Di Minno Alessandro, Frigerio Beatrice, Spadarella Gaia, Ravani Alessio, Sansaro Daniela, Amato Mauro, Kitzmiller Joseph P, Pepi Mauro, Tremoli Elena, Baldassarre Damiano
Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", Naples, Italy.
Blood Rev. 2017 Jul;31(4):193-203. doi: 10.1016/j.blre.2017.02.001. Epub 2017 Feb 5.
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.
全球最常用的口服抗凝剂是维生素K拮抗剂(VKA),如华法林。影响VKA药代动力学的因素很重要,因为偏离其狭窄的治疗窗可能会因抗凝过度导致出血,或因抗凝不足导致血栓形成。除了药效学相互作用(如同时使用非甾体抗炎药会增加出血风险)外,与药物、食物、草药及非处方药的相互作用可能会影响VKA的风险/效益比。直接口服抗凝剂(DOAC),包括Xa因子抑制剂(利伐沙班、阿哌沙班和依度沙班)和凝血酶抑制剂(达比加群)有望取代华法林。3期研究和真实世界评估已证实DOAC的安全性优于VKA。然而,预计会存在一些药代动力学和药效学相互作用。在此,我们对VKA和DOAC进行了批判性综述,重点关注它们与药物、食物、草药及非处方药相互作用的可能性。