Summary Safety Review - PRADAXA (dabigatran etexilate) - Assessing the potential risk of liver injury

May 7, 2018

Product

Pradaxa (dabigatran etexilate)

Potential Safety Issue

Liver injury

Key Messages

• 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).
• Health Canada reviewed the potential risk of liver injury with Pradaxa after receiving reports of severe liver injury in patients treated with Pradaxa.
• 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.

Overview

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 in Canada

• Pradaxa is a prescription drug authorized for sale in Canada as a blood thinner to:
  • prevent the formation of blood clots in the veins of legs or in lungs after knee or hip replacement surgery;
  • treat blood clots and prevent them from reoccurring in the veins of legs and/or lungs;
  • prevent stroke or sudden blocking of a blood vessel due to potential blood clots in patients with an abnormal heart rhythm (atrial fibrillation).
• Dabigatran etexilate has been marketed in Canada since 2008 under the brand name Pradax (later renamed to Pradaxa). Pradaxa is available as capsules taken by mouth.
• In 2016, there were approximately 711,000 prescriptions for Pradaxa filled in Canada. 

Safety Review Findings

• At the time of the review, Health Canada had received 27 Canadian reports^{Footnote a} of severe liver injury related to the use of Pradaxa. Of these reports, 4 were further assessed as they were suspected to be linked to the use of Pradaxa. 3 of the 4 reports, including 1 death, showed a possible link between liver injury and the use of Pradaxa.
• This review also looked at 105 international reports of severe liver injury related to the use of Pradaxa. Of these reports, 16 were further assessed as they were suspected to be linked to the use of Pradaxa. 13 of these 16 reports, including 2 deaths, showed a possible link between liver injury and the use of Pradaxa.
• In most reports that were further assessed by Health Canada, other medical conditions and medications could have caused the liver injury.
• This safety review looked at information from 2 published cases of liver injury suspected to be linked to the use of Pradaxa. These 2 cases were not further reviewed because severe liver injury was not confirmed.
• A review of the scientific literature did not find any published studies that showed an increased risk of liver injury in patients treated with Pradaxa.
• Product labels in the United States and the European Union do not contain any information specific to liver injury.

Conclusions and Actions

• Health Canada's review found that there may be a link between Pradaxa and liver injury.
• Health Canada will be working with the manufacturer to update the safety information for Pradaxa to inform healthcare professionals and patients about the potential for severe liver injury.
• Health Canada will continue to monitor safety information involving Pradaxa, 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 Pharmaceutical and Medical Devices Agency of Japan issued a risk communication^{Footnote 1} 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.