Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of chemotherapy-induced emesis

Abstract

Palonosetron (Aloxi) is a 5-HT(3)-receptor antagonist antiemetic indicated for the prevention of acute and delayed nausea and vomiting following moderately emetogenic chemotherapy and for acute nausea and vomiting following highly emetogenic chemotherapy. Although it is the fourth member of this class to enter the US market, palonosetron is distinguished by distinct pharmacological characteristics. It has a higher binding affinity for the 5-HT(3 )receptor and a terminal serum half-life at least four times greater than any other available agent of this class (approximately 40 h). The high affinity and long half-life may explain the persistence of antiemetic effect throughout the delayed emesis risk period. The indications for palonosetron are supported by one dose-ranging study and three large, randomised, Phase III studies that all demonstrated at least equivalent activity (and in some cases, superior activity) compared to other 5-HT(3)-receptor antagonists. In spite of the pharmacological differences, the side effect profile of palonosetron is comparable to that of other 5-HT(3)-receptor antagonists. Palonosetron may prove valuable in combination therapy for delayed emesis and may be an appropriate agent for clinical settings, such as multiple-day chemotherapy, where acute emesis is repeatedly induced. Palonosetron provides a convenience advantage if multiple-day 5-HT(3)-receptor antagonist therapy is anticipated and is a unique addition to the antiemetic armamentarium.

NCCN Guidelines Insights: Antiemesis, Version 2.2017

“…[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] For the 2017 update, the NCCN panel added recommendations for a new formulation of granisetron-subcutaneous granisetron extended-release injection-in antiemetic regimens for HEC and MEC based on published data and recent FDA approval (see AE-5, AE-6, AE-7, and AE-A 2; pages 886-888 and 890). It is important to note that subcutaneous granisetron extended-release injection is a unique formulation of granisetron using a polymer-based drug delivery system.…”

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis

“…In addition to a longer elimination half-life (t½) that contributes to a longer duration of action, 12,13 palonosetron has a distinctly different receptor binding profle: it acts as an allosteric antagonist with positive cooperativity to the 5-HT 3 receptor, whereas ondansetron and granisetron exhibit simple bimolecular binding. 11 Thus, palonosetron binds more strongly, is a more efficient receptor antagonist, and is less likely to be displaced by serotonin.…”

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

“…dolasetron mesylate, granisetron, ondansetron, palonosetron) was a significant advance in antiemetic therapy, and all of these agents have been shown to be effective in controlling acute nausea and vomiting associated with cancer chemotherapy [20,21]. Palonosetron is a 5-HT 3 receptor antagonist with significantly higher binding affinity and a longer half-life compared with other agents in the same class [20]. In addition, data suggest that palonosetron also differs from other 5-HT 3 antagonists in the duration of 5-HT 3 receptor inhibition [22].…”