Smolders Elise J, Berden Floor Ac, de Kanter Clara Tmm, Kievit Wietske, Drenth Joost Ph, Burger David M
Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands.
Department of Gastroenterology and Hepatology, Radboud university medical center, Nijmegen, The Netherlands.
United European Gastroenterol J. 2017 Aug;5(5):648-657. doi: 10.1177/2050640616678151. Epub 2016 Nov 4.
Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions.
The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients.
We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use. We compiled a list of currently available direct-acting antiviral regimens and cross-checked for potential drug-drug interactions with used co-medication.
The cohort included 461 patients of which 77% used co-medication. We identified 260 drugs used as co-medication. Antidepressants (7.4%), proton pump inhibitors (7.1%) and benzodiazepines (7.1%) were most frequently used. Of the patients, 60% were at risk for a clinically relevant drug-drug interaction with at least one of the direct-acting antiviral regimens. Interactions were most common with paritaprevir/ritonavir/ombitasvir/dasabuvir and least interactions were predicted with grazoprevir/elbasvir.
Co-medication use is rich in frequency and diversity in chronic hepatitis C patients. The majority of patients are at risk for drug-drug interactions which may affect efficacy or toxicity of direct-acting antivirals or co-medication. The most recently introduced direct-acting antivirals are associated with a lower risk of drug-drug interactions.
直接作用抗病毒药物显著改善了慢性丙型肝炎病毒感染的治疗。直接作用抗病毒药物可抑制/诱导药物代谢酶和转运蛋白，同时自身也可能是它们的底物。这增加了药物相互作用的风险。
本研究旨在预测丙型肝炎病毒感染患者联合用药时的药物相互作用。
我们组建了一个全国性的丙型肝炎患者队列，并收集了联合用药的横断面数据。我们编制了一份当前可用的直接作用抗病毒治疗方案清单，并交叉核对与所用联合用药之间潜在的药物相互作用。
该队列包括461名患者，其中77%使用了联合用药。我们确定了260种用作联合用药的药物。最常使用的药物是抗抑郁药（7.4%）、质子泵抑制剂（7.1%）和苯二氮䓬类药物（7.1%）。在这些患者中，60%与至少一种直接作用抗病毒治疗方案存在临床相关药物相互作用的风险。与帕立普韦/利托那韦/奥比他韦/达沙布韦的相互作用最为常见，而与格卡瑞韦/哌仑他韦预测的相互作用最少。
慢性丙型肝炎患者联合用药的频率和种类丰富。大多数患者存在药物相互作用的风险，这可能会影响直接作用抗病毒药物或联合用药的疗效或毒性。最新推出的直接作用抗病毒药物与较低的药物相互作用风险相关。
