Summary Safety Review - Opsumit (macitentan) - Assessing the potential risk of liver injury

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: 2019-03-01

Product

Opsumit (macitentan)

Potential Safety Issue

Liver injury

Key Messages

  • Opsumit (macitentan) is a prescription drug authorized for sale in Canada to treat certain types of pulmonary arterial hypertension (PAH). PAH is high blood pressure in the vessels (arteries) that carry blood from the heart to the lungs.
  • Health Canada reviewed the potential risk of liver injury with the use of Opsumit after becoming aware of international reports of liver injury. These reports led to an update to the United States (US) product safety information for Opsumit.
  • Health Canada's review of the available information concluded that there may be a link between Opsumit use and risk of liver injury.
  • Health Canada will notify Opsumit's manufacturer to update the Canadian product safety information with this new information.

Overview

Health Canada reviewed the potential risk of liver injury with Opsumit (macitentan) use following reports of liver injury internationally that led to an update to the US product safety information for this drug.

At the time of the review, the Canadian product safety information for Opsumit included a warning about potential effects on the liver that had been observed with the group of drugs to which Opsumit belongs. The Canadian product safety information also included requirements for blood tests to monitor liver function.

Pulmonary arterial hypertension (PAH) is a condition where there is high blood pressure in the vessels that carry blood from the heart to the lungs. It is a condition that can be life-threatening or that can have a significant impact on patients' quality of life.

Use in Canada

  • Opsumit (macitentan) is a prescription drug authorized for sale in Canada to treat certain types of PAH.
  • Macitentan has been marketed in Canada since January 2014 under the brand name Opsumit.
  • In Canada, there were over 2,900 prescriptions for Opsumit filled in 2017.

Safety Review Findings

  • At the time of the review, Health Canada looked at 15 Canadian reportsa of liver injury with Opsumit from the Canada Vigilance database. Of these reports, 14 were not found to be relevant to this review (e.g., reports that were duplicates, that did not meet the definition of liver injury, or reports where the patient had a history of liver disease). In the 1 remaining case, it was determined that the liver injury was unlikely to be linked to the use of Opsumit.
  • Health Canada also assessed 16 international reports (1 published1) that were found to be relevant to the review. There was a link between the risk of liver injury and the use of Opsumit in 1 report. The link was found to be possible in 13 reports and unlikely in 1 report. In the remaining 1 report, the link could not be assessed due to the nature of the information provided. Death was reported in 1 of the 13 cases where the risk of liver injury was found to have a possible link with the use of Opsumit. However, the death was not linked to Opsumit, but was the result of disease progression.
  • In the majority of the reports assessed, other factors may have also caused the liver injury, such as: heart failure that results from PAH, other conditions linked with PAH, or the use of other medications for PAH.
  • No published studies assessing the risk of liver injury with the use of Opsumit were identified in the literature.

Conclusions and actions

  • Health Canada's review found that there may be a link between Opsumit and liver injury.
  • Health Canada will notify the manufacturer to update the product safety information for Opsumit in order to inform healthcare professionals and patients about the potential for liver injury.
  • Health Canada will continue to monitor safety information involving Opsumit, 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.
  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of this or other health products.

Additional information

The analysis that contributed to this safety review included 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.

References

  1. Tran, T., Brinker, A.D. et al, Serious Liver Injury Associated with Macitentan: A Case Report, Pharmacotherapy, Vol 38, Number 2, 2018

Footnotes

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

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