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

Abstract

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.

Adverse drug reactions during hepatitis C treatment with direct-acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting syste

“…The most commonly detected preventable criterion was labelled drug‐drug interaction of coadministered drugs with DAA. This finding is in‐line with previous results from other sources that emphasized the critical role of drug‐drug interactions with the pharmacological use of this drug class . Direct antiviral agents are a substrate of CYP3A, CYP2C9, CYP2C19 or P‐glycoprotein, key proteins, involved in the metabolism and/or transport of several drugs .…”

Evaluation of Drug-Drug Interactions between Direct-Acting Anti-Hepatitis C Virus Combination Regimens and the HIV-1 Antiretroviral Agents Raltegravir, Tenofovir, Emtricitabine, Efavirenz, and Rilpivirine

“…Plasma concentrations of paritaprevir, ritonavir, ombitasvir, and dasabuvir were determined using a validated protein precipitation method and online solid-phase extraction method with liquid chromatography and tandem mass spectrometric detection (LC-MS/MS) (19). Plasma concentrations of emtricitabine/tenofovir, rilpivirine, efavirenz/emtricitabine/tenofovir, and raltegravir were determined by validated LC-MS/MS methods at a commercial laboratory (PPD, Middleton, WI).…”

Pharmacokinetic Evaluation of Darunavir Administered Once or Twice Daily in Combination with Ritonavir or the Three-Direct-Acting Antiviral Regimen of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Adults Coinfected with Hepatitis C and Human Immunodeficiency Viruses

“…Plasma concentrations of OBV, PTV, RTV, DSV, and RBV were determined, using validated liquid chromatography methods with tandem mass spectrometric detection, by the Drug Analysis Department at AbbVie (16). The lower limits of quantitation (LLOQ) for OBV, PTV, RTV, DSV, and RBV were established at 0.464 ng/ml (inter-run accuracy [% bias], Ϫ0.8% to 5.0%; inter-run precision [%CV], 1.7% to 8.8%), 0.601 ng/ml (% bias, Ϫ1.9% to 6.5%; %CV, 1.0% to 8.2%), 5.10 ng/ml (% bias, 0.7% to 9.8%; %CV, 2.2% to 7.5%), 4.39 ng/ml (% bias, Ϫ0.6% to 6.7%; %CV, 1.2% to 8.1%), and 18.7 ng/ml (% bias, Ϫ3.6% to 7.9%; %CV, 1.3% to 12.8%), respectively.…”