Summary Safety Review - Amoxicillin-containing Products - Assessing the Potential Risk of Aseptic Meningitis

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: 2021-12-10

Product

Amoxicillin-containing products

Potential Safety Issue

Aseptic meningitis, a condition where the linings of the brain and spinal cord become inflamed without an infectious cause.

Key Messages

  • Amoxicillin-containing products are prescription antibiotics authorized for sale in Canada to treat or prevent certain bacterial infections.
  • Health Canada reviewed the risk of aseptic meningitis with the use of amoxicillin-containing products following the publication of case reports in the literature in the past 3 years concerning this risk.
  • At the time of this review, the Canadian product safety information (Canadian Product Monograph) for some combination products containing amoxicillin and clavulanic acid included information on the risk of aseptic meningitis. The purpose of this review was to assess if additional actions were required for amoxicillin-containing products marketed in Canada.
  • Health Canada's review of the available information concluded that there may be a link between amoxicillin-containing products and the risk of aseptic meningitis.
  • Health Canada will work with the manufacturers to update the Canadian Product Monographs (CPMs) for amoxicillin-containing products that do not already contain this safety information. The Department will also inform healthcare professionals and patients about this risk and changes to the CPMs.

Overview

Health Canada reviewed the potential risk of aseptic meningitis in patients treated with amoxicillin-containing products. The safety review was triggered by case reports published in the literature in the past 3 years concerning this risk.

Use in Canada

  • Amoxicillin-containing products are antibiotics authorized for sale in Canada to treat or prevent certain bacterial infections.
  • Amoxicillin-containing products have been marketed in Canada since 1974 under various brand names. Generic versions of amoxicillin alone, in combination with clavulanic acid, or as part of a kit containing amoxicillin, clarithromycin and lansoprazole, are also available. The amoxicillin-containing products come in different dosage forms including tablets, capsules, oral suspensions, or granules for oral suspensions.
  • There were about 7.2 million prescriptions filled annually in Canada for these products between 2016-2020. Of these, about 2 million prescriptions per year were filled for children less than 18 years of age.

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilance databasea, international databases, and published literature.
  • Health Canada reviewed 21 cases (3 Canadian, 18 international) of aseptic meningitis in patients receiving amoxicillin-containing products, of which 20 were from the scientific literature and 1 (Canadian) was obtained from the Canada Vigilance database. All cases were reported in adults.
  • Of the 21 case reports, 7 cases (1 Canadian) were found to be probably linked and 14 cases (2 Canadian) were possibly linked with the use of amoxicillin-containing products.
    • Of the 7 cases found to be probably linked, 4 were with the use of amoxicillin and 3 with the use of amoxicillin and clavulanic acid.
    • Of the 14 cases found to be possibly linked, 10 were with the use of amoxicillin and 4 were with the use of amoxicillin and clavulanic acid.
  • Health Canada also assessed a study of international cases reported to the World Health Organization database, which supported a link between the risk of aseptic meningitis and the use of amoxicillin.

Conclusions and actions

  • Health Canada's review of the available information concluded that there may be a link between the use of amoxicillin-containing products and the risk of aseptic meningitis.
  • Health Canada will work with the manufacturers to include the risk of aseptic meningitis in the CPMs for amoxicillin-containing products that do not already contain this safety information.
  • The Department will also inform healthcare professionals and patients about this risk and changes to the CPMs through the InfoWatch.
  • Health Canada will continue to monitor safety information involving amoxicillin- 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 amoxicillin-containing products both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.