NERLYNX 40 MG — DIN 02490536

What is NERLYNX?

NERLYNX 40 MG contains NERATINIB (NERATINIB MALEATE) : 40 MG. It is listed in the Health Canada Drug Product Database under DIN 02490536, held by KNIGHT THERAPEUTICS INC., supplied as TABLET for ORAL administration. Health Canada currently lists it as marketed, status dated 20-Dec-2019. Nexara Health is a licensed Canadian wholesale distributor (DEL 3-002896-A) and can source this product for hospitals, pharmacies and clinics. Availability and lead time are confirmed per order.

What is NERLYNX used for?

NERLYNX (neratinib) is indicated for: • The extended adjuvant treatment of women with early-stage hormone receptor positive and HER2-overexpressed/amplified breast cancer, within one year after completion of trastuzumab-based adjuvant therapy. • In combination with capecitabine for the treatment of patients with metastatic HER2-overexpressed/amplified breast cancer, who have received two or more prior anti-HER2-based regimens in the metastatic setting.

Authorized indication as written in the Health Canada product monograph. For healthcare professionals and licensed purchasers; this is not medical advice.

How is it administered?

NERLYNX treatment can cause severe diarrhea. Either a NERLYNX dose escalation or antidiarrheal prophylaxis with loperamide is recommended to lower the incidence and severity of diarrhea. NERLYNX dose interruptions or dose reductions may also be required to manage diarrhea. DOSE ESCALATION PROPHYLAXIS: Initiate NERLYNX at 120 mg daily and increase the dose according to the treatment schedule: • 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 with dose escalation, loperamide 4 mg should be initiated no later than with the first bout of diarrhea, and continued with loperamide 2 mg after every subsequent loose stool, up to 16 mg per day, until diarrhea-free for 12 hours. Then, titrate loperamide to keep diarrhea controlled (1-2 bowel movements per day). ANTIDIARRHEAL PROPHYLAXIS WITH LOPERAMIDE: Administer loperamide during the first 56 days of treatment, starting with the first dose of NERLYNX. For both indications, instruct patients to take loperamide as directed, titrating to 1-2 bowel movements per day. Additional antidiarrheal agents may be required to manage diarrhea in patients with loperamide-refractory diarrhea. • Weeks 1-2 (days 1-14): 4 mg three times daily • Weeks 3-8 (days 15–56): 4 mg twice daily • Weeks 9 and onwards: 4 mg as needed (not to exceed 16 mg per day) Recommended Dose: Extended Adjuvant Treatment of Early-Stage Breast Cancer: 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year at approximately the same time every day. Should be used in combination with endocrine therapy in patients with early-stage hormone receptor-positive and HER2 overexpressed/amplified breast cancer within one year after completion of trastuzumab-based adjuvant therapy. Metastatic Breast Cancer: 240 mg (six 40 mg tablets) given orally once daily with food, at approximately the same time on Day 1 – 21 of a 21-day cycle in combination with capecitabine on Day 1 – 14 of a 21-day cycle until disease progression or unacceptable toxicities. The recommended dose of capecitabine is 1500 mg/m² total daily dose evenly divided into 2 doses of 750 mg/m² each, starting on cycle 1 Day 1. Capecitabine should be taken with food or within 30 minutes after a meal. Administration: NERLYNX tablets should be swallowed whole with a glass of water (tablets should not be chewed, crushed or split prior to swallowing). High-fat meal may lead to higher exposures of NERLYNX than a standard breakfast. Missed Dose: If a patient misses a dose, do not replace missed dose, and instruct the patient to resume NERLYNX with the next scheduled daily dose.

Included because it drives pack selection and wastage. Consult the monograph.

Contraindications

NERLYNX is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Warnings and precautions

Cardiovascular: Decreased Left Ventricular Function. In both extended adjuvant (ExteNET trial) and metastatic (NALA) settings, patients with left ventricular ejection fraction (LVEF) either below institutional lower limit of normal or below 50%, symptomatic congestive heart failure of NYHA class 2 or higher, QTcF > 450 msec, ventricular arrhythmia requiring medical therapy, or with a history of myocardial infarction within 12 months were excluded from the study. In patients with known cardiac risk factors, conduct cardiac monitoring, including assessment of LVEF, as clinically indicated. Gastrointestinal: Diarrhea. Severe diarrhea and sequelae, such as dehydration, hypotension, and renal failure, have been reported during treatment with NERLYNX. Either a two-week NERLYNX dose escalation (with loperamide taken as needed) or antidiarrheal prophylaxis with loperamide for the first 56 days of treatment, is recommended to lower the incidence and severity of diarrhea. Proactively manage diarrhea at the first unformed stool, especially within the first 2 weeks of starting NERLYNX. Measures include adequate oral hydration, avoiding foods that might aggravate diarrhea, and treatment with additional antidiarrheal therapy as needed. When severe diarrhea with dehydration occurs, administer fluid and electrolytes as needed, interrupt NERLYNX and reduce subsequent doses. Permanently discontinue NERLYNX in patients with diarrhea recurring to Grade ≥ 2 at 120 mg NERLYNX daily dose or with Grade 4 diarrhea. Perform stool cultures as clinically indicated to exclude infectious causes of Grade 3 or 4 diarrhea or diarrhea of any grade with complicating features (dehydration, fever, neutropenia). Hepatic / Biliary/Pancreatic: Hepatotoxicity. NERLYNX has been associated with hepatotoxicity, characterized by increased liver enzymes. Liver function tests should be conducted prior to and during NERLYNX treatment. Dose modifications are recommended for patients with treatment-emergent hepatotoxicity. NERLYNX treatment should be permanently discontinued in patients with Grade 4 increases in liver transaminases (> 20x ULN), Grade 4 bilirubin (> 10x ULN), or in those with ALT/AST ≥ 3x ULN and bilirubin > 2x ULN. Reproductive Health: Female and Male Potential. Fertility studies in humans have not been performed with NERLYNX. In a fertility study in rats, neratinib caused no effects on mating or the ability of animals to become pregnant; however, effects on male reproductive organs were observed in chronic, repeated-dose toxicity studies. Women of childbearing potential must be advised to avoid pregnancy while on NERLYNX. Female patients of child-bearing potential must use highly effective contraceptive methods during treatment and for at least 1 month after the last dose. Pregnancy testing is recommended for women of reproductive potential prior to starting treatment with NERLYNX. Men with female partners of reproductive potential should be advised to use effective contraception during treatment with NERLYNX and for 3 months after the final dose.