Drug Interaction Report

Coadministration of niraparib with a P-glycoprotein (P-gp) and/or Breast Cancer Resistance Protein (BCRP) inhibitor may increase the plasma concentration of niraparib, which is a substrate of these efflux transporters. However, due to the high permeability and bioavailability of niraparib, the risk of a clinically relevant interaction with inhibitors of these transporters is unlikely. No dose adjustment is recommended if a P-gp and/or BCRP inhibitor is added to treatment with niraparib.

MONITOR: Coadministration with inhibitors of CYP450 3A4 including grapefruit or grapefruit juice may increase the plasma concentrations of leniolisib, which undergoes extensive CYP450 3A4-mediated first-pass metabolism in the gut wall and liver. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of leniolisib. Some authorities recommend to avoid grapefruit products during leniolisib treatment (UK).