Drug Interaction Report

MONITOR: Coadministration with sirolimus may increase the plasma concentrations of mycophenolic acid. The mechanism of interaction is unknown. In 13 kidney transplant patients receiving concomitant therapy with sirolimus, the mycophenolic acid systemic exposure (AUC from 0 to 12 hours) at 2 weeks, 1 month and 2 months post-transplantation was 88%, 50% and 49% higher, respectively, than in 17 patients receiving concomitant therapy with cyclosporine. At all time points, patients in the sirolimus group had significantly higher dose-normalized mycophenolic acid AUC values than patients in the cyclosporine group. In addition, at months 1 and 2, white blood cell counts were significantly lower in the sirolimus group than in the cyclosporine group. Theoretically, the interaction may also occur with temsirolimus, a drug that is primarily metabolized to sirolimus in vivo.

MANAGEMENT: Mycophenolic acid plasma levels should be monitored more closely following initiation, discontinuation, or change of dosage of sirolimus or temsirolimus.

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.