Department of Pharmacology, Faculty of Medicine, Kocaeli University, 41380, Kocaeli, Turkey.
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, 4031, Basel, Switzerland.
Drug Saf. 2017 Nov;40(11):1091-1098. doi: 10.1007/s40264-017-0567-5.
Direct oral anticoagulants (DOACs) are novel direct-acting medications that are selective for either thrombin or activated factor X. Due to their obvious benefits for patients (fewer interactions, broader therapeutic window, etc.), they are increasingly used as an alternative to warfarin, phenprocoumon, or acenocoumarol. One of the major indications for use of DOACs is stroke prevention in patients with atrial fibrillation (AF). However, interactions still exist, especially in combination with antiarrhythmic drugs (AADs), which are frequently given to AF patients for rhythm or rate control. These interactions are due to the cytochrome P450 system and the P-glycoprotein (permeability glycoprotein or multidrug resistance protein) transport system. For some combinations, dose reduction of the DOAC is recommended and in some cases contraindications exist. In addition, impairment in renal and hepatic function plays an important role in this context. However, compared with pure interactions where data are quite convincing, the latter topic has been studied only rudimentarily. This review summarizes the literature on the safety and interactions of AADs when used with DOACs [dabigatran (a direct inhibitor of factor IIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa)] and the impact of renal and hepatic impairment.
直接口服抗凝剂（DOACs）是新型的直接作用药物，选择性作用于凝血酶或活化的因子 X。由于其对患者具有明显的益处（更少的相互作用，更宽的治疗窗等），它们越来越多地被用作华法林、苯丙香豆素或醋硝香豆素的替代品。DOACs 的主要适应证之一是预防心房颤动（AF）患者的中风。然而，仍然存在相互作用，尤其是与抗心律失常药物（AADs）联合使用时，AADs 经常用于 AF 患者以控制节律或心率。这些相互作用是由于细胞色素 P450 系统和 P-糖蛋白（通透性糖蛋白或多药耐药蛋白）转运系统所致。对于某些组合，建议减少 DOAC 的剂量，在某些情况下存在禁忌症。此外，肾功能和肝功能损害在这方面也起着重要作用。然而，与数据相当有说服力的纯相互作用相比，后者的研究还只是初步的。本文综述了 AAD 与 DOACs[达比加群（直接 IIa 因子抑制剂）和利伐沙班、阿哌沙班和依度沙班（直接 Xa 因子抑制剂）]联合应用时的安全性和相互作用以及肾功能和肝功能损害的影响的文献。
