Jan Wallenborn¹ and Peter Kranke²

¹Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Liebigstr. 20, Leipzig, Germany. ²Department of Anaesthesia and Critical Care, University of Würzburg, Oberdürrbacher Str. 6, Würzburg, Germany.  

Abstract

On the strength of two phase III clinical trials, palonosetron hydrochloride was granted FDA approval in March 2008 for the prevention of postoperative nausea and vomiting (PONV) in the period up to 24 hours after surgery. Palonosetron is superior to the established first-generation 5-hydroxytryptamin-3 receptor antagonists (5-HT₃-RAs) in respect of pharmacokinetic data such as a high receptor binding affinity (pKi = 10.45) and a prolonged mean elimination half-life (40 hours). Clinically, palonosetron 0.075 mg was superior to placebo within the 0 to 24 h period usually investigated. A pooled data analysis of the complete response (CR) rates revealed efficacy in the 0 to 24 h period (when compared to placebo CR = 1.67 [1.38–2.02; P < 0.001, n = 370]) and between 24–72 h after surgery (CR = 1.29 [1.10–1.51; P = 0.002, n = 273]). Overall, the effect of palonosetron in reducing delayed vomiting was not as promising as expected. In the approval studies for PONV the rates of AEs including headache (3%), constipation (2%) and prolongation of the QTc interval (5%) were indistinguishable between palonosetron and placebo. In studies on chemotherapy-induced nausea and vomiting, palonosetron increased the QTc interval (between one and three ms) to a lesser extent than ondansetron or dolasetron (5 ms). The safety profile of palonosetron therefore seems to be favourable so far, making it a preferred perioperative antiemetic in the geriatric population or in multimorbid patients. However, further studies are needed to permit general recommendations, and we still lack comparative trials with older (and less expensive) 5-HT₃-RAs, trials with combined PONV prophylaxis, and trials in the paediatric population.