Drug Interaction Report

MONITOR: Coadministration with deferasirox may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism may involve induction of CYP450 3A4 activity by deferasirox, although in vitro, the drug has been shown to inhibit CYP450 3A4. In healthy volunteers, administration of the CYP450 3A4 probe substrate midazolam in combination with deferasirox resulted in a reduction of midazolam peak concentration by 23% and systemic exposure by 17%. In the clinical setting, this effect may be more pronounced.

MANAGEMENT: Caution is advised if deferasirox must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever deferasirox is added to or withdrawn from therapy.

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.

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.