Neratinib


Generic Medicine Info
Indications and Dosage
Oral
Adjuvant treatment of HER2-positive early carcinoma of breast
Adult: As extended adjuvant treatment in patients who completed adjuvant trastuzumab-based therapy: 240 mg once daily, given continuously until disease recurrence or for up to 1 year. Antidiarrheal prophylaxis is recommended during the first 56 days of therapy; initiate with the 1st neratinib dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Oral
HER2-positive advanced carcinoma of breast, HER2-positive metastatic carcinoma of breast
Adult: In patients who have received ≥2 prior anti-HER2 based regimens in the metastatic setting: 240 mg once daily on days 1-21 of a 21-day cycle; given with capecitabine on days 1-14 of a 21-day cycle, until disease progression or unacceptable toxicity. Antidiarrheal prophylaxis is recommended during the first 56 days of therapy; initiate with the 1st neratinib dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking concomitant strong CYP3A4/P-gp inhibitors: Reduce dose to 40 mg once daily.
Patients taking concomitant moderate CYP3A4/P-gp inhibitors: Reduce dose to 40 mg once daily; if well tolerated, increase to 80 mg for at least 1 week, then to 120 mg for at least 1 week, and to 160 mg as Max daily dose.
Hepatic Impairment
Severe (Child-Pugh class C): Initially, 80 mg once daily.
Administration
Film-Coated Tab: Should be taken with food. Preferably taken in the morning. Swallow whole, do not chew/crush.
Contraindications
Severe hepatic impairment (Child-Pugh class C). Lactation. Concomitant use with strong CYP3A4/P-glycoprotein (P-gp) inducers and PPIs.
Special Precautions
Patient with a significant chronic gastrointestinal disorder with diarrhoea as a major symptom, known cardiac risk factors, symptomatic skin and subcutaneous tissue disorders. Renal impairment. Pregnancy. Patients taking strong or moderate CYP3A4/P-gp inhibitors and moderate CYP3A4/P-gp inducers.
Adverse Reactions
Significant: Severe diarrhoea which may result in dehydration, hypotension, and renal failure; left ventricular dysfunction.
Gastrointestinal disorders: Abdominal pain or distension, nausea, vomiting, stomatitis, dry mouth, dyspepsia.
General disorders and administration site conditions: Fatigue.
Investigations: Increased blood creatinine, decreased weight.
Metabolism and nutrition disorders: Decreased appetite, dehydration.
Musculoskeletal and connective tissue disorders: Muscle spasm.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Epistaxis.
Skin and subcutaneous tissue disorders: Rash, dry skin, nail disorders (e.g. discolouration, onychoclasis), skin fissures.
Patient Counseling Information
This drug may cause fatigue, dizziness, dehydration and syncope, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate pregnancy status and hepatitis B virus screening prior to initiation of therapy. Monitor liver (e.g. AST/ALT, bilirubin) and cardiac function (e.g. LVEF) as clinically indicated; occurrence of diarrhoea, and signs/symptoms of dehydration.
Overdosage
Symptoms: Diarrhoea, nausea, vomiting, dehydration. Management: Supportive treatment.
Drug Interactions
Increased plasma concentrations and exposure with strong or moderate CYP3A4/P-gp inhibitors (e.g. strong inhibitors: atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, lopinavir, ketoconazole, itraconazole, clarithromycin, troleandomycin, voriconazole, cobicistat; moderate inhibitors: ciprofloxacin, ciclosporin, diltiazem, fluconazole, erythromycin, fluvoxamine, verapamil). Decreased plasma concentrations and exposure with moderate CYP3A4/P-gp inducers (e.g. bosentan, efavirenz, etravirine, phenobarbital, primidone, dexamethasone). Reduced absorption with antacids and H2-receptor antagonists. May increase the plasma concentrations of P-gp substrates (e.g. digoxin, dabigatran).
Potentially Fatal: Decreased plasma concentrations and exposure with strong CYP3A4/P-gp inducers (e.g. carbamazepine, phenytoin, rifampicin) and PPIs (e.g. omeprazole, lansoprazole).
Food Interaction
Increased absorption with food. Decreased exposure with St. John’s wort; avoid concomitant use. Increased exposure with grapefruit or pomegranate juice.
Action
Description: Neratinib is a selective and irreversible tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2), HER4 and epidermal growth factor receptor (EGFR). It reduces the autophosphorylation of HER2 and EGFR, resulting in inhibition of downstream signalling of the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K/Akt) pathways, and tumour cell proliferation in vitro.
Pharmacokinetics:
Absorption: Slowly absorbed. Increased absorption with food. Time to peak plasma concentration: 2-8 hours.
Distribution: Plasma protein binding: >99%, to serum albumin and α1-acid glycoprotein.
Metabolism: Metabolised in the liver primarily by CYP3A4, and to a lesser extent by flavin-containing monooxygenase (FMO) to active metabolites M3, M6, M7 and M11.
Excretion: Mainly via faeces (approx 97%); urine (approx 1%). Elimination half-life: 7-17 hours.
Chemical Structure

Chemical Structure Image
Neratinib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9915743, Neratinib. https://pubchem.ncbi.nlm.nih.gov/compound/Neratinib. Accessed Apr. 28, 2021.

Storage
Store between 20-25°C. Protect from moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01EH02 - neratinib ; Belongs to the class of human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors. Used in the treatment of cancer.
References
Anon. Neratinib Maleate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 10/02/2021.

Anon. Neratinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/02/2021.

Buckingham R (ed). Neratinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/02/2021.

Joint Formulary Committee. Neratinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/02/2021.

Nerlynx 40 mg Film-Coated Tablets (Pierre Fabre Médicament Production - Cahors). European Medicines Agency [online]. Accessed 10/02/2021.

Nerlynx Tablet (Puma Biotechnology, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/02/2021.

Specialised Therapeutics Limited. Nerlynx Tablets data sheet 26 June 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 10/02/2021.

Disclaimer: This information is independently developed by MIMS based on Neratinib 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 © 2021 MIMS. All rights reserved. Powered by MIMS.com
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