Bleeding Induced by Rivaroxaban Combined with PK-DDI in Patients with Nonvalvular Atrial Fibrillation and Renal Insufficiency：a Retrospective Cohort Study

doi:10.19803/j.1672-8629.20240399

Abstract

Abstract: Objective To screen the drugs that increase the bleeding risk of pharmacokinetic drug-drug interactions (PK-DDIs) related to rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) and renal insufficiency [15<creatinine clearance(CL_cr)≤60 mL·min^-1] in the real world, and to promote the rational use of drugs in clinical practice. Methods The rivaroxaban PK-DDI catalogue was summarized by searching for the related literature from databases (PubMed, Web of Science, CNKI, Wanfang and VIP), instructions, 2021 European Heart Rhythm Association guidelines, and Lexicomp database. A retrospective cohort study was conducted to investigate NVAF patients with renal insufficiency who were admitted to Xuanwu Hospital of Capital Medical University and took rivaroxaban from November 2022 to October 2023. The patients were divided into the PK-DDI group and non-PK-DDI group. PK-DDI drugs were limited to P-gp and/or CYP3A4 inhibitors, the patients were followed up for 3 months, and the efficacy and safety outcomes of the two groups were compared. Results Sixty-five types of drugs had to be prohibited or used with caution while another 76 types of drugs did not need to be adjusted in dosage. A total of 143 patients were included in the study. The incidence of hemorrhage in the PK-DDI group was higher than in the non-PK-DDI group (P<0.05), but there was no significant difference in the incidence of ischemic stroke between the two groups (P>0.05). The common bleeding event in the PK-DDI group was clinically relevant non-major bleeding (8 cases, 61.5%), and the incidence of bleeding 30 days after treatment was 38.7%. The drugs included amiodarone, ginkgo biloba extract, fluconazole, voriconazole and ocitinib. Conclusion PK-DDIs of rivaroxaban involve a variety of drugs, and the chief targets are P-gp and CYP3A4. The combination of P-gp and/or CYP3A4 inhibitors may increase the risk of bleeding among patients with renal insufficiency who take rivaroxaban, which should never be used in combination with ginkgo biloba extract or voliconazole. When rivaroxaban is used in combination with amiodarone, fluconazole or ocitinib, such parameters should be monitored as prothrombin time (PT), anti-factor Xa levels, or blood concentrations of rivaroxaban.

Key words: Rivaroxaban, Renal Insufficiency, Hemorrhage, P-gp, CYP3A4, Safety, Non-Valvular Atrial Fibrillation, PT, Anti-Factor Xa

CLC Number:

R972

WU Shiqi, SU Su, YAN Suying, ZHANG Qingxia. Bleeding Induced by Rivaroxaban Combined with PK-DDI in Patients with Nonvalvular Atrial Fibrillation and Renal Insufficiency：a Retrospective Cohort Study[J]. Chinese Journal of Pharmacovigilance, 2025, 22(4): 415-419.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240399

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I4/415

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