Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of mitoxantrone, which is a substrate of the efflux transporter also known as ABCB1 or MDR1. The interaction has been studied with cyclosporine, a potent P-gp inhibitor. In a pharmacokinetic study of 38 children with de novo acute myeloid leukemia, mitoxantrone 6 mg/m2 administered daily in combination with cyclosporine resulted in a 42% decrease in mean mitoxantrone clearance and 12% increase in systemic exposure (AUC) compared to mitoxantrone 10 mg/m2 administered daily without cyclosporine. There were no differences in the rates of stomatitis or infection between the two groups, but an increased incidence of hyperbilirubinemia was observed in the cyclosporine group, which rapidly reversed upon conclusion of treatment. Therefore, it appears a 40% dose reduction of mitoxantrone given with cyclosporine produced statistically similar systemic exposure and toxicity as mitoxantrone given alone.

MANAGEMENT: Caution is advised if mitoxantrone is prescribed in combination with a P-gp inhibitor. Patients should be closely monitored for increased adverse effects including cardiotoxicity and myelosuppression.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.