A Review of Daclatasvir Drug–Drug Interactions

作者：Τushar Garimella, Xiaoli You, Reena Wang, Shu‐Pang Huang, Hamza Kandoussi, Marc Bifano, Richard Bertz, Timothy Eley · 发表于：Advances in Therapy · 年份：2016 · DOI：10.1007/s12325-016-0407-5 · 被引用次数：32 · 研究领域：Hepatitis C virus research、HIV/AIDS drug development and treatment、Pharmacogenetics and Drug Metabolism

The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV-based regimens in terms of efficacy and safety, they have a greater susceptibility to drug-drug interactions (DDIs). Daclatasvir (DCV)-the benchmark pangenotypic nonstructural protein 5A inhibitor-has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein. This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug-drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demo...