Drug Interaction Report

Coadministration of niraparib with a P-glycoprotein (P-gp) and/or Breast Cancer Resistance Protein (BCRP) inhibitor may increase the plasma concentration of niraparib, which is a substrate of these efflux transporters. However, due to the high permeability and bioavailability of niraparib, the risk of a clinically relevant interaction with inhibitors of these transporters is unlikely. No dose adjustment is recommended if a P-gp and/or BCRP inhibitor is added to treatment with niraparib.

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.