Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the blood concentrations and pharmacologic effects of everolimus. In a study of healthy volunteers, multiple doses of the potent inducer rifampin increased the oral clearance of everolimus by threefold, representing mean decreases in peak blood concentration (Cmax) and systemic exposure (AUC) of 58% and 63%, respectively. The extent to which other inducers of CYP450 3A4 interact with everolimus is unknown.

MANAGEMENT: Some manufacturers recommend avoiding concomitant use of everolimus with moderate CYP450 3A4 and/or P-gp inducers such as bosentan, efavirenz, and nevirapine. If concomitant use is required, a dose adjustment of everolimus should be considered to achieve the recommended therapeutic range for the condition being treated. Please refer to the manufacturer's labeling for specific dosing information. Everolimus whole blood trough levels should be closely monitored during treatment, particularly 2 weeks after a dose increase and 2 weeks after discontinuation of the inducer.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.