Health Product InfoWatch: December 2025

Contents

• Monthly recap of health product safety information
  • Brukinsa (zanubrutinib), Calquence (acalabrutinib) and Imbruvica (ibrutinib) - Bruton's tyrosine kinase (BTK) inhibitors
  • Unauthorized health products
• New health product safety information
  • Safety brief
    • Bruton's tyrosine kinase (BTK) inhibitors and the risk of serious hepatotoxicity
  • Notice of market authorization with conditions
    • Lyvdelzi (seladelpar): Authorization with conditions
• Scope
• Reporting Adverse Reactions
• Helpful links
• Contact us

Monthly recap of health product safety information

The following is a list of health product advisories, type I drug recalls and summaries of completed safety reviews published in November 2025 by Health Canada.

Brukinsa (zanubrutinib), Calquence (acalabrutinib) and Imbruvica (ibrutinib) - Bruton's tyrosine kinase (BTK) inhibitors

This safety review evaluated the risk of serious hepatotoxicity associated with the use of BTK inhibitors. Health Canada's review found a possible link. Health Canada is working with the manufacturers to update the Canadian product monographs for all BTK inhibitors to include the risk of serious hepatotoxicity.

Summary Safety Review: Brukinsa (zanubrutinib), Calquence (acalabrutinib) and Imbruvica (ibrutinib) - Bruton's tyrosine kinase (BTK) inhibitors

Unauthorized health products

Health Canada advised Canadians about various unauthorized health products being sold at retail locations across Canada or online that may pose serious health risks.

Advisory: Fake Viagra and Cialis seized from Rocky Convenience in Toronto, Ontario
Advisory: Unauthorized drugs seized from Ezra Healing in Kelowna, BC
Advisory: Various unauthorized nitrous oxide products

New health product safety information

The following topics have been selected to raise awareness and encourage reporting of adverse reactions.

Safety brief

Bruton's tyrosine kinase (BTK) inhibitors and the risk of serious hepatotoxicity

Bruton's tyrosine kinase (BTK) inhibitors, including Imbruvica (ibrutinib), Calquence (acalabrutinib), Brukinsa (zanubrutinib), and Jaypirca (pirtobrutinib) are oral therapies authorized in Canada for the treatment of various hematological malignancies.^{Footnote 1 Footnote 2 Footnote 3 Footnote 4} Imbruvica is also indicated for chronic graft-versus-host disease.

Hepatotoxicity caused by drugs, also referred to as drug-induced liver injury (DILI), is a rare but potentially life-threatening adverse drug reaction. It is characterized by elevated liver enzymes and, in serious cases, may progress to liver failure or require liver transplantation. Serious hepatotoxicity has been reported in patients treated with BTK inhibitors.

Health Canada conducted a review of serious hepatotoxicity associated with BTK inhibitors. At the time of review, the Canadian product monograph (CPM) for Imbruvica already contained warnings regarding the risk of hepatotoxicity, including hepatic failure and fatal events. Therefore, case-level evidence for the review focused on Calquence and Brukinsa, as these products did not carry warnings in their CPMs at that time; however, evidence of serious hepatotoxic outcomes with Imbruvica was integrated into the review to support the assessment of a possible class effect. Data for Jaypirca were not evaluated, as this product was not authorized in Canada at the time.

Health Canada reviewed 11 cases (1 Canadian and 10 international) of serious hepatotoxicity in patients treated with Calquence (2 cases) or Brukinsa (9 cases). All 11 cases were found to be possibly linked to the use of the BTK inhibitor. Six of the 11 cases provided adequate data to allow for calculation of the R ratio (a numerical value used to determine the pattern of hepatic injury), which confirmed hepatocellular-type injury. No deaths were reported among the 11 cases.

Health Canada's review of the published literature, clinical trial data for non-marketed BTK inhibitors, and safety information obtained from manufacturers further support a possible class effect for BTK inhibitors and serious hepatotoxicity.

At present, the CPMs for Imbruvica, Calquence and Jaypirca contain warnings regarding hepatotoxicity, which were included independently of this review. Health Canada will continue to work with manufacturers to ensure that CPMs for all BTK inhibitors contain labelling for this risk.

Health Canada will continue to monitor the safety of BTK inhibitors, 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 should new health risks be identified.

Notice of market authorization with conditions

A Notice of Compliance with Conditions (NOC/c) is a form of market authorization with conditions granted to a product on the basis of promising evidence of clinical effectiveness following review of the submission by Health Canada. Communicating a NOC/c is intended to raise awareness on the details of the drug and the type of authorization granted.

Healthcare professionals are encouraged to report to Health Canada any adverse reactions suspected of being associated with marketed health products, including drugs authorized under the NOC/c policy.

The content of these notices reflects current information at the time of publication. Conditions associated with the NOC/c will remain until they have been fulfilled and authorized by Health Canada. For the most up-to-date information, consult Health Canada's NOC database.

Lyvdelzi (seladelpar): Authorization with conditions

Health Canada has issued a Notice of Compliance, under the NOC/c policy, for Lyvdelzi (seladelpar), 10 mg oral capsules. Lyvdelzi is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in adults unable to tolerate UDCA. Patients should be advised of the conditional market authorization for these indications.

For the complete prescribing information and information available for patients/caregivers, please consult the Lyvdelzi Canadian product monograph. The product monograph can be accessed through Health Canada's Drug Product Database, the Gilead Sciences Canada, Inc. website or by contacting Gilead Sciences Canada, Inc. at 1-866-207-4267. Contact the company for a copy of any references, attachments or enclosures.

Scope

This monthly publication is intended primarily for healthcare professionals and includes information on pharmaceuticals, biologics, medical devices and natural health products. It provides a summary of key health product safety information published in the previous month by Health Canada, as well as a selection of new health product safety information meant to raise awareness. New information contained in this issue is not comprehensive but rather represents a selection of clinically relevant items warranting enhanced dissemination.

Reporting Adverse Reactions

Canada Vigilance Program
Telephone: 1-866-234-2345
Fax or mail: Form available on MedEffect Canada

For more information on how to report an adverse reaction, visit the Adverse Reaction and Medical Device Problem Reporting page.

Helpful links

• MedEffect^TM Canada
• Recalls and Safety Alerts Database
• New Safety and Effectiveness Reviews
• Canada Vigilance Adverse Reaction Online Database
• Glossary of Fields in the Canada Vigilance Adverse Reaction Online Database
• Drug Product Database
• Medical Devices Active Licence Listing
• Licensed Natural Health Products Database
• The Drug and Health Product Portal
• Drug Shortages Canada
• Medical Device Shortages
• COVID-19 Vaccines and Treatments Portal

Contact us

Your comments are important to us. Let us know what you think by reaching us at: infowatch-infovigilance@hc-sc.gc.ca

Health Product InfoWatch Editorial Team
Marketed Health Products Directorate
Health Canada
Address Locator 1906C
Ottawa ON K1A 0K9