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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.