Drug Interactions between fosphenytoin and gefitinib

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of gefitinib, which is primarily metabolized by the isoenzyme. When a single 500 mg dose of gefitinib was administered following pretreatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 16 days) in healthy male volunteers, mean gefitinib systemic exposure (AUC) decreased by 83% compared to administration of gefitinib alone. Reduced efficacy of gefitinib may occur.

MANAGEMENT: When used concomitantly with potent CYP450 3A4 inducers, the manufacturer recommends increasing the dosage of gefitinib to 500 mg daily in the absence of severe adverse reactions. The normal recommended dosage of 250 mg once daily may be resumed 7 days after discontinuing the CYP450 3A4 inducer.