Drug Interaction Report

MONITOR: Coadministration with niraparib may increase the plasma concentrations of drugs that are substrates of the multidrug and toxin extrusion (MATE) 1 and/or 2 transporters. The proposed mechanism is MATE 1 and/or 2 inhibition by niraparib. However, the clinical significance of this interaction is unclear.

MANAGEMENT: Caution is recommended if niraparib is used in combination with substrates of the multidrug and toxin extrusion (MATE) 1 and/or 2 transporters like metformin. Monitoring for signs and symptoms of increased exposure to the MATE 1 and 2 substrates should be considered whenever niraparib is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food may reduce the rate and extent of absorption of methylnaltrexone following oral administration. When a single 450 mg oral dose of methylnaltrexone was administered with a high-fat breakfast (approximately 800 to 1000 calories; 60% from fat, 25% from carbohydrate, and 15% from protein) in healthy study subjects, methylnaltrexone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 60% and 43%, respectively, while time to reach Cmax delayed by 2 hours.

MANAGEMENT: Oral methylnaltrexone should be taken with water on an empty stomach at least 30 minutes before the first meal of the day.