Health Product InfoWatch: August 2023

Contents

• Health products mentioned in this issue
• Monthly recap of health product safety information
• New health product safety information
  • Review articles:
    • Domperidone and psychiatric withdrawal events when used off-label for lactation stimulation
    • Medication errors with specific mineral supplements: calcium, iron, magnesium, and zinc
  • Product monograph updates
    • Third generation aromatase inhibitors: Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole)
    • Topamax (topiramate)
  • Notice of market authorization with conditions
    • Lynparza (olaparib)
    • Tecvayli (teclistamab)
• Scope
• Reporting Adverse Reactions
• Helpful links
• Suggestions?
• Copyright

Health products mentioned in this issue

Pharmaceuticals and biologics

• 0.4% Lidocaine Hydrochloride and 5% Dextrose Injection
• 0.9% and 3% Sodium Chloride Injection, USP
• 5% Dextrose Injection, USP
• Arimidex (anastrozole)
• Aromasin (exemestane)
• Domperidone
• Femara (letrozole)
• Gentamicin(E) Sulfate
• Lactated Ringer's Injection
• Lynparza (olaparib)
• Metronidazole Injection, USP
• Tagrisso (osimertinib)
• Tecvayli (teclistamab)
• Topamax (topiramate)

Natural and non-prescription health products

• Mineral Supplements
• Rhinaris Nasal Mist

Other

• Unauthorized health products

Monthly recap of health product safety information

The following is a list of health product advisories, type I recalls and summaries of completed safety reviews published in July 2023 by Health Canada.

Rhinaris Nasal Mist

The Pendopharm Division of Pharmascience Inc. recalled one lot of Rhinaris Nasal Mist due to the risk of microbial growth.

• Advisory: Rhinaris Nasal Mist

Tagrisso (osimertinib)

This safety review evaluated the risk of rhabdomyolysis and other myopathy-related events including myositis and elevated creatine phosphokinase associated with Tagrisso (osimertinib). Health Canada's review found a possible link. Health Canada is working with the manufacturer to update the Canadian product monograph for Tagrisso to include a warning about reported cases of rhabdomyolysis, myositis and elevated creatine phosphokinase.

Summary Safety Review: Tagrisso (osimertinib)

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 health products at T&T Supermarket in North York, Ontario
• Advisory: Unauthorized health products from two Facebook Marketplace sellers, Pinas-Sabay Canada and Y&Y Online Retail
• Advisory: Unauthorized nicotine buccal pouches
• Advisory: Unauthorized Santen brand eye drops at stores in the Greater Toronto Area
• Advisory: Unauthorized sexual enhancement products
• Advisory: Unauthorized skin lightening and skin treatment products

Various Solution bags

Baxter Corporation recalled affected lots of: 0.4% Lidocaine Hydrochloride and 5% Dextrose Injection; 0.9% and 3% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; Gentamicin(E) Sulfate; Lactated Ringer's Injection; and Metronidazole Injection, USP; as the solution bags may be leaking.

• Type 1 drug recall: 0.4% Lidocaine Hydrochloride and 5% Dextrose Injection
• Type 1 drug recall: 0.9% and 3% Sodium Chloride Injection, USP
• Type 1 drug recall: 5% Dextrose Injection, USP
• Type 1 drug recall: Gentamicin(E) Sulfate
• Type 1 drug recall: Lactated Ringer's Injection
• Type 1 drug recall: Metronidazole Injection, USP

New health product safety information

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

Review articles

Domperidone is a prescription drug that has been marketed in Canada since 1985. It is indicated for the symptomatic management of upper gastrointestinal motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis, and prevention of gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.^{Footnote 1} Although domperidone has not been authorized by Health Canada for lactation stimulation, data derived from Canadian sources indicate that it has been prescribed for this off-label indication at doses exceeding the maximum recommended daily dose of 30 mg.^{Footnote 2}

Health Canada reviewed the potential risk of psychiatric withdrawal events, including depression, anxiety, and insomnia, following abrupt discontinuation or tapering of domperidone when it was used for lactation stimulation. A comprehensive review of available evidence identified a total of 9 relevant case reports (4 Canadian and 5 international).^{Footnote 3 - Footnote 8} Psychiatric withdrawal events developed in patients with or without a personal history of psychiatric illness. Most patients had been taking daily doses of domperidone greater than 30 mg, and all patients had been taking domperidone for longer than 4 weeks prior to the initial discontinuation or tapering attempt. The psychiatric withdrawal events were mostly refractory to commonly prescribed medications used to treat depression and anxiety. In some case reports, individualized (slower) tapering regimens helped to manage symptoms. Two limitations were noted in the case series: there was a small number (9) of relevant case reports, and there was a lack of information regarding patients' concomitant breastfeeding patterns relative to domperidone usage. Discontinuation of breastfeeding may be independently associated with psychiatric symptoms.

Health Canada's review of available information found an association between the abrupt discontinuation or tapering of domperidone, used for lactation stimulation, and the development of psychiatric adverse events.

Health Canada will work with manufacturers to update the Canadian product monographs for domperidone-containing products with language in line with the current level of evidence.

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

Minerals are essential substances that our bodies need to develop and function normally.^{Footnote 9} Minerals are commonly used as dietary supplements, which may be prescribed or recommended by healthcare professionals for a variety of reasons.

In Canada, mineral supplements are regulated as natural health products (NHPs) under the Natural Health Products Regulations. These products are widely used by Canadians. In a 2015 survey, the overall prevalence of mineral supplement/vitamin use among Canadian men and women was 38% and 53%, respectively.^{Footnote 10}

Health Canada has reviewed Canadian reports of medication errors, submitted by healthcare professionals, involving mineral supplements, specifically single-ingredient products containing calcium, iron, magnesium, and zinc. These errors have led to overdoses and, in some cases, serious harm. ^{Footnote 11 Footnote 12 Footnote 13} Confusion with the strength of the elemental and salt content, as displayed on the mineral supplement's product label, was identified as a contributing factor for these medication errors. Misinterpretation due to confusion with the labelled strength of mineral supplements can lead to over- or under-dosing. Concerns regarding the labelling of mineral supplements have been raised by healthcare professionals and poison centres across Canada.

The following is a summary of a Canadian case report that was evaluated by Health Canada, describing an error associated with confusion about the labelled strength of a mineral supplement.

Following a review of reported errors, Health Canada has taken steps to provide additional direction to manufacturers to improve the labelling of specific mineral supplements (calcium, iron, magnesium and zinc) to help reduce confusion between the elemental and salt content:

• The Guidance document: Labelling of natural health products was updated in 2022 with a new section that provides recommendations on best practices for labelling of these mineral supplements.
• The Multi-vitamin/Mineral Supplements Monograph has been revised to include guidance on labelling for these mineral supplements.
• Health Canada's application form to obtain a NHP licence has been updated to provide directives on the format for these mineral supplement labels.

The Natural Health Products Regulations have been amended to include new requirements for a Product Facts Table. Any NHP authorized by Health Canada on or after June 21, 2025 must meet the new labelling requirements. Natural health products authorized by Health Canada prior to June 21, 2025 will have until June 22, 2028 to comply with the new labelling requirements. For further information on NHPs and their licence status in Canada, visit Health Canada's Licensed Natural Health Product Database. This database includes information on licensed NHPs, including a product's medicinal ingredients, its recommended use, dosage information, and any risks associated with product use.

Healthcare professionals should be aware that dosing errors have occurred with mineral supplements in practice settings due to label confusion. Healthcare professionals are encouraged to report medication errors involving these products to CMIRPS, a program in which Health Canada participates. Health Canada will continue to monitor medication errors and work with manufacturers to improve the clarity of NHP labels.

Product monograph updates

The following safety labelling updates, which were recently made to the Canadian product monographs, have been selected 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.

The Warnings and Precautions, Adverse Reactions (Post-Market Adverse Reactions), and Patient Medication Information sections of the Canadian product monographs for Arimidex, Aromasin and Femara have been updated with the risks of tendonitis, tenosynovitis and tendon rupture.

The Contraindications, Warnings and Precautions, and Patient Medication Information sections of the Canadian product monograph for Topamax have been updated with the risk of neurodevelopmental disorders.

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.

Health Canada has issued a Notice of Compliance, under the NOC/c policy, for a new indication for Lynparza (olaparib), 100mg and 150mg tablets. Lynparza is now also indicated, in combination with abiraterone and prednisone or prednisolone, for the treatment of adult patients with deleterious or suspected deleterious BRCA mutated (germline and/or somatic) metastatic castration resistant prostate cancer, in whom chemotherapy is not clinically indicated. Patients must have confirmed BRCA mutation before Lynparza treatment is initiated. 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 Lynparza Canadian product monograph. The product monograph can be accessed through Health Canada's Drug Product Database, the AstraZeneca Canada Inc. website or by contacting AstraZeneca Canada Inc. at 1-800-668-6000. Contact the company for a copy of any references, attachments or enclosures.

*Lynparza's updated product monograph with this NOC/c indication is dated July 2023.

Health Canada has issued a Notice of Compliance, under the NOC/c policy, for Tecvayli (teclistamab), 153 mg / 1.7 mL (90 mg / mL) and 30 mg / 3 mL (10 mg / mL), solution for subcutaneous injection. Tecvayli is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. 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 Tecvayli Canadian product monograph. The product monograph can be accessed through Health Canada's Drug Product Database, the Janssen Inc. website or by contacting Janssen Inc. at 1-800-567-3331 or 1-800-387-8781. 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
• 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: List of shortages and discontinuations
• Stop Illegal Marketing of Drugs and Devices
• List of drugs for exceptional importation and sale
• Coronavirus disease (COVID-19)
• Drug and vaccine authorizations for COVID-19: List of authorized drugs, vaccines and expanded indications
• COVID-19 vaccines and treatments portal
• Reported side effects following COVID-19 vaccination in Canada

Suggestions?

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
Telephone: 613-954-6522, Teletypewriter: 1-800-465-7735 (Service Canada)

Copyright

©2023 His Majesty the King in Right of Canada. This publication may be reproduced without permission provided the source is fully acknowledged. The use of this publication for advertising purposes is prohibited. Health Canada does not assume liability for the accuracy or authenticity of the information submitted in case reports.

Adverse reactions (ARs) to health products are considered to be suspicions, as a definite causal association often cannot be determined. Spontaneous reports of ARs cannot be used to estimate the incidence of ARs because ARs remain underreported and patient exposure is unknown.

Due to time constraints relating to the production of this publication, information published may not reflect the most current information.

References