Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of retapamulin, which is primarily metabolized by the isoenzyme. In healthy adult males, coadministration of the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice a day) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of retapamulin by 81% following topical application of retapamulin ointment 1% on abraded skin. However, dosage adjustments are not necessary due to the low systemic exposure to retapamulin following topical application.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.