Drug Interaction Report

MONITOR: Coadministration with tivozanib may increase the plasma concentrations and therapeutic effects of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism, based on in vitro data, is decreased clearance due to inhibition of BCRP-mediated intestinal efflux by tivozanib. The clinical significance of this interaction has not been established; however, it should be taken into consideration with orally administered intestinal BCRP-sensitive substrates such as rosuvastatin.

MANAGEMENT: Caution and clinical monitoring are advised if tivozanib is prescribed with orally administered drugs that are sensitive substrates for BCRP, such as rosuvastatin. If coadministration is necessary, the manufacturer suggests separating the administration times by 2 or more hours.

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.