FIBRISTAL (ulipristal acetate tablets, 5 mg) - Voluntary Withdrawal in Canada due to Risk of Drug-Induced Liver Injury

Starting date:
September 30, 2020
Posting date:
September 30, 2020
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Product withdrawal, Important Safety Information
Audience:
Healthcare Professionals
Identification number:
RA-74063

Last updated:

Audiences

Healthcare professionals including obstetricians, gynecologists, primary care physicians with interest in women’s health, hepatologists, emergency room physicians, and pharmacists.

Key messages

  • Following rare international cases of severe liver injury requiring liver transplantation, the manufacturer of FIBRISTAL, Allergan Inc., is voluntarily withdrawing the product from the Canadian market. FIBRISTAL was approved in Canada to treat signs and symptoms of uterine fibroids in women of reproductive age.
  • On September 24, 2020, Allergan Inc. initiated the recall of FIBRISTAL from the Canadian market to the retail pharmacy level.
  • Healthcare professionals are advised to:
    • not prescribe or dispense FIBRISTAL
    • contact patients under their care who are currently being treated with FIBRISTAL to stop treatment, and review alternative treatment options
    • advise patients who have been taking FIBRISTAL to immediately contact a healthcare professional if they experience signs and symptoms of liver injury such as nausea, vomiting, stomach ache, severe tiredness, yellowing of the eyes or skin, or dark urine, which could occur after stopping treatment
    • perform liver function monitoring within 2-4 weeks after treatment with FIBRISTAL has stopped and investigate further if liver function is abnormal

    

Issue

Rare cases of liver injury, including cases of serious liver impairment requiring liver transplantation, have been reported internationally in patients using ulipristal acetate tablets, 5 mg. It has been determined that it is not possible to identify which patients are most at risk for developing liver injury, or identify measures that could further reduce the risk. No cases of serious liver impairment leading to transplantation have been reported in Canada.

Products affected

FIBRISTAL®, ulipristal acetate tablets, 5 mg.

Ulipristal acetate is also authorized as a single-dose medicine for emergency contraception. The recall does not affect this medication marketed under the brand name ella®.

Background information

FIBRISTAL was authorized in Canada for:

  • preoperative treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive age
  • intermittent treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive age who are not eligible for surgery

The duration of each treatment course is 3 months.

Health Canada conducted a safety review of FIBRISTAL and concluded that there may be a link between its use and risk of serious liver injury. On January 11, 2019, Health Canada informed Canadians of this risk. To address this safety concern, Health Canada worked with Allergan Inc. to update the Canadian Product Monograph for FIBRISTAL and implement the following safety measures:

  • the indication for intermittent treatment was restricted to women of reproductive age who are not eligible for surgery
  • FIBRISTAL was contraindicated in women with a history of and/or active/concomitant hepatic disease
  • more frequent liver function monitoring was required
  • educational materials specific to the risk of liver injury were developed including a Healthcare Professional Brochure and Patient Alert Card

The company was also directed to conduct specific studies to look at the effectiveness of these new safety measures. 

On September 16, 2020, Health Canada announced that it was again reviewing the risk of serious liver injury associated with FIBRISTAL. This review was in response to a recent international case of liver injury requiring liver transplantation, and the European Medicines Agency Pharmacovigilance Risk Assessment Committee’s recommendation to revoke the marketing authorization of the ulipristal acetate medication called ESMYA in Europe. 

On September 24, 2020, Allergan Inc. initiated the recall of FIBRISTAL from the Canadian market due to serious drug-induced liver injury (DILI), including rare international cases of severe liver injury requiring liver transplant.

Who is affected

Information for consumers

FIBRISTAL (also known as ulipristal acetate tablets, 5 mg) is a prescription drug used to treat the signs and symptoms of a type of non-cancerous tumour in the womb (uterine fibroids) in women of child-bearing age.

FIBRISTAL will no longer be available on the Canadian market as it has been associated with drug-induced liver injury, which can be serious in severe cases and life-threatening. Allergan Inc. has determined that it is not possible to identify which patients are most at risk for developing liver injury, or available measures that could further reduce the risk. The European Medicines Agency’s committee that monitors the safety of medications, has recommended the withdrawal of the marketing authorization of the ulipristal acetate medication called ESMYA in Europe.

Patients who are being treated with FIBRISTAL should stop treatment and contact their doctor to discuss other treatment options.

Patients should immediately report to their doctor signs and symptoms of liver injury such as nausea, vomiting, stomach ache, severe tiredness, yellowing of the eyes or skin, or dark urine, which could occur after stopping treatment.

Information for healthcare professionals

Due to serious drug-induced liver injury (DILI), including rare international cases of severe liver injury requiring liver transplant, FIBRISTAL will be removed from pharmacies across Canada after the manufacturer decided to voluntarily withdraw FIBRISTAL from the Canadian market.

Healthcare professionals are advised to:

  • not prescribe or dispense FIBRISTAL prescriptions.
  • contact patients under their care who are currently being treated with FIBRISTAL to:
    • stop FIBRISTAL and review alternative treatment options
    • advise patients to immediately report symptoms of liver injury, which could occur after stopping treatment, such as nausea, vomiting, stomach ache, severe tiredness, yellowing of the eyes or skin, or dark urine
  • perform liver function monitoring within 2-4 weeks after treatment with FIBRISTAL has stopped and investigate further if liver function is abnormal

Action taken by Health Canada

Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect™ e-Notice email notification system as well as through social media channels including LinkedIn and Twitter.

Report health or safety concerns

Health Canada’s ability to monitor the safety of marketed health products depends on healthcare professionals and consumers reporting adverse reactions and medical device incidents. Any case of DILI or other serious or unexpected side effects in patients receiving FIBRISTAL should be reported to Allergan or Health Canada.

Allergan Inc.
85 Enterprise Blvd., Suite 500
Markham, ON L6G 0B5
Toll free: 1-800-668-6424
E-mail: MR-Pharmacovigilance@allergan.com

To correct your mailing address or fax number, contact Allergan Inc.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

  • Calling toll-free at 1-866-234-2345; or
  • Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, contact Health Canada at:

Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Orginal signed by
Peter Janiszewski, PhD
Interim Medical Director
Allergan Inc. 

 

FIBRISTAL® is a registered trademark of Allergan Sales, LLC, used under license by Allergan Inc.

ella® is a registered trademark of Laboratoire HRA Pharma, used under license by Allergan Inc.