Review Article

European Journal of Clinical Pharmacology

, Volume 70, Issue 7, pp 775-789

First online:

Drug interactions and protease inhibitors used in the treatment of hepatitis C: How to manage?

  • Sarah Talavera PonsAffiliated withDepartment of Pharmacy, Clermont-Ferrand University HospitalService Pharmacie, CHU Estaing Email author 
  • , Geraldine LamblinAffiliated withDepartment of Hepato-Gastroenterology, Estaing
  • , Anne BoyerAffiliated withDepartment of Pharmacy, Clermont-Ferrand University Hospital
  • , Valérie SautouAffiliated withDepartment of Pharmacy, Clermont-Ferrand University HospitalEA 4676 C-Biosenss, Université d’Auvergne
  • , Armand AbergelAffiliated withDepartment of Hepato-Gastroenterology, EstaingUnité Mixte de Recherche Université d’Auvergne, CNRS 6284, University of Clermont-Ferrand

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Abstract

Purpose

The first-generation protease inhibitors (PI) boceprevir and telaprevir combined with pegylated interferon have revolutionized the treatment of type-1 hepatitis C by increasing the rates of sustained virologic response. However, they induce drug interactions, and their clinical relevance is difficult to predict. This review compiles available data on drug–drug interactions (DDI) based on their pharmacokinetic and pharmacodynamic properties with the aim of assisting clinicians in managing DDI

Methods

PubMed, drug interaction databases and hepatology and infectious disease conference abstracts were systematically searched using the key search terms “interaction”, “hepatitis C”, “telaprevir” and “boceprevir”. All known interactions were compiled and reclassified according to their pharmacokinetic and pharmacodynamic mechanisms. The state of knowledge of interaction mechanisms are reported and a therapeutic approach is proposed.

Results

Boceprevir and telaprevir are both substrates and potent inhibitors of cytochrome P450 3A4 and the drug transporter P-glycoprotein. They induce overdosage but can sometimes decrease the effect of other drugs by inducing other cytochromes. Overdosage or low dosage mainly affects drugs with a narrow therapeutic range, such as immunosuppressants or antiretrovirals. The distribution and elimination of PI are unaffected by interactions. In terms of pharmacodynamic interactions, PI can trigger drug-induced QT interval prolongation, which means that clinicians should manage such risk factors as potassium/magnesium levels or avoid other QT-prolonging drugs.

Conclusions

Management of hepatitis C therapy is complex. The key to interpreting DDI data is a solid understanding of the pharmacokinetic and pharmacodynamic profiles of the drugs involved. Their ability to inhibit cytochrome P450 3A4 and prolong the QT interval can have significant clinical consequences. This review provides a practical guide to the safe and effective management of therapy with boceprevir and telaprevir.

Keywords

Interaction Telaprevir Boceprevir Management