Summary Safety Review - Oral, Over-the-counter Diphenhydramine - Containing Products - Assessing the Potential Risk of Serious Side Effects in Children

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2022-03-01

Product

Oral, over-the-counter diphenhydramine-containing products

Potential Safety Issue

Serious side effects in children under 2 years of age, or from accidental overdose or problematic use in children under 18 years of age.

Key Messages

  • Most diphenhydramine-containing products (DCPs) are authorized for sale in Canada as over-the-counter (OTC) drugs to relieve symptoms of several medical conditions, including allergies. They belong to a group of drug products known as first-generation antihistamines.
  • In 2019, the Canadian Society of Allergy and Clinical Immunology (CSACI) published a position statement1 recommending the use of newer-generation antihistamines for the treatment of hay fever (allergic rhinitis) and hives (urticaria) because of the side effects associated with first-generation antihistamines. The CSACI statement generated interest from the Canadian public about the safety of DCPs at both the recommended and higher doses, specifically in children.
  • Therefore, as a precaution, Health Canada reviewed known and potential serious side effects with the oral use of DCPs in children under 2 years of age, and from accidental overdose or problematic use in children under 18 years of age. The purpose of the review was to assess whether the types and/or frequencies of risks associated with the authorized use of DCPs continue to be accurately and clearly communicated to consumers and healthcare professionals.
  • Health Canada's review of the available information found no change in the type or frequency of serious side effects associated with the use of DCPs to warrant regulatory action at this time.
  • Health Canada will publish a Health Product InfoWatch article to increase awareness of the potential for rare serious risks associated with the use of these products in children, and to encourage continued reporting of side effects of DCPs to Health Canada. The Department will revisit this topic in 1 year to determine if there is any new information that warrants further assessment and action by Health Canada.
  • Health Canada continues to work with domestic and international partners to ensure alignment and consistency in communicating risks related to DCPs to consumers and healthcare professionals.

Overview

In 2019, the CSACI published a position statement1 recommending the use of newer-generation antihistamines for the treatment of hay fever (allergic rhinitis) and hives (urticaria) because of the side effects associated with first-generation antihistamines.

The statement did not identify new safety information for first-generation antihistamines, however, it generated interest from the Canadian public about the safety of DCPs at recommended or higher doses, specifically in children.

Diphenhydramine has the potential for problematic use and overdose that can lead to serious side effects in children, including seeing and hearing things that are not there (hallucinations), sudden change in the brain's normal electrical activity (seizures), palpitations, difficulty in breathing and coma.

The use of DCPs to treat allergic symptoms is widespread, particularly in children. As a precaution, Health Canada assessed known and potential serious side effects associated with the use of DCPs in children under 2 years of age, and serious side effects related to problematic use and accidental overdose in children under 18 years of age. The purpose of the review was to determine if there was a change in the type and/or frequency of side effects associated with the use of DCPs in these vulnerable populations.

Use in Canada

  • Oral DCPs are authorized for sale in Canada to treat the symptoms of allergies, temporarily relieve dry cough, sneezing and runny nose due to the common cold, or as nighttime sleep aids. These products are available for use in children and adults.
  • There are 83 marketed, OTC, oral DCPs in Canada as of February 8, 2022.
  • Oral DCPs have been marketed in Canada since 1946. They are available as capsules, caplets, tablets, chewable tablets, and liquid formulations (solution, elixir, syrup).

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilance databasea, published literature, and the manufacturer.
  • Health Canada reviewed 52 Canadian case reports involving diphenhydramine use in children, received between December 1983 and March 2019; none were fatal. Of the 52 cases, only 5 contained enough information to determine whether there was a link between the use of diphenhydramine and the reported serious side effects in children:
    • One case involved a child under 2 years of age with difficulty in controlling movements (dyskinesia); this case was found to be probably linked with the use of oral diphenhydramine at the recommended dose.
    • Four cases involved problematic use or overdose in children. Reported side effects included false beliefs (delusions), hallucinations, disorientation, dizziness, hyperactivity, widened (dilated) pupils, rapid heart rate (tachycardia), and seizure, alone or accompanied by vomiting. Two cases were found to be probably linked, and 2 were found to be possibly linked with the use of oral diphenhydramine.
  • Health Canada also reviewed international literature cases. The side effects reported in these cases were consistent with the known safety profile of diphenhydramine.
  • Overall, Health Canada's review found no change in the type or frequency of serious side effects reported with the use of DCPs.

Conclusions and actions

  • Health Canada's review of the available information found no change in the type or frequency of serious side effects associated with the use of DCPs to warrant regulatory action at this time.
  • As a general precaution, in November and December 2021, Health Canada communicated with consumers and caregivers through social media about the proper use and storage of OTC and prescription medications.
  • A Health Product InfoWatch article will be published to increase awareness of the potential for serious risks associated with the use of DCPs in children, and to encourage reporting of diphenhydramine side effects to Health Canada. The topic will be re-visited in 1 year to determine if there is any new information that warrants further assessment and action by Health Canada.
  • The Department continues to work with domestic and international partners to ensure alignment and consistency in communicating risks related to DCPs to consumers and healthcare professionals.
  • Health Canada will continue to monitor safety information involving oral, OTC diphenhydramine-containing products, 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 any new health risks be identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of diphenhydramine-containing drugs both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Fein, M.N., Fischer, D.A., O'Keefe, A.W. et al. CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance adverse reaction online database

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