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Drugs and Health Products

Summary Safety Review - XARELTO (rivaroxaban) - Liver Injury

August 26, 2015

Product

XARELTO (rivaroxaban)

Potential Safety Issue

Liver injury

Key Messages

  • XARELTO (rivaroxaban) is used to:
    • Prevent blood clots from forming (anticoagulant) in patients who have had hip or knee replacement surgeries.
    • Prevent and treat blood clots forming in a deep vein, usually in the leg (deep vein thrombosis), or in a blood vessel that supplies the lungs (pulmonary embolism).
    • Prevent stroke in patients with abnormal heart rhythm (atrial fibrillation).
  • Health Canada completed a safety review following two publications in the scientific literature that described liver injury in 16 patients using XARELTO.
  • The current safety review could not establish a clear link between the use of XARELTO and liver injury. Health Canada will publish an article in the August 2015 issue of the Health Product InfoWatch to encourage the reporting of liver injury that may be linked to using XARELTO.

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 publicationsFootnote 1,Footnote 2 in the scientific literature described liver injury linked to the use of XARELTO in a total of 16 patients.

Use in Canada

  • XARELTO (rivaroxaban) is used to prevent blood clots from forming (anticoagulant) in patients who have had hip or knee replacement surgeries. It is also used to treat or prevent blood clots forming in a deep vein, usually in the leg (deep vein thrombosis), or in a blood vessel that supplies the lungs (pulmonary embolism). Some patients who have irregular heartbeat use this medicine to reduce the risk of having a stroke.
  • XARELTO is an oral medication available through prescription and was first sold in Canada in September 2008.
  • The Canadian prescribing information explains that XARELTO should not be taken by people who have liver disease linked to problems with blood clotting, and have a risk of bleeding.

Safety Review Findings

  • At the time of the review, there were 61 Canadian reports of liver-related harmful effects (adverse events) in patients taking XARELTO that were received through the Canada Vigilance ProgramFootnote a. Health Canada’s assessment of these cases did not show a clear link between XARELTO and liver-related harmful effects.
  • A review of international data from the World Health Organization’s database showed 431 cases of liver injury, and XARELTO was reported as the only drug used in 23 of these cases. A clear link between XARELTO and liver injury could not be determined.
  • At the time of the review, two case reportsFootnote 1,Footnote 2 were published in the scientific literature describing liver injury linked to the use of XARELTO in a total of 16 patients. An increased risk was not found in another studyFootnote 3, which compared the risk of liver injury in patients using XARELTO to patients using a different kind of anticoagulant medication (low molecular weight heparins).
  • A clear link between liver injury and the use of XARELTO could not be established because the information in some of the Canadian and international reports was incomplete. Also, in some of the reports published in the scientific literature, patients had underlying liver diseases before using XARELTO or were taking other medications that may have contributed to the liver injury.

Conclusions and Actions

  • The current safety review by Health Canada did not establish a clear link between the use of XARELTO and liver injury.
  • Health Canada will publish an article in the August 2015 issue of the Health Product InfoWatch to raise awareness and to encourage the reporting of liver-related harmful effects that may be linked to the use of XARELTO.
  • Health Canada will continue to monitor safety information involving XARELTO, 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 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.

References

Footnotes

Footnote 1

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.

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Footnote 2

Russmann S, Niedrig DF, Budmiger M, et al. Rivaroxaban postmarketing risk of liver injury. J Hepatol. 2014; 61:293-300.

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Footnote 3

Caldeira D, Barra M, Santos AT, et al. Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis. Heart. 2014; 100:500-556.

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Footnotes

Footnote a

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

Return to footnote a referrer