Drug Interaction Report

ADJUST DOSE: Coadministration with netupitant or its prodrug, fosnetupitant, may significantly increase the plasma concentrations of dexamethasone. The proposed mechanism is netupitant inhibition of dexamethasone metabolism via CYP450 3A4. When a single 300 mg dose of netupitant was coadministered with a dexamethasone regimen consisting of 20 mg on day 1, followed by 8 mg twice daily from days 2 to Day 4, mean dexamethasone systemic exposure (AUC) was increased by 1.7-fold on day 1 and up to 2.4-fold on day 2 and day 4. The duration of the effect was not studied beyond 4 days.

MANAGEMENT: Dexamethasone should be administered at a reduced dosage when used with netupitant or fosnetupitant. For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, dexamethasone should be dosed according to the product labeling for netupitant-palonosetron or fosnetupitant-palonosetron.