Nerlynx Neratinib Maleate Tablets

1. Indications and Usage
Extended Adjuvant Treatment of HER2-Positive Early Breast Cancer:
Indicated for the extended adjuvant treatment of adult patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, following adjuvant trastuzumab-based therapy.
Treatment of HER2-Positive Metastatic Breast Cancer:
Indicated for the treatment of adult patients with HER2-positive metastatic breast cancer who have received two or more prior anti-HER2 based regimens.
2. Dosage and Administration
Recommended Dosage:
Standard Dose: 240 mg (6 tablets of 40 mg) administered orally once daily, continuously for 1 year.
Administration: Swallow tablets whole. Take with food.
Prophylaxis for Diarrhea:
Prophylaxis with loperamide must be initiated concomitantly with neratinib and continued for the first 56 days to manage diarrhea.
Schedule:
Days 1–14: Loperamide 4 mg, 3 times daily.
Days 15–56: Loperamide 4 mg, 2 times daily.
Week 9 onwards: Loperamide 4 mg as needed to maintain 1–2 bowel movements per day.
Dose Modifications:
If diarrhea occurs, interrupt neratinib until resolved to ≤ Grade 1, then resume at the same or reduced dose (200 mg, 160 mg, or 120 mg).
3. Mechanism of Action
Irreversible Kinase Inhibitor:
Neratinib is an irreversible tyrosine kinase inhibitor of HER2 (ErbB2), EGFR (ErbB1), and HER4 (ErbB4).
Physiological Effect:
It binds covalently to the cysteine residue in the ATP-binding pocket of the receptor, inhibiting autophosphorylation and downstream signaling pathways (such as PI3K/Akt and MAPK), thereby inducing tumor cell apoptosis.
4. Safety and Warnings
Diarrhea:
Severe diarrhea is a common and potentially serious adverse reaction. Prophylactic loperamide is mandatory. Monitor for signs of dehydration and renal failure.
Hepatotoxicity:
Monitor ALT and AST levels prior to initiation and periodically during treatment. Dose interruptions or reductions may be necessary for elevated transaminases.
Embryo-Fetal Toxicity:
Can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the final dose.
5. Adverse Reactions
Most Common:
Diarrhea, nausea, fatigue, vomiting, abdominal pain, increased ALT/AST, rash, decreased appetite, musculoskeletal pain, and dry skin.
6. Drug Interactions
Acid-Reducing Agents:
Proton Pump Inhibitors (PPIs): Avoid co-administration.
H2-Receptor Antagonists: Administer neratinib at least 2 hours before or 10 hours after the H2-antagonist.
Antacids: Administer neratinib at least 3 hours after the antacid.
CYP3A Inhibitors:
Avoid co-administration with strong CYP3A inhibitors (e.g., ketoconazole) as they may increase neratinib exposure.
7. Pharmaceutical Information
Storage:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep in the original package to protect from moisture.