Neratinib

What it is and how it works

Mechanism of Action Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro , neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2, and HER4 in vitro. In vivo , oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.

Indications

is a kinase inhibitor indicated: As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. Extended Adjuvant Treatment of Early-Stage Breast Cancer NERLYNX as a single agent is indicated for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer, to follow adjuvant trastuzumab based therapy . Advanced or Metastatic Breast Cancer NERLYNX in combination with capecitabine is indicated for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting .

Dosage and administration (summary)

Premedication for diarrhea: When not using dose escalation, initiate loperamide with the first dose of NERLYNX and continue during the first 56 days of treatment. After day 56, use loperamide to maintain 1–2 bowel movements per day. ( 2.1 , 2.2 ) Extended adjuvant treatment of early-stage breast cancer: 240 mg (6 tablets) given orally once daily, with food, continuously until disease recurrence or 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/m 2 given orally twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities.

Contraindications

None. None.

Warnings and precautions

Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis ( 2.1 , 2.2 ). If diarrhea occurs despite recommended prophylaxis, treat with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥2 diarrhea that occurs after maximal dose reduction.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, NERLYNX can cause fetal harm when administered to a pregnant woman . There are no available data in pregnant women to inform the drug-associated risk.

Storage and supply

40 mg film-coated tablets are red, oval shaped and debossed with 'W104' on one side and plain on the other side. NERLYNX is available in: Bottles of 180 tablets: NDC 70437-240-18 Bottles of 133 tablets: NDC 70437-240-33 Bottles of 126 tablets: NDC 70437-240-26 Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).

Source: Neratinib (Nerlynx) — US FDA prescribing information, 2026-07-02, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.