Co-Administration of Amiodarone Increases Bleeding by Affecting Rivaroxaban Pharmacokinetics in Patients with Atrial Fibrillation
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Published:2024-07-30
Issue:8
Volume:16
Page:1006
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ISSN:1999-4923
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Container-title:Pharmaceutics
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language:en
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Short-container-title:Pharmaceutics
Author:
Ding Huamin1, Wang Zi2, Wang Jia134ORCID, Yao Yao2, Zhang Chi134ORCID, Lin Houwen34, Zhou Yong13, Gu Zhichun134ORCID, Lv Qianzhou2ORCID, Li Xiaoye2
Affiliation:
1. Department of Pharmacy, Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China 2. Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai 200032, China 3. Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China 4. College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Abstract
This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment.
Funder
Science and Technology Development Foundation of Shanghai Pudong New Area Outstanding Clinical Discipline Project of Shanghai Pudong Academic leader training program of Pudong New Area Health Commission Young Medical Talents Training Program of Pudong Health Bureau of Shanghai Talent Project established by the Chinese Pharmaceutical Association Hospital Pharmacy Department research project on high-quality development of hospital pharmacy, National Institute of Hospital Administration, NHC, China
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