Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir

摘要: Background & Aims Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions 3D regimen OBV, PTV/r, DSV various medications in healthy volunteers inform dosing recommendations HCV-infected patients. Methods Mechanism-based evaluated gemfibrozil, ketoconazole, carbamazepine, warfarin, omeprazole, digoxin, pravastatin, rosuvastatin. Drug-drug commonly used patients amlodipine, furosemide, alprazolam, zolpidem, duloxetine, escitalopram, methadone, buprenorphine/naloxone, oral contraceptives. Ratios geometric means 90% confidence intervals maximum plasma concentration (C max ) area under concentration-time curve (AUC) determine magnitude interaction. Results Coadministration resulted a AUC most DAAs, indicating minimal modest interactions. Carbamazepine decreased PTV, exposures substantially, while gemfibrozil increased substantially. Although coadministration ethinyl estradiol-containing contraceptives elevated alanine aminotransferase levels, progestin-only contraceptive did not. Conclusions The majority can be coadministered without dose adjustment, or clinical monitoring adjustment. no adjustment is necessary when 17 20 medications, contraindicated.