Summary Safety Review - Beta-lactam antibiotics - Assessing the potential risk of severe skin side effects

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: 2018-09-10

Product

Beta-lactam antibioticsa

Potential Safety Issue

Severe skin side effects (Severe Cutaneous Adverse Reactions, SCAR).b

Key Messages

  • Beta-lactam antibiotics are authorized for sale in Canada to treat many types of bacterial infections.
  • Health Canada reviewed the risk of SCAR with beta-lactam antibiotics (including amoxicillin-clavulanic acid) because of information submitted by a manufacturer that suggested a potential risk of SCAR with amoxicillin-clavulanic acid. Since the risk of SCAR is included in the product information for some beta-lactam antibiotics, Health Canada decided to review all beta-lactam antibiotics, focusing on products that do not already include SCAR in their product information.
  • Health Canada's review of the available information established a link between the use of beta-lactam antibiotics and the risk of SCAR.
  • Health Canada will be working with the manufacturers to update the product safety information of beta-lactam antibiotics (that do not already include SCAR) to inform healthcare professionals and patients about the potential risk of SCAR.

Overview

Beta-lactam antibiotics are prescription drugs, which are authorized for sale in Canada to treat many types of bacterial infections.

Health Canada's review of the potential risk of severe skin side effects (SCAR) with beta-lactam antibiotics was triggered after receiving information from a manufacturer that included reports of SCAR with the use of a widely prescribed beta-lactam antibiotic (amoxicillin-clavulanic acid) in Canada. Severe skin side effects are drug reactions that are serious, but rare.

Inconsistent product information about the risk of SCAR for various beta-lactam antibiotics also triggered Health Canada to conduct this review, focusing on products that do not already include SCAR in their product information.

Use in Canada

  • Beta-lactam antibiotics have been marketed in Canada for over 60 years. Penicillin V (phenoxymethylpenicillin) was the first beta-lactam antibiotic marketed in Canada on December 31, 1960.
  • The following beta-lactam antibiotics are currently marketed in Canada: ampicillin, amoxicillin, piperacillin, phenoxymethylpenicillin/penicillin V, penicillin G, cloxacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cephalexin, cefazolin, cefadroxil, cefoxitin, cefuroxime axetil, cefprozil, cefotaxime, ceftazidime, cetriazone, cefixime, cefepime, aztreonam, meropenem, ertapenem, imipenem-cilastatin and ceftolozane-tazobactam.
  • Beta-lactam antibiotics are a widely prescribed group of antimicrobial agents, with about 11.4 million prescriptions filled in Canada in 2016.

Safety Review Findings

  • At the time of the review, Health Canada had received 45 Canadianc reports of SCAR related to beta-lactam antibiotics use. Of these reports, 26 were further assessed as they met the criteria set for this review. Of these 26 reports, 19 were found to have a possible link between the use of beta-lactam antibiotics and SCAR, 4 unlikely to have a link and 3 could not be assessed due to lack of information.
  • A search in the World Health Organization's Adverse Drug Reaction Database found 8855 reports of SCAR in patients treated with beta-lactam antibiotics. Health Canada's review found that there was more frequent reporting of SCAR for the majority of beta-lactam antibiotics than expected in the general population.
  • This safety review also examined the medical and scientific literature. There were 9 published studies and 79 reported cases of SCAR for beta-lactam antibiotics. Health Canada's review of the published studies and cases supported a possible link between SCAR and beta-lactam antibiotics use.

Conclusions and actions

  • Health Canada's review found a possible link between the use of beta-lactam antibiotics and the risk of SCAR.
  • Health Canada will be working with manufacturers to update the product safety information of beta-lactam antibiotics (that do not already include SCAR) to inform healthcare professionals and patients about this potential risk.
  • Health Canada will continue to monitor safety information involving beta-lactam antibiotics, 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 if and when any new health risks are 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 these drugs both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

  1. The following beta-lactam antibiotics are currently marketed in Canada and have been included as part of this review: ampicillin, amoxicillin, piperacillin, phenoxymethylpenicillin/penicillin V, penicillin G, cloxacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cephalexin, cefazolin, cefadroxil, cefoxitin, cefuroxime axetil, cefprozil, cefotaxime, ceftazidime, cetriazone, cefixime, cefepime, aztreonam, meropenem, ertapenem, imipenem-cilastatin and ceftolozane-tazobactam.
  2. Serious but rare drug reactions that include the following: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS).
  3. Canadian reports can be accessed through the Canada Vigilance Online Database.

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