Drug Interactions between aminophylline and deferasirox

GENERALLY AVOID: Coadministration with deferasirox may significantly increase the plasma concentrations of theophylline. The proposed mechanism is deferasirox inhibition of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of theophylline. In a study of healthy volunteers, administration of a single 120 mg dose of theophylline in combination with deferasirox (repeated dosing of 30 mg/kg/day) resulted in an approximate doubling of theophylline systemic exposure (AUC) and elimination half-life. The single-dose peak plasma concentration (Cmax) was not affected, but an increase in theophylline Cmax is expected to occur with chronic dosing.

MANAGEMENT: Given the potential risk for theophylline toxicity, concomitant use with deferasirox should generally be avoided. Dosage adjustment for theophylline may be needed if coadministration with deferasirox is required. Close monitoring of serum theophylline levels is recommended, particularly following the addition, discontinuation, or change of dosage of deferasirox. Patients should be advised to notify their physician if they experience signs of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, seizures, palpitations, and cardiac arrhythmia.