Palonosetron
Clinical data | |
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Pronunciation | /pæləˈnoʊsətrɒn/ pal-ə-NOH-sə-tron |
Trade names | Aloxi |
AHFS/Drugs.com | Monograph |
MedlinePlus | a610002 |
License data |
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Pregnancy category |
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Routes of administration | Intravenous, by mouth |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 97% (oral) |
Protein binding | 62% |
Metabolism | Liver, 50% (mostly CYP2D6-mediated, CYP3A4 and CYP1A2 also involved) |
Elimination half-life | Approximately 40–50 hours |
Excretion | Kidney, 80% (of which 49% unchanged); fecal (5 to 8%) |
Identifiers | |
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JSmol) | |
Specific rotation | [α]D −136° [α]D –94.1° (HCl) |
Melting point | 87 to 88 °C (189 to 190 °F) |
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Palonosetron, sold under the brand name Aloxi, is a medication used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV).[2][4][5] It is a 5-HT3 antagonist.[2][4][5]
Palonosetron is administered intravenously,[6] or as a single oral capsule.[7] It has a longer duration of action than other 5-HT3 antagonists. The oral formulation was approved on August 22, 2008, for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV.[7] It is on the World Health Organization's List of Essential Medicines.[8]
The oral combination netupitant/palonosetron is approved for both acute and delayed CINV.[9][10][11][12]
Adverse effects
The most common adverse effects are headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other
Interactions
Palonosetron does not relevantly inhibit or induce cytochrome P450 liver enzymes. There are case reports about serotonin syndrome when the drug is combined with serotonergic substances such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), two common types of antidepressants.[13][14]
Pharmacology
Mechanism of action
Palonosetron is a 5-HT3 antagonist, commonly known as a setron. These drugs act by blocking serotonin from binding to the 5-HT3 receptor.[15]
Pharmacokinetics
Orally taken palonosetron is absorbed well from the gut and has a
Palonosetron and its metabolites are mainly (to 80–93%) eliminated via the kidney. Biological half-life in healthy persons was 37±12 hours in a study, and 48±19 hours in cancer patients. In 10% of patients, half-life is over 100 hours.[13][14] Most other marketed setrons have half-lives in the range of about two to 15 hours.
Chemistry
The substance is solid at room temperature and melts at 87 to 88 °C (189 to 190 °F).[16] The infusions and capsules contain palonosetron hydrochloride,[13] which is also a solid. The hydrochloride is easily soluble in water, soluble in propylene glycol, and slightly soluble in ethanol and isopropyl alcohol.[14][17]
The molecule has two
Society and culture
Economics
Palonosetron was developed by Helsinn around 2001. In January 2003, Helsinn filed a provisional patent application on palonosetron. Over the next 10 years, Helsinn filed four patent applications that claimed priority to the January 2003 date. Relevant here, Helsinn filed its fourth patent application in 2013. That patent (the ’219 patent) covers a fixed dose of 0.25 mg of palonosetron in a 5 ml solution. While developing the drug, Helsinn entered into a confidential licensing agreement with a company called MGI to sell palonosetron in the United States. This licensing agreement contained chemical information about palonosetron and dosage requirements. However, Helsinn did not file for a patent on palonosetron until two years after they had signed their agreement with MGI. [1]
In 2011
The District Court held that the AIA's “on sale” provision did not apply, because the public disclosure of the agreements did not disclose the 0.25 mg dose. The Federal Circuit reversed, holding that the sale was publicly disclosed, regardless of whether the details of the invention were publicly disclosed in the terms of the sale agreements. The
References
- ^ a b https://www.tga.gov.au/resources/auspar/auspar-palonosetron-hydrochloride
- ^ a b c "Aloxi 250 micrograms solution for injection - Summary of Product Characteristics (SmPC)". (emc). 18 May 2018. Archived from the original on 24 January 2022. Retrieved 23 January 2022.
- ^ "Aloxi 500 micrograms soft capsules - Summary of Product Characteristics (SmPC)". (emc). 18 May 2018. Archived from the original on 24 January 2022. Retrieved 24 January 2022.
- ^ a b c "Aloxi- palonosetron hydrochloride injection". DailyMed. Archived from the original on 24 January 2022. Retrieved 23 January 2022.
- ^ a b c "Aloxi EPAR". European Medicines Agency. Archived from the original on 14 April 2021. Retrieved 23 January 2022.
- PMID 17106506.
- ^ a b Waknine Y (September 4, 2008). "FDA Approvals: Nplate, Aloxi, Vidaza". Medscape. Archived from the original on 2008-12-02. Retrieved 2008-09-04. Freely available with registration.
- hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- ^ "Akynzeo EPAR". European Medicines Agency. Archived from the original on 19 March 2020. Retrieved 23 January 2022.
- ^ a b "Akynzeo: Summary of Product Characteristics" (PDF). European Medicines Agency. Archived (PDF) from the original on 26 June 2016. Retrieved 12 July 2016.
- ^ "Akynzeo 300 mg/0.5 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 11 February 2020. Archived from the original on 24 January 2022. Retrieved 23 January 2022.
- ^ "Akynzeo- netupitant and palonosetron capsule Akynzeo- fosnetupitant and palonosetron injection". DailyMed. Archived from the original on 18 October 2020. Retrieved 24 January 2022.
- ^ a b c d e Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- ^ ISBN 978-3-7741-9846-3.
- )
- ISBN 978-0-911910-00-1.
- ^ a b "Chemistry Revire – Aloxi (Palonosetron HCl) Capsules, 0.5 mg" (PDF). Center for Drug Evaluation and Research. 13 August 2008. Archived (PDF) from the original on 5 August 2019. Retrieved 13 July 2016.