Summary Safety Review - Atypical antipsychotics - Assessing the potential risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Potential 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)
Use in Canada
- Atypical antipsychotics are prescription drugs authorized for sale in Canada to treat mental disorders such as schizophrenia, bipolar disorder, and depression.
- There are 10 different atypical antipsychotics marketed in Canada: aripiprazole, asenapine, brexpiprazolea, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone.
- The first atypical antipsychotic available for sale in Canada was clozapine, introduced in 1991.
- In 2016, there were about 18 million prescriptions filled for atypical antipsychotics.
- At this time, DRESS is listed in the product safety information for olanzapine and ziprasidone.
Safety Review Findings
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Conclusions and actions
- 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.
- Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these and other health products.
- 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.
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.
- 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.
- Canadian reports can be accessed through the Canada Vigilance Online Database.
- Eleven (11) case reports received from the Manufacturers including 4 found in the literature.