Netupitant + Palonosetron


Concise Prescribing Info
Indications/Uses
Prophylaxis of chemotherapy-induced nausea and vomiting.
Dosage/Direction for Use
Adult : PO Each cap contains netupitant 300 mg and palonosetron 0.5 mg: 1 cap approx 1 hour prior to initiation of each chemotherapy cycle.
Dosage Details
Oral
Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Available preparation:
Netupitant 300 mg and palonosetron 0.5 mg
1 cap approx 1 hour prior to initiation of each chemotherapy cycle.
Renal Impairment
Severe or ESRD: Contraindicated.
Hepatic Impairment
Severe (Child-Pugh score >9): Contraindicated.
Contraindications
Severe hepatic and renal (including ESRD) impairment. Pregnancy and lactation.
Special Precautions
Patient with history of constipation or signs of subacute intestinal obstruction; history of QT prolongation, CHF, bradyarrhythmia, electrolyte abnormalities, and conduction disturbance.
Adverse Reactions
Significant: Hypersensitivity (including anaphylaxis), constipation with faecal impaction.
Blood and lymphatic system disorders: Neutropenia, leucocytosis.
Cardiac disorders: Cardiomyopathy, bundle branch block, atrio-ventricular block, conduction disorder.
Gastrointestinal disorders: Dyspepsia, abdominal distension, abdominal pain, flatulence, nausea, hiccups, diarrhoea.
General disorders and administration site conditions: Fatigue, asthenia.
Investigations: Increased hepatic transaminases, blood alkaline phosphatase, creatine phosphokinase, and creatinine; prolonged QT interval, abnormal ST-T segment.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Weakness.
Nervous system disorders: Headache, dizziness, vertigo.
Psychiatric disorders: Somnolence, insomnia.
Skin and subcutaneous tissue disorders: Erythema, alopecia, urticaria.
Vascular disorders: Hypertension.
Potentially Fatal: Serotonin syndrome.
Patient Counseling Information
This drug may cause fatigue, dizziness, and somnolence, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor for signs of serotonin syndrome (e.g. mental status and neuromuscular changes, autonomic instability, gastrointestinal symptoms). Obtain liver and renal function. Perform pregnancy test on all pre-menopausal women prior to treatment.
Drug Interactions
Increased risk of serotonin syndrome with SSRIs and SNRIs.
Netupitant: Plasma concentration is increased by CYP3A4 inhibitors (e.g. ketoconazole) and decreased by CYP3A4 inducers (e.g. rifampicin). Increases exposure to dexamethasone, etoposide, docetaxel, midazolam, erythromycin.
Action
Description: Netupitant is a selective human substance P/neurokinin (NK1) receptor antagonist which increases the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids, thereby inhibiting acute and delayed emesis associated with chemotherapy.
Palonosetron is a selective 5-HT3 receptor antagonist which blocks serotonin on peripheral vagal nerve terminals in the periphery and centrally in the chemoreceptor trigger zone.
Pharmacokinetics:
Absorption: Netupitant: Time to peak plasma concentration: Approx 5 hours.
Palonosetron: Well absorbed. Absolute bioavailability: Approx 97%.
Distribution: Netupitant: Volume of distribution: 1,982 ± 906 L. Plasma protein binding: >99.5% (netupitant); >97% (major metabolites).
Palonosetron: Volume of distribution: 8.3 ± 2.5 L/kg. Plasma protein binding: Approx 62%.
Metabolism: Netupitant: Extensively metabolised in the liver mainly by CYP3A4, and to a lesser extent by CYP2C9 and CYP2D6, to form active metabolites M1, M2, and M3.
Palonosetron: Metabolised by CYP2D6, CYP3A4, and CYP1A2 to form inactive metabolites N-oxide-palonosetron and 6-S-hydroxy-palonosetron.
Excretion: Netupitant: Mainly via faeces (approx 71%); urine (approx 4%). Elimination half-life: 80 ± 29 hours.
Palonosetron: Mainly via urine (85-93%, 40% as unchanged drug); faeces (5-8%). Elimination half-life: 48 ± 19 hours.
Chemical Structure

Chemical Structure Image
Netupitant

Source: National Center for Biotechnology Information. PubChem Database. Netupitant, CID=6451149, https://pubchem.ncbi.nlm.nih.gov/compound/Netupitant (accessed on Jan. 22, 2020)


Chemical Structure Image
Palonosetron

Source: National Center for Biotechnology Information. PubChem Database. Palonosetron, CID=6337614, https://pubchem.ncbi.nlm.nih.gov/compound/Palonosetron (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C.
MIMS Class
ATC Classification
A04AA55 - palonosetron, combinations ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.
References
Akynzeo Capsule (Eisai Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 30/01/2018.

Anon. Netupitant and Palonosetron. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/01/2018.

Buckingham R (ed). Netupitant. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/01/2018.

Buckingham R (ed). Palonosetron Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/01/2018.

Joint Formulary Committee. Palonosetron with Netupitant. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/01/2018.

Disclaimer: This information is independently developed by MIMS based on Netupitant + Palonosetron from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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