Vnitr Lek 2025, 71(7):E1-E6 | DOI: 10.36290/vnl.2025.087
Drug-Drug interaction between rivaroxaban and amiodarone: A systematic review
- 1 II. kardiologická klinika LF UPJŠ a VÚSCH, a. s., Košice, Slovensko
- 2 Klinika gerontológie a geriatrie, LF UPJŠ, Nemocnica sv. Michala, Košice, Slovensko
- 3 I. kardiologická klinika LF UPJŠ a VÚSCH, a. s., Košice, Slovensko
- 4 I. interná klinika LF UPJŠ a UNLP Košice, Slovensko
Background: The concurrent use of rivaroxaban and amiodarone in cardiovascular patients raises concerns about potential drug-drug interactions and increased bleeding risk.
Objective: This systematic review aimed to evaluate the impact of combining amiodarone with rivaroxaban on bleeding events compared to rivaroxaban monotherapy in cardiovascular patients.
Methods: We systematically reviewed observational studies and clinical trials examining bleeding outcomes in patients receiving rivaroxaban with or without concurrent amiodarone therapy. Studies were included if they reported clinical bleeding outcomes, included both combination therapy and monotherapy groups, and provided comparative statistical analyses.
Results: Eight studies comprising over 130.000 patients were analyzed. The combination of rivaroxaban and amiodarone was associated with significantly increased bleeding risk across multiple studies, with hazard ratios ranging from 1.10 to 2.83. The risk difference ranged from 13.94 to 29.7 events per 1000 person-years, with higher risks observed in patients with elevated HAS-BLED scores and renal impairment. Major bleeding events were consistently elevated, although often without reaching statistical significance, and the interaction appeared specific to amiodarone compared to other antiarrhythmic drugs. Pharmacokinetic studies demonstrated increased rivaroxaban plasma concentrations when co-administered with amiodarone, particularly at higher doses and in patients with renal dysfunction.
Conclusions: The combination of rivaroxaban and amiodarone significantly increases bleeding risk compared to rivaroxaban monotherapy, necessitating careful risk-benefit assessment and enhanced monitoring in patients requiring both medications.
Keywords: rivaroxaban, amiodarone, drug interactions, P-glycoprotein, CYP3A4, bleeding risk
Accepted: October 20, 2025; Published: October 31, 2025 Show citation
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