Drug Interaction Report

ADJUST DOSING INTERVAL: Concurrent administration of bile acid sequestrants may delay and/or decrease the absorption of oral corticosteroids. Bile acid sequestrants can bind certain drugs in the intestine to form an insoluble complex that is excreted in the feces. Reduced bioavailability of hydrocortisone has been reported during concomitant administration with cholestyramine and colestipol. It is not known whether the interaction occurs with other bile acid binding resins such as colesevelam or with corticosteroids other than hydrocortisone, but the possibility should be considered.

MANAGEMENT: Oral corticosteroids should be administered at least 1 hour before or 4 to 6 hours after a cholestyramine or colestipol dose, and at least 4 hours before a colesevelam dose.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of 21-desdeflazacort, the active metabolite of deflazacort that is formed by esterases after oral administration and further metabolized by CYP450 3A4 to several inactive metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to 21-desdeflazacort may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Deflazacort should not be administered with grapefruit juice.