PALOX

Indications

• Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy
• Prevention of postoperative nausea and vomiting

Dosage

Children: Dosing for children must be determined based on specific clinical guidelines.

Adults: For moderately emetogenic chemotherapy, the recommended oral dose is 0.5 mg taken approximately 1 hour before chemotherapy. For severely emetogenic chemotherapy, a single intravenous dose of 250 micrograms is administered over 30 seconds, 30 minutes before treatment.

Mechanism of action

Palonosetron functions as a selective serotonin 5-HT3 receptor antagonist. It inhibits 5-HT3 receptors in the gastrointestinal tract and central nervous system, particularly affecting the medullary chemoreceptor zone and the area postrema. By blocking these receptors, palonosetron reduces visceral afferent stimulation to the vomiting center, thereby preventing nausea and vomiting. Its long plasma half-life and potency may contribute to its effectiveness in preventing delayed nausea and vomiting following chemotherapy.

Pharmacodynamics

Palonosetron is classified as an antinauseant and antiemetic. It exhibits a high affinity for 5-HT3 receptors, leading to effective prevention of nausea and vomiting related to chemotherapy and postoperative circumstances. Unlike other 5-HT3 receptor antagonists, palonosetron is structurally distinct and primarily targets serotonin receptors without significant interaction with other receptor types, thus enhancing its specificity and reducing potential side effects.

Pharmacokinetics

Palonosetron demonstrates a long elimination half-life, which supports its efficacy in preventing delayed nausea and vomiting. The pharmacokinetics of palonosetron indicate rapid absorption following intravenous administration, with peak plasma concentrations occurring shortly after dosing. The drug is extensively metabolized in the liver, primarily through cytochrome P450 enzymes, and excreted mainly via urine. It also shows a low potential for drug-drug interactions due to its selective metabolic pathway.

Contra-indications

• Hypersensitivity to palonosetron or any of its excipients
• History of intestinal obstruction
• Severe constipation

Adverse effects

• Headache
• Dizziness
• Constipation
• Fatigue
• Hypotension
• QT interval prolongation
• Neutropenia
• Urticaria
• Sleep disorders
• Nausea
• Vomiting

Interactions

• Other 5-HT3 receptor antagonists
• Neurokinin-1 receptor antagonists
• Drugs that prolong QT interval

Precautions

• Caution in patients with a history of constipation
• Caution in patients with electrolyte disturbances
• Use with caution in elderly patients over 75 years
• Monitor for signs of serotonin syndrome when used with other serotonergic drugs

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential toxicity.

Breast-feeding

Caution is advised, as it is not known if palonosetron is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Palonosetron 250 micrograms/5ml solution for injection
• Palonosetron 50 micrograms per ml oral solution
• Palonosetron 0.5 mg orodispersible film

Mechanism of action

Palonosetron is a selective serotonin 5-HT₃ receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT₃ receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT₃ receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT₃ receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.

Pharmacodynamics

Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT₃ receptor antagonist that is pharmacologically related to other 5-HT₃ receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT₃ receptors, but has little to no affinity for other receptors. The serontonin 5-HT₃ receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.