Drug-Drug Interaction of Omeprazole With the HCV Direct-Acting Antiviral Agents Paritaprevir/Ritonavir and Ombitasvir With and Without Dasabuvir

• Published in: Clinical pharmacology in drug development Vol. 5; no. 4; pp. 269 - 277
• Main Authors: Polepally, Akshanth R., Dutta, Sandeep, Hu, Beibei, Podsadecki, Thomas J., Awni, Walid M., Menon, Rajeev M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016; Wiley Subscription Services, Inc
• Subjects: acid-reducing agent; Adult; Anilides - administration & dosage; Anilides - pharmacokinetics; Anilides - pharmacology; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - pharmacokinetics; Anti-Ulcer Agents - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Area Under Curve; Carbamates - administration & dosage; Carbamates - pharmacokinetics; Carbamates - pharmacology; CYP2C19; Cytochrome P-450 CYP2C19 - drug effects; Cytochrome P-450 CYP2C19 - metabolism; Drug Interactions; Drug Therapy, Combination; drug-drug interaction; Female; hepatitis C virus; Humans; Macrocyclic Compounds - administration & dosage; Macrocyclic Compounds - pharmacokinetics; Macrocyclic Compounds - pharmacology; Male; omeprazole; Omeprazole - administration & dosage; Omeprazole - pharmacokinetics; Omeprazole - pharmacology; Ritonavir - administration & dosage; Ritonavir - pharmacokinetics; Ritonavir - pharmacology; Sulfonamides - administration & dosage; Sulfonamides - pharmacokinetics; Sulfonamides - pharmacology; Uracil - administration & dosage; Uracil - analogs & derivatives; Uracil - pharmacokinetics; Uracil - pharmacology; hepatitis C virus; omeprazole; CYP2C19; drug-drug interaction; acid-reducing agent
• ISSN: 2160-763X; 2160-7648; 2160-7648
• DOI: 10.1002/cpdd.246

Paritaprevir (administered with low‐dose ritonavir), ombitasvir, and dasabuvir are direct‐acting antiviral agents administered as combination regimens for the treatment of chronic hepatitis C virus infection. Drug–drug interactions between 2D (ombitasvir/paritaprevir/ritonavir) or 3D (ombitasvir/paritaprevir/ritonavir and dasabuvir) regimens and omeprazole, a CYP2C19 substrate and acid‐reducing agent, were evaluated in 24 healthy volunteers. Subjects received omeprazole (40 mg once daily) on day 1 and days 20–24 and the 2D or 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily ± dasabuvir 250 mg twice daily) on days 6–24. Compared with omeprazole alone, coadministration with the 2D or 3D regimen decreased omeprazole geometric mean Cmax and AUCt values by 40% to 50%. Ombitasvir, dasabuvir, and ritonavir mean exposures showed <10% change, and paritaprevir mean exposures showed <20% change when the 2D or 3D regimen was administered with omeprazole compared with administration without omeprazole. Although no a priori dose adjustment is needed, a higher omeprazole dose should be considered if clinically indicated when coadministered with the 2D or 3D regimen. No dose adjustment is required for the 2D or 3D regimen when administered with omeprazole, other acid‐reducing agents, or CYP2C19 inhibitors.