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levels should be checked frequently and the dosage adjusted accordingly whenever a CYP450 3A4 inducer is added to or withdrawn from therapy.

MONITOR: Isolated case reports have suggested that the ingestion of alcohol during griseofulvin therapy may rarely cause disulfiram-like reactions, flushing, tachycardia, or increased effects of alcohol. The mechanism is unknown.

MANAGEMENT: Patients should be advised of the possibility of increased adverse effects or a disulfiram-like reaction.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.