Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of uridine diphosphate glucuronosyltransferase (UGT) may decrease the plasma concentrations of deferasirox, which is primarily metabolized by UGT1A1- and UGT1A3-mediated glucuronidation. In healthy volunteers, administration of a single 30 mg/kg dose of deferasirox with the potent UGT inducer rifampin (600 mg/day for 9 days) resulted in a reduction of deferasirox systemic exposure (AUC) by 44%. The effect of other UGT inducers on the pharmacokinetics of deferasirox is unknown.

MANAGEMENT: The concomitant use of deferasirox with potent UGT inducers such as rifampin, phenytoin, phenobarbital, carbamazepine, and ritonavir should generally be avoided. Otherwise, consideration may be given to increasing the initial dosage of deferasirox by 50% during coadministration with potent UGT inducers, with subsequent adjustments made according to serum ferritin levels and clinical response.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.