Summary Safety Review - Sulfamethoxazole containing products - Assessing the potential risk of Drug Reaction 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: 2019-01-07

Product

sulfamethoxazole containing products

Potential Safety Issue

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Key Messages

  • Sulfamethoxazole containing products are prescription drugs authorized for sale in Canada to treat a wide range of infections that are caused by bacteria.
  • Health Canada reviewed the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with sulfamethoxazole containing products. The safety review was triggered because information from an international database suggested that DRESS was being reported at a higher than expected rate for the group of drugs called sulfonamides to which sulfamethoxazole belongs. The product safety information for sulfamethoxazole containing products already includes other types of severe skin reactions.
  • Health Canada's review concluded that there is not enough evidence at this time to establish a link between the risk of DRESS and the use of sulfamethoxazole containing products.
  • Health Canada will continue to monitor safety information involving sulfamethoxazole containing products, as it does for all health products on the Canadian market.

Overview

Health Canada reviewed the potential risk of Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS) with sulfamethoxazole containing products. The review was triggered because Health Canada got information from a WHO international database that suggested DRESS was being reported at a higher rate than expected for a group of drugs called sulfonamides to which sulfamethoxazole belongs.

DRESS is a severe reaction to the use of a drug that affects one or more organs, including the skin. It includes rare but serious and potentially life-threatening side effects to medications, such as fever and severe skin rash with swollen face or peeling of the skin over large areas of the body. Abnormal changes in blood cells or organ function such as the liver and kidney may also occur. These reactions usually happen 2 weeks to 2 months after starting a medication.

Use in Canada

  • Sulfamethoxazole containing products are prescription drugs authorized for sale in Canada to treat a wide range of infections that are caused by bacteria.
  • Sulfamethoxazole was first marketed in Canada in the 1960s in combination with another antibacterial drug, Trimethoprim. There are 7 sulfamethoxazole containing generic products that are available on the Canadian market at this time, including 6 oral products and 1 injectable product.
  • In 2017, there were about 1 million prescriptions filled in Canada for all sulfamethoxazole containing products.

Safety Review Findings

  • At the time of the review, Health Canada received 4 unique Canadian reportsa of DRESS that could be related to sulfamethoxazole use. Health Canada found a possible link between DRESS and sulfamethoxazole in 2 reports. The remaining 2 reports did not provide enough information to assess the role of sulfamethoxazole in the development of DRESS.
  • This safety review also looked at 5 international reports of DRESS that could be related to sulfamethoxazole use. Only 2 of the 5 international reports met the definition of DRESS and included enough information for further review to determine if sulfamethoxazole use was the cause of DRESS. Both of these reports showed a possible link between DRESS and sulfamethoxazole use.
  • Although the trigger for this review was information from a WHO international database that suggested the group of drugs (sulfonamides) had a higher than expected reporting rate for DRESS, the review did not find higher than expected reporting rates specifically with sulfamethoxazole.
  • Health Canada also looked at additional information available from published literature and found 15 international reports and 4 studies of DRESS. The published reports did not use consistent criteria for making the diagnosis of DRESS. Almost half of the international reports (7/15) involved other medications or medical conditions that could have contributed to the development of DRESS. The 4 studies did not provide enough evidence to support sulfamethoxazole as the cause of DRESS.
  • The Canadian product safety information for sulfamethoxazole-containing products includes all other types of severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Although DRESS is not included in the Canadian product safety information, the Warnings and Precautions section includes some signs and symptoms of DRESS, such as severe liver damage (fulminant liver necrosis), hypersensitivity of the respiratory tract (cough, shortness of breath, and lung infiltrates), and an increase in the number of a specific type of white blood cell (eosinophilia). Additionally, impaired kidney function sometimes reported as kidney (renal) failure is included under Adverse Reactions.
  • Health Canada also looked at additional information available from international product safety information. International product safety information includes DRESS only for some sulfamethoxazole containing products in the European Union and Australia whose product information has been updated after 2016.

Conclusions and actions

  • Health Canada's review of the available information concluded that there is not enough evidence at this time to establish a link between the risk of DRESS and the use of sulfamethoxazole containing products. Additionally, some of the signs and symptoms of DRESS are already included in the Canadian product safety information. For these reasons, Health Canada's review concluded that the safety information for these products is appropriate at this time.
  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these and other health products.
  • Health Canada will continue to monitor safety information involving sulfamethoxazole 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 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. Canadian reports can be accessed through the Canada Vigilance Online Database.

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