Drug Interaction Report

GENERALLY AVOID: Coadministration with oral tedizolid may increase the plasma concentrations and the risk of adverse effects of orally administered drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is decreased clearance due to inhibition of BCRP-mediated intestinal efflux by tedizolid. Administration of a single 10 mg dose of rosuvastatin, a known BCRP substrate, to healthy subjects who had received multiple daily doses of tedizolid 200 mg increased rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 70%, respectively.

MANAGEMENT: Consider temporarily interrupting treatment with the BCRP substrate during treatment with tedizolid, especially for BCRP substrates with a narrow therapeutic index. If coadministration cannot be avoided, monitor for adverse reactions related to concomitantly administered BCRP substrate. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

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.