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 pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.