Drug Interaction Report

MONITOR: Corticosteroids may antagonize the effects of antihypertensive medications by inducing sodium and fluid retention. These effects may be more common with the natural corticosteroids (cortisone, hydrocortisone) because they have greater mineralocorticoid activity. Conversely, some calcium channel blockers such as diltiazem and verapamil may increase corticosteroid plasma levels and effects by inhibiting their clearance via CYP450 3A4 metabolism.

MANAGEMENT: Patients on prolonged (i.e., longer than about a week) or high-dose corticosteroid therapy should have blood pressure, electrolyte levels, and body weight monitored regularly, and be observed for the development of edema and congestive heart failure. The dosages of antihypertensive medications may require adjustment.

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.