Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of lusutrombopag, which is a substrate of both efflux transporter proteins. Coadministration with cyclosporine, a P-gp and BCRP dual inhibitor, increased lusutrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 20% each compared with lusutrombopag administration alone.

MANAGEMENT: Caution is advised if lusutrombopag is prescribed in combination with P-gp and/or BCRP inhibitors. Pharmacologic response to lusutrombopag should be monitored more closely following initiation, discontinuation, or change of dosage of the concomitant P-gp or BCRP inhibitor.

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.