Casopitant enhances ondansetron effect on PONV risk
MedWire News: Adding the oral neurokinin-1 receptor antagonist casopitant to ondansetron increases the proportion of patients who remain free of postoperative nausea and vomiting (PONV), shows a phase II study in high-risk patients.
Current monotherapies only reduce PONV incidence by about 30%, say Neil Singla (Lotus Clinical Research Inc, Pasadena, California, USA) and colleagues.
They add that it has recently become apparent that multiple receptors are involved in the etiology of PONV, leading to interest in a multimodal approach to prevent the condition.
The team enrolled 702 nonsmoking women with a history of PONV or motion sickness who were undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Female gender, nonsmoking status, and previous PONV or motion sickness are established risk factors for PONV.
The patients were randomly assigned to receive casopitant given 1 hour before anesthesia at doses of 0, 50, 100, or 150 mg in addition to the serotonin 5-HT3 receptor antagonist ondansetron 4 mg given intravenously 2 to 5 minutes before anesthesia.
During the first 24 hours after surgery, 40% of women taking ondansetron alone achieved a complete response (no PONV and no need for rescue medication). Complete response rates were significantly higher among those taking combined therapy, at 59.3%, 62.1%, and 60.7% with casopitant 50, 100, and 150 mg, respectively.
There were no significant differences between the different casopitant doses, the team notes in the journal Anesthesiology.
The improved response with combined therapy was down to a reduction in the number of patients who vomited, which ranged from 4.3% to 9.3% with combined therapy, compared with 28.6% of patients in the ondansetron only group.
Nausea rates were similar regardless of treatment allocation, although nausea tended to be more severe among patients receiving monotherapy. Adverse event rates were similar between the treatment groups, with headache being the most frequent complaint.
The researchers note that they were "unable to establish a minimally effective dose of casopitant," but cite previous research suggesting that doses lower than 50 mg may be insufficient to avoid the need for rescue medication.
"Because the effect of all three doses of casopitant in combination with ondansetron was similar, in terms of both tolerability and efficacy, the most appropriate choice of dose of casopitant for future development in combination with ondansetron would be 50 mg," they conclude.
"This dose represents the best choice in terms of minimizing patient exposure while retaining efficacy."
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By Eleanor McDermid