Product Information
Registration Status: ActiveALOXI SOFT CAPSULE 500 mcg is approved to be sold in Singapore with effective from 2017-07-07. It is marketed by MUNDIPHARMA PHARMACEUTICALS PTE LTD, with the registration number of SIN15293P.
This product contains Palonosetron 0.50mg in the form of CAPSULE, LIQUID FILLED. It is approved for ORAL use.
This product is manufactured by Catalent Pharma Solutions Inc in UNITED STATES, andHelsinn Birex Pharmaceuticals Ltd. (Primary and Secondary packager) in IRELAND.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Palonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical use.
Indication
For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, as well as prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy. Also used for the prevention of postoperative nausea and vomiting for up to 24 hours post operation.
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.
Pharmacokinetics
- Absorption
- Low oral bioavailability.
- Distribution
- * 8.3 ± 2.5 L/kg
- Metabolism
- Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved.
- Elimination
Clearance
* 160 +/- 35 mL/h/kg
Toxicity
A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.
Active Ingredient/Synonyms
(3aS)-2-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-2,3,3a, 4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one | (3aS)-2,3,3a,4,5,6-hexahydro-2-[(3S)-3-quinuclidinyl]-1H-benz[de]isoquinolin-1-one | Palonosetron | Palonosétron | Palonosetrón | Palonosetronum | Palonosetron |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.