Gastric-acid-mediated drug-drug interactions with direct-acting antiviral medications for hepatitis C virus infection: clinical relevance and mitigation strategies

Drug-drug interactions (DDIs) between direct-acting antiviral (DAA) medications and acid-reducing agents mediated by gastric acid represent an important issue in drug development and treatment, which could lead to impaired bioavailability and subtherapeutic plasma concentrations of DAA drugs and subsequently compromised treatment outcomes. However, identification of clinically relevant drug interactions associated with elevated gastric pH is not well characterized. Here, we present the first comprehensive analysis of the gastric-acid-mediated drug interactions with all novel DAA medications by analyzing and revisiting in vitro data, prospective DDI trials and retrospective assessments based upon Phase II and III studies, aiming toward an in-depth understanding of the clinical implications and mitigation strategies to circumvent such interactions.