Definition

An orally available combination formulation containing netupitant, a selective neurokinin 1 (NK1) receptor antagonist, and the hydrochloride salt form of palonosetron, a selective serotonin (5-hydroxytryptamine; 5-HT) receptor subtype 3 (5-HT3) antagonist, with antiemetic activity. Upon oral administration, palonosetron competitively blocks the action of 5-HT at 5-HT3 receptors located on vagal afferent nerves in the chemoreceptor trigger zone (CTZ). This inhibits acute emesis associated with 5-HT secretion and subsequent 5-HT3 activation. Netupitant competitively binds to and blocks the activity of the human NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1 receptor binding of the endogenous tachykinin neuropeptide substance P (SP). This prevents delayed emesis, which is associated with SP secretion. Altogether, this results in the prevention of chemotherapy-induced nausea and vomiting (CINV).