Sex Differences of Fall-Risk-Increasing Drugs in the Middle-Aged and Elderly: A Pharmacovigilance Analysis of  FDA Adverse Event Reporting System

It’s well known that sex is a risk factor for the occurrence of adverse events (AEs), most of which have found sex differences. Real-world data studies on the sex differences of fall-risk-increasing drugs (FRIDs) are few and far between, with most small-scale retrospective studies based on FRID classes. To determine a list of drugs associated with falling and identify their sex differences in the FDA Adverse Event Reporting System (FAERS), we used preferred terms from the Medical Dictionary for Regulatory Activities to search for AEs. During January 2004 to March 2023, 101,746 fall-related AEs were reported in FAERS from patients aged 50 to 100, with 68492 (67.3%) females and 32547 (32.0%) males. We found 261 signals for females while 284 for males. For females, the top 3 signals with the highest ROR were anethole trithione, clopenthixol, nikethamide (ROR: 388.879, 212.100, 113.944), while the top 3 signals with the highest IC ₀₂₅ were nikethamide, anethole trithione, benzbromarone (IC ₀₂₅ : 3.913, 3.148, 2.486). For males, the top 3 signals with the highest ROR were fluprednidene acetate, potassium hydroxide, ketazolam (ROR: 216.858, 108.429, 108.429), while the top 3 signals with the highest IC ₀₂₅ were clomethiazole, piribedil, melperone (IC ₀₂₅ : 3.311, 3.238, 2.985). Moreover, among the 119 shared signals found between males and females, 33 were biased towards females while 38 towards males. Signals showing significant sex differences were mainly concentrated on agents of the immune, nervous, musculo-skeletal, and cardiovascular systems. We offer a series of common drugs with risk signals and their sex differences in falling through the FAERS database. In the future, it is essential to find more drugs with increasing fall risks and whose sex differences are not fully understood.