Disproportionality Analysis of Fluoroquinolone-Associated Peripheral Neuropathy in the FAERS Database (2007-2024)

Fluoroquinolones (FQs) are among the most frequently prescribed antibiotic classes worldwide. Despite their therapeutic versatility in treating bacterial infections, regulatory authorities recognized risks of persistent and potentially irreversible adverse effects, particularly peripheral neuropathy (PN). However, a comprehensive pharmacovigilance assessment of PN-related adverse events (AEs) across all six FDA-approved FQs remains limited. We therefore analyzed adverse event reports (AERs) associated with these six agents from the FDA Adverse Event Reporting System (FAERS) Public Dashboard spanning 2007-2024 Q3, following READUS-PV guidelines. Disproportionality analysis was conducted to identify potential safety signals for PN-related AEs reported with FQ use following deduplication and exclusion of cases involving non-FQ concomitant medications. Positive disproportionality signals were observed for the commonly prescribed FQs (ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin), with seven distinct PN manifestations generating signals. Notably, we detected PN-related signals for gemifloxacin, a relatively new FQ with limited prior evaluation of neurotoxicity. Univariate logistic regression revealed that women and adults aged 18-64 years were more frequently represented in FQ-associated PN-related AERs, whereas men and patients aged ≥ 65 years were disproportionately represented among cases with fatal outcomes. Combination therapy with multiple FQs generated disproportionality signals exceeding those with FQ monotherapy. These findings underscore the need for increased vigilance when prescribing FQs, particularly for mild infections where risks may outweigh benefits. Strengthened clinical monitoring for early signs of PN is advisable when FQ treatment becomes unavoidable. Further controlled epidemiological studies are needed to validate these signals and define at-risk groups, alongside mechanistic research aimed at supporting the development of neuroprotective strategies.