Objective: In 2018, the Pharmacological Risk Assessment Committee alerted to a potential relationship between accumulated hydrochlorothiazide dosage and the risk of non-melanoma skin cancer. To study this relationship we used data from the Spanish Pharmacovigilance System for Medicinal Products of Human Use.
Materials and methods: Following a case search for every thiazide potentially associated with (SMQ/MedDRA) "Malignant Skin Neoplasms and not Otherwise Specified Skin Neoplasms", a series of disproportionality analyses were conducted by estimating the reporting odds ratio (95% confidence interval). Registered adverse drug reactions and disproportionality through the reported odds ratio were the main outcome measures.
Results: For basal cell carcinoma, reporting odds ratio was 4.8 (2.2 - 10.7); squamous cell carcinoma 3.2 (0.9 - 10.5); malignant melanoma, 0.8 (0.2 - 3.5). We found both disproportionality and association between hydrochlorothiazide and basal cell carcinoma, but none of these were found regarding malignant skin melanoma. In the case of squamous cell carcinoma, the lower confidence interval limit was below 1, thus the disproportionality value was not statistically significant. The accumulated hydrochlorothiazide dose was 36,714 mg for basal cell carcinoma; 98,288 mg for squamous cell carcinoma; and 38,444 mg for malignant melanoma.
Conclusion: The results in Spain, where sun exposure is significant, are consistent with the data in the Pharmacological Risk Assessment Committee's alert, which were obtained in Denmark for both basal cell carcinoma and malignant melanoma. However, the results for squamous cell carcinoma did not reach statistical significance, although the reporting odds ratio value suggested a potential relationship between hydrochlorothiazide and squamous cell carcinoma.