Led by Danish-based researchers, the study showed a substantially increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), associated with long-term hydrochlorothiazide use.
Prescribers should advise patients taking hydrochlorothiazide-containing products to regularly check for and report any suspicious skin lesions or moles. Patients should also be counselled to limit their exposure to sunlight and UV rays and to use adequate sun protection. The MHRA recommends that use of hydrochlorothiazide be reconsidered in patients who have previously had skin cancer.
Based on nationwide Danish registry data, the case-control study compared cumulative use of hydrochlorothiazide from 1995 to 2012 in people diagnosed with SCC or basal cell carcinoma (BCC) to hydrochlorothiazide use in cancer-free control groups. In total, 71,533 BCC and 8,629 SCC cases were identified and matched by age and gender to 1,430,883 and 172,462 controls, respectively.
On average, people who took hydrochlorothiazide daily for at least 6 years (cumulative dose ≥50g) were 29% more likely to develop BCC and almost four times more likely to develop SCC than those who did not take hydrochlorothiazide.
A clear dose-response relationship was found for both types of skin cancer with the highest odds ratios observed in the upper exposure category (≥200g cumulative dose): 1.54 (95% CI 1.38–1.71) for BCC and 7.38 (95% CI 6.32–8.60) for SCC.
The photosensitising actions of hydrochlorothiazide could be a mechanism for the increased skin cancer risk. The researchers did not find similar associations between non-melanoma skin cancer and use of other diuretics or antihypertensives.
The researchers previously demonstrated a strong dose-response association between use of hydrochlorothiazide and SCC of the lip, which prompted their latest study.