Akynzeo® (Netupitant/Palonosetron): A Comprehensive Pharmacological and Clinical Review for the Prophylaxis of Chemotherapy-Induced Nausea and Vomiting

Executive Summary

Netupitant/palonosetron, marketed as Akynzeo®, is a fixed-dose combination antiemetic that represents a significant advancement in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This agent uniquely targets two distinct and critical CINV signaling pathways through its dual components: netupitant, a highly selective and long-acting neurokinin-1 (NK1) receptor antagonist, and palonosetron, a second-generation serotonin-3 (5-HT3) receptor antagonist with a distinct pharmacological profile.[1] This dual mechanism provides comprehensive protection against both the acute phase of CINV, primarily mediated by serotonin, and the delayed phase, which is predominantly driven by substance P.

Administered as a single oral capsule or intravenous infusion prior to chemotherapy, Akynzeo® is indicated, in combination with dexamethasone, for the prevention of acute and delayed CINV associated with both highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).[3] Pivotal clinical trials have demonstrated its superior efficacy over palonosetron monotherapy and non-inferiority, with potential advantages in delayed CINV control, when compared to multi-day aprepitant-based regimens.[4] The synergistic interaction and complementary long-acting pharmacokinetic profiles of its components enable sustained antiemetic coverage for up to five days from a single dose, simplifying guideline-recommended prophylaxis and potentially enhancing patient adherence. The safety profile is well-characterized and generally favorable, with the most common adverse events including headache, asthenia, fatigue, and constipation.[3] However, its potent and prolonged inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme by netupitant necessitates careful management of drug-