Use of Hydrochlorothiazide in the United States Following Label Update About Skin Cancer Risk

On August 20, 2020, the United States (U.S.) Food and Drug Administration (FDA) issued a Drug Safety Communication (DSC) along with labeling updates to inform the public about a small increased risk of non-melanoma skin cancer (NMSC) associated with hydrochlorothiazide (HCTZ) use. This study aims to assess whether the DSC impacted HCTZ use in the U.S.

We conducted a trend analysis in the Sentinel Distributed Database using national healthcare administrative data from January 2017 to November 2022. We identified two cohorts each month: An overall cohort of all enrollees and a skin cancer cohort of those with a history of NMSC. For each cohort, we plotted the monthly proportion of patients receiving HCTZ-containing products among those receiving any thiazide diuretics. We performed interrupted time series analyses to quantify the impact of the DSC on these monthly proportions. Secondary analyses were conducted on the proportion of HCTZ users among patients receiving any antihypertensives.

In the overall cohort, the DSC was only associated with a statistically significant but clinically negligible trend change of monthly HCTZ proportion within this cohort (0.018%; 95% CI, 0.012%-0.025%). Similar results were observed in the skin cancer cohort. The secondary analysis found no significant level change or trend change in the monthly proportion of HCTZ use among antihypertensive users.

We did not observe significant changes in HCTZ use following the DSC about its NMSC risk, among the overall population and those with a history of NMSC. Our findings were in accordance with the DSC recommendation.