Source: FDA, National Drug Code (US) Revision Year: 2024
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 [see Clinical Studies (14.1)].
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 [see Clinical Studies (14.2)].
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.
Table 1. Loperamide Prophylaxis:
| 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)].
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.
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/m² given orally twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities.
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)].
Table 2. NERLYNX Dose Escalation and Treatment Schedule:
| 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)].
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.
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 3to 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.
Table 3. NERLYNX Monotherapy Dose Modifications for Adverse Reactions:
| 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) |
Table 4. Recommended Dosage Modifications for Adverse Reactions with NERLYNX Monotherapy:
| Adverse Reaction | Severity† | Action/Dose Modification |
|---|---|---|
| Diarrhea [see Warnings and Precautions (5.1)] | • Grade 1 diarrhea [increase of <4 stools per day over baseline] • Grade 2 diarrhea [increase of 4–6 stools per day over baseline] lasting ≤5 days • Grade 3 diarrhea [increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; limiting self-care activities of daily living] lasting ≤2 days | • Adjust antidiarrheal treatment • Diet modifications • Fluid intake of ~2 L/day should be maintained to avoid dehydration • Once event resolves to ≤ Grade 1 or baseline, start loperamide 4 mg with each subsequent NERLYNX administration |
| • Any grade with complicated features* • Grade 2 diarrhea lasting longer than 5 days‡ • Grade 3 diarrhea lasting longer than 2 days‡ | • Interrupt NERLYNX treatment • Diet modifications • Fluid intake of ~2 L/day should be maintained to avoid dehydration • If diarrhea resolves to ≤ Grade 1 in one week or less, then resume NERLYNX treatment at the same dose • If diarrhea resolves to ≤ Grade 1 in longer than one week, then resume NERLYNX treatment at reduced dose (see Table 3) • Once event resolves to ≤ Grade 1 or baseline, start loperamide 4 mg with each subsequent NERLYNX administration | |
| • Grade 4 diarrhea [life-threatening consequences; urgent intervention indicated] | • Permanently discontinue NERLYNX treatment | |
| • Diarrhea recurs to Grade 2 or higher at 120 mg per day | • Permanently discontinue NERLYNX treatment | |
| Hepatotoxicity [see Warnings and Precautions (5.2)] | • Grade 3 ALT or AST (>5–20× ULN) OR • Grade 3 bilirubin (>3–10× ULN) | • Hold NERLYNX until recovery to ≤ Grade 1 • Evaluate alternative causes • Resume NERLYNX at the next lower dose level if recovery to ≤ Grade 1 occurs within 3 weeks. If Grade 3 ALT or AST, or bilirubin occurs again despite one dose reduction, permanently discontinue NERLYNX. |
| • Grade 4 ALT or AST (>20× ULN) OR • Grade 4 bilirubin (>10× ULN) | • Permanently discontinue NERLYNX • Evaluate alternative causes | |
| Other [see Adverse Reactions (6.1)] | • Grade 3 | • Hold NERLYNX until recovery to ≤Grade 1 or baseline within 3 weeks of stopping treatment. Then resume NERLYNX at the next lower dose level. |
| • Grade 4 | • Discontinue NERLYNX permanently |
ALT=Alanine Aminotransferase; AST=Aspartate Aminotransferase; ULN=Upper Limit Normal
† Per CTCAE v4.0
* Complicated features include dehydration, fever, hypotension, renal failure, or Grade 3 or 4 neutropenia.
‡ Despite being treated with optimal medical therapy
Table 5. NERLYNX in Combination with Capecitabine Dose Modifications for Adverse Reactions:
| 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) |
Table 6. Recommended Dosage Modifications for Adverse Reactions with NERLYNX in Combination with Capecitabine:
| Adverse Reaction | Severity† | Action/Dose Modification |
|---|---|---|
| Diarrhea [see Warnings and Precautions (5.1)] | • Grade 1 Diarrhea [Increase of <4 stools per day over baseline] • Grade 2 Diarrhea [Increase of 4–6 stools per day over baseline] lasting ≤5 days • Grade 3 Diarrhea [Increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; limiting self-care and activities of daily living] lasting ≤2 days | • Adjust antidiarrheal treatment • Continue NERLYNX and capecitabine at full doses • Diet modifications • Fluid intake of ~2 L/day should be maintained to avoid dehydration • Once the event resolves to Grade ≤1 or baseline, start loperamide 4 mg with each subsequent NERLYNX administration |
| • Persisting and intolerable Grade 2 Diarrhea lasting >5 days • Grade 3 Diarrhea lasting >2 days • Grade 4 Diarrhea [Life-threatening consequences; urgent intervention indicated] | • Adjust antidiarrheal treatment • Hold NERLYNX and capecitabine until recovery to Grade ≤1 or baseline • Diet modifications • Fluid intake of ~2 L/day should be maintained intravenously, if needed • If recovery occurs: o ≤1 week after withholding treatment, resume same doses of NERLYNX and capecitabine o Within 1–3 weeks after withholding treatment, reduce NERLYNX dose to 160 mg and maintain the same dose of capecitabine • If event occurs a second time and the NERLYNX dose has not already been decreased, reduce NERLYNX dose to 160 mg (maintain the same dose of capecitabine). If NERLYNX dose has already been reduced, then reduce the dose of capecitabine to 550 mg/m² given twice dailya (maintain the same dose of NERLYNX). • If subsequent events occur, reduce the dose of NERLYNX or capecitabine to the next lower dose level in an alternate fashion (i.e., reduce capecitabine to 375 mg/m² given twice dailya if NERLYNX was previously reduced, or reduce NERLYNX to 120 mg if capecitabine was previously reduced) • Once the event resolves to Grade ≤1 or baseline, start loperamide 4 mg with each subsequent NERLYNX administration | |
| Hepatotoxicity [see Warnings and Precautions (5.2)] | • Grade 3 ALT or AST (>5–20× ULN) OR • Grade 3 bilirubin (>3–10× ULN) | • Hold NERLYNX until recovery to ≤Grade 1 • Evaluate alternative causes • Resume NERLYNX at the next lower dose level if recovery to ≤ Grade 1 occurs within 3 weeks. If Grade 3 ALT or AST, or bilirubin occurs again despite one dose reduction, permanently discontinue NERLYNX. |
| • Grade 4 ALT or AST (>20× ULN) OR • Grade 4 bilirubin (>10× ULN) | • Permanently discontinue NERLYNX • Evaluate alternative causes | |
| Other [see Adverse Reactions (6.1)] | • Grade 3 | • Hold NERLYNX until recovery to Grade ≤1 or baseline within 3 weeks of stopping treatment. Then resume NERLYNX at the next lower dose level. |
| • Grade 4 | • Discontinue NERLYNX permanently |
ALT=Alanine Aminotransferase; AST=Aspartate Aminotransferase; ULN=Upper Limit Normal
† Per CTCAE v4.0
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/m² dosing.
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)].
Avoid concomitant use with NERLYNX [see Drug Interactions (7.1)].
Take NERLYNX at least 2 hours before the next dose of the H 2-receptor antagonist or 10 hours after the H2-receptor antagonist [see Drug Interactions (7.1)].
Separate dosing of NERLYNX by 3 hours after antacids [see Drug Interactions (7.1)].
There is no specific antidote, and the benefit of hemodialysis in the treatment of NERLYNX overdose is unknown. In the event of an overdose, administration should be withheld and general supportive measures undertaken.
In the clinical trial setting, a limited number of patients reported overdose. The adverse reactions experienced by these patients were diarrhea, nausea, vomiting, and dehydration. The frequency and severity of gastrointestinal disorders (diarrhea, abdominal pain, nausea, and vomiting) appear to be dose related.
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
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