WOODCLIFF LAKE, NJ -- March 3, 2008 -- The US Food and Drug Administration (FDA) has approved palonosetron hydrochloride (Aloxi) injection for the prevention of postoperative nausea and vomiting for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated.
Available in the United States since 2003, palonosetron is the only 5-hydroxytryptamine-3 (5-HT3) receptor antagonist approved by the FDA for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.
The new indication is based on one double-blind phase 3 study that evaluated the efficacy of 3 doses of palonosetron compared with placebo for the prevention of postoperative nausea and vomiting. In the trial, 574 patients undergoing elective gynaecologic or abdominal laparoscopic surgery (predominately in the outpatient setting) were randomised to receive 1 of 3 single intravenous doses of palonosetron (0.025 mg, 0.050 mg, or 0.075 mg) or placebo before administration of anaesthesia. The effectiveness of palonosetron in postoperative nausea and vomiting was assessed on the day of surgery (0-24 hr) and for 2 subsequent days (24-72 hr).
The trial successfully met its coprimary endpoint of complete response -- defined as no emesis or use of rescue medication -- for the 0- to 24-hour time period: 42.8% of patients treated with the approved dose of palonosetron 0.075 mg experienced a complete response, compared with 25.9% of patients given placebo (P = .0035). For the coprimary endpoint of complete response for the 24- to 72-hour postoperative period, 48.6% of patients treated with palonosetron 0.075 mg experienced a complete response, compared with 40.7% of patients given placebo (P = .1877).
Palonosetron 0.075 mg also reduced the severity of nausea compared with placebo. This result was supported by phase 2 postoperative nausea and vomiting trial results, which demonstrated that palonosetron significantly reduced the severity of nausea compared with placebo (P = .009).
The incidence of adverse reactions was indistinguishable among all treatment groups, including placebo. The most frequently observed side effects with palonosetron were electrocardiogram (ECG) QT prolongation (5%), bradycardia (4%), headache (3%), and constipation (2%).
Included in the updated label with the new indication were the results of a study, in 221 healthy volunteers, on the effects of palonosetron (at doses of 0.25 mg, 0.75 mg, and 2.25 mg) compared with moxifloxacin on several ECG intervals, a potential safety concern of drugs in the 5-HT3 receptor antagonist class. The study demonstrated that palonosetron had no significant effect on any ECG interval, including QTc duration (cardiac repolarisation), at doses up to 2.25 mg.
SOURCE: Eisai Corporation of North America
E-Mail this DGNews to a colleague
