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monitoring as well as dosage adjustments may be appropriate for the immunosuppressant whenever maribavir is added to or withdrawn from therapy.

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.