Summary Safety Review - ULORIC (febuxostat) - Assessing a Possible 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: 2016-06-13

Product

Uloric (febuxostat)

Potential Safety Issue

Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS).

Key Messages

  • Uloric (febuxostat) is used to lower blood uric acid levels in patients with gout (a painful inflammation of a joint due to uric acid forming hard crystals).
  • A safety review was started after finding international cases of Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS) suspected of being linked with the use of febuxostat.
  • Health Canada has reviewed all the information available and concluded that the data, though limited, suggested a possible link between DRESS and febuxostat. The Canadian prescribing information for Uloric has been updated to include the risk of DRESS. Health Canada has also published an article in the Health Product InfoWatch to raise awareness and encourage reporting by patients and healthcare professionals.

Overview

Health Canada carried out a safety review after finding international cases of DRESS suspected of being linked with the use of Uloric (febuxostat). DRESS describes a group of rare, but serious and potentially life-threatening, side effects of a medication, with symptoms such as fever, severe skin rash with swollen face or peeling of the skin over large areas of the body, etc. These reactions usually happen two weeks to two months after starting a medication.

Use in Canada

  • Febuxostat is an oral medication used to lower uric acid levels in patients with gout (a painful inflammation of a joint due to uric acid forming hard crystals).
  • Febuxostat has been marketed in Canada under the brand name Uloric since 2010.
  • At the time of review, there were approximately 82,000 prescriptions per year for Uloric in Canada. In comparison, the most commonly used medication to treat gout, allopurinol, had 2,903,282 prescriptions in the same timeframe. Allopurinol has been available on the Canadian market for decades.

Safety Review Findings

  • At the time of this review, Health Canada had received 1 Canadian report of DRESS in a patient taking febuxostat.a This case was also published in the scientific literature.1
  • Three additional international cases of DRESS in association with febuxostat therapy were reported in the scientific literature.
  • The World Health Organization (WHO) Global Individual Case Safety Reports Database System (VigiBase) had received 13 international cases of DRESS suspected of being associated with the use of febuxostat.b
  • Ten cases of DRESS suspected of being associated with the use of febuxostat worldwide had been reported to Health Canada by the manufacturer, 2 of which were also published in the scientific literature.
  • Allopurinol is also known to be associated with serious skin reactions including DRESS. Many of the patients that have reported serious skin and hypersensitivity reactions with febuxostat had also reported previous skin reactions to allopurinol.

Conclusions and actions

  • Health Canada has reviewed all the information available and concluded that the data, though limited, suggested a possible link between DRESS and febuxostat.
  • Health Canada has asked the manufacturer of Uloric (febuxostat) to include DRESS in the Canadian prescribing information. The risk of DRESS has been added to the list of serious skin and hypersensitivity reactions.
  • The Canadian prescribing information for Uloric (febuxostat) also mentions that many of the patients who have had serious skin reactions with this product also reported similar skin reactions while using allopurinol. Febuxostat should be used with caution in patients who have experienced previous skin reactions to allopurinol.
  • Health Canada also published an article in the May 2015 edition of the Health Product InfoWatch to inform patients and healthcare professionals of this risk.
  • Health Canada will continue to monitor side effect information for febuxostat, 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 both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Doré M, Frenette AJ, Mansour AM, et al. Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels. Ann Pharmacother 2014;48(5):648-51.

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.
  2. World Health Organization (WHO) adverse reaction information provided by: The WHO collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO.

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