Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine:Three case reports

作     者：Michael Braude Dilip T Ratnam Louise Marsh Joshua H Abasszade Anouk T Dev 

作者机构：Department of Gastroenterology and HepatologyMonash HealthClayton 3168VICAustralia General PracticeMargaret River Medical CentreMargaret River 6285Australia 

出 版 物：《World Journal of Gastrointestinal Pharmacology and Therapeutics》 (世界胃肠药理与治疗学杂志（英文版）（电子版）)

年 卷 期：2023年第14卷第4期

页      面：33-38页

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

主　　题：Antiepileptic drugs Drug interactions Hepatitis C virus Sustained virological response Health care access Case repor 

摘      要：BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment *** co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 *** also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite *** and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment *** presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or ***,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein *** SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure ***-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated *** therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve *** virological response at 12 wk was achieved in each patient with no adverse *** DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV w