Summary Safety Review - Piperacillin Containing Products (alone or in combination with tazobactam) - Assessing the Potential Risk of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)

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: 2016-02-24

Product

Piperacillin containing products (alone or in combination with tazobactam)

Potential Safety Issue

Assessing the Potential Risk of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)

Key Messages

  • Piperacillin is an antibiotic that is available alone or in combination with a product that enhances piperacillin activity (tazobactam). Both products are administered into a vein (intravenously) or in a muscle (intramuscularly) and are used to treat different types of infections.
  • Following published cases of DRESS with the drug combination piperacillin and tazobactam, Health Canada carried out a safety review for all piperacillin containing products.
  • Health Canada's safety review concluded that there is evidence of a link between the drug combination piperacillin and tazobactam and DRESS. Additionally, a contributing role for piperacillin alone and DRESS could not be ruled out. Health Canada has begun updating the Canadian prescribing information for the drug combination piperacillin-tazobactam to include a warning statement for the risk of DRESS, and as a potential side effect for piperacillin alone. Also, Health Canada will issue a Health Product InfoWatch article about these changes.

Overview

Health Canada carried out a safety review to evaluate the potential link between the antibiotic drug combination piperacillin and tazobactam or piperacillin alone and DRESS following published cases of DRESS associated with the drug combination. DRESS describes a group of rare but serious and potentially life-threatening adverse reactions to medications, such as fever, severe skin rash with swollen face or peeling of the skin over large areas of the body, etc. These reactions usually occur two weeks to two months after starting a medication.

Use in Canada

  • Piperacillin is an antibiotic that is available alone or in combination with a product that enhances piperacillin activity (tazobactam). They are both administered into a vein (intravenously) or in a muscle (intramuscularly) and are used to treat infections in different parts of the body.
  • The drug combination piperacillin and tazobactam has been marketed in Canada since 1993. Piperacillin alone has been marketed in Canada since 1982. In 2014, the drug combination piperacillin and tazobactam was used approximately 100 times more often than piperacillin alonea.

Safety Review Findings

  • At the time of Health Canada’s review, two cases of DRESS suspected of being linked with the drug combination piperacillin and tazobactam were reported in Canadab. Upon further review, both cases of DRESS were considered linked with piperacillin-tazobactam drug combination.
  • A Health Canada review of the published scientific and medical literature identified 17 published cases of DRESS linked with the drug combination piperacillin and tazobactam. One case out of 17 resulted in death; however a direct role for the drug combination could not be established due to pre-existing health problems. In 10 cases, the patients recovered after stopping the combination treatment with or without additional treatment reported. The six remaining cases could not be assessed further because the information contained in the reports was incomplete.
  • Additional investigation of a subset of the 17 cases, suggests that the role played by piperacillin alone could not be excluded.

Conclusions and actions

  • Health Canada's safety review concluded that there is evidence of a link between the drug combination piperacillin and tazobactam and DRESS. Additionally, a contributing role for piperacillin alone and DRESS could not be ruled out.
  • After reviewing the available evidence, Health Canada has begun updating the Canadian prescribing information for the drug combination of piperacillin and tazobactam with a warning statement for the risk for DRESS and the inclusion of DRESS as a potential side effect to piperacillin alone.
  • Health Canada will publish an article in the Health Product InfoWatch to communicate the update of labelling associated with drug combination "piperacillin and tazobactam" and piperacillin alone. This publication is intended to raise awareness among health care professionals and to encourage the reporting of similar adverse reactions.
  • Health Canada will continue to monitor side effect information involving piperacillin and tazobactam, 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 adverse reaction reports and what is known about the use of this drug combination both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.
Footnotes

  1. This data was provided by IMS Health Canada Inc. and is copyright protected. Prior to reproduction or other use of this data, it is necessary to seek the authorization of IMS Health Canada Inc.
  2. Canadian reports can be accessed through the Canada Vigilance Online Database.

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