Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy.
Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Como, Italy.
Clin Drug Investig. 2020 Nov;40(11):1001-1008. doi: 10.1007/s40261-020-00962-y.
Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, are susceptible to drug-drug interactions (DDIs). Hepatitis C direct-acting antiviral agents (DAAs), via P-glycoprotein or CYP3A4 inhibition, may increase DOAC exposure with relevant bleeding risk. We performed a systematic review on DDIs between DOACs and DAAs.
Two reviewers independently identified studies through electronic databases, until 7 July 2020, supplementing the search by reviewing conference abstracts and the ClinicalTrials.gov website.
Of 1386 identified references, four articles were finally included after applying the exclusion criteria. Three phase I clinical studies in healthy volunteers assessed interactions between dabigatran and glecaprevir/pibrentasvir, odalasvir/simeprevir, or sofosbuvir/velpatasvir/voxilaprevir, showing an increase in the dabigatran area under the concentration-time curve (AUC) by 138%, 103%, and 161%, respectively.
DOACs and DAAs are under-investigated for DDI risk. Real-world studies are needed to assess the clinical relevance of the pharmacokinetic interactions with dabigatran and describe the actual spectrum of possible DDIs between DAAs and other DOACs.
直接口服抗凝剂（DOACs）作为细胞色素 P450（CYP）3A4 和/或 P-糖蛋白的底物，易发生药物-药物相互作用（DDI）。丙型肝炎直接作用抗病毒药物（DAAs）通过 P-糖蛋白或 CYP3A4 抑制，可能会增加 DOAC 的暴露量，从而增加相关出血风险。我们对 DOACs 和 DAAs 之间的 DDI 进行了系统评价。
两名审查员通过电子数据库独立识别研究，直到 2020 年 7 月 7 日，通过审查会议摘要和 ClinicalTrials.gov 网站补充搜索。
在 1386 篇确定的参考文献中，经过排除标准后，最终有 4 篇文章被纳入。三项在健康志愿者中进行的 I 期临床试验评估了达比加群与 glecaprevir/pibrentasvir、odalasvir/simeprevir 或 sofosbuvir/velpatasvir/voxilaprevir 之间的相互作用，分别使达比加群的浓度-时间曲线下面积（AUC）增加了 138%、103%和 161%。
DOACs 和 DAAs 的 DDI 风险研究不足。需要进行真实世界的研究来评估达比加群与这些药物相互作用的临床相关性，并描述 DAAs 和其他 DOACs 之间可能发生的 DDI 的实际范围。
