Drug Interaction Report

MONITOR: Coadministration of maribavir may increase the plasma concentrations of immunosuppressant drugs that are substrates of CYP450 3A4 and/or P-glycoprotein (P-gp), such as cyclosporine, everolimus, sirolimus, and tacrolimus. The proposed mechanism is decreased clearance of the immunosuppressant drugs due to inhibition of P-gp-mediated drug efflux and CYP450 3A4 by maribavir. In a pharmacokinetic study, tacrolimus peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 38% and 51%, respectively, when maribavir (400 mg twice daily) was concomitantly administered with a stable, twice daily dose of tacrolimus (0.5 to 16 mg total daily dose).

MANAGEMENT: Caution is advised when maribavir is used concurrently with cyclosporine, everolimus, sirolimus, or tacrolimus. Frequent clinical and laboratory monitoring as well as dosage adjustments may be appropriate for the immunosuppressant whenever maribavir is added to or withdrawn from therapy.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.