Summary Safety Review - Atypical antipsychotics - Assessing the potential risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Product

Atypical antipsychotics

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)

Key Messages

• Atypical antipsychotics are authorized for sale in Canada to treat mental disorders including schizophrenia, bipolar disorder, and depression.
• 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 risk^a.
• 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.
• Health Canada will work with the manufacturers to update the product safety information for these additional atypical antipsychotics to reflect the risk of DRESS.

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 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, brexpiprazole^a, 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 report^b 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 reports^c (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.

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 these drugs both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.