Drug Interaction Report

GENERALLY AVOID: Coadministration with erdafitinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter, resulting in increased toxicity of these drugs. In vitro, erdafitinib has been shown to be an inhibitor of P-gp. However, no pharmacokinetic data are available from drug interaction studies.

MANAGEMENT: Concomitant use of erdafitinib and P-gp substrates should generally be avoided. If concomitant use is required, administer erdafitinib at least 6 hours before or after administration of P-gp substrates with narrow therapeutic ranges.

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.