Palonosetron

Palonosetron Hydrochloride Injection is a serotonin-3 (5-HT 3 ) receptor antagonist indicated in adults for: Moderately emetogenic cancer chemotherapy - prevention of acute and delayed nausea and vomiting associated with initial and repeat courses ( 1.1) Highly emetogenic cancer chemotherapy - prevention of acute nausea and vomiting associated with initial and repeat courses. Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated. Palonosetron Hydrochloride Injection is indicated in pediatric patients aged 1 month to less than 17 years for: Prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy

Palonosetron is a 5-HT 3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT 3 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 thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT 3 receptors located on vagal afferents to initiate the vomiting reflex.

Chemotherapy-Induced Nausea and Vomiting *Note different dosing units in pediatrics Age Dose* Infusion Time Adults 0. 2 5 mg x 1 Infuse over 30 seconds beginning approx. 30 min before the start of chemo Pediatrics (1 month to less than 17 years) 2 0 micrograms per k ilogram (max 1.5 mg) x 1 Infuse over 15 minutes beginning approx. 30 min before the start of chemo Postoperative Nausea and Vomiting. Adult Dosage: a single 0.075 mg intravenous dose administered over 10 seconds immediately before the induction of anesthesia.

Palonosetron Hydrochloride Injection is contraindicated in patients known to have hypersensitivity to the drug or any of its components.

Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other selective 5-HT 3 receptor antagonists. Serotonin syndrome has been reported with 5-HT 3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions in chemotherapy-induced nausea and vomiting in adults (incidence ≥5%) are headache and constipation. The most common adverse reactions in postoperative nausea and vomiting (incidence ≥ 2%) are QT prolongation, bradycardia, headache, and constipation.

Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low. Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs).

Storage Store at controlled temperature of 20–25°C (68°F–77°F). Excursions permitted to 15–30°C (59-86°F). Protect from freezing. Protect from light.