The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a drug safety alert following the publication of research showing an increased risk of non-melanoma skin cancer with hydrochlorothiazide-containing products.
Two recent pharmaco-epidemiological studies using national data from Denmark have shown a cumulative, dose-dependent increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), including lip SCC, with exposure to hydrochlorothiazide. Adjusted odds ratios (ORs) of BCC with ever-use, high cumulative use and highest cumulative use of hydrochlorothiazide were 1.08 (95% CI 1.05-1.10), 1.29 (95% CI 1.23-1.35) and 1.54 (95% CI 1.38-1.71), respectively. ORs for SCC were 1.75 (95% CI 1.66-1.85), 3.98 (95% CI 3.68-4.31) and 7.38 (95% CI 6.32-8.60), while for lip cancer the rates were 2.1 (95% CI 1.7-2.6), 3.9 (95% CI 3.0-4.9) and 7.7 (95% CI 5.7-10.5), respectively.
Based on the results, best estimate of the increased risk is 7.7-fold for SCC and 1.5-fold for BCC with hydrochlorothiazide 12.5mg daily for 44 years or 25 mg daily for 22 years.
Similar associations were not seen for other diuretics and other hypertensives, including bendroflumethiazide, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and furosemide.
The MHRA estimates that approximately 28,000 patients in the UK are currently taking hydrochlorothiazide-containing medicines.
The agency is advising doctors to inform patients of the risk, particularly with long-term use, and stress the need to regularly check and report any suspicious skin lesions or moles. Furthermore, it says prescribers should reconsider the use of hydrochlorothiazide in patients who have had previous skin cancer and to examine all suspicious moles or skin lesions, potentially including histological examination of biopsies.
