Fluoroquinolones (FQs) are widely used antimicrobial agents known for their strong efficacy against a broad range of infections. Despite their extensive use and generally acceptable tolerance profile, safety concerns remain. This study aimed to evaluate the incidence, severity, and outcomes of fluoroquinolone (FQ)-related adverse drug reactions (ADRs) using reports from a regional spontaneous ADR reporting system. A retrospective cross-sectional observational design was employed, including all patients with documented ADRs associated with fluoroquinolones or other antibiotics (ABs) reported to the Regional Pharmacovigilance Center (PVC) database from January 2019 to December 2022. Data were obtained from the Saudi ADR reporting system of the PVC, which aligns with the MedWatch ADR reporting format of the U.S. Food and Drug Administration (FDA). A total of 605 antibiotic-related ADR reports were analyzed. Fluoroquinolones accounted for the highest proportion of reported ADRs (177; 29.3%), followed by penicillins (100; 23.4%) and cephalosporins (90; 21%). No statistically significant difference was observed in FQ-related ADRs between males (104; 58%) and females (OR: 1.17, 95% CI: 0.82–1.67, P = 0.386). However, individuals aged 40 years or older had a significantly higher incidence of FQ-related ADRs (OR: 1.56, 95% CI = 1.09–2.22, P = 0.015). Most FQ-associated ADRs were of moderate severity (157; 88.7%), required medical intervention (83; 46.9%), and resolved following treatment (154; 87%). In addition, patients exposed to FQs were approximately four times more likely to develop neurological adverse events (OR: 4.15, 95 % CI = 2.48–6.93, P < 0.001). Fluoroquinolones had a higher frequency of ADRs than other antibiotic classes. Continuous monitoring of antibiotic safety is essential to enhance awareness among healthcare professionals and the public regarding appropriate antibiotic use and to restrict fluoroquinolone use to infections where alternative treatments are ineffective.
