Braude M, Ratnam DT, Marsh L, Abasszade JH, Dev AT. Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports. World J Gastrointest Pharmacol Ther 2023; 14(4): 33-38 [PMID: 37484883 DOI: 10.4292/wjgpt.v14.i4.33]
Corresponding Author of This Article
Michael Braude, MBBS, PhD, FRACP, Department of Gastroenterology and Hepatology, Monash Health, 246 Clayton Road, Clayton 3168, VIC, Australia. mrh.braude@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Pharmacol Ther. Jul 5, 2023; 14(4): 33-38 Published online Jul 5, 2023. doi: 10.4292/wjgpt.v14.i4.33
Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports
Michael Braude, Dilip T Ratnam, Louise Marsh, Joshua H Abasszade, Anouk T Dev
Michael Braude, Dilip T Ratnam, Joshua H Abasszade, Anouk T Dev, Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, VIC, Australia
Louise Marsh, General Practice, Margaret River Medical Centre, Margaret River 6285, Australia
Author contributions: Braude M designed and drafted the manuscript; Ratnam DT and Dev AT provided hypothesis generation, patient care and hepatology expertise; Marsh L provided patient data and clinical support; Braude M and Abasszade JH edited the manuscript; and all authors contributed to drafting of the manuscript.
Informed consent statement: Informed consent was obtained from each patient.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michael Braude, MBBS, PhD, FRACP, Department of Gastroenterology and Hepatology, Monash Health, 246 Clayton Road, Clayton 3168, VIC, Australia. mrh.braude@gmail.com
Received: April 2, 2023 Peer-review started: April 2, 2023 First decision: April 20, 2023 Revised: May 26, 2023 Accepted: June 19, 2023 Article in press: June 19, 2023 Published online: July 5, 2023
Abstract
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 barriers. DAAs co-prescribed with several first-generation 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 induction. Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time. Sofosbuvir-velpatasvir 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 failure. This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible, impractical or unacceptable. However, 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 induction.
CASE 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 disorders. Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants. DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration, and taken with meals to improve absorption. Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.
CONCLUSION
DAA therapies, including glecaprevir-pibrentasvir, warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine, particularly if AED substitution is not feasible.
Core Tip: Current hepatitis C virus (HCV) direct-acting antiviral (DAA) therapies are not recommended in patients who are co-prescribed carbamazepine. For glecaprevir-pibrentasvir, this is primarily due to carbamazepine’s potent induction of cytochrome P450 3A4 and P-glycoprotein which reduces DAA plasma concentration and may therefore lead to virological failure. Despite theoretical reduction in DAA bioavailability, glecaprevir-pibrentasvir, prescribed over 12-wk, may be an effective treatment for non-cirrhotic patients with HCV who are co-prescribed carbamazepine. Glecaprevir-pibrentasvir should be considered for management of HCV in non-cirrhotic patients who are unable to substitute carbamazepine therapy. Further pharmacokinetic and potency data are required, in addition to further data in patients with cirrhosis.
