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.

KEYWORDS:

• Clomiphene
• adverse event
• drug safety
• FAERS
• pharmacovigilance

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

B Yang contributed to the study design. Y Shao, L Ma and J Zhou collected the data and analysis. Y Shao wrote and edited the manuscript. All authors approved the submission of the final manuscript.

Acknowledgments

We would like to thank the Food and Drug Administration Adverse Event Reporting System.

Ethics

The manuscript does not describe a clinical trial. The research is based on the FDA Adverse Event Reporting System (FAERS) database, which is a public database. Therefore, there is no requirement for an ethics statement or informed consent from patients.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2358972

Additional information

Funding

This paper was funded by the Science and Technology Bureau of Jiaxing City [grant numbers 2022AY30022 and 2023AY31021].