Drug Interaction Report

ADJUST DOSE: Coadministration with inhibitors of organic anion transporting polypeptide (OATP) 1B1 and/or 1B3 may significantly increase the plasma concentrations of atogepant, which is a substrate of the hepatic uptake transporters. When atogepant was administered in healthy study subjects with single-dose rifampin, an OATP 1B1/1B3 inhibitor, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.9-fold, respectively.

MANAGEMENT: The recommended dosage of atogepant is 10 mg or 30 mg once daily when used concomitantly with OATP 1B1/1B3 inhibitors.

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.