What is the clinical evidence from this study?

Study design: Observational. Population: Conditions requiring direct oral anticoagulants (e.g., non-valvular atrial fibrillation) (n=253645). Intervention: Dabigatran coadministered with fluoroquinolones vs. Dabigatran monotherapy. Primary outcome: Reporting odds of bleeding events (FAERS analysis) (adj. ROR 4.68, 95% CI 3.41-6.55).

What does this research mean for the field?

Coadministration of dabigatran with fluoroquinolones significantly increases the reporting odds of bleeding compared to dabigatran monotherapy, whereas other direct oral anticoagulants do not show this increased risk. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 13, 2026Frontiers in Pharmacology1 citationsOpen Access

Hemorrhagic risk of concomitant direct oral anticoagulants and fluoroquinolones: integration of pharmacovigilance and therapeutic drug monitoring

JXJiao XuSoochow University YLYue-dong LiSoochow University JHJun-ping HanSoochow University

Key Result

Coadministration of dabigatran with fluoroquinolones significantly increased the reporting odds of bleeding (adj. ROR 4.68) compared to dabigatran monotherapy.

Study Design

Type

Observational (n=253,645)

Blinding

Single-blind

Multicenter

Structured PICO

Does coadministration of fluoroquinolones increase the risk of bleeding and plasma concentrations in patients taking direct oral anticoagulants?

Population

An integrated study comprising a FAERS pharmacovigilance analysis of 253,645 DOAC-associated adverse event reports and a prospective cohort of 50 adults with non-valvular atrial fibrillation to assess bleeding risk with concomitant fluoroquinolones.

Exposure

Coadministration of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) and fluoroquinolones (levofloxacin, moxifloxacin, or ciprofloxacin).

Comparator

Direct oral anticoagulant monotherapy without fluoroquinolones.

Outcome

Reporting odds ratio (ROR) for bleeding events (FAERS database) and peak/trough dabigatran plasma concentrations (TDM cohort).safety

Coadministration of dabigatran and certain fluoroquinolones (like levofloxacin) significantly increases dabigatran plasma concentrations and the reporting odds of bleeding, suggesting alternative antibiotics or enhanced monitoring are needed.

Main Result

Odds Ratio: 4.68 (95% CI 3.41–6.55)

Limitations

The FAERS database is subject to underreporting, reporting bias, incomplete data entry, and potential exposure misclassification.
Uncontrolled confounding in the FAERS analysis due to uncaptured clinical variables such as genetic polymorphisms, renal function variations, and concomitant medications.
The prospective therapeutic drug monitoring cohort was relatively small (n=50) with infrequent bleeding events and limited post hoc power.
Discrepancy between the pharmacokinetic effect of moxifloxacin and its FAERS signal highlights the challenge of interpreting drug-drug interaction signals from spontaneous reports.

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 interaction that may increase the reporting odds of bleeding between dabigatran and certain FQNs (e.g., levofloxacin). Other DOACs appear safer with FQNs coadministration. For dabigatran patients requiring FQNs, alternative agents or enhanced monitoring should be considered.

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