Neratinib is a kinase inhibitor indicated for the following uses:

• As monotherapy, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer following completion of adjuvant trastuzumab-based therapy.
• In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have previously received two or more anti-HER2-based treatment regimens in the metastatic setting.

Neratinib is an irreversible tyrosine kinase inhibitor that targets EGFR (HER1), HER2, and HER4 receptors. It belongs to the 4-anilinoquinoline class of protein kinase inhibitors and works by blocking intracellular signaling pathways responsible for tumor cell growth and survival.

Premedication for diarrhea: When not using dose escalation, initiate loperamide with the first dose of Neratinib and continue during the first 56 days of treatment. After day 56, use loperamide to maintain 1–2 bowel movements per day.

Extended adjuvant treatment of early-stage breast cancer: 240 mg (6 tablets) given orally once daily, with food, continuously until disease recurrence for up to one year.

Advanced or metastatic breast cancer: 240 mg (6 tablets) given orally once daily with food on Days 1–21 of a 21-day cycle plus capecitabine (750 mg/m² given orally twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities.

Dose escalation: A two-week dose escalation for Neratinib may also be initiated.

Hepatic impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment.

Dose Modifications

• Recommended starting dose: 240 mg daily
• First dose reduction: 200 mg daily
• Second dose reduction: 160 mg daily
• Third dose reduction: 120 mg daily

Gastric acid reducing agents: Avoid using Neratinib together with proton pump inhibitors. Neratinib should be taken at least 2 hours before or 10 hours after H2-receptor antagonists, or at least 3 hours after taking antacids.

Strong CYP3A4 inhibitors: Concomitant use should be avoided.

P-gp and moderate CYP3A4 dual inhibitors: Concomitant use should be avoided.

Strong or moderate CYP3A4 inducers: Concomitant use should be avoided.

Certain P-gp substrates: Monitor for adverse reactions when used together, especially where small concentration changes may cause serious side effects.

Neratinib is contraindicated in patients with known hypersensitivity to Neratinib or any component of this product.

The most common side effects include

• diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, increased liver enzymes, nail disorders, dry skin, abdominal bloating, nose bleeding, weight loss, and urinary tract infection.
• When used with capecitabine, additional side effects may include constipation, dizziness, back pain, joint pain, upper respiratory tract infection, renal impairment, and weakness.

Neratinib can cause fetal harm when used during pregnancy. Pregnant women should be informed about the possible risk to the fetus. It is not known whether Neratinib passes into human milk. Both males and females of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose.

Diarrhea: Diarrhea should be managed with dose escalation or loperamide prophylaxis. If severe diarrhea occurs, additional antidiarrheal treatment, fluids, and electrolytes may be needed. Neratinib should be withheld in severe or persistent cases and permanently discontinued in Grade 4 diarrhea or persistent Grade ≥2 diarrhea after maximum dose reduction.

Hepatotoxicity: Neratinib should be withheld in Grade 3 liver abnormalities and permanently discontinued in Grade 4 liver abnormalities.

Embryo-Fetal Toxicity: Neratinib may cause fetal harm. Patients should be advised to use effective contraception and be informed about fetal risk.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Older patients may have a slightly higher incidence of serious adverse reactions compared to younger adults.

Hepatic Impairment: No dose adjustment is needed in mild to moderate hepatic impairment, but dose reduction is required in severe hepatic impairment.

In case of overdose, treatment should be stopped and general supportive care should be provided.

Tyrosine Kinase Inhibitor

Do not store above 30°C. Keep away from light and out of the reach of children.