P&T Portfolio: Aloxi

October 20, 2003

Palonosetron Injection (Aloxi) for use in patients with chemotherapy induced nausea.

 

HEALTH-SYSTEM EDITION

P & T PORTFOLIO

Generic name

Palonosetron injection

Proprietary name/manufacturer

Aloxi/MGI

FDA-approved indication

Palonosetron is approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy and for the prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Pharmacology

Palonosetron is a potent, highly selective serotonin-3 (5-HT3) receptor antagonist with a strong receptor-binding affinity. Administration of cytotoxic agents induces the release of serotonin (5-HT) from the enterochromaffin cells of the gastrointestinal tract. The binding of serotonin to 5-HT3 receptors located on vagal neurons in the periphery signals the vomiting center in the brain thereby inducing nausea and vomiting. Palonosetron binds to the receptor, thus inhibiting the binding of serotonin and preventing chemotherapy-induced nausea and vomiting.

Efficacy

Several controlled clinical trials have demonstrated the efficacy of palonosetron in the prevention of nausea and vomiting associated with moderately and highly emetogenic chemotherapy and in the prevention of delayed nausea and vomiting associated with moderately emetogenic chemotherapy. Primary endpoint was complete response (absence of vomiting and use of rescue medication). In these studies, palonosetron was effective during the acute phase (0-24 hours) in 63%-81% of patients receiving moderately emetogenic chemotherapy and in 59% of patients receiving highly emetogenic chemotherapy. In addition, palonosetron was effective during the delayed phase (24-120 hours) in 54%-74% of patients receiving moderately emetogenic chemotherapy. Palonosetron appears to be similar in efficacy to dolasetron (Anzemet, Aventis) and more effective than single-dose ondansetron (Zofran, GlaxoSmithKline) in controlling acute nausea and vomiting associated with moderately emetogenic chemotherapy and more effective than either of these agents for the prevention of delayed nausea and vomiting associated with these agents. It also has demonstrated similar efficacy to ondansetron for the prevention of acute nausea and vomiting induced by highly emetogenic chemotherapy.

Pharmacokinetics

Protein binding62%
Volume of distribution8.3 L/kg
MetabolismCYP2D6, and to a lesser extent by CYP3A4, and CYP1A2 to N-oxide and hydroxy metabolites
ExcretionUrine (80%)
Half-life40 hours

 

Contraindications

Hypersensitivity to any product components

Precautions

Administer with caution in patients who have or may develop prolongation of cardiac conduction intervals, particularly QTc.

Adverse effects

The most common adverse effects of palonosetron, occurring in 1%-9% of patients, include headache (9%); constipation (5%); diarrhea (1%); dizziness (1%); nonsustained tachycardia, bradycardia, hypotension (1%); weakness (1%); hyperkalemia (1%); and anxiety (1%).

Dose

Usual dose: 0.25 mg IV administered over 30 seconds as a single dose approximately 30 minutes before the start of chemotherapy. Repeated dosing within a seven-day interval is not recommended.

Conclusion/comments

Palonosetron is a selective 5-HT3 receptor antagonist with an extended half-life that has demonstrated efficacy for the prevention of acute nausea and vomiting associated with moderately and highly emetogenic cancer chemotherapy and for the prevention of delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy. It is the first 5-HT3 antagonist approved for the prevention of delayed chemotherapy-induced nausea and vomiting. Comparative studies between palonosetron and other antiemetic agents, alone or in combination, are not available. A disadvantage is that palonosetron is administered by injection only. Unlike some other 5-HT3 receptor antagonists, palonosetron is not FDA-approved for pediatric use. The manufacturer of palonosetron will closely monitor potential gastrointestinal and cardiovascular adverse effects and will communicate its findings to the FDA via 15-day postmarketing reports.

 

Published October 2003. Content based on medical literature and product information available at that time.

 

 

P&T Portfolio: Aloxi. Drug Topics Oct. 20, 2003;147.