Drug Interaction Report

MONITOR: Coadministration with levacetylleucine may increase the plasma concentrations (AUC) and adverse effects of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. Levacetylleucine is a P-gp inhibitor in vitro. However, clinical data are not available.

MANAGEMENT: If coadministration is clinically necessary, more frequent clinical monitoring for P-gp substrate related adverse reactions is advised and dose adjustments may be required, particularly when levacetylleucine is initiated or withdrawn from concomitant therapy. Consultation with package labeling of the concomitant medication may be advisable.

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.