November 2024 Update from Health Product InfoWatch

Monthly Overview of Health Product Safety Notifications

Below is a compilation of health product advisories, type I drug recalls and summaries of concluded safety reviews released in October 2024 by Health Canada.

Apo-Amitriptyline and Elavil

Some batches of Apo-Amitriptyline and Elavil were recalled due to potential exceedance of the interim acceptable intake limit for N-nitroso-nortriptyline (NNORT), a designated impurity.

Methotrexate Injection BP

In light of the ongoing shortage of Methotrexate Injection BP (without preservative), 25 mg/mL in Canada, Health Canada has permitted the temporary importation and sale of US-authorized Methotrexate for Injection, USP (preservative-free) from Fresenius Kabi Canada Ltd. It is crucial to note discrepancies in dosage forms, reconstitution needs, and concentration, among other features.

Health Product Risk Communication: Methotrexate Injection BP

Unauthorized Health Products

Health Canada has alerted Canadians regarding various unauthorized health products available in retail outlets or online that may present significant health hazards.

Advisory: Unauthorized sexual enhancement products

Updates on Health Product Safety Information

The following subjects aim to raise awareness and promote reporting of adverse reactions.

Review article

Pseudoephedrine-containing products and the associated risks of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome

Key points

The evaluation by Health Canada confirmed a rare association between pseudoephedrine-containing products and the risk of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), correlating with findings from the European Medicines Agency (EMA).
Health Canada advises that product labels for natural health and non-prescription products with pseudoephedrine should inform users about the risks of PRES and RCVS, alongside mitigation strategies. Prescription products already have appropriate warnings.
Despite being rare, serious consequences may arise without early intervention, including intracranial hemorrhage, ischemic stroke, and death. Notably, severe hypertension and kidney issues are significant risk factors.
Patients should be directed to stop using any pseudoephedrine products immediately and seek medical assistance if they experience signs of PRES or RCVS, including sudden severe headaches, nausea, confusion, or seizures.
Healthcare professionals are urged to report any adverse reactions believed to be linked with pseudoephedrine products to the Canada Vigilance Program.

Pseudoephedrine acts as a decongestant in various marketed products. It stimulates alpha-adrenergic receptors, resulting in vasoconstriction in respiratory tissues.^{Footnote 1} It also has a lesser impact on beta-adrenergic receptors and is frequently utilized to alleviate nasal congestion from acute respiratory infections and allergic rhinitis.

PRES and RCVS are distinct neurological syndromes characterized by a range of serious symptoms.^{Footnote 2}^{Footnote 3}^{Footnote 4} These conditions can escalate to severe incidents if not promptly managed, highlighting the importance of recognizing their signs and symptoms.

The EMA’s recent safety evaluation determined that pseudoephedrine-containing products present risks for both PRES and RCVS.^{Footnote 5}^{Footnote 6} Following extensive analysis, a total of 34 cases linked these products to the development of either syndrome, although no fatalities were noted, and most cases improved post-treatment.

Health Canada continues to align with EMA’s findings, suggesting enhancements in awareness, including updated labeling practices for pseudoephedrine products. Clear recognitions of risks enhance prevention strategies against the severe complications tied to these conditions.

Healthcare professionals should inquire about the usage of non-prescription medications or natural products among their patients, advocating for discontinuation and medical evaluation in cases of adverse symptoms. Any negative reactions linked with pseudoephedrine products should be reported to the Canada Vigilance Program. The agency remains committed to monitoring risks associated with these products and is prepared to undertake suitable actions to ensure Canadian health safety.

Product Monograph Update

Recent safety labeling updates included in Canadian product monographs are highlighted for your information. A complete registry of safety labeling updates for pharmaceuticals can be found on Health Canada’s Product monograph brand safety updates page. Comprehensive details are accessible via Health Canada’s Drug Product Database.

Brilinta (ticagrelor) and Crestor (rosuvastatin calcium)

The updates in the Drug Interactions and Patient Medication Information sections of Brilinta (ticagrelor) and Crestor (rosuvastatin calcium) highlight the risk of myopathy including rhabdomyolysis linked to interactions between these two medications.

Key messages for healthcare professionals:^{Footnote 7}^{Footnote 8}

Ticagrelor co-administration raises the levels of rosuvastatin in plasma.
This increase can potentially heighten the risk of myopathy, including severe cases like rhabdomyolysis.
Healthcare providers should weigh the cardiovascular benefits of rosuvastatin against these risks.

Scope

This monthly report is primarily directed towards healthcare professionals, offering insights on pharmaceuticals, biologics, medical devices, and natural health products. It summarizes critical safety information disseminated in the prior month by Health Canada and features selected new health product safety material aimed at enhancing awareness. The information provided is selective and emphasizes clinically pertinent details.

Reporting Adverse Reactions

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

For further information on reporting adverse reactions, please visit the Adverse Reaction and Medical Device Problem Reporting page.

Useful Links

Get in Touch

Your feedback matters! Connect with 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

Footnote 1

Pseudoephedrine drug information. Lexicomp. UpToDate. Accessed August 27, 2024.

Return to footnote 1

Footnote 2

Geocadin RG. Posterior reversible encephalopathy syndrome. N Engl J Med. 2023;388(23):2171-8. doi:10.1056/NEJMra2114482

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Footnote 3

Ando Y, Ono Y, Sano A, Fujita N, Ono S. Posterior reversible encephalopathy syndrome: A review of the literature. Intern Med. 2022;61(2):135-41. doi:10.2169/internalmedicine.7520-21

Return to footnote 3

Footnote 4

Nesheiwat O, Al-Khoury L. Reversible cerebral vasoconstriction syndromes. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Updated June 14, 2024.

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Footnote 5