直接抗丙型肝炎病毒药物的药物相互作用

Drug-drug interactions associated with direct-acting antiviral agents for hepatitis C

临床上与丙型肝炎直接抗病毒药物(direct-acting antiviral agents,DAA)相关的药物相互作用(drug-drug interaction,DDI)普遍存在,DDI的机制包括抑制或诱导细胞色素酶CYP450活性、抑制或激活多种转运蛋白和改变血浆蛋白结合。对治疗的影响主要有两方面,其一是合并用药影响DAA的暴露量,导致疗效降低或药品不良反应(ADRs)增多;其二是DAA影响合并用药的浓度,导致相应症状甚至发生严重不良事件。本文概述了DAA与临床常用药物,如血脂调节药、免疫抑制剂、抗反转录酶病毒药、中草药等药物合用的3种情况:(1)合用后DAA或合用药物浓度增加几倍甚至十几倍,产生严重ADRs,禁止合用;(2)合用后可能产生明显ADRs,需要加强监测、调整给药剂量和给药间隔时间;(3)预测合用后不会产生明显ADRs。

Drug-drug interactions（DDI）associated with direct-acting antiviral agents（DAA）for hepatitis C are generally observed in clinical practice,the mechanisms of which include inhibiting or inducing CYP450 enzyme activity,inhibiting or activating multiple protein transporters and altering plasma protein binding.DDI associated with DAA have two major implications for treatment.First,concomitant medication may affect the exposure level of DAA,resulting in decreased efficacy or increased adverse drug reactions（ADRs）.Second,DAA may affect the concentration of concomitant medication,leading to corresponding symptoms or even serious adverse events.There are three scenarios in co-administration of DAA and commonly used drugs such as lipid-regulating drugs,immunosuppressants,antiretroviral drugs and Chinese herbal medicines：（1）drug concentration of DAA or concomitant medication increased by several times（or even dozens of times）,leading to serious adverse events and should not be co-administrated;（2）potential clinically significant ADRs which may require additional monitoring,alteration of drug dosage or dosing interval;（3）no clinically significant interaction was expected.