Health Product InfoWatch: March 2025

Contents

• Monthly recap of health product safety information
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide)
  • Isotretinoin
  • Kids by Babyganics SPF 50 mineral sunscreen totally tropical
  • Lacosamide Injection, USP
  • Oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban and warfarin)
  • Unauthorized Health Products
• New health product safety information
  • Review article
    • Systemic fluoropyrimidines and severe toxicity in patients with dihydropyrimidine dehydrogenase deficiency
  • Product monograph update
    • Arava (leflunomide)
  • Notice of market authorization with conditions
    • Qalsody (tofersen): 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 February 2025 by Health Canada.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide)

This safety review evaluated the risks of suicide, self-harm and suicidal/self-harm ideation with the use of GLP-1 RAs. Health Canada’s review concluded that the available evidence does not support a causal link between GLP-1 RAs and suicide, self-harm, and suicidal/self-harm ideation in the general type 2 diabetes mellitus (T2DM) population. For obese patients, regardless of underlying T2DM status, the existing evidence is inconsistent and inconclusive. Health Canada has also published a review article to share additional information with healthcare professionals. Health Canada will continue to monitor the safety of GLP-1 RAs.

Safety Summary Review: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide)

Isotretinoin

This safety review evaluated the risk of sacroiliitis with the use of isotretinoin-containing products. Health Canada’s review found a possible link. Health Canada is working with the manufacturers to update the Canadian product monographs for isotretinoin-containing products to include the risk of sacroiliitis.

Safety Summary Review: Isotretinoin

Kids by Babyganics SPF 50 mineral sunscreen totally tropical

SC Johnson & Son, Inc. recalled certain lots of Babyganics sunscreen products after an impurity (a solvent known as monoglyme or 1,2-dimethoxyethane) was found in the rollerball and continuous spray formulas at levels exceeding the allowable limit. This impurity may pose health risks.

Advisory: Kids by Babyganics SPF 50 mineral sunscreen totally tropical

Lacosamide Injection, USP

One lot of Lacosamide Injection, USP (10mg/mL) was recalled due to the presence of particulate matter.

Type 1 drug recall: Lacosamide Injection, USP

Oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban and warfarin)

This safety review evaluated the risk of splenic rupture with the use of oral anticoagulants. Health Canada’s review found a possible link. Health Canada is working with the manufacturers to update the Canadian product monographs for all oral anticoagulants to include the risk of atraumatic splenic rupture.

Safety Summary Review: Oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban and warfarin)

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: Unauthorized sexual enhancement products

New health product safety information

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

Review article

Systemic fluoropyrimidines and severe toxicity in patients with dihydropyrimidine dehydrogenase deficiency

Systemic fluoropyrimidines are a class of prescription drugs that includes capecitabine tablets and fluorouracil (5-fluorouracil) injection. In Canada, they are authorized to treat various types of cancers alone or in combination with other drugs.^{Reference 1} Capecitabine tablets and fluorouracil injection are potent drugs and should be prescribed only by physicians experienced with cancer chemotherapeutic drugs.^{Reference 2Reference 3}

Severe, life-threatening, or fatal adverse reactions (e.g., stomatitis, diarrhea, neutropenia, and neurotoxicity) associated with fluoropyrimidines have been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. DPD is an enzyme involved in the metabolism of capecitabine and fluorouracil, and is encoded by the dihydropyrimidine dehydrogenase (DPYD) gene. Patients with certain mutations in the DPYD gene that cause a complete or near complete absence of DPD activity (DPD deficiency) are at the highest risk for severe, life-threatening, or fatal adverse reactions, while those with certain DPYD variants causing partial DPD deficiency have been shown to have an increased risk of severe toxicity. Use of capecitabine tablets or fluorouracil injection is contraindicated in patients with known complete absence of DPD activity (complete DPD deficiency) as no dose has been deemed safe for these patients.^{Reference 2Reference 3}

Health Canada recommends that testing for DPD deficiency be considered before treatment with capecitabine tablets and fluorouracil injection, based on local availability and current guidelines.^{Reference 2Reference 3} Genotype testing is a common approach to test for DPD deficiency. While there are 4 main DPYD variants associated with a partial to complete absence of DPD activity (c.1905+1G>A, c.2846A>T, c.1679T>G, and c.1236G>A [synonymous variant c. 1129-5923C>G]), evidence for these variants has been largely established from patients of European ancestry. The predictive utility of these variants may be limited in other ethnic or racial populations, where other variants associated with an increased risk may be prevalent (e.g., c.557A>G in patients of African ancestry). Testing options for the DPYD genotype can range from targeted analysis of specific variants to sequencing of the entire coding region. Some patients, such as those of non-European ancestry, may carry other risk variants that are not commonly included in targeted genetic tests.^{Reference 4}

Between January 1, 2019 and February 5, 2025, Health Canada received 10 Canadian reports of adverse reactions involving severe toxicity associated with systemic fluoropyrimidines (6 related to capecitabine tablets and 4 to fluorouracil injection) in patients with DPD deficiency. Of the 10 cases, 6 had a fatal outcome. Of the 6 fatal cases, one involved prospective DPYD genotype testing that failed to identify the patient’s DPD deficiency. Variations in the DPYD gene were later confirmed upon full gene sequencing. For the other 5 fatal cases, it could not be confirmed whether DPYD genotype testing failed to identify the patient’s DPD deficiency due to limited available information.

Healthcare professionals are encouraged to report any adverse reactions suspected of being associated with fluoropyrimidines to the Canada Vigilance Program.

Health Canada will continue to monitor the safety of fluoropyrimidines, 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.

Product monograph update

The following safety labelling update, which was recently made to the Canadian product monograph, has been included for your awareness. A complete list of safety labelling updates for pharmaceuticals is available on Health Canada's Product monograph brand safety updates page. Canadian product monographs can be accessed through Health Canada's Drug Product Database.

Arava (leflunomide)

The Warnings and Precautions, Adverse Reactions (Post-Market Adverse Reactions), and Patient Medication Information sections of the Canadian product monograph for Arava^{Footnote *} have been updated with the risk of impaired wound healing after surgery.

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.

Qalsody (tofersen): Authorization with conditions

Health Canada has issued a Notice of Compliance, under the NOC/c policy, for Qalsody (tofersen), 100 mg / 15 mL (6.7 mg / mL) solution for intrathecal injection. Qalsody is indicated for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene. Patients should be advised of the conditional market authorization for this indication.

For the complete prescribing information and information available for patients/caregivers, please consult the Qalsody Canadian product monograph. The product monograph can be accessed through Health Canada’s Drug Product Database, the Biogen Canada Inc. website or by contacting Biogen Canada Inc. at 1-416-234-7999. 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™ Canada
• Recalls and Safety Alerts Database
• New Safety and Effectiveness Reviews
• 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

References