Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Br J Clin Pharmacol. 2018 May;84(5):961-971. doi: 10.1111/bcp.13519. Epub 2018 Feb 21.
Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications.
This post hoc analysis pooled data from nine studies which evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of frequently used concomitant medications of interest (CMOIs) were analysed [antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs (LLDs)] and categorized as amber or green according to their DDI potential with SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant medications not recommended to be coadministered with SMV were not included. The composite primary endpoint was defined as the frequency of either discontinuation, interruption or dose modification of the CMOI during 12 weeks of SMV treatment.
Few patients met the composite endpoint in the various subgroups. Patients on amber CMOIs tended to experience CMOI modification more often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference in the frequency of adverse events between patients taking green and those taking amber CMOIs.
In this large pooled analysis, coadministration of the evaluated commonly prescribed medications with known or potential PK interactions with SMV was manageable and resulted in few adjustments of concomitant medications. Our method could serve as a blueprint for the evaluation of the impact of DDIs.
直接作用抗病毒药物（DAA）可用于治疗丙型肝炎（HCV），但可能与伴随药物发生药物-药物相互作用（DDI）。人们对这些 DDI 的实际临床影响知之甚少。我们评估了simeprevir 与经常开的伴随药物之间可能发生的药代动力学（PK）相互作用的临床影响。
这项事后分析汇集了九项评估simeprevir（SMV）为基础的无干扰素 HCV 治疗的研究数据。分析了三类经常使用的潜在药物相互作用药物（CMOI）[抗高血压药（AHD）、抗焦虑药（AXD）和降脂药（LLD）]，根据它们与 SMV 的 DDI 潜力，将其分为绿色或琥珀色（绿色：无 DDI；琥珀色：潜在/已知 PK 相互作用）。未推荐与 SMV 同时使用的伴随药物不包括在内。主要复合终点定义为在 12 周 SMV 治疗期间，CMOI 停药、中断或剂量调整的频率。
在各个亚组中，只有少数患者符合复合终点标准。服用琥珀色 CMOI 的患者比服用绿色 CMOI 的患者更常发生 CMOI 调整（13.4%-19.4%比 3.1%-10.8%）。服用绿色和琥珀色 CMOI 的患者之间不良事件的频率没有差异。
在这项大型的汇总分析中，评估的常用伴随药物与 SMV 已知或潜在 PK 相互作用的联合使用是可控的，且很少需要调整伴随药物。我们的方法可以作为评估 DDI 影响的蓝图。
