Hemorrhagic risk of concomitant direct oral anticoagulants and fluoroquinolones: integration of pharmacovigilance and therapeutic drug monitoring
Abstract
Background Direct oral anticoagulants (DOACs) and fluoroquinolone antibiotics (FQNs) are often co-prescribed. A pharmacokinetic interaction is plausible, as DOACs are P-glycoprotein (P-gp) substrates and several FQNs can bind to and affect P-gp activity. However, robust clinical evidence characterizing the associated hemorrhagic reporting signal remains limited. Methods We conducted an integrated pharmacoepidemiological and therapeutic drug monitoring (TDM) study. Disproportionality analysis was performed using FDA Adverse Event Reporting System (FAERS) data (2010–2025), calculating adjusted reporting odds ratios (adj. ROR) and Ω shrinkage values. Concurrently, a prospective observational cohort (n = 50) measured trough and peak plasma concentrations of dabigatran with and without levofloxacin or moxifloxacin. Results FAERS analysis identified a significant reporting signal for bleeding for dabigatran coadministered with FQNs (adj. ROR = 4.68, 95% CI: 3.41–6.55), particularly levofloxacin (adj. ROR = 6.12) and ciprofloxacin (adj. ROR = 3.84). No significant signals were found for rivaroxaban, apixaban, or edoxaban. Consistently, TDM showed significantly elevated peak dabigatran concentrations with levofloxacin (133.36 ng/mL, P = 0.008) and moxifloxacin (138.20 ng/mL, P < 0.001) compared to monotherapy (65.34 ng/mL), alongside a numerical trend towards more bleeding events. Conclusion This integrated analysis provides suggestive evidence for a pharmacokinetically plausible…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 50 participants or records.
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