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.

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.

ADJUST DOSING INTERVAL: Administration of enteric coated mycophenolic acid with meals may alter its pharmacokinetics relative to administration in the fasting state. When mycophenolic acid 720 mg was administered with a high-fat meal, there was a 33% decrease in the peak plasma concentration (Cmax); a 3.5-hour increase in delay time for the rise of plasma mycophenolic acid; and a 5-hour delay in the time to reach peak plasma concentration (Tmax). However, no effect was observed on the systemic exposure of mycophenolic acid.

MANAGEMENT: To avoid variability in drug absorption between doses, enteric coated formulations of mycophenolic acid should be taken on an empty stomach, one hour before or two hours after food intake. The tablets should be swallowed whole and not crushed, chewed or divided in order to maintain the integrity of the enteric coating.