Drug Detail:Nerlynx (Neratinib [ ne-ra-ti-nib ])
Generic Name: NERATINIB MALEATE 40mg
Dosage Form: tablet
Drug Class: EGFR inhibitors HER2 inhibitors
Premedication for Diarrhea
When not using dose escalation [see Dosage and Administration ( 2.2)], administer antidiarrheal prophylaxis during the first 56 days of treatment and initiate with the first dose of NERLYNX [see Warnings and Precautions (5.1) and Adverse Reactions ( 6.1)] .
Instruct patients to take loperamide as directed in Table 1. Titrate loperamide to 1–2 bowel movements per day.
| Time on NERLYNX | Loperamide Dose and Frequency |
|---|---|
| Weeks 1–2 (days 1–14) | 4 mg three times daily |
| Weeks 3–8 (days 15–56) | 4 mg twice daily |
| Weeks 9–Discontinuation of NERLYNX | 4 mg as needed, not to exceed 16 mg per day; titrate dosing to achieve 1–2 bowel movements per day |
If diarrhea occurs despite prophylaxis, treat with additional antidiarrheals, fluids and electrolytes as clinically indicated. NERLYNX dose interruptions and dose reductions may also be required to manage diarrhea [see Dosage and Administration ( 2.3)] .
Recommended Dose and Schedule
Extended Adjuvant Treatment of Early-Stage Breast Cancer
The recommended dose of NERLYNX is 240 mg (six tablets) given orally once daily, with food, continuously until disease recurrence or for up to one year.
Advanced or Metastatic Breast Cancer
The recommended dose of NERLYNX is 240 mg (six 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.
Dose Escalation
A two-week dose escalation for NERLYNX may be considered instead of starting at the 240 mg daily dose for patients with early-stage breast cancer and metastatic breast cancer, as described in Table 2 [see Warnings and Precautions (5.1) and Adverse Reactions ( 6.1)] .
| Time on NERLYNX | NERLYNX Dose |
|---|---|
| Week 1 (days 1–7) | 120 mg daily (three 40 mg tablets) |
| Week 2 (days 8–14) | 160 mg daily (four 40 mg tablets) |
| Week 3 and onwards | 240 mg daily (six 40 mg tablets, recommended dose) |
If diarrhea occurs, treat with antidiarrheal medications, fluids, and electrolytes as clinically indicated. NERLYNX dose interruptions and dose reductions may also be required to manage diarrhea [see Dosage and Administration ( 2.3)] .
Administration Instructions
Instruct patients to take NERLYNX at approximately the same time every day. NERLYNX tablets should be swallowed whole (tablets should not be chewed, crushed, or split prior to swallowing).
If a patient misses a dose, do not replace missed dose, and instruct the patient to resume NERLYNX with the next scheduled daily dose.
Dosage Modifications for Adverse Reactions
NERLYNX dose modification is recommended based on individual safety and tolerability. Management of some adverse reactions may require dose interruption and/or dose reduction as shown in Table 3 to Table 6.
Discontinue NERLYNX for patients with adverse reactions that fail to recover to Grade 0–1 or baseline, with toxicities that result in a treatment delay >3 weeks, or if unable to tolerate 120 mg daily. Additional clinical situations may result in dose adjustments as clinically indicated (e.g., intolerable toxicities, persistent Grade 2 adverse reactions, etc.).
When NERLYNX is used in combination with capecitabine, refer to the capecitabine prescribing information for dose modifications of capecitabine.
| Dose Level | NERLYNX Dose |
|---|---|
| Recommended starting dose | 240 mg daily (six 40 mg tablets) |
| First dose reduction | 200 mg daily (five 40 mg tablets) |
| Second dose reduction | 160 mg daily (four 40 mg tablets) |
| Third dose reduction | 120 mg daily (three 40 mg tablets) |
| Adverse Reaction | Severity† | Action/Dose Modification |
|---|---|---|
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ALT=Alanine Aminotransferase; AST=Aspartate Aminotransferase; ULN=Upper Limit Normal |
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† Per CTCAE v4.0 |
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* Complicated features include dehydration, fever, hypotension, renal failure, or Grade 3 or 4 neutropenia. |
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‡ Despite being treated with optimal medical therapy |
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| Diarrhea [see Warnings and Precautions ( 5.1)] |
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| Hepatotoxicity [see Warnings and Precautions ( 5.2)] |
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| Other [see Adverse Reactions ( 6.1)] |
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| Dose Level | NERLYNX Dose |
|---|---|
| Recommended starting dose | 240 mg daily (six 40 mg tablets) |
| First dose reduction | 160 mg daily (four 40 mg tablets) |
| Second dose reduction | 120 mg daily (three 40 mg tablets) |
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ALT=Alanine Aminotransferase; AST=Aspartate Aminotransferase; ULN=Upper Limit Normal |
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† Per CTCAE v4.0 |
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a Since capecitabine is provided as 150 mg or 500 mg tablets, it is recommended that the capecitabine dose reduction(s) is(are) rounded down to the nearest 500 mg or multiple of 150 mg for the twice daily dose. If the patient's body surface area is >2.0, the standard of care for the study center can be utilized for capecitabine mg/m 2 dosing. |
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| Adverse Reaction | Severity† | Action/Dose Modification |
| Diarrhea [see Warnings and Precautions ( 5.1)] |
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| Hepatotoxicity [see Warnings and Precautions ( 5.2)] |
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| Other [see Adverse Reactions ( 6.1)] |
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Dosage Modifications for Hepatic Impairment
Reduce the NERLYNX starting dose to 80 mg in patients with severe hepatic impairment (Child Pugh C). No dose modifications are recommended for patients with mild to moderate hepatic impairment (Child Pugh A or B) [see Use in Specific Populations ( 8.6) and Clinical Pharmacology ( 12.3)] .
Dosage Modifications for Gastric Acid Reducing Agents
Proton pump inhibitors (PPI): Avoid concomitant use with NERLYNX [see Drug Interactions ( 7.1)] .
H2-receptor antagonists: Take NERLYNX at least 2 hours before the next dose of the H 2-receptor antagonist or 10 hours after the H 2-receptor antagonist [see Drug Interactions ( 7.1)] .
Antacids: Separate dosing of NERLYNX by 3 hours after antacids [see Drug Interactions ( 7.1)] .
