Drug Interactions between cobicistat and Mavyret

MONITOR: Coadministration with cobicistat may significantly increase the plasma concentrations of glecaprevir. The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of glecaprevir by cobicistat. Inhibition of P-glycoprotein-mediated intestinal efflux and CYP450 3A4-mediated metabolism of glecaprevir may also contribute. When glecaprevir-pibrentasvir 300 mg-120 mg once daily was administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 150 mg/150 mg/200 mg/10 mg once daily to 11 study subjects, glecaprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) increased by approximately 2.5-, 3.1- and 4.6-fold, respectively. Pibrentasvir Cmax was unaffected, but AUC and Cmin increased by nearly 1.6- and 1.9-fold, respectively. In addition, elvitegravir Cmax, AUC and Cmin were also increased by approximately 1.4-, 1.5- and 1.7-fold, respectively, while tenofovir AUC and Cmin were increased by nearly 1.3- and 1.4-fold, respectively. High plasma levels of glecaprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) and bilirubin elevations.

MANAGEMENT: According to the manufacturer, no dosage adjustment is necessary for glecaprevir-pibrentasvir during coadministration with cobicistat. However, the potential for increased adverse effects of glecaprevir-pibrentasvir should be considered.