Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: PIERRE FABRE MEDICAMENT, Les Cauquillous, 81500 Lavaur, France
Nerlynx is indicated for the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago.
Nerlynx treatment should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products.
The recommended dose of Nerlynx is 240 mg (six 40 mg tablets) taken orally once daily, continuously for one year. Nerlynx should be taken with food, preferably in the morning. Patients should initiate treatment within 1 year after completion of trastuzumab therapy.
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 1, Table 2, Table 3, and Table 4.
Nerlynx should be discontinued for patients who:
Additional clinical situations may result in dose adjustments as clinically indicated (e.g. intolerable toxicities, persistent Grade 2 adverse reactions, etc.).
Table 1. Nerlynx dose modifications for adverse reactions:
| Dose level | Nerlynx dose |
|---|---|
| Recommended starting dose | 240 mg daily |
| First dose reduction | 200 mg daily |
| Second dose reduction | 160 mg daily |
| Third dose reduction | 120 mg daily |
Table 2. Nerlynx dose modifications and management – general toxicities*:
| Severity of toxicity† | Action |
|---|---|
| Grade 3 | Stop Nerlynx until recovery to Grade ≤1 or baseline within 3 weeks of stopping treatment. Then resume Nerlynx at the next lower dose level. If grade 3 toxicity does not recover within 3 weeks, discontinue Nerlynx permanently. |
| Grade 4 | Discontinue Nerlynx permanently. |
* Refer to Table 3 and Table 4 below for management of diarrhoea and hepatotoxicity
† Per CTCAE v4.0
Diarrhoea management requires the correct use of an anti-diarrhoeal medicinal product, dietary changes, and appropriate dose modifications of Nerlynx. Guidelines for adjusting doses of Nerlynx in the setting of diarrhoea are shown in Table 3.
Table 3. Dose modifications for diarrhoea:
| Severity of diarrhoea* | Action |
|---|---|
| • Grade 1 diarrhoea [increase of <4 stools per day over baseline] • Grade 2 diarrhoea [increase of 4-6 stools per day over baseline] lasting <5 days • Grade 3 diarrhoea [increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; limiting self-care activities of daily living] lasting ≤2 days | • Adjust anti-diarrhoeal treatment • Diet modifications • Fluid intake of ~2 L/day should be maintained to avoid dehydration • Once event resolves to Grade ≤1 or baseline, consider restarting anti-diarrhoeal prophylaxis, if appropriate with each subsequent Nerlynx administration (refer to section 4.4). |
| • Any grade with complicated features† • Grade 2 diarrhoea lasting 5 days or longer‡ • Grade 3 diarrhoea lasting between 2 days and 3 weeks‡ | • Interrupt Nerlynx treatment • Diet modifications • Fluid intake of ~2 L/day should be maintained to avoid dehydration • If diarrhoea resolves to Grade ≤1 in one week or less, then resume Nerlynx treatment at the same dose. • If diarrhoea resolves to Grade ≤1 in longer than one week, then resume Nerlynx treatment at reduced dose (see Table 1). • Once event resolves to Grade ≤1 or baseline, consider restarting anti-diarrhoeal prophylaxis, if appropriate with each subsequent Nerlynx administration (refer to section 4.4). • If grade 3 diarrhoea persists longer than 3 weeks, discontinue Nerlynx permanently. |
| • Grade 4 diarrhoea [life-threatening consequences; urgent intervention indicated] | • Permanently discontinue Nerlynx treatment |
| • Diarrhoea recurs to Grade 2 or higher at 120 mg per day | • Permanently discontinue Nerlynx treatment |
* 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
Guidelines for dose adjustment of Nerlynx in the event of liver toxicity are shown in Table 4. (see section 4.4).
Table 4. Dose modifications for hepatotoxicity:
| Severity of hepatotoxicity* | Action |
|---|---|
| • Grade 3 ALT (>5-20 x ULN) OR • Grade 3 bilirubin (>3-10 x ULN) | • Stop 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 bilirubin occurs again despite one dose reduction, permanently discontinue Nerlynx. • If grade 3 hepatotoxicity persists longer than 3 weeks, discontinue Nerlynx permanently |
| • Grade 4 ALT (>20 x ULN) OR • Grade 4 bilirubin (>10 x ULN) | • Permanently discontinue Nerlynx • Evaluate alternative causes |
ULN = Upper Limit Normal; ALT = Alanine Aminotransferase
* Per CTCAE v4.0
Missed doses should not be replaced and treatment should resume with the next scheduled daily dose (see section 4.9).
Concomitant administration of neratinib with grapefruit or pomegranate/grapefruit or pomegranate juice is not recommended (see sections 4.4 and 4.5).
If the inhibitor cannot be avoided, reduce Nerlynx dose:
After discontinuation of a strong or moderate CYP3A4/P-gp inhibitor, resume previous dose of Nerlynx 240 mg (see sections 4.4, 4.5 and 5.2).
If H2-receptor antagonists are used, Nerlynx should be taken at least 2 hours before or 10 hours after the intake of the H2-receptor antagonist. Separate dosing of Nerlynx and antacids by at least 3 hours should be applied (see sections 4.4, 4.5 and 5.2).
No dose adjustment is necessary in patients with mild to moderate renal impairment. Nerlynx has not been studied in patients with severe renal impairment including patients on dialysis. Treatment of patients with severe renal impairment or on dialysis is not recommended (see section 5.2).
No dose adjustment is required in patients with Child-Pugh A or B (mild to moderate) hepatic impairment (see section 5.2).
No dose adjustment is required. There is no data in patients ≥85 years of age.
There is no relevant use of Nerlynx in the paediatric population in the indication of breast cancer.
Nerlynx is for oral use. The tablets should be swallowed whole preferably with water and should not be crushed or dissolved. The tablets should be taken with food, preferably in the morning (see section 5.2).
There is no specific antidote, and the benefit of haemodialysis 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, adverse reactions associated with overdose were most commonly diarrhoea, with or without nausea, vomiting and dehydration.
In a dose escalation study in healthy volunteers, single oral doses of Nerlynx up to 800 mg were administered. The frequency and severity of gastrointestinal disorders (diarrhoea, abdominal pain, nausea and vomiting) appeared to be dose-related. Single doses of Nerlynx greater than 800 mg have not been administered in the clinical studies.
3 years.
Keep the bottle tightly closed in order to protect from moisture.
This medicinal product does not require any special temperature storage conditions.
60 mL white high density polyethylene (HDPE) round bottle with child-resistant, polypropylene closure, and foil induction inner seal.
An HDPE desiccant canister with 1 g silica gel is enclosed with the tablets in each bottle.
Each bottle contains 180 tablets.
This medicinal product may pose a risk to the environment (see section 5.3).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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