Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 that can also inhibit P-glycoprotein (P-gp) may significantly increase the plasma concentrations of rivaroxaban, which is a substrate of both the isoenzyme and efflux transporter. The risk of bleeding associated with rivaroxaban may be increased. When rivaroxaban was coadministered with the dual P-gp and potent CYP450 3A4 inhibitor, ketoconazole (400 mg once daily), mean steady-state rivaroxaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.7- and 2.6-fold, respectively. Likewise, coadministration with ritonavir 600 mg twice a day increased the mean steady-state rivaroxaban Cmax by 1.6-fold and AUC by 2.5-fold. Significant increases in pharmacodynamic effects of rivaroxaban were observed with both drugs.

MANAGEMENT: Concomitant use of rivaroxaban with dual P-gp and potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of rivaroxaban during and for 2 weeks after treatment with itraconazole.