Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of sirolimus and tacrolimus, both of which are primarily metabolized by the isoenzyme.

MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant drug levels, caution is advised during concomitant therapy with CYP450 3A4 inducers. Sirolimus and tacrolimus blood levels should be checked frequently and the dosage adjusted accordingly whenever a CYP450 3A4 inducer is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

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.