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 apixaban, which is a substrate of both the isoenzyme and efflux transporter. The risk of bleeding associated with apixaban may be increased. When apixaban was coadministered with the dual P-gp and potent CYP450 3A4 inhibitor, ketoconazole (400 mg once daily), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 1.6- and 2-fold, respectively. The systemic exposure may be increased even more in patients with significant renal impairment.

MANAGEMENT: The use of apixaban should either be avoided or the dosage reduced during concomitant systemic treatment with dual P-gp and potent CYP450 3A4 inhibitors. In addition, some authorities recommend avoiding concomitant use of apixaban during and for 2 weeks after treatment with itraconazole. For patients receiving apixaban 5 mg or 10 mg twice daily, the prescribing information recommends reducing the dosage by 50%. In patients already taking apixaban at a dosage of 2.5 mg twice daily (e,g., patients meeting at least 2 of the following criteria: age >=80 years; body weight <=60 kg; serum creatinine >=1.5 mg/dL), coadministration with dual P-gp and potent CYP450 3A4 inhibitors should be avoided.