Safety assessment of clomiphene: a real-world pharmacovigilance analysis from the Food and Drug Administration adverse event reporting system.

ABSTRACT

BACKGROUND: Clomiphene is widely used for the treatment of anovulatory infertility, yet there remain many unrecognized adverse events (AEs). The objective of this study is to provide a comprehensive overview of the safety profile of clomiphene. METHODS: The data were derived from the first quarter of 2004 to the third quarter of 2023 from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The detection of new AE signals involved the use of four algorithms reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). RESULTS: A total of 16,677,289 AE reports were acquired from the FAERS database, and there were 2,620 AEs specifically reported in 720 patients following clomiphene use. The AEs encompassed 102 preferred terms (PTs) across 24 system organ classes (SOCs). Some new AEs were identified, including conjoined twins (0.5%), Potter's syndrome (0.3%), genitalia external ambiguous (0.3%), esophageal atresia (0.6%), and anal atresia (0.3%). CONCLUSIONS: Although the majority of AEs aligned with the drug instruction, some new AE signals such as conjoined twins and genitalia external ambiguous were not captured. Well-designed studies are required to demonstrate the safety of clomiphene.