Drug Interactions between lapatinib and mirabegron

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.

Food reduces the oral absorption and bioavailability of mirabegron. According to the product labeling, administration of a 50 mg tablet with a high-fat meal decreased mirabegron peak plasma concentration (Cmax) and systemic exposure (AUC) by 45% and 17%, respectively, whereas administration with a low-fat meal decreased mirabegron Cmax and AUC by 75% and 51%, respectively. In phase 3 clinical studies demonstrating both safety and efficacy, mirabegron was administered without regards to food content and intake. Therefore, mirabegron can be taken with or without food at the recommended dosage.