Real-world safety profile of Levofloxacin: Pharmacovigilance signals, co-medication patterns, and signal validation

Abstract

Objective

To characterize epidemiological features and co-medication patterns of Levofloxacin-associated adverse events (AEs) using spontaneous reports and cross-validate pharmacovigilance signals against the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods

We retrospectively analyzed spontaneous reports for Levofloxacin from the Adverse Drug Reaction Monitoring Center (2020–2024). Patient demographics, regimens, and clinical outcomes were evaluated. Co-medication patterns were identified using association rule mining. Disproportionality analyses were employed for signal detection, with findings cross-validated in FAERS.

Results

Among 4,353 reports, 7.14% were severe. The median age was 57 years (male-to-female ratio 1.29:1). Parenteral administration for respiratory, urogenital, and skin infections was predominant. Analysis of 575 co-medication cases yielded 11 significant association rules. The reported AEs manifested primarily as skin and appendages disorders, gastrointestinal disorders, and vascular/coagulation disorders, with 96.76% of patients showing favorable outcomes. At the System Organ Class level, 5 significant signals were detected, with general disorders and administration site conditions showing the strongest signal intensity (ROR = 4.98). At the Preferred Term level, 40 signals were identified, 27 of which were cross-validated in FAERS, including infusion site pruritus (highest intensity, ROR = 39.77).

Conclusions

Cross-validation with FAERS confirmed Levofloxacin's established safety profile, characterized by frequent Skin and Appendages Disorders and strong signals for injection site reactions. Notably, co-medication patterns suggest caution when combining Levofloxacin with cephalosporins. Individualized risk assessment and vigilant monitoring are essential to mitigate potential risks.