Summary Safety Review - Brilinta (ticagrelor) - Assessing the Potential Risk of Central Sleep Apnea

Review decision

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.


Issued: 2020-10-28

Product

Brilinta (ticagrelor)

Potential Safety Issue

Central sleep apnea (CSA), a condition in which breathing repeatedly stops and starts during sleep

Key Messages

  • 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.
  • 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.
  • 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.
  • 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.

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 in Canada

  • Brilinta has been marketed in Canada since 2011 and is available as 60 mg and 90 mg tablets.
  • 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.
  • 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.
  • 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).
  • There were about 2 million prescriptions for Brilinta filled in Canada between 2014 and 2019.

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilancea database, international databases, and published literature.
  • 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.
  • 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.
  • 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.

Conclusions and actions

  • Health Canada's review concluded that there may be a link between the use of Brilinta (ticagrelor) and the risk of CSA.
  • Health Canada has requested that the manufacturer of Brilinta update the Canadian product safety information to add a warning about this potential safety issue.
  • 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.
  • 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.
  • 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.

Additional 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 Brilinta (ticagrelor) both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. 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

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.

Report a problem or mistake on this page
Please select all that apply:
Date modified: