Summary Safety Review - Fibristal (5 mg ulipristal acetate) - Assessing the potential risk of rare but serious 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: 2018-09-07

Product

Fibristal (5 mg ulipristal acetate)

Potential Safety Issue

Serious liver injury

Key Messages

  • Fibristal (5 mg ulipristal acetate) is a prescription drug authorized for sale in Canada to treat the signs and symptoms of a type of non-cancerous tumour in the womb (uterine fibroids) in women of child-bearing age.
  • Health Canada reviewed the risk of liver injury with the use of Fibristal after becoming aware of four international reports of liver injury leading to liver transplants.
  • In March 2018, as an interim measure while the safety review was ongoing, Health Canada issued an Information Update. It informed healthcare professionals of the need to monitor liver function during and after treatment, and recommended not to use Fibristal in patients with liver disease.
  • Health Canada's review of the available information concluded that there may be a link between Fibristal use and risk of serious liver injury.
  • Health Canada is working with Fibristal's manufacturer to better understand its effects on the liver, to update the Canadian product information with new restrictions for use and recommendations to monitor liver function, and to communicate this risk to healthcare professionals and patients.

Overview

Health Canada reviewed the potential risk of serious liver injury with Fibristal (5 mg ulipristal acetate) following reports of four international cases of liver injury leading to liver transplantation. In March 2018, as an interim measure while the review was ongoing, Health Canada communicated the need to monitor liver function during and after treatment, and recommended not to use Fibristal in patients with liver disease.

Uterine fibroids are non-cancerous (benign) tumours of the womb. While not life-threatening, they can lead to significant impairment of patients' quality of life as they may cause excessive uterine bleeding, pain, infertility and bulk symptoms (i.e., bloating and urinary symptoms).

Ulipristal acetate 30 mg is sold in Canada under the brand name Ella. It is a single-dose prescription drug used for emergency contraception. The review showed that no cases of liver injury have been reported with the use of Ella.

Use in Canada

  • Fibristal (5 mg ulipristal acetate) is a prescription drug which is authorized for sale in Canada to treat signs and symptoms of uterine fibroids in women of child bearing age who are eligible for surgery. It is also authorized for on and off (intermittent) treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of childbearing age. The duration of each treatment course is three months.
  • Fibristal has been marketed in Canada since 2013.
  • In 2017, there were more than 63,000 prescriptions filled in Canada.

Safety Review Findings

  • Health Canada reviewed 31 reports (7 Canadiana and 24 international) of serious liver injury with Fibristal use. A possible link between liver injury and Fibristal was found in the majority of the cases (20 cases, including 5 Canadian cases). In 6 cases (including 1 Canadian case), the link was found to be unlikely mostly because of the patients' medical condition prior to Fibristal use. In 5 cases (including 1 Canadian case), there was not enough information provided and these could not be assessed. The vast majority of cases recovered or were recovering at the time of reporting (18 of 22 cases for which information was provided).
  • Of the 20 cases having a possible link between Fibristal use and liver injury, 11 cases (2 of which were Canadian cases) reported the use of other medications or medical conditions which may have also contributed to liver injury. No pattern in the timing between Fibristal use and liver injury was found.
  • There were 4 international cases of liver injury which led to liver transplant. In one case, the outcome was death. The death in this case could not be linked to Fibristal because there was not enough information available. No cases of liver transplant were reported in Canada.
  • A review of the existing published literature did not identify any publications that would raise concerns about liver safety for Fibristal. There was no suggestion of liver injury from earlier research studies (both animal and human data).
  • The mechanism by which Fibristal could potentially cause liver injury is unknown at this time.
  • The European Medicines Agency (EMA) updated their product information for Fibristal to include the risk of liver injury and that liver function should be monitored. Fibristal is not marketed in the United States of America.

Conclusions and actions

  • Health Canada's review of the available information concluded that there may be a link between the use of Fibristal and serious liver injury.
  • Health Canada is working with the manufacturer to better understand the effects of Fibristal on the liver, and to update the Canadian product information. The updated product information will clarify when to use Fibristal, and recommend monitoring liver function before, during and after stopping treatment.
  • In addition, an Information Update and a Health Professional Risk Communication will be published and distributed to further inform Canadians and healthcare professionals about this risk.
  • Health Canada will continue to monitor safety information involving Fibristal 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 this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

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

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