Cardiovascular safety signals of oral versus topical minoxidil in FAERS: a disproportionality analysis (analytic cohort 2012–2025)

Oral minoxidil, including low-dose regimens, is increasingly used off-label for alopecia 1,2 , but cardiovascular safety remains a clinical concern. We compared cardiovascular adverse event reporting patterns for oral versus topical minoxidil using a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS). FAERS data (2004Q1–2025Q3) were imported and deduplicated; minoxidil reports were restricted to primary/secondary suspect (PS/SS) drugs and eligible reports from 2012–2025. Exposure was classified as ORAL, TOPICAL, BOTH, or UNKNOWN using a standardized route/dose-form dictionary. Signals for Core and Expanded cardiovascular MedDRA Preferred Terms (PTs) were assessed using reporting odds ratios (RORs) with 95% confidence intervals; sensitivity analyses included alopecia-restricted cohorts excluding hypertension indications. In the primary ORAL-vs-TOPICAL cohort (559 oral; 56,947 topical), 23 Core-list PTs and 31 Expanded-list PTs met the signal definition. Strongest primary signals included pericardial effusion (ROR 307; 95% CI 158–597), hypertensive crisis (ROR 1037; 95% CI 133–8117), pulmonary hypertension (ROR 932; 95% CI 118–7368), and pulmonary oedema (ROR 1965; 95% CI 114–33,813). In an alopecia-restricted sensitivity cohort excluding hypertension/blood-pressure indications (146 oral; 24,367 topical), hemodynamic and effusion-related signals (e.g., tachycardia, palpitations, orthostatic hypotension, syncope, and pericardial effusion) persisted, supporting that these findings are not solely explained by hypertension indications. Oral minoxidil PS/SS reports showed disproportionate reporting of several cardiovascular PTs versus topical minoxidil. Indication-restricted analyses suggest that some extreme blood-pressure signals in the primary analysis reflect confounding by hypertension indication, while hemodynamic and effusion-related signals persist and merit clinical awareness and further study. These findings do not establish causality or absolute risk.