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.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.