Drug Interaction Report

ADJUST DOSE: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly 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. According to the product labeling, when deflazacort was administered following multiple doses of clarithromycin, a strong CYP450 3A4 and P-glycoprotein inhibitor, mean total exposure to 21-desdeflazacort increased by approximately 3-fold compared to administration of deflazacort alone.

MANAGEMENT: The manufacturer suggests using one-third of the recommended dosage of deflazacort when coadministered with potent or moderate CYP450 3A4 inhibitors. Some authorities recommend avoiding concomitant use of deflazacort and CYP450 3A inhibitors unless the benefit outweighs the risk, in which case patients should be monitored for systemic corticosteroid side effects.

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.