Drug Interactions between colesevelam and mycophenolate mofetil

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).