lorazepam are available on the Canadian market. Thiopental is authorized for sale, but is not currently sold, in Canada."}],"finding_list":[{"field_id":1564,"order_no":1,"bullet":"At the time of the review, Health Canada did a search for Canadiana and international reports of potential negative effects on the development of children's brains related to the use of sedative and anesthetic drugs in pregnant women or in young children. There were a total of 137 Canadian reports and 110 international reports. However, due to multiple factors (e.g., symptoms described in the reports did not meet the definition of neurodevelopmental disorders, as described above; use of the drug was different; problem reported was not in pregnant women or children up to and including 5 years of age), Health Canada was unable to use these 247 reports to draw any conclusions."},{"field_id":1564,"order_no":2,"bullet":"Published animal studies in pregnant or young animals and studies in children did not show consistent evidence of negative effects on the development of children's brains with the use of these sedative and anesthetic drugs."}],"conclusion_list":[{"field_id":1565,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there is limited evidence suggesting a link between the use of these sedative and anesthetic drugs and neurodevelopmental disorders. The Department will post an Information Update to raise awareness about this issue to parents and healthcare professionals."},{"field_id":1565,"order_no":2,"bullet":"Pregnant women, parents and caregivers should discuss any questions or concerns about the safety of sedatives, general and anesthetic drugs and the necessity of a procedure with their healthcare professional."},{"field_id":1565,"order_no":3,"bullet":"In addition, Health Canada will also look into working with the Drug Safety and Effectiveness Network (DSEN) to look into further studying this issue to better understand the effects that sedative and anesthetic drugs have on the development of children's brains."},{"field_id":1565,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving sedative and anesthetic drugs as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00186","review_date":null,"drug_name":"Barbed (knotless) sutures","safety_issue":"Blockage of the small intestine (small bowel obstruction)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1572,"overview":"Health Canada reviewed the potential risk of blockage of the small intestine when barbed sutures are used. Health Canada conducted the review after becoming aware of published reports that a portion of a barbed suture used during surgeries became hooked onto a part of the small intestine, leading to a blockage and another surgery.
","use_canada":1573,"findings":1574,"conclusion":1575,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Barbed (knotless) sutures - Assessing the potential risk of intestine blockage (small bowel obstruction)","created_date":"2018-01-05","modified_date":null,"key_message_list":[{"field_id":1572,"order_no":1,"bullet":"Barbed sutures (also known as knotless sutures) are medical devices that are used to close tissues or wounds. "},{"field_id":1572,"order_no":2,"bullet":"Reports were published that a portion of barbed suture used during surgeries appeared to hook onto part of the small intestine, leading to a blockage and another surgery."},{"field_id":1572,"order_no":3,"bullet":"After reviewing the available information, Health Canada has confirmed the potential for barbed sutures used in surgeries in the stomach area and below (e.g., abdomen or pelvic regions) to hook onto the small intestine and create a blockage. "},{"field_id":1572,"order_no":4,"bullet":"Health Canada will work with manufacturers to update the safety information for all barbed sutures to include details about this potential risk. Health Canada will also publish a Health Product Risk Communication to raise awareness of this potential risk and the updated safety information."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1573,"order_no":1,"bullet":"Barbed sutures are medical devices authorized for sale in Canada to close tissues or wounds. They have many thorn-like barbs along the length of the thread so the suture can pass through tissue in one direction but not the other, eliminating the need for tying a knot."},{"field_id":1573,"order_no":2,"bullet":"Barbed sutures have been marketed in Canada since 2009. They are available in various versions (i.e., some are absorbed by the body over time, while others are not) and are currently sold in Canada by four different manufacturers."}],"finding_list":[{"field_id":1574,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of problems regarding barbed sutures and blockage of the intestine."},{"field_id":1574,"order_no":2,"bullet":"A review of published medical reports found 27 cases of blockage of the small intestine that were specifically linked to the use of barbed sutures. Out of these 27 cases, the blockage was noticed anywhere between 1 day and 4 months after surgery, with most cases between 2 and 4 weeks after surgery. All 27 cases required another surgery to treat the blockage. Most patients were able to leave the hospital during the first week after the surgery, but one patient with more severe intestinal damage had to have part of the small intestine removed, and spent an extra 2 months in the hospital."},{"field_id":1574,"order_no":3,"bullet":"It seems that the intestine becomes blocked when either the cut end of the thread or a barb sticks into the wall of the small intestine, causing a kink. Some authors of the reported cases suggest that either cutting the end of the suture so that it is even with the surface of the tissue or covering the cut end of the suture with another device, such as a barrier or clip, may reduce the risk of intestinal blockage with barbed sutures. However, some cases of blockage have been reported even when a barrier or clip is used."}],"conclusion_list":[{"field_id":1575,"order_no":1,"bullet":"Health Canada's review of the available information has confirmed the potential for barbed sutures used in surgeries in the stomach area and below to hook onto the small intestine and result in a blockage."},{"field_id":1575,"order_no":2,"bullet":"The current safety information for barbed sutures does not describe this risk. Therefore, Health Canada will work with manufacturers to update the safety information for all barbed sutures to include details about this potential risk. Health Canada will also publish a Health Product Risk Communication to raise awareness of this potential risk and the updated safety information."},{"field_id":1575,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving barbed sutures, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00187","review_date":null,"drug_name":"Avonex (interferon beta-1a)","safety_issue":"An inflammatory disease that affects one or more organs (sarcoidosis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1580,"overview":"During routine regulatory activities, Health Canada found international reports that indicated a possible link between the use of Avonex and sarcoidosis. Given this, Health Canada recently reviewed the potential risk of sarcoidosis linked to the use of Avonex. Sarcoidosis is a disease where lumps (granulomas) form in the body as a result of inflammation. This disease affects several organs in the body, particularly the lungs (pulmonary sarcoidosis), the nervous system (neuro-sarcoidosis), and the skin (cutaneous sarcoidosis).
","use_canada":1581,"findings":1582,"conclusion":1583,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is currently known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - AVONEX (interferon beta-1a) - Assessing the Potential Risk of an Inflammatory Disease that Affects One or More Organs (Sarcoidosis)","created_date":"2018-01-08","modified_date":null,"key_message_list":[{"field_id":1580,"order_no":1,"bullet":"Avonex is used to treat some forms of multiple sclerosis (MS), a disease of the central nervous system."},{"field_id":1580,"order_no":2,"bullet":"Health Canada recently reviewed the potential risk of sarcoidosis linked to the use of Avonex after finding international reports of this risk in individuals treated with Avonex."},{"field_id":1580,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of Avonex and the risk of sarcoidosis. Health Canada will continue to monitor the safety of Avonex."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1581,"order_no":1,"bullet":"Avonex is a prescription medication which is authorized for sale in Canada to treat some forms of multiple sclerosis (MS). It reduces damage to the central nervous system, and thus slows down the worsening of the disease."},{"field_id":1581,"order_no":2,"bullet":"Avonex is given by injection into the muscle once a week."},{"field_id":1581,"order_no":3,"bullet":"Avonex has been marketed in Canada since 2005 as a liquid in pre-filled syringes, and since 2011 as a liquid in pre-filled auto injectors."}],"finding_list":[{"field_id":1582,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of sarcoidosis in MS patients who had been treated with Avonex."},{"field_id":1582,"order_no":2,"bullet":"This safety review looked at 81 international sarcoidosis reports with Avonex use in the World Health Organization's Adverse Drug Reaction Database, almost all of which were considered serious by the reporting healthcare professionals. Among these, only 5 reports had enough information to be further assessed, one of which was found to be directly linked to treatment with Avonex."},{"field_id":1582,"order_no":3,"bullet":"The manufacturer also provided 102 international reports of sarcoidosis with Avonex use. Among these, 15 reports met the criteria for further assessment by Health Canada. Although 14 of the 15 reports were considered possibly linked to Avonex, none were found to be directly linked to its use."},{"field_id":1582,"order_no":4,"bullet":"Health Canada could not conclude from this review whether Avonex played a role in the development of sarcoidosis. The development of sarcoidosis in individuals using Avonex was not found to be greater than in the general population. Other factors, such as the large number of individuals using this medication over a 20-year market presence, use of other medications, presence of other medical conditions, and the increased risk of sarcoidosis in MS patients, also contributed to this conclusion."},{"field_id":1582,"order_no":5,"bullet":"A search of the scientific literature identified 10 reports of sarcoidosis in patients who had been treated with interferon beta-1a, the active ingredient found in Avonex. Of these reports, only 1 included treatment with the brand Avonex. A link between sarcoidosis and Avonex could not be made in this particular report because of the use of other medications at the same time, or the presence of other health problems."}],"conclusion_list":[{"field_id":1583,"order_no":1,"bullet":"Health Canada's review of the available information did not find a link between the use of Avonex and the risk of sarcoidosis."},{"field_id":1583,"order_no":2,"bullet":"Health Canada has asked the manufacturer of Avonex to actively monitor the risk of sarcoidosis in patients worldwide and to report these to Health Canada."},{"field_id":1583,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this and other health products."},{"field_id":1583,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Avonex, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00188","review_date":null,"drug_name":"DPP-4 inhibitors (gliptins): alogliptin, saxagliptin, sitagliptin, and linagliptin","safety_issue":"Skin reaction (bullous pemphigoid)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1588,"overview":"Health Canada reviewed the risk of a skin reaction known as bullous pemphigoid with the use of DPP-4 inhibitors because of international reports of this reaction with the use of these products. These cases were identified as part of information submitted by the manufacturers of these products. Bullous pemphigoid is a rare disease involving an abnormal response from the body's immune system which results in a skin reaction. The disease may cause blisters commonly seen on a person's abdomen, arms or legs. If it is not treated, patients may have problems with their body fluids (e.g., dehydration, electrolyte imbalance) or skin infections, or they may die from the body's response to infection (i.e., death due to sepsis).
","use_canada":1589,"findings":1590,"conclusion":1591,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Dipeptidylpeptidase-4 inhibitors - Assessing the potential risk of a skin reaction (bullous pemphigoid)","created_date":"2018-01-25","modified_date":null,"key_message_list":[{"field_id":1588,"order_no":1,"bullet":"DPP-4 inhibitors, known as gliptins, are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults."},{"field_id":1588,"order_no":2,"bullet":"Health Canada reviewed the risk of a skin reaction known as bullous pemphigoid with the use of DPP-4 inhibitors because of international reports in patients treated with these products. These reports were part of safety information submitted by the manufacturers of these products."},{"field_id":1588,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between any of the DPP-4 inhibitors and the risk of bullous pemphigoid. Health Canada has asked that manufacturers update the product safety information for all DPP-4 inhibitors to include warnings for this risk."},{"field_id":1588,"order_no":4,"bullet":"Patients taking DPP-4 inhibitors should contact their healthcare provider if they experience blisters or a breakdown of the skin which could be signs of bullous pemphigoid. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1589,"order_no":1,"bullet":"DPP-4 inhibitors, also known as gliptins, are prescription drugs authorized for sale in Canada to treat type 2 diabetes in adults. They are used along with an appropriate diet and exercise to control blood sugar. In some cases, they are used with another anti-diabetic drug."},{"field_id":1589,"order_no":2,"bullet":"There are currently four different gliptins on the Canadian market: sitagliptin, saxagliptin, linagliptin and alogliptin. These drugs are also available in products that combine them with other drugs that treat type 2 diabetes."},{"field_id":1589,"order_no":3,"bullet":"In 2008, sitagliptin became the first gliptin sold in Canada. There were around 5.7 million prescriptions for DPP-4 inhibitors in 2016."}],"finding_list":[{"field_id":1590,"order_no":1,"bullet":"At the time of the review, Health Canada had not received Canadian reports of bullous pemphigoid related to the use of DPP-4 inhibitors since their marketing in Canada."},{"field_id":1590,"order_no":2,"bullet":"While Health Canada was carrying out the safety review, the safety information for two of the four DPP-4 inhibitors (sitagliptin and linagliptin) was updated with warnings regarding the potential risk of bullous pemphigoid. Therefore, international reports for sitagliptin and linagliptin were not further assessed."},{"field_id":1590,"order_no":3,"bullet":"A total of 24 serious international reports of potential bullous pemphigoid with the use of alogliptin (16) or saxagliptin (8) were identified by manufacturers and from a search in the Canada Vigilance database. All 24 reports were considered to show a possible link between the skin reaction and the drug. Other factors such as older age, the presence of other medical conditions, and the use of certain drugs linked to this skin reaction were observed and could have also played a role. Of the 24 reports, three deaths were reported, one of which was considered to be possibly linked to bullous pemphigoid from using the DPP-4 inhibitor."},{"field_id":1590,"order_no":4,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found that, internationally, cases of bullous pemphigoid have been reported more often than expected with the use of DPP-4 inhibitors available in Canada."},{"field_id":1590,"order_no":5,"bullet":"Health Canada reviewed 16 publications regarding DPP-4 inhibitors and the potential risk of bullous pemphigoid. Three publications showed a potential link between bullous pemphigoid and the use of any of the DPP-4 inhibitors. The remaining publications referred to patient reports in association with specific DPP-4 inhibitors."}],"conclusion_list":[{"field_id":1591,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the use of DPP-4 inhibitors and the risk of bullous pemphigoid. Health Canada has asked that manufacturers update the product safety information for all DPP-4 inhibitors to contain warnings for this risk."},{"field_id":1591,"order_no":2,"bullet":"In addition, Health Canada will publish a notice in the Health Product InfoWatch to inform Canadians and healthcare professionals of this new safety information."},{"field_id":1591,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these and any other health products."},{"field_id":1591,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving DPP-4 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00189","review_date":null,"drug_name":"SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin)","safety_issue":"Rare brain condition (posterior reversible encephalopathy syndrome) in patients who have developed high levels of acids in the blood (diabetic ketoacidosis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1596,"overview":"After receiving two Canadian case reports involving canagliflozin, Health Canada reviewed the potential risk of PRES in patients treated with SGLT2 inhibitors who have developed DKA. SGLT2 inhibitors have been linked to an increased risk of DKA, which is a serious complication of diabetes.
Posterior reversible encephalopathy syndrome is a rare condition which can affect the brain and is characterized by sudden changes in the nervous system including headaches, confusion, seizures, and vision trouble. It can develop in association with many conditions, such as severe infection or DKA, and drugs. When PRES is caused by a drug, it is important to stop the use of the drug as soon as possible to avoid complications.
","use_canada":1597,"findings":1598,"conclusion":1599,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1600,"title":"Summary Safety Review - SGLT2 inhibitors - Assessing the potential risk of a rare brain condition (posterior reversible encephalopathy syndrome) in patients who have developed high levels of acids in the blood (diabetic ketoacidosis)","created_date":"2018-02-08","modified_date":null,"key_message_list":[{"field_id":1596,"order_no":1,"bullet":"SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body through the urine."},{"field_id":1596,"order_no":2,"bullet":"After receiving two Canadian case reports, Health Canada reviewed the potential risk of posterior reversible encephalopathy syndrome (PRES) in patients treated with SGLT2 inhibitors who had developed diabetic ketoacidosis (DKA). "},{"field_id":1596,"order_no":3,"bullet":"Health Canada's review of the available information did not find a link between the use of SGLT2 inhibitors and the risk of PRES in patients who have developed DKA. Health Canada will continue to monitor the safety of SGLT2 inhibitors."}],"footnotes_list":[{"field_id":1600,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1597,"order_no":1,"bullet":"SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body through the urine. SGLT2 inhibitors are used along with diet and exercise either alone or in combination with other specific agents that control blood sugar."},{"field_id":1597,"order_no":2,"bullet":"There are currently three different SGLT2 inhibitors on the Canadian market: canagliflozin, dapagliflozin, and empagliflozin. These drugs are also available in products that combine them with other drugs that treat type 2 diabetes."},{"field_id":1597,"order_no":3,"bullet":"Canagliflozin was the first SGLT2 inhibitor sold in Canada in 2014. In 2016, there were around 1.5 million prescriptions of SGLT2 inhibitors filled in Canada."}],"finding_list":[{"field_id":1598,"order_no":1,"bullet":"At the time of the review, Health Canada had received two unique Canadiana reports of PRES in patients treated with SGLT2 inhibitors who had developed DKA. Both reports involved canagliflozin and suggested that PRES could possibly be associated with the drug. However, other risk factors such as DKA and severe infection could have played a role in the events."},{"field_id":1598,"order_no":2,"bullet":"A search in the World Health Organization database for reports of PRES with the use of SGLT2 inhibitors did not identify any additional reports."},{"field_id":1598,"order_no":3,"bullet":"A search for published information found no additional reports or other evidence for a link between SGLT2 inhibitors and PRES."}],"conclusion_list":[{"field_id":1599,"order_no":1,"bullet":"Health Canada's review of the available information did not find enough evidence to make a link between the use of SGLT2 inhibitors and the risk of PRES in patients who have developed DKA."},{"field_id":1599,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products."},{"field_id":1599,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving SGLT2 inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00190","review_date":null,"drug_name":"Ruxolitinib","safety_issue":"Liver (hepatic) injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1606,"overview":"Health Canada carried out a safety review after receiving information that included an international report of a suspected serious liver injury from an ongoing study that used ruxolitinib to treat patients. The manufacturer was asked to provide all available data on this drug and the risk of liver injury. The product information already recommends that healthcare professionals test the patient's blood to check liver function before starting treatment with ruxolitinib and at regular periods afterward to see how patients respond to the treatment, or to see if ruxolitinib is having an unwanted effect and to adjust the dose if necessary. However, the risk of liver injury or liver failure with the use of ruxolitinib is not mentioned.
","use_canada":1607,"findings":1608,"conclusion":1609,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1610,"title":"Summary Safety Review - Ruxolitinib - Assessing the potential risk of liver injury","created_date":"2018-02-26","modified_date":null,"key_message_list":[{"field_id":1606,"order_no":1,"bullet":"Ruxolitinib is a prescription drug authorized for sale in Canada to treat adult patients with certain types of blood cancers. Health Canada carried out a safety review after receiving information that included an international report of a suspected serious liver injury from an ongoing study that used ruxolitinib to treat patients."},{"field_id":1606,"order_no":2,"bullet":"Although the risk of liver injury is not mentioned in the safety information for ruxolitinib, it recommends that healthcare professionals test the patient's blood before and during treatment for signs of liver problems."},{"field_id":1606,"order_no":3,"bullet":"Health Canada's review concluded that the evidence does not show a link between ruxolitinib and the risk of liver injury. The safety information for the drug is appropriate at this time. Health Canada will continue to monitor the safety of ruxolitinib."}],"footnotes_list":[{"field_id":1610,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1607,"order_no":1,"bullet":"Ruxolitinib is a prescription drug used to treat adult patients with an enlarged spleen (i.e. splenomegaly) and to help control the symptoms caused by myelofibrosis, a rare form of blood cancer. It is also used to control the excess amount of red blood cells in the blood in certain patients with polycythemia vera, a type of blood cancer."},{"field_id":1607,"order_no":2,"bullet":"Ruxolitinib has been marketed in Canada since 2012 under the brand name Jakavi and is available as tablets taken by mouth."}],"finding_list":[{"field_id":1608,"order_no":1,"bullet":"At the time of the review, Health Canada received one Canadian reporta of liver injury (i.e., liver failure) in a patient treated with ruxolitinib. The review of this case showed that the liver failure was likely due to the worsening (i.e., progression) of the disease for which the patient received ruxolitinib and not the drug itself."},{"field_id":1608,"order_no":2,"bullet":"This safety review looked at information collected by the manufacturer. Health Canada reviewed 25 international patient reports of liver injury or liver failure with the use of ruxolitinib. These reports provided information about the patients' symptoms and blood tests that indicated liver injury or liver failure. The symptoms happened during treatment with ruxolitinib or within 30 days of stopping the treatment."},{"field_id":1608,"order_no":3,"bullet":"A possible link between liver problems and the use of ruxolitinib was found in 11 reports and included the report from the study that triggered the review. However, it was not possible to determine whether ruxolitinib itself caused the liver problems because in general, patients with myelofibrosis and polycythemia vera often have liver problems due to their disease and also take other medications that may affect the liver. In 13 of the 25 reports, the liver problems were likely due to other causes such as other drugs or the disease itself. In the remaining report there was not enough information provided to determine whether or not ruxolitinib caused the liver injury."}],"conclusion_list":[{"field_id":1609,"order_no":1,"bullet":"Health Canada's review concluded that the evidence does not show a link between ruxolitinib and the risk of liver injury. The safety information for the drug is appropriate at this time because it recommends that healthcare professionals test the patient's blood to check the liver before starting treatment with ruxolitinib and at regular periods afterward."},{"field_id":1609,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving ruxolitinib, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00191","review_date":null,"drug_name":"Ophthalmic Viscosurgical Devices (OVDs) manufactured by Alcon Laboratories","safety_issue":"Inflammation of the front part of the eye (Toxic Anterior Segment Syndrome, TASS)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1616,"overview":"Toxic Anterior Segment Syndrome (TASS) is a type of inflammation of the front part of the eye that can happen following certain eye surgeries, such as cataract surgery. If TASS is not treated it may cause vision loss and the patient may need additional surgeries to repair the eye or prevent further damage.
In January 2017, Health Canada was made aware of 10 reports of TASS from 3 eye surgery centres in British Colombia. The OVDs being used were manufactured by Alcon Laboratories. Health Canada requested Alcon Laboratories to submit an assessment of all reports of TASS with the use of any of its OVD products.
","use_canada":1617,"findings":1618,"conclusion":1619,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international safety information and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Ophthalmic Viscosurgical Devices - Assessing the potential risk of inflammation of the front part of the eye (Toxic Anterior Segment Syndrome)","created_date":"2018-03-02","modified_date":null,"key_message_list":[{"field_id":1616,"order_no":1,"bullet":"Ophthalmic Viscosurgical Devices (OVDs) are medical devices licensed for sale in Canada. They are liquids or gels used during certain eye surgeries, such as cataract surgery, to open a space between the layers of the eye and to protect the eye during the procedure."},{"field_id":1616,"order_no":2,"bullet":"Health Canada received Canadian reports for OVDs manufactured by Alcon Laboratories that describe patients who had Toxic Anterior Segment Syndrome (TASS), a type of inflammation of the front part of the eye."},{"field_id":1616,"order_no":3,"bullet":"Health Canada reviewed the available information related to the reports of OVDs manufactured by Alcon Laboratories and TASS, but a link could not be confirmed. Health Canada will continue to monitor the safety of OVDs."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1617,"order_no":1,"bullet":"OVDs are medical devices licensed for sale in Canada and used in certain eye surgeries, most often cataract surgery. OVDs are special liquids or gels that are used to open a space between the layers of the eye and to protect the eye during the procedure."},{"field_id":1617,"order_no":2,"bullet":"During this review, 5 OVDs manufactured by Alcon Laboratories were assessed: DuoVisc Viscoelastic Solution, Provisc Viscoelastic Solution, Viscoat Ophthalmic Viscoelastic Device, Cellugel Viscosurgical Device and DisCoVisc Ophthalmic Viscosurgical Device."},{"field_id":1617,"order_no":3,"bullet":"DisCoVisc has been licensed in Canada since 2006 and the rest of the products have been licensed in Canada since 1999."}],"finding_list":[{"field_id":1618,"order_no":1,"bullet":"Based on the information provided by Alcon Laboratories, there have been 44 Canadian reports of TASS between 2010 and February 2017 associated with the use of their OVDs, including the 10 reports that triggered this review. There have been fewer than 2 reports of TASS for every 1,000 OVDs sold. Internationally, there were 414 reports of TASS during this time, less than 1 report of TASS for every 1,000 OVDs sold. The manufacturer's investigation found that all of the OVD batches involved in these reports met quality standards and it could not be concluded that there was any link between the TASS reactions and the use of OVDs."},{"field_id":1618,"order_no":2,"bullet":"The manufacturer was able to follow up for 350 of the 414 TASS reports. A total of 226 patients had recovered after treatment with corticosteroids, antibiotics or unspecified treatment, 2 patients were hospitalized and recovered after treatment with corticosteroids and antibiotics, 6 patients recovered with another eye surgery, 5 patients were referred to another eye specialist (i.e., retinal specialist) for further evaluation because they still had symptoms. For 111 reports, no information about treatment or the patient outcome was provided."},{"field_id":1618,"order_no":3,"bullet":"In general, it is difficult to determine the cause of TASS since many products and devices are used during eye surgeries that could contribute to the condition, such as fluids used to rinse the eye (i.e., irrigating solutions), tools used during the procedure, lens implants (i.e., intraocular lenses as well as the polishing, cleaning and sterilizing compounds), and other medications, preservatives, or detergents."},{"field_id":1618,"order_no":4,"bullet":"The Instruction for Use (IFU) manuals issued by Alcon Laboratories for their OVDs describe that inflammation and iritis have been reported (which can be symptoms of TASS), but a link to the use of the OVDs has not been established."},{"field_id":1618,"order_no":5,"bullet":"The IFU also recommends that the OVD be removed or flushed from the eyes as much as possible at the end of the surgery."}],"conclusion_list":[{"field_id":1619,"order_no":1,"bullet":"Health Canada's review of the available information could not establish a link between the OVDs manufactured by Alcon Laboratories and the reports of TASS."},{"field_id":1619,"order_no":2,"bullet":"Health Canada reminds healthcare professionals about the importance of following the Instruction for Use manuals issued by the manufacturers of OVDs and encourages reporting of any side effects associated with the use of OVDs."},{"field_id":1619,"order_no":3,"bullet":"Health Canada will continue to monitor safety information related to TASS and the use of OVDs, as it does for all medical devices on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely actions if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00192","review_date":null,"drug_name":"Clozapine","safety_issue":"Effectiveness of measures to monitor low numbers of white blood cells (agranulocytosis) with clozapine use","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1624,"overview":"Clozapine is a prescription drug authorized for sale in Canada to manage symptoms of schizophrenia when other drugs have not helped.
Clozapine was developed in the 1960s. In 1975, clozapine was removed from the Canadian market because of reports of life-threatening infections and deaths linked with low numbers of white blood cells (i.e., agranulocytosis). Clozapine was re-introduced to the Canadian market in 1991, but patients must be enrolled in a patient registry program to monitor their white blood cell levels before their next prescription can be filled.
Between 1991 and 2003, clozapine was distributed by a single manufacturer, and patients were monitored by this manufacturer's specific registry. The introduction of generic clozapine has led to the establishment of other registries. In June 2004, Health Canada issued a safety communication to inform healthcare professionals that the product safety information had been revised related to concerns about information sharing between registries. During routine safety review activities, concerns were raised about whether or not these processes to monitor for low numbers of white blood cells were effective.
In 2017, Health Canada decided to review all available evidence related to the effectiveness of the white blood cell monitoring measures currently in place for clozapine.
","use_canada":1625,"findings":1626,"conclusion":1627,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of clozapine both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1628,"title":"Summary Safety Review - Clozapine - Assessing the effectiveness of monitoring for low numbers of white blood cells","created_date":"2018-03-09","modified_date":"2018-07-26","key_message_list":[{"field_id":1624,"order_no":1,"bullet":"Clozapine is a prescription drug authorized for sale in Canada to manage symptoms of schizophrenia in adults when other drugs have not helped."},{"field_id":1624,"order_no":2,"bullet":"One of the known risks of clozapine use is that it can lower the number of white blood cells (i.e., agranulocytosis), which may lead to life-threatening infections. Patients must be enrolled in a registry program to monitor their white blood cell levels before their prescriptions can be refilled."},{"field_id":1624,"order_no":3,"bullet":"During routine safety review activities, concerns were raised about whether the processes to monitor for low numbers of white blood cells were effective. Health Canada decided to review all the available evidence related to the effectiveness of the white blood cell monitoring measures currently in place for clozapine."},{"field_id":1624,"order_no":4,"bullet":"Health Canada's review concluded that the monitoring measures in place for low numbers of white blood cells are acceptable, but that the risk of agranulocytosis should continue to be monitored."},{"field_id":1624,"order_no":5,"bullet":"Therefore, Health Canada is reminding healthcare professionals to follow the recommendations regarding switching of a patient from one brand of clozapine to another, as highlighted in the current product safety information."},{"field_id":1624,"order_no":6,"bullet":"The Department has also asked manufacturers of clozapine to submit, in two years, a report of all data collected related to the risk of low numbers of white blood cells when clozapine is used."}],"footnotes_list":[{"field_id":1628,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1625,"order_no":1,"bullet":"Clozapine is marketed under the brand name Clozaril and generic products are also available."}],"finding_list":[{"field_id":1626,"order_no":1,"bullet":"From 1991 to the time of the review in 2017, Health Canada received 92 Canadian reportsa of low numbers of white blood cells in patients using clozapine who later died. A review of these reports found that 11 of the deaths were possibly linked to clozapine use. For the remaining reports, another cause of death was more likely."},{"field_id":1626,"order_no":2,"bullet":"Monitoring the risk of low white blood cell counts is still important for the safe use of clozapine. The evidence found in the published literature and from patient reports submitted to Health Canada showed that the risk of low numbers of white blood cells remains for over a year after starting treatment. Therefore, the monitoring should continue throughout the duration of use. In some cases, the ongoing monitoring was helpful in detecting the decrease in the number of white blood cells before the patient became too sick."},{"field_id":1626,"order_no":3,"bullet":"Concerns were also raised regarding patients being switched from using one clozapine product to another without being appropriately monitored."}],"conclusion_list":[{"field_id":1627,"order_no":1,"bullet":"Health Canada's review concluded that the monitoring measures in place for low numbers of white blood cells are acceptable, but that the risk should still be monitored. Therefore, Health Canada has asked that the manufacturers of clozapine submit a report of all the data collected related to the risk of low numbers of white blood cells when clozapine is used. Health Canada has requested that the report be submitted in two years rather than one, given that the risk is rather low due to the monitoring system (around 1 case/1000 patient-year) and the limited information that could be obtained after 1 year."},{"field_id":1627,"order_no":2,"bullet":"Health Canada reminds healthcare professionals to follow the recommendations regarding switching of a patient from one brand of clozapine to another. These recommendations are highlighted in the current product safety information and in the safety communication issued in 2004."},{"field_id":1627,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving clozapine, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00193","review_date":null,"drug_name":"SurgiWrap adhesion barrier film","safety_issue":"Foreign body reactions (FBRs, reactions to foreign materials in the body) that may mimic the local re-appearance of cancer","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1634,"overview":"Health Canada reviewed the potential risk of FBRs to SurgiWrap, which could produce a mass that may look like a re-appearance of cancer. Some scientific publications have described this risk after surgery for women's reproductive system cancers (i.e., gynaecological cancers).
SurgiWrap adhesion barrier film is a physical barrier placed inside the body during surgery to prevent adhesions, which are types of internal scar tissue that can form around the surgical area. It is also used to help with healing by acting as a temporary support for soft tissue.
","use_canada":1635,"findings":1636,"conclusion":1637,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - SurgiWrap Adhesion Barrier Film - Assessing the potential risk of foreign body reactions that mimic local re-appearance of cancer","created_date":"2018-03-09","modified_date":null,"key_message_list":[{"field_id":1634,"order_no":1,"bullet":"SurgiWrap is a medical device authorized for sale in Canada to be placed inside the body during surgery to prevent internal scar tissues (adhesions) from forming."},{"field_id":1634,"order_no":2,"bullet":"Health Canada reviewed the potential risk of the development of foreign body reactions (FBRs) to SurgiWrap which could produce a mass that mimics a local re-appearance of cancer. This safety review was triggered after Health Canada became aware of published articles that suggested this risk which could lead to additional and unnecessary medical procedures and increase stress for patients."},{"field_id":1634,"order_no":3,"bullet":"Health Canada's review of the available information did not find enough evidence to link SurgiWrap to the development of FBRs mimicking the re-appearance of cancer. Since the Instruction for Use manual for SurgiWrap contains a warning for FBRs, Health Canada concluded that no additional safety measures are needed at this time. Health Canada will continue to monitor the safety of SurgiWrap."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1635,"order_no":1,"bullet":"SurgiWrap is a medical device authorized for sale in Canada to be placed inside the body during surgery to help with the procedure and to prevent adhesions from forming. It is also used to help with healing by acting as a temporary support for soft tissue."},{"field_id":1635,"order_no":2,"bullet":"SurgiWrap has been marketed in Canada since 2003."}],"finding_list":[{"field_id":1636,"order_no":1,"bullet":"During the review, Health Canada identified one Canadian report of the development of a FBR to SurgiWrap. However, the report did not suggest mimicking re-appearance of cancer."},{"field_id":1636,"order_no":2,"bullet":"Health Canada reviewed six international reports of FBRs to SurgiWrap. These reports also did not suggest mimicking of cancer re-appearance."},{"field_id":1636,"order_no":3,"bullet":"Health Canada reviewed four publications suggesting that FBRs mimicking cancer re-appearance are linked to SurgiWrap. However, it was not possible to conclude such a link due to a lack of patient information and medical history in these publications."}],"conclusion_list":[{"field_id":1637,"order_no":1,"bullet":"Health Canada's review concluded that there is currently not enough evidence to link the use of SurgiWrap to the development of FBRs mimicking the local re-appearance of cancer. No Canadian reports of FBRs were found that describe this side effect. The safety information for this product is suitable at this time as the Instructions for Use manual already contains a warning that FBRs may occur."},{"field_id":1637,"order_no":2,"bullet":"Healthcare professionals are encouraged to consider this potential risk for the management of patients with cancer when SurgiWrap is used."},{"field_id":1637,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this and other health products."},{"field_id":1637,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving SurgiWrap, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00194","review_date":null,"drug_name":"Halaven (eribulin mesylate)","safety_issue":"Severe skin side effects (Severe Cutaneous Adverse Reactions, SCAR), which include: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Acute Generalized Exanthematous Pustulosis (AGEP), and Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS).","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1642,"overview":"Health Canada reviewed the potential risk of SCAR with the use of Halaven because reports of a skin side effect (erythema multiforme) that could potentially have been a case of SCAR had been noted in Canada. The safety review focused on a specific set of side effects which included: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Acute Generalized Exanthematous Pustulosis (AGEP), and Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS). While rare, these side effects can lead to hospitalization and death in some cases.
","use_canada":1643,"findings":1644,"conclusion":1645,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Halaven (eribulin mesylate) - Assessing the potential Risk of severe skin side effects","created_date":"2018-03-12","modified_date":null,"key_message_list":[{"field_id":1642,"order_no":1,"bullet":"Halaven is a prescription drug that is authorized for sale in Canada to treat some types of breast cancers and soft-tissue cancers (liposarcomas)."},{"field_id":1642,"order_no":2,"bullet":"Health Canada reviewed the risk of rare severe skin side effects (Severe Cutaneous Adverse Reactions, SCAR) with the use of Halaven because a case of a skin side effect (erythema multiforme) that could potentially have been a case of SCAR had been reported in Canada."},{"field_id":1642,"order_no":3,"bullet":"Health Canada's review of the available information did not find enough information to make a direct link between the use of Halaven and the potential risk of SCAR. Health Canada concluded that the current product safety information covers the potential risk of SCAR and that no additional warnings are required. Health Canada will continue to monitor the safety of Halaven."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1643,"order_no":1,"bullet":"Halaven is a prescription drug that is authorized for sale in Canada to treat certain types of breast and soft-tissue (liposarcomas) cancers."},{"field_id":1643,"order_no":2,"bullet":"Halaven has been marketed in Canada since 2012."}],"finding_list":[{"field_id":1644,"order_no":1,"bullet":"A search for cases of SCAR in the Canada Vigilance database uncovered a report of a skin side effect (erythema multiforme) that could potentially have been a case of SCAR, which prompted a broader search. Given the seriousness of the SCAR conditions, a safety review was triggered, however, no Canadian reports of SCAR were found. This safety review looked at 22 international cases of SCAR with the use of Halaven from the manufacturer's global safety database. Of these 22 cases, 17 were excluded from further review as they either did not have enough information, were not found to be related to SCAR, or there were other medications used by the patient that may have caused SCAR. The remaining 5 cases were found to be possibly linked to the use of Halaven. Among these 5 cases, there was 1 death which could not be linked to Halaven because there was not enough information."},{"field_id":1644,"order_no":2,"bullet":"There was no published literature which suggested a direct link between Halaven and the potential risk of SCAR."},{"field_id":1644,"order_no":3,"bullet":"Both SJS and TEN have already been included in the product safety information by Health Canada, the European Medicines Agency (EMA), and the US Food and Drug Administration (FDA)."},{"field_id":1644,"order_no":4,"bullet":"Overall, there was not enough evidence to suggest a direct link between Halaven and the potential risk of SCAR."}],"conclusion_list":[{"field_id":1645,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough evidence to establish a direct link between the use of Halaven and the potential risk of SCAR. The current product safety information covers the potential risk of SCAR and no additional warnings are required."},{"field_id":1645,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1645,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Halaven, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00195","review_date":null,"drug_name":"Omnipod Insulin Management System","safety_issue":"Malfunctions with the device","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1650,"overview":"In 2014, Health Canada completed a first safety review for the Omnipod because a high number of complaints, reporting high level of blood sugar (hyperglycemia), were received at the time of the review. The review did not find a need for additional safety measures and recommended to actively monitor issues with the Omnipod.
As part of the recommended active monitoring of the Omnipod, Health Canada saw an increase in the number of complaints in the last 3 years about device malfunctions. As a result, Health Canada started another safety review that included an assessment of detailed information provided by the manufacturer and all new complaints reported since the 2014 safety review.
","use_canada":1651,"findings":1652,"conclusion":1653,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this medical device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Omnipod Insulin Management System - Assessing the potential risk of malfunctions with the device","created_date":"2018-03-21","modified_date":null,"key_message_list":[{"field_id":1650,"order_no":1,"bullet":"The Omnipod Insulin Management System (Omnipod) is licensed for sale in Canada to manage blood sugar levels in people with diabetes who need insulin."},{"field_id":1650,"order_no":2,"bullet":" Health Canada reviewed the risk of malfunctions with the Omnipod because of an increase in the number of complaints in the last 3 years, as part of active monitoring of the device. Some of the complaints reported serious consequences to patients such as high or low level of blood sugar resulting in hospitalisations. "},{"field_id":1650,"order_no":3,"bullet":" Health Canada's review concluded that there is no new safety risk for the Omnipod. Health Canada will continue to monitor the safety of the Omnipod. "}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1651,"order_no":1,"bullet":"The Omnipod is a medical device licensed for sale in Canada since 2009 to manage blood sugar levels in people with diabetes who need insulin. It delivers insulin for up to 3 days."},{"field_id":1651,"order_no":2,"bullet":"The Omnipod contains 2 parts:Health Canada reviewed the potential risk of liver injury with Pradaxa after receiving reports of severe liver injury from the manufacturer. The manufacturer was asked to provide all available data on Pradaxa and the risk of liver injury.
","use_canada":1659,"findings":1660,"conclusion":1661,"additional":"The Pharmaceutical and Medical Devices Agency of Japan issued a risk communication1 and updated the product label on September 12, 2017 to include liver injury (i.e. 'acute hepatic failure, hepatic function disorder, and jaundice').
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1704,"footnotes":1662,"title":"Summary Safety Review - PRADAXA (dabigatran etexilate) - Assessing the potential risk of liver injury","created_date":"2018-05-07","modified_date":null,"key_message_list":[{"field_id":1658,"order_no":1,"bullet":"Pradaxa (dabigatran etexilate) is a blood thinner authorized for sale in Canada to prevent blood clots from forming in the veins of legs or in lungs after knee or hip replacement surgery.; to treat blood clots and prevent them from reoccurring in the veins of legs and/or lungs; to prevent stroke or sudden blocking of a blood vessel due to potential blood clots in patients with an abnormal heart rhythm (atrial fibrillation). "},{"field_id":1658,"order_no":2,"bullet":" Health Canada reviewed the potential risk of liver injury with Pradaxa after receiving reports of severe liver injury in patients treated with Pradaxa."},{"field_id":1658,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between Pradaxa and liver injury. Health Canada will be working with the manufacturers to update the safety information for Pradaxa to inform healthcare professionals and patients about this risk."}],"footnotes_list":[{"field_id":1662,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1704,"order_no":1,"bullet":"Summary of investigation results Dabigatran etexilate methanesulfonate"}],"use_canada_list":[{"field_id":1659,"order_no":1,"bullet":"Pradaxa is a prescription drug authorized for sale in Canada as a blood thinner to:In 2014, Health Canada reviewed the potential risk of slow heartbeat, known as bradycardia, with the use of sevoflurane in children with Down syndrome (DS). The product safety information for sevoflurane was updated in Canada to mention the possibility of this risk. Before the 2014 safety review, the product safety information already mentioned that bradycardia is an adverse reaction that could happen in both adults and children in general. Health Canada re-assessed this issue following the publication of additional adverse reaction reports of bradycardia in children with DS that were given sevoflurane.
","use_canada":1669,"findings":1670,"conclusion":1671,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1672,"title":"Summary Safety Review - Sevoflurane - Re-Assessing the potential risk of slow heartbeat (bradycardia) in children with Down syndrome","created_date":"2018-04-09","modified_date":null,"key_message_list":[{"field_id":1668,"order_no":1,"bullet":"Sevoflurane is an anesthetic drug used by healthcare professionals during surgeries or other medical procedures in children and adults."},{"field_id":1668,"order_no":2,"bullet":"Health Canada re-assessed the potential risk of slow heartbeat (bradycardia) with the use of sevoflurane in children with Down syndrome (DS), because of evidence published since the last safety review."},{"field_id":1668,"order_no":3,"bullet":"Health Canada's review concluded that there is a link between sevoflurane and the risk of bradycardia in children with DS. Health Canada has recommended that the manufacturers of sevoflurane products strengthen the existing product safety information to include the evidence reported in published studies about this risk in children with DS."}],"footnotes_list":[{"field_id":1672,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1669,"order_no":1,"bullet":"Sevoflurane is an anesthetic drug used by healthcare professionals during surgeries or other medical procedures in children and adults."},{"field_id":1669,"order_no":2,"bullet":"Sevoflurane is given as a gas, inhaled through a breathing mask or through a breathing tube attached to the anesthesia machine."},{"field_id":1669,"order_no":3,"bullet":"Sevoflurane has been marketed in Canada since 1995."}],"finding_list":[{"field_id":1670,"order_no":1,"bullet":"At the time of the current review, Health Canada had received 1 Canadian reporta of bradycardia in a child with DS, possibly related to the use of sevoflurane. The report described that bradycardia happened around the time sevoflurane was given to the child but further information was not provided."},{"field_id":1670,"order_no":2,"bullet":"The current safety review identified 17 international reports of bradycardia in children with DS that were treated with sevoflurane. In 3 reports, there was a link between bradycardia and the use of sevoflurane. In 11 reports, the link between sevoflurane and bradycardia was possible, but there were other factors such as heart defects or other medications being given that may have also slowed the heart. In 2 reports, it was considered that the slow heartbeat was likely caused by the medical procedure rather than sevoflurane. The remaining report could not be assessed because it did not provide enough information."},{"field_id":1670,"order_no":3,"bullet":"Two published studies about sevoflurane use suggest that children with DS are more likely to experience bradycardia than children without DS."},{"field_id":1670,"order_no":4,"bullet":"Additionally, evidence suggests that children with DS are more at risk of bradycardia, even if they are not receiving medications. For example, heart defects are more frequent in children with DS and their nervous system could react differently to stress, by slowing down the heartbeat."}],"conclusion_list":[{"field_id":1671,"order_no":1,"bullet":"Health Canada's review concluded that there is a link between sevoflurane and the risk of bradycardia in children with DS. Health Canada has recommended that the manufacturers of sevoflurane products strengthen the existing product safety information to include the data reported in published studies about this risk in children with DS."},{"field_id":1671,"order_no":2,"bullet":"In addition, Health Canada will publish a notice in the Health Product InfoWatch to inform Canadians and healthcare professionals of this updated information."},{"field_id":1671,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this and any other health products."},{"field_id":1671,"order_no":4,"bullet":"Health Canada will continue to monitor side effects involving sevoflurane, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00202","review_date":null,"drug_name":"Imatinib mesylate (Gleevec and generics)","safety_issue":"Disorders affecting tendons","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1718,"overview":"Health Canada carried out a safety review after receiving Canadian and international reports of tendon disorders in patients treated with Gleevec.
Tendon disorders are medical conditions that result in the tendons not functioning normally. A tendon is a flexible but non-elastic piece of tissue in the body that attaches a muscle to a bone.
","use_canada":1719,"findings":1720,"conclusion":1721,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1722,"title":"Summary Safety Review - Imatinib mesylate (GLEEVEC and generics) - Assessing the potential risk of tendon disorders","created_date":"2018-06-08","modified_date":null,"key_message_list":[{"field_id":1718,"order_no":1,"bullet":"Imatinib is a drug authorized for sale in Canada to treat cancer (chemotherapy). It is used to treat several solid tumours or blood cancers."},{"field_id":1718,"order_no":2,"bullet":"Health Canada reviewed the potential risk of tendon disorders with the use of imatinib after receiving Canadian and international reports of tendon disorders in patients treated with Gleevec."},{"field_id":1718,"order_no":3,"bullet":"Health Canada's review of the available information did not find a link between the use of imatinib and the risk of tendon disorders. Health Canada will continue to monitor the safety of products containing imatinib."}],"footnotes_list":[{"field_id":1722,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1719,"order_no":1,"bullet":"Imatinib belongs to a class of cancer drugs called tyrosine kinase inhibitors. It is used to treat several solid tumours such as certain tumours of the gastrointestinal tract, or blood cancers such as chronic myeloid leukemia."},{"field_id":1719,"order_no":2,"bullet":"Imatinib has been marketed in Canada since 2001 under the brand name Gleevec. It is available as tablets taken by mouth."},{"field_id":1719,"order_no":3,"bullet":"Generic versions of imatinib are also available."}],"finding_list":[{"field_id":1720,"order_no":1,"bullet":"The review identified 6 Canadiana and 36 international reports of tendon disorders in patients treated with Gleevec that had enough information for assessment. The review of these reports could not conclude whether the tendon disorders were caused by imatinib. Other reasons could have explained the events that were observed, such as accidents, the presence of other diseases (e.g., diabetes), and the use of other medication (e.g., quinolone antibiotics) known to cause tendon disorders."},{"field_id":1720,"order_no":2,"bullet":"A search for published information found 1 long-term safety study that reported 3 serious cases of tendon injury among 832 patients treated with imatinib for more than 2 years. However, there was not enough information to further assess these cases."},{"field_id":1720,"order_no":3,"bullet":"At the time of the review, there have been no international regulatory actions taken with respect to this issue."}],"conclusion_list":[{"field_id":1721,"order_no":1,"bullet":"Health Canada's review of the available information did not find a link between the use of imatinib and the risk of tendon disorders."},{"field_id":1721,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1721,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving imatinib to identify and assess potential harms, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00198","review_date":null,"drug_name":"Atypical antipsychotics","safety_issue":"Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS - a severe reaction to the use of a drug that affects one or more organs)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1678,"overview":"Health Canada reviewed the potential risk of DRESS with the use of atypical antipsychotics, following the manufacturers' voluntary update of the product safety information for Zyprexa (olanzapine) and Zeldox (ziprasidone) to include the risk of DRESS.
DRESS describes a group of rare but serious and potentially life-threatening side effects to medications, such as fever, severe skin rash with swollen face or peeling of the skin over large areas of the body, etc. These reactions usually happen 2 weeks to 2 months after starting a medication.
","use_canada":1679,"findings":1680,"conclusion":1681,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1682,"title":"Summary Safety Review - Atypical antipsychotics - Assessing the potential risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2018-04-10","modified_date":null,"key_message_list":[{"field_id":1678,"order_no":1,"bullet":"Atypical antipsychotics are authorized for sale in Canada to treat mental disorders including schizophrenia, bipolar disorder, and depression. "},{"field_id":1678,"order_no":2,"bullet":"When the manufacturers of 2 atypical antipsychotics (Zyprexa (olanzapine) and Zeldox (ziprasidone)) voluntarily updated the product safety information to include the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Health Canada decided to review all marketed atypical antipsychotics for this riska."},{"field_id":1678,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the risk of DRESS and the use of 6 other atypical antipsychotics including clozapine, quetiapine, risperidone, aripiprazole, paliperidone and lurasidone."},{"field_id":1678,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the product safety information for these additional atypical antipsychotics to reflect the risk of DRESS."}],"footnotes_list":[{"field_id":1682,"order_no":1,"bullet":"Brexpiprazole was not assessed in this review as it was marketed after Health Canada decided to review the potential risk of DRESS with atypical antipsychotics."},{"field_id":1682,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":1682,"order_no":3,"bullet":"Eleven (11) case reports received from the Manufacturers including 4 found in the literature."}],"reference_list":[],"use_canada_list":[{"field_id":1679,"order_no":1,"bullet":"Atypical antipsychotics are prescription drugs authorized for sale in Canada to treat mental disorders such as schizophrenia, bipolar disorder, and depression."},{"field_id":1679,"order_no":2,"bullet":"There are 10 different atypical antipsychotics marketed in Canada: aripiprazole, asenapine, brexpiprazolea, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone."},{"field_id":1679,"order_no":3,"bullet":"The first atypical antipsychotic available for sale in Canada was clozapine, introduced in 1991."},{"field_id":1679,"order_no":4,"bullet":"In 2016, there were about 18 million prescriptions filled for atypical antipsychotics."},{"field_id":1679,"order_no":5,"bullet":"At this time, DRESS is listed in the product safety information for olanzapine and ziprasidone."}],"finding_list":[{"field_id":1680,"order_no":1,"bullet":"At the time of the review, the potential risk of DRESS was already listed in the product information of olanzapine and ziprasidone. As such, the review focused on the remaining atypical antipsychotics."},{"field_id":1680,"order_no":2,"bullet":"Health Canada found 5 Canadian reportsb of DRESS that could be linked to atypical antipsychotic use. These 5 reports did not have enough information to confirm the side effect of DRESS. As such, Health Canada could not conclude whether atypical antipsychotic use played a role in the development of DRESS in these 5 reports."},{"field_id":1680,"order_no":3,"bullet":"This safety review also looked at 43 international reports of DRESS that could be linked to atypical antipsychotic use. Only 11 of the 43 international reports met the definition of DRESS. Of these 11 reportsc (involving quetiapine (5), aripiprazole (3), risperidone (2) and clozapine (1)), 2 showed a likely link and 7 showed a possible link between DRESS and the involved atypical antipsychotic. The remaining 2 reports showed an unlikely link. The majority of patients involved in these reports recovered or were recovering at the time of the report after having stopped the use of the drug."},{"field_id":1680,"order_no":4,"bullet":"Health Canada also looked at additional information available from the published literature and international product labels. A search of the scientific literature found mainly reports of DRESS potentially linked to olanzapine, ziprasidone, quetiapine, aripiprazole, and clozapine."},{"field_id":1680,"order_no":5,"bullet":"Since asenapine is 1 of the newest atypical antipsychotics to be marketed in Canada, no reports describing DRESS were found. Health Canada has requested that the manufacturer of asenapine collect more information over a 3 year period to assess this potential risk with asenapine use."},{"field_id":1680,"order_no":6,"bullet":"The United States Food and Drug Administration (FDA) has included DRESS in the product safety information for olanzapine, ziprasidone, clozapine, and quetiapine. Additionally, the European Medicines Agency (EMA) has included DRESS in the product safety information for olanzapine."}],"conclusion_list":[{"field_id":1681,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the risk of DRESS and the use of 6 other atypical antipsychotics including clozapine, quetiapine, risperidone, aripiprazole, paliperidone and lurasidone. Health Canada will be working with the manufacturers to update the product safety information for these atypical antipsychotics to include the risk of DRESS."},{"field_id":1681,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these and other health products."},{"field_id":1681,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving atypical antipsychotics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00199","review_date":null,"drug_name":"Percutaneous radiofrequency (RF) ablation catheters","safety_issue":"Risk of an abnormal connection between the heart and digestive tract (atrioesophageal fistula, AEF)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1688,"overview":"Health Canada reviewed the potential risk of AEF after receiving Canadian reports related to the use of percutaneous RF ablation catheters that are used in heart procedures to treat patients with irregular heartbeats. This risk is not specific to any one device or manufacturer. While rare, AEF can be life-threatening. The Instructions for Use for some of these devices do not mention the potential risk.
","use_canada":1689,"findings":1690,"conclusion":1691,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Percutaneous radiofrequency ablation catheters - Assessing the potential risk of an abnormal connection between the heart and digestive tract (atrioesophageal fistula)","created_date":"2018-04-16","modified_date":null,"key_message_list":[{"field_id":1688,"order_no":1,"bullet":"Percutaneous RF ablation catheters are medical devices authorized for sale in Canada. They are used in heart procedures to treat patients with irregular heartbeats (i.e., arrhythmias). "},{"field_id":1688,"order_no":2,"bullet":"Health Canada reviewed the potential risk of an abnormal connection forming between the heart and the digestive tract known as an atrioesophageal fistula (AEF) after receiving rare Canadian reports related to the use of these catheters. "},{"field_id":1688,"order_no":3,"bullet":"Health Canada's review concluded that there is a potential link between the use of these catheters and the development of AEF. This risk is not specific to any one device or manufacturer. "},{"field_id":1688,"order_no":4,"bullet":"Health Canada will work with the manufacturers of these catheters to update the Instructions for Use to warn about this risk. A Health Product InfoWatch notice will be issued once the updates are completed. Health Canada will also issue a Health Product Risk Communication to healthcare professionals to inform them of this safety information."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1689,"order_no":1,"bullet":"Percutaneous RF ablation catheters are medical devices authorized for sale in Canada to treat patients with irregular heartbeats (i.e. arrhythmias) when treatment with drugs has failed. The catheters are flexible tubes put into the heart to give heat to certain parts of the heart muscles, to treat the abnormal electrical signals that cause an irregular heartbeat."},{"field_id":1689,"order_no":2,"bullet":"There are 31 licensed percutaneous RF ablation catheters currently sold in Canada by 5 different manufacturers."}],"finding_list":[{"field_id":1690,"order_no":1,"bullet":"At the time of the review, Health Canada had received 4 Canadian cases of AEF related to the use of these catheters for heart procedures. A strong link between the use of the catheter and the AEF was found in 2 cases. The link was considered possible in the remaining 2 cases. Death occurred in 3 of these patients, with the cause of death probably due to the catheter use in only 1 case."},{"field_id":1690,"order_no":2,"bullet":"Another 4 Canadian patient reports of AEF including 3 deaths were found in the published literature. Considering the limited information provided, the reports could not be assessed to determine if there was a link between the use of the catheter and the AEF."},{"field_id":1690,"order_no":3,"bullet":"A review of the medical literature found that an important risk factor for developing AEF is the close distance between the heart and digestive tract. It has been proposed that the heat made by the catheter to treat the heart may damage the area between the heart and digestive tract. This could create an abnormal opening between these 2 organs. This distance may be shorter in patients with ongoing irregular heartbeats that may have an enlarged heart (i.e., an enlarged left atrium) and in patients with low body weight. Other factors that may increase the risk of AEF include a history of acid reflux (i.e. gastroesophageal reflux), use of higher power settings with the device during the treatment, and potential injury to the digestive tract related to general anaesthesia."},{"field_id":1690,"order_no":4,"bullet":"The review showed that the AEF may not be found in a timely fashion as it may develop several days to weeks following the procedure and the symptoms are not specific to AEF. It also showed that timely management of this potentially life-threatening condition may improve the patient outcome."}],"conclusion_list":[{"field_id":1691,"order_no":1,"bullet":"Health Canada's review concluded that there is a potential link between the use of the percutaneous RF ablation catheters and the development of AEF. This risk is not specific to any one device or manufacturer."},{"field_id":1691,"order_no":2,"bullet":"Health Canada will work with the manufacturers of these catheters to update the Instructions for Use to warn about this risk. A Health Product InfoWatch notice will be issued once the updates are completed. Health Canada will also issue a Health Product Risk Communication to healthcare professionals to inform them of this safety information."},{"field_id":1691,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving these catheters, as it does for all health products on the Canadian market, to identify and assess potential harms, and take appropriate and timely action if any new health risks are identified."}]},{"template":2,"link_id":"SSR00200","review_date":null,"drug_name":"Gadolinium based contrast agents","safety_issue":"Gadolinium build-up in the brain and potential brain and nervous system (neurological) side effects","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1696,"overview":"In 2016, Health Canada reviewed the risk of gadolinium build-up in the brain and potential neurological side effects in light of published studies showing that gadolinium may accumulate in the brain when GBCAs are given repeatedly. The neurological effects of these build-ups are not known.
Following this review, Health Canada published an Information Update in January of 2017. The product information for GBCAs was updated in June 2017 to include warnings about the potential for gadolinium build-up in the brain, and advice to use the lowest dose needed and to carefully consider whether repeated doses are required. Because new information was becoming available, including from the European Medicines Agency, manufacturers and published literature, a second review was initiated in 2017. Health Canada reviewed the additional information to see if there was any evidence to support taking further action.
","use_canada":1697,"findings":1698,"conclusion":1699,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Gadolinium based contrast agents - Assessing the risk of gadolinium build-up in the brain and potential brain and nervous system (neurological) side effects","created_date":"2018-05-01","modified_date":null,"key_message_list":[{"field_id":1696,"order_no":1,"bullet":"Gadolinium based contrast agents (GBCAs) are authorized for sale in Canada to make it easier to view certain body tissues on magnetic resonance imaging (MRI) scans. There are two structurally distinct categories of commercially available GCBAs in Canada: linear and macrocyclic. Both types are marketed in Canada."},{"field_id":1696,"order_no":2,"bullet":"In 2016, Health Canada reviewed the risk of gadolinium build-up in the brain and the unknown potential neurological side effects because some published studies showed that gadolinium may stay in the brain when GBCAs are given repeatedly. Health Canada's review concluded that the risk of gadolinium build-up in the brain is higher with repeated doses of both types of GBCAs, and with the use of linear GBCAs compared to macrocyclic GBCAs; however, no neurological side effects were found in either of these situations. The product information for all GBCAs was updated in June 2017 to include warnings about the potential for gadolinium build-up in the brain, and advice to use the lowest dose needed and to carefully consider whether repeated doses are required."},{"field_id":1696,"order_no":3,"bullet":"Health Canada carried out a second review in 2017 because new information was emerging, including: a review from the European Medicines Agency; reports from the manufacturers; and scientific publications. Health Canada's second review concluded that children and pregnant women may be at greater risk of gadolinium build-up in the brain."},{"field_id":1696,"order_no":4,"bullet":"Health Canada is working with the manufacturers to make additional changes to the product information to include warnings that the use of macrocyclic GBCAs may be preferable to linear GBCAs in patients who may need repeated GBCA doses, as well as in children and pregnant women. Patients having an MRI scan using GBCAs should contact their healthcare provider if they have any questions or concerns."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1697,"order_no":1,"bullet":"GBCAs are authorized for sale in Canada to make it easier to view certain body tissues on MRI scans. Gadolinium is a chemical element found in GBCAs."},{"field_id":1697,"order_no":2,"bullet":"GBCAs are either of the linear or macrocyclic type, based on their differing chemical structures. Both types are presently marketed in Canada. In 2016, the majority of GBCAs used in Canada were of the macrocyclic type. There are currently eight GBCAs authorized for sale in Canada:Health Canada reviewed the potential risk of pancreatitis with the use of isoniazid. The safety review was triggered because in the United States the product safety information for isoniazid was updated to include the risk of pancreatitis. Pancreatitis is an inflammatory disease of the pancreas and is most commonly caused by gallstones and alcohol use, but can also be caused by a drug reaction (drug-induced pancreatitis).
","use_canada":1707,"findings":1708,"conclusion":1709,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1710,"footnotes":1711,"title":"Summary Safety Review - Isoniazid - Assessing the potential risk of inflammation of the pancreas (pancreatitis)","created_date":"2018-05-10","modified_date":null,"key_message_list":[{"field_id":1706,"order_no":1,"bullet":"Isoniazid is a prescription drug authorized for sale in Canada to treat tuberculosis (TB), a disease caused by bacteria that mainly affects the lungs, although it may affect other organs or parts of the body. "},{"field_id":1706,"order_no":2,"bullet":"Health Canada reviewed the potential risk of inflammation of the pancreas (pancreatitis) with the use of isoniazid. The review was triggered after the United States Food and Drug Administration (US FDA) updated the product safety information for isoniazid to include this risk."},{"field_id":1706,"order_no":3,"bullet":"Health Canada's review found that there is a link between the use of isoniazid and the risk of pancreatitis. "},{"field_id":1706,"order_no":4,"bullet":"Health Canada is working with the manufacturer to update the safety information for all isoniazid products to include information about this potential risk. "}],"footnotes_list":[{"field_id":1711,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1710,"order_no":1,"bullet":"Badalov N. et al. Drug-Induced Acute Pancreatitis: An Evidence-Based Review. Clin. Gastroenterol. Hepatol. 5, 648 (2007)."},{"field_id":1710,"order_no":2,"bullet":"Balani A.R. & Grendell J.H. Drug-induced pancreatitis: Incidence, management and prevention. Drug Saf. 31, 823-837 (2008)."},{"field_id":1710,"order_no":3,"bullet":"Prevent and manage drug-induced pancreatitis by identifying the offending agent and understanding the underlying mechanisms. Drugs & Therapy Perspectives 25, 19-22 (2009)."},{"field_id":1710,"order_no":4,"bullet":"Gubergrits N., Klotchkov A., Lukashevich G. & Maisonneuve P. The risk of contracting drug-induced pancreatitis during treatment for pulmonary tuberculosis. J. Pancreas 16, 278-282 (2015)."}],"use_canada_list":[{"field_id":1707,"order_no":1,"bullet":"Isoniazid is a prescription drug authorized for sale in Canada to treat TB, a disease caused by bacteria that mainly affects the lungs, although it may affect other organs or parts of the body."},{"field_id":1707,"order_no":2,"bullet":"Isoniazid can be used alone (prevention) or in combination with other anti-tuberculosis drugs for treatment."},{"field_id":1707,"order_no":3,"bullet":"Isoniazid has been marketed in Canada since 1997 under the brand name PDP-Isoniazid."}],"finding_list":[{"field_id":1708,"order_no":1,"bullet":"At the time of the review, Health Canada had received 3 Canadian reportsa of pancreatitis in patients receiving isoniazid. In these reports, the timing of isoniazid use and the development of pancreatitis was either unclear or did not match the diagnosis of drug-induced pancreatitis. As such, Health Canada removed these 3 cases from further assessment."},{"field_id":1708,"order_no":2,"bullet":"Health Canada also reviewed 14 international published reports of pancreatitis and the use of isoniazid. Of these, 3 reports were considered to be likely linked to the use of isoniazid, 9 were possibly linked and 1 case was considered unlikely to be linked. The remaining report could not be assessed because there was not enough information."},{"field_id":1708,"order_no":3,"bullet":"The review also looked at the published scientific literature. These publications suggest that there is a link between isoniazid use and the potential risk of pancreatitis, although in some cases there may have been other factors that played a role in causing pancreatitis.1, 2, 3, 4"},{"field_id":1708,"order_no":4,"bullet":"Both the US FDA and the European Medicines Agency (EMA) list the risk of pancreatitis in the isoniazid product safety information."}],"conclusion_list":[{"field_id":1709,"order_no":1,"bullet":"Health Canada's review concluded that there is a rare potential risk of pancreatitis with the use of isoniazid."},{"field_id":1709,"order_no":2,"bullet":"Health Canada is working with the manufacturer to update the Canadian safety information on isoniazid products to inform about this risk."},{"field_id":1709,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving isoniazid products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00203","review_date":null,"drug_name":"Enterra Therapy System by Medtronic","safety_issue":"Lack of effect","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1728,"overview":"Health Canada reviewed Enterra's potential lack of effect after receiving international reports suggesting the device may not work for certain patients with gastroparesis. Gastroparesis occurs in people with conditions such as diabetes, who have had stomach surgery, or who use certain drugs such as opioid pain relievers. It may also have an unknown cause.
The review focused on the lack of effect when the device was working properly, without any malfunctions. Enterra was determined to be not effective when the patient's symptoms and quality of life did not get better, or when results of tests continued to indicate abnormal stomach emptying after placement of the device.
","use_canada":1729,"findings":1730,"conclusion":1731,"additional":"At the time of the review, Health Canada was not aware of any measures taken by international regulatory authorities (United States' Food and Drug Administration, United Kingdom's Medicines and Healthcare Products Regulatory Agency, and Australia's Therapeutic Goods Administration) on this issue.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1736,"footnotes":0,"title":"Summary Safety Review - Enterra Therapy System - Assessing the potential lack of effect","created_date":"2018-05-25","modified_date":"2018-06-08","key_message_list":[{"field_id":1728,"order_no":1,"bullet":"The Enterra Therapy System (Enterra) is a medical device licensed for sale in Canada. It is used to treat patients who have significant, long-term nausea, vomiting and abdominal pain due to problems with food moving through the stomach too slowly and where no signs of blockage exist (gastroparesis), and when medications have not helped. The device is placed inside the body to give electrical signals to the stomach wall."},{"field_id":1728,"order_no":2,"bullet":"Health Canada reviewed the potential lack of effect with the use of Enterra following international reports suggesting the device was not providing the expected health benefit to a large number of patients using it."},{"field_id":1728,"order_no":3,"bullet":"Health Canada's review of the available information concluded that certain patients with gastroparesis may not benefit from the use of this device even when it's working correctly. Effectiveness of medical devices can differ from patient to patient. This risk is outlined in the medical literature and in the device's Instructions for Use."},{"field_id":1728,"order_no":4,"bullet":"Health Canada will continue to monitor Enterra's safety and effectiveness, and will reassess these if new information becomes available."}],"footnotes_list":[],"reference_list":[{"field_id":1736,"order_no":1,"bullet":"Bielefeldt K. Adverse events of gastric electrical stimulators recorded in the Manufacturer and User Device Experience (MAUDE) Registry. Auton Neurosci. 2017 Jan;202:40-44."}],"use_canada_list":[{"field_id":1729,"order_no":1,"bullet":"Enterra is a medical device licensed for sale in Canada to treat patients who have significant, long-term nausea and vomiting due to gastroparesis and when medications have not helped. The device is placed inside the body to give electrical signals to the stomach wall."},{"field_id":1729,"order_no":2,"bullet":"Enterra has:Pancreatitis is an inflammatory disease of the pancreas. It is s most commonly caused by gallstones and alcohol use, but can also be caused by a reaction to a drug (drug-induced pancreatitis). Acute pancreatitis is characterized by a sudden onset of abdominal pain which is often severe, while chronic pancreatitis is, in most cases, characterized by repeated or on-going abdominal pain which can develop after repeated episodes of acute pancreatitis.
","use_canada":1739,"findings":1740,"conclusion":1741,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1742,"title":"Summary Safety Review - Sodium/glucose cotransporter 2 (SGLT2) inhibitors - Assessing the potential risk of inflammation of the pancreas (acute and chronic pancreatitis)","created_date":"2018-07-20","modified_date":null,"key_message_list":[{"field_id":1738,"order_no":1,"bullet":"SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body by eliminating it through the urine."},{"field_id":1738,"order_no":2,"bullet":"Health Canada reviewed the potential risk of pancreatitis with the use of SGLT2 inhibitors because of Canadian reports and case reports published in the scientific literature that indicated a possible link."},{"field_id":1738,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of SGLT2 inhibitors and the risk of acute pancreatitis. However, there was limited evidence to suggest a link with chronic pancreatitis."},{"field_id":1738,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the product safety information for SGLT2 inhibitors to inform healthcare professionals and patients about this risk."}],"footnotes_list":[{"field_id":1742,"order_no":1,"bullet":"Ertugliflozin was not assessed in this review as it was authorized for sale after Health Canada decided to review the potential risk of inflammation of the pancreas with SGLT2 inhibitors"},{"field_id":1742,"order_no":2,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1739,"order_no":1,"bullet":"SGLT2 inhibitors are prescription drugs authorized for sale in Canada to lower blood sugar in adults with type 2 diabetes. They work by helping remove excess sugar from the body by eliminating it through the urine. SGLT2 inhibitors are used, along with diet and exercise, either alone or in combination with other specific agents that control blood sugar."},{"field_id":1739,"order_no":2,"bullet":"There are currently 4 different SGLT2 inhibitors on the Canadian market: canagliflozin, dapagliflozin, empagliflozin and ertugliflozina. These drugs are also available in combination with other drugs that treat type 2 diabetes."},{"field_id":1739,"order_no":3,"bullet":"In 2014, canagliflozin was the first SGLT2 inhibitor sold in Canada. In 2016, the most recent data year available, there were more than 2 million prescriptions of SGLT2 inhibitors filled in Canada."}],"finding_list":[{"field_id":1740,"order_no":1,"bullet":"At the time of the review, Health Canada had received 20 Canadian reportsb of acute pancreatitis related to the use of SGLT2 inhibitors and no reports of chronic pancreatitis. Of these reports, 1 was further assessed as it met the criteria defined for this review. This Canadian report showed a possible link between acute pancreatitis and the use of an SGLT2 inhibitor."},{"field_id":1740,"order_no":2,"bullet":"The review also looked at 476 international reports and 6 published cases of pancreatitis related to the use of SGLT2 inhibitors. Of these reports, 28 cases of acute pancreatitis, but no cases of chronic pancreatitis, were further assessed as they met the criteria defined for this review. Of the 28 reports, 18 showed a possible link between acute pancreatitis and the use of a SGLT2 inhibitor. In most of the remaining reports, other medical conditions and medications could have caused the pancreatitis."},{"field_id":1740,"order_no":3,"bullet":"A review of the scientific literature did not find any published studies that showed an increased risk of pancreatitis in patients treated with SGLT2 inhibitors."},{"field_id":1740,"order_no":4,"bullet":"Product safety information in the United States and the European Union do not contain any information specific to pancreatitis."}],"conclusion_list":[{"field_id":1741,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the use of SGLT2 inhibitors and acute pancreatitis."},{"field_id":1741,"order_no":2,"bullet":"Health Canada is working with the manufacturers to update the product safety information on SGLT2 inhibitors to inform about this risk."},{"field_id":1741,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving SGLT2 inhibitors to identify and assess potential harms, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00205","review_date":null,"drug_name":"Remicade (infliximab)","safety_issue":"Blistering skin condition known as linear IgA bullous dermatosis","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1748,"overview":"Remicade is a prescription drug used to treat adults and children with inflammation of the skin (psoriasis), joints (rheumatoid or psoriatic arthritis) and intestines (Crohn's disease and ulcerative colitis) caused by an imbalance of the body's own defense system (autoimmune disease).
Remicade is an immune system protein (antibody), which blocks a naturally occurring chemical known as TNF-α (Tumour Necrosis Factor-alpha) that causes inflammation in the body.
Health Canada reviewed the potential risk of a blistering skin condition known as linear IgA bullous dermatosis with the use of Remicade, following published reports of this risk in patients treated with Remicade.
","use_canada":1749,"findings":1750,"conclusion":1751,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1752,"title":"Summary Safety Review - REMICADE (infliximab) - Assessing the potential risk of a blistering skin condition known as linear IgA bullous dermatosis","created_date":"2018-07-23","modified_date":null,"key_message_list":[{"field_id":1748,"order_no":1,"bullet":"Remicade is authorized for sale in Canada to treat adults and children with inflammation of the skin (psoriasis), joints (rheumatoid or psoriatic arthritis), and intestines (Crohn's disease and ulcerative colitis) that result from an imbalance of the body's defense system (autoimmune disease). "},{"field_id":1748,"order_no":2,"bullet":"Health Canada reviewed the potential risk of a blistering skin condition known as linear IgA bullous dermatosis with the use of Remicade, following published reports of this risk in patients treated with Remicade. "},{"field_id":1748,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Remicade and the risk of linear IgA bullous dermatosis. Health Canada has worked with the manufacturer of Remicade to update the product safety information to include the risk of this blistering skin condition."}],"footnotes_list":[{"field_id":1752,"order_no":1,"bullet":"The Canadian report can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1749,"order_no":1,"bullet":"Remicade is a prescription drug authorized for sale in Canada. It has been marketed in Canada since 2001."}],"finding_list":[{"field_id":1750,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian reporta of a blistering skin condition in a patient treated with Remicade. This report showed that there was a potential link between the use of Remicade and the blistering skin condition."},{"field_id":1750,"order_no":2,"bullet":"The safety review also looked at information from 6 case reports (including the Canadian report) provided by the manufacturer of Remicade. It was determined that, in 4 of these cases, the blistering skin disease was potentially related to the Remicade treatment, while the remaining 2 cases could not be assessed due to missing information."},{"field_id":1750,"order_no":3,"bullet":"Review of data from these cases and the scientific literature supported a possible link between the use of Remicade and the risk of the blistering skin condition."},{"field_id":1750,"order_no":4,"bullet":"Since the blistering skin condition has only been reported in a small number of patients using Remicade, it was concluded that the risk of it happening with the use of the drug is rare."},{"field_id":1750,"order_no":5,"bullet":"The European Medicines Agency has updated the product safety information for Remicade to include the risk of this blistering skin condition. Product safety information in the United States does not contain any information specific to this blistering skin condition."}],"conclusion_list":[{"field_id":1751,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Remicade and the risk of the blistering skin condition."},{"field_id":1751,"order_no":2,"bullet":"Health Canada has worked with the manufacturer of Remicade to update the product safety information to include the risk of this blistering skin condition."},{"field_id":1751,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Remicade, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00206","review_date":null,"drug_name":"Imbruvica (ibrutinib)","safety_issue":"Abnormal heart rhythm (ventricular tachyarrhythmia)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1758,"overview":"Ibrutinib belongs to a class of cancer drugs called protein kinase inhibitors. It is used for the treatment of adult patients who have a cancer of the bone marrow called chronic lymphocytic leukemia, or have other types of cancer of the blood affecting white blood cells such as Mantle cell lymphoma and Waldenström's macroglobulinemia. It is also used in patients who suffer from a medical complication after receiving transplanted tissue from a donor. This medical complication is called refractory chronic graft versus host disease.
Ventricular tachyarrhythmia is a particular type of serious, life-threatening irregular heart rate that could lead to light-headedness, palpitations, chest pain or eventually sudden death.
","use_canada":1759,"findings":1760,"conclusion":1761,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1762,"footnotes":1763,"title":"Summary Safety Review - IMBRUVICA (ibrutinib) - Assessing the potential risk of a serious and life-threatening abnormal heart rhythm (ventricular tachyarrhythmia)","created_date":"2018-07-26","modified_date":null,"key_message_list":[{"field_id":1758,"order_no":1,"bullet":"Ibrutinib is a drug authorized for sale in Canada to treat bone marrow and white blood cell cancers. It is also used for the treatment of patients who suffer from refractory chronic graft versus host disease after receiving transplanted tissue from a donor."},{"field_id":1758,"order_no":2,"bullet":"Health Canada reviewed the potential risk of a type of abnormal heart rhythm called ventricular tachyarrhythmia with the use of ibrutinib following the publication of an article1 describing a potential link."},{"field_id":1758,"order_no":3,"bullet":"Health Canada's review of the available information found that there may be a link between ibrutinib and ventricular tachyarrhythmia. Health Canada has worked with the manufacturer of ibrutinib to update the product safety information to include ventricular tachyarrhythmia."}],"footnotes_list":[{"field_id":1763,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1762,"order_no":1,"bullet":"Lampson B, Yu L, Glynn R et al; Ventricular arrhythmias and sudden death in patients taking ibrutinib. Blood, 4 May 2017, Vol 129. No. 18, pp. e2581-2584"}],"use_canada_list":[{"field_id":1759,"order_no":1,"bullet":"Ibrutinib has been marketed in Canada since 2014 under the brand name Imbruvica. It is available as capsules taken by mouth."},{"field_id":1759,"order_no":2,"bullet":"There have been 22,917 prescriptions of ibrutinib in Canada since its approval in 2014."}],"finding_list":[{"field_id":1760,"order_no":1,"bullet":"At the time of the review, Health Canada had received 5 Canadian reportsa of ventricular tachyarrhythmia suspected to be linked to ibrutinib. Of these reports, 1 was further assessed as it met the criteria for this review. This Canadian report showed a likely link between ibrutinib and ventricular tachyarrhythmia."},{"field_id":1760,"order_no":2,"bullet":"The review also looked at 150 international reports of ventricular tachyarrhythmia suspected to be linked to ibrutinib. Of these reports, 23 were further assessed as they met the criteria for this review. Of the 23 reports, 3 showed a likely link and 20, with one reporting death, were found to have a possible link between ibrutinib and ventricular tachyarrhythmia."},{"field_id":1760,"order_no":3,"bullet":"In 9 of the 24 cases that were looked at (1 Canadian and 23 international), other factors could have played a role in the ventricular tachyarrhythmia such as the patient's medical history and other medications used."},{"field_id":1760,"order_no":4,"bullet":"Product safety information of ibrutinib in the United States, Europe and New Zealand has been updated to include ventricular tachyarrhythmia. In addition, the United Kingdom published a safety communication on the risk of ventricular tachyarrhythmia with ibrutinib."}],"conclusion_list":[{"field_id":1761,"order_no":1,"bullet":"Health Canada's review of the available information found that there may be a link between ibrutinib and ventricular tachyarrhythmia."},{"field_id":1761,"order_no":2,"bullet":"Health Canada has worked with the manufacturer of ibrutinib to update the product safety information to include ventricular tachyarrhythmia. Health Canada will post an InfoWatch PM Update for Imbruvica to inform healthcare professionals and patients about this risk."},{"field_id":1761,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving ibrutinib to identify and assess potential harms, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00207","review_date":null,"drug_name":"Methadose, Metadol-D (methadone hydrochloride)","safety_issue":"Risk of serious harm (including death) in children breastfed by mothers in methadone treatment","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1770,"overview":"Health Canada reviewed this safety issue because a published article reported 2 Canadian cases of death in children who had methadone in their blood because they were breastfed by mothers in methadone maintenance programs for opioid addiction.
Small amounts of methadone can be passed to children through breast milk. Canadian and international treatment guidelines for opioid addiction encourage breastfeeding by mothers in methadone maintenance programs, although both mothers and children should be closely monitored2. The benefits and risks of breastfeeding during methadone maintenance treatment should be carefully considered.
Reports of serious side effects including death are very rare in children who were being breastfed by mothers in methadone maintenance programs.
","use_canada":1771,"findings":1772,"conclusion":1773,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1774,"footnotes":1792,"title":"Summary Safety Review - METHADOSE and METADOL-D - Assessing the potential risk of serious harm in children exposed to methadone through breast milk","created_date":"2018-08-03","modified_date":null,"key_message_list":[{"field_id":1770,"order_no":1,"bullet":"Methadose and Metadol-D are methadone-containing drugs used to treat addiction to opioids (such as heroin) in adults. They work to prevent withdrawal symptoms, which are side effects caused by stopping the use of other opioids."},{"field_id":1770,"order_no":2,"bullet":"Health Canada became aware of a published article1 that reported 2 Canadian cases of death in children who had increased levels of methadone in their blood because they were being breastfed by mothers in treatment programs for opioid addiction (methadone maintenance programs)."},{"field_id":1770,"order_no":3,"bullet":"Health Canada's review of the available information found that there may be a link between methadone and the risk of serious harm (including death) in children exposed through breast milk. Health Canada will be working with the manufacturers of Methadose and Metadol-D to strengthen the existing product information to specifically include the risk of serious harm, including death, in children exposed to methadone through breast milk."}],"footnotes_list":[{"field_id":1792,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1774,"order_no":1,"bullet":"Madadi P, Kelly L, Ross C, Kepron C, Edwards J, Koren G. Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants. Journal of Forensic Sciences. 2016;61:1-5"},{"field_id":1774,"order_no":2,"bullet":"College of Physicians and Surgeons of Ontario: Methadone Maintenance Treatment Program Standards and Clinical Guidelines https://www.cpso.on.ca/uploadedFiles/members/MMT-Guidelines.pdf (consulted on February 2, 2018)"}],"use_canada_list":[{"field_id":1771,"order_no":1,"bullet":"Methadose (Methadone Hydrochloride Oral Concentrate) and Metadol-D (Methadone Hydrochloride Tablets, Oral Solution and Concentrate) are authorized for sale in Canada to treat opioid addiction in adults."},{"field_id":1771,"order_no":2,"bullet":"Methadone is a synthetic opioid and is considered a controlled narcotic substance that is available only by prescription."},{"field_id":1771,"order_no":3,"bullet":"Methadose and Metadol-D have been marketed in Canada since 2013 and 2014 respectively."},{"field_id":1771,"order_no":4,"bullet":"There were about 11 million prescriptions for Methadose and Metadol-D filled in Canada in 2017."}],"finding_list":[{"field_id":1772,"order_no":1,"bullet":"At the time of the review, there were only 2 Canadian casesa of methadone toxicity in children exposed through breast milk, both of which involved death. Both reports were found to have a possible link between methadone and serious harm (including death) in children exposed through breast milk."},{"field_id":1772,"order_no":2,"bullet":"This safety review also looked at 13 international cases of methadone toxicity in children exposed through breast milk, 10 of which involved death. A possible link between methadone and the risk of serious harm (including death) in children exposed through breast milk was found in 12 of these cases. The remaining case did not have enough information to be assessed."},{"field_id":1772,"order_no":3,"bullet":"Small amounts of methadone can be passed to children through breast milk and breastfeeding may, in very rare cases, put children at risk of serious side effects including trouble breathing (severe respiratory depression), heart problems and death."},{"field_id":1772,"order_no":4,"bullet":"It is possible that genetic factors may be a reason why some children are more sensitive to the effects of methadone than others, but these genetic factors are not well understood. Genetic testing in 2 of the cases involving death suggested that the children may have been especially sensitive to the effects of methadone."},{"field_id":1772,"order_no":5,"bullet":"Scientific literature and various Canadian and international guidelines encourage breastfeeding among mothers maintained on methadone. However, the benefits and risks of breastfeeding during methadone maintenance treatment should be carefully considered."},{"field_id":1772,"order_no":6,"bullet":"In all cases that were reviewed, there were factors that made assessment of the cases difficult. These included lack of information about the mother's methadone dose, cause of death, and medical history or drug use that may have contributed to the serious side effects."},{"field_id":1772,"order_no":7,"bullet":"The product information for Methadose and Metadol-D advises caution when methadone is used to treat nursing women. For both products, the product information notes that the benefits and risks of breastfeeding while on methadone therapy should be carefully weighed and that breastfeeding mothers and their children should be monitored closely."},{"field_id":1772,"order_no":8,"bullet":"The European Medicines Agency and the United States Food and Drug Administration both have similar product information listing the risk of serious harm to children who are exposed to methadone through breast milk."}],"conclusion_list":[{"field_id":1773,"order_no":1,"bullet":"Health Canada's review of the available information found that there may be a link between methadone and the risk of serious harm (including death) in children breast fed by mothers in methadone treatment."},{"field_id":1773,"order_no":2,"bullet":"Health Canada will be working with the manufacturers of Methadose and Metadol-D to strengthen their product information to warn of the risk of serious harm, including death, in children exposed to methadone through breast milk."},{"field_id":1773,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these or other health products."},{"field_id":1773,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving methadone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00208","review_date":null,"drug_name":"prednisone and prednisolone (glucocorticoids) for oral use","safety_issue":"Serious complication called scleroderma renal crisis (SRC) in patients with systemic sclerosis","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1780,"overview":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1785,"title":"Summary Safety Review - Oral prednisone and prednisolone (glucocorticoids) - Assessing the potential risk of a serious complication called scleroderma renal crisis in patients with systemic sclerosis","created_date":"2018-08-07","modified_date":null,"key_message_list":[{"field_id":1780,"order_no":1,"bullet":"Prednisone and prednisolone are prescription drugs authorized for sale in Canada for a number of uses, including treating allergies and inflammation. They work by decreasing the body's reaction to some diseases and by reducing inflammation."},{"field_id":1780,"order_no":2,"bullet":"Health Canada reviewed the potential risk of scleroderma renal crisis (SRC) with the use of oral prednisone and prednisolone products in patients with systemic sclerosis. The review was triggered after the European Medicines Agency (EMA) updated the product safety information for oral and injectable prednisone and prednisolone products on July 6, 2017, to include this risk."},{"field_id":1780,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of oral prednisone and prednisolone, especially at higher doses, and the risk of SRC in patients with systemic sclerosis."},{"field_id":1780,"order_no":4,"bullet":"Health Canada will be working with the manufacturers to update the Canadian product safety information for oral prednisone and prednisolone products to inform healthcare professionals and patients about this risk."}],"footnotes_list":[{"field_id":1785,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1782,"order_no":1,"bullet":"Prednisone and prednisolone are available in Canada in a variety of forms and combinations. The current review focused only on prednisone and prednisolone products for oral use since this route delivers higher doses of the product throughout the body. Injectable prednisone and prednisolone are not marketed in Canada."},{"field_id":1782,"order_no":2,"bullet":"Oral prednisone and prednisolone products have been marketed in Canada since the 1950s."},{"field_id":1782,"order_no":3,"bullet":"In 2017, more than 3.2 million prescriptions of these products were filled in Canada. Only a small percentage of the total was for use in patients with systemic sclerosis."}],"finding_list":[{"field_id":1783,"order_no":1,"bullet":"At the time of the review, Health Canada had received 2 Canadian reportsa of SRC related to the use of prednisone (none for prednisolone). In both reports, there was a possible link found between SRC and the use of prednisone. No Canadian deaths were reported."},{"field_id":1783,"order_no":2,"bullet":"This review also looked at 6 published international reports of SRC related to the use of prednisone (1 report) and prednisolone (5 reports). In all 6 reports, there was a possible link found between SRC and the use of prednisone or prednisolone, especially at higher doses."},{"field_id":1783,"order_no":3,"bullet":"Of the 6 international reports, 3 involved death. A possible link between death and the use of prednisolone was found in 1 of these cases. The remaining 2 cases could not be assessed as there was not enough information."},{"field_id":1783,"order_no":4,"bullet":"Seven out of 8 possible cases of prednisone and prednisolone associated with SRC had other factors present (i.e. medical conditions, other medications) that could have caused SRC."},{"field_id":1783,"order_no":5,"bullet":"A review of the scientific literature found 6 published studies and 3 review articles that supported an increased risk of SRC in patients with systemic sclerosis treated with prednisone or prednisolone, especially at higher doses."},{"field_id":1783,"order_no":6,"bullet":"The EMA updated the product safety information of oral and injectable prednisone and prednisolone products on July 6, 2017, to include safety information specific to the risk of SRC in patients with systemic sclerosis."},{"field_id":1783,"order_no":7,"bullet":"The EMA is the only known major foreign regulator to have taken action regarding this risk with these products."}],"conclusion_list":[{"field_id":1784,"order_no":1,"bullet":"Health Canada's review of the available information has concluded that there may be a link between the use of oral prednisone and prednisolone products, especially at higher doses, and SRC in patients with systemic sclerosis."},{"field_id":1784,"order_no":2,"bullet":"Health Canada will be working with the manufacturers to update the Canadian product safety information for oral prednisone and prednisolone products to inform about this risk."},{"field_id":1784,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving oral prednisone and prednisolone products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00224","review_date":null,"drug_name":"Gentiane Violet Liquid Topical (gentian violet) and Hydrofera Antibacterial Foam Dressings","safety_issue":"Cancer","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1948,"overview":"Gentian violet has been used in health products for both humans and animals. In humans, gentian violet has been used to treat infections of the skin, and as an antibacterial dye in external foam wound dressings.
In 2014, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) completed an assessment (toxicological evaluation) of certain veterinary drugs (including gentian violet) residues in food. They concluded that gentian violet can alter genetic material and cause cancer (genotoxic carcinogen). Therefore, an acceptable daily intake (ADI) cannot be established. Based on the JECFA's conclusion, the Codex Alimentarius Commission, which develops international food standards to protect consumer health and to facilitate fair trading practices in foods, recommended in 2018 that regulatory authorities prevent exposure to residues of gentian violet in food.1 Following this recommendation, Health Canada decided to review the risk of cancer with the use of gentian violet-containing human health products, in addition to veterinary products.
","use_canada":1949,"findings":1950,"conclusion":1951,"additional":"The analysis that contributed to this risk assessment included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these drugs and medical devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
If manufacturers of medical devices or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":1952,"footnotes":1953,"title":"Summary Safety Review - Gentian violet-containing human health products - Assessing the potential risk of cancer","created_date":"2019-06-12","modified_date":"2019-06-27","key_message_list":[{"field_id":1948,"order_no":1,"bullet":"Gentiane Violet Liquid Topical (gentian violet) is a non-prescription drug that has been used to treat infections of the skin (cutaneous) and inside the nose, mouth, and vagina (mucocutaneous). Gentian violet can also be found in Hydrofera Antibacterial Foam Dressings, which are used as external dressings for wounds."},{"field_id":1948,"order_no":2,"bullet":"Health Canada conducted two health risk assessments on gentian violet-containing human therapeutic products: one on the medical devices (Hydrofera antibacterial foam dressings) and one on the non-prescription drug product (Gentiane Violet Liquid Topical). These assessments were triggered by the World Health Organization's Codex Alimentarius Commission recommending that regulatory authorities prevent exposure to gentian violet in food because of its potential to cause cancer.1 "},{"field_id":1948,"order_no":3,"bullet":"Health Canada's risk assessment of medical devices containing gentian violet (Hydrofera antibacterial foam dressings), based on the limited exposure to gentian violet, did not find a risk of cancer. However, no evidence to support the safety of the devices for pregnant and nursing women has been provided, and as a precaution, Health Canada worked with the manufacturers and updated the Instructions for Use to include additional information"},{"field_id":1948,"order_no":4,"bullet":"Health Canada's risk assessment of the non-prescription drug product concluded that there is evidence based on animal studies in the scientific literature of a potential for a link between gentian violet and cancer. In studies, cases of cancer in animals following oral exposure of gentian violet were noted. There have been no reported cases of cancer in humans associated with the use of topical gentian violet in Canada or internationally."},{"field_id":1948,"order_no":5,"bullet":"Health Canada notified the manufacturer of Gentiane Violet Liquid Topical of the results of the assessment. The manufacturer agreed to voluntarily discontinue marketing of their product in Canada and their health product drug licence has been cancelled."},{"field_id":1948,"order_no":6,"bullet":"An Information Update has been published to give Canadians more details about this risk, what consumers should do, and further actions taken by Health Canada."},{"field_id":1948,"order_no":7,"bullet":"Following a separate risk assessment for veterinary drugs, manufacturers of these products also agreed to voluntarily discontinue marketing their products in Canada and their drug licence has been cancelled."}],"footnotes_list":[{"field_id":1953,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"},{"field_id":1953,"order_no":2,"bullet":"VigiBase is the WHO global database of individual case safety reports. This information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. This information does not represent the opinion of the World Health Organization."}],"reference_list":[{"field_id":1952,"order_no":1,"bullet":"Codex Alimentarius Commission: 02-06 July 2018"}],"use_canada_list":[{"field_id":1949,"order_no":1,"bullet":"Gentiane Violet Liquid Topical has been marketed in Canada since 1951. The first licence for a Hydrofera Antibacterial Foam Dressing was issued in 2012."},{"field_id":1949,"order_no":2,"bullet":"Gentiane Violet Liquid Topical is a non-prescription drug product used to treat infections of the skin (cutaneous), including the nose, mouth, and vagina (mucocutaneous). As a result of Health Canada's risk assessment, the manufacturer of the product informed Health Canada in May 2019 that they will voluntarily stop marketing this product in Canada and their health product licence has been cancelled."},{"field_id":1949,"order_no":3,"bullet":"Hydrofera Antibacterial Foam Dressings are medical devices used as external dressings for wounds such as sores (e.g., pressure ulcers, venous stasis ulcers, arterial ulcers, diabetic ulcers), skin graft donor sites, abrasions and cuts (lacerations), superficial burns, post-surgical incisions, and other external wounds."},{"field_id":1949,"order_no":4,"bullet":"In animals, gentian violet has been used topically for the treatment of surface wounds and eye infections."}],"finding_list":[{"field_id":1950,"order_no":1,"bullet":"Health Canada received 4 Canadian reportsa of adverse events associated with the use of gentian violet-containing drug products. The reported adverse events include localized skin reactions, pain, discomfort, and local discoloration. Of these 4 reports, 2 involve infants (2 months and 5 months of age). These reports confirm the use of gentian violet to treat oral thrush in infants."},{"field_id":1950,"order_no":2,"bullet":"Health Canada also identified 50 international reports involving the use of a gentian violet-containing drug product from VigiBaseb, 4 of which were considered serious."},{"field_id":1950,"order_no":3,"bullet":"While there have been no Canadian nor international reports of cancer associated with the human use of gentian violet, animal studies show a link between gentian violet and cancer when ingested. It is unknown if applying gentian violet to the skin (topical application) has the same cancer causing effect."},{"field_id":1950,"order_no":4,"bullet":"Some evidence suggests health products containing gentian violet are being used in infants and breastfeeding mothers. As such, it is possible that when gentian violet is applied to the nipple of the breast and/or used to treat thrush, it may be ingested by infants."},{"field_id":1950,"order_no":5,"bullet":"Health Canada also reviewed the risk of cancer with the use of Hydrofera Antibacterial Foam Dressings. The gentian violet in these medical devices is not intended to be released, absorbed or ingested under normal conditions of use. Evidence shows that because of the structure and composition of the medical devices, little to no gentian violet is released to the human body. Although the exposure to gentian violet from these medical devices is limited, no evidence to support the safety of the devices for pregnant and nursing women was provided to Health Canada by the manufacturer. As a precaution, Health Canada worked with the manufacturer to strengthen the device safety information to better inform users."}],"conclusion_list":[{"field_id":1951,"order_no":1,"bullet":"Health Canada conducted two health risk assessments on gentian violet-containing products: one focused on a non-prescription drug product and the other on medical devices (foam dressings)."},{"field_id":1951,"order_no":2,"bullet":"Health Canada's risk assessment of the non-prescription drug product concluded that there is evidence in the scientific literature, based on animal studies, that there is a potential for gentian violet to cause cancer. Although no cases of cancer associated with the use of topical gentian violet were found, oral exposure of gentian violet has been shown in animal studies to cause cancer."},{"field_id":1951,"order_no":3,"bullet":"Health Canada contacted the manufacturer and notified them of the results of the assessment noting the potential risk of cancer with the use of gentian violet-containing drug products. The manufacturer of Gentiane Violet Liquid Topical voluntarily discontinued the sale of the product in Canada in May 2019, and their health product drug licence has been cancelled."},{"field_id":1951,"order_no":4,"bullet":"Consumers are advised to stop using Gentiane Violet Liquid Topical and return it to their local pharmacy for proper disposal."},{"field_id":1951,"order_no":5,"bullet":"Health Canada's assessment of gentian violet-containing medical devices found that because of the structure and composition of the medical devices, little to no gentian violet is released to the human body. However, no evidence to support the safety of the devices for pregnant and nursing women was provided to Health Canada by the manufacturer."},{"field_id":1951,"order_no":6,"bullet":"As a precaution, Health Canada worked with the manufacturer to strengthen the device safety information to better inform users."},{"field_id":1951,"order_no":7,"bullet":"Additionally, any new medical device licence applications listing gentian violet as a component will be reviewed to determine maximum exposure risks."},{"field_id":1951,"order_no":8,"bullet":"Health Canada has also looked at veterinary drugs that contain gentian violet and manufacturers of the 9 impacted veterinary drug products have agreed to voluntarily discontinue marketing their products in Canada and their drug licence have been cancelled."},{"field_id":1951,"order_no":9,"bullet":"An Information Update has been published to give Canadians more details about this risk, what consumers should do, and further actions taken by Health Canada."}]},{"template":2,"link_id":"SSR00209","review_date":null,"drug_name":"Beta-lactam antibioticsa","safety_issue":"Severe skin side effects (Severe Cutaneous Adverse Reactions, SCAR).b","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1792,"overview":"Beta-lactam antibiotics are prescription drugs, which are authorized for sale in Canada to treat many types of bacterial infections.
Health Canada's review of the potential risk of severe skin side effects (SCAR) with beta-lactam antibiotics was triggered after receiving information from a manufacturer that included reports of SCAR with the use of a widely prescribed beta-lactam antibiotic (amoxicillin-clavulanic acid) in Canada. Severe skin side effects are drug reactions that are serious, but rare.
Inconsistent product information about the risk of SCAR for various beta-lactam antibiotics also triggered Health Canada to conduct this review, focusing on products that do not already include SCAR in their product information.
","use_canada":1793,"findings":1794,"conclusion":1795,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1796,"title":"Summary Safety Review - Beta-lactam antibiotics - Assessing the potential risk of severe skin side effects","created_date":"2018-09-10","modified_date":null,"key_message_list":[{"field_id":1792,"order_no":1,"bullet":"Beta-lactam antibiotics are authorized for sale in Canada to treat many types of bacterial infections."},{"field_id":1792,"order_no":2,"bullet":"Health Canada reviewed the risk of SCAR with beta-lactam antibiotics (including amoxicillin-clavulanic acid) because of information submitted by a manufacturer that suggested a potential risk of SCAR with amoxicillin-clavulanic acid. Since the risk of SCAR is included in the product information for some beta-lactam antibiotics, Health Canada decided to review all beta-lactam antibiotics, focusing on products that do not already include SCAR in their product information."},{"field_id":1792,"order_no":3,"bullet":"Health Canada's review of the available information established a link between the use of beta-lactam antibiotics and the risk of SCAR. "},{"field_id":1792,"order_no":4,"bullet":"Health Canada will be working with the manufacturers to update the product safety information of beta-lactam antibiotics (that do not already include SCAR) to inform healthcare professionals and patients about the potential risk of SCAR. "}],"footnotes_list":[{"field_id":1796,"order_no":1,"bullet":"The following beta-lactam antibiotics are currently marketed in Canada and have been included as part of this review: ampicillin, amoxicillin, piperacillin, phenoxymethylpenicillin/penicillin V, penicillin G, cloxacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cephalexin, cefazolin, cefadroxil, cefoxitin, cefuroxime axetil, cefprozil, cefotaxime, ceftazidime, cetriazone, cefixime, cefepime, aztreonam, meropenem, ertapenem, imipenem-cilastatin and ceftolozane-tazobactam."},{"field_id":1796,"order_no":2,"bullet":"Serious but rare drug reactions that include the following: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS)."},{"field_id":1796,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1793,"order_no":1,"bullet":"Beta-lactam antibiotics have been marketed in Canada for over 60 years. Penicillin V (phenoxymethylpenicillin) was the first beta-lactam antibiotic marketed in Canada on December 31, 1960."},{"field_id":1793,"order_no":2,"bullet":"The following beta-lactam antibiotics are currently marketed in Canada: ampicillin, amoxicillin, piperacillin, phenoxymethylpenicillin/penicillin V, penicillin G, cloxacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cephalexin, cefazolin, cefadroxil, cefoxitin, cefuroxime axetil, cefprozil, cefotaxime, ceftazidime, cetriazone, cefixime, cefepime, aztreonam, meropenem, ertapenem, imipenem-cilastatin and ceftolozane-tazobactam."},{"field_id":1793,"order_no":3,"bullet":"Beta-lactam antibiotics are a widely prescribed group of antimicrobial agents, with about 11.4 million prescriptions filled in Canada in 2016."}],"finding_list":[{"field_id":1794,"order_no":1,"bullet":"At the time of the review, Health Canada had received 45 Canadianc reports of SCAR related to beta-lactam antibiotics use. Of these reports, 26 were further assessed as they met the criteria set for this review. Of these 26 reports, 19 were found to have a possible link between the use of beta-lactam antibiotics and SCAR, 4 unlikely to have a link and 3 could not be assessed due to lack of information."},{"field_id":1794,"order_no":2,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found 8855 reports of SCAR in patients treated with beta-lactam antibiotics. Health Canada's review found that there was more frequent reporting of SCAR for the majority of beta-lactam antibiotics than expected in the general population."},{"field_id":1794,"order_no":3,"bullet":"This safety review also examined the medical and scientific literature. There were 9 published studies and 79 reported cases of SCAR for beta-lactam antibiotics. Health Canada's review of the published studies and cases supported a possible link between SCAR and beta-lactam antibiotics use."}],"conclusion_list":[{"field_id":1795,"order_no":1,"bullet":"Health Canada's review found a possible link between the use of beta-lactam antibiotics and the risk of SCAR."},{"field_id":1795,"order_no":2,"bullet":"Health Canada will be working with manufacturers to update the product safety information of beta-lactam antibiotics (that do not already include SCAR) to inform healthcare professionals and patients about this potential risk."},{"field_id":1795,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving beta-lactam antibiotics, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00210","review_date":null,"drug_name":"Fibristal (5 mg ulipristal acetate)","safety_issue":"Serious liver injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1802,"overview":"Health Canada reviewed the potential risk of serious liver injury with Fibristal (5 mg ulipristal acetate) following reports of four international cases of liver injury leading to liver transplantation. In March 2018, as an interim measure while the review was ongoing, Health Canada communicated the need to monitor liver function during and after treatment, and recommended not to use Fibristal in patients with liver disease.
Uterine fibroids are non-cancerous (benign) tumours of the womb. While not life-threatening, they can lead to significant impairment of patients' quality of life as they may cause excessive uterine bleeding, pain, infertility and bulk symptoms (i.e., bloating and urinary symptoms).
Ulipristal acetate 30 mg is sold in Canada under the brand name Ella. It is a single-dose prescription drug used for emergency contraception. The review showed that no cases of liver injury have been reported with the use of Ella.
","use_canada":1803,"findings":1804,"conclusion":1805,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1806,"title":"Summary Safety Review - Fibristal (5 mg ulipristal acetate) - Assessing the potential risk of rare but serious liver injury","created_date":"2018-09-07","modified_date":null,"key_message_list":[{"field_id":1802,"order_no":1,"bullet":"Fibristal (5 mg ulipristal acetate) is a prescription drug authorized for sale in Canada to treat the signs and symptoms of a type of non-cancerous tumour in the womb (uterine fibroids) in women of child-bearing age."},{"field_id":1802,"order_no":2,"bullet":"Health Canada reviewed the risk of liver injury with the use of Fibristal after becoming aware of four international reports of liver injury leading to liver transplants."},{"field_id":1802,"order_no":3,"bullet":"In March 2018, as an interim measure while the safety review was ongoing, Health Canada issued an Information Update. It informed healthcare professionals of the need to monitor liver function during and after treatment, and recommended not to use Fibristal in patients with liver disease."},{"field_id":1802,"order_no":4,"bullet":"Health Canada's review of the available information concluded that there may be a link between Fibristal use and risk of serious liver injury."},{"field_id":1802,"order_no":5,"bullet":"Health Canada is working with Fibristal's manufacturer to better understand its effects on the liver, to update the Canadian product information with new restrictions for use and recommendations to monitor liver function, and to communicate this risk to healthcare professionals and patients."}],"footnotes_list":[{"field_id":1806,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[],"use_canada_list":[{"field_id":1803,"order_no":1,"bullet":"Fibristal (5 mg ulipristal acetate) is a prescription drug which is authorized for sale in Canada to treat signs and symptoms of uterine fibroids in women of child bearing age who are eligible for surgery. It is also authorized for on and off (intermittent) treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of childbearing age. The duration of each treatment course is three months."},{"field_id":1803,"order_no":2,"bullet":"Fibristal has been marketed in Canada since 2013."},{"field_id":1803,"order_no":3,"bullet":"In 2017, there were more than 63,000 prescriptions filled in Canada."}],"finding_list":[{"field_id":1804,"order_no":1,"bullet":"Health Canada reviewed 31 reports (7 Canadiana and 24 international) of serious liver injury with Fibristal use. A possible link between liver injury and Fibristal was found in the majority of the cases (20 cases, including 5 Canadian cases). In 6 cases (including 1 Canadian case), the link was found to be unlikely mostly because of the patients' medical condition prior to Fibristal use. In 5 cases (including 1 Canadian case), there was not enough information provided and these could not be assessed. The vast majority of cases recovered or were recovering at the time of reporting (18 of 22 cases for which information was provided)."},{"field_id":1804,"order_no":2,"bullet":"Of the 20 cases having a possible link between Fibristal use and liver injury, 11 cases (2 of which were Canadian cases) reported the use of other medications or medical conditions which may have also contributed to liver injury. No pattern in the timing between Fibristal use and liver injury was found."},{"field_id":1804,"order_no":3,"bullet":"There were 4 international cases of liver injury which led to liver transplant. In one case, the outcome was death. The death in this case could not be linked to Fibristal because there was not enough information available. No cases of liver transplant were reported in Canada."},{"field_id":1804,"order_no":4,"bullet":"A review of the existing published literature did not identify any publications that would raise concerns about liver safety for Fibristal. There was no suggestion of liver injury from earlier research studies (both animal and human data)."},{"field_id":1804,"order_no":5,"bullet":"The mechanism by which Fibristal could potentially cause liver injury is unknown at this time."},{"field_id":1804,"order_no":6,"bullet":"The European Medicines Agency (EMA) updated their product information for Fibristal to include the risk of liver injury and that liver function should be monitored. Fibristal is not marketed in the United States of America."}],"conclusion_list":[{"field_id":1805,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Fibristal and serious liver injury."},{"field_id":1805,"order_no":2,"bullet":"Health Canada is working with the manufacturer to better understand the effects of Fibristal on the liver, and to update the Canadian product information. The updated product information will clarify when to use Fibristal, and recommend monitoring liver function before, during and after stopping treatment."},{"field_id":1805,"order_no":3,"bullet":"In addition, an Information Update and a Health Professional Risk Communication will be published and distributed to further inform Canadians and healthcare professionals about this risk."},{"field_id":1805,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Fibristal as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00211","review_date":null,"drug_name":"Sunscreen products (chemical action sunscreens)","safety_issue":"Skin reactions","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1812,"overview":"In 2017, Health Canada received a greater than usual number of reports describing skin reactions with the use of some sunscreen products, and became aware of some media reports of skin reactions in children with the use of sunscreen. Health Canada carried out a safety review to assess the risk of skin reactions with the use of sunscreen products. As a part of the safety review, Health Canada considered relevant scientific and medical literature, evaluated reports submitted by Canadians, and reviewed the information requested from 3 manufacturers of sunscreen products in Canada (Banana Boat, Coppertone, and Aveeno).
Sunscreens that protect individuals from both ultraviolet A (UVA) and ultraviolet B (UVB) rays are labelled as 'broad spectrum.' Sunscreens that are labelled as 'water resistant' or 'sweat-resistant' will stay on the skin when wet (for the time indicated on the label). A Sun Protection Factor (SPF) on the label of sunscreen products indicates the relative sun protection offered by the product.
Sunscreen is meant to be applied generously (and evenly) 15 minutes before sun exposure and reapplied at least every 2 hours. For use on children less than 6 months of age, a healthcare professional should be consulted.
Some sunscreen products are labelled 'hypoallergenic', but it is still possible for these products to cause an allergic reaction in some individuals, since people can be allergic to a wide range of substances.
","use_canada":1813,"findings":1814,"conclusion":1815,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1816,"title":"Summary Safety Review - Sunscreen products - Assessing the potential risk of skin reactions","created_date":"2018-11-26","modified_date":"2020-06-26","key_message_list":[{"field_id":1812,"order_no":1,"bullet":"The use of a broad-spectrum (UVA and UVB protection) sunscreen that has a sun protection factor (SPF) of 30 or higher is recommended to prevent sunburns and reduce the risk of developing skin cancer. The use of sunscreen is an important part of overall sun safety practices."},{"field_id":1812,"order_no":2,"bullet":"In 2017, Health Canada received a greater than usual number of reports describing skin reactions with the use of some sunscreen products, and became aware of some media reports of skin reactions in children with the use of sunscreen. As a result, Health Canada carried out a safety review to assess the risk of skin reactions with sunscreen products."},{"field_id":1812,"order_no":3,"bullet":"Health Canada's review concluded that there are no new safety concerns with sunscreen products, but that rare, mild to moderate skin reactions may develop in individuals who have an allergy or sensitivity to one or more ingredients in sunscreen products. The benefits of the regular use of sunscreen to prevent sunburn and reduce the risk of skin cancer continue to greatly outweigh any risk of local skin reactions."},{"field_id":1812,"order_no":4,"bullet":"An Information Update and additional educational materials (i.e. web content and social media communications) will be made available to Canadians and healthcare professionals in order to increase awareness about the rare risk of local skin reactions, improve sun safety behaviour, and encourage the continued use of sunscreen to prevent sunburn and reduce the risk of developing skin cancer. "}],"footnotes_list":[{"field_id":1816,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1813,"order_no":1,"bullet":"Sunscreen products are authorized for sale in Canada to help prevent sunburns."},{"field_id":1813,"order_no":2,"bullet":"There are currently over 1,600 authorized sunscreen products in Canada. All sunscreen products contain one or more active ingredients that offer protection from UV rays. Sunscreen products may contain chemical UV filters, physical UV filters, or both.Health Canada reviewed the potential risk of a drug interaction between ruxolitinib and rosuvastatin (a P-gp substrate) after receiving a Canadian report of a suspected interaction between these 2 drugs. The report included a description of a suspected mechanism of interaction, which prompted Health Canada to include other drugs known to utilize the same transport mechanism, known as P-gp, in the safety review. The current product information for ruxolitinib states that ruxolitinib has no effect on P-gp transporters, based on earlier laboratory studies.
","use_canada":1823,"findings":1824,"conclusion":1825,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1826,"title":"Summary Safety Review - JAKAVI (ruxolitinib) - Assessing the potential risk of drug interactions with P-glycoprotein (P-gp) substrates (including rosuvastatin)","created_date":"2018-10-09","modified_date":null,"key_message_list":[{"field_id":1822,"order_no":1,"bullet":"Jakavi (ruxolitinib) is a prescription drug authorized for sale in Canada to treat adult patients with certain types of blood cancers. "},{"field_id":1822,"order_no":2,"bullet":"Health Canada carried out a safety review after receiving information on a Canadian report of a suspected drug interaction between ruxolitinib and rosuvastatin leading to increased blood cholesterol levels. P-glycoprotein (P-gp) substrates, including rosuvastatin, are drugs that are transported by P-glycoprotein in the body. The review also looked at the potential for ruxolitinib to interact with other P-gp substrates. "},{"field_id":1822,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of ruxolitinib and the risk of interactions with P-gp substrates. Health Canada will continue to monitor the safety of ruxolitinib and will take appropriate and timely action if and when any new health risks are identified."}],"footnotes_list":[{"field_id":1826,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1823,"order_no":1,"bullet":"Ruxolitinib is a prescription drug used to treat adult patients with an enlarged spleen (splenomegaly) and to help control the symptoms caused by myelofibrosis, a rare form of blood cancer. It is also used to control the excess amount of red blood cells in certain patients with polycythemia vera, a type of blood cancer."},{"field_id":1823,"order_no":2,"bullet":"Ruxolitinib has been marketed in Canada since 2012 under the brand name Jakavi and is available as tablets taken by mouth."}],"finding_list":[{"field_id":1824,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian reporta of increased blood cholesterol due to a potential interaction between ruxolitinib and rosuvastatin. The review of this case could not conclude whether ruxolitinib interacted with rosuvastatin and/or played a role in the increased blood cholesterol observed in the patient. This is because patients with polycythemia vera may develop higher blood cholesterol levels when their disease is being treated."},{"field_id":1824,"order_no":2,"bullet":"The review also looked at 2 articles in the published literature which did not suggest an interaction between ruxolitinib and other drugs that are known to be transported by P-gp (e.g. digoxin, dabigatran and cyclosporine)."},{"field_id":1824,"order_no":3,"bullet":"Available evidence at the time of review suggested that an interaction between ruxolitinib and rosuvastatin was unlikely because ruxolitinib did not appear to inhibit P-gp at doses typically used in patient treatment. Neither rosuvastatin nor ruxolitinib appear to directly interact with P-gp transporters."}],"conclusion_list":[{"field_id":1825,"order_no":1,"bullet":"Health Canada's review concluded that the available evidence does not suggest an interaction between ruxolinitib and rosuvastatin or other drugs that are transported by P-gp. Therefore, it is unlikely that any observed increase in blood cholesterol was due to a ruxolitinib interaction with rosuvastatin in the Canadian report. The safety information for these products is appropriate at this time."},{"field_id":1825,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving ruxolitinib, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00213","review_date":null,"drug_name":"Vascular endothelial growth factor receptor tyrosine kinase inhibitorsa","safety_issue":"Artery Dissections and Artery Aneurysms","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1832,"overview":"Health Canada began to review the group of VEGFR TKI drugs for the potential risk of artery dissections and aneurysms after receiving a Canadian case of artery dissection with the use of the VEGFR TKI drug Sutent.
An artery dissection is a tear of the inside lining of an artery. An artery aneurysm is a balloon-like bulge in the wall of a blood vessel that carries oxygen to various tissues in the body (artery). A rupture of the aneurysm can cause bleeding and may lead to death.
These disorders of the arterial wall occur more frequently in the largest artery of the body (the aorta), but can also develop in any other artery. High blood pressure (hypertension) and the build-up of plaques inside arteries (atherosclerosis) are major risk factors for artery dissections and/or aneurysms (D/A). Hypertension is a well-known side effect of VEGFR TKIs.
","use_canada":1833,"findings":1834,"conclusion":1835,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1836,"footnotes":1837,"title":"Summary Safety Review - Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) - Assessing the potential risk of abnormal structural changes of the artery walls including rupture (Artery Dissections and Artery Aneurysms)","created_date":"2018-12-03","modified_date":null,"key_message_list":[{"field_id":1832,"order_no":1,"bullet":"Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are prescription drugs authorized for sale in Canada for the treatment of various types of cancer, including kidney, liver and soft tissue cancers."},{"field_id":1832,"order_no":2,"bullet":"Health Canada reviewed the potential risk of 2 types of abnormal structural changes of the artery walls (artery dissections and artery aneurysms) with the use of VEGFR TKIs. This review was triggered by the publication of a Canadian case of artery dissection with the use of the VEGFR TKI drug Sutent1."},{"field_id":1832,"order_no":3,"bullet":"Health Canada's review of the available information found that there may be a link between the use of VEGFR TKIs and the risk of artery dissections and aneurysms (including rupture), in individuals with or without high blood pressure (hypertension)."},{"field_id":1832,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the product safety information for all VEGFR TKIsa to inform the Canadian public and healthcare professionals about this risk."}],"footnotes_list":[{"field_id":1837,"order_no":1,"bullet":"Authorized VEGFR TKIs in Canada: Sutent (sunitinib), Nexavar (sorafenib), Inlyta (axitinib), Votrient (pazopanib), Iclusig (ponatinib), Stivarga (regorafenib), Caprelsa (vandetanib) and Lenvima (lenvatinib). Cabozantinib was not assessed, as it was not authorized for sale at the time of the review of the risks of artery dissections/artery aneurysms with VEGFR TKIs."},{"field_id":1837,"order_no":2,"bullet":"For this report, the Marketed Health Products Directorate of Health Canada used the IQVIA Canadian Drug Store and Hospital (CDH) Purchases Audit, which measures the dollar value and unit volume of pharmaceutical products purchased by Canadian retail pharmacy outlets and hospitals. Data for CDH are collected from a representative sample of 2997 drug stores and 801 hospitals and long-term care facilities (May 2018). The sample data are then projected to the universe of drug stores and hospitals, to reflect all purchases across Canada."},{"field_id":1837,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1836,"order_no":1,"bullet":"Hatem, R. Potential Sunitinib-Induced Coronary Artery and Aortic Dissections. Canadian Journal of Cardiology. 2017; 33(6):830."}],"use_canada_list":[{"field_id":1833,"order_no":1,"bullet":"There are currently 8 VEGFR TKIs marketed in Canada: Sutent (sunitinib), Nexavar (sorafenib), Inlyta (axitinib), Votrient (pazopanib), Iclusig (ponatinib), Stivarga (regorafenib), Caprelsa (vandetanib) and Lenvima (lenvatinib)a. These products are available as tablets or capsules. They are prescribed for the treatment of various types of advanced/metastatic cancers, including kidney (renal cell carcinoma), liver (hepatocellular carcinoma), thyroid, and soft tissue cancers (sarcomas), as well as certain types of blood cancers (leukemia and lymphoma)."},{"field_id":1833,"order_no":2,"bullet":"Sutent (sunitinib) and Nexavar (sorafenib) were the first 2 VEGFR TKIs marketed in Canada, in 2006."},{"field_id":1833,"order_no":3,"bullet":"In 2017, there were more than 1.2 million tablets/capsules of VEGFR TKIs dispensed in Canadab. The 3 most commonly prescribed VEGFR TKIs were Votrient (about 428,000 tablets), Sutent (about 284,000 capsules) and Nexavar (about 212,000 tablets)."}],"finding_list":[{"field_id":1834,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 Canadian reportc of artery dissection and 1 Canadian report of artery aneurysm suspected to be linked to Sutent use. Health Canada also looked at 208 international reports of artery D/A suspected to be linked to the use of VEGFR TKIs."},{"field_id":1834,"order_no":2,"bullet":"Of the 210 reports (2 Canadian and 208 international), 80 reports (43 artery dissections and 37 artery aneurysms) were further reviewed as they contained the necessary information for a thorough assessment."},{"field_id":1834,"order_no":3,"bullet":"Of the 43 reports of artery dissections, 20 showed a possible link between VEGFR TKIs use and artery dissections. In 2 of these reports, dissection occurred without hypertension. For the remaining 23 reports, the dissection was more likely due to another medical condition (3 reports), or the link could not be assessed due to insufficient information (20 reports)."},{"field_id":1834,"order_no":4,"bullet":"Of the 37 reports of artery aneurysms, only 3 had a documented absence of aneurysm prior to VEGFR TKI use and were further assessed. Of these 3 reports, 1 report showed a possible link between VEGFR TKI use and the artery aneurysm; in the other 2 reports, the aneurysm was either due to another condition, or the link could not be assessed due to insufficient information. The review of the remaining 34 reports revealed a worsening of the condition, with a rupture of the aneurysm in the majority of cases (23/34) during VEGFR TKI use."},{"field_id":1834,"order_no":5,"bullet":"Of the 46 reports that were further assessed to find if VEGFR TKIs use was the cause of the artery D/A (43 artery dissections and 3 artery aneurysms), 10 deaths were reported (9 artery dissections and 1 artery aneurysm). Of these, 3 deaths were found to have a possible link with VEGFR TKI use; 1 was more likely due to another condition, and in 6 reports the link could not be assessed due to insufficient information."},{"field_id":1834,"order_no":6,"bullet":"In Canada, the United States and the European Union, the product safety information for all VEGFR TKIs (except Lenvima) does not contain any information specific to artery dissections and/or aneurysms."}],"conclusion_list":[{"field_id":1835,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the use of VEGFR TKIs and artery dissections/artery aneurysms."},{"field_id":1835,"order_no":2,"bullet":"Health Canada is working with the manufacturers to update the product safety information of all VEGFR TKIs to inform about this risk. A communication about this risk will be published in the Health Product InfoWatch, once the product safety information is updated."},{"field_id":1835,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving VEGFR TKIs to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00214","review_date":null,"drug_name":"sulfamethoxazole containing products","safety_issue":"Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1844,"overview":"Health Canada reviewed the potential risk of Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS) with sulfamethoxazole containing products. The review was triggered because Health Canada got information from a WHO international database that suggested DRESS was being reported at a higher rate than expected for a group of drugs called sulfonamides to which sulfamethoxazole belongs.
DRESS is a severe reaction to the use of a drug that affects one or more organs, including the skin. It includes rare but serious and potentially life-threatening side effects to medications, such as fever and severe skin rash with swollen face or peeling of the skin over large areas of the body. Abnormal changes in blood cells or organ function such as the liver and kidney may also occur. These reactions usually happen 2 weeks to 2 months after starting a medication.
","use_canada":1845,"findings":1846,"conclusion":1847,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1848,"title":"Summary Safety Review - Sulfamethoxazole containing products - Assessing the potential risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)","created_date":"2019-01-07","modified_date":null,"key_message_list":[{"field_id":1844,"order_no":1,"bullet":"Sulfamethoxazole containing products are prescription drugs authorized for sale in Canada to treat a wide range of infections that are caused by bacteria."},{"field_id":1844,"order_no":2,"bullet":"Health Canada reviewed the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with sulfamethoxazole containing products. The safety review was triggered because information from an international database suggested that DRESS was being reported at a higher than expected rate for the group of drugs called sulfonamides to which sulfamethoxazole belongs. The product safety information for sulfamethoxazole containing products already includes other types of severe skin reactions."},{"field_id":1844,"order_no":3,"bullet":"Health Canada's review concluded that there is not enough evidence at this time to establish a link between the risk of DRESS and the use of sulfamethoxazole containing products."},{"field_id":1844,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving sulfamethoxazole containing products, as it does for all health products on the Canadian market. "}],"footnotes_list":[{"field_id":1848,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1845,"order_no":1,"bullet":"Sulfamethoxazole containing products are prescription drugs authorized for sale in Canada to treat a wide range of infections that are caused by bacteria."},{"field_id":1845,"order_no":2,"bullet":"Sulfamethoxazole was first marketed in Canada in the 1960s in combination with another antibacterial drug, Trimethoprim. There are 7 sulfamethoxazole containing generic products that are available on the Canadian market at this time, including 6 oral products and 1 injectable product."},{"field_id":1845,"order_no":3,"bullet":"In 2017, there were about 1 million prescriptions filled in Canada for all sulfamethoxazole containing products."}],"finding_list":[{"field_id":1846,"order_no":1,"bullet":"At the time of the review, Health Canada received 4 unique Canadian reportsa of DRESS that could be related to sulfamethoxazole use. Health Canada found a possible link between DRESS and sulfamethoxazole in 2 reports. The remaining 2 reports did not provide enough information to assess the role of sulfamethoxazole in the development of DRESS."},{"field_id":1846,"order_no":2,"bullet":"This safety review also looked at 5 international reports of DRESS that could be related to sulfamethoxazole use. Only 2 of the 5 international reports met the definition of DRESS and included enough information for further review to determine if sulfamethoxazole use was the cause of DRESS. Both of these reports showed a possible link between DRESS and sulfamethoxazole use."},{"field_id":1846,"order_no":3,"bullet":"Although the trigger for this review was information from a WHO international database that suggested the group of drugs (sulfonamides) had a higher than expected reporting rate for DRESS, the review did not find higher than expected reporting rates specifically with sulfamethoxazole."},{"field_id":1846,"order_no":4,"bullet":"Health Canada also looked at additional information available from published literature and found 15 international reports and 4 studies of DRESS. The published reports did not use consistent criteria for making the diagnosis of DRESS. Almost half of the international reports (7/15) involved other medications or medical conditions that could have contributed to the development of DRESS. The 4 studies did not provide enough evidence to support sulfamethoxazole as the cause of DRESS."},{"field_id":1846,"order_no":5,"bullet":"The Canadian product safety information for sulfamethoxazole-containing products includes all other types of severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Although DRESS is not included in the Canadian product safety information, the Warnings and Precautions section includes some signs and symptoms of DRESS, such as severe liver damage (fulminant liver necrosis), hypersensitivity of the respiratory tract (cough, shortness of breath, and lung infiltrates), and an increase in the number of a specific type of white blood cell (eosinophilia). Additionally, impaired kidney function sometimes reported as kidney (renal) failure is included under Adverse Reactions."},{"field_id":1846,"order_no":6,"bullet":"Health Canada also looked at additional information available from international product safety information. International product safety information includes DRESS only for some sulfamethoxazole containing products in the European Union and Australia whose product information has been updated after 2016."}],"conclusion_list":[{"field_id":1847,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there is not enough evidence at this time to establish a link between the risk of DRESS and the use of sulfamethoxazole containing products. Additionally, some of the signs and symptoms of DRESS are already included in the Canadian product safety information. For these reasons, Health Canada's review concluded that the safety information for these products is appropriate at this time."},{"field_id":1847,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these and other health products."},{"field_id":1847,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving sulfamethoxazole containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00215","review_date":null,"drug_name":"Hydrochlorothiazide","safety_issue":"Non-melanoma skin cancer; specifically, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1854,"overview":"Health Canada reviewed the potential risk of non-melanoma skin cancer (NMSC) with hydrochlorothiazide use. The safety review was triggered by the publication of two recent studies 1, 2 suggesting a higher risk of NMSC with prolonged use (three years or more) of hydrochlorothiazide.
NMSC is the most commonly diagnosed cancer in Canada. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two major types of NMSC. NMSC is generally curable if treated early and rarely causes death. One in 8 Canadians will develop BCC in their lifetime and 1 in 20 will develop SCC in their lifetime.
Exposure to sun, ultraviolet light and/or drugs that increase the sensitivity of the skin to light are important risk factors for NMSC. Light coloured skin and a personal or family history of skin cancer are also important risk factors.
Hydrochlorothiazide is routinely used to treat high blood pressure and excess build-up of fluid in the body. It is known to increase the sensitivity of the skin to light (e.g., sunburns easily).
","use_canada":1855,"findings":1856,"conclusion":1857,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1858,"footnotes":0,"title":"Summary Safety Review - Hydrochlorothiazide - Assessing the potential risk of non-melanoma skin cancer","created_date":"2019-01-30","modified_date":null,"key_message_list":[{"field_id":1854,"order_no":1,"bullet":"Hydrochlorothiazide is a prescription drug authorized for sale in Canada to treat high blood pressure and excess build-up of fluid in the body. "},{"field_id":1854,"order_no":2,"bullet":"Health Canada reviewed the risk of non-melanoma skin cancer (NMSC) related to the use of hydrochlorothiazide alone or in combination with other drugs. This review was triggered by two recently published studies1, 2 suggesting a higher risk of NMSC with prolonged use of hydrochlorothiazide. "},{"field_id":1854,"order_no":3,"bullet":"Health Canada's review of the relevant evidence concluded that prolonged use (three years or more) of hydrochlorothiazide has a potential risk of non-melanoma skin cancer that is at least four times the risk of not using hydrochlorothiazide."},{"field_id":1854,"order_no":4,"bullet":"Health Canada will notify the manufacturers to update the product safety information for all hydrochlorothiazide-containing products, and inform the Canadian public and healthcare professionals about this potential risk and the preventive measures to consider when taking hydrochlorothiazide."}],"footnotes_list":[],"reference_list":[{"field_id":1858,"order_no":1,"bullet":"Pedersen SA, Gaist D, Schmidt SAJ, Holmich LR, Friis S, Pottegard A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018;78(4):673-681."},{"field_id":1858,"order_no":2,"bullet":"Pottegard A, Hallas J, Olesen M et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 2017;282(4):322-331."}],"use_canada_list":[{"field_id":1855,"order_no":1,"bullet":"Hydrochlorothiazide is a prescription drug authorized for sale in Canada to treat high blood pressure and excess build-up of fluid."},{"field_id":1855,"order_no":2,"bullet":"Hydrochlorothiazide has been marketed in Canada since 1976, and is marketed alone or in combination with other drugs."},{"field_id":1855,"order_no":3,"bullet":"There are around 13 million prescriptions filled for hydrochlorothiazide-containing products every year in Canada."}],"finding_list":[{"field_id":1856,"order_no":1,"bullet":"Health Canada reviewed the relevant studies on the topic. Data from studies were combined to estimate the overall risk of NMSC with the use of hydrochlorothiazide. The level of the certainty for the findings was also assessed."},{"field_id":1856,"order_no":2,"bullet":"Five studies analyzing data from thousands of patients investigated the risk of NMSC with the use of hydrochlorothiazide alone or in combination with other drugs. All relevant studies were from North America and Europe, with a majority of patients of light-coloured skin. Studies had important limitations in their designs and methods."},{"field_id":1856,"order_no":3,"bullet":"Health Canada's review found that the risks for SCC and BCC increase with prolonged use (three years or more) of hydrochlorothiazide. After several years of use, the risk could be up to 4 times higher for SCC and 1.25 times higher for BCC compared to the risk in patients not treated with hydrochlorothiazide. Although substantial uncertainty exists regarding these findings, risk estimates reflect the current best evidence addressing the topic. NMSC is therefore considered a potential risk of prolonged hydrochlorothiazide treatment."}],"conclusion_list":[{"field_id":1857,"order_no":1,"bullet":"Health Canada's review of the relevant evidence suggests that there might be a risk of NMSC with prolonged use of hydrochlorothiazide. Given the substantial uncertainty for the findings, NMSC should be considered a potential risk of prolonged hydrochlorothiazide treatment."},{"field_id":1857,"order_no":2,"bullet":"Patients taking hydrochlorothiazide should be informed of the potential risk of NMSC and advised to regularly check their skin for new marks or growths as well as changes to existing ones. Patients should report any suspicious skin marks or growths to their healthcare professional. Patients should be advised to limit exposure to sunlight, avoid the use of tanning equipment, and use adequate sun protection (e.g., SPF 30 or higher, clothing, and a hat) to minimize the risk of skin cancer."},{"field_id":1857,"order_no":3,"bullet":"Alternatives to hydrochlorothiazide may be considered for patients who are at a particularly high risk for NMSC (e.g., light-colored skin, known personal or family history of skin cancer, ongoing immunosuppressive therapy, etc.)."},{"field_id":1857,"order_no":4,"bullet":"Health Canada will notify the manufacturers to update the product safety information of all hydrochlorothiazide-containing products to inform about this potential risk and the preventive measures to consider when taking hydrochlorothiazide."},{"field_id":1857,"order_no":5,"bullet":"An Information Update and a Health Product Info Watch will be published to further inform Canadians and healthcare professionals about this potential risk."},{"field_id":1857,"order_no":6,"bullet":"Health Canada will continue to monitor safety information involving hydrochlorothiazide to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00220","review_date":null,"drug_name":"Opsumit (macitentan)","safety_issue":"Liver injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1906,"overview":"Health Canada reviewed the potential risk of liver injury with Opsumit (macitentan) use following reports of liver injury internationally that led to an update to the US product safety information for this drug.
At the time of the review, the Canadian product safety information for Opsumit included a warning about potential effects on the liver that had been observed with the group of drugs to which Opsumit belongs. The Canadian product safety information also included requirements for blood tests to monitor liver function.
Pulmonary arterial hypertension (PAH) is a condition where there is high blood pressure in the vessels that carry blood from the heart to the lungs. It is a condition that can be life-threatening or that can have a significant impact on patients' quality of life.
","use_canada":1907,"findings":1908,"conclusion":1909,"additional":"The analysis that contributed to this safety review included Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1910,"footnotes":1911,"title":"Summary Safety Review - Opsumit (macitentan) - Assessing the potential risk of liver injury","created_date":"2019-03-01","modified_date":null,"key_message_list":[{"field_id":1906,"order_no":1,"bullet":"Opsumit (macitentan) is a prescription drug authorized for sale in Canada to treat certain types of pulmonary arterial hypertension (PAH). PAH is high blood pressure in the vessels (arteries) that carry blood from the heart to the lungs. "},{"field_id":1906,"order_no":2,"bullet":"Health Canada reviewed the potential risk of liver injury with the use of Opsumit after becoming aware of international reports of liver injury. These reports led to an update to the United States (US) product safety information for Opsumit. "},{"field_id":1906,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between Opsumit use and risk of liver injury."},{"field_id":1906,"order_no":4,"bullet":"Health Canada will notify Opsumit's manufacturer to update the Canadian product safety information with this new information."}],"footnotes_list":[{"field_id":1911,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[{"field_id":1910,"order_no":1,"bullet":"Tran, T., Brinker, A.D. et al, Serious Liver Injury Associated with Macitentan: A Case Report, Pharmacotherapy, Vol 38, Number 2, 2018"}],"use_canada_list":[{"field_id":1907,"order_no":1,"bullet":"Opsumit (macitentan) is a prescription drug authorized for sale in Canada to treat certain types of PAH."},{"field_id":1907,"order_no":2,"bullet":"Macitentan has been marketed in Canada since January 2014 under the brand name Opsumit."},{"field_id":1907,"order_no":3,"bullet":"In Canada, there were over 2,900 prescriptions for Opsumit filled in 2017."}],"finding_list":[{"field_id":1908,"order_no":1,"bullet":"At the time of the review, Health Canada looked at 15 Canadian reportsa of liver injury with Opsumit from the Canada Vigilance database. Of these reports, 14 were not found to be relevant to this review (e.g., reports that were duplicates, that did not meet the definition of liver injury, or reports where the patient had a history of liver disease). In the 1 remaining case, it was determined that the liver injury was unlikely to be linked to the use of Opsumit."},{"field_id":1908,"order_no":2,"bullet":"Health Canada also assessed 16 international reports (1 published1) that were found to be relevant to the review. There was a link between the risk of liver injury and the use of Opsumit in 1 report. The link was found to be possible in 13 reports and unlikely in 1 report. In the remaining 1 report, the link could not be assessed due to the nature of the information provided. Death was reported in 1 of the 13 cases where the risk of liver injury was found to have a possible link with the use of Opsumit. However, the death was not linked to Opsumit, but was the result of disease progression."},{"field_id":1908,"order_no":3,"bullet":"In the majority of the reports assessed, other factors may have also caused the liver injury, such as: heart failure that results from PAH, other conditions linked with PAH, or the use of other medications for PAH."},{"field_id":1908,"order_no":4,"bullet":"No published studies assessing the risk of liver injury with the use of Opsumit were identified in the literature."}],"conclusion_list":[{"field_id":1909,"order_no":1,"bullet":"Health Canada's review found that there may be a link between Opsumit and liver injury."},{"field_id":1909,"order_no":2,"bullet":"Health Canada will notify the manufacturer to update the product safety information for Opsumit in order to inform healthcare professionals and patients about the potential for liver injury."},{"field_id":1909,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Opsumit, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."},{"field_id":1909,"order_no":4,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this or other health products."}]},{"template":2,"link_id":"SSR00216","review_date":null,"drug_name":"Cough and cold products containing opioids (including codeine, hydrocodone or normethadone)","safety_issue":"Opioid use disorders and related harms in children and adolescents","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1864,"overview":"The growing number of overdoses and harms caused by opioids is a major public health concern in Canada. As part of a national strategy to better inform patients on the risks of all prescription opioid-containing products, Health Canada has recently updated the product safety information of these drugs for the risks of problematic drug use. Opioid-related harms have been increasing in Canada in children and adolescents (under 18 years of age), and a published study suggested that early use of opioids is a factor that can lead to opioid-related harms later in life1. Individuals with opioid use disorder continue to use opioids, even when they know it is harmful. Opioid-related harms can include, but are not limited to, the use of an opioid in a way that is not as intended or prescribed.
In light of the current crisis and the approach used by other regulators for similar products, Health Canada reviewed the risks of opioid use disorder and related harms for codeine-, hydrocodone-, and normethadone-containing cough and cold products in children and adolescents.
","use_canada":1865,"findings":1866,"conclusion":1867,"additional":"The analysis that contributed to this safety review included scientific and medical literature, national and provincial surveys, and both Canadiana and internationalb reports, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1868,"footnotes":1869,"title":"Summary Safety Review - Opioid-containing cough and cold products - Assessing the potential risk of opioid use disorder and related harms in children and adolescents","created_date":"2019-02-18","modified_date":null,"key_message_list":[{"field_id":1864,"order_no":1,"bullet":"The growing number of overdoses and harms caused by opioids is a major public health concern in Canada. Cough and cold products containing opioids (including codeine, hydrocodone or normethadone) are authorized for sale in Canada to treat cough and cold symptoms in adults and children. "},{"field_id":1864,"order_no":2,"bullet":"Health Canada reviewed the risk of opioid use disorder and related harms from these products after the United States Food and Drug Administration (US FDA) advised against using these products in children and adolescents in 2018. Health Canada's safety review found limited evidence to link opioid-containing cough and cold products with opioid use disorders and related harms in children and adolescents."},{"field_id":1864,"order_no":3,"bullet":"These products are linked to other known harms (i.e., breathing problems), and there is limited evidence to support the effectiveness of these products in children and adolescents. There are other products available in Canada to help relieve the symptoms of cough and cold in children."},{"field_id":1864,"order_no":4,"bullet":"Therefore, Health Canada, as a precautionary measure, is advising Canadians against the use of these products among children and adolescents under 18 years of age. Health Canada will notify the manufacturers to update the product safety information of opioid-containing cough and cold products to limit the recommended age of use (indication) to adults only, 18 years of age and older. These actions align Canada with US and European practices and product safety information."},{"field_id":1864,"order_no":5,"bullet":"Health Canada will also inform Canadians and healthcare professionals about these updates through an Information Update and a Health Product InfoWatch communication."}],"footnotes_list":[{"field_id":1869,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":1869,"order_no":2,"bullet":"International reports were accessed through the World Health Organization's Adverse Drug Reaction Database"}],"reference_list":[{"field_id":1868,"order_no":1,"bullet":"Miech, Richard et al. \"Prescription Opioids in Adolescence and Future Opioid Misuse\" Pediatrics vol. 136,5 (2015): e1169-77."}],"use_canada_list":[{"field_id":1865,"order_no":1,"bullet":"Opioid-containing cough and cold products have been marketed in Canada since the 1950s. There are 3 prescription opioid drugs authorized to treat cough symptoms in Canada: codeine, hydrocodone, and normethadone."},{"field_id":1865,"order_no":2,"bullet":"Low-dose codeine is also available without a prescription in most provinces to treat cough symptoms."},{"field_id":1865,"order_no":3,"bullet":"Currently, codeine products are not recommended for children under 12 years of age, and hydrocodone and normethadone products are not recommended for children under 6 years of age."},{"field_id":1865,"order_no":4,"bullet":"Use of these products in children and adolescents (under 18 years of age) represents a small proportion (4%) of the total opioid cough and cold prescriptions dispensed in Canada."},{"field_id":1865,"order_no":5,"bullet":"The use of prescription opioid-containing cough and cold products has been declining in Canadian children and adolescents over the past 5 years."}],"finding_list":[{"field_id":1866,"order_no":1,"bullet":"At the time of this review, Health Canada found limited information on reports of opioid use disorder among children and adolescents related to the use of opioid-containing cough medications from either Canadiana or international reports."},{"field_id":1866,"order_no":2,"bullet":"Like other opioids, codeine, hydrocodone, and normethadone may lead to opioid use disorder. However, it is often difficult to detect and recognize the signs and symptoms of opioid use disorder in children and adolescents, and these may go unreported."},{"field_id":1866,"order_no":3,"bullet":"A review done by the Canadian Agency for Drugs and Technologies in Health found a lack of published evidence to support codeine use in children for cough and cold symptoms."},{"field_id":1866,"order_no":4,"bullet":"Health Canada reviewed the published literature, which suggests that adolescents are at a greater risk of problematic opioid use and overdose, while younger children are at a greater risk of accidental poisoning."},{"field_id":1866,"order_no":5,"bullet":"The scientific literature also suggests a possible link between exposure to opioid-containing products in adolescence and a higher risk of problematic opioid use later in life."},{"field_id":1866,"order_no":6,"bullet":"National and provincial data indicate a concerning increase in opioid-related harms in children and adolescents."}],"conclusion_list":[{"field_id":1867,"order_no":1,"bullet":"While Health Canada's safety review found limited evidence to link opioid-containing cough and cold products with opioid use disorders in children and adolescents, there is published literature that suggests a possible link between exposure to opioid-containing products in adolescence and a higher risk of opioid-related harms later in life."},{"field_id":1867,"order_no":2,"bullet":"There is limited evidence to support the effectiveness of opioid-containing products to treat cough and cold symptoms in children and adolescents. Additionally, there are other products available in Canada to help relieve the symptoms of cough and cold in children."},{"field_id":1867,"order_no":3,"bullet":"For these reasons, Health Canada is advising Canadians against the use of cough and cold products containing codeine, hydrocodone and normethadone for children and adolescents (under 18 years old)."},{"field_id":1867,"order_no":4,"bullet":"Health Canada will publish an Information Update and a Health Product InfoWatch communication for opioid-containing cough and cold products to inform Canadians, healthcare professionals and patients about the change to the recommended age of use for these products."},{"field_id":1867,"order_no":5,"bullet":"Health Canada will consult with the Drug Safety and Effectiveness Network (DSEN) to study the presence of opioid use disorder and related harms with the use of opioid-containing products. Health Canada continues to monitor side effect information involving opioid-containing cough and cold products, and has requested manufacturers of prescription opioid products to submit risk management plans to track and monitor these risks in the Canadian population. Health Canada will take appropriate and timely action if and when any new health risks are identified."},{"field_id":1867,"order_no":6,"bullet":"Given the broad availability of non-prescription codeine-containing products and their potential for problematic use, Health Canada has initiated a review of all non-prescription codeine-containing products in children and adolescents."}]},{"template":2,"link_id":"SSR00217","review_date":null,"drug_name":"Ferriprox (deferiprone)","safety_issue":"Brain and nervous system (neurological) disorders","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1876,"overview":"Health Canada reviewed the potential risk of neurological disorders such as difficulty walking or difficulty with the coordination of movement in children when Ferriprox is used at recommended doses. This safety review was triggered after 2 reports1, 2 were published suggesting this risk in children taking Ferriprox. At the time of the review, the product safety information for Ferriprox included a warning to inform that similar neurological disorders have been observed in 2 children treated with 2.5 times the recommended doses of Ferriprox.
","use_canada":1877,"findings":1878,"conclusion":1879,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":1880,"footnotes":1881,"title":"Summary Safety Review - Ferriprox (deferiprone) - Assessing the potential risk of brain and nervous system (neurological) disorders in children","created_date":"2019-02-25","modified_date":null,"key_message_list":[{"field_id":1876,"order_no":1,"bullet":"Ferriprox (deferiprone) is a prescription drug authorized for sale in Canada to remove excess iron accumulated in the body from blood transfusions in the treatment of thalassemia syndromes (genetic diseases of blood production). Ferriprox is recommended for use when other iron removal therapies do not work well enough."},{"field_id":1876,"order_no":2,"bullet":"Health Canada assessed the potential risk of brain and nervous system (neurological) disorders, such as difficulty walking or difficulty with the coordination of movement in children treated with Ferriprox at recommended doses. Health Canada's review was triggered by 2 published cases1, 2. "},{"field_id":1876,"order_no":3,"bullet":"The product safety information for Ferriprox already warns of this risk when children are treated with 2.5 times the recommended dose of Ferriprox."},{"field_id":1876,"order_no":4,"bullet":"Health Canada's review concluded that there may be a link between Ferriprox and the risk of neurological disorders in children treated at recommended doses. Health Canada will notify the manufacturer to update the safety information for Ferriprox to warn that cases of neurological disorders in children have also been observed at recommended doses of Ferriprox."}],"footnotes_list":[{"field_id":1881,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":1880,"order_no":1,"bullet":"Economou M, Teli A, Gourtsa V, Vargiami E, Zafeiriou D. Neurological Involvement in a Thalassemic Child Receiving Deferiprone. J Pediatr Hematol Oncol 2016;38(5):406."},{"field_id":1880,"order_no":2,"bullet":"Parakh N, Sharma R, Prakash O et al. Neurological Complications and Cataract in a Child With Thalassemia Major Treated With Deferiprone. J Pediatr Hematol Oncol 2015;37(7):e433-e434."}],"use_canada_list":[{"field_id":1877,"order_no":1,"bullet":"Ferriprox (deferiprone) is a prescription drug authorized for sale in Canada for the treatment of patients with excess accumulated iron from repeated blood transfusions as part of the treatment of thalassemia syndromes (genetic diseases of blood production). Ferriprox is recommended for use when other iron removal (i.e. chelation) therapies do not work well enough."},{"field_id":1877,"order_no":2,"bullet":"Deferiprone has been marketed in Canada since July 2016 under the brand name Ferriprox. This drug is available only through a controlled distribution program called Ferriprox Assist."}],"finding_list":[{"field_id":1878,"order_no":1,"bullet":"At the time of the review, Health Canada had not received any Canadian reportsa of neurological disorders linked to the use of Ferriprox in children."},{"field_id":1878,"order_no":2,"bullet":"Health Canada's safety review found 2 international casereports1, 2 of neurological disorders in children that were treated with Ferriprox at recommended doses. In one report, there was a link between neurological disorders and the use of Ferriprox. In the other report, the link between neurological disorders and the use of Ferriprox was possible, but there were other factors (such as, the treatment condition, and other neurological/medical conditions) that may have also caused the neurological disorders."},{"field_id":1878,"order_no":3,"bullet":"In 2017, the European Medicines Agency (EMA) included the risk of neurological disorders in children when exposed at the recommended doses of deferiprone in the product safety information for Ferriprox. This risk of neurological disorders at recommended doses is not labelled in the United States."}],"conclusion_list":[{"field_id":1879,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between Ferriprox and neurological disorders in children when it is used at recommended doses, and not only at higher doses as currently referenced in the product safety information."},{"field_id":1879,"order_no":2,"bullet":"Health Canada will notify the manufacturer to update the current warnings in the safety information to reflect that cases of neurological disorders in children have also been observed at recommended doses of Ferriprox. Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this or other health products."},{"field_id":1879,"order_no":3,"bullet":"Health Canada will continue to monitor the safety information involving Ferriprox, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if or when new health risks are identified."}]},{"template":2,"link_id":"SSR00223","review_date":null,"drug_name":"Breast Implants","safety_issue":"Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)","safetyissue_title":"Potential Safety Issues","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1938,"overview":"This safety review on BIA-ALCL is an update to one completed in June 2017, and focused on reviewing all new information and proposing additional ways to further reduce the risk of BIA-ALCL. Since the original safety review, there has been an increase in the number of BIA-ALCL cases reported to Health Canada and internationally. Furthermore, new articles in the medical literature have been published, and new information has been provided by international regulatory agencies on this topic.
BIA-ALCL is a serious but rare type of non-Hodgkin lymphoma (a cancer that affects the immune system) that may develop many months or years after a breast implant procedure. The first case was described in 19971. It is not a cancer of the breast tissue. BIA-ALCL usually presents as an accumulation of fluid (known as seroma fluid) between the implant and the surrounding tissue, but can also present as a lump/mass. The cause is currently unknown. The rate of BIA-ALCL in Canada varies depending on the type of breast implant, from 1 in 3,565 for Allergan Biocell macro-textured breast implants to 1 in 16,703 for Mentor Siltex micro-textured breast implants. Health Canada has received 26 confirmed Canadian cases of BIA-ALCL, of which 22 (85%) involve Allergan's Biocell macro-textured breast implants. There are no reported Canadian cases of BIA-ALCL associated with smooth breast implants.
","use_canada":1939,"findings":1940,"conclusion":1941,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these medical devices both in Canada and internationally.
For additional information about Health Canada's assessment, contact the Marketed Health Products Directorate.
If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":1942,"footnotes":0,"title":"Summary Safety Review - Breast Implants - Assessing the potential risk of cancer (Breast implant associated anaplastic large cell lymphoma)","created_date":"2019-05-28","modified_date":"2019-05-30","key_message_list":[{"field_id":1938,"order_no":1,"bullet":"Breast implants are medical devices licensed for sale in Canada to increase breast size, correct or improve the results of a previous breast implant surgery, correct breast unevenness, or rebuild breast tissue following surgery. Breast implants marketed in Canada are made of a smooth or textured silicone shell and are filled with silicone gel or sterile salt water (saline)."},{"field_id":1938,"order_no":2,"bullet":"Health Canada completed an update to its 2017 safety review on Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), a rare but serious complication linked with breast implants. This updated review was triggered by newly reported Canadian cases, as well as newly published literature and information issued by international regulatory agencies."},{"field_id":1938,"order_no":3,"bullet":"Although the cause of BIA-ALCL is not fully understood, the available scientific and clinical evidence strongly suggests an increased risk of BIA-ALCL in individuals with highly textured (macro-textured) implants in comparison with those having less textured (micro-textured) or smooth implants. Biocell breast implants made by Allergan are the only macro-textured implants currently available in Canada."},{"field_id":1938,"order_no":4,"bullet":"Health Canada's updated safety review found an increased risk of BIA-ALCL with the use of macro-textured breast implants. On May 27, 2019, Health Canada notified Allergan of the suspension of the licences for Biocell breast implants."},{"field_id":1938,"order_no":5,"bullet":"For the remaining authorized breast implants sold in Canada, Health Canada will:Health Canada reviewed the potential risk of suicidal ideation with use of Proscar or Propecia (finasteride) due to reported cases of suicidal ideation and self-injury received in Canada and internationally. The cases led to the investigation of the possible relationship between finasteride use and suicidal ideation through a number of assessments.
The topic of finasteride and suicide/self-injury has been monitored on an ongoing basis by Health Canada since 2011. A first safety review was completed in 2012, and it was recommended that the topic be re-assessed in 2 years. A second safety review was completed in 2014, where the information at that time could not confirm if there was a link or not between finasteride use and suicide/self-injury. It was recommended as a precautionary measure to inform physicians of the potential risk and assess the topic again after another 2 years. As a result of this recommendation and reported cases, Health Canada began this safety review.
","use_canada":1889,"findings":1890,"conclusion":1891,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1892,"title":"Summary Safety Review - Proscar and Propecia (finasteride) - Assessing the potential risk of suicidal thoughts and/or behaviour (suicidal ideation)","created_date":"2019-02-26","modified_date":null,"key_message_list":[{"field_id":1888,"order_no":1,"bullet":"There are two finasteride-containing prescription drug products for oral use sold in Canada. Proscar (5 mg tablet) is indicated to treat prostate gland enlargement (Benign Prostatic Hyperplasia, or BPH), and Propecia (1 mg tablet) for the treatment of hair loss in men."},{"field_id":1888,"order_no":2,"bullet":"Health Canada reviewed the risk of suicidal thoughts and/or behaviours (suicidal ideation) with Proscar and Propecia (finasteride) use. The safety review was triggered because of Canadian and international reported casesa,b of suicidal ideation and self-injury. "},{"field_id":1888,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between Proscar and Propecia (finasteride) and the risk of suicidal ideation. Health Canada has notified the manufacturer to update the Canadian product information on this potential safety issue."}],"footnotes_list":[{"field_id":1892,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":1892,"order_no":2,"bullet":"World Health Organization Adverse Drug Reaction Database was accessed through VigiBase."}],"reference_list":[],"use_canada_list":[{"field_id":1889,"order_no":1,"bullet":"Proscar and Propecia (finasteride) are prescription drugs that are authorized for sale in Canada to treat prostate gland enlargement (benign prostatic hyperplasia or BPH), and male pattern hair loss, respectively."},{"field_id":1889,"order_no":2,"bullet":"Finasteride has been marketed in Canada since 1992 under the brand name Proscar, and since 1998 under the brand name Propecia. Generic versions of finasteride are also available. Proscar is available as an oral 5 mg tablet and Propecia is available as an oral 1 mg tablet."}],"finding_list":[{"field_id":1890,"order_no":1,"bullet":"At the time of the review, Health Canada had received 26 Canadian reportsa of events related to suicide or self-injury with the use of finasteride. Between 2012 and 2016, the Canadian reporting rate for finasteride and suicide/self-injury-related events increased by 2.5 times. In the assessment of the Canadian reports, a cause and effect relationship could not be confirmed or denied, and as a result, a link between finasteride and suicide/self-injury-related events was deemed possible."},{"field_id":1890,"order_no":2,"bullet":"A search in the World Health Organization's Adverse Drug Reaction Database found 368 international reportsb of suicide/self-injury-related events reported in patients treated with finasteride, up to September 16, 2018."},{"field_id":1890,"order_no":3,"bullet":"There were 5 studies reviewed that were published between 2015-2018 on finasteride and suicide-related events. These publications support a link between finasteride use and the risk of suicidal ideation."},{"field_id":1890,"order_no":4,"bullet":"In 2018, the European Medicines Agency (EMA) added a warning in the product information for Proscar and Propecia that suicidal ideation had been reported in patients treated with finasteride (1 mg and 5 mg), and that patients should be monitored for psychiatric symptoms. Currently, the United States Food and Drug Administration has not required labelling for this risk for Proscar or Propecia."},{"field_id":1890,"order_no":5,"bullet":"The international reports, literature, and regulatory information that were reviewed could neither confirm nor deny a cause and effect relationship between finasteride and suicide/ self-injury."}],"conclusion_list":[{"field_id":1891,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between Proscar and Propecia (finasteride) and the risk of suicidal ideation."},{"field_id":1891,"order_no":2,"bullet":"Health Canada has notified the manufacturer to update the Canadian product information to include a warning on this potential safety issue."},{"field_id":1891,"order_no":3,"bullet":"Health Canada will continue to monitor safety information related to Proscar and Propecia (finasteride), as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00219","review_date":null,"drug_name":"Gilenya (fingolimod)","safety_issue":"Worsening multiple sclerosis (MS) symptoms after product withdrawal (rebound effect)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1898,"overview":"Health Canada reviewed the potential risk of worsening MS symptoms (rebound effect) after Gilenya withdrawal. The safety review was triggered by reports of severe MS symptoms following the withdrawal of Gilenya. Severe worsening of MS symptoms were mostly reported within 12 weeks (with rare cases reported up to 24 weeks) following withdrawal of Gilenya.
","use_canada":1899,"findings":1900,"conclusion":1901,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Gilenya (fingolimod) - Assessing the potential risk of worsening multiple sclerosis symptoms after product withdrawal (rebound effect)","created_date":"2019-02-28","modified_date":null,"key_message_list":[{"field_id":1898,"order_no":1,"bullet":"Gilenya (fingolimod) is authorized for sale in Canada to treat multiple sclerosis (MS), a condition that leads to the damage of the nervous system causing physical disability. It is specifically recommended for patients who have had a poor response to, or are unable to tolerate, one or more of the other therapies for MS."},{"field_id":1898,"order_no":2,"bullet":"Health Canada reviewed the potential risk of worsening MS symptoms after Gilenya withdrawal (rebound effect). The review was triggered by reports of severe MS symptoms following the withdrawal of Gilenya."},{"field_id":1898,"order_no":3,"bullet":"Health Canada's safety review concluded that there may be a link between Gilenya withdrawal and the risk of worsening MS symptoms (rebound effect). The product safety information for Gilenya has been updated to inform Canadians and healthcare professionals about this potential safety issue."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1899,"order_no":1,"bullet":"Gilenya is a prescription drug authorized for sale in Canada to treat MS, to reduce the frequency of signs and symptoms of MS, and to delay the progression of physical disability."},{"field_id":1899,"order_no":2,"bullet":"Gilenya is recommended in patients who have had a poor response to, or are unable to tolerate, one or more of the other therapies for MS."},{"field_id":1899,"order_no":3,"bullet":"Gilenya was first marketed in Canada in March 2011."}],"finding_list":[{"field_id":1900,"order_no":1,"bullet":"At the time of the review, Health Canada identified 29 international reports of severe worsening of MS disease progression after Gilenya withdrawal. Most patients (27/29) required treatment for the symptoms they experienced and, at the time of reporting, the majority of patients partially recovered following treatment with other agents (18/27). Twelve of these 29 patients required hospitalization."},{"field_id":1900,"order_no":2,"bullet":"This safety review also looked at information from the manufacturer and the scientific literature about the risk of rebound effect after Gilenya withdrawal. The information from the manufacturer and the scientific literature supported the potential risk of worsening MS symptoms after Gilenya withdrawal."},{"field_id":1900,"order_no":3,"bullet":"Product information for Gilenya now includes information about the risk of worsening MS symptoms after Gilenya withdrawal. It also recommends monitoring patients for development of severe worsening of MS symptoms after withdrawal of Gilenya and beginning appropriate treatment as needed. This information can be found in the Warnings and Precautions section of the product information for Gilenya."}],"conclusion_list":[{"field_id":1901,"order_no":1,"bullet":"Health Canada's safety review concluded that there may be a link between the withdrawal of Gilenya and the worsening of MS symptoms (rebound effect)."},{"field_id":1901,"order_no":2,"bullet":"The product safety information for Gilenya has been updated to inform Canadians and healthcare professionals about this potential safety issue."},{"field_id":1901,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this health product."},{"field_id":1901,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Gilenya, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00221","review_date":null,"drug_name":"Intragastric Balloons","safety_issue":"Inflamed pancreas, developing a hole (perforation) in the esophagus and stomach, and unexpected balloon enlargement (overinflation)","safetyissue_title":"Potential Safety Issues","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1918,"overview":"Health Canada reviewed the potential risks of inflammation of the pancreas, developing a hole (perforation) in the esophagus and stomach, and unexpected balloon enlargement (overinflation) when fluid-filled intragastric balloons (IBs) are used as temporary implants to help with weight loss in some overweight or obese individuals.
IBs are medical devices for temporary use (6 or 12 month maximum use) that are inserted and removed using a tube with a camera and light (endoscope) placed down through the mouth, throat and esophagus into the stomach. They give the feeling of fullness and are used for weight loss along with other measures (e.g. diet and exercise) in patients above a certain body mass index (BMI).
","use_canada":1919,"findings":1920,"conclusion":1921,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of this device both in Canada and internationally.
For more information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1922,"title":"Summary Safety Review - Intragastric balloons - Assessing the potential risk of inflamed pancreas, developing a hole (perforation) in the esophagus and stomach, and unexpected balloon enlargement (overinflation)","created_date":"2019-04-17","modified_date":null,"key_message_list":[{"field_id":1918,"order_no":1,"bullet":"Intragastric balloons (IBs) are fluid or air-filled medical devices placed in the stomach to act as a space-occupying device. They are devices for temporary use (6 or 12 months maximum, according to the licence) for weight loss along with other measures (diet, exercise) in some overweight or obese patients. All IBs available in Canada are fluid-filled devices."},{"field_id":1918,"order_no":2,"bullet":"Health Canada completed a safety review on the potential risk of inflammation of the pancreas, developing a hole (perforation) in the esophagus and stomach, and unexpected balloon enlargement (overinflation) in patients using fluid-filled IBs. This review followed Canadian and international reports of these complications (including deaths), in patients being treated with IBs."},{"field_id":1918,"order_no":3,"bullet":"Health Canada's review of the available information has confirmed a link between the use of fluid-filled IBs and all of the risks previously mentioned. In most cases, removal of the device is required. Of particular concern are IB-related cases of esophageal and/or stomach wall perforations, which can potentially cause death and typically require emergency surgical treatment."},{"field_id":1918,"order_no":4,"bullet":"Health Canada will work with the medical device manufacturers to strengthen the device safety information (Instructions for Use) for all fluid-filled IBs by including these potential risks. Health Canada will also publish a Health Product Risk Communication to raise awareness of these risks and will continue to monitor the safety and effectiveness of these devices."}],"footnotes_list":[{"field_id":1922,"order_no":1,"bullet":"Search Medical Device Incidents"}],"reference_list":[],"use_canada_list":[{"field_id":1919,"order_no":1,"bullet":"Intragastric balloons (IBs) are medical devices licensed in Canada as devices for temporary use that help with weight loss in patients above a certain BMI (typically 27 or more)."},{"field_id":1919,"order_no":2,"bullet":"There were 4 IB systems licensed for sale in Canada at the time the scientific review was carried out. All were fluid-filled devices and regulated as class III medical devices. The first of these models was originally licensed for sale in Canada in 2006. At the time this Summary Safety Review was finalized, 2 IB systems remained actively licensed in Canada."}],"finding_list":[{"field_id":1920,"order_no":1,"bullet":"At the time of the review, Health Canada had received 2 domestic and 2 international reportsa of side effects related to the use of IBs. One report described a hole (perforation) of the stomach, and another case described an injury to the stomach wall during device insertion. The other 2 reports involved deaths in IB users. However, there was not enough information in these 2 reports to confirm the exact cause of the deaths."},{"field_id":1920,"order_no":2,"bullet":"Health Canada also looked at the medical literature related to IB side effects. There were 17 cases of pancreas inflammation found and confirmed by blood testing and x-rays. Most patients were treated by device removal and all recovered. The literature suggests that the injury is caused by mechanical pressure placed on the pancreas by the IB via the stomach wall."},{"field_id":1920,"order_no":3,"bullet":"There were 2 cases of esophageal perforation found in the literature - 1 after a difficult device insertion and 1 after difficult device removal. Both patients recovered. Perforation of the esophagus is a known, rare complication that can occur during a procedure with an endoscope, regardless of whether an IB is involved."},{"field_id":1920,"order_no":4,"bullet":"There was only 1 detailed case of unexpected overinflation of an IB found in the literature. The event was confirmed by imaging, the balloon was removed, and the patient recovered. Mention of other balloon overinflation cases was found in the literature, but no other cases were described in detail. International databases were also found to contain multiple reports of this complication leading to early removal of the IB."},{"field_id":1920,"order_no":5,"bullet":"A total of 26 literature cases of stomach perforation in IB patients were found, including 6 deaths. Patients who appeared to be at higher risk included those who did not use their prescribed heartburn medications and those who had previously undergone stomach surgery. The estimated risk of a stomach perforation spanning the full thickness of the stomach in IB users is believed to be 0.1 to 0.2%, but the frequency of partial thickness injuries (ulcer) to the stomach wall is likely higher. Overall, perforation of the stomach is a serious complication and most cases required rapid and significant surgical intervention beyond simple removal of the balloon. The literature suggests that cases of severe stomach pain in IB users should be considered as possible stomach perforations until proven otherwise."}],"conclusion_list":[{"field_id":1921,"order_no":1,"bullet":"Health Canada's review of the available information has confirmed that there is a link between the use of intragastric balloons (IBs) and cases of pancreas inflammation, developing a hole (perforation) in the esophagus and stomach, and unexpected balloon enlargement (overinflation). Most cases require removal of the balloon. Cases of esophageal and/or stomach perforation can potentially cause death and typically require emergency surgery to repair."},{"field_id":1921,"order_no":2,"bullet":"Health Canada will notify medical device manufacturers to make sure that the Instructions for Use of all IB devices sold in Canada includes details about these potential risks. Health Canada will also publish a Health Product Risk Communication to increase awareness of these potential risks, as well as assess results from ongoing studies."},{"field_id":1921,"order_no":3,"bullet":"Health Canada will contact manufacturers to work together to update the Instructions for Use of IBs. If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca)."},{"field_id":1921,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving IBs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if any new health risks are identified."}]},{"template":2,"link_id":"SSR00222","review_date":null,"drug_name":"Cellex Photopheresis System","safety_issue":"Blood clots formed in a vein (Venous Thromboembolism, VTE) or in the lungs (Pulmonary Embolism, PE)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1928,"overview":"Cellex Photophoresis System (CPS) is a medical device licensed in Canada used to treat the effects on skin of a type of cancer of the immune system (cutaneous T-cell lymphoma) which is not responding to other treatment. It is also used to treat systemic sclerosis, a rare disease involving an abnormal response from the body's immune system that causes changes in the texture and appearance of the skin, and frequently involves the internal organs.
It is used in a process where the patient's blood is withdrawn and the white blood cells are separated out. The rest of the blood (red blood cells and plasma) is immediately returned to the patient's circulation. The white blood cells are exposed to ultraviolet-A (UVA) radiation in the presence of a light-activated drug (photoactive drug). The UVA radiation and photoactive drug activates the immune cells to enhance the patient's immune response. After irradiation, the white blood cells are also returned to the patient's circulation.
In early 2018, the US FDA announced they would assess the risk of venous thromboembolism (VTE) with the use of CPS. Venous thromboembolism (VTE) is a condition in which a blood clot forms in a vein. When VTE occurs in a deep vein (e.g., in a leg), it is called deep vein thrombosis (DVT). This type of blood clot can break away from the original site and travel to other parts of the body, blocking a blood vessel in other organs, such as the lungs, causing pulmonary embolism (PE). A thromboembolic event can include either a VTE or a PE.
The US FDA received 7 reports of VTE, including pulmonary embolism (PE), in patients using CPS, 2 of which involved death. In Canada, there were 29 incidents of side effects related to the use of CPS, and 1 of these cases reported a blood clotting incident.
","use_canada":1929,"findings":1930,"conclusion":1931,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this medical device both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":1932,"title":"Summary Safety Review - Cellex Photopheresis System and Venous Thromboembolism & Pulmonary Embolism","created_date":"2019-05-03","modified_date":null,"key_message_list":[{"field_id":1928,"order_no":1,"bullet":"Cellex Photopheresis System (CPS) is a medical device used to treat the effects on skin of a type of cancer of the immune system (cutaneous T-cell lymphoma) which is not responding to other treatment. It is also used to treat systemic sclerosis."},{"field_id":1928,"order_no":2,"bullet":"Health Canada's review of the potential risk of blood clotting (thromboembolism) with the use of CPS followed a report by the United States Food and Drug Administration (US FDA) of 7 cases of thromboembolic events (2 of which involved death) in patients using CPS."},{"field_id":1928,"order_no":3,"bullet":"Health Canada's review concluded that the majority of the thromboembolic events reported worldwide happened after use of CPS to treat graft-versus-host-disease (GvHD), a condition which is not intended for treatment by CPS. GvHD is a disease where transplanted bone marrow or blood stem cells attack the body of the patient."},{"field_id":1928,"order_no":4,"bullet":"Health Canada has notified the manufacturer of CPS to update the device safety information (Instructions for Use) to add a warning that treatment of patients with GvHD is not an authorized intended use in Canada."}],"footnotes_list":[{"field_id":1932,"order_no":1,"bullet":"Search Medical Device Incidents"}],"reference_list":[],"use_canada_list":[{"field_id":1929,"order_no":1,"bullet":"Cellex Photophoresis System (CPS) is a medical device licensed in Canada to treat the skin manifestation of a type of cancer of the immune system (cutaneous T-cell lymphoma) that is not responding to other treatment."},{"field_id":1929,"order_no":2,"bullet":"It is also used to treat systemic sclerosis."},{"field_id":1929,"order_no":3,"bullet":"CPS has been sold in Canada by the manufacturer Therakos since 2009."}],"finding_list":[{"field_id":1930,"order_no":1,"bullet":"At the time of the review, Health Canada had received one report of an incident of blood clotting after using CPSa. Not enough information was provided in the report to clarify whether the use of CPS contributed to the cause of the blood clot."},{"field_id":1930,"order_no":2,"bullet":"Information given by the manufacturer of CPS, at Health Canada's request, identified 18 blood clotting (thromboembolic) events worldwide. In 8 of the 18 reports, the thromboembolic events happened within hours to 20 days after CPS treatment. Of the 18 events, 16 were thromboembolic incidents in patients being treated for graft-versus-host-disease (GvHD), which itself is a factor that increases risk for thromboembolic events. Treatment of GvHD is not an intended use of CPS. Additionally, 11 of the 18 reports had other risk factors for pulmonary embolism (PE) or deep vein thrombosis (DVT)."},{"field_id":1930,"order_no":3,"bullet":"A search of the scientific literature did not find any articles related to the thromboembolic issue with CPS use or similar medical devices. There were some articles that focused on the role or effectiveness of treating blood cells with UVA light-activated drugs (photopheresis) in the treatment of GvHD."},{"field_id":1930,"order_no":4,"bullet":"A literature review by the manufacturer on the root cause of thromboembolic events after photophoresis treatment has identified several risk factors, including cancer-linked factors, cancer treatment (anti-neoplastic therapy) - linked factors, increased risk with using catheters in veins for a long period of time (dwelling venous catheters), GvHD, and previous thromboembolic events."}],"conclusion_list":[{"field_id":1931,"order_no":1,"bullet":"Health Canada's review of the available information concluded that the majority of the thromboembolic events occurred after the use of CPS for the treatment of graft versus host disease (GvHD). Treatment of GvHD is not an intended use of CPS."},{"field_id":1931,"order_no":2,"bullet":"Considering the seriousness of the reported side effect with the off-label use of CPS, Health Canada has notified the manufacturer of CPS to update the device's Instructions for Use to include a warning that treatment of patients with GvHD is not an authorized use in Canada."},{"field_id":1931,"order_no":3,"bullet":"The manufacturer of CPS has notified customers of CPS of the risk of thromboembolic events when treating patients with GvHD."},{"field_id":1931,"order_no":4,"bullet":"If the manufacturer or industry associations require more information, they are encouraged to contact the Therapeutic Products Directorate."}]},{"template":2,"link_id":"SSR00225","review_date":null,"drug_name":"Opdivo (nivolumab) and Yervoy (ipilimumab) used alone, or in combination.","safety_issue":"Hemophagocytic Lymphohistiocytosis (HLH), a condition where large numbers of immune cells (activated macrophages) destroy other blood cells.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1960,"overview":"Following reports in medical literature, Health Canada reviewed the potential risk of Hemophagocytic Lymphohistiocytosis (HLH) with Opdivo or Yervoy used alone, or in combination.
HLH is a life-threatening overreaction of the immune system where a large number of immune cells attack and destroy other blood cells. HLH is characterized by a large release of certain proteins by immune cells in the blood (referred to as a \"cytokine storm\" or \"cytokine release syndrome\"), as well as the accumulation of activated immune cells (lymphocytes and macrophages) in organs and tissues.
","use_canada":1961,"findings":1962,"conclusion":1963,"additional":"The analysis that contributed to this risk assessment included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these drugs and medical devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
If manufacturers of medical devices or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":0,"footnotes":1964,"title":"Summary Safety Review - Opdivo (nivolumab) and Yervoy (ipilimumab) used alone, or in combination - Assessing the potential risk of Hemophagocytic Lymphohistiocytosis (HLH)","created_date":"2019-06-24","modified_date":null,"key_message_list":[{"field_id":1960,"order_no":1,"bullet":"Opdivo (nivolumab) and Yervoy (ipilimumab) can be used alone, or in combination, to treat different types of cancers, including cancers of the skin, kidney, lung, and liver."},{"field_id":1960,"order_no":2,"bullet":"Health Canada completed a safety review of the risk of Hemophagocytic Lymphohistiocytosis (HLH - a condition where a large number of immune cells attack and destroy other blood cells) associated with the use of these products following reports of HLH published in medical literature. "},{"field_id":1960,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of these products and the development of HLH."},{"field_id":1960,"order_no":4,"bullet":"Health Canada will work with the manufacturer of Opdivo and Yervoy to ensure that the product safety information is appropriate."},{"field_id":1960,"order_no":5,"bullet":"If consumers have any concerns they are advised to speak with their healthcare professional."}],"footnotes_list":[{"field_id":1964,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[],"use_canada_list":[{"field_id":1961,"order_no":1,"bullet":"Opdivo (nivolumab) and Yervoy (ipilimumab) are prescription drugs authorized for sale in Canada to treat different types of cancers. Used either alone, or in combination, they help prevent or stop the growth of a tumour (antineoplastic). Both Opdivo and Yervoy are administered directly into a vein by intravenous infusion under the supervision of a physician experienced in treating cancer."},{"field_id":1961,"order_no":2,"bullet":"Opdivo has been marketed in Canada since October 2015, and Yervoy since March 2012."}],"finding_list":[{"field_id":1962,"order_no":1,"bullet":"The use of Opdivo and Yervoy (alone or in combination) is known to cause a range of immune-related side effects."},{"field_id":1962,"order_no":2,"bullet":"At the time of the review, Health Canada had received 1 Canadian reporta of a cancer patient who developed HLH after treatment with Opdivo, in combination with Yervoy. This report was considered serious and involved death."},{"field_id":1962,"order_no":3,"bullet":"Health Canada also looked at 21 international reports of HLH following treatment with Opdivo and Yervoy, either used alone or in combination. All reports were considered serious, and 6 of the 21 involved death."},{"field_id":1962,"order_no":4,"bullet":"Health Canada could not confirm whether the use of Opdivo or Yervoy was the cause of the reported deaths in the Canadian or the international reports."},{"field_id":1962,"order_no":5,"bullet":"Health Canada also looked at the scientific and medical literature. The articles reviewed suggest that there may be a link between the use of drugs that are in the PD-1 inhibitors class (such as Opdivo), and the development of HLH."},{"field_id":1962,"order_no":6,"bullet":"Health Canada's assessment could not rule out a link between Opdivo and Yervoy and the development of HLH."}],"conclusion_list":[{"field_id":1963,"order_no":1,"bullet":"Health Canada's review of all the available information has concluded that there may be a link between the use of Opdivo and Yervoy alone, or in combination, and the risk of HLH."},{"field_id":1963,"order_no":2,"bullet":"Health Canada will work with the manufacturer to determine the appropriate changes to the product safety information."},{"field_id":1963,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any adverse reactions related to the use of this, or other health products."},{"field_id":1963,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Opdivo and Yervoy, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if any new health risks are identified."}]},{"template":2,"link_id":"SSR00226","review_date":null,"drug_name":"Systemic fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin and norfloxacin)","safety_issue":"Aneurysm (a balloon-like bulge) and dissection (a separation or tear in the layers of the wall) of the aorta (the major blood vessel that carries blood from the heart to the body)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1970,"overview":"Health Canada carried out a safety review of the potential risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones. The safety review was triggered by published studies, including one study conducted in Canada1.
An aortic dissection is a tear of the inside lining of the aorta, the major blood vessel that carries blood from the heart to the rest of the body. An aortic aneurysm is a balloon-like bulge in the wall of the aorta. A rupture of the aneurysm can cause bleeding and, in the most serious cases, may lead to death. Patients with an aortic aneurysm frequently do not show any symptoms and the aneurysm may not be diagnosed until it ruptures. Both aortic dissection and ruptured aneurysm can cause severe pain and death.
While a tear and bulge can occur in any artery, they are most common in the aorta.
High blood pressure (hypertension) and the build-up of plaques inside arteries (atherosclerosis) are major risk factors for aortic dissections and/or aneurysms.
","use_canada":1971,"findings":1972,"conclusion":1973,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information about Health Canada's safety review, please contact the Marketed Health Products Directorate.
If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate.
","full_review":"","references":1974,"footnotes":1975,"title":"Summary Safety Review - Fluoroquinolones - Assessing the potential risk of aneurysm (a balloon-like bulge) and dissection (a separation or tear in the layers of the wall) of the aorta (a major blood vessel)","created_date":"2019-06-27","modified_date":null,"key_message_list":[{"field_id":1970,"order_no":1,"bullet":"Fluoroquinolones are antibiotic prescription drugs that are authorized for sale in Canada to treat many types of bacterial infections, including urinary tract and respiratory infections."},{"field_id":1970,"order_no":2,"bullet":"Following published studies1-4 that found an increased risk of aortic aneurysm and aortic dissection in patients treated with fluoroquinolones, Health Canada carried out a safety review."},{"field_id":1970,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between systemic fluoroquinolone use and the risk of aortic aneurysm and dissection."},{"field_id":1970,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the product safety information for all systemic fluoroquinolones to include information about this potential risk."}],"footnotes_list":[{"field_id":1975,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":1975,"order_no":2,"bullet":"PRAC recommendations on signals adopted at the 3-6 September 2018 PRAC meeting; available at https://www.ema.europa.eu/documents/prac-recommendation/prac-recommendations-signals-adopted-3-6-september-2018-prac-meeting_en-0.pdf"},{"field_id":1975,"order_no":3,"bullet":"The United States Food and Drug Administration (US FDA) drug safety communication issued on December 20th 2018; available at: https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm; accessed on January 16, 2019"}],"reference_list":[{"field_id":1974,"order_no":1,"bullet":"Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open. 2015;5(11):e010077"},{"field_id":1974,"order_no":2,"bullet":"Lee C, Gabriel Lee M, Chen Y, Lee S, Chen Y, Chen S, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-47."},{"field_id":1974,"order_no":3,"bullet":"Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: Nationwide cohort study. BMJ. 2018;360:k678."},{"field_id":1974,"order_no":4,"bullet":"Lee C, Lee M-G, Hsieh R, Porta L, Lee W, Lee S, et al. Oral Fluoroquinolone and the Risk of Aortic Dissection. J Am Coll Cardiol. 2018;72(12):1369-78."}],"use_canada_list":[{"field_id":1971,"order_no":1,"bullet":"Fluoroquinolones have been marketed in Canada since 1986. They are available as generics and brand names: Cipro (ciprofloxacin), Avelox (moxifloxacin), levofloxacin, and norfloxacin."},{"field_id":1971,"order_no":2,"bullet":"Fluoroquinolones are prescription drugs authorized for sale in Canada to treat many types of bacterial infections, including urinary and respiratory tract infections. They can be taken by mouth (oral), injection, or inhalation. There are some fluoroquinolones that can be applied to the eyes and ears."},{"field_id":1971,"order_no":3,"bullet":"The review was limited to several oral, injectable, and inhalation fluoroquinolones available in Canada. As products that are applied to the eyes and ears have not been reported to cause aneurysms or dissections of the aorta, Health Canada's review did not assess these products."},{"field_id":1971,"order_no":4,"bullet":"Around 4 million prescriptions are filled every year for fluoroquinolones."}],"finding_list":[{"field_id":1972,"order_no":1,"bullet":"At the time of the review, Health Canada received 28 international published reports, and 4 Canadian reportsa of aortic aneurysms and dissections with the use of fluoroquinolones. Of the Canadian reports, 3 were further assessed as they met the criteria defined for this review. One report showed a possible link between aortic aneurysm and the use of levofloxacin. The other 2 cases could not be assessed due to insufficient information."},{"field_id":1972,"order_no":2,"bullet":"Health Canada also looked at the scientific literature and focussed on 4 published studies. Although there were limitations to these studies, they showed an approximately two-fold increased risk of aortic aneurysm and dissection in patients treated with fluoroquinolones, including one Canadian study1 ."},{"field_id":1972,"order_no":3,"bullet":"The European Medicines Agency (EMA)b and the United States Food and Drug Administration (US FDA)c are updating the product safety information for fluoroquinolones to include the risk of aortic aneurysm and dissection."}],"conclusion_list":[{"field_id":1973,"order_no":1,"bullet":"Health Canada's review of the available information has concluded that there may be a link between the use of systemic fluoroquinolones (given by mouth, by injection, or by inhalation) and aortic aneurysm and dissection. Given the frequent use of fluoroquinolones in Canada and the information reviewed, these side effects are considered rare."},{"field_id":1973,"order_no":2,"bullet":"Health Canada recommended that the product safety information for all systemic fluoroquinolone products be updated to include information about this rare but serious adverse effect. In addition, Health Canada will inform Canadians and healthcare professionals of this new safety information in the Health Product InfoWatch."},{"field_id":1973,"order_no":3,"bullet":"Health Canada is working with the manufacturers to update the product safety information of all systemic fluoroquinolone products marketed in Canada."},{"field_id":1973,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving fluoroquinolones, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00227","review_date":null,"drug_name":"Propofol-containing products","safety_issue":"Prolonged erection of the penis (priapism)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1982,"overview":"A safety review was initiated by Health Canada to evaluate the available information regarding the potential risk of priapism with the use of propofol-containing products. These products are used to make a patient relaxed, calm or sleepy (sedation) or unconscious (anesthesia) during surgery or medical procedures.
Priapism is a prolonged, and usually painful, erection of the penis not caused by sexual stimulation. It is a rare, but potentially serious, medical condition. Failure to treat this condition promptly may result in permanent disability, such as the inability to get and keep an erection firm enough for sex (erectile dysfunction).
Health Canada's review was triggered by a Canadian report of priapism in a patient that was sedated with a propofol-containing product for a medical procedure.
","use_canada":1983,"findings":1984,"conclusion":1985,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these drugs both in Canada and internationally.
For additional information about Health Canada's safety review, please contact the Marketed Health Products Directorate.
If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":0,"footnotes":1986,"title":"Summary Safety Review - Propofol-containing products - Assessing the potential risk of prolonged erection of the penis (priapism)","created_date":"2019-07-12","modified_date":null,"key_message_list":[{"field_id":1982,"order_no":1,"bullet":"Propofol-containing products are sedative/anesthetic drugs used by health care professionals during surgeries, or other medical procedures, in children and adults."},{"field_id":1982,"order_no":2,"bullet":"Health Canada reviewed the risk of prolonged and painful erection not caused by sexual stimulation (priapism) with propofol-containing products because of a reported Canadian case."},{"field_id":1982,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between propofol-containing products and the risk of priapism."},{"field_id":1982,"order_no":4,"bullet":"Health Canada will notify the manufacturers of propofol-containing products to update the Canadian product safety information to inform Canadians and health care professionals about this potential safety issue."}],"footnotes_list":[{"field_id":1986,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":1983,"order_no":1,"bullet":"Propofol-containing products are prescription drugs which are authorized for sale in Canada and used by health care professionals to make a patient (adult or child) relaxed, calm or sleepy (sedation) or unconscious (anesthesia) during surgery or medical procedures."},{"field_id":1983,"order_no":2,"bullet":"Propofol-containing products have been marketed in Canada since 1993 under the brand name Diprivan. Generic versions of propofol are also available. Propofol is available as a 10 mg/mL solution for injection."}],"finding_list":[{"field_id":1984,"order_no":1,"bullet":"At the time of the review, Health Canada had received 1 unique Canadian reporta of priapism related to the use of propofol-containing products. A review of this report found a possible link between propofol-containing products and priapism."},{"field_id":1984,"order_no":2,"bullet":"This safety review also looked at 10 international published reports. The link between propofol-containing products and priapism was likely in 2 reports and possible in 7 reports. In 1 report, the priapism was found unlikely to be caused by propofol-containing products."},{"field_id":1984,"order_no":3,"bullet":"In the majority of the reports (9/11), priapism happened between 5 minutes to 2 hours after propofol was administered."},{"field_id":1984,"order_no":4,"bullet":"Most patients (10/11) recovered after treatment of the priapism with only 1 reporting long-term disability (ongoing erectile dysfunction)."}],"conclusion_list":[{"field_id":1985,"order_no":1,"bullet":"Health Canada's review found that there may be a link between propofol-containing products and the risk of priapism."},{"field_id":1985,"order_no":2,"bullet":"Health Canada has already approved the addition of the risk of priapism to the Canadian product information for Diprivan 1%. Health Canada will notify the manufacturers of other propofol-containing products to update the Canadian product safety information to inform Canadians and health care professionals about this potential safety issue."},{"field_id":1985,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving propofol-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00228","review_date":null,"drug_name":"U by Kotex Sleek and U by Kotex Click Menstrual Tampons","safety_issue":"Tampons coming apart during removal and potential adverse reactions (side effects) if pieces are not all removed from the body","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":1992,"overview":"As part of its post-market surveillance, Health Canada observed an increase in the number of incidents reported since 2017 related to U by Kotex Sleek and U by Kotex Click tampons coming apart during removal. Some users needed medical attention to remove tampon pieces left in the body, or had adverse reactions such as infections, vaginal irritation, abdominal pain, fever, nausea or headaches.
A menstrual tampon is a soft material product that is inserted into the vagina to absorb blood during a woman's menstrual period. It may or may not come with an applicator to help insertion. A tampon may have an attached string to help remove it. Using tampons may present certain health risks, including toxic shock syndrome (TSS), a condition resulting from bacteria getting into the body (bloodstream) and releasing toxins. It is a rare but serious infection that has initial symptoms similar to the flu. These risks are increased if tampons are left in too long.
More information on menstrual tampons, including information to help users minimize the potential health risks of tampon use, can be found here.
","use_canada":1993,"findings":1994,"conclusion":1995,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of these medical devices both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - U by Kotex Sleek and U by Kotex Click Tampons - Assessing the risk of tampons coming apart during removal and potential adverse reactions (side effects)","created_date":"2019-07-18","modified_date":null,"key_message_list":[{"field_id":1992,"order_no":1,"bullet":"U by Kotex Sleek and U by Kotex Click are menstrual tampons."},{"field_id":1992,"order_no":2,"bullet":"Health Canada's safety review was triggered by an increase in the number of complaints/incidents reported in Canada related to U by Kotex Sleek and U by Kotex Click tampons, with the majority of reports describing tampons coming apart during removal."},{"field_id":1992,"order_no":3,"bullet":"Health Canada requested more information from the manufacturer after a small number of reports described symptoms that could have been related to toxic shock syndrome (TSS). TSS is a condition resulting from bacteria getting into the body and releasing toxins."},{"field_id":1992,"order_no":4,"bullet":"In response to reports of U by Kotex Sleek tampons coming apart and of adverse reactions, the manufacturer initiated a voluntary recall (product removal) of certain batches (lots) in December 2018."},{"field_id":1992,"order_no":5,"bullet":"A recall of the U by Kotex Click tampons was not necessary given the lower rate of tampons coming apart and the use of different manufacturing equipment."},{"field_id":1992,"order_no":6,"bullet":"Based on a review of all available information, Health Canada concluded that the voluntary recall done by the manufacturer was satisfactory."},{"field_id":1992,"order_no":7,"bullet":"Health Canada will work with the manufacturer to monitor the effectiveness of the corrective measures taken to address the risk of tampons coming apart during use, and will continue to actively monitor the safety of these medical devices."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":1993,"order_no":1,"bullet":"U by Kotex Sleek and U by Kotex Click are menstrual tampons."},{"field_id":1993,"order_no":2,"bullet":"These tampons are widely available in Canada and are manufactured by Kimberly-Clark."}],"finding_list":[{"field_id":1994,"order_no":1,"bullet":"Health Canada observed an increase in the number of reports related to U by Kotex Sleek and U by Kotex Click tampons coming apart during removal. In the majority of reports, there was no reported injury to the user, but some needed medical attention to remove tampon pieces left in the body. A small number of reports described symptoms that could have been related to toxic shock syndrome (TSS), such as abdominal pain, fever, headache, infection, nausea, vaginal irritation, and vomiting."},{"field_id":1994,"order_no":2,"bullet":"On December 11, 2018, the manufacturer announced a recall to withdraw certain batches of U by Kotex Sleek tampons from the Canadian market due to a manufacturing issue that made them more likely to come apart during removal."},{"field_id":1994,"order_no":3,"bullet":"As part of this safety review, Health Canada requested more information from the manufacturer. This information clarified that:Pelvic organ prolapse (POP) is a drop or bulge (prolapse) of pelvic organs because weakened tissue and muscle can no longer support them.
Pelvic organ prolapse usually involves one or more pelvic organs, such as the bladder, the tube that empties the bladder (urethra), the womb (uterus), or the rectum. When pelvic floor muscles and tissues are weak or damaged, these organs can drop from their normal position and bulge into the wall of the vagina. There are different degrees of prolapse depending on how far the organ(s) have bulged. Symptoms of POP depend on the type and severity of the prolapse, and can include incontinence, difficulty urinating or painful intercourse. While POP is not a life-threatening condition, it can have a significant negative impact on quality of life.
Surgery may be an option for women when other therapies fail. Surgical procedures may involve entering through the vagina or the abdomen, and may include using surgical mesh. Over the past decade, there have been reports of complications related to the use of synthetic surgical mesh for the transvaginal repair of POP.
These reports have triggered many regulatory actions internationally, including several safety reviews and communications by Health Canada1-3. In 2014, Health Canada completed a safety review and recommended that healthcare professionals:
Despite the issuance of communications about this safety issue, as well as newly published literature, clinical guidelines, and information issued by international regulatory agencies, there remain ongoing concerns about surgical mesh products used transvaginally. As a result, Health Canada updated the 2014 safety review. This new review includes updated Canadian-specific reports of incidents and device usage data, clinical literature and guidelines, ongoing international regulatory activities, and input from Canadian medical associations on the use of these devices.
","use_canada":2001,"findings":2002,"conclusion":2003,"additional":"Since the completion of this safety review4, all manufacturers have notified Health Canada that licences for non-absorbable, synthetic surgical mesh products indicated for the transvaginal repair of POP are to be cancelled. All unused products indicated for the transvaginal repair of posterior compartment POP are being actively removed from the market. Healthcare providers have been notified of the revised recommended patient population for the use of non-absorbable, synthetic mesh for transvaginal repair of bladder and uterus prolapse.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these medical devices both in Canada and internationally.
For additional information about Health Canada's assessment, contact the Marketed Health Products Directorate.
If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":2004,"footnotes":2005,"title":"Summary Safety Review - Surgical mesh products - Assessing the potential risk of complications associated with transvaginal implantation of non-absorbable synthetic surgical mesh for the treatment of pelvic organ prolapse (POP)","created_date":"2019-07-26","modified_date":"2019-07-29","key_message_list":[{"field_id":2000,"order_no":1,"bullet":"Pelvic organ prolapse (POP) is a drop or bulge (prolapse) of pelvic organs because weakened tissue and muscle can no longer support them. Pelvic organ prolapse can involve the bladder (anterior compartment), the uterus (apical compartment), and/or the rectum (posterior compartment)."},{"field_id":2000,"order_no":2,"bullet":"Synthetic, non-absorbable surgical mesh products indicated for the treatment of POP are classified as medical devices in Canada. Implantation of the mesh by surgeons takes place either through the vagina (transvaginally) or through an incision in the abdomen (transabdominally)."},{"field_id":2000,"order_no":3,"bullet":"Health Canada has updated its previous safety reviews on complications of transvaginally implanted synthetic surgical mesh used for the repair of POP. The update was triggered by ongoing safety concerns, newly published literature and clinical guidelines, and information issued by international regulatory agencies."},{"field_id":2000,"order_no":4,"bullet":" Health Canada's safety review found that compared to other treatment options, the transvaginal implantation of non-absorbable synthetic surgical mesh to treat posterior compartment prolapse (such as the rectum) poses a greater risk of complications including pain, repeated infections, and mesh erosion (or exposure) through surrounding tissues."},{"field_id":2000,"order_no":5,"bullet":"Health Canada's review also found that the use of non-absorbable synthetic mesh for the transvaginal surgical repair of anterior (bladder) and/or apical (uterus) prolapse should only be used for patients who have significant risk factors for recurrence of POP or recurrent POP, or for whom alternative surgical treatments are not appropriate."},{"field_id":2000,"order_no":6,"bullet":"As a result of the safety review, Health Canada will:Health Canada's review of the potential risk of suicidal thoughts and behaviours (suicidality) with the use of hormonal birth control products was triggered by a safety review conducted by the EMA. The EMA's safety review was based on a published study suggesting a higher risk of suicide/first suicide attempts among users of hormonal birth control products compared to non-users. The risk was found to be higher for the hormone-containing patch placed on the skin (transdermal patch), the vaginal ring and progestin-only products, in comparison to the combined oral contraceptive (COC) products.1 The EMA's safety review led to an update to the European product safety information with a new warning statement about the risk of depression with the use of hormonal birth control products (similar to the current Canadian warning), linking suicidality to depression in severe cases. It is important to note that depression is the most common illness diagnosed among those who commit suicide, and it is well known that severe depression could lead to suicide.2
In Health Canada's review, suicidality was defined as suicidal thoughts and behaviours (completed suicide, suicide attempt, preparatory acts towards imminent suicidal behaviour, and serious thoughts about taking one's own life). Health Canada assessed the risk of suicidality for each type of hormonal birth control producta to determine if there was a need for further monitoring and/or the implementation of additional risk minimization measures.
","use_canada":2013,"findings":2014,"conclusion":2015,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2016,"footnotes":2017,"title":"Summary Safety Review - Hormonal Birth Control Products (excluding Emergency Birth Control Products) - Assessing the Potential Risk of Suicidal Thoughts and Behaviours (suicidality)","created_date":"2019-08-06","modified_date":"2019-09-19","key_message_list":[{"field_id":2012,"order_no":1,"bullet":"Hormonal birth control products are prescription drugs and medical devices that contain hormones and are used to prevent pregnancy. Many hormonal birth control products are authorized for sale in Canada; for a complete list, see footnote.a "},{"field_id":2012,"order_no":2,"bullet":"Health Canada reviewed the potential risk of suicidal thoughts and behaviours (suicidality) with the use of hormonal birth control products. This review was triggered by a safety review conducted by the European Medicines Agency (EMA). "},{"field_id":2012,"order_no":3,"bullet":"Health Canada's review of the available information found that there is not enough evidence at this time to support a link between the use of hormonal birth control products and the risk of suicidality. "},{"field_id":2012,"order_no":4,"bullet":"The product safety information for hormonal birth control products in Canada currently includes warning statements about the risk of depression and mood changes. "},{"field_id":2012,"order_no":5,"bullet":"Based on the evidence reviewed, no revisions to the product safety information were deemed necessary and the current labelling was found to sufficiently address the risks of depression and mood changes. "},{"field_id":2012,"order_no":6,"bullet":"Health Canada will continue to monitor safety information involving hormonal birth control products, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2017,"order_no":1,"bullet":"Authorized Hormonal Contraceptivess in Canada include: Levonorgestrel (Jaydess, Kyleena, Mirena, etc); Etonogestrel/Ethinyl estradiol (prnuvaring®); Desogestrel (Apri 21, Apri 28, linessa 28); Norgestrel (Lo-femenal 21); Norgestimate (Centrisa 21, Centrisa 28); Norethindrone acetate (Loestrin 1.5/30, lolo); Norethindrone (Brevicon 0.5/35 tablets); Ethynodiol diacetate (Demulen); Medroxyprogesterone acetate (Depo-provera sterile aqueous suspension); Norelgestromin (Evra); Estradiol valerate (Natazia); Drospirenone (Drospirenone and Ethinyl estradiol, Mya, Nikki, Yasmin, Yaz, Zamine, Zarah); Ethinyl estradiol (Ovral); Cyproterone acetate (Cléo, Cyestra, Diane, etc); Progesterone (Act progesterone injection); Medroxyprogesterone acetate (Apo-medroxy, Medroxy, Meprogest, Nu-Medroxy, etc)."},{"field_id":2017,"order_no":2,"bullet":"For this report, the Marketed Health Products Directorate of Health Canada used the IQVIA Canadian Drug Store (Compuscript database [CS]), which measures the dollar value and unit volume of pharmaceutical products purchased by Canadian retail pharmacy outlets. Data for CS are collected from a representative sample of 2998 drug stores (November 2018). The sample data are then projected to the universe of drug stores, to reflect all purchases across Canada."},{"field_id":2017,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2016,"order_no":1,"bullet":"Skovlund CW, Morch LS, Kessing LV, Lange T and Lidegaard O. Association of Hormonal Contraception with Suicide Attempts and Suicides. Am J Psychiatry 2017, appiajp201717060616."},{"field_id":2016,"order_no":2,"bullet":"Mocicki EK. Epidemiology of completed and attempted suicide: Toward a framework for prevention. Clinical Neuroscience Research. 2001; 1:310-23."}],"use_canada_list":[{"field_id":2013,"order_no":1,"bullet":"Hormonal birth control products have been used for many decades to prevent pregnancy."},{"field_id":2013,"order_no":2,"bullet":"They are considered to be one of the most widely used pharmaceuticals by women worldwide. In Canada, hormonal birth control products are broadly used, with more than 10 million prescriptions dispensed in 2018.b"},{"field_id":2013,"order_no":3,"bullet":"Over the last 6 years, combined oral contraceptive (COC) products with ethinyl estradiol and levonorgestrel (e.g., Alesse, Alysena, Aviane, Indayo, Lutera, Mini-Ovral, Ovima, Portia, Seasonique, Triquilar) were the birth control products most commonly dispensed in Canada."}],"finding_list":[{"field_id":2014,"order_no":1,"bullet":"At the time of the review, Health Canada had received 121 Canadian reportsc for suicidality since January 1, 1965. After screening all reports, 98 reports were excluded, mainly for the lack of information. As such, 23 case reports underwent assessment as part of this review, of which 11 were related specifically to Depo-Provera (an injectable hormonal birth control product). Based on the review, a link between the use of hormonal birth control products and the potential risk of suicidality was found to be likely in 1 report, possible in 20 reports and could not be assessed in 2 reports. Serious thoughts about suicide was the most common event in these reports."},{"field_id":2014,"order_no":2,"bullet":"Of the 20 reports where the link between the use of hormonal birth control products and the potential risk of suicidality was deemed possible, only 1 case report was of a completed suicide. In this case, the patient was using the hormonal birth control Depo-Provera. However, there were also other significant factors which may have contributed to this suicide, besides the use of Depo-Provera."},{"field_id":2014,"order_no":3,"bullet":"The product safety information for all hormonal birth control products in Canada includes a warning statement about the risk of depression/mood changes. The risk of suicidality is specifically listed in the product safety information for Depo-Provera. The majority (11/23) of the Canadian reports assessed assessed as part of this review were related to Depo-Provera."},{"field_id":2014,"order_no":4,"bullet":"The link between the use of hormonal birth control products and the risk of suicidality remains unclear, however scientific and medical literature seems to supports a link between depression/mood changes and the use of hormonal birth control products."}],"conclusion_list":[{"field_id":2015,"order_no":1,"bullet":"Health Canada's review concluded that there was not enough evidence to support a direct link between the use of hormonal birth control products and the risk of suicidality."},{"field_id":2015,"order_no":2,"bullet":"The current Canadian labelling of hormonal birth control products includes a warning about the risk of depression/mood changes. Suicidality is specifically labelled for Depo-Provera."},{"field_id":2015,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving hormonal birth control products to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00231","review_date":null,"drug_name":"Tapazole (methimazole) and generics","safety_issue":"Inflammation of the pancreas (acute pancreatitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2024,"overview":"Acute pancreatitis is an inflammatory disease of the pancreas that is most commonly caused by gallstones and alcohol use, but can also be caused by a drug reaction (drug-induced pancreatitis). It is characterized by a sudden onset of abdominal pain that is often severe.
Health Canada reviewed the potential risk of acute pancreatitis with the use of methimazole when product safety information for methimazole- and carbimazole-containing products was updated in Europe to include the risk of acute pancreatitis. Information on carbimazole was also considered in Health Canada's review, although this product is not marketed in Canada.
","use_canada":2025,"findings":2026,"conclusion":2027,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of methimazole, both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2028,"title":"Summary Safety Review - Methimazole - Assessing the Potential Risk of Inflammation of the Pancreas (Acute Pancreatitis)","created_date":"2019-09-12","modified_date":null,"key_message_list":[{"field_id":2024,"order_no":1,"bullet":"Methimazole, also known as thiamazole, is a prescription drug authorized for sale in Canada to treat hyperthyroidism, a condition where too much thyroid hormone is produced. It is also used in preparation for radioactive iodine therapy or surgical removal of an overactive thyroid gland, and in cases where the overactive thyroid gland cannot be removed."},{"field_id":2024,"order_no":2,"bullet":"Health Canada reviewed the potential risk of inflammation of the pancreas (acute pancreatitis) with the use of methimazole after being made aware of international reports."},{"field_id":2024,"order_no":3,"bullet":"Health Canada's review of available evidence concluded that there is a link between methimazole and the risk of acute pancreatitis."},{"field_id":2024,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the Canadian product safety information for all methimazole products to inform healthcare professionals and patients about this risk."}],"footnotes_list":[{"field_id":2028,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2025,"order_no":1,"bullet":"Methimazole is a prescription drug authorized for sale in Canada to treat hyperthyroidism, a condition in which too much thyroid hormone is produced. It is also used in preparation for radioactive iodine therapy or surgical removal of the overactive thyroid gland."},{"field_id":2025,"order_no":2,"bullet":"Methimazole, also called thiamazole, has been marketed in Canada for more than 60 years under the brand name Tapazole, and is available as 5 mg and 10 mg oral tablets. Generic versions have also been authorized for sale in Canada."},{"field_id":2025,"order_no":3,"bullet":"Use of methimazole oral tablets has remained relatively steady in Canada over the last 5 years at approximately 200,000 prescriptions annually."}],"finding_list":[{"field_id":2026,"order_no":1,"bullet":"This safety review is based on 8 robust international published case reports of acute pancreatitis with the use of methimazole (6) or carbimazole (2). Of these 8, 4 reports were found to be linked to the use of methimazole (3) or carbimazole (1), and 4 reports were possibly linked to the use of methimazole or carbimazole."},{"field_id":2026,"order_no":2,"bullet":"The review also looked at 1 published study that did not observe a relationship between methimazole use and acute pancreatitis. However, there were limitations to this study including small sample size, which makes it difficult to confirm a relationship."},{"field_id":2026,"order_no":3,"bullet":"At the time of the review, Health Canada received 21 Canadian reportsa of potential acute pancreatitis related to methimazole use. These reports were not assessed further because the cases did not meet the criteria of the review. Specifically, these cases did not report the actual adverse event of interest, or the timing of methimazole use and the development of pancreatitis was unclear, or the reports did not match the diagnosis of drug-induced pancreatitis."}],"conclusion_list":[{"field_id":2027,"order_no":1,"bullet":"Health Canada's review of the available information found that there is a link between methimazole use and the risk of acute pancreatitis."},{"field_id":2027,"order_no":2,"bullet":"Health Canada is working with the manufacturers to update the Canadian product safety information on methimazole products to inform about this risk."},{"field_id":2027,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving methimazole products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00232","review_date":null,"drug_name":"Avalon Fetal Monitor FM20, Avalon Fetal Monitor FM30, Avalon Fetal Monitor FM40 and Avalon Fetal Monitor FM50 manufactured by Philips Medizin Systeme Boeblingen GmbH","safety_issue":"Inaccurate heart rate tracking of unborn babies (fetuses)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2034,"overview":"In 2017, Health Canada received incident reports related to the Avalon Fetal Monitor and inaccurate fetal heart rate monitoring, including outcomes of deaths of fetuses (stillbirths) and the potential need for immediate care at birth. As a result, Health Canada conducted a safety review to assess the potential safety risks associated with this device.
The Avalon Fetal Monitor is a continuous electronic fetal monitoring device, which allows healthcare professionals providing obstetrical care to analyze fetal heart rate changes during labour and delivery. Inaccurate monitoring could lead to unnecessary interventions, or failure to identify abnormal fetal heart rate patterns (sign of fetal distress) and the need for intervention.
At the time of the review, Health Canada had not received similar reports with other continuous fetal heart rate monitors currently licensed in Canada.
","use_canada":2035,"findings":2036,"conclusion":2037,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of this device both in Canada and internationally.
For additional information about Health Canada's assessment, please contact the Marketed Health Products Directorate.
If manufacturers or industry associations require more information at this time, they are encouraged to contact the Therapeutic Products Directorate (hc.tpdgeneral-generaldpt.sc@canada.ca).
","full_review":"","references":0,"footnotes":2038,"title":"Summary Safety Review - Avalon Fetal Monitor - Assessing the potential risk of inaccurate heart rate tracking of unborn babies (fetuses)","created_date":"2019-10-09","modified_date":null,"key_message_list":[{"field_id":2034,"order_no":1,"bullet":"The Avalon Fetal Monitor is a medical device licensed in Canada for heart rate tracking (monitoring) of the mother and unborn baby or babies (fetus or fetuses). It can be used during labour and delivery."},{"field_id":2034,"order_no":2,"bullet":"Health Canada's safety review was triggered by Canadian reports related to the use of the Avalon Fetal Monitor that describe possible inaccurate heart rate tracking including outcomes of deaths of fetuses (stillbirths) and the potential need for immediate care at birth."},{"field_id":2034,"order_no":3,"bullet":"The review did not find enough information to establish a link between the use of the device and poor fetal outcomes."},{"field_id":2034,"order_no":4,"bullet":"While the Avalon Fetal Monitor Instructions for Use (IFU) contains detailed information regarding the correct use of the device, key instructions are not highlighted. As a result, users may not be aware of certain key steps during the use of the device, which could contribute to inaccurate fetal heart rate monitoring."},{"field_id":2034,"order_no":5,"bullet":"Health Canada has worked with the manufacturer to update the IFU to ensure that important instructions are appropriately highlighted in order to help further reduce the risk associated with inaccurate monitoring."},{"field_id":2034,"order_no":6,"bullet":"A Health Product Risk Communication has been published to give healthcare professionals more details about this risk and to communicate the changes that have been approved for the IFU."}],"footnotes_list":[{"field_id":2038,"order_no":1,"bullet":"Search Medical Device Incidents (https://hpr-rps.hres.ca/mdi_landing.php?lang=en)"}],"reference_list":[],"use_canada_list":[{"field_id":2035,"order_no":1,"bullet":"The Avalon Fetal Monitor is a medical device authorized for sale in Canada to monitor the heart rate of the mother and fetus or fetuses before and during labour and delivery."},{"field_id":2035,"order_no":2,"bullet":"Continuous electronic fetal heart rate monitoring during labour helps healthcare professionals identify possible fetal distress and provide timely intervention if needed."},{"field_id":2035,"order_no":3,"bullet":"The Avalon Fetal Monitor has been sold in Canada since 2006 by Philips Medizin Systeme Boeblingen GmbH. There are 4 models available: FM20, FM30, FM40, and FM50."}],"finding_list":[{"field_id":2036,"order_no":1,"bullet":"At the time of the review, Health Canada had looked at all incident reports related to the Avalon Fetal Monitor and inaccurate fetal heart rate monitoring. The review assessed reports involving poor fetal outcomes. There were 8 Canadian reportsa of fetal death and 2 reports of a potential need for immediate care at birth. While inaccurate fetal heart rate monitoring was found to have occurred, there was not enough information to confirm the cause of the outcomes, or whether the Avalon Fetal Monitor played a role in the outcomes of these cases."},{"field_id":2036,"order_no":2,"bullet":"The cause of fetal death during labour and delivery is complex and difficult to identify because many factors may be involved. In these incidents, there was no evidence of device malfunction."},{"field_id":2036,"order_no":3,"bullet":"There were also international reports of fetal or newborn baby (neonatal) deaths, poor neonatal outcome, and unnecessary caesarean section (C-sections) in cases where the Avalon Fetal Monitor had been used."},{"field_id":2036,"order_no":4,"bullet":"The review showed that inaccurate fetal heart rate monitoring could be caused by accidental recording of the mother's heart rate. Scientific literature suggests that this could happen with all continuous fetal heart rate monitors that use Doppler ultrasound to track fetal heart rate."},{"field_id":2036,"order_no":5,"bullet":"In 2009, the manufacturer of the Avalon Fetal Monitor issued a recall to provide more information to help healthcare professionals better recognize potential inaccurate fetal heart rate readings and manage the associated risks. This recall did not involve product removal from the market. This information has since been included into the newer versions of the Instructions for Use."},{"field_id":2036,"order_no":6,"bullet":"In 2014, the manufacturer put in place additional risk mitigation measures, including introducing new accessory and software updates to help users identify potential inaccuracies. Starting with software version Revision J.3, an audible alarm was added to notify users when the maternal heart rate is potentially being mistaken for the fetal heart rate, or when a fetal heart rate is potentially being mistaken for another fetal heart rate in the case of twins or triplets. Even with these actions, Health Canada received new reports in 2017 related to the Avalon Fetal Monitor and inaccurate fetal heart rate monitoring."},{"field_id":2036,"order_no":7,"bullet":"Health Canada's review also found that not all Avalon Fetal Monitor units being used in Canada have the latest software version installed."}],"conclusion_list":[{"field_id":2037,"order_no":1,"bullet":"Overall, Health Canada's review of the available information found that inaccurate fetal heart rate monitoring is occurring, but there was insufficient evidence to establish a link between the use of the Avalon Fetal Monitor and the reported incidents. There was no evidence of device malfunction in these incidents."},{"field_id":2037,"order_no":2,"bullet":"While the Avalon Fetal Monitor Instructions for Use (IFU) contains detailed information regarding the correct use of the device, key instructions are not prominently highlighted. As a result, users may not be aware of certain key steps during the use of the device, which could contribute to inaccurate FHR monitoring."},{"field_id":2037,"order_no":3,"bullet":"Health Canada has worked with the manufacturer to update the IFU to ensure that important instructions are appropriately highlighted in order to help further reduce the risk associated with inaccurate monitoring. Health Canada has issued a Health Product Risk Communication to increase awareness of how to reduce the risk of inaccurate fetal heart rate monitoring and to communicate the changes that have been approved for the IFU."},{"field_id":2037,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving fetal heart rate monitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00233","review_date":null,"drug_name":"Xarelto (rivaroxaban)","safety_issue":"Liver injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2044,"overview":"Health Canada reviewed the potential risk of liver injury with Xarelto (rivaroxaban) in 2015. The 2015 safety review was completed after 2 international publications in scientific literature 1, 2 described liver injury in 16 patients using Xarelto. The 2015 review did not find a definitive link between the use of Xarelto and liver injury because the information in some of the Canadian and international reports was incomplete. The reports published in the scientific literature showed that patients had underlying liver diseases before using Xarelto, or were taking other medications that may have contributed to the liver injury. Following completion of the review, Health Canada published an article in the August 2015 issue of the Health Product InfoWatch to summarize the Department's understanding of the risk of liver injury associated with Xarelto use.
In 2019, Health Canada reviewed all new available evidence regarding the potential risk of liver injury with Xarelto.
","use_canada":2045,"findings":2046,"conclusion":2047,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2048,"footnotes":2049,"title":"Summary Safety Review - Xarelto (rivaroxaban) - Assessing the potential risk of liver injury","created_date":"2019-10-23","modified_date":null,"key_message_list":[{"field_id":2044,"order_no":1,"bullet":"Health Canada reviewed the potential risk of liver injury with Xarelto, as a follow-up to a review of Xarelto and the risk of liver injury completed in 2015."},{"field_id":2044,"order_no":2,"bullet":"Health Canada's review of the available information did not establish a definitive link between the use of Xarelto and the risk of liver injury."},{"field_id":2044,"order_no":3,"bullet":"Health Canada will continue to monitor the safety of Xarelto."}],"footnotes_list":[{"field_id":2049,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":2049,"order_no":2,"bullet":"VigiBase is the World Health Organization global database of individual case safety reports. This information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. This information does not represent the opinion of the World Health Organization."}],"reference_list":[{"field_id":2048,"order_no":1,"bullet":"Liakoni E, Ratz Bravo AE, Terracciano L, Heim M, & Krahenbuhl S. Symptomatic hepatocellular liver injury with hyperbilirubinemia in two patients treated with rivaroxaban. JAMA Intern Med. 2014; 174:1683-1686."},{"field_id":2048,"order_no":2,"bullet":"Russmann S, Niedrig DF, Budmiger M, et al. Rivaroxaban postmarketing risk of liver injury. J Hepatol. 2014; 61:293-300."}],"use_canada_list":[{"field_id":2045,"order_no":1,"bullet":"Xarelto (rivaroxaban ) is a prescription drug authorized for sale in Canada to:Health Canada reviewed the potential risk of abnormal blood sugar (glucose) levels (dysglycemia) with the use of DAAs. This assessment was triggered by updates made to the European product safety information for DAAs to include warnings about the use of these products in diabetic patients. These updates included recommendations to closely monitor glucose levels and modify patients' diabetic medications to prevent low blood sugar levels (hypoglycemia).
HCV infection can potentially decrease the liver's ability to perform its different roles, one of which is the control of blood sugar. A potential complication seen in patients with HCV infection is the loss of blood sugar control and higher levels of sugar in the blood, which can in turn lead to type II diabetes mellitus (T2DM). Patients with chronic HCV infection are 3.8 times more likely to have T2DM than non-infected individuals1.
","use_canada":2057,"findings":2058,"conclusion":2059,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, in addition to what is known about the use of these medications both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2060,"footnotes":2061,"title":"Summary Safety Review - Direct-acting antivirals - Assessing the potential risk of abnormal blood sugar levels (dysglycemia)","created_date":"2020-02-17","modified_date":null,"key_message_list":[{"field_id":2056,"order_no":1,"bullet":"Direct-acting antivirals (DAAs) are prescription drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis), or liver cancer (hepatocellular carcinoma)."},{"field_id":2056,"order_no":2,"bullet":"Health Canada reviewed the potential risk of abnormal blood sugar (glucose) levels (dysglycemia) with the use of DAAs, including both high blood sugar levels (hyperglycemia) and low blood sugar levels (hypoglycemia). This review was triggered by updates made to the European product safety information for DAAs to include warnings about hypoglycemia for diabetic patients who use these products."},{"field_id":2056,"order_no":3,"bullet":"Health Canada's review concluded that there is a link between DAAs and dysglycemia, with evidence supporting the link between DAAs and hypoglycemia in diabetic patients."},{"field_id":2056,"order_no":4,"bullet":"Health Canada will work with manufacturers to update the Canadian product information for DAAs to inform Canadians and health care professionals about the risk of dysglycemia in diabetic patients."}],"footnotes_list":[{"field_id":2061,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":2061,"order_no":2,"bullet":"VigiBase is the WHO global database of individual case safety reports. This information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. This information does not represent the opinion of the World Health Organization."}],"reference_list":[{"field_id":2060,"order_no":1,"bullet":"Greenberg PD, Rosman AS, Eldeiry LS, Naqvi Z, Bräu N. Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha and ribavirin for chronic hepatitis C. J Viral Hepat. 2006 Sep;13(9):613-617."}],"use_canada_list":[{"field_id":2057,"order_no":1,"bullet":"DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection. Chronic HCV infection is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis), or liver cancer (hepatocellular carcinoma)."},{"field_id":2057,"order_no":2,"bullet":"This review included the following products available in Canada: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir), Zepatier (grazoprevir, elbasvir) and Maviret (glecaprevir, pibrentasvir). These products may either contain a single DAA or multiple DAAs together."},{"field_id":2057,"order_no":3,"bullet":"The first DAA was authorized for sale in Canada in 2013."},{"field_id":2057,"order_no":4,"bullet":"Overall, an estimated total of 140,000 prescriptions for DAAs were dispensed in 2018."}],"finding_list":[{"field_id":2058,"order_no":1,"bullet":"At the time of the review, the Canadian Product Information for Daklinza (daclatasvir) already included the risk of dysglycemia in diabetic patients. Additionally, the Canadian Product Safety Information of sofosbuvir-containing products recommended the close monitoring of blood glucose levels in diabetic patients and suggested that the dose of diabetes medications may need to be adjusted during treatment."},{"field_id":2058,"order_no":2,"bullet":"Until February 20, 2019, Health Canada had received 564 Canadian cases reporting either hypoglycemia, hyperglycemia and/or new onset diabetes with the use of DAAs. Of these reportsa, 538 reports were excluded mainly for lack of information or because they were duplicates. Twenty-six (26) cases were retained. Health Canada also reviewed the scientific literature and found 10 additional international cases. Among a total of 36 case reports assessed,Health Canada conducted a follow-up assessment of a review completed in 2017, which investigated the link between the potential risk of new or returning HCC and the use of DAAs. This latest review was triggered by Canadian and international case reports submitted to Health Canada after the first review was completed in 2017 and new evidence from published scientific literature.
","use_canada":2079,"findings":2080,"conclusion":2081,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these medications both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2083,"footnotes":2082,"title":"Summary Safety Review - Direct-Acting Antivirals - Assessing the Potential Risk of New or Returning Liver Cancer named Hepatocellular Carcinoma","created_date":"2020-04-02","modified_date":null,"key_message_list":[{"field_id":2078,"order_no":1,"bullet":"Direct-acting antivirals (DAAs) are prescription drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection in adult patients, which is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) or a type of liver cancer called Hepatocellular Carcinoma (HCC)."},{"field_id":2078,"order_no":2,"bullet":"Health Canada reviewed the potential risk of new or returning HCC with the use of DAAs. This was a follow-up to the previous review completed in 2017, which examined the use of DAAs and the risk of HCC1. This review was triggered by newly reported Canadian casesa and new evidence from published scientific literature."},{"field_id":2078,"order_no":3,"bullet":"Health Canada's review concluded that the available information did not support a link between the use of DAAs and new or returning HCC. Health Canada will continue to monitor the safety of DAAs."}],"footnotes_list":[{"field_id":2082,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":2082,"order_no":2,"bullet":"VigiBase is the WHO global database of individual case safety reports. This information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. This information does not represent the opinion of the World Health Organization."}],"reference_list":[{"field_id":2083,"order_no":1,"bullet":"Summary Safety Review - Direct-Acting Antivirals - Assessing the Potential Risk of Liver Cancer Recurrence"}],"use_canada_list":[{"field_id":2079,"order_no":1,"bullet":"DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection in adult patients."},{"field_id":2079,"order_no":2,"bullet":"This review included the following products available in Canada, which contain one or many DAAs together: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir), Zepatier (grazoprevir, elbasvir) and Maviret (glecaprevir, pibrentasvir)."},{"field_id":2079,"order_no":3,"bullet":"The first DAA was authorized for sale in Canada in 2013."},{"field_id":2079,"order_no":4,"bullet":"About 140,000 prescriptions for DAAs have been given to Canadian patients in 2018."}],"finding_list":[{"field_id":2080,"order_no":1,"bullet":"Following the review completed in 2017, Health Canada received a total of 125 reports (86 Canadian reports and 39 international published reports of new or returning HCC). Of these 125 reports, 41 cases of new or returning HCC were found to have a possible link with the use of DAAs. However, these reports presented limited information and did not include information on other factors that could contribute to new or returning HCC. Furthermore, based on the information provided, it was difficult to rule out the presence of HCC prior to treatment with DAAs. These limitations prevented Health Canada from establishing a link between new or returning HCC with the use of DAAs."},{"field_id":2080,"order_no":2,"bullet":"A search in Vigibaseb, the World Health Organization's Adverse Drug Reaction Database, found 1669 cases related to new or returning HCC in patients treated with DAAs. There was not enough information in these reports to make a link between the use of DAAs and HCC."},{"field_id":2080,"order_no":3,"bullet":"This safety review also looked at scientific literature published following the review in 2017. Health Canada reviewed a total of 70 studies, of which 59 involved patients. Overall, the reviewed literature did not support a link between the use of DAAs and an increased risk of new or returning HCC in patients who have been treated for HCC."}],"conclusion_list":[{"field_id":2081,"order_no":1,"bullet":"Health Canada's 2019 review of the available information did not make a link between the use of DAAs and new or returning HCC."},{"field_id":2081,"order_no":2,"bullet":"Health Canada will continue to monitor safety information involving DAAs, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00237","review_date":null,"drug_name":"Tapazole (methimazole) and generics","safety_issue":"Inflammation of the blood vessels (vasculitis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2090,"overview":"Health Canada reviewed the potential risk of vasculitis with the use of methimazole. Vasculitis is an inflammation of blood vessels that may prevent blood from reaching organs in the body. The safety review was initiated when Health Canada became aware that US FDA updated the product safety information for methimazole with new information on the risk of vasculitis.
","use_canada":2091,"findings":2092,"conclusion":2093,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Methimazole - Assessing the Potential Risk of Inflammation of the Blood Vessels (Vasculitis)","created_date":"2020-04-21","modified_date":null,"key_message_list":[{"field_id":2090,"order_no":1,"bullet":"Methimazole is a prescription drug authorized for sale in Canada to treat conditions where too much thyroid hormone is produced."},{"field_id":2090,"order_no":2,"bullet":"Health Canada reviewed the potential risk of inflammation of blood vessels (vasculitis) with the use of methimazole. The review was triggered by updates made by the United States Food and Drug Administration (US FDA) to the product safety information for methimazole related to this risk."},{"field_id":2090,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there is a link between the risk of vasculitis and the use of methimazole."},{"field_id":2090,"order_no":4,"bullet":"Health Canada is working with manufacturers to update the safety information of all methimazole products to include information about this potential risk."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":2091,"order_no":1,"bullet":"Methimazole is a prescription drug authorized for sale in Canada to:Health Canada reviewed the potential risk of necrotising fasciitis in children treated with ibuprofen during a chickenpox infection. The review only focused on non-prescription ibuprofen-containing products since most ibuprofen products used in children are authorized for sale in Canada as non-prescription drugs. Prescription ibuprofen products1, which contain higher doses of ibuprofen, should not be used in children younger than 12 years of age.
This safety review was triggered by a published case of a 4-year-old girl with a chickenpox infection who started showing symptoms of necrotising fasciitis after the use of ibuprofen. Necrotising fasciitis is also known as flesh-eating disease, a rare infection of the deep layers of the skin that spreads quickly in the body and can lead to death. The symptoms of necrotising fasciitis include a red, warm, or swollen area of skin, severe pain, and fever.
","use_canada":2099,"findings":2100,"conclusion":2101,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is currently known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2102,"footnotes":0,"title":"Summary Safety Review - Ibuprofen- Assessing the Potential Risk of Serious Infection of the Deep Layers of the Skin (Necrotising Fasciitis) in Children with Chickenpox Infection","created_date":"2020-05-29","modified_date":null,"key_message_list":[{"field_id":2098,"order_no":1,"bullet":"Most ibuprofen-containing products are authorized for sale in Canada as non-prescription drugs to treat fever, reduce pain, and relieve inflammation in adults and children. Some ibuprofen-containing products1 are only available by prescription."},{"field_id":2098,"order_no":2,"bullet":"This review was triggered by a published international case2 of necrotising fasciitis in a child with a chickenpox infection linked with ibuprofen use."},{"field_id":2098,"order_no":3,"bullet":"Health Canada's review of the available information did not find a link between the use of ibuprofen and the risk of necrotising fasciitis in children with chickenpox infection."},{"field_id":2098,"order_no":4,"bullet":"Health Canada will continue to monitor the safety of ibuprofen."}],"footnotes_list":[],"reference_list":[{"field_id":2102,"order_no":1,"bullet":"Prescription Drug List, Government of Canada, Health Canada, Health Products"},{"field_id":2102,"order_no":2,"bullet":"Darmasseelane K, Banks T, Rjabova T. 2018. Necrotising fasciitis as a complication of primary varicella infection in an immunocompetent child. BMJ Case Rep 2018. doi:10.1136/bcr-2018-225018."},{"field_id":2102,"order_no":3,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"use_canada_list":[{"field_id":2099,"order_no":1,"bullet":"Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain, reduce fever, and relieve inflammation in adults and children. Most ibuprofen products are authorized for sale in Canada as non-prescription drugs."},{"field_id":2099,"order_no":2,"bullet":"Ibuprofen has been marketed in Canada since 1972, alone or in combination with other drugs."},{"field_id":2099,"order_no":3,"bullet":"There were around 5 billion (5,177,133,500) units of single ingredient ibuprofen products sold in Canada between October 2006 through September 2018."}],"finding_list":[{"field_id":2100,"order_no":1,"bullet":"Health Canada reviewed the available information from published clinical studies as well as suspected cases of necrotising fasciitis reported in the Canada Vigilance database3 and international databases."},{"field_id":2100,"order_no":2,"bullet":"During the review, Health Canada noticed that health authorities in France and New Zealand added cautionary risk statements in the safety information of children's non-prescription ibuprofen products in order to reduce the risk of necrotising fasciitis in children with chicken pox infection."},{"field_id":2100,"order_no":3,"bullet":"The literature case report that triggered the Health Canada's review involved a 4-year-old healthy girl with chicken pox who started showing symptoms of necrotising fasciitis after the use of ibuprofen. She was given two doses of ibuprofen before the emergency room visit where she was diagnosed with necrotising fasciitis. The girl was hospitalized and treated with antibiotics and required multiple operations (surgical procedures). Although the case report indicates that ibuprofen did not cause necrotising fasciitis in the patient it recommends avoiding or using ibuprofen carefully in children with chicken pox."},{"field_id":2100,"order_no":4,"bullet":"The international published studies, which suspected a possible link between the risk of necrotising fasciitis and use of ibuprofen in children with chickenpox, had several limitations including lack of detailed information on whether the patient was already suffering from necrotising fasciitis when ibuprofen was given to relieve symptoms. The review of these studies did not find sufficient evidence for an increased risk of necrotising fasciitis with the use of ibuprofen in children with a chickenpox infection."},{"field_id":2100,"order_no":5,"bullet":"At the time of the review, Health Canada reviewed 27 international unique case reports of necrotising fasciitis in children with chickenpox who used ibuprofen. Of the 27 cases, 7 cases of necrotising fasciitis were found to be possibly linked with the use of ibuprofen in children with chickenpox, 6 cases of necrotising fasciitis were found to be unlikely to be linked, and the remaining 14 cases of necrotising fasciitis did not have enough information to indicate a conclusive link between necrotising fasciitis and the use of ibuprofen in children with chickenpox. To date, no Canadian cases of necrotising fasciitis in children with chickenpox who used ibuprofen have been reported to Health Canada."},{"field_id":2100,"order_no":6,"bullet":"The Canadian product monograph for ibuprofen products provides the following risk information which may help to mitigate the potential risk:Health Canada reviewed the potential risk of liver and bile duct damage with the use of ketamine-containing products after the French regulatory agency (Agence nationale de sécurité du médicament et des produits de santé) published a risk communication and updated product safety information for these products to include the risk of liver and bile duct damage.
","use_canada":2109,"findings":2110,"conclusion":2111,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2112,"title":"Summary Safety Review - Ketamine - Assessing the Potential Risk of Liver and Bile Duct Damage","created_date":"2020-06-10","modified_date":null,"key_message_list":[{"field_id":2108,"order_no":1,"bullet":"Ketamine-containing products are anesthetic drugs used by healthcare professionals during surgeries or medical procedures."},{"field_id":2108,"order_no":2,"bullet":"Health Canada reviewed the risk of potential damage to the liver and bile duct with ketamine use. This review was triggered by information from international regulatory agencies."},{"field_id":2108,"order_no":3,"bullet":"Health Canada's review concluded that there is a potential link between the use of ketamine-containing products and damage to the liver and bile duct."},{"field_id":2108,"order_no":4,"bullet":"Health Canada will work with manufacturers to update the Canadian product safety information for all ketamine-containing products, and inform the public and healthcare professionals of this potential risk."}],"footnotes_list":[{"field_id":2112,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2109,"order_no":1,"bullet":"In Canada, ketamine-containing products are authorized for use by healthcare professionals to make patients unconscious (anesthesia) during surgery or medical procedures."},{"field_id":2109,"order_no":2,"bullet":"Ketamine has been marketed in Canada since 1972 under the brand name Ketalar and is available as 10 mg/mL and 50 mg/mL injection for intramuscular or intravenous use only by healthcare professionals. Generic versions of ketamine are also available for sale in Canada."},{"field_id":2109,"order_no":3,"bullet":"In 2019, 1,907,962 units of 10 mg/mL ketamine injection and 964,460 units of 50 mg/mL ketamine injection were sold to Canadian drugstores and hospitals."}],"finding_list":[{"field_id":2110,"order_no":1,"bullet":"The review was triggered by a risk communication published by the French regulatory agency related to the potential risk of liver and bile duct damage with the use of ketamine-containing products."},{"field_id":2110,"order_no":2,"bullet":"Health Canada reviewed information from searches of the Canada Vigilance databasea and international databases of published literature and clinical studies."},{"field_id":2110,"order_no":3,"bullet":"Health Canada's assessment focused on 19 international epidemiologic studies conducted in many patients and 22 individual patient case reports (21 international and one Canadian) of liver and bile duct damages related to ketamine use."},{"field_id":2110,"order_no":4,"bullet":"The review of the 19 epidemiologic studies could not confirm or refute a link between the liver and/or bile duct damages and the use of ketamine due to various study method limitations, such as the presence of confounding factors, possibility of pre-existing liver damage prior to the use of ketamine, or a small number of participants in the study."},{"field_id":2110,"order_no":5,"bullet":"Of the 22 individual case reports, one report was found to be probably linked to the use of ketamine, 17 reports were found to be possibly linked; one report was not likely to be linked, and 3 reports did not have enough information to be assessed. Only one of the 22 case reports was from Canada where liver and bile duct damage was found to be possibly linked to the use of ketamine."},{"field_id":2110,"order_no":6,"bullet":"Findings from the epidemiologic studies and case reports showed that:Following early results of a large ongoing safety study that showed an increased risk of VTE in patients treated with Xeljanz (tofacitinib), Health Canada reviewed the potential risk of VTE linked with the use of JAK inhibitors. Given that there were already serious warnings for VTE in the product safety information for Olumiant (baricitinib), another JAK inhibitor, the safety review focussed on the safety findings of the other JAK inhibitors marketed in Canada at the time of the review, Xeljanz/ Xeljanz XR (tofacitinib) and Jakavi (ruxolitinib).
","use_canada":2119,"findings":2120,"conclusion":2121,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2122,"footnotes":0,"title":"Summary Safety Review - Xeljanz and Xeljanz XR (tofacitinib) and Jakavi (ruxolitinib) - Janus Kinase (JAK) inhibitors - Assessing the Potential Risk of Blood Clots in the Deep Veins (Venous Thromboembolic Events)","created_date":"2020-06-18","modified_date":null,"key_message_list":[{"field_id":2118,"order_no":1,"bullet":"Janus Kinase (JAK) inhibitors are prescription drugs authorized for sale in Canada to treat various conditions.Health Canada reviewed the potential risk of a worsening of a slow and irregular heartbeat (bradyarrhythmia) in patients with a history of bradyarrhythmia as well as the risk of developing a partial or complete block in the transmission of heart impulses (second and third-degree atrioventricular [AV] block) in patients treated with Brilinta. The safety review was triggered by published international reports of second-and third-degree AV block in patients taking Brilinta.
Bradyarrhythmia is a slow and irregular heart rate of less than 60 beats per minute. In second and third-degree AV block, the transmission of heart impulses (electrical signals) from the upper chambers of the heart (atria) to the lower chambers (ventricles) is partly or completely interrupted, leading to bradyarrhythmia.
","use_canada":2129,"findings":2130,"conclusion":2131,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of Brilinta both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2132,"title":"Summary Safety Review - Brilinta (ticagrelor) - Assessing the Potential Risks of a Worsening of a Slow and Irregular Heartbeat (Bradyarrhythmia) and Partial or Complete Block in the Transmission of Heart Impulses (Second- and Third-Degree Atrioventricular Block)","created_date":"2020-07-06","modified_date":null,"key_message_list":[{"field_id":2128,"order_no":1,"bullet":"Brilinta is a prescription drug authorized for sale in Canada that is used with low-dose acetylsalicylic acid (ASA), for example Aspirin, to decrease the risk of having a stroke, another heart attack, or dying from heart or blood vessel disease."},{"field_id":2128,"order_no":2,"bullet":"This safety review was triggered by published international reports of partial or complete block in the transmission of heart impulses (second-and third-degree atrioventricular [AV] block) in patients treated with Brilinta."},{"field_id":2128,"order_no":3,"bullet":"Health Canada reviewed the following 2 potential risks with the use of Brilinta:Health Canada reviewed the potential risk of skin cancer with the use of Picato. The review was triggered by new safety information from international clinical trials that found an increased risk of skin cancer in patients treated with Picato.
","use_canada":2139,"findings":2140,"conclusion":2141,"additional":"The analysis that contributed to this safety review included information from clinical trials, Canadian and international case reports, scientific and medical literature, and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2142,"title":"Summary Safety Review - Picato (ingenol mebutate) - Assessing the Potential Risk of Skin Cancer","created_date":"2020-07-02","modified_date":null,"key_message_list":[{"field_id":2138,"order_no":1,"bullet":"Picato (ingenol mebutate) is a prescription drug authorized for sale in Canada for use on the skin (topically) in adults to treat actinic keratosis (AK), a condition where thick, hard and scaly patches appear on skin caused by too much exposure to the sun (UV exposure)."},{"field_id":2138,"order_no":2,"bullet":"Health Canada reviewed the risk of skin cancer with Picato based on new safety information from international clinical trials that found an increased risk of skin cancer in patients treated with this drug."},{"field_id":2138,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between Picato and the risk of skin cancer."},{"field_id":2138,"order_no":4,"bullet":"Health Canada will ask for additional information from the manufacturer to determine whether Picato continues to be an effective and safe treatment option for actinic keratosis (AK)."}],"footnotes_list":[{"field_id":2142,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2139,"order_no":1,"bullet":"Picato (ingenol mebutate) is a prescription drug authorized for sale in Canada for topical use in adults to treat actinic keratosis (AK), a condition where thick, hard, and scaly patches appear on skin that has been damaged by too much sun (UV) exposure."},{"field_id":2139,"order_no":2,"bullet":"Ingenol mebutate has been marketed in Canada since 2013 under the brand name Picato. Picato is a gel for use on the skin (topically) available in 2 strengths, 0.015% and 0.05%."},{"field_id":2139,"order_no":3,"bullet":"There were about 5,000 prescriptions filled for Picato in Canada in 2019."}],"finding_list":[{"field_id":2140,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, evidence given by the manufacturer, and studies published in scientific and medical literature."},{"field_id":2140,"order_no":2,"bullet":"Health Canada's review focused on 43 international clinical trials and found that there was enough evidence to link the use of Picato with skin cancer."},{"field_id":2140,"order_no":3,"bullet":"Health Canada reviewed 29 case reports (including one Canadian case ) of skin cancer in patients treated with Picato. Of the 29 cases, 26 cases were found to be possibly linked. In the other 3 cases (including the Canadian case), a link was found to be unlikely because of the presence of the skin cancer inside and outside of the area treated with the drug. Assessing whether the skin cancer was related to the use of Picato was challenging in all 29 cases due to several factors including a medical history of skin cancer or use of other medications known to increase the risk of skin cancer."},{"field_id":2140,"order_no":4,"bullet":"Health Canada assessed 12 studies published in scientific and medical literature in order to determine the link between the use of Picato and skin cancer. Health Canada's review found that 6 of the 12 studies had evidence of skin cancer with the use of Picato."},{"field_id":2140,"order_no":5,"bullet":"The European Medicines Agency (EMA) has also reviewed this safety issue. In April 2020, it concluded that Picato may increase the risk of skin cancer and that its risks outweigh its benefits. On February 11, 2020, the manufacturer voluntarily withdrew the product from the European market."},{"field_id":2140,"order_no":6,"bullet":"Picato is currently authorized for sale in other countries including the United States of America, Australia, and New Zealand."}],"conclusion_list":[{"field_id":2141,"order_no":1,"bullet":"Health Canada's review found that there may be a link between Picato and the risk of skin cancer."},{"field_id":2141,"order_no":2,"bullet":"Health Canada will ask for additional information from the manufacturer to determine whether the benefits of the use of Picato continue to outweigh its risks as a treatment option for AK."},{"field_id":2141,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Picato to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when new health risks are identified."}]},{"template":2,"link_id":"SSR00243","review_date":null,"drug_name":"Methadone-containing products used to treat opioid dependence","safety_issue":"Lack of effect when switching between different methadone products used for the treatment of opioid dependence","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2148,"overview":"Health Canada reviewed the potential risk of lack of effect, which may present as drug withdrawal, with methadone-containing products used to treat opioid dependence. The review was triggered by recent reports received from Canadian patients and healthcare professionals suggesting that some patients experienced symptoms of opioid withdrawal after being switched from one methadone product to another.
","use_canada":2149,"findings":2150,"conclusion":2151,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of methadone used to treat addiction to opioids both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2152,"title":"Summary Safety Review - Methadone-Containing Products Used to Treat Opioid Dependence - Assessing the Potential Risk of Lack of Effect when Switching between Different Products","created_date":"2020-07-17","modified_date":null,"key_message_list":[{"field_id":2148,"order_no":1,"bullet":"Some methadone-containing products are authorized in Canada for use in opioid dependent patients requiring substitution treatment to prevent side effects developed when these patients stop using other opioids (opioid withdrawal symptoms)."},{"field_id":2148,"order_no":2,"bullet":"Health Canada reviewed the risk of lack of effect after receiving reports from Canadian healthcare professionals and patients suggesting that some patients experienced symptoms of opioid withdrawal after being switched from one methadone-containing product to another."},{"field_id":2148,"order_no":3,"bullet":"A safety review completed by Health Canada has found that there may be a link between switching methadone-containing products used to treat opioid dependence and the risk of lack of effect, which may present as withdrawal symptoms. Patients experiencing withdrawal symptoms need to be seen often by their healthcare professional and may need an adjustment in the dose of methadone."},{"field_id":2148,"order_no":4,"bullet":"Health Canada will be working with the manufacturers to update the Canadian product safety information to warn of this potential safety issue."}],"footnotes_list":[{"field_id":2152,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2149,"order_no":1,"bullet":"Methadone-containing products used to treat opioid dependence have been available in Canada since the 1960s. Methadone hydrochloride oral solution (1 mg/mL) and methadone hydrochloride oral concentrate (10 mg/mL) products prepared by the manufacturers and used to treat opioid dependence in adults have been marketed in Canada since 2001 under the brand names Metadol-D, Methadose, and Sandoz Methadone. Jamp Methadone Oral Concentrate and Odan-Methadone have also been authorized for use in Canada since January 2020, as of the date of this communication, they are not marketed. Methadone powder is also available to pharmacists to make (compound) their own methadone solutions. After being mixed with a flavoured liquid, these products are dispensed to patients and taken by mouth (orally)."},{"field_id":2149,"order_no":2,"bullet":"There were about 13 million prescriptions filled in 2019 for methadone-containing products used to treat opioid dependence."}],"finding_list":[{"field_id":2150,"order_no":1,"bullet":"Health Canada reviewed the scientific and medical literature, Canadian and international information including case reports in the Canada Vigilance databasea as well as information received from manufacturers, Canadian healthcare professionals and patients."},{"field_id":2150,"order_no":2,"bullet":"Health Canada's review looked at 22 Canadian reports (12 from the Canada Vigilance database and 10 provided by the manufacturers) linked with a lack of effect of methadone-containing liquid products (taken orally) used to treat opioid dependence."},{"field_id":2150,"order_no":3,"bullet":"These reports suggested that these methadone-containing products did not work as well to ease withdrawal symptoms and patients who had generally been on stable methadone treatment for a long time, as they reported experiencing withdrawal symptoms after being switched from one methadone product to another. Assessing whether the lack of effect was specifically related to one methadone-containing product and why the withdrawal symptoms happened was challenging due to lack of information. However, a link between methadone-containing products used for opioid dependence and lack of effect could not be ruled out in these cases."},{"field_id":2150,"order_no":4,"bullet":"The Department also contacted over 40 Canadian healthcare professionals, professional associations and patient treatment centers in order to gather feedback regarding this safety issue from healthcare professionals and patients. In total, 7 responses were received (5 from healthcare professionals and 2 from patients). The 5 responses received from healthcare professionals reported changes in how patients responded to the treatment for opioid drug dependence after being switched from one methadone-containing product to another. The problem was fixed by increasing the dose of the methadone-containing product they were taking, by switching to a new methadone-containing product, or by switching back to the original methadone-containing product. One of the 2 patient responses also described that the new methadone-containing products were not working as well as the old one."},{"field_id":2150,"order_no":5,"bullet":"Health Canada also assessed 5 published studies found in the Canadian scientific literature discussing the issue of lack of effect when patients treated for opioid dependence in British Columbia (Canada) were switched from one methadone-containing product to another. These studies generally found that some patients did worse following a product change. However, the studies did not identify specific causes for the observed lack of effect."},{"field_id":2150,"order_no":6,"bullet":"Canadian and international literature, as well as feedback from Canadian healthcare professionals, suggest that psychosocial factors may play a role and some patients do not tolerate methadone-containing product changes."},{"field_id":2150,"order_no":7,"bullet":"While the cause has not been linked to any specific problem with the methadone-containing product used following a switch, withdrawal symptoms can be serious and patients should consult with their healthcare professional if they have concerns about switching products or if they experience withdrawal symptoms."}],"conclusion_list":[{"field_id":2151,"order_no":1,"bullet":"Health Canada's review found there may be a link between methadone and the risk of lack of effect, which may present as drug withdrawal, when switching between methadone-containing products, although the reason for this is unclear. Patients experiencing withdrawal symptoms need to be seen often by their health care professional and may need an adjustment in the dose of methadone."},{"field_id":2151,"order_no":2,"bullet":"Health Canada will be working with manufacturers to update the Canadian product information to warn of this potential safety issue."},{"field_id":2151,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of methadone or other health products."},{"field_id":2151,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving methadone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00244","review_date":null,"drug_name":"HYDROmorph Contin and generic hydromorphone controlled release capsules.","safety_issue":"Increased risk of serious infections such as infection of the inner lining of the heart chambers and valves (infective endocarditis), and bloodborne infections caused by human immunodeficiency virus (HIV) or hepatitis C virus (HCV) linked to the injection of the content of oral hydromorphone controlled release capsules into the veins.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2158,"overview":"Health Canada reviewed the potential increased risk of infections (such as IE and bloodborne infections caused by HIV or HCV) related to the problematic use of the oral hydromorphone controlled release capsules (injection of the content of the capsules into the veins) when compared to other oral opioid products among people who inject drugs. The review was triggered by a study published in the CMAJ and discussions between Health Canada and the authors of the study.
The article described that the equipment (for instance, cookers and filters) used to prepare the content of the hydromorphone controlled release capsules for injection was shared and re-used more often for hydromorphone than for other opioid products. The authors proposed that this practice could lead to more germs being present and, as a result, could increase the chances of spreading infections such as IE, and bloodborne infections caused by HIV or HCV. It was further suggested that the equipment is reused and shared more often because it is more difficult to extract hydromorphone from the other components (excipients) in the capsules than it is for other opioid products (for instance, extracting oxycodone from controlled release products) and users believe that the equipment may contain residual hydromorphone.
This safety review does not apply to the authorized oral use of hydromorphone controlled release capsules.
","use_canada":2159,"findings":2160,"conclusion":2161,"additional":"Manipulating opioid products and using them in ways they are not intended to be used can lead to serious consequences, including overdose and death.
Additional information on opioid overdose, short and long-term effects of opioids, safe use of opioids, and where to get help is available at About Opioids.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug, both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2162,"footnotes":2163,"title":"Summary Safety Review - Hydromorphone Controlled Release Capsules - Assessing the Increased Risk of Serious Infections Linked to the Injection of the Content of the Capsules into Veins","created_date":"2020-09-10","modified_date":null,"key_message_list":[{"field_id":2158,"order_no":1,"bullet":"Hydromorphone controlled release capsules are prescription opioid drugs authorized for sale in Canada to be taken by mouth (orally) for the long term management of pain when:Health Canada reviewed the potential risk of HLH in patients treated with Imbruvica (ibrutinib). The safety review was triggered by 5 published international cases and one Canadian case of HLH in patients taking Imbruvica.
HLH is a life-threatening overreaction of the immune system where a large number of immune cells attack and destroy other blood cells. HLH is characterized by a large release of certain proteins by immune cells in the blood (referred to as a \"cytokine storm\" or \"cytokine release syndrome\"), as well as the accumulation of activated immune cells (lymphocytes and macrophages) in organs and tissues.
","use_canada":2171,"findings":2172,"conclusion":2173,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2174,"footnotes":2175,"title":"Summary Safety Review - Imbruvica (ibrutinib) - Assessing the Potential Risk of Hemophagocytic Lymphohistiocytosis","created_date":"2020-09-15","modified_date":null,"key_message_list":[{"field_id":2170,"order_no":1,"bullet":"Imbruvica (ibrutinib) is a drug authorized for sale in Canada to treat certain types of bone marrow and white blood cell cancers, alone or in combination with other therapies. It is also used for the treatment of patients who suffer from refractory chronic graft versus host disease after receiving transplanted tissue from a donor."},{"field_id":2170,"order_no":2,"bullet":"Health Canada reviewed the potential risk of HLH, a rare life-threatening condition where a large number of immune cells attack and destroy other blood cells, with Imbruvica use. This review was triggered by 5 international cases published in scientific and medical literature and one case reported in Canada.a"},{"field_id":2170,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of Imbruvica and the risk of HLH. Health Canada will continue to monitor the safety of Imbruvica, as it does for all health products on the Canadian market, to identify and assess potential harms."}],"footnotes_list":[{"field_id":2175,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2174,"order_no":1,"bullet":"Ambinder AJ, Hambley B, Shanbhag S, Merrill SA. Ibrutinib-associated hemophagocytic lymphohistiocytosis: A case series from Johns Hopkins. Am J Hematol 2019;94(11):E296-E299."},{"field_id":2174,"order_no":2,"bullet":"Cavallari M, Ciccone M, Falzoni S et al. Hemophagocytic Lymphohistiocytosis after EBV reactivation and ibrutinib treatment in relapsed/refractory Chronic Lymphocytic Leukemia. Leuk Res Rep 2017;7:11-13."},{"field_id":2174,"order_no":3,"bullet":"Poole A, Girard N, Clayton F, Tantravahi SK. Rapid onset of hemophagocytic lymphohistiocytosis in a patient with refractory chronic lymphocytic leukemia treated with ibrutinib. Leuk Lymphoma 2017;58(5):1258-1261."},{"field_id":2174,"order_no":4,"bullet":"Kleynberg RL, Schiller GJ. Secondary hemophagocytic lymphohistiocytosis in adults: an update on diagnosis and therapy. Clin Adv Hematol Oncol 2012;10(11):726-732."},{"field_id":2174,"order_no":5,"bullet":"La RP, Horne A, Hines M et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 2019;133(23):2465-2477."}],"use_canada_list":[{"field_id":2171,"order_no":1,"bullet":"Imbruvica (ibrutinib) is a prescription drug authorized for sale in Canada to treat:Health Canada reviewed the available post-market evidence to assess the long-term safety and effectiveness of SIMS used to treat SUI.
Health Canada is aware of various complications related to SIMS and other surgical meshes used to treat SUI since 2009. Prior to this safety review, Health Canada completed 3 safety reviews related to these devices and communicated on the safety issues.1,2,3
In 2014, information on the complications related to the use of these devices was added to the device label.","use_canada":2183,"findings":2184,"conclusion":2185,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international incident reports, clinical consultation, and what is known about the use of these medical devices both in Canada and internationally.
For additional information about Health Canada's assessment of medical devices, contact the Medical Devices Directorate (hc.meddevices-instrumentsmed.sc@canada.ca).
","full_review":"","references":2186,"footnotes":2187,"title":"Summary Safety Review - Single Incision Mini-sling - Assessing the Long-term (beyond 3 years) Safety and Effectiveness","created_date":"2020-09-18","modified_date":null,"key_message_list":[{"field_id":2182,"order_no":1,"bullet":"In Canada, single incision mini-slings (SIMS) are medical devices used to treat stress urinary incontinence (SUI), or the accidental leaking of urine during physical activity, in women."},{"field_id":2182,"order_no":2,"bullet":"Health Canada reviewed the long-term (beyond 3 years) safety and effectiveness of SIMS used to treat SUI. This was a follow-up to reviews completed in 2009, 2013, and 2014 assessing various complications related to the use of SIMS and similar devices."},{"field_id":2182,"order_no":3,"bullet":"Given the lack of high-quality post-market information, Health Canada has asked SIMS' manufacturers for additional information related to the long-term safety and effectiveness."},{"field_id":2182,"order_no":4,"bullet":"The department will review the information within one year."}],"footnotes_list":[{"field_id":2187,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2186,"order_no":1,"bullet":"Surgical Mesh - Complications associated with transvaginal implantation for the treatment of stress urinary incontinence and pelvic organ prolapse - Notice to Hospitals."},{"field_id":2186,"order_no":2,"bullet":"Information regarding the transvaginal implantation of surgical mesh devices for the treatment of pelvic organ prolapse and stress urinary incontinence."},{"field_id":2186,"order_no":3,"bullet":"Surgical Mesh - Complications associated with transvaginal implantation of surgical mesh for the treatment of stress urinary incontinence and pelvic organ prolapse."},{"field_id":2186,"order_no":4,"bullet":"Welk B, Carlson K, Baverstock RJ, et al. Canadian Urological Association position statement on the use of transvaginal mesh. Canadian Urological Association Journal. 2017 Jun; 11(6Suppl2):S105-S107. [PMC]"},{"field_id":2186,"order_no":5,"bullet":"Surgical Treatment of Female Stress Urinary Incontinence (SUI): AUA/SUFU Guideline (2017). American Urological Association aunet.org. Published 2017. Accessed July 14, 2020."},{"field_id":2186,"order_no":6,"bullet":"Urinary incontinence and pelvic organ prolapse in women: management. nice.org.uk. Published April 02, 2019. Updated June 24, 2019. Accessed July 14, 2020"},{"field_id":2186,"order_no":7,"bullet":"Chapple, CR, Cruz F, Deffieux X, et al. Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence. Eur Urol. 2017 Sep;72(3):424-431 doi: 10.1016/j.eururo.2017.03.048. Epub 2017 Apr 14. [Pubmed]"},{"field_id":2186,"order_no":8,"bullet":"Berger AA, Tan-Kim J, Menefee SA. Long-term Risk of Reoperation After Synthetic Mesh Midurethral Sling Surgery for Stress Urinary Incontinence. Obstet Gynecol. 2019 Nov;134(5):1047-1055. doi: 10.1097/AOG.0000000000003526. [Pubmed]"}],"use_canada_list":[{"field_id":2183,"order_no":1,"bullet":"In Canada, SIMS used to treat SUI in women are Class III medical devices, the second highest risk class of medical device."},{"field_id":2183,"order_no":2,"bullet":"SIMS are made from non-absorbable synthetic material and are intended as a permanent implant."},{"field_id":2183,"order_no":3,"bullet":"At the time of this safety review, there were 2 SIMS devices licensed for sale in Canada for the treatment of SUI:Health Canada reviewed the potential risk of birth defects in babies with the use of mesalazine-containing products in pregnant women. The safety review was initiated following international reports received from a manufacturer of birth defects in babies whose mothers were treated with mesalazine during pregnancy.
","use_canada":2195,"findings":2196,"conclusion":2197,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of mesalazine-containing products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2198,"title":"Summary Safety Review - Mesalazine-containing products - Assessing the Potential Risk of Birth Defects","created_date":"2020-09-24","modified_date":null,"key_message_list":[{"field_id":2194,"order_no":1,"bullet":"Mesalazine-containing products are authorized for sale in Canada for the treatment and/or prevention of symptoms of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease."},{"field_id":2194,"order_no":2,"bullet":"Health Canada reviewed the potential risk of birth defects in babies with the use of mesalazine in pregnant women. The review was triggered by international reports of birth defects in babies whose mothers were treated with mesalazine during pregnancy."},{"field_id":2194,"order_no":3,"bullet":"Health Canada's review of the available information did not confirm a link between the risk of birth defects in babies and the use of mesalazine in pregnant women."},{"field_id":2194,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving mesalazine-containing products, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2198,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2195,"order_no":1,"bullet":"Mesalazine-containing products are prescription drugs for the treatment and/or prevention of symptoms caused by inflammatory bowel disease including ulcerative colitis and Crohn's Disease. Mesalazine is also known as mesalamine, 5-aminosalicyclic acid, and 5-ASA."},{"field_id":2195,"order_no":2,"bullet":"Mesalazine-containing products have been marketed under different brand names in Canada since 1993. In 2019, mesalazine-containing products were marketed in Canada in many strengths and dosage forms for oral and rectal use under the brand names: Asacol, Asacol 800, Mezavant, Mezera, Pentasa, Salofalk and Teva-5 ASA"},{"field_id":2195,"order_no":3,"bullet":"There are about 125,000 prescriptions filled per year for all mesalazine-containing products by women who could become pregnant."}],"finding_list":[{"field_id":2196,"order_no":1,"bullet":"Health Canada reviewed the scientific and medical literature, Canadian and international information, including case reports in the Canada Vigilance databasea as well as information received from manufacturers."},{"field_id":2196,"order_no":2,"bullet":"This safety review assessed 43 case reports (41 international and 2 Canadian) of birth defects in babies whose mothers were treated with mesalazine during pregnancy. Of the 43 case reports, 14 reports were found to be possibly linked to the use of mesalazine-containing products during pregnancy, 8 reports were not likely to be linked and 21 reports (including 2 Canadian case reports) did not have enough information to be assessed."},{"field_id":2196,"order_no":3,"bullet":"Assessing the risk of birth defects in babies related to the use of mesalazine-containing products during pregnancy in these reports was challenging because of incomplete case details and other contributing factors, such as women taking other medications beside mesalazine during pregnancy or having other existing medical conditions. The review of these cases did not support a link between the birth defects in babies and the use of mesalazine-containing products in pregnant women."},{"field_id":2196,"order_no":4,"bullet":"Health Canada also looked at additional information available from 12 studies in published literature (11 international and one Canadian). The review of these studies did not find a link between the risk of birth defects in babies and the use of mesalazine during pregnancy."},{"field_id":2196,"order_no":5,"bullet":"Based on all of the available scientific and medical evidence, the lack of a known cause for birth defects, and no observation of a clear pattern of birth defects related to the use of mesalazine in pregnant women, the benefits of treatment with mesalazine continue to outweigh this risk. The current clinical guidelines also recommend the continued use of mesalazine during pregnancy as the underlying disease suffered by the pregnant women (inflammatory bowel disease) may harm the unborn child."}],"conclusion_list":[{"field_id":2197,"order_no":1,"bullet":"Health Canada's safety review of the available information could not confirm a link between the risk of birth defects in babies and the use of mesalazine-containing products during pregnancy."},{"field_id":2197,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of mesalazine-containing products."},{"field_id":2197,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving mesalazine-containing products as it does for all health products on the Canadian market. Health Canada will take appropriate and timely actions if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00255","review_date":null,"drug_name":"Tamiflu (oseltamivir) and generics","safety_issue":"Bleeding (haemorrhages)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2278,"overview":"Health Canada reviewed the potential risk of bleeding (haemorrhages) in general with the use of oseltamivir to determine whether additional actions were required in Canada. The safety review was started when Health Canada became aware that the PMDA updated the product safety information for oseltamivir with new information on the risk of haemorrhages in general.
","use_canada":2279,"findings":2280,"conclusion":2281,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of oseltamivir both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2282,"title":"Summary Safety Review - Tamiflu (oseltamivir) and generics - Assessing the Potential Risk of Haemorrhages","created_date":"2021-01-08","modified_date":null,"key_message_list":[{"field_id":2278,"order_no":1,"bullet":"Oseltamivir is a prescription drug authorized for sale in Canada to treat or prevent the onset of flu."},{"field_id":2278,"order_no":2,"bullet":"Health Canada reviewed the potential risk of bleeding (haemorrhages) in general with the use of oseltamivir. "},{"field_id":2278,"order_no":3,"bullet":"The Canadian product safety information for oseltamivir includes information specifically on the risk of gut (gastrointestinal) bleeding based on experience with its use after marketing."},{"field_id":2278,"order_no":4,"bullet":"The current review was triggered by updates made by the Japanese Pharmaceutical and Medical Devices Agency (PMDA) to the product safety information for oseltamivir related to the risk of bleeding in general. The purpose of this review was to assess if additional actions were required in Canada."},{"field_id":2278,"order_no":5,"bullet":"The information reviewed was inconclusive regarding the risk of bleeding in general. However, the review concluded that there may be a link between the use of oseltamivir and the risk of lower gastrointestinal bleeding."},{"field_id":2278,"order_no":6,"bullet":"Given that the product safety information for oseltamivir already includes the risk of gastrointestinal bleeding, no updates are required at this time."},{"field_id":2278,"order_no":7,"bullet":"Health Canada will continue to monitor safety information of oseltamivir."}],"footnotes_list":[{"field_id":2282,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2279,"order_no":1,"bullet":"Oseltamivir is a prescription drug authorized for sale in Canada to treat or prevent the onset of flu."},{"field_id":2279,"order_no":2,"bullet":"Oseltamivir has been marketed in Canada since 1999 under the brand name Tamiflu and is currently available as 30 mg, 45 mg, and 75 mg capsules, and as a 6 mg/mL powder for oral suspension. Generic versions of Tamiflu are also available for sale in Canada."},{"field_id":2279,"order_no":3,"bullet":"There were about 1 million prescriptions for oseltamivir filled in Canada between 2015 and 2019."}],"finding_list":[{"field_id":2280,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance database a, international databases, and published literature."},{"field_id":2280,"order_no":2,"bullet":"Health Canada reviewed 59 case reports (4 Canadian, 55 international) of bleeding in patients receiving oseltamivir. Of the 59 case reports, 42 reports showed a possible link between oseltamivir use and haemorrhages, with 22 of these involving bleeding in the lower gut (gastrointestinal bleeding). Three cases were unlikely to be linked to oseltamivir use, and 14 cases (4 Canadian) could not be assessed due to several contributing factors such as incomplete information about pre-existing medical conditions, lack of detailed information in the reports, and co-existing infections that may have contributed to the adverse event."},{"field_id":2280,"order_no":3,"bullet":"Health Canada also reviewed 5 articles published in the scientific literature on the risk of bleeding and oseltamivir use. There was limited information to support a link between the potential risk of bleeding and the use of oseltamivir in 4 of the 5 articles."},{"field_id":2280,"order_no":4,"bullet":"In addition, Health Canada reviewed 4 articles from the published scientific literature for a potential interaction between oseltamivir and warfarin, a blood thinner medication that may cause bleeding. Overall, the review did not find evidence to support an interaction between oseltamivir and warfarin leading to increased bleeding."},{"field_id":2280,"order_no":5,"bullet":"The information reviewed was inconclusive regarding the risk of bleeding in general. However, the review concluded that there may be a link between the use of oseltamivir and the risk of lower gastrointestinal bleeding."}],"conclusion_list":[{"field_id":2281,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of oseltamivir and the risk of lower gastrointestinal haemorrhages. The Canadian product safety information for oseltamivir already includes information on the risk of gastrointestinal bleeding. Therefore, the safety information for oseltamivir is appropriate at this time."},{"field_id":2281,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of oseltamivir and other health products to the Canada Vigilance program."},{"field_id":2281,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving oseltamivir to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00248","review_date":null,"drug_name":"Brilinta (ticagrelor)","safety_issue":"Central sleep apnea (CSA), a condition in which breathing repeatedly stops and starts during sleep","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2204,"overview":"Health Canada reviewed the potential risk of CSA in patients treated with Brilinta (ticagrelor). The safety review was triggered by the publication, in the British Journal of Clinical Pharmacology, of 2 confirmed cases of CSA after starting treatment with Brilinta.
","use_canada":2205,"findings":2206,"conclusion":2207,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international Information and what is known about the use of Brilinta (ticagrelor) both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2208,"footnotes":2209,"title":"Summary Safety Review - Brilinta (ticagrelor) - Assessing the Potential Risk of Central Sleep Apnea","created_date":"2020-10-28","modified_date":null,"key_message_list":[{"field_id":2204,"order_no":1,"bullet":"Brilinta (ticagrelor) is a prescription drug authorized for sale in Canada that is used with low-dose acetylsalicylic acid (ASA), for example Aspirin, to decrease the risk of having a stroke, a heart attack, or dying from heart or blood vessel disease."},{"field_id":2204,"order_no":2,"bullet":"This safety review was triggered by the publication of 2 confirmed cases of central sleep apnea (CSA) in the British Journal of Clinical Pharmacology1. In both cases, CSA occurred after starting treatment with Brilinta. CSA is a condition in which breathing repeatedly stops and starts during sleep."},{"field_id":2204,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Brilinta and the risk of CSA."},{"field_id":2204,"order_no":4,"bullet":"Health Canada will work with the manufacturer to update the Canadian product safety information for Brilinta to add a warning about this potential safety issue."}],"footnotes_list":[{"field_id":2209,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2208,"order_no":1,"bullet":"Puel V, Théophile H, Godard I, Raymond N, Miremont-Salamé G, Gosse P, Pépin JL, Pariente A. Ticagrelor and central sleep apnoea: Impact of withdrawal and reintroduction. Br J Clin Pharmacol. 2019 Aug;85(8):1855-1858"}],"use_canada_list":[{"field_id":2205,"order_no":1,"bullet":"Brilinta has been marketed in Canada since 2011 and is available as 60 mg and 90 mg tablets."},{"field_id":2205,"order_no":2,"bullet":"In Canada, Brilinta, when given with low dose acetylsalicylic acid, is used to lower the risk of having a stroke, a heart attack, or dying from a heart or blood vessel disease."},{"field_id":2205,"order_no":3,"bullet":"Brilinta 90 mg tablets are given to patients who have recently had a heart attack or severe chest pain (unstable angina),and Brilinta 60 mg tablets are given to patients who require prolonged treatment (more than one year) after having a heart attack."},{"field_id":2205,"order_no":4,"bullet":"Brilinta 60 mg tablets can also be given to patients with no previous heart attacks and who have coronary artery disease and type 2 diabetes, and have previously had a procedure to open a blocked or narrowed heart blood vessel (percutaneous coronary intervention)."},{"field_id":2205,"order_no":5,"bullet":"There were about 2 million prescriptions for Brilinta filled in Canada between 2014 and 2019."}],"finding_list":[{"field_id":2206,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilancea database, international databases, and published literature."},{"field_id":2206,"order_no":2,"bullet":"At the time of the review, Health Canada had received 2 Canadian reportsa of CSA related to Brilinta use. These 2 reports didn't have enough information to be assessed."},{"field_id":2206,"order_no":3,"bullet":"Literature and adverse reaction database searches found 9 case reports (None Canadian, 9 international) that included enough information for review. Four of the 9 cases were from the Canada Vigilance database. In 8 of these reports, a link between Brilinta use and CSA could not be ruled out; 4 reports were found to be probably linked to the use of Brilinta, 4 reports were possibly linked and one report was not likely to be linked."},{"field_id":2206,"order_no":4,"bullet":"Health Canada also looked at additional information available from 2 studies in published literature. Both studies had a number of weaknesses in their design and reported conflicting results. There is not enough information in these studies to establish a link between Brilinta use and CSA at this time."}],"conclusion_list":[{"field_id":2207,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the use of Brilinta (ticagrelor) and the risk of CSA."},{"field_id":2207,"order_no":2,"bullet":"Health Canada has requested that the manufacturer of Brilinta update the Canadian product safety information to add a warning about this potential safety issue."},{"field_id":2207,"order_no":3,"bullet":"Once the product safety information for Brilinta is updated, a communication will be published in the Health Product InfoWatch, to further inform healthcare professionals and patients about the potential risk."},{"field_id":2207,"order_no":4,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Brilinta and other health products to the Canada Vigilance program."},{"field_id":2207,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving Brilinta as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified."}]},{"template":2,"link_id":"SSR00249","review_date":null,"drug_name":"Direct-acting antiviral products containing a protease inhibitor","safety_issue":"Worsening liver function (hepatic decompensation) and liver failure (hepatic failure) in some patients with pre-existing significant liver disease","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2216,"overview":"Health Canada reviewed the potential risk of worsening liver function and liver failure with the use of direct-acting antiviral products containing a protease inhibitor. The safety review was triggered by a U.S. FDA drug safety communication warning about these risks in chronic hepatitis C virus-infected patients with advanced liver disease.
","use_canada":2217,"findings":2218,"conclusion":2219,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of direct-acting antiviral products containing a protease inhibitor both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2220,"title":"Summary Safety Review - Direct-acting antiviral products containing a Protease Inhibitor - Assessing the Potential Risks of Hepatic Decompensation and Hepatic Failure","created_date":"2020-12-02","modified_date":null,"key_message_list":[{"field_id":2216,"order_no":1,"bullet":"Direct-acting antiviral products containing a protease inhibitor are authorized for sale in Canada to treat chronic (long-lasting) hepatitis C virus infection."},{"field_id":2216,"order_no":2,"bullet":"Health Canada reviewed the risk of worsening liver function and liver failure with the use of direct-acting antiviral products containing a protease inhibitor. This review was triggered by a United States Food and Drug Administration (U.S. FDA) drug safety communication."},{"field_id":2216,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of direct-acting antiviral products containing a protease inhibitor and the risk of worsening liver function and liver failure in some patients with pre-existing significant liver disease."},{"field_id":2216,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the Canadian product safety information for direct-acting antiviral products containing a protease inhibitor to include information about these risks."}],"footnotes_list":[{"field_id":2220,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2217,"order_no":1,"bullet":"Direct-acting antiviral products containing a protease inhibitor are prescription drugs authorized for sale in Canada to treat chronic (long-lasting) hepatitis C virus infection."},{"field_id":2217,"order_no":2,"bullet":"Direct-acting antiviral products containing a protease inhibitor have been marketed under different brand names in Canada since 2016. At the time of this review, Maviret (glecaprevir, pibrentasvir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir) and Zepatier (grazoprevir, elbasvir) are authorized for sale in Canada as fixed dose combination products."},{"field_id":2217,"order_no":3,"bullet":"There were about 30,000 prescriptions in total filled for these products annually in 2018 and 2019."}],"finding_list":[{"field_id":2218,"order_no":1,"bullet":"Health Canada reviewed information from searches of the Canada Vigilance databasea, international databases, from manufacturers and published scientific and medical literature"},{"field_id":2218,"order_no":2,"bullet":"At the time of the review, Health Canada had received 53 case reports for Maviret (1 Canadian), 23 case reports for Vosevi (6 Canadian) and 18 case reports for Zepatier (1 Canadian) related to worsening liver function and liver failure."},{"field_id":2218,"order_no":3,"bullet":"Health Canada's review found that there may be a link between the use of direct-acting antiviral products containing a protease inhibitor and worsening liver function and liver failure. For Maviret, 51 cases (1 Canadian) showed a possible link and 2 cases could not be assessed due to insufficient information in the reports. For Vosevi, 15 cases (3 Canadian) were found to be possibly linked, 1 case was not likely to be linked, and 7 cases (3 Canadian) did not have enough information to be assessed. For Zepatier, 16 cases (1 Canadian) were considered possibly linked, and 2 cases could not be assessed due to insufficient information in the reports. For most of these cases, contributing factors including existing medical conditions and other medications taken by the patient could not be ruled out. Pre-existing significant liver disease was present in all of the cases."},{"field_id":2218,"order_no":4,"bullet":"Health Canada also reviewed 2 studies from the published scientific literature. These studies did not provide additional information beyond what was obtained from the above case reports."}],"conclusion_list":[{"field_id":2219,"order_no":1,"bullet":"Health Canada's review concluded that there may be a link between the use of direct-acting antiviral products containing a protease inhibitor and the risks of worsening liver function and liver failure in some patients with pre-existing significant liver disease."},{"field_id":2219,"order_no":2,"bullet":"Health Canada has requested that the manufacturers of direct-acting antiviral products containing a protease inhibitor update the Canadian product safety information to include information about these risks."},{"field_id":2219,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving direct-acting antiviral products containing a protease inhibitor, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00250","review_date":null,"drug_name":"Bacitracin for injection products","safety_issue":"Kidney injury (nephrotoxicity) and sudden, severe, potentially life-threatening allergic (anaphylactic) reactions","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2226,"overview":"Health Canada reviewed the potential risks of nephrotoxicity and anaphylactic reactions with the use of bacitracin for injection products further to the U.S. FDA issued Drug Safety Communication dated January 31, 2020. In that communication, the FDA requested all current U.S. manufacturers of bacitracin for injection to voluntarily withdraw their product from the U.S. market. The FDA review determined that U.S. healthcare professionals no longer use bacitracin for injection for the only approved indication of treating infants with pneumonia and empyema caused by staphylococcus. The FDA also considered the availability of other approved, effective treatments that do not have the same serious risks, including nephrotoxicity and anaphylactic reactions.
Health Canada's review did not include non-prescription bacitracin-containing products marketed as ointments, since no safety concerns for these products were identified in the U.S. FDA's Drug Safety Communication.
","use_canada":2227,"findings":2228,"conclusion":2229,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of bacitracin for injection products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2230,"title":"Summary Safety Review - Bacitracin for Injection Products - Assessing the Potential Risks of Nephrotoxicity and Anaphylactic Reactions","created_date":"2020-12-02","modified_date":null,"key_message_list":[{"field_id":2226,"order_no":1,"bullet":"Bacitracin for injection products are drugs authorized for sale in Canada to treat:Health Canada reviewed the potential risk of drug reaction with eosinophilia and systemic symptoms (DRESS) with clobazam use after becoming aware of international case reports published in the medical literature.
DRESS is a rare, but serious, and potentially life-threatening drug reaction that includes fever, severe skin rash or peeling of the skin over large areas of the body, swollen face and high white blood cell count, affecting 1 or more organs. The symptoms of DRESS typically appear within 2 weeks to 2 months after starting a medication.
DRESS is also known as Drug Rash with Eosinophilia and Systemic Symptoms, Drug Induced Hypersensitivity Syndrome or DRESS syndrome.
","use_canada":2237,"findings":2238,"conclusion":2239,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of clobazam both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2240,"footnotes":2241,"title":"Summary Safety Review - Clobazam-containing products - Assessing the Potential Risk of Drug Reaction with Eosinophilia and Systemic Symptoms","created_date":"2020-12-09","modified_date":null,"key_message_list":[{"field_id":2236,"order_no":1,"bullet":"Clobazam is authorized for sale in Canada as an add-on therapy in patients whose epilepsy is not well controlled on their current antiepileptic drugs."},{"field_id":2236,"order_no":2,"bullet":"Health Canada reviewed the potential risk of DRESS with clobazam use after becoming aware of international case reports published in medical literature."},{"field_id":2236,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of clobazam and the potential risk of DRESS."},{"field_id":2236,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the Canadian product safety information for clobazam-containing products to include the risk of DRESS."}],"footnotes_list":[{"field_id":2241,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2240,"order_no":1,"bullet":"Kardaun S.H. Sekula P. Valeyrie-Allanore L. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Original Multisystem Adverse Drug Reaction. Results from the Prospective RegiSCAR Study. British Journal of Dermatology. 2013; 169:1071-1080"},{"field_id":2240,"order_no":2,"bullet":"Manyas et al., 2020, Let A Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Associated With Clobazam, Pediatric Emergency Care:Volume 36, Number 3, March 2020, e75"},{"field_id":2240,"order_no":3,"bullet":"Marzec S, Solomon J, Nguyen N, Rajbhandari P. Red as a beet but not quite so sweet. Hospital Medicine. 2018 Apr 8-11; Orlando, Fla. Abstract 406"},{"field_id":2240,"order_no":4,"bullet":"Razanapinaritra et al., 2019. DRESS syndrome induced by clobazam in a child: A new case. Revue française d'allergologie 59 (2019) 346-9."}],"use_canada_list":[{"field_id":2237,"order_no":1,"bullet":"Clobazam is a prescription drug authorized in Canada as add-on therapy in patients whose epilepsy is not well controlled on their current antiepileptic drugs."},{"field_id":2237,"order_no":2,"bullet":"Clobazam has been marketed in Canada since 1991. It is currently available as 10 mg clobazam tablets."},{"field_id":2237,"order_no":3,"bullet":"There were about 444,000 prescriptions filled for clobazam in 2019, 10% of which were for children."}],"finding_list":[{"field_id":2238,"order_no":1,"bullet":"Health Canada reviewed information provided by the manufacturers, data from clinical studies, information resulting from searches of the Canada Vigilance databasea , and the published literature."},{"field_id":2238,"order_no":2,"bullet":"Health Canada's review focused on 2 Canadian cases and 18 international cases of DRESS in patients taking clobazam. From those cases, only 4 (international) met the criteria for further assessment to determine if there was a link between the use of clobazam and DRESS. Three of them were published in the medical literature and involved children."},{"field_id":2238,"order_no":3,"bullet":"In all 4 cases, a link between clobazam use and DRESS could not be ruled out. Two cases were found to be probably linked to the use of clobazam. The 2 other cases were found to be possibly linked to clobazam use, however, these patients were also taking other medications that have been known to cause DRESS."},{"field_id":2238,"order_no":4,"bullet":"There are no confirmed cases of DRESS in Canada associated with the use of Clobazam."}],"conclusion_list":[{"field_id":2239,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of clobazam and the potential risk of DRESS."},{"field_id":2239,"order_no":2,"bullet":"Health Canada will work with the manufacturers to update the Canadian product safety information for clobazam-containing products to include the risk of DRESS."},{"field_id":2239,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of clobazam and other health products to the Canada Vigilance Program."},{"field_id":2239,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving clobazam-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00252","review_date":null,"drug_name":"Carboplatin-containing products","safety_issue":"Posterior Reversible Encephalopathy Syndrome (PRES), a rare and serious brain condition","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2248,"overview":"Health Canada reviewed the potential risk of Posterior Reversible Encephalopathy Syndrome (PRES) with carboplatin-containing products following a safety labelling update for PRES and these products in New Zealand.
PRES is a rare and serious brain condition, which can include headaches, seizures, visual problems, nausea and vomiting. This condition is also known as Reversible Posterior Leukoencephalopathy Syndrome.
","use_canada":2249,"findings":2250,"conclusion":2251,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international information, and what is known about the use of carboplatin both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2252,"title":"Summary Safety Review - Carboplatin-containing products - Assessing the Potential Risk of Posterior Reversible Encephalopathy Syndrome","created_date":"2020-12-16","modified_date":null,"key_message_list":[{"field_id":2248,"order_no":1,"bullet":"Carboplatin-containing products are authorized for sale in Canada to treat ovarian cancer."},{"field_id":2248,"order_no":2,"bullet":"Health Canada reviewed the risk of Posterior Reversible Encephalopathy Syndrome (PRES) with the use of carboplatin-containing products. The review was triggered by a safety labelling update for carboplatin-containing products related to this risk in New Zealand."},{"field_id":2248,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of carboplatin-containing products and the risk of PRES."},{"field_id":2248,"order_no":4,"bullet":"Health Canada will work with the manufacturers of carboplatin-containing products to update the Canadian product safety information to include the risk of PRES."}],"footnotes_list":[{"field_id":2252,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2249,"order_no":1,"bullet":"Carboplatin-containing products are prescription drugs that are authorized for sale in Canada to treat ovarian cancer."},{"field_id":2249,"order_no":2,"bullet":"Carboplatin was first marketed in Canada in 1986 under the brand name Paraplatin (no longer marketed). Generic versions of carboplatin are still available in Canada. Carboplatin-containing products are available as 10 mg/mL sterile solutions for injection."}],"finding_list":[{"field_id":2250,"order_no":1,"bullet":"Health Canada reviewed information from searches of the Canada Vigilance databasea and scientific and medical literature."},{"field_id":2250,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of PRES related to carboplatin use."},{"field_id":2250,"order_no":3,"bullet":"Health Canada's review focused on 19 international case reports of PRES with the use of carboplatin-containing products (16 of them published in the medical literature)."},{"field_id":2250,"order_no":4,"bullet":"Health Canada concluded that a link between carboplatin use and PRES was possible in all 19 case reports."},{"field_id":2250,"order_no":5,"bullet":"In all 19 cases, other factors that are known to be associated with PRES were present, such as the patients' general poor health, and several chemotherapy drugs given to the patients at the same time."}],"conclusion_list":[{"field_id":2251,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of carboplatin-containing products and the risk of PRES."},{"field_id":2251,"order_no":2,"bullet":"Health Canada will work with manufacturers to update the Canadian product safety information for carboplatin-containing products to include the risk of PRES."},{"field_id":2251,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of carboplatin and other health products to the Canada Vigilance Program."},{"field_id":2251,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving carboplatin-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00253","review_date":null,"drug_name":"Tramadol-containing products","safety_issue":"Hallucinations, such as seeing or hearing things that are not there","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2258,"overview":"Health Canada reviewed the risk of hallucinations with tramadol-containing products. The safety review was triggered by information submitted from a manufacturer showing an increase in the number of reported cases (Canadian and international reports) of hallucinations with tramadol use at normal doses.
","use_canada":2259,"findings":2260,"conclusion":2261,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of tramadol-containing products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2262,"title":"Summary Safety Review - Tramadol-containing products - Assessing the Potential Risk of Hallucinations","created_date":"2020-12-29","modified_date":null,"key_message_list":[{"field_id":2258,"order_no":1,"bullet":"Tramadol-containing products are authorized for sale in Canada to treat moderate to moderately severe pain in adults who require treatment for several days or more."},{"field_id":2258,"order_no":2,"bullet":"Health Canada reviewed the risk of hallucinations with the use of tramadol-containing products. This review was triggered by an increase in the number of reported cases (Canadian and international) of hallucinations in patients treated with these products."},{"field_id":2258,"order_no":3,"bullet":"Health Canada's review of the available information has established a link between the use of tramadol-containing products at normal doses and the risk of seeing or hearing things that are not there (visual and auditory hallucinations), particularly in patients over 65 years of age."},{"field_id":2258,"order_no":4,"bullet":"Health Canada will work with manufacturers to update the Canadian product safety information for tramadol-containing products to include the risk of visual and auditory hallucinations at normal doses, including a higher risk in patients over 65 years of age."}],"footnotes_list":[{"field_id":2262,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2259,"order_no":1,"bullet":"Tramadol-containing products are prescription drugs authorized for sale in Canada to treat moderate to moderately severe pain in adults who require treatment for many days or more."},{"field_id":2259,"order_no":2,"bullet":"Tramadol has been marketed in Canada since 2005 and is available alone or in combination with acetaminophen. It is marketed under the brand names Zytram XL, Tridural, Ralivia, Ultram, Durela and Tramacet. Generic versions of tramadol-containing products are also available for sale in Canada."},{"field_id":2259,"order_no":3,"bullet":"Tramadol-containing products are available as immediate release and controlled release tablets or capsules. The immediate release formulations are available in strengths of 37.5 mg (in combination with 325 mg of acetaminophen) and 50 mg tramadol hydrochloride alone. Extended and controlled release formulations are available at doses ranging from 100 to 400 mg tramadol hydrochloride."},{"field_id":2259,"order_no":4,"bullet":"There were about 1.6 million tramadol prescriptions filled in Canada in 2019, a 4% increase compared to 2015. Tramadol prescriptions have been steadily increasing over the last few years, especially for patients over 65 years of age."}],"finding_list":[{"field_id":2260,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, scientific and medical literature as well as information received from one of the manufacturers."},{"field_id":2260,"order_no":2,"bullet":"At the time of the review, Health Canada had received 54 Canadian reports of hallucinations related to the use of tramadol-containing products. Of the 54 Canadian reports, only 2 met the criteria for further assessment to determine if there was a link between the use of tramadol and hallucinations. The remaining 52 reports could not be assessed due to several contributing factors such as incomplete information in the reports, or the patients were taking other medications at the same time that may have contributed to this risk."},{"field_id":2260,"order_no":3,"bullet":"Health Canada reviewed 24 serious case reports (2 Canadian and 22 international) of hallucinations with the use of tramadol-containing products. Of the 24 case reports, 1 case (an elderly patient) was found to be probably linked, 18 cases (including 2 Canadian cases) were possibly linked, with 11 of these 18 cases involving elderly patients, 1 case was not likely to be linked, and 4 cases did not have enough information to be assessed."},{"field_id":2260,"order_no":4,"bullet":"Health Canada also assessed a review from the published scientific literature that included 101 cases of hallucinations with the use of tramadol. Most reported hallucinations were visual and/or auditory and occurred in patients older than 65 years of age. Health Canada's review of the published study supported a possible link between hallucinations and tramadol use."}],"conclusion_list":[{"field_id":2261,"order_no":1,"bullet":"Health Canada's review of the available information has established a link between the use of tramadol-containing products, at normal doses, and the risk of visual and auditory hallucinations, especially in patients over 65 years of age."},{"field_id":2261,"order_no":2,"bullet":"Health Canada will work with manufacturers to update the Canadian product safety information for tramadol products to include the risk of visual and auditory hallucinations at normal doses, including a higher risk in patients over 65 years of age."},{"field_id":2261,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving tramadol-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00254","review_date":null,"drug_name":"It is well known that continued treatment with SSRIs and SNRIs can cause sexual problems (dysfunction) such as low sexual desire, problems maintaining an erection, orgasm problems, genital or nipple numbness, etc.
Health Canada reviewed the potential risk of persistent or worsening sexual dysfunction, as well as the appearance of new symptoms of sexual dysfunction after stopping SSRI or SNRI treatment. The safety review was triggered by information received from the European Medicines Agency, which was contacted by a group of physicians and scientists concerned that stopping SSRI or SNRI treatment could result in persistent, worsening, or new symptoms of sexual dysfunction.
","use_canada":2269,"findings":2270,"conclusion":2271,"additional":"The analysis that contributed to this safety review included scientific and medical literature, information provided by drug manufacturers and physicians concerned about the risk, and Canadian and international adverse reaction reports, and what is known about the use of SSRIs and SNRIs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2272,"title":"Summary Safety Review - Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-norepinephrine Reuptake Inhibitors (SNRIs) - Assessing the Potential Risk of Sexual Dysfunction despite Treatment Discontinuation","created_date":"2021-01-06","modified_date":null,"key_message_list":[{"field_id":2268,"order_no":1,"bullet":"SSRIs and SNRIs are prescription drugs authorized for sale in Canada to treat depression. Certain SSRI and SNRI products are also authorized for use in other conditions such as anxiety disorders and pain."},{"field_id":2268,"order_no":2,"bullet":"Health Canada reviewed the potential risk of persistent or worsening sexual dysfunction, as well as the appearance of new symptoms of sexual dysfunction after stopping SSRI or SNRI treatment. This safety review was triggered by information received from the European Medicines Agency's Pharmacovigilance Risk Assessment Committee."},{"field_id":2268,"order_no":3,"bullet":"Health Canada's review could not confirm, nor rule out, a causal link between stopping SSRI or SNRI treatment and persistent sexual dysfunction. The review found rare cases of long lasting sexual symptoms persisting after stopping SSRI or SNRI treatment."},{"field_id":2268,"order_no":4,"bullet":"Health Canada's review could not make conclusions about worsening or new symptoms of sexual dysfunction as the available studies were not designed to assess this."},{"field_id":2268,"order_no":5,"bullet":"Health Canada will work with manufacturers to update the product safety information for all SSRIs and SNRIs to recommend that healthcare professionals inform patients about the potential risk of long lasting (possibly weeks to years) sexual dysfunction despite discontinuation of SSRIs or SNRIs."}],"footnotes_list":[{"field_id":2272,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2269,"order_no":1,"bullet":"In Canada, SSRIs and SNRIs are prescription drugs authorized for treating depression with certain products also authorized for other conditions such as anxiety disorders and pain."},{"field_id":2269,"order_no":2,"bullet":"SSRIs authorized for use in Canada include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vilazodone and vortioxetine."},{"field_id":2269,"order_no":3,"bullet":"SNRIs authorized for use in Canada include desvenlafaxine, duloxetine, levomilnacipran and venlafaxine."},{"field_id":2269,"order_no":4,"bullet":"Over 37 million SSRI and SNRI prescriptions were filled in Canada in 2019."}],"finding_list":[{"field_id":2270,"order_no":1,"bullet":"Health Canada reviewed information from published and unpublished population-based (epidemiologic) studies and case reports of individual patients. Information was obtained from searches of international databases of published literature, drug manufacturers, physicians concerned about this issue, as well as searches of the Canada Vigilance databasea."},{"field_id":2270,"order_no":2,"bullet":"Epidemiologic studies reporting sexual dysfunction with SSRIs or SNRIs use were not specifically designed to assess a link between treatment discontinuation and persistent, worsening, or new symptoms of sexual dysfunction, so were not included because of concerns about the accuracy of their findings."},{"field_id":2270,"order_no":3,"bullet":"Health Canada's review of case reports focused on the outcome of persistent sexual dysfunction. Existing assessment tools were not designed to assess the link between treatment discontinuation and changes in patient symptoms (such as worsening of existing symptoms, or the appearance of new symptoms of sexual dysfunction)."},{"field_id":2270,"order_no":4,"bullet":"Of the 58 case reports of sexual dysfunction, 43 cases (16 Canadian, 27 international) of persistent sexual dysfunction were considered possibly linked to previous use and discontinuation of SSRI or SNRI treatment. The remaining 15 cases could not be assessed because there was not enough information. In some of these case reports, symptoms lasted long after treatment discontinuation (weeks to years)."}],"conclusion_list":[{"field_id":2271,"order_no":1,"bullet":"Health Canada's review could not confirm, nor rule out, a causal link between stopping SSRI or SNRI treatment and persistent sexual dysfunction."},{"field_id":2271,"order_no":2,"bullet":"Health Canada's review could not make conclusions about worsening or new symptoms of sexual dysfunction as the studies were not designed to assess this."},{"field_id":2271,"order_no":3,"bullet":"Health Canada will work with manufacturers to update the product safety information for all SSRIs and SNRIs to recommend that healthcare professionals inform patients about the potential risk of long lasting (possibly weeks to years) sexual symptoms persisting after stopping SSRI or SNRI treatment."},{"field_id":2271,"order_no":4,"bullet":"A Health Product InfoWatch Label Update will also be published."},{"field_id":2271,"order_no":5,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of SSRIs and SNRIs and other health products to the Canada Vigilance program."},{"field_id":2271,"order_no":6,"bullet":"Health Canada will continue to monitor safety information involving SSRIs and SNRIs to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00256","review_date":null,"drug_name":"Sofosbuvir-containing products","safety_issue":"Severe cutaneous adverse reactions (SCAR), a group of serious, potentially life-threatening, adverse reactions to drugs that involve the skin and inner lining of some organs.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2288,"overview":"Health Canada reviewed the potential risk of severe cutaneous adverse reactions (SCAR) in patients treated with sofosbuvir-containing products. The safety review was initiated when Health Canada became aware that the EMA updated the product safety information for all sofosbuvir-containing products with new information on the risk of Stevens - Johnson syndrome (SJS). The purpose of this review was to determine whether similar actions were required in Canada.
SCAR is a group of serious, potentially life-threatening, adverse reactions to drugs that involve the skin and inner lining of some organs. This safety review focused on specific types of SCAR: SJS and Toxic Epidermal Necrolysis (TEN) (a more severe form of SJS), Acute Generalized Exanthematous Pustulosis (AGEP), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Erythema Multiforme (EM) and Bullous Dermatitis (BD). While rare, SCAR can lead to hospitalization and death in some cases.
","use_canada":2289,"findings":2290,"conclusion":2291,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of sofosbuvir-containing products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2292,"title":"Summary Safety Review - Sofosbuvir-containing products - Assessing the Potential Risk of Severe Cutaneous Adverse Reactions","created_date":"2021-01-27","modified_date":null,"key_message_list":[{"field_id":2288,"order_no":1,"bullet":"Sofosbuvir-containing products are authorized for sale in Canada to treat chronic hepatitis C virus infection. "},{"field_id":2288,"order_no":2,"bullet":"Health Canada reviewed the potential risk of severe cutaneous adverse reactions (SCAR) with the use of sofosbuvir-containing products. This safety review was triggered by updates made by the European Medicines Agency (EMA) to the product safety information for sofosbuvir-containing products to include the risk of Stevens - Johnson syndrome (SJS), a type of SCAR. The purpose of this review was to determine if similar actions were required in Canada."},{"field_id":2288,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of sofosbuvir-containing products and the risk of Stevens - Johnson syndrome, but did not confirm a link with other types of SCAR. "},{"field_id":2288,"order_no":4,"bullet":"Health Canada will be working with the manufacturer to update the Canadian product safety information for sofosbuvir-containing products to inform healthcare professionals and patients about the risk of SJS."}],"footnotes_list":[{"field_id":2292,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2289,"order_no":1,"bullet":"Sofosbuvir-containing products are prescription drugs authorized for sale in Canada to treat chronic hepatitis-C virus infection."},{"field_id":2289,"order_no":2,"bullet":"Sofosbuvir has been marketed in Canada as a single-ingredient product since 2014 (Sovaldi), and as a combination product with other ingredients since 2014 (Harvoni), 2016 (Epclusa), and 2017 (Vosevi)."},{"field_id":2289,"order_no":3,"bullet":"Sovaldi is available in 400 mg sofosbuvir tablets. Harvoni comes in tablets of 90 mg/400 mg ledipasvir/sofosbuvir. Epclusa is available in tablets of 400 mg/100 mg sofosbuvir/velpatasvir. And, Vosevi comes in tablets of 400 mg/100mg/100 mg sofosbuvir/velpatasvir/voxilaprevir."},{"field_id":2289,"order_no":4,"bullet":"There were about 100,000 prescriptions filled annually in Canada for these products between 2015 and 2019."}],"finding_list":[{"field_id":2290,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, published literature and information provided by the manufacturer."},{"field_id":2290,"order_no":2,"bullet":"Health Canada reviewed 13 case reports (all foreign) of SCAR in patients receiving sofosbuvir-containing products. Of the 13 case reports, 6 reports involved SJS/TEN (4 SJS, 1 TEN and 1 unclear whether SJS or TEN), 5 reports involved EM, and 2 involved BD.Health Canada reviewed the potential risk of encephalopathy in patients treated with ceftriaxone-containing products. The safety review was triggered by a publication in the Journal of the Neurological Sciences reporting brain related adverse drug reactions with the use of ceftriaxone1.
","use_canada":2299,"findings":2300,"conclusion":2301,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of ceftriaxone-containing products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2302,"footnotes":2303,"title":"Summary Safety Review - Ceftriaxone-containing products - Assessing the Potential Risk of Encephalopathy","created_date":"2021-02-03","modified_date":null,"key_message_list":[{"field_id":2298,"order_no":1,"bullet":"Ceftriaxone is a prescription antibiotic drug authorized for sale in Canada to treat a wide range of bacterial infections in many different parts of the body or to prevent infections during surgery."},{"field_id":2298,"order_no":2,"bullet":"Health Canada reviewed the potential risk of encephalopathy, a disease that affects the brain leading to changes in the way the brain works. This review was triggered by a study published in the Journal of the Neurological Sciences."},{"field_id":2298,"order_no":3,"bullet":"Health Canada's review of the available information concluded that there is a possible link between the use of ceftriaxone and the risk of encephalopathy."},{"field_id":2298,"order_no":4,"bullet":"Health Canada will work with the manufacturers of ceftriaxone-containing products to update the Canadian product safety information to include the risk of encephalopathy."}],"footnotes_list":[{"field_id":2303,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2302,"order_no":1,"bullet":"Lacroix C et al. Serious central nervous system side effects of cephalosporins: a national analysis of serious reports registered in the French pharmacovigilance database. J Neurol Sci. Mar 15, 2019. 398: 196-20"}],"use_canada_list":[{"field_id":2299,"order_no":1,"bullet":"Ceftriaxone is a prescription antibiotic drug authorized for sale in Canada since 1987 to treat a wide range of bacterial infections such as urinary tract infections, lower respiratory tract infections, bronchitis, meningitis, and gonorrhea, or to prevent infections during surgery. This antibiotic is mainly used in the hospital setting and is given to patients by a healthcare professional as an injection into a vein or muscle."},{"field_id":2299,"order_no":2,"bullet":"Ceftriaxone is available in Canada as sterile powder for injectable solution, in amounts ranging from 0.25 to 10 grams per vial."},{"field_id":2299,"order_no":3,"bullet":"Two to 3 million vials of ceftriaxone were sold per year in Canada from 2015 to 2019."}],"finding_list":[{"field_id":2300,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases and scientific and medical literature."},{"field_id":2300,"order_no":2,"bullet":"Health Canada reviewed 29 cases (5 Canadian and 24 international) of encephalopathy reported with the use of ceftriaxone. The 24 international cases included 18 reported to the Canada Vigilance database and 6 that were only available through the scientific and medical literature. Of the 29 cases, 17 (including 2 Canadian) were found to be possibly linked to the use of ceftriaxone, 8 cases (including 3 Canadian) were not likely to be linked, and 4 cases did not have enough information to be assessed. None reported drug-related death."},{"field_id":2300,"order_no":3,"bullet":"Assessing the risk of encephalopathy related to the use of ceftriaxone-containing products in these reports was challenging due to incomplete case details and other contributing factors, including existing medical conditions and other medications taken by the patients."},{"field_id":2300,"order_no":4,"bullet":"Health Canada also assessed 5 studies and 3 review articles from the published scientific literature. The review of these publications supported a link between the risk of encephalopathy and the use of ceftriaxone."}],"conclusion_list":[{"field_id":2301,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of ceftriaxone-containing products and the risk of encephalopathy."},{"field_id":2301,"order_no":2,"bullet":"Health Canada will work with the manufacturers of ceftriaxone-containing products to update the Canadian product safety information to include the risk of encephalopathy."},{"field_id":2301,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of ceftriaxone-containing products and other health products to the Canada Vigilance Program."},{"field_id":2301,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving ceftriaxone-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00258","review_date":null,"drug_name":"Tecentriq (atezolizumab)","safety_issue":"Autoimmune Hemolytic Anemia (AIHA), a condition where the body's immune system attacks and destroys its own red blood cells.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2310,"overview":"Health Canada reviewed the potential risk of AIHA in patients treated with Tecentriq. This review was triggered by safety information from clinical trials and from published scientific literature that support a possible link between the use of Tecentriq and the risk of AIHA.
","use_canada":2311,"findings":2312,"conclusion":2313,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Tecentriq both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2314,"title":"Summary Safety Review - Tecentriq (atezolizumab) - Assessing the Potential Risk of Autoimmune Hemolytic Anemia","created_date":"2021-02-03","modified_date":null,"key_message_list":[{"field_id":2310,"order_no":1,"bullet":"Tecentriq (atezolizumab) is a prescription drug authorized for sale in Canada, to be used alone or in combination with other drugs, for the treatment of certain types of lung and liver cancer. It is also authorized with conditions on the manufacturer to treat certain types of breast and bladder cancer."},{"field_id":2310,"order_no":2,"bullet":"Health Canada reviewed the potential risk of autoimmune hemolytic anemia (AIHA) with the use of Tecentriq. This review was triggered by safety information from clinical trials and from scientific literature suggesting a link between the use of Tecentriq and AIHA."},{"field_id":2310,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of Tecentriq and the risk of AIHA."},{"field_id":2310,"order_no":4,"bullet":"Health Canada is working with the manufacturer of Tecentriq to update the Canadian product safety information to include a warning for the risk of AIHA. "}],"footnotes_list":[{"field_id":2314,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2311,"order_no":1,"bullet":"Tecentriq (atezolizumab) is a prescription drug authorized for sale in Canada, to be used alone or in combination with other drugs, for the treatment of certain types of lung and liver cancer. Tecentriq is also authorized, with conditions on the manufacturer, to treat certain types of breast and bladder cancer."},{"field_id":2311,"order_no":2,"bullet":"Tecentriq is administered directly into a vein, under the supervision of a physician experienced in treating cancer."},{"field_id":2311,"order_no":3,"bullet":"Tecentriq is available in Canada as single-use vials containing either 1200 mg atezolizumab/20 mL or 840 mg atezolizumab/14 mL."},{"field_id":2311,"order_no":4,"bullet":"Tecentriq has been marketed in Canada since 2017."}],"finding_list":[{"field_id":2312,"order_no":1,"bullet":"Health Canada reviewed information received from the manufacturer, as well as information from searches of the Canada Vigilance Dabatasea, international databases, and published literature."},{"field_id":2312,"order_no":2,"bullet":"Health Canada's review focused on 36 case reports (one Canadian, 35 foreign) in order to assess the link between the use of Tecentriq and the risk of AIHA. Of the 36 case reports, 5 reports (none Canadian) met the criteria for further assessment. A link between Tecentriq use and AIHA could not be ruled out for these 5 reports; 3 reports were found to be probably linked to the use of Tecentriq and 2 reports were possibly linked. The remaining 31 reports could not be assessed further due to factors such as limited information in the reports, or patients taking other medications at the same time that could also cause AIHA."},{"field_id":2312,"order_no":3,"bullet":"Health Canada also looked at additional information available from 56 studies in published scientific literature. Health Canada's review of these published studies supported a possible link between the use of Tecentriq and the risk of AIHA."}],"conclusion_list":[{"field_id":2313,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Tecentriq and the risk of AIHA."},{"field_id":2313,"order_no":2,"bullet":"Health Canada is working with the manufacturer to update the Canadian product safety information for Tecentriq to include the risk of AIHA."},{"field_id":2313,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Tecentriq, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00259","review_date":null,"drug_name":"Cefuroxime-containing products","safety_issue":"Kounis syndrome, a condition where there is a sudden reduction of blood flow to the heart caused by a severe allergic reaction","safetyissue_title":"Potential Safety Issues","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2320,"overview":"Health Canada reviewed the potential risk of Kounis syndrome with the use of cefuroxime-containing products. The safety review was triggered by foreign case reports published in the medical literature.
Kounis syndrome may occur when an allergic event, including a severe allergic reaction (anaphylactic reaction), results in a sudden reduction of blood flow to the heart. This rare condition may be due in part to a sudden narrowing of the arteries and could lead to the weakening of the heart.
Severe allergic reactions are life-threatening conditions which require a rapid response and for which there are well established clinical guidelines for their diagnosis and treatment (which includes the prompt use of intramuscular epinephrine, etc.). The Canadian safety information for cefuroxime-containing products warns against the risk of severe allergic reactions and recommends the prompt use of intramuscular epinephrine.
","use_canada":2321,"findings":2322,"conclusion":2323,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of cefuroxime-containing products both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2324,"title":"Summary Safety Review - Cefuroxime-containing products - Assessing the Potential Risk of Kounis Syndrome","created_date":"2021-03-04","modified_date":null,"key_message_list":[{"field_id":2320,"order_no":1,"bullet":"Cefuroxime is a prescription antibiotic drug authorized for sale in Canada to treat a wide range of bacterial infections in many different parts of the body, or to prevent infections during surgery."},{"field_id":2320,"order_no":2,"bullet":"Health Canada reviewed the potential risk of Kounis syndrome with the use of cefuroxime-containing products after becoming aware of cases reported in the published literature."},{"field_id":2320,"order_no":3,"bullet":"Health Canada's review of the available information could not confirm a link between the use of cefuroxime-containing products and the risk of Kounis syndrome."},{"field_id":2320,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving cefuroxime-containing products, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2324,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2321,"order_no":1,"bullet":"Cefuroxime is a prescription antibiotic drug authorized for sale in Canada since 1980 to treat a wide range of bacterial infections in many different parts of the body such as the brain (meningitis), respiratory and urinary tracts, skin, soft tissues, bones and joints. Cefuroxime can also be used to treat gonorrhea (a sexually transmitted disease) or to prevent infections during surgery."},{"field_id":2321,"order_no":2,"bullet":"Cefuroxime is available as granules for oral (by mouth) suspension under the brand name Ceftin. It is also available as generics in 250 and 500 mg tablets. Injectable cefuroxime products are available as generics, as 0.75, 1.5 or 7.5 g/vial sterile lyophilized powder for reconstitution."}],"finding_list":[{"field_id":2322,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases and published literature."},{"field_id":2322,"order_no":2,"bullet":"Health Canada assessed 10 case reports (all foreign) of Kounis syndrome related to cefuroxime use, including 9 published in the literature. Of the 10 case reports, 8 were found to be possibly linked to the use of cefuroxime while 2 cases did not have enough information to be assessed. No fatalities were reported."},{"field_id":2322,"order_no":3,"bullet":"Assessing the risk of Kounis syndrome related to the use of cefuroxime-containing products in these reports was challenging due to several contributing factors, including incomplete case details, inconsistent definitions of Kounis syndrome being used, existing medical conditions and other medications taken by the patients."},{"field_id":2322,"order_no":4,"bullet":"The review of these reports did not support a link between the use of cefuroxime-containing products and the risk of Kounis syndrome. There was insufficient information in these reports to confirm the role of cefuroxime as being the trigger of the severe allergic reactions, and the role of other medications as the cause of Kounis syndrome could not be ruled out."}],"conclusion_list":[{"field_id":2323,"order_no":1,"bullet":"Health Canada's review of the available information could not confirm a link between the use of cefuroxime-containing products and the risk of Kounis syndrome."},{"field_id":2323,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of cefuroxime-containing products and other health products to the Canada Vigilance Program."},{"field_id":2323,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving cefuroxime-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00260","review_date":null,"drug_name":"Remicade (infliximab), Humira (adalimumab), Enbrel (etanercept) and Erelzi (biosimilar etanercept)","safety_issue":"Mycosis fungoides, a type of cancer involving white blood cells, called T lymphocytes, which grow out of control in the skin.","safetyissue_title":"Potential Safety Issues","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2330,"overview":"Health Canada reviewed the potential risk of mycosis fungoides in patients treated with anti-TNF alpha products following the publication, in the WHO Pharmaceutical Newsletter, of mycosis fungoides cases resulting from the administration of infliximab (Remicade) reported by the Australian Therapeutic Goods Administration.
Mycosis fungoides is a type of cancer involving white blood cells, called T-lymphocytes, which grow out of control in the skin. It is a form of cutaneous T-cell lymphoma.
","use_canada":2331,"findings":2332,"conclusion":2333,"additional":"The analysis that contributed to this safety review included safety information from the manufacturers, scientific and medical literature, and information from international regulators about anti-TNF alpha products.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary safety review - Remicade (infliximab), Humira (adalimumab), Enbrel (etanercept) and Erelzi (biosimilar etanercept) - Assessing the Potential Risk of Mycosis Fungoides","created_date":"2021-03-18","modified_date":null,"key_message_list":[{"field_id":2330,"order_no":1,"bullet":"Remicade, Humira, Enbrel and Erelzi belong to a class of drugs called Tumor Necrosis Factor (TNF) alpha-blockers (or anti-TNF alpha). These drugs are authorized for sale in Canada to treat adults and children who have inflammatory conditions of the skin (psoriasis, hidradenitis suppurativa), joints (rheumatoid or psoriatic arthritis, ankylosing spondylitis), intestines (Crohn's disease or ulcerative colitis), or the eyes (non-infectious uveitis)."},{"field_id":2330,"order_no":2,"bullet":"Health Canada reviewed the potential risk of mycosis fungoides, a form of lymphoma, with the use of Remicade, Humira, Enbrel or Erelzi. This review was triggered by reports of mycosis fungoides in patients treated with Remicade, which were published in the World Health Organization (WHO) Pharmaceuticals Newsletter."},{"field_id":2330,"order_no":3,"bullet":"The Canadian product safety information for all anti-TNF alpha products have information on the risk of lymphoma. The purpose of this review was to assess whether additional regulatory actions were required in Canada specific to the risk of mycosis fungoides."},{"field_id":2330,"order_no":4,"bullet":"Health Canada's review of the available information concluded that a link between the risk of mycosis fungoides and the use of anti-TNF alpha products could not be confirmed given limitations in the available information. As the product safety information for all anti-TNF alpha products already mentions the risk of lymphoma (which includes mycosis fungoides), no updates specific for mycosis fungoides are required at this time."},{"field_id":2330,"order_no":5,"bullet":"Health Canada will continue to monitor safety information of all anti-TNF alpha products."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":2331,"order_no":1,"bullet":"Anti-TNF alpha products are prescription drugs authorized for sale in Canada to treat adults and children with inflammation of the skin (psoriasis, hidradenitis suppurativa), joints (rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis), intestines (Crohn's disease or ulcerative colitis), or the eyes (non-infectious uveitis). This inflammation occurs when the body's immune system attacks its own tissues (autoimmune disease)."},{"field_id":2331,"order_no":2,"bullet":"Anti-TNF alpha products are proteins (antibodies) that block a naturally produced chemical in the body known as TNF-alpha that causes inflammation in the body."},{"field_id":2331,"order_no":3,"bullet":"Anti-TNF alpha products have been marketed in Canada since 2001 under the brand names Remicade, Humira, Enbrel, Cimzia, Simponi and Erelzi (biosimilar of Enbrel)."},{"field_id":2331,"order_no":4,"bullet":"Cimzia and Simponi were not included in this assessment because they have only recently been authorized for sale in Canada and there have not been cases of mycosis fungoides reported with them in Canada."},{"field_id":2331,"order_no":5,"bullet":"Anti-TNF alpha products are widely used. In 2019, the total number of prescriptions filled were 233,080 (Remicade), 449,085 (Humira), 144,637 (Enbrel) and 9,505 (Erelzi)."},{"field_id":2331,"order_no":6,"bullet":"Anti-TNF alpha products come in different strengths and formulations:Health Canada reviewed the potential risks of choroidal effusion (CE), acute myopia (AM) and acute angle-closure glaucoma (AACG) with the use of diuretics, including acetazolamide. The safety review was triggered by updates made by the European Medicines Agency to include these risks in the product safety information for certain diuretics.
At the time of the review, the Canadian product safety information for some diuretics included information related to one or all of these eye disorders. The purpose of this review was to assess if additional actions were required for diuretics marketed in Canada.
","use_canada":2339,"findings":2340,"conclusion":2341,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports, and what is known about the use of diuretics, including acetazolamide-containing products, both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2342,"title":"Summary Safety Review - Diuretics, Including Acetazolamide - Assessing the Potential Risk of Certain Eye Disorders","created_date":"2021-03-19","modified_date":null,"key_message_list":[{"field_id":2338,"order_no":1,"bullet":"Diuretics (water pills) are authorized for sale in Canada to treat various medical conditions, but are mainly used to reduce swelling caused by a build up of body fluids (edema) and to lower high blood pressure. Acetazolamide, which has diuretic properties, is authorized for sale in Canada to treat increased pressure in the eye (glaucoma), certain types of seizures, overdose from acetylsalicylic acid (ASA) and edema."},{"field_id":2338,"order_no":2,"bullet":"Health Canada reviewed the risks of choroidal effusion (CE), acute myopia (AM) and acute angle-closure glaucoma (AACG) with the use of diuretics, including acetazolamide-containing products. This safety review was triggered by updates made to the product safety information for certain diuretics by the European Medicines Agency."},{"field_id":2338,"order_no":3,"bullet":"At the time of the review, the Canadian product safety information for some diuretics included information related to one or all of these eye disorders. The purpose of this review was to assess if additional actions were required for diuretics marketed in Canada."},{"field_id":2338,"order_no":4,"bullet":"Health Canada's review of the available information showed a link between the use of certain diuretics, namely products containing hydrochlorothiazide, chlorthalidone, indapamide and acetazolamide, and the risks of CE with AM or with AACG or with both AM and AACG. Health Canada's review also concluded that there might be a link between the diuretic Zaroxolyn (metolazone) and the risk of these eye disorders."},{"field_id":2338,"order_no":5,"bullet":"Health Canada will work with manufacturers of affected products to update the Canadian product safety information to add a warning about the risks of CE with AM or with AACG or with both AM and AACG. Health Canada will also inform healthcare professionals about these updates through a Health Product InfoWatch communication."}],"footnotes_list":[{"field_id":2342,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."},{"field_id":2342,"order_no":2,"bullet":"These drug products are not currently marketed in Canada."}],"reference_list":[],"use_canada_list":[{"field_id":2339,"order_no":1,"bullet":"Diuretics are prescription drugs authorized for sale in Canada to treat various medical conditions, but are mainly used to reduce swelling caused by a build up of body fluids (edema) and to lower high blood pressure. Acetazolamide is authorized for sale in Canada to treat increased pressure in the eye (glaucoma), certain types of seizures and overdose from acetylsalicylic acid (ASA). Acetazolamide for Injection is also authorized to treat edema."},{"field_id":2339,"order_no":2,"bullet":"Diuretics, including acetazolamide, have been marketed in Canada since 1968 under different brand names. Single ingredient and combination products are available. Generic versions of diuretics are also available."},{"field_id":2339,"order_no":3,"bullet":"Diuretics, including acetazolamide, are widely used in Canada. There were over 31 million prescriptions for these drugs filled in 2019."}],"finding_list":[{"field_id":2340,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases and published literature."},{"field_id":2340,"order_no":2,"bullet":"Health Canada reviewed 49 cases (1 Canadian, 48 foreign) of choroidal effusion, acute myopia or acute angle-closure glaucoma with the use of diuretics, including acetazolamide. The 48 foreign cases included 7 reported to the Canada Vigilance database and 41 that were only available through the scientific literature."},{"field_id":2340,"order_no":3,"bullet":"Health Canada's review found a link between the use of certain diuretics and the risks of CE with AM or with AACG or with both AM and AACG. For hydrochlorothiazide, 7 cases (1 Canadian) showed a possible link and 1 case was not likely to be linked. For chlorthalidone, 4 cases were considered possibly linked and 1 case could not be assessed due to insufficient information in the report. For indapamide, 7 cases were found to be possibly linked and 1 case was unlikely to be linked. For furosemide, 1 case was found to be possibly linked, 2 cases were not likely to be linked and 1 case did not have enough information to be assessed. Of the 19 acetazolamide cases reviewed, 1 case was found to be probably linked, 12 cases were possibly linked, 1 case was unlikely to be linked and 5 cases could not be assessed. The remaining 5 cases were considered unlikely to have a link (spironolactone, triamterene, methyclothiazideb, azosemideb) or did not have enough information to be assessed (xipamideb)."},{"field_id":2340,"order_no":4,"bullet":"At the time of the review, no information was found to support a link between Zaroxolyn and the risk of eye disorders. However, given the similar chemical structure of Zaroxolyn to chlorthalidone and indapamide, the risks of CE, AM or AACG with Zaroxolyn use could not be excluded."},{"field_id":2340,"order_no":5,"bullet":"While the published literature supported a link between the risks of CE, AM or AACG with certain diuretics, including acetazolamide, it did not identify a clear biological mechanism to explain how diuretics, including acetazolamide, could lead to these eye disorders."}],"conclusion_list":[{"field_id":2341,"order_no":1,"bullet":"Health Canada's review of the available information showed a link between the use of certain diuretics, namely products containing hydrochlorothiazide, chlorthalidone, indapamide and acetazolamide, and the risks of CE with AM or with AACG or with both AM and AACG. In addition, Health Canada's review concluded that there might be a link between Zaroxolyn and the risk of these eye disorders."},{"field_id":2341,"order_no":2,"bullet":"Health Canada will work with manufacturers to update the Canadian product safety information for products containing hydrochlorothiazide, chlorthalidone, indapamide and acetazolamide as well as Zaroxolyn to add a warning about the risks of CE with AM or with AACG or with both AM and AACG. Health Canada will also inform healthcare professionals about these updates through a Health Product InfoWatch communication."},{"field_id":2341,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of diuretics, including acetazolamide, and other health products to the Canada Vigilance Program."},{"field_id":2341,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving diuretics, including acetazolamide-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00262","review_date":null,"drug_name":"Artemisia annua-containing products (also known as Sweet wormwood-containing products)","safety_issue":"Risk of liver injury","safetyissue_title":"Potential Safety Issues","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2348,"overview":"Health Canada reviewed the potential risk of liver injury with Artemisia annua-containing products. The review was triggered after the New Zealand Medicines and Medical Devices Safety Authority (MedSafe)1 and the Therapeutic Goods Administration of Australia (TGA)2 published risk communications to advise consumers and healthcare professionals about the potential risk of liver injury with the use of products containing Artemisia annua extract.
","use_canada":2349,"findings":2350,"conclusion":2351,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this natural health product both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2352,"footnotes":2353,"title":"Summary Safety Review - Artemisia annua-containing Products - Assessing the Potential Risk of Liver Injury","created_date":"2021-03-24","modified_date":null,"key_message_list":[{"field_id":2348,"order_no":1,"bullet":"Artemisia annua-containing products are natural health products authorized for sale in Canada for various indications such as the relief of cold symptoms or occasional constipation, or for symptom management of diarrhea."},{"field_id":2348,"order_no":2,"bullet":"Health Canada reviewed the potential risk of liver injury with the use of Artemisia annua-containing products. This safety review was triggered by public advisories issued by MedSafe of New Zealand and by the Therapeutic Goods Administration (TGA) of Australia related to the potential risk of liver injury with the use of Artemisia annua-containing products available in those countries."},{"field_id":2348,"order_no":3,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Artemisia annua-containing products and the risk of liver injury in Canada. At the time of this review, Health Canada found that the available information for Artemisia annua-containing products related to this risk in Canada is too limited to warrant regulatory action."},{"field_id":2348,"order_no":4,"bullet":"The Artemisia annua-containing products of concern in New Zealand and Australia are not marketed in Canada. In contrast to the reported uses in New Zealand and Australia (chronic joint pain), the reported uses in Canada are different and typically of shorter duration (1 to 8 weeks). Health Canada will continue to monitor the safety of Artemisia annua-containing products in Canada."}],"footnotes_list":[{"field_id":2353,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"}],"reference_list":[{"field_id":2352,"order_no":1,"bullet":"Artemisia annua (Sweet wormwood, Sweet Annie, Qing hao) extract marketed as Arthrem: risk of harm to the liver - statement under section 98 of the Medicines Act 1981; Medsafe"},{"field_id":2352,"order_no":2,"bullet":"Arthrem capsules Safety advisory - potential risk of harm to the liver"}],"use_canada_list":[{"field_id":2349,"order_no":1,"bullet":"Artemisia annua-containing products are natural health products (NHPs) authorized for sale in Canada for various indications such as, the relief of cold symptoms or occasional constipation, or for symptom management of diarrhea."},{"field_id":2349,"order_no":2,"bullet":"Artemisia annua-containing products have been authorized in Canada under several brand names. There are over 160 authorized Artemisia annua-containing NHPs available in several dosage forms that include tablets, capsules, granules, powders, and oral drops. Over 40 of these products contain Artemisia annua as the only (single) medicinal ingredient."},{"field_id":2349,"order_no":3,"bullet":"The Artemisia annua-containing products of concern in New Zealand and Australia are not marketed in Canada. In contrast to the reported uses in New Zealand and Australia (chronic join pain), the reported uses in Canada are different and typically of shorter duration (1 to 8 weeks)."},{"field_id":2349,"order_no":4,"bullet":"In Canada, Artemisia annua-containing products can be accessed by individuals without a prescription for self-administration."}],"finding_list":[{"field_id":2350,"order_no":1,"bullet":"Health Canada reviewed the available information from published clinical studies as well as case reports of liver injury from the Canada Vigilance databasea and international databases."},{"field_id":2350,"order_no":2,"bullet":"At the time of the review, Health Canada had received 4 Canadian reports of liver injury potentially related to the use of Artemisia annua-containing products. Health Canada's review of these case reports did not find a link between the products and liver injury due to a lack of detailed information in these reports."},{"field_id":2350,"order_no":3,"bullet":"A review of 61 international cases of liver injury related to the use of an Artemisia annua-containing product was also completed. The assessment was unable to determine a link between potential risk of liver injury and the use of Artemisia annua-containing products due to insufficient information within these case reports."},{"field_id":2350,"order_no":4,"bullet":"The mechanism by which Artemisia annua could cause liver injury is not well understood."}],"conclusion_list":[{"field_id":2351,"order_no":1,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Artemisia annua-containing products and the risk of liver injury in Canada. At the time of this review, Health Canada found that the available information for Artemisia annua-containing products related to this risk in Canada is too limited to warrant regulatory action."},{"field_id":2351,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Artemisia annua-containing products to the Canada Vigilance Program."},{"field_id":2351,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Artemisia annua, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00263","review_date":null,"drug_name":"Dental Amalgam","safety_issue":"Negative health effects from mercury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2360,"overview":"Dental amalgam is used to replace broken or decayed areas of teeth, such as cavities. Dental amalgam contains mercury. Mercury can have negative effects on health, including brain and kidney function.
In 1996, Health Canada published a report2 on the safety of dental amalgam. That report included a position statement with recommendations following a detailed review. The position statement1 drew no clear link between mercury in dental amalgam and negative health effects, but advised minimizing the use of dental amalgam in children, pregnant women and patients with kidney disease, as a precaution.
A safety review was conducted in 2020 as a follow-up to consider recent information and determine if the recommendations in the 1996 report are still valid.
","use_canada":2361,"findings":2362,"conclusion":2363,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international incident reports, and what is known about the use of these medical devices both in Canada and internationally.
Following the completion of the safety review by Health Canada, the U.S. FDA published an updated safety communication in September 2020 outlining recommendations for certain high-risk groups regarding mercury-containing dental amalgam. The findings of our risk assessment on dental amalgam are consistent with this recent communication by the FDA, as well as with recommendations from other international regulatory agencies.
For additional information about Health Canada's assessment of medical devices, contact the Medical Devices Directorate.
","full_review":"","references":2364,"footnotes":2365,"title":"Summary safety review - Dental Amalgam - Assessing the Potential Risk of Negative Health Effects from Mercury","created_date":"2021-03-31","modified_date":null,"key_message_list":[{"field_id":2360,"order_no":1,"bullet":"In Canada, dental amalgam is a medical device used to replace broken or decayed areas of teeth, such as cavities."},{"field_id":2360,"order_no":2,"bullet":"In 1996, Health Canada published a position statement1 that recommended minimizing the use of amalgam in children, pregnant women and patients with kidney disease. In 2020, Health Canada reviewed recent information to determine if the recommendations in the 1996 report are still valid."},{"field_id":2360,"order_no":3,"bullet":"Health Canada's 2020 review concluded that there is no clear link between mercury in dental amalgam and negative health effects. However, bulk (loose) dental amalgam powders, which have to be mixed with liquid mercury by hand, are known to pose an unnecessary risk of mercury exposure for the dental healthcare professional. The 1996 Health Canada position statement on dental amalgam remains appropriate. Health Canada's findings are consistent with the conclusions of professional dental associations and international regulatory agencies."},{"field_id":2360,"order_no":4,"bullet":"Health Canada has worked with manufacturers to discontinue the licenses of bulk dental amalgam powders in Canada."}],"footnotes_list":[{"field_id":2365,"order_no":1,"bullet":"Canadian reports can be accessed through Health Canada's Medical Device Incidents page."}],"reference_list":[{"field_id":2364,"order_no":1,"bullet":"The Safety of Dental Amalgam, II. Health Canada Position Statement on Dental Amalgam"},{"field_id":2364,"order_no":2,"bullet":"The Safety of Dental Amalgam"}],"use_canada_list":[{"field_id":2361,"order_no":1,"bullet":"Dental amalgam has been used in Canada for over 100 years to replace broken or decayed areas within teeth, such as cavities. At the time of the 2020 review, there were 46 dental amalgam products authorized for sale in Canada."},{"field_id":2361,"order_no":2,"bullet":"Dental amalgam is a mixture of liquid mercury and a metal powder composed of silver, tin and copper. Typically, these come in closed capsules that already contain measured amounts of the metal powder and mercury. The metal powder and mercury are mixed by placing the entire capsule in specially designed equipment."},{"field_id":2361,"order_no":3,"bullet":"Dental amalgam products with bulk (loose) metal powder separate from the liquid mercury are also available. In this case, the metal powder and liquid mercury have to be mixed manually by the dental healthcare professional. At the time of the 2020 review, six products containing bulk metal powder were authorized for sale in Canada. However, they were not being used in Canada."},{"field_id":2361,"order_no":4,"bullet":"The use of dental amalgam for the repair of decayed or broken teeth is decreasing in Canada."}],"finding_list":[{"field_id":2362,"order_no":1,"bullet":"Health Canada reviewed information from incident reports, medical and scientific literature, and information published by international regulatory agencies."},{"field_id":2362,"order_no":2,"bullet":"A search of the medical device incident reporting databases in Canada and the United States (U.S.) identified 2 Canadian casesa and 49 cases in the U.S. over the past 25 years, describing negative health effects potentially related to the use of dental amalgam. There was not enough information in the reports to support a link between the symptoms (double vision, imbalance, weakness) and dental amalgam."},{"field_id":2362,"order_no":3,"bullet":"Health Canada also reviewed 29 articles published between 2014 and 2019. Overall, the review did not find evidence to support a clear link between the use of dental amalgam and negative health effects from mercury. However, children, pregnant women, and patients with kidney disease may be more vulnerable to the effects of mercury."},{"field_id":2362,"order_no":4,"bullet":"The safety of dental amalgam has been reviewed by organizations both within Canada and internationally, including the Canadian Agency for Drugs and Technologies in Health (CADTH), the U.S. Food and Drug Administration (FDA), and the European Commission's Scientific Committee on Emerging and Newly Identified Risk (SCENIHR). The general consensus is that the available information does not support a clear link between the use of dental amalgam and negative health effects."},{"field_id":2362,"order_no":5,"bullet":"The Canadian and American Dental Associations maintain that dental amalgam is safe for the repair and restoration of teeth."}],"conclusion_list":[{"field_id":2363,"order_no":1,"bullet":"Health Canada's 2020 review of the available safety information concluded that there is no clear link between mercury in dental amalgam and negative health effects."},{"field_id":2363,"order_no":2,"bullet":"This safety review did not find new evidence to suggest a change in the overall safety profile for dental amalgam. Therefore, the 1996 Health Canada position statement1 on dental amalgam remains valid. As a precaution, use of dental amalgam in children, pregnant women, and patients with kidney disease should be minimized, as recommended in the 1996 Health Canada position statement."},{"field_id":2363,"order_no":3,"bullet":"Although pre-measured dental amalgam capsules are considered safe, bulk dental amalgam powders, which have to be mixed with liquid mercury by hand, are known to pose an unnecessary risk of mercury exposure for the dental healthcare professional. Following its safety review, Health Canada worked with manufacturers to discontinue the licenses of bulk dental amalgam powders in Canada."},{"field_id":2363,"order_no":4,"bullet":"Health Canada will continue to monitor information on the benefits and risks associated with the use of dental amalgam and take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00264","review_date":null,"drug_name":"Veklury (remdesivir)","safety_issue":"Acute kidney injury, a sudden decrease in kidney function; or acute renal failure, kidney failure over a very short period of time.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2372,"overview":"Health Canada reviewed the potential risks of acute kidney injury and acute renal failure with Veklury (remdesivir) to analyse the emerging information and determine if further measures were needed in Canada. This safety review was initiated following the submission of international case reports of AKI/ARF from the manufacturer.
\nAt the time of the review, the CPM for Veklury included information on potential kidney toxicity and recommended blood tests before and during Veklury treatment to check for kidney problems. Veklury should not be given with drugs that reduce kidney function or used in patients with severe kidney problems.
","use_canada":2373,"findings":2374,"conclusion":2375,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of Veklury both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2376,"title":"Summary Safety Review - Veklury (remdesivir) - Assessing the Potential Risks of Acute Kidney Injury (AKI) and Acute Renal Failure (ARF)","created_date":"2021-04-09","modified_date":null,"key_message_list":[{"field_id":2372,"order_no":1,"bullet":"Veklury (remdesivir) is authorized for sale in Canada to treat coronavirus disease 2019 (COVID-19) in adults and adolescents with pneumonia (a lung infection) and requiring oxygen. This authorization includes conditions on the manufacturer to provide additional information to Health Canada on the drug's performance, along with active safety monitoring."},{"field_id":2372,"order_no":2,"bullet":"Health Canada reviewed the potential risks of acute kidney injury (AKI) and acute renal failure (ARF) with the use of Veklury. The safety review was triggered by international case reports, received from the manufacturer, of AKI/ARF in patients treated with Veklury."},{"field_id":2372,"order_no":3,"bullet":"At the time of the review, the Canadian product safety information (Canadian Product Monograph) for Veklury included information on potential kidney toxicity and recommended measuring kidney function before starting Veklury and during treatment. It also advised against using Veklury with drugs that reduce kidney function, or in patients with severe kidney problems. The purpose of this review was to assess if additional actions were required in Canada."},{"field_id":2372,"order_no":4,"bullet":"Based on Health Canada's review of the available information, a direct link between the use of Veklury and the risk of AKI/ARF could not be established. The available information does not suggest a change in the overall safety profile for Veklury. Presently, the Canadian Product Monograph (CPM) for Veklury provides appropriate information on kidney toxicity and recommendations on usage, therefore, no updates are required at this time."},{"field_id":2372,"order_no":5,"bullet":"Health Canada will continue to monitor the safety of Veklury, as it does for all health products on the Canadian market, to identify and assess potential harms."}],"footnotes_list":[{"field_id":2376,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2373,"order_no":1,"bullet":"Veklury is a prescription drug authorized for sale in Canada to treat coronavirus disease 2019 (COVID-19) in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia and requiring oxygen. This authorization includes conditions requiring the manufacturer to provide additional information to Health Canada on the drug's performance, along with active safety monitoring."},{"field_id":2373,"order_no":2,"bullet":"Veklury has been marketed in Canada since October 2020. Currently, Veklury is available for sale as a sterile powder for solution for infusion (100 mg/vial). The sterile solution (100 mg/20mL) formulation is not marketed at this time."},{"field_id":2373,"order_no":3,"bullet":"There were about 21,000 vials purchased by Canadian hospitals from September to December 2020."}],"finding_list":[{"field_id":2374,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, published literature, and information received from the manufacturer."},{"field_id":2374,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of AKI/ARF related to Veklury use."},{"field_id":2374,"order_no":3,"bullet":"Health Canada reviewed 88 international case reports of AKI/ARF in patients receiving Veklury. 60 of these foreign cases were from the Canada Vigilance database. Of the 88 case reports, 64 cases were found to be possibly linked with the use of Veklury, 14 cases were unlikely to be linked, and 10 cases did not have enough information to be further assessed. In all 64 cases assessed as possibly linked, the role of Veklury in causing AKI/ARF could not be established due to several contributing factors such as, other medications taken by the patients, existing medical conditions and/or COVID-19 illness that may have contributed to AKI/ARF."},{"field_id":2374,"order_no":4,"bullet":"Health Canada also looked at additional information available from 10 articles in published scientific literature and 4 studies provided by the manufacturer on the risk of AKI/ARF with Veklury use. Overall, there is limited information suggesting that treatment with Veklury in COVID-19 patients can lead to AKI/ARF."}],"conclusion_list":[{"field_id":2375,"order_no":1,"bullet":"Health Canada's review could not establish a direct link between the use of Veklury and the risk of AKI/ARF. The Canadian product safety information for Veklury includes information on kidney toxicity and recommendations on usage. Therefore, the safety information for Veklury is appropriate at this time."},{"field_id":2375,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Veklury and other health products to the Canada Vigilance Program."},{"field_id":2375,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Veklury, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00265","review_date":null,"drug_name":"AstraZeneca COVID-19 Vaccine and COVISHIELD","safety_issue":"Reports of very rare Thrombosis (blood clots) in combination with thrombocytopenia (low blood platelets)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2382,"overview":"Health Canada reviewed the risk of blood clots in combination with low blood platelets following immunization with AstraZeneca COVID-19 Vaccine and COVISHIELD to evaluate emerging information and determine if further measures are needed to mitigate the risk in Canada. This safety review was initiated after cases of blood clots following immunization with AstraZeneca COVID-19 Vaccine were reported in Europe.
As of April 12, 2021, no regulatory authorities have restricted use of the vaccine, although public health authorities in Canada and several other countries, including France, Germany and Australia, have recently restricted use of the vaccine to older age groups.
","use_canada":2383,"findings":2384,"conclusion":2385,"additional":"The analysis that contributed to this safety review included information provided by the manufacturer, consultations with scientific experts, Canadian and international information, and what is known about the use of AstraZeneca COVID-19 Vaccine and COVISHIELD both in Canada and internationally.
As of April 10, 2021, 221,484 doses of AstraZeneca COVID-19 Vaccine and 488,038 doses of COVISHIELD have been administered in Canada.
The COVID-19 vaccines and treatments portal provides information for consumers, healthcare professionals and researchers on vaccines and treatments authorized for COVID-19, as well as those currently under review.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2386,"footnotes":0,"title":"Summary Safety Review - AstraZeneca and COVISHIELD COVID-19 Vaccines - Assessing the Potential Risk of Thrombosis in combination with Thrombocytopenia","created_date":"2021-04-19","modified_date":null,"key_message_list":[{"field_id":2382,"order_no":1,"bullet":"AstraZeneca COVID-19 Vaccine and COVISHIELD are authorized in Canada for active immunization of individuals 18 years of age and over for the prevention of coronavirus disease 2019 (COVID-19)."},{"field_id":2382,"order_no":2,"bullet":"Health Canada reviewed the risk of blood clots in combination with low platelets with the use of AstraZeneca COVID-19 Vaccine and COVISHIELD after cases were reported in Europe following immunization with AstraZeneca COVID-19 Vaccine."},{"field_id":2382,"order_no":3,"bullet":"Health Canada's review of the available information concluded that a link between the use of AstraZeneca COVID-19 Vaccine and COVISHIELD and the risk of these blood clots with low platelets is possible. The risk of these events is very rare, and the overall benefits of the vaccine in protecting Canadians from COVID-19 continue to outweigh its potential risks."},{"field_id":2382,"order_no":4,"bullet":"Health Canada did not identify risk factors, such as age or gender, for these very rare events, and is not restricting the use of the vaccine at this time."},{"field_id":2382,"order_no":5,"bullet":"A potential mechanism for the combination of blood clots with low platelets is the triggering of an immune response by the vaccine, leading to a condition similar to that seen sometimes in patients treated with the blood thinner medication heparin."},{"field_id":2382,"order_no":6,"bullet":"Health Canada worked with the manufacturers of AstraZeneca COVID-19 Vaccine and COVISHIELD to update the Canadian Product Monographs (CPM) for these products to include new safety information about these events. Health Canada also communicated1 to Canadians and healthcare professionals about this risk."},{"field_id":2382,"order_no":7,"bullet":"Health Canada will continue to monitor the safety of AstraZeneca COVID-19 Vaccine and COVISHIELD. Health Canada will also continue to work closely with international regulators to review information as it becomes available on these very rare events, and will make further updates to the CPM or take other actions as needed."}],"footnotes_list":[],"reference_list":[{"field_id":2386,"order_no":1,"bullet":"Health Canada provides update on the AstraZeneca and COVISHIELD COVID-19 vaccines"}],"use_canada_list":[{"field_id":2383,"order_no":1,"bullet":"AstraZeneca COVID-19 Vaccine and COVISHIELD are authorized for sale in Canada for active immunization of individuals 18 years of age and over for the prevention of COVID-19. This authorization includes conditions requiring the manufacturer to provide additional information to Health Canada on the vaccine's effectiveness, along with active safety monitoring."},{"field_id":2383,"order_no":2,"bullet":"AstraZeneca COVID-19 Vaccine is manufactured by AstraZeneca and COVISHIELD is manufactured by Serum Institute of India. Health Canada reviewed the manufacturing information for these vaccines and found them to be comparable, which means individuals could complete the vaccination course with either AstraZeneca COVID-19 Vaccine or COVISHIELD."},{"field_id":2383,"order_no":3,"bullet":"AstraZeneca COVID-19 Vaccine and COVISHIELD have been authorized in Canada since February 2021. Currently, AstraZeneca COVID-19 Vaccine and COVISHIELD are available as solutions for injection into the muscle, in multiple dose vials."},{"field_id":2383,"order_no":4,"bullet":"As of April 3, 2021, 6,158 doses of AstraZeneca COVID-19 Vaccine and 478,535 doses of COVISHIELD have been administered in Canada."}],"finding_list":[{"field_id":2384,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance database, international databases, and information received from the manufacturers and international regulators."},{"field_id":2384,"order_no":2,"bullet":"At the time of the review, Health Canada was aware of one report of a Canadian vaccine recipient who experienced blood clots with low platelets following immunization with COVISHIELD."},{"field_id":2384,"order_no":3,"bullet":"Health Canada's review considered all currently available information. This included information submitted by the manufacturers in response to terms and conditions that were put in place by Health Canada. Health Canada also reviewed information shared by international regulators, including their assessment of the reports received in their jurisdictions."},{"field_id":2384,"order_no":4,"bullet":"A link between these events and AstraZeneca COVID-19 Vaccine and COVISHIELD was considered possible. Health Canada's findings are in line with the conclusions of international regulators."},{"field_id":2384,"order_no":5,"bullet":"The potential risk of blood clots with low platelets is very rare. Based on their vaccination rate as of March 31, 2021, the United Kingdom Medicines and Healthcare Products Regulatory Agency estimated the overall risk of these blood clots to be approximately 4 people in a million who receive the vaccine. Reported cases of these adverse events have been seen after the first dose, usually within the first 14 days after immunization."},{"field_id":2384,"order_no":6,"bullet":"Health Canada's review of available information from Europe, the United Kingdom and the manufacturers did not identify any specific risk factors, such as age or gender for these events. It is recognized that the benefit versus risk of receiving the vaccine may vary by age due to differences in the risk of severe disease associated with COVID-19 illness, which continues to change as the nature of the pandemic changes."},{"field_id":2384,"order_no":7,"bullet":"A potential mechanism for the combination of blood clots with low platelets is the triggering of an immune response by the vaccine, leading to a condition similar to heparin-induced thrombocytopenia seen sometimes in patients treated with the blood thinner medication heparin."}],"conclusion_list":[{"field_id":2385,"order_no":1,"bullet":"Health Canada's review of the available information concluded that a link between the use of AstraZeneca COVID-19 Vaccine and COVISHIELD and the risk of blood clots with low platelets is possible. The risk of these events is very rare."},{"field_id":2385,"order_no":2,"bullet":"The benefits of AstraZeneca COVID-19 Vaccine and COVISHIELD in preventing COVID-19 continue to outweigh the risk of very rare events of blood clots in combination with low platelets. At this time, information provided by the manufacturers demonstrate the potential benefits of the vaccine across all age groups."},{"field_id":2385,"order_no":3,"bullet":"Health Canada's review of available information from Europe, the United Kingdom and the manufacturers did not identify specific risk factors, such as age or gender, for these very rare events. Therefore, Health Canada is not restricting the use of the vaccine at this time for certain populations or age groups. The risk of severe disease associated with COVID-19 illness varies with age and continues to change as the nature of the pandemic changes."},{"field_id":2385,"order_no":4,"bullet":"Health Canada has published information for vaccine recipients on signs and symptoms of these events and when to seek medical attention. Health Canada has also provided healthcare professionals with information to identify and promptly treat these conditions according to available evidence and clinical guidelines."},{"field_id":2385,"order_no":5,"bullet":"Health Canada worked with the manufacturers of AstraZeneca COVID-19 Vaccine and COVISHIELD to update the CPMs for these products with this safety information. Health Canada also requested that the manufacturers update the risk management plans for the AstraZeneca COVID-19 Vaccine and COVISHIELD to reflect the latest information about this safety issue, and to include plans for studies that will address remaining knowledge gaps."},{"field_id":2385,"order_no":6,"bullet":"Health Canada will continue to monitor the safety of AstraZeneca COVID-19 Vaccine and COVISHIELD, as it does for all health products on the Canadian market. Health Canada will also continue to work closely with international regulators, the manufacturers, the Public Health Agency of Canada, and Provincial and Territorial public health authorities to review information as it becomes available on these very rare events, and will make further updates to the CPMs or take other actions as needed."}]},{"template":2,"link_id":"SSR00266","review_date":null,"drug_name":"Janssen COVID-19 Vaccine","safety_issue":"Reports of very rare cases of blood clots (thrombosis) in combination with low blood platelets (thrombocytopenia)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2392,"overview":"Health Canada reviewed the risk of unusual blood clots in combination with low blood platelets following vaccination with Janssen COVID-19 Vaccine to evaluate emerging information and determine if further measures are needed to mitigate the risk in Canada. This safety review was initiated after cases of blood clots with low platelets following administration of Janssen COVID-19 Vaccine were reported in the US.
On April 13, 2021, the US paused the use of the Janssen COVID-19 Vaccine as a precautionary measure, pending investigation of the reported cases of rare blood clots in combination with low levels of blood platelets following vaccination. At that time, Janssen COVID-19 Vaccine was only used in the US, and over 6.8 million Americans had received the vaccine.
","use_canada":2393,"findings":2394,"conclusion":2395,"additional":"The analysis that contributed to this safety review included information provided by the manufacturer, consultations with scientific experts, and what is known about the use of Janssen COVID-19 Vaccine internationally.
On April 23, 2021, the US lifted the pause on Janssen COVID-19 Vaccine and use of the vaccine resumed. As of this date, a total of 15 cases of blood clots with low platelets, out of 7.9 million doses administered, have been reported to the US Food and Drug Administration.
The COVID-19 vaccines and treatments portal provides information for consumers, healthcare professionals and researchers on vaccines and treatments authorized for COVID-19, as well as those currently under review.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2396,"footnotes":0,"title":"Summary safety review - Janssen COVID-19 Vaccine - Assessing the Potential Risk of Thrombosis in combination with Thrombocytopenia","created_date":"2021-05-04","modified_date":null,"key_message_list":[{"field_id":2392,"order_no":1,"bullet":"Janssen COVID-19 Vaccine is authorized in Canada for active immunization for the prevention of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older."},{"field_id":2392,"order_no":2,"bullet":"Health Canada reviewed the risk of unusual blood clots in combination with low platelets with the use of Janssen COVID-19 Vaccine after cases were reported in the United States (US) following administration of Janssen COVID-19 Vaccine."},{"field_id":2392,"order_no":3,"bullet":"Health Canada's review of the available information concluded that a link between the use of Janssen COVID-19 Vaccine and the risk of blood clots with low platelets is possible. No specific risk factors, such as age or gender, have been identified at this time."},{"field_id":2392,"order_no":4,"bullet":"The reported combination of unusual blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in protecting Canadians from COVID-19 outweigh the risks."},{"field_id":2392,"order_no":5,"bullet":"A potential mechanism for the combination of blood clots and low platelets is the triggering of an immune response by the vaccine, leading to a condition similar to that seen in some patients treated with the blood thinner medication heparin."},{"field_id":2392,"order_no":6,"bullet":"Health Canada worked with the manufacturer to update the Canadian Product Monograph (CPM) for Janssen COVID-19 Vaccine to reflect current knowledge of this safety issue. Health Canada also communicated1 to vaccine recipients and healthcare professionals about this risk."},{"field_id":2392,"order_no":7,"bullet":"Health Canada will continue to monitor the safety of Janssen COVID-19 Vaccine. Health Canada will also continue to work closely with international regulators to review information as it becomes available on these very rare events, and will make further updates to the CPM or take other actions as needed."}],"footnotes_list":[],"reference_list":[{"field_id":2396,"order_no":1,"bullet":"Janssen COVID-19 Vaccine and the Risk of Thrombosis with Thrombocytopenia"},{"field_id":2396,"order_no":2,"bullet":"Summary Safety Review - AstraZeneca and COVISHIELD COVID-19 Vaccines - Assessing the Potential Risk of Thrombosis in combination with Thrombocytopenia"}],"use_canada_list":[{"field_id":2393,"order_no":1,"bullet":"Janssen COVID-19 Vaccine is authorized for sale in Canada for active immunization for the prevention of COVID-19 caused by SARS-CoV-2 virus in individuals 18 years of age and older. This authorization includes conditions requiring the manufacturer to provide additional information to Health Canada on the vaccine's effectiveness, along with active safety monitoring."},{"field_id":2393,"order_no":2,"bullet":"Janssen COVID-19 Vaccine has been authorized in Canada since March 2021. The vaccine is expected to be distributed and administered in Canada in early May 2021."},{"field_id":2393,"order_no":3,"bullet":"Janssen COVID-19 Vaccine is available as a suspension for injection into the muscle, in multiple dose vials."}],"finding_list":[{"field_id":2394,"order_no":1,"bullet":"Health Canada reviewed the available information from international databases, the manufacturer and international regulators."},{"field_id":2394,"order_no":2,"bullet":"At the time of the review, Health Canada took into consideration all currently available information including 8 reports of blood clots associated with low platelets, 1 of which had a fatal outcome, from the US. Of the 8 cases, 2 were found to be probably linked and 6 were possibly linked to the use of Janssen COVID-19 Vaccine."},{"field_id":2394,"order_no":3,"bullet":"All cases occurred within 3 weeks following vaccination and mostly in women under 50 years of age. These cases are similar to those that were reported after administration of the AstraZeneca COVID-19 Vaccine and COVISHIELD2."},{"field_id":2394,"order_no":4,"bullet":"A link between blood clots with low platelets and Janssen COVID-19 Vaccine is considered possible. The potential risk of blood clots and low platelets is very rare. Health Canada's findings are in line with the conclusions of international regulators."},{"field_id":2394,"order_no":5,"bullet":"Based on the available information, no specific risk factors, such as age or gender, for these events have been identified."},{"field_id":2394,"order_no":6,"bullet":"A potential mechanism for the combination of blood clots with low platelets is the triggering of an immune response by the vaccine, leading to a condition similar to heparin-induced thrombocytopenia seen sometimes in patients treated with the blood thinner medication heparin."}],"conclusion_list":[{"field_id":2395,"order_no":1,"bullet":"Health Canada's review of the available information concluded that a link between the use of Janssen COVID-19 Vaccine and the risk of blood clots with low platelets is possible. The risk of these events is very rare."},{"field_id":2395,"order_no":2,"bullet":"The overall benefits of Janssen COVID-19 Vaccine in preventing COVID-19 outweigh the risk of very rare events of blood clots in combination with low platelets."},{"field_id":2395,"order_no":3,"bullet":"Health Canada's review of available information did not identify specific risk factors, such as age or gender, for these very rare events. Therefore, Health Canada is not restricting the use of the vaccine for certain populations or age groups. The risk of severe disease associated with COVID-19 illness varies with age and continues to change as the nature of the pandemic changes."},{"field_id":2395,"order_no":4,"bullet":"Health Canada has published information for vaccine recipients on signs and symptoms to monitor after vaccine administration and when to seek medical attention. Health Canada has also provided healthcare professionals with information to identify and promptly treat this condition according to current evidence and clinical guidelines."},{"field_id":2395,"order_no":5,"bullet":"Health Canada worked with the manufacturer of Janssen COVID-19 Vaccine to update the CPM with this safety information. Health Canada also requested that the manufacturer update the risk management plan for the Janssen COVID-19 Vaccine to reflect the latest information about this safety issue, and to include plans for studies that will address remaining knowledge gaps."},{"field_id":2395,"order_no":6,"bullet":"Health Canada will continue to monitor the safety of Janssen COVID-19 Vaccine, as it does for all health products on the Canadian market. Health Canada will also continue to work closely with international regulators, the manufacturers, the Public Health Agency of Canada, as well as the Provincial and Territorial public health authorities, to review information as it becomes available on these very rare events, and will make further updates to the CPM or take other actions as needed."}]},{"template":2,"link_id":"SSR00267","review_date":null,"drug_name":"Opdivo (nivolumab)","safety_issue":"Health Canada reviewed the potential risks of autoimmune hemolytic anemia, aplastic anemia, cytokine release syndrome and tumor lysis syndrome with the use of Opdivo, either alone or in combination with Yervoy. These reviews were triggered by safety information provided by the manufacturer and information from the published medical literature.
Autoimmune hemolytic anemia is a condition where the body's immune system attacks and destroys its own red blood cells. Aplastic anemia is a condition where the body stops producing enough new blood cells.
Cytokines are small proteins that are important in cell function. High levels of cytokines may cause increased inflammation throughout the body. Cytokine release syndrome is a serious and potentially life-threatening inflammatory reaction where the immune system responds too aggressively to an infection or certain medications resulting in a large, rapid release of cytokines into the blood from immune cells. The symptoms of cytokine release syndrome can include fever, headache, tiredness and multiple organ damage.
Tumor lysis syndrome is a potentially life-threatening condition that can occur during cancer treatment. When cancer cells break down (die) from cancer treatment, they release their contents (salts and proteins) into the blood. When cancer cells break down quickly, these substances rise faster than the kidneys can remove them from the blood. This causes changes to the chemical balance in the blood, which can affect the functioning of several organs, most commonly the kidneys, heart and brain.
","use_canada":2403,"findings":2404,"conclusion":2405,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Opdivo both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2406,"title":"Summary Safety Review - Opdivo (nivolumab) - Assessing the Potential Risks of Certain Blood Disorders, and Cytokine Release and Tumor Lysis Syndromes","created_date":"2021-05-19","modified_date":"2021-06-09","key_message_list":[{"field_id":2402,"order_no":1,"bullet":"Opdivo (nivolumab) is a prescription drug authorized for sale in Canada, for use alone or in combination with Yervoy (ipilimumab), to treat certain types of cancers of the skin, head and neck, blood cells, lungs, kidneys, liver and colon. Some of the authorized uses include conditions requiring the manufacturer to provide additional information."},{"field_id":2402,"order_no":2,"bullet":"Health Canada reviewed the following potential risks with Opdivo, used alone or in combination with Yervoy:Progressive multifocal leukoencephalopathy, a rare but serious and potentially fatal brain infection.
","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2412,"overview":" Health Canada reviewed the potential risk of a rare brain infection known as progressive multifocal leukoencephalopathy with the use of Pomalyst or Thalomid following reported cases of PML in patients taking Pomalyst.
PML is an opportunistic infection in the brain caused by the John Cunningham (JC) virus. It is most frequently associated with a weakened immune system. PML is often fatal; therefore, it is important to detect it early so it can be appropriately managed.
Dopamine agonist withdrawal syndrome (DAWS), a group of mental and physical symptoms occurring after stopping or reducing the dose of dopamine agonists
","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2422,"overview":" Health Canada reviewed the potential risk of DAWS with the use of the dopamine agonists apomorphine, bromocriptine, cabergoline, pergolide, pramipexole, quinagolide, ropinirole, and rotigotine following a manufacturer-initiated CPM update to include DAWS under the Warnings and Precautions section for Mirapex (pramipexole).
DAWS may occur after reducing the dose of or stopping some dopamine agonists, and includes symptoms such as apathy, anxiety, depression, fatigue, sweating, panic attacks, insomnia, irritability and pain.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of dopamine agonists both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
In 2007, increased numbers of reports in the Canada Vigilance database prompted Health Canada to advise healthcare professionals to watch for drug interactions and risk factors that could result in changes to the electrical activity of the heart (QT prolongation) in patients using domperidone.3
\nIn 2012, 2 studies showed an increased risk of serious abnormal heart rhythms (cardiac arrhythmias) in patients taking domperidone at doses exceeding 30 mg daily as well as in patients over 60 years of age. This prompted Health Canada to update the Canadian Product Monographs (CPMs) for domperidone to advise healthcare professionals to use the lowest possible dose of the drug, and to be cautious when prescribing it to patients at high risk of abnormal heart rhythms. At that time, Health Canada informed Canadians about this risk and changes to the CPMs.4
\nIn 2014, 2 more safety reviews were carried out in response to new information received from a foreign regulator about domperidone safety and Health Canada’s consultation with Canadian healthcare professionals, respectively. The 2 reviews confirmed the risk of serious abnormal heart rhythms and sudden cardiac death related to domperidone use. As a result, the CPMs were further updated in 2015 to include a maximum daily dose recommendation, and new restrictions for use in patients with certain medical conditions or taking other drugs.
\nIn 2021, Health Canada carried out a follow-up to the 2014 safety reviews of domperidone and serious ventricular arrhythmia, QT interval prolongation and sudden cardiac death. This latest safety review was triggered by the publication of a Canadian study2 on the risk of heart effects with domperidone when used for lactation promotion, an off-label use in Canada. The purpose of the current review was to consider recent information, for both the approved and off-label use, and determine if additional measures were warranted.
","use_canada":2505,"findings":2506,"conclusion":2507,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of domperidone both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2508,"footnotes":2509,"title":"Summary Safety Review - Domperidone - Assessing the Potential Risks of Serious Ventricular Arrhythmias, QT Interval Prolongation and Sudden Cardiac Death","created_date":"2021-12-30","modified_date":"2022-12-08","key_message_list":[{"field_id":2504,"order_no":1,"bullet":"Domperidone is authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal conditions, and to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson's disease."},{"field_id":2504,"order_no":2,"bullet":"In 2021, Health Canada carried out a follow-up safety review to 1 previously completed in 2014.1 The current review was triggered by the publication of a Canadian study on the risk of heart effects with domperidone when used for lactation promotion, which is an off-label (non-authorized) use of the drug.2"},{"field_id":2504,"order_no":3,"bullet":"Health Canada's review found no additional safety concerns with domperidone use and the risks of serious ventricular arrhythmias, QT interval prolongation or sudden cardiac death. The current product safety labelling (Canadian Product Monograph) for domperidone, related to these risks, is appropriate. No updates are needed at this time."},{"field_id":2504,"order_no":4,"bullet":"Health Canada will continue to monitor the safety of domperidone. Health Canada will also publish an Infowatch article to raise awareness and remind healthcare professionals of the cardiac risks and the maximum daily dose recommendations, as well as to encourage continued reporting of suspected safety issues with the use of domperidone."}],"footnotes_list":[{"field_id":2509,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2508,"order_no":1,"bullet":"Summary Safety Review - Domperidone - Serious abnormal heart rhythms and sudden death (cardiac arrest) - Health Canada. Issued: 2015-01-27."},{"field_id":2508,"order_no":2,"bullet":"Moriello C, Paterson JM, Reynier P, Dahl M, Aibibula W, Fisher A, et al. Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ Open. 2021 20210514;9(2):E500-9."},{"field_id":2508,"order_no":3,"bullet":"Djelouah I, Scott C. Domperidone: heart rate and rhythm disorders. Canadian Adverse Reaction Newsletter 2007;17(1)."},{"field_id":2508,"order_no":4,"bullet":"Health Canada Public Communication: Domperidone maleate - Association with serious abnormal heart rhythms and sudden death (cardiac arrest). Posting date: March 7, 2012."}],"use_canada_list":[{"field_id":2505,"order_no":1,"bullet":"Domperidone is a prescription drug authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal disorders, as well as to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson's disease."},{"field_id":2505,"order_no":2,"bullet":"Domperidone was first marketed in Canada in 1985 and is available as a 10 mg tablet."},{"field_id":2505,"order_no":3,"bullet":"There were approximately 1.7 million prescriptions filled for domperidone in 2020, which represents approximately 120 million domperidone tablets."}],"finding_list":[{"field_id":2506,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea and published literature for both the approved and off-label use of domperidone."},{"field_id":2506,"order_no":2,"bullet":"Health Canada reviewed 15 cases (8 Canadian and 7 international) of serious ventricular arrhythmia, QT interval prolongation, and/or sudden cardiac death/cardiac arrest following the use of domperidone for both the approved and off-label use. Of the 15 cases, 6 (3 Canadian) were found to have a possible link with domperidone use. The remaining 9 cases (3 Canadian) did not have enough information to be further assessed."},{"field_id":2506,"order_no":3,"bullet":"The Canadian study that triggered this review found that the risk of cardiac side effects is very low in individuals using domperidone off-label to promote lactation."},{"field_id":2506,"order_no":4,"bullet":"Health Canada's safety review also looked at the scientific literature published since 2014, and did not find any new information about serious ventricular arrhythmia, QT interval prolongation, or sudden cardiac death following the use of domperidone for both the approved and off-label use."}],"conclusion_list":[{"field_id":2507,"order_no":1,"bullet":"Health Canada's review of the available information found no new safety information related to the risks of serious ventricular arrhythmia, QT interval prolongation or sudden cardiac death for both the approved and off-label use of domperidone. As a result, no further updates to the CPMs are warranted."},{"field_id":2507,"order_no":2,"bullet":"Health Canada will publish an Infowatch article to raise awareness and remind healthcare professionals of the cardiac risks for both the approved and off-label use, and the maximum daily dose recommendations."},{"field_id":2507,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to continue reporting any side effects related to the use of domperidone, and other health products, to the Canada Vigilance Program."},{"field_id":2507,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving domperidone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00270","review_date":null,"drug_name":"Kadcyla (trastuzumab emtansine)","safety_issue":"Tumor Lysis Syndrome, a condition that occurs when cancer cells are killed rapidly, releasing their contents into the blood, causing blood chemical imbalance and organ damage.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2432,"overview":"Health Canada reviewed the potential risk of tumor lysis syndrome with the use of Kadcyla. The review was triggered by reports of suspected tumor lysis syndrome in patients using Kadcyla that were provided by the manufacturer.
Tumor lysis syndrome is a potentially life-threatening condition that can occur during cancer treatment. When cancer cells are killed by the cancer treatment, they release their contents (salts and proteins) into the blood. When cancer cells break down faster than the kidneys can remove these substances from the blood, it can cause changes to the chemical balance in the blood, which may result in damage to organs, most commonly the kidneys, heart and brain.
","use_canada":2433,"findings":2434,"conclusion":2435,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of Kadcyla both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2436,"title":"Summary Safety Review - Kadcyla (trastuzumab emtansine) - Assessing the Potential Risk of Tumor Lysis Syndrome","created_date":"2021-06-24","modified_date":null,"key_message_list":[{"field_id":2432,"order_no":1,"bullet":"Kadcyla (trastuzumab emtansine) is a prescription drug authorized for sale in Canada for the treatment of early or late stage breast cancer."},{"field_id":2432,"order_no":2,"bullet":"Health Canada reviewed the risk of tumor lysis syndrome with the use of Kadcyla. This review was triggered by summary information received from the manufacturer."},{"field_id":2432,"order_no":3,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Kadcyla and the risk of tumor lysis syndrome in Canada. At the time of this review, Health Canada found the available information for Kadcyla related to this risk in Canada is too limited to warrant regulatory action."},{"field_id":2432,"order_no":4,"bullet":"Health Canada has asked the manufacturer for additional information about the risk of tumor lysis syndrome related to the use of Kadcyla in Canada and in other jurisdictions, and will review this information as it becomes available to determine if any measures are needed at that time."},{"field_id":2432,"order_no":5,"bullet":"Health Canada will continue to monitor the safety of Kadcyla, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2436,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2433,"order_no":1,"bullet":"Kadcyla is a prescription drug authorized for sale in Canada for the treatment of early or late stage breast cancer."},{"field_id":2433,"order_no":2,"bullet":"Kadcyla is administered as an infusion directly into a vein (intravenous), under the supervision of a physician experienced in treating cancer."},{"field_id":2433,"order_no":3,"bullet":"Kadcyla is available in vials as lyophilized powder containing 100 mg and 160 mg trastuzumab emtansine, respectively."},{"field_id":2433,"order_no":4,"bullet":"Kadcyla has been marketed in Canada since 2013. Approximately 2,344 Canadian patients have been treated with Kadcyla to date."}],"finding_list":[{"field_id":2434,"order_no":1,"bullet":"Health Canada reviewed information received from the manufacturer, as well as information from searches of the Canada Vigilance Databasea, international databases and published literature."},{"field_id":2434,"order_no":2,"bullet":"Health Canada reviewed 17 cases (10 Canadian and 7 foreign) of tumor lysis syndrome in patients treated with Kadcyla. Of the 17 cases, 4 Canadian cases were found to be unlikely linked to the use of Kadcyla. The remaining 13 cases (6 Canadian and 7 foreign) did not have enough information in the reports for further review. It was difficult to establish a link between tumor lysis syndrome and Kadcyla use due to missing information or the presence of other contributing factors (chemotherapy treatment and underlying medical conditions) in the 17 cases."},{"field_id":2434,"order_no":3,"bullet":"At the time of the review, Health Canada did not find any reports in the scientific literature to support a link between tumor lysis syndrome and Kadcyla use."}],"conclusion_list":[{"field_id":2435,"order_no":1,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Kadcyla and the risk of tumor lysis syndrome in Canada. At the time of this review, Health Canada found the available information for Kadcyla related to this risk in Canada too limited to warrant regulatory action."},{"field_id":2435,"order_no":2,"bullet":"Health Canada has asked the manufacturer for additional information about the risk of tumor lysis syndrome related to the use of Kadcyla in Canada and in other jurisdictions, and will review this information to determine if any measures are needed at that time."},{"field_id":2435,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Kadcyla and other health products to the Canada Vigilance Program."},{"field_id":2435,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Kadcyla, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if any new health risks are identified."}]},{"template":2,"link_id":"SSR00271","review_date":null,"drug_name":"Veklury (remdesivir)","safety_issue":"Sinus bradycardia, when the heart beats more slowly than usual","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2442,"overview":"Health Canada reviewed the potential risk of sinus bradycardia with the use of Veklury following the submission of international case reports of sinus bradycardia from the manufacturer.
\nSinus bradycardia occurs when the heart beats slower than normal. Sinus bradycardia can very rarely cause symptoms, such as dizziness, tiredness, shortness of breath, and chest discomfort.
","use_canada":2443,"findings":2444,"conclusion":2445,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Veklury both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2446,"title":"Summary Safety Review - Veklury (remdesivir) - Assessing the Potential Risk of Sinus Bradycardia","created_date":"2021-08-18","modified_date":null,"key_message_list":[{"field_id":2442,"order_no":1,"bullet":"Veklury (remdesivir) is authorized for sale in Canada to treat COVID-19 in adults and adolescents with pneumonia and requiring oxygen."},{"field_id":2442,"order_no":2,"bullet":"Health Canada reviewed the potential risk of sinus bradycardia with the use of Veklury. The safety review was triggered by international case reports of sinus bradycardia in patients treated with Veklury, received as part of the conditions on the manufacturer to provide additional information to Health Canada."},{"field_id":2442,"order_no":3,"bullet":"Health Canada's review of the available information concluded that a link between the use of Veklury and the risk of sinus bradycardia is possible."},{"field_id":2442,"order_no":4,"bullet":"Health Canada will work with the manufacturer of Veklury to update the Canadian product safety information to include the potential risk of sinus bradycardia."}],"footnotes_list":[{"field_id":2446,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[],"use_canada_list":[{"field_id":2443,"order_no":1,"bullet":"Veklury is a prescription drug authorized for sale in Canada to treat COVID-19 in adults and adolescents (aged 12 years and older with body weight of at least 40 kg) with pneumonia and requiring oxygen. This authorization includes conditions requiring the manufacturer to provide additional information to Health Canada on the drug's performance, along with active safety monitoring."},{"field_id":2443,"order_no":2,"bullet":"Veklury has been marketed in Canada since October 2020 as a sterile powder for solution for infusion (100 mg/vial)."},{"field_id":2443,"order_no":3,"bullet":"There were about 45,000 vials purchased by Canadian hospitals from October 2020 through April 2021."}],"finding_list":[{"field_id":2444,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, published literature, clinical trials, and information received from the manufacturer."},{"field_id":2444,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of sinus bradycardia related to Veklury use. However, there was 1 Canadian case from the published literature."},{"field_id":2444,"order_no":3,"bullet":"Health Canada assessed 47 (46 international and 1 Canadian) case reports of sinus bradycardia in patients receiving Veklury. Thirty of the international cases were from the Canada Vigilance database. Of the 47 case reports, 39 cases were found to be possibly linked to the use of Veklury, 6 cases were unlikely to be linked, and 2 cases did not have enough information to be further assessed. In all 39 cases assessed as possibly linked, existing medical conditions and/or COVID-19 illness may have contributed to sinus bradycardia."},{"field_id":2444,"order_no":4,"bullet":"Health Canada also looked at additional information available from 11 articles in published scientific literature and 7 studies provided by the manufacturer on the risk of sinus bradycardia with Veklury use. In general, there is limited information from these sources suggesting that treatment of COVID-19 patients with Veklury can lead to sinus bradycardia."}],"conclusion_list":[{"field_id":2445,"order_no":1,"bullet":"Health Canada's review of the available information concluded that a link between the use of Veklury and the risk of sinus bradycardia is possible."},{"field_id":2445,"order_no":2,"bullet":"Health Canada will work with the manufacturer of Veklury to update the Canadian product safety information to inform healthcare professionals and patients about the potential risk of sinus bradycardia."},{"field_id":2445,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Veklury, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00272","review_date":null,"drug_name":"Fluoroquinolone antibiotics (ciprofloxacin-, levofloxacin-, moxifloxacin- and norfloxacin-containing products) administered by injection or by mouth (systemic) and by breathing in (inhaled).","safety_issue":"Leaking heart valves (heart valve regurgitation).","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2452,"overview":"Health Canada reviewed the potential risk of heart valve regurgitation in patients treated with systemic or inhaled fluoroquinolones following information received from the EMA related to this risk.
Health Canada's review did not include fluoroquinolone products for use in the eyes (ophthalmic) or ears (otic), since this risk has not been reported with these formulations.
","use_canada":2453,"findings":2454,"conclusion":2455,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2456,"footnotes":2457,"title":"Summary Safety Review - Systemic and Inhaled Fluoroquinolone Antibiotics - Assessing the Potential Risk of Heart Valve Regurgitation","created_date":"2021-08-27","modified_date":null,"key_message_list":[{"field_id":2452,"order_no":1,"bullet":"Fluoroquinolones are a group of prescription antibiotic drugs authorized for sale in Canada to treat a wide range of bacterial infections, including urinary and respiratory tract infections."},{"field_id":2452,"order_no":2,"bullet":"Health Canada reviewed the potential risk of heart valve regurgitation with the use of fluoroquinolones. The safety review was triggered by information received from the European Medicines Agency (EMA) related to this risk."},{"field_id":2452,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of systemic or inhaled fluoroquinolones and the risk of heart valve regurgitation. The Canadian product information about the risk of heart valve regurgitation for systemic or inhaled fluoroquinolones is similar to the United States Food and Drug Administration's (US FDA) product safety information for fluoroquinolones on this risk."},{"field_id":2452,"order_no":4,"bullet":"Health Canada will continue to monitor the safety of fluoroquinolones, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2457,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2456,"order_no":1,"bullet":"Etminan M, Sodhi M, Ganjizadeh-Zavareh S, Carleton B, Kezouh A, Brophy JM. Oral Fluoroquinolones and Risk of Mitral and Aortic Regurgitation. J Am Coll Cardiol. 2019;74(11):1444-1450. doi:10.1016/j.jacc.2019.07.035."},{"field_id":2456,"order_no":2,"bullet":"Finkle W.D., Ridgeway G., Greenland S., Irwin D.E., Juneau P., Palmer L. Risk of aortic valve and neuropsychiatric disorders following an initial prescription for levofloxacin or ciprofloxacin in the elderly. Pharmacoepidemiol.Drug Saf. 2017;26:391-392. [abstract only]"}],"use_canada_list":[{"field_id":2453,"order_no":1,"bullet":"Fluoroquinolones are a group of prescription antibiotic drugs authorized for sale in Canada to treat a wide range of bacterial infections, including urinary and respiratory tract infections. They can be administered by mouth (oral), by injection, by inhalation, or applied to the eyes and ears."},{"field_id":2453,"order_no":2,"bullet":"Fluoroquinolones have been marketed in Canada since 1986 under different brand names and generics of ciprofloxacin, moxifloxacin, levofloxacin, and norfloxacin."},{"field_id":2453,"order_no":3,"bullet":"About 2 million systemic and inhaled fluoroquinolone prescriptions are filled in Canadian retail pharmacies every year."}],"finding_list":[{"field_id":2454,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, and published literature."},{"field_id":2454,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of heart valve regurgitation related to fluoroquinolone use."},{"field_id":2454,"order_no":3,"bullet":"Health Canada reviewed 5 international case reports of heart valve regurgitation in patients receiving a fluoroquinolone that were retrieved from the Canada Vigilance database. Of the 5 case reports, 2 cases were found to be possibly linked with the use of a fluoroquinolone, 2 cases were unlikely to be linked, and one case did not have enough information to be assessed further."},{"field_id":2454,"order_no":4,"bullet":"Health Canada's review of 2 articles in the scientific literature did not support a link between heart valve regurgitation and the use of fluoroquinolones. The first study1 reported an increased risk of heart valve regurgitation with fluoroquinolone use; however, limitations in the study design make the findings difficult to interpret. The second study2 did not have enough information to be assessed further."}],"conclusion_list":[{"field_id":2455,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the use of systemic or inhaled fluoroquinolones and the risk of heart valve regurgitation."},{"field_id":2455,"order_no":2,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of fluoroquinolones, and other health products, to the Canada Vigilance Program."},{"field_id":2455,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving fluoroquinolones, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00273","review_date":null,"drug_name":"Gadolinium-based contrast agents","safety_issue":"Birth defects (congenital anomalies), death of the unborn baby (stillbirth) and baby's death in the first month of life (neonatal death)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2464,"overview":"Health Canada reviewed the potential risks of congenital anomalies, stillbirth and neonatal death with the use of GBCAs during pregnancy. This safety review was initiated following updates made by the US FDA to the product information for all GBCAs to include the potential risks of stillbirth and neonatal death with the use of these agents during pregnancy.
At the time of the review, the CPMs for GBCAs include warnings to limit the use of these agents during pregnancy unless the potential benefit justifies the potential risk to the fetus, and that the use of a specific type of GBCA may be preferable during pregnancy. The purpose of this review was to assess whether additional warnings or other actions were required in Canada.
","use_canada":2465,"findings":2466,"conclusion":2467,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of GBCAs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2468,"title":"Summary Safety Review - Gadolinium-Based Contrast Agents - Assessing the Potential Risks of Congenital Anomalies, Stillbirth and Neonatal Death","created_date":"2021-09-22","modified_date":null,"key_message_list":[{"field_id":2464,"order_no":1,"bullet":"Gadolinium-based contrast agents (GBCAs) are authorized for sale in Canada to make certain body tissues easier to see during a magnetic resonance imaging (MRI) or a magnetic resonance angiography (MRA) scan."},{"field_id":2464,"order_no":2,"bullet":"Health Canada reviewed the potential risks of birth defects (congenital anomalies), death of the unborn baby (stillbirth) and baby's death in the first month of life (neonatal death) with the use of GBCAs during pregnancy. The review was triggered by updates made by the United States Food and Drug Administration (US FDA) to the product safety information of all GBCAs to include the potential risks of stillbirth and neonatal death with the use of these agents during pregnancy."},{"field_id":2464,"order_no":3,"bullet":"Health Canada's review of the available information found no link between the use of GBCAs during pregnancy and the risk of congenital anomalies. However, at this time, there is not enough information to rule out a link between the use of GBCAs during pregnancy and the risks of stillbirth and neonatal death."},{"field_id":2464,"order_no":4,"bullet":"As a precaution, given the potential for serious harm to unborn babies (fetuses) and infants, Health Canada will work with the manufacturers of GBCAs to include the potential risks of stillbirth and neonatal death in their Canadian Product Monographs (CPMs) to raise awareness among healthcare professionals and encourage reporting of these potential safety issues."}],"footnotes_list":[{"field_id":2468,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"},{"field_id":2468,"order_no":2,"bullet":"World Health Organization's Adverse Drug Reaction Database VigiLyze"}],"reference_list":[],"use_canada_list":[{"field_id":2465,"order_no":1,"bullet":"GBCAs are authorized for sale in Canada to make it easier to view certain body structures on MRI or MRA scans, allowing healthcare professionals to see abnormal tissues."},{"field_id":2465,"order_no":2,"bullet":"GBCAs are available in vials as a solution to be injected into the veins. Gadolinium is the chemical element present in the active ingredients of these health products. GBCAs are classified into 2 types based on their chemical structure: linear agents and macrocyclic agents. Both types are presently marketed in Canada. In 2019, the majority of GBCAs used in Canada were of the macrocyclic type, which may be preferable in pregnancy. There are currently 8 GBCAs authorized for sale in Canada:Health Canada reviewed the potential risk of limbal stem cell deficiency with the use of contact lenses. This review was triggered by an article, published in The Ocular Surface Journal2, suggesting that some contact lens users may have developed signs of LSCD, and emphasized that these users may not look for professional care since most of them have not yet developed any symptoms.
Limbal stem cell deficiency is a rare condition where stem cells in the border of the cornea and the white of the eye do not produce enough new cells to replace the old ones in the cornea. In early stages, it can have no symptoms, or nonspecific symptoms such as pain, light sensitivity, decreased vision or tearing, which can be related to other medical conditions, and not specifically to LSCD. It can progress to scarring of the cornea, inflammation (keratitis) and formation of new blood vessels (vascularization), which can lead to loss of vision.
","use_canada":2475,"findings":2476,"conclusion":2477,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of contact lenses both in Canada and internationally.
For additional information, contact the Medical Devices Directorate.
","full_review":"","references":2478,"footnotes":0,"title":"Summary Safety Review - Contact Lenses - Assessing the Potential Risk of Limbal Stem Cell Deficiency","created_date":"2021-09-24","modified_date":null,"key_message_list":[{"field_id":2474,"order_no":1,"bullet":"Contact lenses are prescription or non-prescription medical devices authorized for sale in Canada for various indications, mainly to correct vision."},{"field_id":2474,"order_no":2,"bullet":"Health Canada reviewed the risk of limbal stem cell deficiency (LSCD) with the use of contact lenses. This safety review was triggered by a published study suggesting a possible link between contact lens use and this rare condition."},{"field_id":2474,"order_no":3,"bullet":"Health Canada's review of the available information has found a possible link between the use of contact lenses and the risk of limbal stem cell deficiency."},{"field_id":2474,"order_no":4,"bullet":"Health Canada has updated the It's Your Health1 article on contact lenses to inform healthcare professionals and contact lens users of the possible risk of LSCD with the use of contact lenses."}],"footnotes_list":[],"reference_list":[{"field_id":2478,"order_no":1,"bullet":"Contact Lenses, It's Your Health"},{"field_id":2478,"order_no":2,"bullet":"Rossen J, Amram A, Milani B, et al. (2016) Contact Lens-induced Limbal Stem Cell Deficiency. The Ocular Surface, 14(4):419-434."}],"use_canada_list":[{"field_id":2475,"order_no":1,"bullet":"Contact lenses are prescription or non-prescription medical devices authorized for sale in Canada, mainly to correct vision. Contact lenses do not have to be purchased directly from an eye care practitioner."},{"field_id":2475,"order_no":2,"bullet":"Contact lenses are marketed in Canada under various brand names."}],"finding_list":[{"field_id":2476,"order_no":1,"bullet":"Health Canada reviewed information from Canadian and US incident reporting databases, medical and scientific literature, and information published by international regulatory agencies."},{"field_id":2476,"order_no":2,"bullet":"At the time of the review, Health Canada had received 12 Canadian reports of possible LSCD associated with the use of contact lenses. LSCD was usually described as corneal scarring, keratitis, or vision impairment. Only 1 of these reports described it as vascularization. These 12 reports had insufficient information for a detailed assessment."},{"field_id":2476,"order_no":3,"bullet":"Health Canada also reviewed 9 articles from the published scientific literature, which supported a possible link between the risk of LSCD and the use of contact lenses."}],"conclusion_list":[{"field_id":2477,"order_no":1,"bullet":"Health Canada's review of the available information has found a possible link between the use of contact lenses and the rare risk of limbal stem cell deficiency."},{"field_id":2477,"order_no":2,"bullet":"Health Canada has updated the It's Your Health1 article on contact lenses to inform healthcare professionals and contact lens users of the possible risk of LSCD with the use of contact lenses."},{"field_id":2477,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving contact lenses, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00275","review_date":null,"drug_name":"Aimovig (erenumab)","safety_issue":"Non-fatal stroke, non-fatal heart attack and death related to diseases affecting the heart and blood vessels (cardiovascular death)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2484,"overview":"Health Canada reviewed the potential risk of non-fatal stroke, non-fatal heart attack and cardiovascular death with the use of Aimovig. This safety review was triggered by new information from safety reports, related to these potential risks, received from the manufacturer.
A stroke happens when the blood supply to part of the brain is stopped or lowered, blocking brain tissue from getting enough oxygen and nutrients, leading to the death of brain cells. A heart attack happens when blood flow, bringing oxygen and nutrients, to the heart muscle is lowered or cut off completely. The heart muscle may be damaged, and heart function could be weakened. Depending on the extent of the brain or heart tissue injury, there could be long-term health consequences or cardiovascular death in rare situations.
","use_canada":2485,"findings":2486,"conclusion":2487,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of Aimovig both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2488,"title":"Summary Safety Review - Aimovig (erenumab) - Assessing the Potential Risks of Non-Fatal Stroke, Non-Fatal Heart Attack and Cardiovascular Death","created_date":"2021-12-08","modified_date":"2021-12-17","key_message_list":[{"field_id":2484,"order_no":1,"bullet":"Aimovig (erenumab) is a prescription drug authorized for sale in Canada to prevent migraines in adults who have 4 or more migraine days per month."},{"field_id":2484,"order_no":2,"bullet":"Health Canada reviewed the risks of non-fatal stroke, non-fatal heart attack and death related to the diseases affecting the heart and blood vessels (cardiovascular death) with the use of Aimovig. This review was triggered by new safety information, related to these potential risks, received from the manufacturer."},{"field_id":2484,"order_no":3,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Aimovig and the risks of non-fatal stroke, non-fatal heart attack or cardiovascular death."},{"field_id":2484,"order_no":4,"bullet":"Health Canada will continue to monitor the safety of Aimovig, as it does for all health products on the Canadian market."}],"footnotes_list":[{"field_id":2488,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2485,"order_no":1,"bullet":"Aimovig is a prescription drug authorized for sale in Canada to prevent migraines in adults who have 4 or more migraine days per month."},{"field_id":2485,"order_no":2,"bullet":"Erenumab, the active ingredient in Aimovig, is a monoclonal antibody that blocks the function of a protein called calcitonin gene-related peptide that can cause a migraine."},{"field_id":2485,"order_no":3,"bullet":"Aimovig is authorized to be sold as 70 mg/mL and 140 mg/mL solutions for injection under the skin (subcutaneous) through single-dose pre-filled autoinjector or single-dose pre-filled syringe."},{"field_id":2485,"order_no":4,"bullet":"Aimovig has been marketed in Canada since 2018. Approximately 19,982 new Aimovig prescriptions have been dispensed in Canada to date."}],"finding_list":[{"field_id":2486,"order_no":1,"bullet":"Health Canada reviewed information received from the manufacturer, and information from searches of the Canada Vigilance databasea, international databases, and published literature."},{"field_id":2486,"order_no":2,"bullet":"Health Canada considered 196 case reports (134 international and 62 Canadian) for this safety review. Ten cases (all Canadian) met the criteria for further assessment to determine if there was a link between Aimovig use and the risk of non-fatal stroke, non-fatal heart attack or cardiovascular death."},{"field_id":2486,"order_no":3,"bullet":"Health Canada's assessment of the 10 Canadian cases could not confirm a link between the use of Aimovig and non-fatal stroke, non-fatal heart attack, or cardiovascular death. These cases either included factors such as other medications taken by the patients or medical conditions that may have contributed to these risks, or contained insufficient medical information."},{"field_id":2486,"order_no":4,"bullet":"At the time of the review, Health Canada did not find any reports in the scientific literature to support a link between non-fatal stroke, non-fatal heart attack or cardiovascular death and Aimovig use."}],"conclusion_list":[{"field_id":2487,"order_no":1,"bullet":"Health Canada's review of the available information could not confirm a link between the use of Aimovig and non-fatal stroke, non-fatal heart attack or cardiovascular death."},{"field_id":2487,"order_no":2,"bullet":"Health Canada continues to encourage consumers and healthcare professionals to report any side effects related to the use of Aimovig and other health products to the Canada Vigilance Program."},{"field_id":2487,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving Aimovig, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00276","review_date":null,"drug_name":"Amoxicillin-containing products","safety_issue":"Aseptic meningitis, a condition where the linings of the brain and spinal cord become inflamed without an infectious cause.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2494,"overview":"Health Canada reviewed the potential risk of aseptic meningitis in patients treated with amoxicillin-containing products. The safety review was triggered by case reports published in the literature in the past 3 years concerning this risk.
","use_canada":2495,"findings":2496,"conclusion":2497,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of amoxicillin-containing products both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2498,"title":"Summary Safety Review - Amoxicillin-containing Products - Assessing the Potential Risk of Aseptic Meningitis","created_date":"2021-12-10","modified_date":null,"key_message_list":[{"field_id":2494,"order_no":1,"bullet":"Amoxicillin-containing products are prescription antibiotics authorized for sale in Canada to treat or prevent certain bacterial infections."},{"field_id":2494,"order_no":2,"bullet":"Health Canada reviewed the risk of aseptic meningitis with the use of amoxicillin-containing products following the publication of case reports in the literature in the past 3 years concerning this risk."},{"field_id":2494,"order_no":3,"bullet":"At the time of this review, the Canadian product safety information (Canadian Product Monograph) for some combination products containing amoxicillin and clavulanic acid included information on the risk of aseptic meningitis. The purpose of this review was to assess if additional actions were required for amoxicillin-containing products marketed in Canada."},{"field_id":2494,"order_no":4,"bullet":"Health Canada's review of the available information concluded that there may be a link between amoxicillin-containing products and the risk of aseptic meningitis."},{"field_id":2494,"order_no":5,"bullet":"Health Canada will work with the manufacturers to update the Canadian Product Monographs (CPMs) for amoxicillin-containing products that do not already contain this safety information. The Department will also inform healthcare professionals and patients about this risk and changes to the CPMs."}],"footnotes_list":[{"field_id":2498,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2495,"order_no":1,"bullet":"Amoxicillin-containing products are antibiotics authorized for sale in Canada to treat or prevent certain bacterial infections."},{"field_id":2495,"order_no":2,"bullet":"Amoxicillin-containing products have been marketed in Canada since 1974 under various brand names. Generic versions of amoxicillin alone, in combination with clavulanic acid, or as part of a kit containing amoxicillin, clarithromycin and lansoprazole, are also available. The amoxicillin-containing products come in different dosage forms including tablets, capsules, oral suspensions, or granules for oral suspensions."},{"field_id":2495,"order_no":3,"bullet":"There were about 7.2 million prescriptions filled annually in Canada for these products between 2016-2020. Of these, about 2 million prescriptions per year were filled for children less than 18 years of age."}],"finding_list":[{"field_id":2496,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, and published literature."},{"field_id":2496,"order_no":2,"bullet":"Health Canada reviewed 21 cases (3 Canadian, 18 international) of aseptic meningitis in patients receiving amoxicillin-containing products, of which 20 were from the scientific literature and 1 (Canadian) was obtained from the Canada Vigilance database. All cases were reported in adults."},{"field_id":2496,"order_no":3,"bullet":"Of the 21 case reports, 7 cases (1 Canadian) were found to be probably linked and 14 cases (2 Canadian) were possibly linked with the use of amoxicillin-containing products.\nHealth Canada reviewed the risks of serious heart-related problems and cancer with the use of Xeljanz/Xeljanz XR.
Health Canada started this safety review after the manufacturer advised of a clinical research study showing an increased risk of serious heart-related problems and cancer (lymphoma and lung cancer). This clinical research study looked at the long-term safety of Xeljanz/Xeljanz XR in patients suffering from rheumatoid arthritis, an immune system disease that causes damage and inflammation of joints, who were 50 years of age or older with at least 1 additional cardiovascular risk factor.1
","use_canada":2517,"findings":2518,"conclusion":2519,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Xeljanz/Xeljanz XR both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2520,"footnotes":0,"title":"Summary Safety Review - Xeljanz/Xeljanz XR (tofacitinib) - Assessing the Potential Risks of Serious Heart-related Problems and Cancer","created_date":"2022-01-12","modified_date":null,"key_message_list":[{"field_id":2516,"order_no":1,"bullet":"Xeljanz/Xeljanz XR (tofacitinib) is authorized for sale in Canada for the treatment of inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis, when other medicines do not work."},{"field_id":2516,"order_no":2,"bullet":"Health Canada reviewed the risks of serious heart-related problems (heart attack, stroke or cardiovascular death) and cancer (malignancies) with the use of Xeljanz/Xeljanz XR after a clinical research study showed an increase in these risks."},{"field_id":2516,"order_no":3,"bullet":"At the time of the review, the Canadian Product Monograph (CPM) for Xeljanz/Xeljanz XR included warnings and precautions for cancer and information on heart attacks. The purpose of this review was to assess whether additional warnings or other actions were required in Canada."},{"field_id":2516,"order_no":4,"bullet":"Health Canada's review of information from the clinical research study found a link between the use of Xeljanz/Xeljanz XR and the risks of serious heart-related problems and cancer. These risks were increased especially in older patients, in patients who are current or past smokers, and in patients with cardiovascular or cancer risk factors."},{"field_id":2516,"order_no":5,"bullet":"Health Canada has worked with the manufacturer to update the CPM to highlight the risks of serious heart-related problems and cancer, including a warning statement about the use of Xeljanz/Xeljanz XR in specific populations."},{"field_id":2516,"order_no":6,"bullet":"Health Canada will also communicate important safety information with the use of Xeljanz/Xeljanz XR to healthcare professionals and the public through a Health Product Risk Communication and a Public Advisory."},{"field_id":2516,"order_no":7,"bullet":"Based on findings from the clinical research study with Xeljanz/Xeljanz XR, Health Canada is reviewing the risks of serious heart-related problems, cancer, and blood clots (thrombosis) with 2 other drugs in the same drug class as Xeljanz/Xeljanz XR. Health Canada will inform the public of any new safety findings, as needed, once the review is completed."}],"footnotes_list":[],"reference_list":[{"field_id":2520,"order_no":1,"bullet":"Health Canada Public Communication: Health Canada has initiated a safety review on Xeljanz and Xeljanz XR (tofacitinib), used to treat arthritis and ulcerative colitis. Posting date: April 6, 2021."}],"use_canada_list":[{"field_id":2517,"order_no":1,"bullet":"Xeljanz and Xeljanz XR are prescription drugs authorized for sale in Canada to treat rheumatoid arthritis when other medicines do not work. Xeljanz is also authorized to treat psoriatic arthritis, an inflammation of the joints with red scaly patches on the skin, or ulcerative colitis, a large intestine inflammation causing sores and bleeding, when other medicines do not work."},{"field_id":2517,"order_no":2,"bullet":"Xeljanz has been marketed in Canada since 2014 and is currently available as 5 mg and 10 mg tablets. Xeljanz XR has been marketed in Canada since 2018 and is currently available as 11 mg extended-release tablets."},{"field_id":2517,"order_no":3,"bullet":"The number of prescriptions filled has been increasing from about 11,000 to 65,000 in Canadian retail pharmacies between 2016 and 2020."}],"finding_list":[{"field_id":2518,"order_no":1,"bullet":"Health Canada reviewed the clinical research study findings."},{"field_id":2518,"order_no":2,"bullet":"This study compared Xeljanz/Xeljanz XR with another type of drug used to treat arthritis called tumor necrosis factor inhibitors in patients with rheumatoid arthritis, who were 50 years of age or older with at least 1 additional cardiovascular risk factor."},{"field_id":2518,"order_no":3,"bullet":"The study found an increased risk of serious heart-related problems and cancer in patients treated with Xeljanz/Xeljanz XR. This information established a link between the use of Xeljanz/Xeljanz XR and these risks. Serious heart-related problems and cancer were increased especially in older patients, in patients who are current or past smokers, and in patients with cardiovascular or cancer risk factors."}],"conclusion_list":[{"field_id":2519,"order_no":1,"bullet":"Health Canada's review of the clinical research study found a link between the use of Xeljanz/Xeljanz XR and the risks of serious heart-related problems and cancer."},{"field_id":2519,"order_no":2,"bullet":"Health Canada has worked with the manufacturer to update the CPM to highlight the risks of serious heart-related problems and cancer, including a warning statement about the use of Xeljanz/Xeljanz XR in older patients, patients who are current or past smokers, and patients with cardiovascular or cancer risk factors."},{"field_id":2519,"order_no":3,"bullet":"Health Canada will also communicate important safety information with the use of Xeljanz/Xeljanz XR to healthcare professionals and the public through a Health Product Risk Communication and a Public Advisory."},{"field_id":2519,"order_no":4,"bullet":"Based on findings from the clinical research study with Xeljanz/Xeljanz XR, Health Canada is reviewing the risks of serious heart-related problems, cancer, and thrombosis with 2 other drugs in the same drug class as Xeljanz/Xeljanz XR. Health Canada will inform the public of any new safety findings, as needed, once the review is completed."},{"field_id":2519,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving Xeljanz/Xeljanz XR, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00279","review_date":null,"drug_name":"Esophageal Stents","safety_issue":"Bilateral vocal cord paralysis, a rare, but serious, medical condition which occurs when the nerve impulses to the vocal cords are disrupted resulting in issues with speaking, breathing and swallowing.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2526,"overview":"Health Canada reviewed the potential risk of bilateral vocal cord paralysis with esophageal stents. This review was triggered by published case reports describing the development of this serious medical condition following esophageal stent placement.
Bilateral vocal cord paralysis is a rare, but serious, medical condition that can affect speaking, breathing and swallowing. Breathing problems can be life-threatening, and other complications may include choking on, or inhaling food or liquid into the airways.
","use_canada":2527,"findings":2528,"conclusion":2529,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of esophageal stents both in Canada and internationally.
For additional information, contact the Medical Devices Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Esophageal Stents - Assessing the Potential Risk of Bilateral Vocal Cord Paralysis","created_date":"2022-01-13","modified_date":null,"key_message_list":[{"field_id":2526,"order_no":1,"bullet":"Esophageal stents are medical devices placed in the esophagus to keep open an area that has become narrow due to cancer or scarring, or to seal off leaks in the esophagus. The metal or plastic hollow tubes allow food and liquids to pass from the mouth to the stomach."},{"field_id":2526,"order_no":2,"bullet":"Health Canada reviewed the risk of bilateral vocal cord paralysis with esophageal stents. This safety review was triggered by published case reports suggesting a possible link between the use of esophageal stents and this rare condition."},{"field_id":2526,"order_no":3,"bullet":"Health Canada's review of the available information did not establish a link between the use of esophageal stents and the risk of bilateral vocal cord paralysis."},{"field_id":2526,"order_no":4,"bullet":"Health Canada will continue to monitor the safety of esophageal stents."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":2527,"order_no":1,"bullet":"Esophageal stents are medical devices authorized for sale in Canada that help allow for the proper passage of food and drink from the mouth to the stomach, through the esophagus. They are metal or plastic hollow tubes placed inside the esophagus to widen areas that have become narrow due to cancer or scarring, or to seal off leaks in the esophagus. Esophageal stents may only be implanted by a physician."},{"field_id":2527,"order_no":2,"bullet":"Esophageal stents have been marketed in Canada since 1998 under various brand names."}],"finding_list":[{"field_id":2528,"order_no":1,"bullet":"Health Canada reviewed information from the Canadian incident reporting database, and medical and scientific literature."},{"field_id":2528,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of bilateral vocal cord paralysis related to esophageal stent placement."},{"field_id":2528,"order_no":3,"bullet":"Health Canada reviewed 7 articles from the published scientific literature. The literature reviewed could not conclude whether esophageal stents was associated with bilateral vocal cord paralysis, since this rare condition can also occur as a result of disease progression or as a consequence of other medical conditions that require stent placement."}],"conclusion_list":[{"field_id":2529,"order_no":1,"bullet":"Health Canada's review of the available information did not establish a link between the use of esophageal stents and the risk of bilateral vocal cord paralysis."},{"field_id":2529,"order_no":2,"bullet":"Health Canada encourages healthcare professionals to report any side effects related to the use of esophageal stents."},{"field_id":2529,"order_no":3,"bullet":"Health Canada will continue to monitor safety information involving esophageal stents, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00280","review_date":null,"drug_name":"Airvo 2 Humidifier","safety_issue":"Breathing problems because of undetected, accidental disconnection of Airvo 2 from the patient.","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2534,"overview":"Health Canada has received incident reports about the accidental disconnection of the Airvo 2 Humidifier nasal cannula from patients.
\nHealth Canada reviewed the potential risk of breathing problems associated with the undetected, accidental disconnection of the cannula from patients, and the lack of an alarm to warn of the incident. The purpose of the review was to assess whether additional actions were required for this device.
","use_canada":2535,"findings":2536,"conclusion":2537,"additional":"The analysis that contributed to this safety review included Canadian incident reports and the instructions for use provided by the manufacturer.
\nFor additional information, contact the Medical Devices Directorate.
","full_review":"","references":0,"footnotes":0,"title":"Summary Safety Review - Airvo 2 Humidifier - Assessing the Potential Risk of Breathing Problems Associated with Undetected, Accidental Disconnection of Nasal Cannula","created_date":"2022-01-25","modified_date":null,"key_message_list":[{"field_id":2534,"order_no":1,"bullet":"The Airvo 2 is a medical device that delivers high flow warmed and humidified breathing gases to patients. It is authorized to be used in hospitals and long-term care facilities to provide patients who can breathe on their own with extra help."},{"field_id":2534,"order_no":2,"bullet":"Health Canada reviewed the risk of breathing problems associated with the Airvo 2 Humidifier when there is an undetected, accidental disconnection of the tube in the patient's nose (nasal cannula)."},{"field_id":2534,"order_no":3,"bullet":"This review was triggered by a fatal Canadian incident report describing an undetected nasal cannula disconnection. The purpose of the review was to assess whether the current labelling and directions for use are appropriate and if additional actions are required."},{"field_id":2534,"order_no":4,"bullet":"Health Canada's review of the available information concluded that the design of the Airvo 2 Humidifier is appropriate for its use, and its instructions for use are clear. This product is not intended for life support and patient monitoring should be performed at all times."},{"field_id":2534,"order_no":5,"bullet":"Health Canada will continue to monitor the safety of the Airvo 2 Humidifier."}],"footnotes_list":[],"reference_list":[],"use_canada_list":[{"field_id":2535,"order_no":1,"bullet":"The Airvo 2 Series Humidifier is a medical device that has been authorized in Canada since 2012."},{"field_id":2535,"order_no":2,"bullet":"The Airvo 2 Humidifier delivers warmed and humidified respiratory gases (air and oxygen) to the nose of the patient who can breathe on their own. It is used to help the patient breathe more easily. The Airvo 2 delivers gases to the patient's nose through a tube that has 2 prongs held in place by a strap that goes around the patient's head."}],"finding_list":[{"field_id":2536,"order_no":1,"bullet":"Health Canada reviewed information from incident reports and documentation provided by the manufacturer."},{"field_id":2536,"order_no":2,"bullet":"At the time of the review, Health Canada had received 9 incident reports (all Canadian) related to the Airvo 2 Humidifier, including 1 where the patient had died. The fatal incident involved an undetected disconnection of the cannula where no alarm sounded. Three reports mentioned the lack of an audible alarm due to a faulty speaker and electrical resistance, and 1 reported the alarm was inadequate without further information. The remaining 4 reports did not involve any aspect of the alarm system."},{"field_id":2536,"order_no":3,"bullet":"Health Canada’s review concluded that the user and technical manuals for the Airvo 2 Humidifier provide appropriate directions for use and information about alarms:\nHealth Canada reviewed the potential risk of hypoglycemia with methadone use. This safety review was triggered by a published case in the US suggesting that patients using methadone could experience hypoglycemia.
Hypoglycemia is a condition in which your blood sugar level is lower than normal. Signs and symptoms of hypoglycemia may include shakiness, sweating and irritability. As hypoglycemia gets worse, symptoms may include confusion and loss of consciousness.
","use_canada":2543,"findings":2544,"conclusion":2545,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international adverse reaction reports, and what is known about the use of methadone both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2546,"footnotes":2547,"title":"Summary Safety Review - Methadone - Assessing the Potential Risk of Hypoglycemia","created_date":"2022-02-09","modified_date":null,"key_message_list":[{"field_id":2542,"order_no":1,"bullet":"Methadone is authorized in Canada for the relief of severe pain in patients who have previously used opioids, or as substitution treatment in patients with opioid dependence."},{"field_id":2542,"order_no":2,"bullet":"Health Canada reviewed the potential risk of hypoglycemia (low blood sugar) with methadone use after becoming aware of a published case1 in the United States (US) concerning this risk."},{"field_id":2542,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between methadone use and the risk of hypoglycemia."},{"field_id":2542,"order_no":4,"bullet":"Health Canada will be working with the manufacturers to update the Canadian product safety information (Canadian product monograph) for methadone to include the risk of hypoglycemia."}],"footnotes_list":[{"field_id":2547,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database"},{"field_id":2547,"order_no":2,"bullet":"World Health Organization's Adverse Drug Reaction Database"}],"reference_list":[{"field_id":2546,"order_no":1,"bullet":"Otalora Y, Inkollu S, Ursu S. Methadone induced hypoglycemia, improved on dose adjustment. J Clin Transl Endocrinol Case Rep. 2020;18(100071):100071."}],"use_canada_list":[{"field_id":2543,"order_no":1,"bullet":"Methadone is authorized in Canada for the relief of severe pain in patients who have previously used opioids, or for use in opioid dependent patients requiring substitution treatment to prevent side effects when patients stop using other opioids (opioid withdrawal symptoms)."},{"field_id":2543,"order_no":2,"bullet":"Methadone has been available in Canada since the 1960s."},{"field_id":2543,"order_no":3,"bullet":"Methadose (10 mg/mL oral concentrate), Metadol-D (1, 5, 10, 25 mg tablets, 1 mg/mL oral solution, and 10 mg/mL oral concentrate), Sandoz Methadone (10 mg/mL oral concentrate), Jamp Methadone Oral Concentrate (10 mg/mL oral concentrate), and Odan-Methadone (10 mg/mL oral concentrate) are authorized for sale in Canada for opioid substitution treatment in patients with opioid dependence. Methadone powder is also available to pharmacists to make methadone solutions. After being mixed with a flavoured liquid, these products are dispensed to patients and taken orally."},{"field_id":2543,"order_no":4,"bullet":"Metadol (1, 5, 10, 25 mg tablets, 1 mg/mL oral solution, and 10 mg/mL oral concentrate) and pms-Methadone (1, 5, 10, 25 mg tablets) are authorized for sale in Canada for the relief of severe pain, generally in adults who have previously used opioids."},{"field_id":2543,"order_no":5,"bullet":"There were about 12 million prescriptions for methadone filled in Canada in 2020."}],"finding_list":[{"field_id":2544,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, the World Health Organization's Adverse Drug Reaction Databaseb, and the published literature."},{"field_id":2544,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of hypoglycemia related to methadone use."},{"field_id":2544,"order_no":3,"bullet":"This safety review looked at 19 international cases of hypoglycemia in adults after methadone use, many of which included incomplete information or described patients who were taking other medications or suffering from medical conditions (kidney disease and/or diabetes) that may contribute to hypoglycemia."},{"field_id":2544,"order_no":4,"bullet":"Despite these limitations, Health Canada found sufficient evidence to determine a probable link between methadone use and the risk of hypoglycemia in 3 cases and a possible link in 9 cases. An additional 2 cases were unlikely to be linked with methadone use, while the remaining 5 cases did not have enough information to be further assessed.In 2019, the CSACI published a position statement1 recommending the use of newer-generation antihistamines for the treatment of hay fever (allergic rhinitis) and hives (urticaria) because of the side effects associated with first-generation antihistamines.
The statement did not identify new safety information for first-generation antihistamines, however, it generated interest from the Canadian public about the safety of DCPs at recommended or higher doses, specifically in children.
Diphenhydramine has the potential for problematic use and overdose that can lead to serious side effects in children, including seeing and hearing things that are not there (hallucinations), sudden change in the brain's normal electrical activity (seizures), palpitations, difficulty in breathing and coma.
The use of DCPs to treat allergic symptoms is widespread, particularly in children. As a precaution, Health Canada assessed known and potential serious side effects associated with the use of DCPs in children under 2 years of age, and serious side effects related to problematic use and accidental overdose in children under 18 years of age. The purpose of the review was to determine if there was a change in the type and/or frequency of side effects associated with the use of DCPs in these vulnerable populations.
","use_canada":2555,"findings":2556,"conclusion":2557,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of diphenhydramine-containing drugs both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2558,"footnotes":2559,"title":"Summary Safety Review - Oral, Over-the-counter Diphenhydramine - Containing Products - Assessing the Potential Risk of Serious Side Effects in Children","created_date":"2022-03-01","modified_date":null,"key_message_list":[{"field_id":2554,"order_no":1,"bullet":"Most diphenhydramine-containing products (DCPs) are authorized for sale in Canada as over-the-counter (OTC) drugs to relieve symptoms of several medical conditions, including allergies. They belong to a group of drug products known as first-generation antihistamines."},{"field_id":2554,"order_no":2,"bullet":"In 2019, the Canadian Society of Allergy and Clinical Immunology (CSACI) published a position statement1 recommending the use of newer-generation antihistamines for the treatment of hay fever (allergic rhinitis) and hives (urticaria) because of the side effects associated with first-generation antihistamines. The CSACI statement generated interest from the Canadian public about the safety of DCPs at both the recommended and higher doses, specifically in children."},{"field_id":2554,"order_no":3,"bullet":"Therefore, as a precaution, Health Canada reviewed known and potential serious side effects with the oral use of DCPs in children under 2 years of age, and from accidental overdose or problematic use in children under 18 years of age. The purpose of the review was to assess whether the types and/or frequencies of risks associated with the authorized use of DCPs continue to be accurately and clearly communicated to consumers and healthcare professionals."},{"field_id":2554,"order_no":4,"bullet":"Health Canada's review of the available information found no change in the type or frequency of serious side effects associated with the use of DCPs to warrant regulatory action at this time."},{"field_id":2554,"order_no":5,"bullet":"Health Canada will publish a Health Product InfoWatch article to increase awareness of the potential for rare serious risks associated with the use of these products in children, and to encourage continued reporting of side effects of DCPs to Health Canada. The Department will revisit this topic in 1 year to determine if there is any new information that warrants further assessment and action by Health Canada."},{"field_id":2554,"order_no":6,"bullet":"Health Canada continues to work with domestic and international partners to ensure alignment and consistency in communicating risks related to DCPs to consumers and healthcare professionals."}],"footnotes_list":[{"field_id":2559,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance adverse reaction online database"}],"reference_list":[{"field_id":2558,"order_no":1,"bullet":"Fein, M.N., Fischer, D.A., O'Keefe, A.W. et al. CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol"}],"use_canada_list":[{"field_id":2555,"order_no":1,"bullet":"Oral DCPs are authorized for sale in Canada to treat the symptoms of allergies, temporarily relieve dry cough, sneezing and runny nose due to the common cold, or as nighttime sleep aids. These products are available for use in children and adults."},{"field_id":2555,"order_no":2,"bullet":"There are 83 marketed, OTC, oral DCPs in Canada as of February 8, 2022."},{"field_id":2555,"order_no":3,"bullet":"Oral DCPs have been marketed in Canada since 1946. They are available as capsules, caplets, tablets, chewable tablets, and liquid formulations (solution, elixir, syrup)."}],"finding_list":[{"field_id":2556,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, published literature, and the manufacturer."},{"field_id":2556,"order_no":2,"bullet":"Health Canada reviewed 52 Canadian case reports involving diphenhydramine use in children, received between December 1983 and March 2019; none were fatal. Of the 52 cases, only 5 contained enough information to determine whether there was a link between the use of diphenhydramine and the reported serious side effects in children:This safety review on BIA-ALCL is an update to the 20171 and 20192 safety reviews on this topic. The 2019 safety review found an increased risk of BIA-ALCL with the use of macro-textured breast implants. As a result, Health Canada suspended the medical device licences of Biocell macro-textured breast implants, which were the only macro-textured breast implants available in Canada at that time.
\nSince the publication of the 2019 safety review, there has been an increase in the number of BIA-ALCL cases reported to Health Canada and internationally. New information has also been published in the scientific literature and by international regulatory agencies. The purpose of this update was to consider new information and determine if additional measures are needed to help mitigate the risk of BIA-ALCL. Even though macro-textured breast implants have not been available in Canada since May 2019, they remain implanted in some people.
\nBIA-ALCL is a serious but rare type of non-Hodgkin lymphoma, a cancer that affects the immune system, that may develop many months or years after a breast implant procedure. It is not a cancer of the breast tissue. BIA-ALCL usually, but not necessarily, presents as an accumulation of fluid between the implant and the surrounding tissue. It can also present as a lump or a mass. The cause of BIA-ALCL is not fully understood.
","use_canada":2567,"findings":2568,"conclusion":2569,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international medical device incident reports, and what is known about the use of these medical devices both in Canada and internationally.
\nFor additional information about Health Canada's assessment, contact the Medical Devices Directorate.
","full_review":"","references":2570,"footnotes":0,"title":"Summary Safety Review - Breast Implants - Assessing the Potential Risk of Breast Implant-Associated Anaplastic Large Cell Lymphoma","created_date":"2022-04-06","modified_date":null,"key_message_list":[{"field_id":2566,"order_no":1,"bullet":"Health Canada completed safety reviews in 20171 and 20192 on Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a rare but serious cancer of the immune system linked with breast implants. This updated review was performed as part of Health Canada’s commitment to monitor for newly reported Canadian cases of BIA-ALCL."},{"field_id":2566,"order_no":2,"bullet":"The updated review found that the estimated risk of BIA-ALCL continues to vary according to surface texture of the breast implant:\nHealth Canada reviewed the potential risk of DRESS with the use of valacyclovir-containing products. This safety review was triggered by updates made by the European Medicines Agency to the product safety information for valacyclovir-containing products to include the risk of DRESS.
\nDRESS is a rare, but serious, and potentially life-threatening drug reaction that includes fever, severe skin rash or peeling of the skin over large areas of the body, swollen face and high white blood cell count, affecting 1 or more organs. The symptoms of DRESS typically appear within 2 weeks to 2 months after starting a medication.
\nDRESS is also known as drug rash with eosinophilia and systemic symptoms, drug induced hypersensitivity syndrome or DRESS syndrome.
","use_canada":2577,"findings":2578,"conclusion":2579,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of valacyclovir both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2580,"footnotes":2581,"title":"Summary Safety Review - Valacyclovir-containing Products - Assessing the Potential Risk of Drug Reaction with Eosinophilia and Systemic Symptoms","created_date":"2022-05-24","modified_date":null,"key_message_list":[{"field_id":2576,"order_no":1,"bullet":"Valacyclovir is authorized for sale in Canada to treat cold sores (herpes labialis) and shingles (herpes zoster) and to treat, suppress or reduce the transmission of genital herpes."},{"field_id":2576,"order_no":2,"bullet":"Health Canada reviewed the potential risk of DRESS with the use of valacyclovir-containing products. The safety review was triggered by a labelling update for valacyclovir-containing products related to this risk in Europe."},{"field_id":2576,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of valacyclovir-containing products and the potential risk of DRESS."},{"field_id":2576,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the Canadian product safety information for valacyclovir-containing products to include the risk of DRESS."}],"footnotes_list":[{"field_id":2581,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2580,"order_no":1,"bullet":"Ingen-Housz-Oro S, Bernier C, Gener G, Fichel F, Barbaud A, Lebrun-Vignes B and Assier H (2019) Valaciclovir: a culprit drug for drug reaction with eosinophilia and systemic symptoms not to be neglected. Three cases. Br. J. Dermatol. 180 (3): 666-667."}],"use_canada_list":[{"field_id":2577,"order_no":1,"bullet":"Valacyclovir is a prescription antiviral drug authorized in Canada to treat herpes infections, such as cold sores (herpes labialis) and shingles (herpes zoster). It is also used to treat, suppress or reduce the transmission of genital herpes."},{"field_id":2577,"order_no":2,"bullet":"Valacyclovir has been marketed in Canada since 1996. It is currently available as 500 mg and 1,000 mg tablets, under the brand name Valtrex, or as generics."},{"field_id":2577,"order_no":3,"bullet":"More than 2 million prescriptions were dispensed annually by Canadian retail pharmacies between 2017-2021. Valacyclovir can also be used in the hospital setting."}],"finding_list":[{"field_id":2578,"order_no":1,"bullet":"Health Canada reviewed information provided by the manufacturer of the brand name product, and from searches of the Canada Vigilance databasea and the published literature."},{"field_id":2578,"order_no":2,"bullet":"Health Canada reviewed 115 cases (3 Canadian, 112 international) of DRESS in patients taking valacyclovir. Of the 115 cases, 26 (international) met the criteria for further assessment to determine if there was a link between the use of valacyclovir and DRESS."},{"field_id":2578,"order_no":3,"bullet":"Of the 26 case reports, 4 cases, including 3 published in the scientific literature1, were found to be probably linked to the use of valacyclovir. Twenty-one cases, including 1 death, were found to be possibly linked, and 1 case was unlikely to be linked to the use of valacyclovir. In 25 of the 26 cases, patients were also taking other medications known to cause DRESS."}],"conclusion_list":[{"field_id":2579,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of valacyclovir-containing products and the potential risk of DRESS."},{"field_id":2579,"order_no":2,"bullet":"Health Canada will work with the manufacturers to update the Canadian product safety information for valacyclovir-containing products to include the risk of DRESS."},{"field_id":2579,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of valacyclovir and other health products to the Canada Vigilance Program."},{"field_id":2579,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving valacyclovir-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00285","review_date":null,"drug_name":"Cholinesterase inhibitors (donepezil-, rivastigmine- and galantamine-containing products)","safety_issue":"Serious abnormal heart rhythm caused by abnormal electrical activity in the lower chambers of the heart (QT interval prolongation and torsade de pointes).","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2588,"overview":"Health Canada reviewed the risk of QT interval prolongation and torsade de pointes with the use of cholinesterase inhibitors. This safety review was initiated when Health Canada learned that the EMA had updated the product safety information related to this risk for 2 cholinesterase inhibitors (donepezil and galantamine).
\nAt the time of review, the CPM for cholinesterase inhibitors included differing information about QT interval prolongation and/or torsade de pointes. The purpose of this review was to assess whether additional warnings or other actions for QT interval prolongation and torsade de pointes were required in Canada.
","use_canada":2589,"findings":2590,"conclusion":2591,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of cholinesterase inhibitors both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2592,"title":"Summary Safety Review - Cholinesterase Inhibitors (donepezil-, rivastigmine- and galantamine-containing products) - Assessing the Potential Risk of QT Interval Prolongation and Torsade de Pointes","created_date":"2022-07-19","modified_date":null,"key_message_list":[{"field_id":2588,"order_no":1,"bullet":"Cholinesterase inhibitors (donepezil-, rivastigmine- and galantamine-containing products) are authorized for sale in Canada to treat dementia (memory loss and mental changes) associated with Alzheimer's disease and/or Parkinson’s disease."},{"field_id":2588,"order_no":2,"bullet":"Health Canada reviewed the risk of QT interval prolongation and torsade de pointes associated with the use of cholinesterase inhibitors. This safety review was triggered by updates made to the product safety information for 2 cholinesterase inhibitors (donepezil and galantamine) by the European Medicines Agency (EMA). "},{"field_id":2588,"order_no":3,"bullet":"At the time of the review, the Canadian product safety information (Canadian product monograph [CPM]) for cholinesterase inhibitors included differing information about QT interval prolongation and/or torsade de pointes. The purpose of this review was to assess whether any actions were required in Canada."},{"field_id":2588,"order_no":4,"bullet":"Health Canada’s review of available information supported a link between the use of all 3 cholinesterase inhibitors and the risk of QT interval prolongation and torsade de pointes. This risk is increased in patients with a history of certain heart conditions; a history or family history of QT interval prolongation; low levels of certain electrolytes, such as magnesium, potassium or calcium in the blood; or taking certain medications that can affect heart rhythm at the same time as the cholinesterase inhibitors."},{"field_id":2588,"order_no":5,"bullet":"Health Canada will work with the manufacturers of all cholinesterase inhibitors to strengthen the information in the CPM about the risk of QT interval prolongation and torsade de pointes. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication."}],"footnotes_list":[{"field_id":2592,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2589,"order_no":1,"bullet":"Cholinesterase inhibitors are prescription drugs authorized for sale in Canada to treat dementia (memory loss and mental changes) associated with Alzheimer's disease and/or Parkinson’s disease."},{"field_id":2589,"order_no":2,"bullet":"Cholinesterase inhibitors have been marketed in Canada since 1997 under different brand names. Generic versions of all 3 cholinesterase inhibitors are also available. Cholinesterase inhibitors are currently available in various dosage forms, including patches, tablets (including rapidly disintegrating), capsules (including extended-release), and oral solution."},{"field_id":2589,"order_no":3,"bullet":"Cholinesterase inhibitors are widely used in Canada. About 3 million prescriptions were dispensed annually by Canadian retail pharmacies between 2016 and 2020, with donepezil being the most frequently dispensed, followed by galantamine and then rivastigmine."}],"finding_list":[{"field_id":2590,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases and published literature."},{"field_id":2590,"order_no":2,"bullet":"Health Canada reviewed 53 case reports (1 Canadian, 52 international) of QT interval prolongation and torsade de pointes in patients taking cholinesterase inhibitors. Of the 53 reports, 35 were for donepezil, 10 (1 Canadian) for galantamine, and 8 for rivastigmine.\nHealth Canada reviewed the potential risk of TMA with the use of Nexavar. This safety review was triggered by a U.S. Food and Drug Administration update to the product safety information for Nexavar to include the risk of TMA, as well as international case reports published in the medical literature.
Thrombotic microangiopathy is a group of rare, but serious and life-threatening conditions, involving the formation of clots in the small blood vessels. These clots can cause damage to organs and body systems by blocking proper blood flow. Thrombotic microangiopathy is a medical emergency and requires rapid intervention. A number of factors, including congenital conditions (those present at birth), infection, cancer and drugs, can cause TMA.
","use_canada":2599,"findings":2600,"conclusion":2601,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of Nexavar both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2602,"footnotes":2603,"title":"Summary Safety Review - Nexavar (sorafenib) - Assessing the Potential Risk of Thrombotic Microangiopathy","created_date":"2022-08-11","modified_date":null,"key_message_list":[{"field_id":2598,"order_no":1,"bullet":"Nexavar (sorafenib) is a prescription drug authorized for sale in Canada to treat advanced forms of liver, kidney and thyroid cancers."},{"field_id":2598,"order_no":2,"bullet":"Health Canada reviewed the potential risk of TMA with the use of Nexavar. The safety review was triggered by a labelling update in the United States (U.S.) and international case reports published in the medical literature."},{"field_id":2598,"order_no":3,"bullet":"Health Canada's review concluded that there may be a link between the use of Nexavar and the risk of TMA."},{"field_id":2598,"order_no":4,"bullet":"Health Canada will work with the manufacturer to update the Canadian product safety information (Canadian product monograph [CPM]) for Nexavar to include the risk of TMA."}],"footnotes_list":[{"field_id":2603,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2602,"order_no":1,"bullet":"Ajmal M.S., Balasubramanyam S., Tran C., Yan J., Dhingra S., & Mandayam, S. A case series of secondary thrombotic microangiopathy. American Journal of Kidney Diseases. Conference: NKF 2019 Spring Clinical Meetings Abstracts. Boston United States, 73(5), 647-648."},{"field_id":2602,"order_no":2,"bullet":"Hanna, R.M., Selamet, U., Hasnain, H., El-Masry, M., Saab, S., Wallace, W. D., Yanny,B. Wilson, J. Development of focal segmental glomerulosclerosis and thrombotic microangiopathy in a liver transplant patient on sorafenib for hepatocellular carcinoma: A case report. (2018). Transplantation Proceedings, 50(10), 4033-4037."},{"field_id":2602,"order_no":3,"bullet":"Nissaisorakarn V, Srisung W, Salvatore S, Srivatan V. Combined tacrolimus and sorafenib associated thrombotic microangiopathy [abstract]. Am Soc Nephrol 2017. Abstract: PUB484"},{"field_id":2602,"order_no":4,"bullet":"Overkleeft E.N.M., Goldschmeding R., van Reekum F., et al. Nephrotic syndrome caused by the angiogenesis inhibitor sorafenib. Annal Oncol 2010; 21:184-185."},{"field_id":2602,"order_no":5,"bullet":"Usui J., Glezerman I.G. Salvatore S.P., et al. Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature. Hum Pathol 2014;45:1918-1927."},{"field_id":2602,"order_no":6,"bullet":"Yilmaz S., Özçakar Z.B., Taktak A., et al. Anti-VEGF-related thrombotic microangiopathy in a child presenting with nephrotic syndrome.Pediatr Nephrol 2016; 31:1029-1032."}],"use_canada_list":[{"field_id":2599,"order_no":1,"bullet":"Nexavar is a prescription drug authorized in Canada for the treatment of liver cancer (hepatocellular carcinoma) that cannot be treated by surgery, late-stage kidney cancer (renal cell carcinoma) and late-stage thyroid cancer (thyroid carcinoma)."},{"field_id":2599,"order_no":2,"bullet":"Nexavar has been marketed in Canada since 2006. It is currently available as 200 mg tablets."},{"field_id":2599,"order_no":3,"bullet":"The yearly number of prescriptions dispensed by Canadian retail pharmacies for Nexavar decreased from approximately 1,700 prescriptions in 2016 to approximately 700 prescriptions in 2021."}],"finding_list":[{"field_id":2600,"order_no":1,"bullet":"Health Canada reviewed information provided by the manufacturer, and information resulting from searches of the Canada Vigilance databasea and the published literature."},{"field_id":2600,"order_no":2,"bullet":"Health Canada reviewed 28 cases (1 Canadian, 27 international) of TMA in patients taking Nexavar. Of the 28 cases, 12 (all international) met the criteria for further assessment to determine if there was a link between the use of Nexavar and TMA."},{"field_id":2600,"order_no":3,"bullet":"All 12 cases, including 6 published in the scientific literature1-6, were found to be possibly linked to the use of Nexavar. Three deaths were reported (2 of which were assessed as having a possible link to Nexavar and 1 unlikely to be linked)."},{"field_id":2600,"order_no":4,"bullet":"There were no Canadian cases of TMA found to be linked to the use of Nexavar."}],"conclusion_list":[{"field_id":2601,"order_no":1,"bullet":"Health Canada's review of the available information concluded that there may be a link between the use of Nexavar and the risk of TMA."},{"field_id":2601,"order_no":2,"bullet":"Health Canada will work with the manufacturer to update the CPM for Nexavar to include the risk of TMA."},{"field_id":2601,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Nexavar and other health products to the Canada Vigilance Program."},{"field_id":2601,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving Nexavar, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified."}]},{"template":2,"link_id":"SSR00287","review_date":null,"drug_name":"Xeljanz/Xeljanz XR (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib) - Janus Kinase (JAK) Inhibitors","safety_issue":"Serious heart-related problems (heart attack, stroke or cardiovascular death), blood clots (thrombosis), cancer (malignancies) and death (all-cause mortality)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2610,"overview":"Xeljanz/Xeljanz XR, Olumiant and Rinvoq belong to a class of drugs called JAK inhibitors that interfere with inflammation, immune response and growth factors in order to treat several diseases. These products have similar mechanisms of action and are authorized for the treatment of chronic inflammatory diseases.
Health Canada completed a safety review in 2019 that found a link between the use of Xeljanz/Xeljanz XR and the risk of blood clots, especially among patients at increased risk of thrombosis. The Department then completed a safety review in 2021 that found a link between the use of Xeljanz/Xeljanz XR and the risks of serious heart-related problems and cancer, especially among patients with rheumatoid arthritis who are older, current or past smokers, and those who have cardiovascular or cancer risk factors. Based on these findings, the CPM for Xeljanz/Xeljanz XR was updated with strengthened warnings about these risks in May 2022.
In 2022, Health Canada completed a review of the potential risks of serious heart-related problems, blood clots, cancer and death with the use of 2 JAK inhibitors indicated for inflammatory conditions (Olumiant and Rinvoq) to determine the need for labelling changes across the JAK inhibitors drug class. As part of this review, the Department also updated its 2019 review on the risk of blood clots with the use of Xeljanz/Xeljanz XR.
","use_canada":2611,"findings":2612,"conclusion":2613,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of Xeljanz/Xeljanz XR, Olumiant, and Rinvoq both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2614,"footnotes":2615,"title":"Summary Safety Review - Xeljanz/Xeljanz XR (tofacinitib), Olumiant (baricitinib) and Rinvoq (upadacitinib) - Janus Kinase (JAK) Inhibitors - Assessing the Potential Risks of Serious Heart-related Problems, Blood Clots, Cancer and Death","created_date":"2022-09-16","modified_date":null,"key_message_list":[{"field_id":2610,"order_no":1,"bullet":"Xeljanz/Xeljanz XR (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib) are prescription drugs belonging to the JAK inhibitors drug class. They are authorized for sale in Canada for the treatment of chronic inflammatory diseases when other medicines do not work."},{"field_id":2610,"order_no":2,"bullet":"Health Canada reviewed the potential risks of serious heart-related problems, blood clots, cancer and death with the use of Olumiant and Rinvoq. The Department also reviewed the risk of blood clots with the use of Xeljanz/Xeljanz XR as part of an update to its 2019 review of this product."},{"field_id":2610,"order_no":3,"bullet":"Health Canada's review of the available information found that the risks of serious heart-related problems, blood clots, cancer and death cannot be excluded for Olumiant and Rinvoq, and that there continues to be an increased risk of blood clots associated with the use of Xeljanz/Xeljanz XR."},{"field_id":2610,"order_no":4,"bullet":"As a precautionary measure, Health Canada is working with the manufacturers to update and align these risks in the Canadian product monographs (CPMs) for JAK inhibitors indicated for chronic inflammatory diseases. "},{"field_id":2610,"order_no":5,"bullet":"Health Canada will communicate these updates to healthcare professionals and the public through a Health Product Risk Communication and Public Advisory."},{"field_id":2610,"order_no":6,"bullet":"Health Canada is also working with the manufacturers to update and align the CPMs of other JAK inhibitors, for which the findings are relevant."}],"footnotes_list":[{"field_id":2615,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[{"field_id":2614,"order_no":1,"bullet":"Ytterberg, S. R., Bhatt, D. L., Mikuls, T. R., Koch, G. G., Fleischmann, R., Rivas, J. L., Germino, R., Menon, S., Sun, Y., Wang, C., Shapiro, A. B., Kanik, K. S., Connell, C. A., & ORAL Surveillance Investigators (2022). Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. The New England journal of medicine, 386(4), 316–326."}],"use_canada_list":[{"field_id":2611,"order_no":1,"bullet":"Xeljanz/Xeljanz XR, Olumiant and Rinvoq are prescription drugs authorized for sale in Canada for the treatment of chronic inflammatory diseases, when other medicines do not work.Health Canada has been evaluating the post-market safety and effectiveness of vaginal surgical mesh devices since 2009 in response to regulatory activities initiated by the U.S. Food and Drug Administration (FDA) at that time. In 2009, Health Canada completed a safety review evaluating the complications of vaginal surgical mesh devices for the repair of SUI and pelvic organ prolapse (POP). As a result of the review, Health Canada issued a Notice to Hospitals1 that discussed the complications associated with these devices for the treatment of SUI and POP.
Since 2012, Health Canada has completed post-market safety reviews2, 3 related to the use of vaginal surgical mesh devices, including, in 2014, a comprehensive assessment of the devices included in the current review. The risk mitigation activities resulting from these assessments include:
In 2022 and as a follow-up to previously completed reviews assessing various complications related to the use of SMUS and similar devices, Health Canada completed an assessment of the long-term (at or beyond 5 years) safety and effectiveness of SMUS for SUI in women. This assessment evaluated the risk of complications (infection, pain, bleeding, urinary dysfunction, erosion/migration of mesh, sexual dysfunction, nerve and/or muscle damage, damage to pelvic structures and surrounding tissues or organs, and a need for surgical correction).
","use_canada":2623,"findings":2624,"conclusion":2625,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international clinical guidelines, incident and regulatory information, as well as consultations with Canadian medical societies and women with lived and living experiences.
For additional information, contact the Medical Devices Directorate.
","full_review":"","references":2626,"footnotes":0,"title":"Summary Safety Review - Standard Synthetic Mid-urethral Sling - Assessing Long-term Safety and Effectiveness","created_date":"2022-11-14","modified_date":null,"key_message_list":[{"field_id":2622,"order_no":1,"bullet":"Standard synthetic mid-urethral slings are medical devices authorized for sale in Canada to treat stress urinary incontinence (SUI), which is the accidental leaking of urine on effort or exertion, or on sneezing or coughing, in women."},{"field_id":2622,"order_no":2,"bullet":"Health Canada reviewed the long-term (at or beyond 5 years) safety and effectiveness of SMUS used for the treatment of SUI."},{"field_id":2622,"order_no":3,"bullet":"This review is a follow-up to previously completed post-market safety reviews assessing various complications related to the use of SMUS and similar devices."},{"field_id":2622,"order_no":4,"bullet":"Health Canada's review of the available information concluded that there is no new (not previously known) or increased risk of complications associated with the long-term (at or beyond 5 years) use of SMUS, and the risk of developing chronic pain and/or mesh erosion is lower over the longer term (after 5 or more years)."},{"field_id":2622,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving synthetic vaginal surgical mesh devices to identify and assess potential new harms."}],"footnotes_list":[],"reference_list":[{"field_id":2626,"order_no":1,"bullet":"Health Professional Risk Communication - Surgical Mesh - Complications Associated with Transvaginal Implantation of Surgical Mesh for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse. Health Canada. Issued: 2010-02-05"},{"field_id":2626,"order_no":2,"bullet":"Summary Safety Review - Surgical mesh products made from non-absorbable synthetic (polypropylene) material that are used for the transvaginal repair of pelvic organ prolapse (POP). Health Canada. Issued: 2019-07-26"},{"field_id":2626,"order_no":3,"bullet":"Summary Safety Review - Single incision mini-sling (SIMS) made from non-absorbable synthetic material (polypropylene). Health Canada. Issued: 2020-09-18"},{"field_id":2626,"order_no":4,"bullet":"Health Professional Risk Communication - Surgical Mesh - Complications Associated with Transvaginal Implantation for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse - Notice to Hospitals. Health Canada. Issued: 2014-05-13"},{"field_id":2626,"order_no":5,"bullet":"Information Update - Information Regarding the Transvaginal Implantation of Surgical Mesh Devices for the Treatment of Pelvic Organ Prolapse and Stress Urinary Incontinence. Health Canada. Issued: 2014-05-13"},{"field_id":2626,"order_no":6,"bullet":"Information Update - Status of non-absorbable synthetic surgical mesh for the transvaginal repair of pelvic organ prolapse in Canada. Health Canada. Issued: 2019-07-26"},{"field_id":2626,"order_no":7,"bullet":"Vaginal surgical mesh. Health Canada"},{"field_id":2626,"order_no":8,"bullet":"Medical Devices incident reporting database. Health Canada"},{"field_id":2626,"order_no":9,"bullet":"MAUDE - Manufacturer and User Facility Device Experience. U.S. Food and Drug Administration"},{"field_id":2626,"order_no":10,"bullet":"SOGC statement in response to College des Médecins in Quebec’s report on urethral slings. The Society of Obstetricians and Gynaecologists of Canada (SOGC)"},{"field_id":2626,"order_no":11,"bullet":"Welk, B., Carlson, K. V., Baverstock, R. J., Steele, S. S., Bailly, G. G., & Hickling, D. R. (2017). Canadian Urological Association position statement on the use of transvaginal mesh. Canadian Urological Association Journal, 11(6S2), S105-7."},{"field_id":2626,"order_no":12,"bullet":"Walter, J.E., Brennand, E.A., Lemos, N., Cundiff, G.W. (2021). Letter: Canadian Society of Pelvic Medicine Response to the Collège des Médecins du Québec Rapport d'Enquête. Journal of Obstetrics and Gynaecology Canada, 43 (3), 298-299."}],"use_canada_list":[{"field_id":2623,"order_no":1,"bullet":"In Canada, SMUS are 1 option used to treat SUI in women and are Class III medical devices."},{"field_id":2623,"order_no":2,"bullet":"Standard synthetic mid-urethral slings are made primarily from non-absorbable synthetic materials (e.g., polypropylene) and are intended to be permanently implanted."},{"field_id":2623,"order_no":3,"bullet":"At the time of this safety review, there were 7 active medical device licences in Canada for SMUS for the treatment of SUI:Health Canada reviewed the evidence for the risks of tendonitis, tenosynovitis, and tendon rupture related to the use of third generation aromatase inhibitors to determine whether regulatory actions would be required in Canada. The safety review was triggered by a labelling update for letrozole, to include the risks of tendonitis and tendon rupture, in Europe. While the EMA's safety assessment was limited to letrozole, they did not rule out the possibility that the risk of tendon disorders may be associated with all third generation aromatase inhibitors.
At the time of the review, the CPMs for third generation aromatase inhibitors included information on the risk of tenosynovitis of the hands.
A tendon is a rope-like fibrous tissue that attaches muscle to bone. A thin fibrous sheath surrounds the tendon. Disorders of the tendon include tendon inflammation (tendonitis), tendon tears (tendon rupture) and inflammation of the tendon sheath (tenosynovitis). Tendon disorders can cause serious physical limitations and, in some cases, require surgery.
","use_canada":2633,"findings":2634,"conclusion":2635,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of third generation aromatase inhibitors both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2636,"title":"Summary Safety Review - Third Generation Aromatase Inhibitors (anastrozole, exemestane, letrozole) - Assessing the Potential Risk of Tendon Disorders","created_date":"2023-01-17","modified_date":null,"key_message_list":[{"field_id":2632,"order_no":1,"bullet":"Third generation aromatase inhibitors are authorized in Canada for the treatment of breast cancer in women who have reached menopause."},{"field_id":2632,"order_no":2,"bullet":"Health Canada reviewed the risk of tendon disorders related to the use of third generation aromatase inhibitors. This review was triggered by an update to the letrozole product safety information to include the risks of tendonitis and tendon rupture, made by the European Medicines Agency (EMA)."},{"field_id":2632,"order_no":3,"bullet":"At the time of the review, the Canadian product monographs (CPMs) for third generation aromatase inhibitors included information on the risk of tenosynovitis of the hands."},{"field_id":2632,"order_no":4,"bullet":"Health Canada's review concluded that there is likely a link between the use of third generation aromatase inhibitors and the risks of tendonitis and tenosynovitis. A link with tendon rupture could not be ruled out."},{"field_id":2632,"order_no":5,"bullet":"Health Canada is working with the manufacturers of third generation aromatase inhibitors to update the product safety information in the CPMs to include these risks. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication."}],"footnotes_list":[{"field_id":2636,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database."}],"reference_list":[],"use_canada_list":[{"field_id":2633,"order_no":1,"bullet":"Third generation aromatase inhibitors are prescription drugs authorized for sale in Canada for the treatment of breast cancer in women who have reached menopause."},{"field_id":2633,"order_no":2,"bullet":"There are currently 3 aromatase inhibitors on the Canadian market: Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole). Generic versions of all 3 aromatase inhibitors are available in Canada."},{"field_id":2633,"order_no":3,"bullet":"Between June 2015 and May 2021, the average annual total prescriptions (including new and refill prescriptions) dispensed by Canadian retail pharmacies to women aged 40 or older, were 247,271 prescriptions for anastrozole, 243,238 prescriptions for letrozole, and 39,048 prescriptions for exemestane."}],"finding_list":[{"field_id":2634,"order_no":1,"bullet":"Health Canada reviewed information from published and unpublished population-based studies and case reports of individual patients. Information was obtained from searches of international databases of published literature, drug manufacturers, as well as searches of the Canada Vigilance databasea."},{"field_id":2634,"order_no":2,"bullet":"Health Canada reviewed 5 randomized controlled trials (RCTs) that included a total of 28,873 patients. Reported events of tendonitis and tenosynovitis, which were uncommon in occurrence (less than 1%), were found to be likely linked to the use of third generation aromatase inhibitors. A link with tendon rupture, which was rare in occurrence (less than 0.1%), could not be ruled out."},{"field_id":2634,"order_no":3,"bullet":"Health Canada also reviewed 25 case reports (2 Canadian and 23 international) of tendon rupture (10 cases) and tendonitis (15 cases). Health Canada did not review case reports of tenosynovitis as there was insufficient information in these reports to separate tenosynovitis from other labelled adverse events involving the muscles and bones. Of the 10 reported cases of tendon rupture, 4 involved the use of anastrozole, 4 letrozole and 2 exemestane (1 Canadian). Of the 15 reported cases of tendonitis, 7 involved the use of anastrozole (1 Canadian), 4 involved letrozole and 4 exemestane. Across the assessed cases, tendonitis and tendon rupture affected both upper and lower limbs."},{"field_id":2634,"order_no":4,"bullet":"These 25 case reports included other medications and/or conditions that could have contributed to the reported adverse events. From these case reports, a link between the risk of tendon rupture and tendonitis with the use of a third generation aromatase inhibitor could not be ruled out."}],"conclusion_list":[{"field_id":2635,"order_no":1,"bullet":"Health Canada's review of the available RCTs and case reports concluded that there is likely a link between the use of third generation aromatase inhibitors and the risks of tendonitis and tenosynovitis, which were uncommon in occurrence. A link with tendon rupture, which was rare in occurrence, could not be ruled out."},{"field_id":2635,"order_no":2,"bullet":"Health Canada is working with the manufacturers of third generation aromatase inhibitors to update the CPMs to include these risks. Health Canada will inform healthcare professionals about these updates through a Health product InfoWatch communication."},{"field_id":2635,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of aromatase inhibitors and other health products to the Canada Vigilance Program."},{"field_id":2635,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving aromatase inhibitors, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risks be identified."}]},{"template":2,"link_id":"SSR00290","review_date":null,"drug_name":"Finasteride-containing products","safety_issue":"Suicide, suicidal thoughts (suicidal ideation) and self-injury","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2642,"overview":"Health Canada has been monitoring the risk of suicidal ideation with the use of finasteride since 2012. Health Canada completed 2 safety reviews in 2012 and 2015, and the information available at the time was considered too limited to determine whether there was a link between the use of finasteride and suicidal thoughts and behaviours (suicidality).
\nIn 2019, following reports of Canadian and international cases of suicide, suicidal ideation and self-injury with the use of finasteride, Health Canada completed a third safety review that found a possible link between finasteride and the risk of suicidal ideation. The CPMs of finasteride were updated to include the risk of suicidal ideation.
\nIn 2022, Health Canada completed a review of the risk of suicidal ideation and potential risks of suicide and self-injury with the use of finasteride. This latest safety review was triggered by the publication of a media article1 that discussed the potential risk of suicide in patients using Propecia (finasteride) for male pattern hair loss. The purpose of the current review was to consider recent information and determine if additional measures were warranted.
","use_canada":2643,"findings":2644,"conclusion":2645,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of finasteride both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2646,"footnotes":2647,"title":"Summary Safety Review - Finasteride - Assessing the Potential Risks of Suicide, Suicidal Thoughts (Suicidal Ideation) and Self-injury","created_date":"2023-01-19","modified_date":null,"key_message_list":[{"field_id":2642,"order_no":1,"bullet":"Finasteride is authorized for sale in Canada for the treatment and control of prostate gland enlargement (benign prostatic hyperplasia), and for the treatment of male pattern hair loss (androgenetic alopecia). "},{"field_id":2642,"order_no":2,"bullet":"Health Canada reviewed the risk of suicidal ideation and potential risks of suicide and self-injury with the use of finasteride. The safety review was triggered by the publication of a media article that discussed the potential risk of suicide in patients using Propecia (finasteride) for male pattern hair loss."},{"field_id":2642,"order_no":3,"bullet":"Health Canada's review of the available information found a possible link between the use of finasteride and the risks of suicidal ideation and self-injury. At this time, there is not enough information to establish a link for the risk of suicide."},{"field_id":2642,"order_no":4,"bullet":"Health Canada is working with the manufacturers to update the product safety information in the Canadian product monographs (CPM) for finasteride-containing products to strengthen the warning statements on the risks of suicidal ideation and self-injury, and to include information about patient screening for psychiatric risk factors prior to starting treatment, as well as continuous patient monitoring during and after stopping treatment. "},{"field_id":2642,"order_no":5,"bullet":"Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication. "}],"footnotes_list":[{"field_id":2647,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"},{"field_id":2647,"order_no":2,"bullet":"World Health Organization’s Adverse Drug Reaction Database.
"}],"reference_list":[{"field_id":2646,"order_no":1,"bullet":"Levine, D., Terhune, C., \"Exclusive: Merck anti-baldness drug Propecia has long trail of suicide reports, records show,\" REUTERS, February 3, 2021.
"}],"use_canada_list":[{"field_id":2643,"order_no":1,"bullet":"Finasteride is a prescription drug authorized for sale in Canada for the treatment and control of prostate gland enlargement (benign prostatic hyperplasia), and for the treatment of male pattern hair loss (androgenetic alopecia)."},{"field_id":2643,"order_no":2,"bullet":"Finasteride has been marketed in Canada since 1992 under the brand name Proscar (5 mg tablets), and since 1998 under the brand name Propecia (1 mg tablets). Generic versions of finasteride are also available on the Canadian market."},{"field_id":2643,"order_no":3,"bullet":"Approximately 8.7 million prescriptions of finasteride were dispensed by Canadian retail pharmacies between 2016 and 2022."}],"finding_list":[{"field_id":2644,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, the World Health Organization’s Adverse Drug Reaction databaseb, and the scientific literature."},{"field_id":2644,"order_no":2,"bullet":"Health Canada reviewed 401 cases (29 Canadian and 372 international) of suicide, suicidal ideation and/or self-injury in patients using finasteride from the Canada Vigilance database. Of the 401 cases, 25 (10 Canadian) met the criteria for further assessment to determine if there was a link between the use of finasteride and suicide, suicidal ideation and self-injury."},{"field_id":2644,"order_no":3,"bullet":"Of the 25 cases, 23 (9 Canadian) were found to be possibly linked to the use of finasteride. Two cases (1 Canadian) could not be assessed. Eight of the 14 international cases were fatal (resulted in a completed suicide)."},{"field_id":2644,"order_no":4,"bullet":"In 17 of the 25 cases assessed by Health Canada, patients were 40 years of age or younger and taking finasteride for male pattern hair loss."},{"field_id":2644,"order_no":5,"bullet":"The number of cases of suicide, suicidal ideation and self-injury reported to Health Canada is considered to be low in individuals treated with finasteride (approximately 1 Canadian case for every 10.1 million tablets dispensed in Canada)."},{"field_id":2644,"order_no":6,"bullet":"Health Canada also reviewed 16 publications in the scientific literature. There is a growing body of scientific evidence regarding the association between the use of finasteride and the risks of suicide, suicidal ideation and self-injury. Although there were limitations, the publications reviewed supported a possible link between the use of finasteride and suicidal ideation during treatment and following discontinuation of finasteride, especially in patients treated for male pattern hair loss."}],"conclusion_list":[{"field_id":2645,"order_no":1,"bullet":"Health Canada’s review of the available information found a possible link between the use of finasteride and the risks of suicidal ideation and self-injury. At this time, there is not enough information to establish a link between the use of finasteride and the risk of suicide."},{"field_id":2645,"order_no":2,"bullet":"Health Canada is working with the manufacturers to update the CPMs for finasteride-containing products to strengthen the warning statements on the risks of suicidal ideation and self-injury, and to include information about patient screening for psychiatric risk factors prior to starting treatment, as well as continuous patient monitoring during and after stopping treatment."},{"field_id":2645,"order_no":3,"bullet":"Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication."},{"field_id":2645,"order_no":4,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of finasteride and other health products to the Canada Vigilance Program."},{"field_id":2645,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving finasteride, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should any new health risk be identified."}]},{"template":2,"link_id":"SSR00291","review_date":null,"drug_name":"Cephalosporins (cephalexin-, cefazolin-, cefadroxil-, cefoxitin-, cefuroxime-, cefprozil-, cefotaxime-, ceftazidime-, ceftriaxone-, cefixime-, cefepime-, ceftobiprole- and ceftolozane-tazobactam-containing products)","safety_issue":"Seizures","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2654,"overview":"Health Canada reviewed the potential risk of seizures with the use of cephalosporins. This safety review was triggered by a U.S. Food and Drug Administration update to the product safety information for a cefazolin-containing product to include the risk of seizures.
","use_canada":2655,"findings":2656,"conclusion":2657,"additional":"The analyses that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of cephalosporins both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2658,"title":"Summary Safety Review - Cephalosporins - Assessing the Potential Risk of Seizures","created_date":"2023-01-23","modified_date":null,"key_message_list":[{"field_id":2654,"order_no":1,"bullet":"Cephalosporins are a group of prescription antibiotic drugs authorized for sale in Canada to treat a wide range of bacterial infections, including urinary and respiratory tract infections.
"},{"field_id":2654,"order_no":2,"bullet":"Health Canada reviewed the potential risk of seizures with the use of cephalosporins. The safety review was triggered by a labelling update for a cefazolin-containing product marketed in the United States (U.S.).
"},{"field_id":2654,"order_no":3,"bullet":"Health Canada’s review concluded that there may be a link between the use of cephalosporins and the risk of seizures.
"},{"field_id":2654,"order_no":4,"bullet":"At the time of the safety review, the risk of seizures was already included in the product safety information in the Canadian product monograph (CPM) for some cephalosporins. Health Canada will work with the manufacturers to update the CPM for the cephalosporins that do not already include this risk.
"}],"footnotes_list":[{"field_id":2658,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[],"use_canada_list":[{"field_id":2655,"order_no":1,"bullet":"Cephalosporins are a group of prescription antibiotic drugs authorized for sale in Canada to treat a wide range of bacterial infections, including urinary and respiratory tract infections.
"},{"field_id":2655,"order_no":2,"bullet":"Cephalosporins have been marketed in Canada for over 50 years under different brand names and generics of cephalexin, cefazolin, cefadroxil, cefoxitin, cefuroxime, cefprozil, cefotaxime, ceftazidime, ceftriaxone, cefixime, cefepime, ceftobiprole, and ceftolozane-tazobactam.
"},{"field_id":2655,"order_no":3,"bullet":"Cephalosporins are a widely prescribed group of antibiotic drugs, with approximately 3.6 million prescriptions filled in Canadian retail pharmacies every year.
"}],"finding_list":[{"field_id":2656,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, as well as medical and scientific literature.
"},{"field_id":2656,"order_no":2,"bullet":"Health Canada reviewed 84 cases (7 Canadian and 77 international) of seizures in patients taking cephalosporins. Of the 84 cases, 13 were found to be probably linked to the use of cephalosporins. Sixty-two cases (4 Canadian) were found to be possibly linked, and 3 cases were unlikely to be linked to the use of cephalosporins. Six cases (3 Canadian) could not be assessed.
"}],"conclusion_list":[{"field_id":2657,"order_no":1,"bullet":"Health Canada’s review of the available information concluded that there may be a link between the use of cephalosporins and the risk of seizures.
"},{"field_id":2657,"order_no":2,"bullet":"At the time of the safety review, the risk of seizures was already included in the CPM for some cephalosporins. Health Canada will work with the manufacturers to update the CPM for the cephalosporins that do not already include this risk.
"},{"field_id":2657,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of cephalosporins and other health products to the Canada Vigilance Program.
"},{"field_id":2657,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving cephalosporins, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.
"}]},{"template":2,"link_id":"SSR00292","review_date":null,"drug_name":"Rocuronium-containing products","safety_issue":"Fixed dilated pupils (mydriasis)","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2664,"overview":"Health Canada reviewed the potential risk of mydriasis with the use of rocuronium. The safety review was triggered by international case reports published in the literature concerning this risk1,2.
\nMydriasis is a condition in which the pupil is not responsive to external light stimulation and remains large (dilated) for a prolonged period. Mydriasis may be a sign that the patient is experiencing a serious medical condition that requires urgent attention. It may also occur in response to the use of certain drugs.
","use_canada":2665,"findings":2666,"conclusion":2667,"additional":"The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of rocuronium both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2668,"footnotes":2669,"title":"Summary Safety Review - Rocuronium - Assessing the Potential Risk of Mydriasis","created_date":"2023-02-09","modified_date":null,"key_message_list":[{"field_id":2664,"order_no":1,"bullet":"Rocuronium is authorized for sale in Canada to relax muscles during an operation as part of the general anesthesia and to facilitate assisted breathing (mechanical ventilation) in patients requiring intensive care.
"},{"field_id":2664,"order_no":2,"bullet":"Health Canada reviewed the potential risk of mydriasis with the use of rocuronium. The safety review was triggered by international case reports published in the literature concerning this risk.
"},{"field_id":2664,"order_no":3,"bullet":"Health Canada’s review of the available information found a link between the use of rocuronium and the risk of mydriasis in mechanically ventilated adult patients with systemic infection, and in newborn infants undergoing surgery. Mydriasis is expected to reverse when rocuronium is discontinued.
"},{"field_id":2664,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for rocuronium-containing products to include the risk of mydriasis. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.
"}],"footnotes_list":[{"field_id":2669,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[{"field_id":2668,"order_no":1,"bullet":"Rodrigues, E., da Costa G., Braga D., Pinto J., Lessa M. (2021). Rocuronium-Induced Dilated Nonreactive Pupils in a Patient With Coronavirus Disease 2019: A Case Report. A&A Practice 15(7):p e01491.
"},{"field_id":2668,"order_no":2,"bullet":"Zakynthinos G., Tsolaki V., Bardaka F., Makris D. (2021). Fixed dilated pupils in Covid-19 ARDS patients under rocuronium, reversed after discontinuation. Journal of Critical Care, Volume 65, 259-260.
"}],"use_canada_list":[{"field_id":2665,"order_no":1,"bullet":"Rocuronium is a prescription drug that belongs to a group of drugs referred to as muscle relaxants. Rocuronium is authorized for sale in Canada to relax muscles during an operation as part of the general anesthesia and to facilitate mechanical ventilation in patients requiring intensive care.
"},{"field_id":2665,"order_no":2,"bullet":"Rocuronium has been marketed in Canada since 1995. It is currently available as a 10 mg / mL solution for injection. Various generic rocuronium products are available in Canada.
"},{"field_id":2665,"order_no":3,"bullet":"Rocuronium is administered by a healthcare professional and is usually used in a hospital setting.
"}],"finding_list":[{"field_id":2666,"order_no":1,"bullet":"Health Canada reviewed information provided by manufacturers, from foreign regulatory agencies, and from searches of the Canada Vigilance databasea and published literature.
"},{"field_id":2666,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of mydriasis related to the use of rocuronium.
"},{"field_id":2666,"order_no":3,"bullet":"Health Canada reviewed 9 international cases of mydriasis in patients administered rocuronium. Of the 9 cases assessed, 3 were found to be probably linked to the use of rocuronium, 2 were found to be possibly linked, 1 was unlikely to be linked and 3 could not be assessed.
"},{"field_id":2666,"order_no":4,"bullet":"Three cases (2 probable and 1 possible) involved adult patients with serious infection requiring mechanical ventilation. All 3 cases resolved following discontinuation of rocuronium.
"},{"field_id":2666,"order_no":5,"bullet":"Two cases (1 probable and 1 possible) involved newborn infants undergoing surgery. One newborn infant experiencing prolonged general muscle relaxation received medication to reverse the mydriasis. The remaining case resolved following discontinuation of rocuronium.
"},{"field_id":2666,"order_no":6,"bullet":"Health Canada also reviewed articles published in the scientific literature, which explain how rocuronium may lead to mydriasis.
"}],"conclusion_list":[{"field_id":2667,"order_no":1,"bullet":"Health Canada's review of the available information found a link between the use of rocuronium and the risk of mydriasis in mechanically ventilated adult patients with systemic infection, and in newborn infants undergoing surgery. Mydriasis is expected to reverse when rocuronium is discontinued.
"},{"field_id":2667,"order_no":2,"bullet":"Health Canada will work with the manufacturers to update the CPM for rocuronium-containing products to include the risk of mydriasis.
"},{"field_id":2667,"order_no":3,"bullet":"Health Canada will also inform healthcare professionals about this update through a Health product InfoWatch communication.
"},{"field_id":2667,"order_no":4,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of rocuronium and other health products to the Canada Vigilance Program.
"},{"field_id":2667,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving rocuronium, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.
"}]},{"template":2,"link_id":"SSR00293","review_date":null,"drug_name":"Cloxacillin-containing products","safety_issue":"Acute kidney injury (AKI), a sudden decrease in renal function","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2676,"overview":"Health Canada reviewed the potential risk of AKI with the use of cloxacillin. This safety review was triggered by case reports of AKI received through Health Canada’s Canada Vigilance Program.
","use_canada":2677,"findings":2678,"conclusion":2679,"additional":"The analysis that contributed to this safety review included scientific literature, Canadian and international information, and what is known about the use of cloxacillin both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":0,"footnotes":2680,"title":"Summary safety review - Cloxacillin - Assessing the Potential Risk of Acute Kidney Injury","created_date":"2023-03-22","modified_date":null,"key_message_list":[{"field_id":2676,"order_no":1,"bullet":"Cloxacillin is a prescription antibiotic drug authorized for sale in Canada to treat various bacterial infections.
"},{"field_id":2676,"order_no":2,"bullet":"Health Canada reviewed the potential risk of AKI with the use of cloxacillin. The safety review was triggered by reported cases of AKI in patients taking cloxacillin.
"},{"field_id":2676,"order_no":3,"bullet":"Health Canada’s review of the available information did not establish a link between the use of cloxacillin and the risk of AKI.
"},{"field_id":2676,"order_no":4,"bullet":"Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for cloxacillin-containing products to note that cases have been reported and to increase awareness of this potential risk.
"}],"footnotes_list":[{"field_id":2680,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[],"use_canada_list":[{"field_id":2677,"order_no":1,"bullet":"Cloxacillin is a prescription antibiotic drug authorized for sale in Canada to treat various bacterial infections.
"},{"field_id":2677,"order_no":2,"bullet":"Cloxacillin has been marketed in Canada since the mid-1960s. It is available as oral capsules, granules for oral solution and powder for reconstituted solution for injection.
"},{"field_id":2677,"order_no":3,"bullet":"The number of prescriptions dispensed by Canadian retail pharmacies for cloxacillin decreased from approximately 135,000 prescriptions in 2016 to approximately 68,000 prescriptions in 2021.
"}],"finding_list":[{"field_id":2678,"order_no":1,"bullet":"Health Canada reviewed the available information from searches of Canadian and international reports in the Canada Vigilance databasea, and the scientific literature.
"},{"field_id":2678,"order_no":2,"bullet":"Health Canada reviewed 20 cases (9 Canadian and 11 international) of AKI in patients taking cloxacillin from the Canada Vigilance database. Of the 20 cases, 16 (7 Canadian) were found to be possibly linked to the use of cloxacillin, 3 (1 Canadian) were unlikely to be linked, and 1 (Canadian) could not be assessed due to insufficient clinical information. Three deaths (1 Canadian) were reported among the 16 cases that were assessed as having a possible link to the use of cloxacillin. The role of cloxacillin in these events could not be determined, as other medications and life-threatening medical conditions, including severe infections, could have contributed.
"},{"field_id":2678,"order_no":3,"bullet":"In the 16 cases found to be possibly linked to use of cloxacillin, all patients had risk factors or were on other medications which were known to cause AKI.
"},{"field_id":2678,"order_no":4,"bullet":"Health Canada’s review of the scientific literature found a wide range of incidence rates of AKI in patients using cloxacillin. Overall, evidence of a link between cloxacillin and AKI in the scientific literature was inconclusive due to study limitations and contributing risk factors in patients.
"}],"conclusion_list":[{"field_id":2679,"order_no":1,"bullet":"Health Canada’s review of the available information did not establish a link between the use of cloxacillin and the risk of AKI.
"},{"field_id":2679,"order_no":2,"bullet":"Health Canada will work with the manufacturers to update the CPM for cloxacillin-containing products to note that cases have been reported and to increase awareness of this potential risk.
"},{"field_id":2679,"order_no":3,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of cloxacillin, and other health products, to the Canada Vigilance Program.
"},{"field_id":2679,"order_no":4,"bullet":"Health Canada will continue to monitor safety information involving cloxacillin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.
"}]},{"template":2,"link_id":"SSR00294","review_date":null,"drug_name":"Proglycem (diazoxide)","safety_issue":"Pericardial effusion, an accumulation of fluid in the space around the heart","safetyissue_title":"Potential Safety Issue","findings_title":"Safety Review Findings","issue":"","background":"","objective":"","key_findings":"","key_messages":2686,"overview":"Health Canada reviewed the potential risk of pericardial effusion with the use of Proglycem. This safety review was triggered by published cases in the scientific literature.
\nPericardial effusion is the accumulation of fluid in the space around the heart. It can evolve into cardiac tamponade, a life-threatening condition, if there is too much fluid or if it accumulates too quickly. In this event, the fluid compresses the heart and could cause it to stop functioning properly.
","use_canada":2687,"findings":2688,"conclusion":2689,"additional":"The analysis that contributed to this safety review included scientific and medical literature, international information, and what is known about the use of Proglycem both in Canada and internationally.
\nFor additional information, contact the Marketed Health Products Directorate.
","full_review":"","references":2690,"footnotes":2691,"title":"Summary safety review - Proglycem (diazoxide) - Assessing the Potential Risk of Pericardial Effusion","created_date":"2023-03-24","modified_date":null,"key_message_list":[{"field_id":2686,"order_no":1,"bullet":"Proglycem (diazoxide) is authorized for sale in Canada to manage low blood sugar (hypoglycaemia) in infants, children and adults caused by a higher-than-normal amount of insulin in the blood (hyperinsulinism) associated with specific tumors, surgeries, maternal or fetal medical conditions, delivery-related complications or genetic conditions, when other medical therapy or surgical management has been unsuccessful or is not feasible.
"},{"field_id":2686,"order_no":2,"bullet":"Health Canada reviewed the potential risk of pericardial effusion with the use of Proglycem. The safety review was triggered by published cases in the scientific literature.
"},{"field_id":2686,"order_no":3,"bullet":"A very small number of international cases, including cases occurring in infants and children, have been observed.
"},{"field_id":2686,"order_no":4,"bullet":"Health Canada’s review of the available information found a possible link between the use of Proglycem and the risk of pericardial effusion.
"},{"field_id":2686,"order_no":5,"bullet":"Health Canada is working with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Proglycem with a warning about cases of pericardial effusion having been observed, including in infants and children. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.
"}],"footnotes_list":[{"field_id":2691,"order_no":1,"bullet":"Canadian reports can be accessed through the Canada Vigilance Online Database.
"}],"reference_list":[{"field_id":2690,"order_no":1,"bullet":"Avatapalle B, Banerjee I, Malaiya N, Padidela R. Echocardiography monitoring for diazoxide induced pericardial effusion. BMJ Case Rep. 2012
"},{"field_id":2690,"order_no":2,"bullet":"Maffre I, Vincenti M, Dalla Vale F, Amouroux C, Werner O, Meilhac A, de Barry G, Amedro P. Diazoxide Causality Assessment of a Pericardial Effusion in a Child with Kabuki Syndrome. J Clin Res Pediatr Endocrinol. 2019 May 28;11(2):218-219.
"}],"use_canada_list":[{"field_id":2687,"order_no":1,"bullet":"Proglycem is a prescription drug authorized for sale in Canada to manage low blood sugar (hypoglycaemia) in infants, children and adults caused by a higher-than-normal amount of insulin in the blood (hyperinsulinism) associated with specific tumors, surgeries, maternal or fetal medical conditions, delivery-related complications or genetic conditions, when other medical therapy or surgical management has been unsuccessful or is not feasible. Proglycem works by preventing the release of insulin from the pancreas.
"},{"field_id":2687,"order_no":2,"bullet":"Diazoxide has been marketed in Canada for over 35 years. It is currently available as 100 mg capsules, under the brand name Proglycem.
"},{"field_id":2687,"order_no":3,"bullet":"The estimated yearly number of Proglycem capsules dispensed by Canadian retail pharmacies and used in hospitals increased from approximately 75,000 capsules in 2017 to approximately 130,000 capsules in 2021.
"}],"finding_list":[{"field_id":2688,"order_no":1,"bullet":"Health Canada reviewed information provided by the manufacturer, and from searches of the Canada Vigilance databasea and the published literature.
"},{"field_id":2688,"order_no":2,"bullet":"At the time of the review, Health Canada had not received any Canadian reports of pericardial effusion related to the use of Proglycem.
"},{"field_id":2688,"order_no":3,"bullet":"Health Canada reviewed 8 international cases of pericardial effusion in patients taking Proglycem from the Canada Vigilance database. Of the 8 cases assessed, 6 were in infants and children.
"},{"field_id":2688,"order_no":4,"bullet":"Of the 8 cases, 2 (both published in the scientific literature1,2) were found to be probably linked to the use of Proglycem, 4 were found to be possibly linked and 2 were unlikely to be linked.
"}],"conclusion_list":[{"field_id":2689,"order_no":1,"bullet":"Health Canada’s review of the available information concluded that there is a possible link between the use of Proglycem and the risk of pericardial effusion.
"},{"field_id":2689,"order_no":2,"bullet":"Health Canada is working with the manufacturer to update the CPM for Proglycem with a warning about cases of pericardial effusion having been observed, including in infants and children.
"},{"field_id":2689,"order_no":3,"bullet":"Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.
"},{"field_id":2689,"order_no":4,"bullet":"Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Proglycem and other health products to the Canada Vigilance Program.
"},{"field_id":2689,"order_no":5,"bullet":"Health Canada will continue to monitor safety information involving Proglycem, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.
"}]}]