No Pharmacokinetic Interaction Between the Hepatitis C Virus Inhibitors Elbasvir/Grazoprevir and Famotidine or Pantoprazole

• Published in: Clinical and translational science 2017-09, Vol.10 (5), p.360-365
• Main Authors: Feng, H‐P, Vaddady, P, Guo, Z, Liu, F, Panebianco, D, Levine, V, Caro, L, Butterton, JR, Iwamoto, M, Yeh, WW
• Format: Article
• Language: English
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - adverse effects; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacology; Acids; Adult; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Benzofurans - adverse effects; Benzofurans - blood; Benzofurans - pharmacokinetics; Benzofurans - pharmacology; Bioavailability; Clinical trials; Cytochrome; Demography; Drug dosages; Drug Interactions; Famotidine; Famotidine - adverse effects; Famotidine - pharmacokinetics; Famotidine - pharmacology; FDA approval; Female; Gastric juice; Hepacivirus - drug effects; Hepatitis; Hepatitis C; Humans; Imidazoles - adverse effects; Imidazoles - blood; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Infections; Male; Middle Aged; Pharmacokinetics; Quinoxalines - adverse effects; Quinoxalines - blood; Quinoxalines - pharmacokinetics; Quinoxalines - pharmacology; Reducing agents; Secretion; Substance abuse treatment; Time Factors; Viruses; Young Adult
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12465

Use of agents to suppress gastric acid secretion is common among patients with hepatitis C virus (HCV) infection. The aims of this open‐label, three‐period, fixed‐sequence study were to evaluate the effect of famotidine and pantoprazole on the pharmacokinetics and safety of elbasvir/grazoprevir fixed‐dose combination (FDC) in 16 healthy subjects. Elbasvir and grazoprevir each exhibited similar pharmacokinetics following single‐dose administration of elbasvir/grazoprevir with or without famotidine or pantoprazole. Geometric mean ratios (GMRs) of grazoprevir AUC(0,∞), Cmax, and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 0.89–1.17. Similarly, GMRs of elbasvir AUC(0,∞), Cmax, and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 1.02–1.11. These results indicate that gastric acid‐reducing agents do not modify the pharmacokinetics of elbasvir or grazoprevir in a clinically relevant manner and may be coadministered with elbasvir/grazoprevir in HCV‐infected patients without restriction.