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.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.