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Drug–drug interactions during antiviral therapy for chronic hepatitis C

Nature Reviews Gastroenterology & Hepatology volume 10, pages 596–606 (2013)Cite this article

Subjects

Abstract

The emergence of direct-acting antiviral agents (DAAs) for HCV infection represents a major advance in treatment. The NS3 protease inhibitors, boceprevir and telaprevir, were the first DAAs to receive regulatory approval. When combined with PEG-IFN and ribavirin, these agents increase rates of sustained virologic response in HCV genotype 1 to ∼70%. However, this treatment regimen is associated with several toxicities. In addition, both boceprevir and telaprevir are substrates for and inhibitors of the drug transporter P-glycoprotein and the cytochrome P450 enzyme 3A4 and are, therefore, prone to clinically relevant drug interactions. Several new DAAs for HCV are in late stages of clinical development and are likely to be approved in the near future. These include the protease inhibitors, simeprevir and faldaprevir, the NS5A inhibitor, daclatasvir, and the nucleotide polymerase inhibitor, sofosbuvir. Herein, we review the clinical pharmacology and drug interactions of boceprevir, telaprevir and these investigational DAAs. Although boceprevir and telaprevir are involved in many interactions, these interactions are manageable if health-care providers proactively identify and adjust treatments. Emerging DAAs seem to have a reduced potential for drug interactions, which will facilitate their use in the treatment of HCV.

Key Points

  • Direct-acting antiviral agents (DAAs) represent a major advance in the treatment of chronic HCV infection

  • Boceprevir and telaprevir, the first DAAs to receive regulatory approval, are involved in many clinically important drug–drug interactions

  • Providers must proactively screen for potential drug–drug interactions with boceprevir and telaprevir before and during treatment and adjust therapies as needed

  • Many investigational DAAs have fewer, but are not devoid of, drug–drug interactions

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Figure 1: Concept of a therapeutic range.
Figure 2: An algorithm for screening, adjusting and monitoring for potential drug interactions with DAAs.
Figure 3: Protocol for using triple therapy in patients with recurrent HCV after liver transplantation.

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Acknowledgements

J. J. Kiser acknowledges financial support from NIH grant R03 DK096121.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 East Montview Boulevard, V20-C238, Aurora, 80045, CO, USA

    Jennifer J. Kiser

  2. Hepatology and Transplant Centre, University of Colorado, 1635 Aurora Court, B154, Aurora, 80045, CO, USA

    James R. Burton Jr & Gregory T. Everson

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All authors researched data for the article, wrote the article, made substantial contributions to discussion of content, and reviewed/edited the manuscript before submission.

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Correspondence to Jennifer J. Kiser.

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Competing interests

J. J. Kiser receives or has recently received research support from Merck, Vertex and Janssen and served as a consultant for Bristol-Myers Squibb. J. R. Burton Jr receives research support from Gilead, Abbvie and Vertex. G. T. Everson has participated in advisory boards for Roche-Genentech, Merck, Vertex, Bristol-Myers Squibb, GlobeImmune, Abbott, Eisai, Novartis, Pfizer, Gilead, Biotest and Janssen-Tibotec. He has had consultant agreements with Roche-Genentech, Novartis, Bristol-Myers Squibb, Eisai, Kadmon, Vertex, Abbott, Biotest and Janssen-Tibotec. He serves on a data and safety monitoring board for Centocor. He holds equity interest in Source and HepQuant LLC and is a manager of HepQuant LLC. He has had clinical trials research grants from Roche-Genentech, Schering-Plough/Merck, Vertex, GlobeImmune, Gilead, Novartis, BMS, Pfizer, Source, Eisai, GlaxoSmithKline, Pharmassett, Ortho Biotech, Janssen-Tibotec, Amgen, Medtronic and Abbott-Abbvie.

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Kiser, J., Burton, J. & Everson, G. Drug–drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol 10, 596–606 (2013). https://doi.org/10.1038/nrgastro.2013.106

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