Instructions for Neratinib

1. Generic name: Neratinib

Product name: Nerlynx

All names: Neratinib, Neratinib, Helian, Neratinib, Neratinib Maleate Tablets, Neratinib Maleate

2. Indications:

1. Extended adjuvant treatment for early breast cancer:

Neratinib is indicated as a single agent for the long-term adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer who are receiving adjuvant trastuzumab-based therapy.

2. Advanced or metastatic breast cancer:

Neratinib 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 anti-HER2-based treatment regimens in the metastatic setting.

3. Usage and dosage:

1. Before use: It is recommended that patients take antidiarrheal prophylaxis during the first two cycles (56 days ) of neratinib treatment, and should start from the first dose. Titrate loperamide to 1 to 2 bowel movements per day. In weeks 1-2 (days 1-14), take 4 mg three times a day; in weeks 3-8 (days 15-56), take 4 mg twice a day; in weeks 9-52 (days 57-365), take 4 mg as needed (no more than 16 mg per day).

2. Recommended dosage:

(1) Extended adjuvant treatment of early breast cancer: The recommended dose of neratinib is 240 mg (6 tablets), taken orally once a day with food, until the disease recurs or for up to one year.

(2) Advanced or metastatic breast cancer: The recommended dose of neratinib is 240 mg (6 tablets), taken orally once a day with food on days 1 to 21 of a 21-day cycle, plus carbs Petabine (750 mg/m2 orally twice daily) on days 1-14 of a 21-day cycle until disease progression or unacceptable toxicity.

(3) Dose escalation: For patients with early-stage breast cancer and metastatic breast cancer, consideration may be given to increasing the dose of neratinib by two weeks instead of starting at a dose of 240 mg per day. The dose in week 1 (days 1-7) is 120 mg per day (three 40 mg tablets); the dose in week 2 (days 8-14) is 160 mg per day (four 40 mg tablets); the dose in week 3 and beyond is 240 mg per day (six 40 mg tablets).

3. Dose adjustment: If patients experience adverse reactions when using neratinib, such as the adverse reactions fail to return to grade 0-1 or baseline levels, toxicity causes treatment delay for >3 weeks, or patients who cannot tolerate 120 mg daily should discontinue neratinib. Other clinical conditions may result in dosage adjustments as clinically indicated.

(1)Neratinibmonotherapy dose adjustment: the first dose was reduced to 200mg daily; the second dose was reduced to daily160mg; the third dose was reduced to daily120mg.

(2)Neratinib combined with capecitabine treatment Dose adjustment: the first dose is reduced to 160 mg daily; the second dose is reduced to 120 mg daily.

(3) Hepatic impairment: For patients with severe hepatic impairment (Child Pugh C), reduce the starting dose of neratinib to 80 mg; for patients with mild to moderate hepatic impairment (Child Pugh A or B), no dose adjustment is recommended

(4) Gastric acid reducers: Avoid proton pump inhibitors (PPI) concurrent use with neratinib ; at least under Take a dose of neratinib 2 hours before or 10 hours after an H2 receptor antagonist; give neratinib alone 3 hours after an antacid.

4. Adverse reactions:

In clinical studies of extended adjuvant treatment of early breast cancer, the most common adverse reactions of neratinib (≥5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle cramps, indigestion, elevated AST or ALT, nail abnormalities, dry skin, abdominal distension, nose bleeding, weight loss, and urinary tract infection. In advanced or metastatic breast cancerIn clinical studies, the most common adverse reactions in the plus capecitabine group were diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight loss, dizziness, back pain, joint pain, urinary tract infection, upper respiratory tract infection, abdominal distension, renal damage and muscle spasm.

5. Storage:

Neratinib is stored at controlled room temperature,20°C to 25°C (68°F to 77°F); tolerance is 15°C to 30°C (59°F to 86°F).

6. Special groups:

1. Women: Based on the findings and mechanism of action of animal studies, neratinib can cause fetal damage when administered to pregnant women. Therefore, it is recommended that women of reproductive potential use effective contraception during treatment with neratinib and for at least 1 month after the last dose; lactating women should not breastfeed while taking neratinib and for at least 1 month after the last dose.

2. Men: It is recommended that male patients with female partners of reproductive potential use effective contraceptive measures during treatment and within 3 months after the last dose of neratinib.

7. Mechanism of action:

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

NeratinibThe original drug is marketed in China as neratinib maleate tablets and is covered by Class B medical insurance, but reimbursement is limited to patients who meet the indications. SpecificationsThe price of each box of 40mg*180 tablets may be around 7,000 yuan. Generic drugs of Neratinib are also sold overseas. The ingredients are basically the same as those of the original drug. The price of 40mg*180 tablets produced by a Bangladeshi pharmaceutical factory may be around 4,000 yuan per box (the price may fluctuate due to exchange rates).