Nerlynx

Nerlynx treatment should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. Posology 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. Dose 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 1, Table 2, Table 3, and Table 4. g. ). 3 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. 0 Dose modifications for diarrhoea 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. 4). 4 Severity of diarrhoea* Action • 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). 4). • If grade 3 diarrhoea persists longer than 3weeks, discontinue Nerlynx permanently. 0 † Complicated features include dehydration, fever, hypotension, renal failure, or Grade 3 or 4 neutropenia ‡ Despite being treated with optimal medical therapy Dose modifications for hepatotoxicity Guidelines for dose adjustment of Nerlynx in the event of liver toxicity are shown in Table 4.

0%). 1%). 2%). Tabulated list of adverse reactions The table below lists adverse reactions observed with neratinib based on the assessment of pooled data from 1 710 patients. The MedDRA frequency convention and system organ class database has been utilised for the classification of frequency: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1 000 to < 1/100) Rare (≥ 1/10 000 to < 1/1 000) Very rare (< 1/10 000) Not known (cannot be estimated from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 5:

Adverse drug reactions due to Nerlynx in monotherapy breast cancer studies System Organ Class Frequency Adverse Drug Reaction Infections and infestations Common Urinary tract infection Metabolism and nutrition disorders Very Common Decreased appetite Common Dehydration Nervous system disorders Common Syncope 10 System Organ Class Frequency Adverse Drug Reaction Respiratory, thoracic and mediastinal disorders Common Epistaxis Gastrointestinal disorders Very Common Diarrhoea, vomiting, nausea, abdominal pain, abdominal pain upper, and stomatitis1 Common Abdominal distension, dry mouth and dyspepsia Hepatobiliary disorders Common Alanine aminotransferase increased, and aspartate aminotransferase increased Uncommon Blood bilirubin increased Skin and subcutaneous tissue disorders Very Common Rash2 Common Nail disorder3, skin fissures and dry skin Musculoskeletal and connective tissue disorders Very Common Muscle spasms Renal and urinary disorders Common Blood creatinine increased Uncommon Renal failure General disorders and administration site conditions Very common Fatigue Investigations Common Weight decreased 1 Includes stomatitis, aphthous stomatitis, mouth ulceration, oral mucosal blistering, and mucosal inflammation.

2 Includes rash, rash erythematous, rash follicular, rash generalised, rash pruritic, and rash pustular. 3 Includes nail disorder, paronychia, onychoclasis, and nail discolouration. 6% experienced at least 1 episode of diarrhoea. 5% of Nerlynx patients.

8). The diarrhoea may be severe and associated with dehydration. Diarrhoea generally occurs early during the first or second week of treatment with Nerlynx and may be recurrent. Patients should be instructed to initiate prophylactic treatment with an anti-diarrhoeal medicinal product with the first dose of Nerlynx, and maintain regular dosing of the anti-diarrhoeal medicinal product during the first 1-2 months of Nerlynx treatment, titrating to 1-2 bowel movements per day.

Elderly Elderly patients (≥65 years of age) are at a higher risk of renal insufficiency and dehydration which may be a complication of diarrhoea and these patients should be carefully monitored. Patients with a significant chronic gastrointestinal disorder Patients with a significant chronic gastrointestinal disorder with diarrhoea as a major symptom were not included in the pivotal study, and should be carefully monitored.

2). Liver function Hepatotoxicity has been reported in patients treated with Nerlynx. 2). Patients who experience ≥ Grade 3 diarrhoea requiring intraveinous fluid treatment or any signs or symptoms of hepatotoxicity, such as worsening of fatigue, nausea, vomiting, jaundice, right upper quadrant pain or tenderness, fever, rash, or eosinophilia, should be evaluated for changes in liver function tests.

Fractionated bilirubin and prothrombin time should also be collected during hepatotoxicity evaluation. Left ventricular function Left ventricular dysfunction has been associated with HER2 inhibition. Nerlynx has not been studied in patients with less than lower limit of normal left ventricular ejection fraction (LVEF) or with significant cardiac history.

In patients with known cardiac risk factors, conduct cardiac monitoring, including assessment of LVEF, as clinically indicated. Proton pump inhibitors, H2-receptor antagonists and antacids Treatments that increase gastrointestinal pH may lower the absorption of neratinib, thus decreasing systemic exposure.

1. 2).