Drug Interaction Report

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.

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.