Product Information
Registration Status: ActiveAKYNZEO CAPSULE 300MG/0.5MG is approved to be sold in Singapore with effective from 2016-06-08. It is marketed by MUNDIPHARMA PHARMACEUTICALS PTE LTD, with the registration number of SIN15031P.
This product contains Netupitant 300mg, and Palonosetron 0.5mg in the form of CAPSULE, GELATIN-COATED. It is approved for ORAL use.
This product is manufactured by Helsinn Birex Pharmaceuticals Ltd. (Intermediate Netupitant Tablets and final drug product) in UNITED STATES, andCATALENT PHARMA SOLUTIONS LLC (Intermediate Palonosetron softgels) 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
Netupitant is an antiemitic drug approved by the FDA in October 2014 for use in combination with palonosetron for the prevention of acute and delayed vomiting and nausea associated with cancer chemotherapy including highly emetogenic chemotherapy. Netupitant is a neurokinin 1 receptor antagonist. The combination drug is marketed by Eisai Inc. and Helsinn Therapeutics (U.S.) Inc. under the brand Akynzeo®.
Indication
Netupitant is an antiemitic drug approved by the FDA in October 2014 for use in combination with palonosetron for the prevention of acute and delayed vomiting and nausea associated with cancer chemotherapy including highly emetogenic chemotherapy.
Mechanism of Action
Delayed emesis (vomiting) has been largely associated with the activation of tachykinin family neurokinin 1 (NK1) receptors (broadly distributed in the central and peripheral nervous systems) by substance P. As shown in in vitro and in vivo studies, netupitant inhibits substance P mediated responses.
Pharmacokinetics
- Absorption
- Upon oral administration of a single dose of netupitant, netupitant started to be measurable in plasma between 15 minutes and 3 hours after dosing. Plasma concentrations reached Cmax in approximately 5 hours. There was a greater than dose-proportional increase in the systemic exposure with the dose increase from 10 mg to 300 mg and a dose-proportional increase in systemic exposure with a dose increase from 300 mg to 450 mg.
- Distribution
- In cancer patients, Vz/F: 1982 ± 906 L (mean ± SD).
- Metabolism
- Once absorbed, netupitant is extensively metabolized to form three major metabolites: desmethyl derivative, M1; N-oxide derivative, M2; and OH-methyl derivative, M3. Metabolism is mediated primarily by CYP3A4 and to a lesser extent by CYP2C9 and CYP2D6. Metabolites M1, M2 and M3 were shown to bind to the substance P/neurokinin 1 (NK1) receptor.
- Elimination
Clearance
estimated systemic clearance of 20.3 ± 9.2 L/h (mean ± SD).
Toxicity
Daily oral administration of netupitant in rats at doses up to 30 mg/kg (1.9 times the human AUC in male rats and 3.7 times the human AUC in female rats at the recommended human dose) had no effects on fertility or reproductive performance.
Active Ingredient/Synonyms
2-[3,5-Bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-3-pyridinyl]propanamide | Netupitant |
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.
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.