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Drug–Drug Interaction of Omeprazole With the HCV Direct‐Acting Antiviral Agents Paritaprevir/Ritonavir and Ombitasvir With and Without Dasabuvir
Author(s) -
Polepally Akshanth R.,
Dutta Sandeep,
Hu Beibei,
Podsadecki Thomas J.,
Awni Walid M.,
Me Rajeev M.
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.246
Subject(s) - ombitasvir , dasabuvir , paritaprevir , ritonavir , medicine , omeprazole , pharmacology , regimen , virology , hepatitis c virus , viral load , ribavirin , virus , antiretroviral therapy , human immunodeficiency virus (hiv)
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 C max and AUC t 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.