Drug Interactions between edoxaban and Vosevi

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of edoxaban, which is a substrate of the efflux transporter. In healthy volunteers, single-dose edoxaban systemic exposure (AUC) increased approximately 80% to 90% by erythromycin, dronedarone, and ketoconazole; 70% to 80% by cyclosporine and quinidine; 50% by verapamil; and 40% by amiodarone. The peak plasma concentration (Cmax) of edoxaban also increased by approximately 45% to 90% with these drugs.

MANAGEMENT: When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned. Other P-gp inhibitors were not permitted in the study, and patients on antiretroviral therapy (ritonavir, nelfinavir, indinavir, saquinavir) as well as cyclosporine were excluded from the study. Following discontinuation of the P-gp inhibitor, edoxaban dosage should be returned to the regular dosage of 60 mg once daily. No dosage adjustment is recommended for edoxaban when used in the treatment of nonvalvular atrial fibrillation.

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of edoxaban, which is a substrate of the efflux transporter. In healthy volunteers, single-dose edoxaban systemic exposure (AUC) increased approximately 80% to 90% by erythromycin, dronedarone, and ketoconazole; 70% to 80% by cyclosporine and quinidine; 50% by verapamil; and 40% by amiodarone. The peak plasma concentration (Cmax) of edoxaban also increased by approximately 45% to 90% with these drugs. Data evaluating the interaction between edoxaban and voxilaprevir are lacking.

MANAGEMENT: When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned. Other P-gp inhibitors were not permitted in the study, and patients on antiretroviral therapy (ritonavir, nelfinavir, indinavir, saquinavir) as well as cyclosporine were excluded from the study. Following discontinuation of the P-gp inhibitor, edoxaban dosage should be returned to the regular dosage of 60 mg once daily. No dosage adjustment is recommended for edoxaban when used in the treatment of nonvalvular atrial fibrillation.

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.