Fernandez Silvia, Lenoir Camille, Samer Caroline Flora, Rollason Victoria
Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, 1206 Geneva, Switzerland.
J Pers Med. 2021 Mar 30;11(4):250. doi: 10.3390/jpm11040250.
Rivaroxaban has become an alternative to vitamin K antagonists, which are considered to be at higher risk of drug-drug interactions (DDI) and more difficult to use. However, DDI do occur. We systematically reviewed studies that evaluated them and analysed DDI and subsequent adverse drug reactions (ADR) reported in spontaneous reports and VigiBase. We systematically searched articles that explored DDI with rivaroxaban up to 20 August 2018 via Medline, Embase and Google Scholar. Data from VigiBase came from spontaneous reports recovered up to 2 January 2018, where Omega was used to detect signals and identify potential interactions in terms of triplets with two drugs and one ADR. We identified 31 studies and 28 case reports. Studies showed significant variation in the pharmacokinetic for rivaroxaban, and an increased risk of haemorrhage or thromboembolic events due to DDI was highlighted in case reports. From VigiBase, a total of 21,261 triplets were analysed and the most reported was rivaroxaban-aspirin-gastrointestinal haemorrhage. In VigiBase, only 34.8% of the DDI reported were described or understood, and most were pharmacodynamic DDI. These data suggest that rivaroxaban should be considered to have significant potential for DDI, especially with CYP3A/P-gp modulators or with drugs that impair haemostasis.
利伐沙班已成为维生素K拮抗剂的替代药物，后者被认为存在较高的药物相互作用（DDI）风险且使用起来更为困难。然而，药物相互作用确实会发生。我们系统回顾了评估这些相互作用的研究，并分析了自发报告和药物警戒数据库（VigiBase）中报告的药物相互作用及随后的药物不良反应（ADR）。我们通过Medline、Embase和谷歌学术系统检索了截至2018年8月20日探讨利伐沙班药物相互作用的文章。VigiBase的数据来自截至2018年1月2日收集的自发报告，其中使用Omega来检测信号并根据两种药物和一种药物不良反应的三联组识别潜在相互作用。我们识别出31项研究和28例病例报告。研究表明利伐沙班的药代动力学存在显著差异，病例报告中强调了由于药物相互作用导致出血或血栓栓塞事件的风险增加。从VigiBase中，共分析了21261个三联组，报告最多的是利伐沙班 - 阿司匹林 - 胃肠道出血。在VigiBase中，报告的药物相互作用中只有34.8%得到了描述或理解，且大多数是药效学药物相互作用。这些数据表明，利伐沙班应被视为具有显著的药物相互作用潜力，尤其是与CYP3A/P - 糖蛋白调节剂或与影响止血的药物之间。
