Drug Interactions between elbasvir / grazoprevir and mibefradil

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of grazoprevir, which is a substrate of the isoenzyme. In 8 study subjects, administration of a single 100 mg dose of grazoprevir with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily) increased grazoprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 13%, 200% and 100%, respectively, compared to administration of grazoprevir alone. High plasma levels of grazoprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) elevations. Ketoconazole also increased the Cmax, AUC and Cmin of a single 50 mg dose of elbasvir by 29%, 80% and 89%, respectively.

MANAGEMENT: Concomitant use of elbasvir-grazoprevir with potent CYP450 3A4 inhibitors should generally be avoided.

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of elbasvir, which is a substrate of the isoenzyme. In 10 study subjects, administration of elbasvir (50 mg once daily) with the potent CYP450 3A4 inhibitors atazanavir/ritonavir (300 mg/100 mg once daily) increased elbasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 4.15-fold, 4.76-fold and 6.45-fold, respectively, compared to elbasvir alone. Likewise, administration with lopinavir/ritonavir 400 mg/100 mg twice daily increased elbasvir Cmax, AUC, and Cmin by 2.87-, 3.71-, and 4.58-fold, respectively (n=10), while administration with darunavir/ritonavir 600 mg/100 mg twice daily increased elbasvir Cmax, AUC, and Cmin by 1.67-, 1.66-, and 1.82-fold, respectively (n=10). Another potent CYP450 3A4 inhibitor, ketoconazole (400 mg once daily), increased the Cmax, AUC, and Cmin of a single 50 mg dose of elbasvir by 1.29-, 1.80, and 1.89-fold, respectively (n=7).

MANAGEMENT: Concomitant use of elbasvir with potent CYP450 3A4 inhibitors should generally be avoided.