Drug Interaction Report

GENERALLY AVOID: Coadministration with bile acid sequestrants or activated charcoal may decrease the bioavailability of mycophenolic acid. In 12 healthy volunteers, pretreatment with cholestyramine (4 g three times a day for 4 days) decreased the systemic exposure (AUC) of mycophenolic acid (from mycophenolate mofetil 1.5 g single dose) by 40% compared to administration of mycophenolate mofetil alone. The proposed mechanism is interruption of enterohepatic recirculation due to binding of recirculating mycophenolic acid glucuronide (a product of the first-pass metabolism of mycophenolic acid) with cholestyramine in the intestine. Some degree of enterohepatic recirculation is also anticipated following intravenous administration of mycophenolate mofetil, thus the interaction is not limited to the oral route.

MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant blood levels, mycophenolic acid products should not be administered with cholestyramine or other agents that may interfere with enterohepatic recirculation or bind bile acids (e.g., activated charcoal).

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.