title: Profile of netupitant/palonosetron (NEPA) fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV).
abstract: Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy.
authors.affiliation: Cancer Care Program, Eastern Europe, World Health Organization, Mishawaka, IN, USA; Indiana University School of Medicine, South Bend, IN, USA; South Bend Medical Services Corporation, IN, USA.
authors.forename: Rudolph M
authors.initials: RM
authors.lastname: Navari
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D015394:Molecular Structure; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D000077924:Palonosetron; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011812:Quinuclidines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*; D010879:Piperazines; D044482:Benzeneacetamides
chemical_list: D004338:Drug Combinations; D007546:Isoquinolines; D000077924:Palonosetron; D011725:Pyridines; D011812:Quinuclidines; C000595957:netupitant, palosentron drug combination; C508854:netupitant; D010879:Piperazines; D044482:Benzeneacetamides
keywords: 5-HT3 receptor antagonists; NK-1 receptor antagonists; chemotherapy-induced nausea and vomiting; netupitant; palonosetron