Efficacy and Pharmacokinetics of Glecaprevir and Pibrentasvir With Concurrent Use of Acid-Reducing Agents in Patients With Chronic HCV Infection

Steven Flamm, K Rajender Reddy, Neddie Zadeikis, Tarek Hassanein, Bruce R Bacon, Andreas Maieron, Stefan Zeuzem, Marc Bourliere, Jose L Calleja, Matthew P Kosloski, Rajneet K Oberoi, Chih-Wei Lin, Yao Yu, Sandra Lovell, Dimitri Semizarov, Federico J Mensa

Research output: Journal article (peer-reviewed)Journal article

17 Citations (Scopus)


BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.

METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.

RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.

CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).

Original languageEnglish
Pages (from-to)527-535.e6
JournalClinical Gastroenterology and Hepatology
Issue number3
Publication statusPublished - Feb 2019


  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antiviral Agents/administration & dosage
  • Benzimidazoles/administration & dosage
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Combinations
  • Drug Interactions
  • Female
  • Hepatitis C, Chronic/drug therapy
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors/administration & dosage
  • Pyrrolidines/administration & dosage
  • Quinoxalines/administration & dosage
  • Sulfonamides/administration & dosage
  • Sustained Virologic Response
  • Treatment Outcome
  • Young Adult


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