Summary Safety Review - Valacyclovir-containing Products - Assessing the Potential Risk of Drug Reaction with Eosinophilia and Systemic Symptoms

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: 2022-05-24

Product

Valacyclovir-containing products

Potential Safety Issue

Drug reaction with eosinophilia and systemic symptoms (DRESS), a rare, but serious, and potentially life-threatening drug reaction that includes fever, rash, high white blood cell count, and affects 1 or more organs.

Key Messages

  • Valacyclovir is authorized for sale in Canada to treat cold sores (herpes labialis) and shingles (herpes zoster) and to treat, suppress or reduce the transmission of genital herpes.
  • Health Canada reviewed the potential risk of DRESS with the use of valacyclovir-containing products. The safety review was triggered by a labelling update for valacyclovir-containing products related to this risk in Europe.
  • Health Canada's review concluded that there may be a link between the use of valacyclovir-containing products and the potential risk of DRESS.
  • Health Canada will work with the manufacturers to update the Canadian product safety information for valacyclovir-containing products to include the risk of DRESS.

Overview

Health Canada reviewed the potential risk of DRESS with the use of valacyclovir-containing products. This safety review was triggered by updates made by the European Medicines Agency to the product safety information for valacyclovir-containing products to include the risk of DRESS.

DRESS is a rare, but serious, and potentially life-threatening drug reaction that includes fever, severe skin rash or peeling of the skin over large areas of the body, swollen face and high white blood cell count, affecting 1 or more organs. The symptoms of DRESS typically appear within 2 weeks to 2 months after starting a medication.

DRESS is also known as drug rash with eosinophilia and systemic symptoms, drug induced hypersensitivity syndrome or DRESS syndrome.

Use in Canada

  • Valacyclovir is a prescription antiviral drug authorized in Canada to treat herpes infections, such as cold sores (herpes labialis) and shingles (herpes zoster). It is also used to treat, suppress or reduce the transmission of genital herpes.
  • Valacyclovir has been marketed in Canada since 1996. It is currently available as 500 mg and 1,000 mg tablets, under the brand name Valtrex, or as generics.
  • More than 2 million prescriptions were dispensed annually by Canadian retail pharmacies between 2017-2021. Valacyclovir can also be used in the hospital setting.

Safety Review Findings

  • Health Canada reviewed information provided by the manufacturer of the brand name product, and from searches of the Canada Vigilance databasea and the published literature.
  • Health Canada reviewed 115 cases (3 Canadian, 112 international) of DRESS in patients taking valacyclovir. Of the 115 cases, 26 (international) met the criteria for further assessment to determine if there was a link between the use of valacyclovir and DRESS.
  • Of the 26 case reports, 4 cases, including 3 published in the scientific literature1, were found to be probably linked to the use of valacyclovir. Twenty-one cases, including 1 death, were found to be possibly linked, and 1 case was unlikely to be linked to the use of valacyclovir. In 25 of the 26 cases, patients were also taking other medications known to cause DRESS.

Conclusions and actions

  • Health Canada's review of the available information concluded that there may be a link between the use of valacyclovir-containing products and the potential risk of DRESS.
  • Health Canada will work with the manufacturers to update the Canadian product safety information for valacyclovir-containing products to include the risk of DRESS.
  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of valacyclovir and other health products to the Canada Vigilance Program.
  • Health Canada will continue to monitor safety information involving valacyclovir-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 valacyclovir both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Ingen-Housz-Oro S, Bernier C, Gener G, Fichel F, Barbaud A, Lebrun-Vignes B and Assier H (2019) Valaciclovir: a culprit drug for drug reaction with eosinophilia and systemic symptoms not to be neglected. Three cases. Br. J. Dermatol. 180 (3): 666-667.

Footnotes

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