Phase II Study to Evaluate the Safety and Efficacy of the Oral Neurokinin-1 Receptor Antagonist Casopitant (GW679769) Administered with Ondansetron for the Prevention of Postoperative and Postdischarge Nausea and Vomiting in High-risk Patients

• Published in: Anesthesiology (Philadelphia) Vol. 113; no. 1; pp. 74 - 82
• Main Authors: Singla, Neil K., Singla, Sonia K., Chung, Frances, Kutsogiannis, Demetrios J., Blackburn, Linda, Lane, Stephen R., Levin, Jeremey, Johnson, Brendan, Pergolizzi, Joseph V.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.07.2010
• Subjects: Administration, Oral; Adolescent; Adult; Anesthesia; Anesthesia, General - methods; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antiemetics - administration & dosage; Antiemetics - adverse effects; Biological and medical sciences; Cholecystectomy, Laparoscopic; Constipation - chemically induced; Dizziness - chemically induced; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Gynecologic Surgical Procedures; Headache - chemically induced; Humans; Medical sciences; Middle Aged; Neurokinin-1 Receptor Antagonists; Ondansetron - administration & dosage; Piperazines - administration & dosage; Piperazines - adverse effects; Piperidines - administration & dosage; Piperidines - adverse effects; Postoperative Nausea and Vomiting - prevention & control; Risk Factors; Treatment Outcome; Young Adult; Human; Postoperative; NK1 Tachykinin receptor; Serotonin antagonist; Oral administration; Nausea; Prevention; Vomiting; 5-HT3 Serotonine receptor; Phase II trial; Risk factor; Casopitant; Digestive diseases; Anesthesia; Antiemetic; Ondansetron
• ISSN: 0003-3022; 1528-1175; 1528-1175
• DOI: 10.1097/ALN.0b013e3181d7b13a

In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride. The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis). A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events. Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.