Summary safety review - Cloxacillin - Assessing the Potential Risk of Acute Kidney Injury

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: 2023-03-22

Product

Cloxacillin-containing products

Potential Safety Issue

Acute kidney injury (AKI), a sudden decrease in renal function

Key Messages

  • Cloxacillin is a prescription antibiotic drug authorized for sale in Canada to treat various bacterial infections.

  • Health Canada reviewed the potential risk of AKI with the use of cloxacillin. The safety review was triggered by reported cases of AKI in patients taking cloxacillin.

  • Health Canada’s review of the available information did not establish a link between the use of cloxacillin and the risk of AKI.  

  • Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for cloxacillin-containing products to note that cases have been reported and to increase awareness of this potential risk.

Overview

Health Canada reviewed the potential risk of AKI with the use of cloxacillin. This safety review was triggered by case reports of AKI received through Health Canada’s Canada Vigilance Program.

Use in Canada

  • Cloxacillin is a prescription antibiotic drug authorized for sale in Canada to treat various bacterial infections.

  • Cloxacillin has been marketed in Canada since the mid-1960s. It is available as oral capsules, granules for oral solution and powder for reconstituted solution for injection.   

  • The number of prescriptions dispensed by Canadian retail pharmacies for cloxacillin decreased from approximately 135,000 prescriptions in 2016 to approximately 68,000 prescriptions in 2021.

Safety Review Findings

  • Health Canada reviewed the available information from searches of Canadian and international reports in the Canada Vigilance databasea, and the scientific literature.

  • Health Canada reviewed 20 cases (9 Canadian and 11 international) of AKI in patients taking cloxacillin from the Canada Vigilance database. Of the 20 cases, 16 (7 Canadian) were found to be possibly linked to the use of cloxacillin, 3 (1 Canadian) were unlikely to be linked, and 1 (Canadian) could not be assessed due to insufficient clinical information. Three deaths (1 Canadian) were reported among the 16 cases that were assessed as having a possible link to the use of cloxacillin. The role of cloxacillin in these events could not be determined, as other medications and life-threatening medical conditions, including severe infections, could have contributed.

  • In the 16 cases found to be possibly linked to use of cloxacillin, all patients had risk factors or were on other medications which were known to cause AKI.

  • Health Canada’s review of the scientific literature found a wide range of incidence rates of AKI in patients using cloxacillin. Overall, evidence of a link between cloxacillin and AKI in the scientific literature was inconclusive due to study limitations and contributing risk factors in patients.

Conclusions and actions

  • Health Canada’s review of the available information did not establish a link between the use of cloxacillin and the risk of AKI.

  • Health Canada will work with the manufacturers to update the CPM for cloxacillin-containing products to note that cases have been reported and to increase awareness of this potential risk.

  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of cloxacillin, and other health products, to the Canada Vigilance Program.

  • Health Canada will continue to monitor safety information involving cloxacillin, 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.

Additional information

The analysis that contributed to this safety review included scientific literature, Canadian and international information, and what is known about the use of cloxacillin 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.