Summary Safety Review - Hydrochlorothiazide - Assessing the potential risk of non-melanoma skin cancer

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: 2019-01-30

Product

Hydrochlorothiazide

Potential Safety Issue

Non-melanoma skin cancer; specifically, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin

Key Messages

  • Hydrochlorothiazide is a prescription drug authorized for sale in Canada to treat high blood pressure and excess build-up of fluid in the body.
  • Health Canada reviewed the risk of non-melanoma skin cancer (NMSC) related to the use of hydrochlorothiazide alone or in combination with other drugs. This review was triggered by two recently published studies1, 2 suggesting a higher risk of NMSC with prolonged use of hydrochlorothiazide.
  • Health Canada's review of the relevant evidence concluded that prolonged use (three years or more) of hydrochlorothiazide has a potential risk of non-melanoma skin cancer that is at least four times the risk of not using hydrochlorothiazide.
  • Health Canada will notify the manufacturers to update the product safety information for all hydrochlorothiazide-containing products, and inform the Canadian public and healthcare professionals about this potential risk and the preventive measures to consider when taking hydrochlorothiazide.

Overview

Health Canada reviewed the potential risk of non-melanoma skin cancer (NMSC) with hydrochlorothiazide use. The safety review was triggered by the publication of two recent studies 1, 2 suggesting a higher risk of NMSC with prolonged use (three years or more) of hydrochlorothiazide.

NMSC is the most commonly diagnosed cancer in Canada. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two major types of NMSC. NMSC is generally curable if treated early and rarely causes death. One in 8 Canadians will develop BCC in their lifetime and 1 in 20 will develop SCC in their lifetime.

Exposure to sun, ultraviolet light and/or drugs that increase the sensitivity of the skin to light are important risk factors for NMSC. Light coloured skin and a personal or family history of skin cancer are also important risk factors.

Hydrochlorothiazide is routinely used to treat high blood pressure and excess build-up of fluid in the body. It is known to increase the sensitivity of the skin to light (e.g., sunburns easily).

Use in Canada

  • Hydrochlorothiazide is a prescription drug authorized for sale in Canada to treat high blood pressure and excess build-up of fluid.
  • Hydrochlorothiazide has been marketed in Canada since 1976, and is marketed alone or in combination with other drugs.
  • There are around 13 million prescriptions filled for hydrochlorothiazide-containing products every year in Canada.

Safety Review Findings

  • Health Canada reviewed the relevant studies on the topic. Data from studies were combined to estimate the overall risk of NMSC with the use of hydrochlorothiazide. The level of the certainty for the findings was also assessed.
  • Five studies analyzing data from thousands of patients investigated the risk of NMSC with the use of hydrochlorothiazide alone or in combination with other drugs. All relevant studies were from North America and Europe, with a majority of patients of light-coloured skin. Studies had important limitations in their designs and methods.
  • Health Canada's review found that the risks for SCC and BCC increase with prolonged use (three years or more) of hydrochlorothiazide. After several years of use, the risk could be up to 4 times higher for SCC and 1.25 times higher for BCC compared to the risk in patients not treated with hydrochlorothiazide. Although substantial uncertainty exists regarding these findings, risk estimates reflect the current best evidence addressing the topic. NMSC is therefore considered a potential risk of prolonged hydrochlorothiazide treatment.

Conclusions and actions

  • Health Canada's review of the relevant evidence suggests that there might be a risk of NMSC with prolonged use of hydrochlorothiazide. Given the substantial uncertainty for the findings, NMSC should be considered a potential risk of prolonged hydrochlorothiazide treatment.
  • Patients taking hydrochlorothiazide should be informed of the potential risk of NMSC and advised to regularly check their skin for new marks or growths as well as changes to existing ones. Patients should report any suspicious skin marks or growths to their healthcare professional. Patients should be advised to limit exposure to sunlight, avoid the use of tanning equipment, and use adequate sun protection (e.g., SPF 30 or higher, clothing, and a hat) to minimize the risk of skin cancer.
  • Alternatives to hydrochlorothiazide may be considered for patients who are at a particularly high risk for NMSC (e.g., light-colored skin, known personal or family history of skin cancer, ongoing immunosuppressive therapy, etc.).
  • Health Canada will notify the manufacturers to update the product safety information of all hydrochlorothiazide-containing products to inform about this potential risk and the preventive measures to consider when taking hydrochlorothiazide.
  • An Information Update and a Health Product Info Watch will be published to further inform Canadians and healthcare professionals about this potential risk.
  • Health Canada will continue to monitor safety information involving hydrochlorothiazide to identify and assess potential risks, as it does for all health products on the Canadian market. 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.

References

  1. Pedersen SA, Gaist D, Schmidt SAJ, Holmich LR, Friis S, Pottegard A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018;78(4):673-681.
  2. Pottegard A, Hallas J, Olesen M et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 2017;282(4):322-331.

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