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.
Severe (Child-Pugh class C): Initially, 80 mg once daily.
Film-Coated Tab: Should be taken with food. Preferably taken in the morning. Swallow whole, do not chew/crush.
Severe hepatic impairment (Child-Pugh class C). Lactation. Concomitant use with strong CYP3A4/P-glycoprotein (P-gp) inducers and PPIs.
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.
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.
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.
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).
Increased absorption with food. Decreased exposure with St. John’s wort; avoid concomitant use. Increased exposure with grapefruit or pomegranate juice.
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.
Store between 20-25°C. Protect from moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01EH02 - neratinib ; Belongs to the class of human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors. Used in the treatment of cancer.
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