Neratinib

What is Neratinib?

• Neratinib (Nerlynx) is a kinase inhibitor used for the treatment of breast cancer.

What are the uses of this medicine?

Neratinib (Nerlynx) is used:

• alone to treat adults with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and who have previously been treated with trastuzumab-based therapy.
• with a medicine called capecitabine to treat adults with HER2-positive breast cancer that has spread to other parts of the body (metastatic) and who have received 2 or more anti-HER2 therapy medicines for metastatic breast cancer.

How does this medicine work?

• Neratinib (ne ra' ti nib) is a small molecule tyrosine kinase receptor inhibitor with potent activity against human epidermal growth factor receptor 2 (HER2 or ErbB2).
• These tyrosine kinase receptors are often mutated and over expressed in tumor tissue and cause unregulated cell growth and proliferation.
• This mutation is present in 20% of breast cancers and is particularly overexpressed in early stage cancers.
• Inhibition of the unregulated receptor can lead to reversal of progression of the cancer, although clinical responses are sometimes limited by the development of tumor resistance caused by further mutations in the receptor gene.
• In several large controlled trials, adjuvant therapy with neratinib was shown to improve progression free survival in patients with early stage, HER2-positive breast cancer.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Avoid concomitant use with proton pump inhibitors. Separate Nerlynx by at least 2 hours before or 10 hours after H 2-receptor antagonists. Or separate Nerlynx by at least 3 hours after antacids.
• Avoid concomitant use of Nerlynx with strong CYP3A4 inhibitors (eg:itraconazole, ketoconazole, clarithromycin).
• Avoid concomitant use of Nerlynx with P-gp and moderate CYP3A4 dual inhibitors.
• Avoid concomitant use of Nerlynx with strong or moderate CYP3A4 inducers.
• Monitor for adverse reactions of P-gp substrates for which miminal concentration change may lead to serious adverse reactions when used concomitantly with Nerlynx.

Is this medicine FDA approved?

• It was approved for use in the United States in 2017.

How should this medicine be used?

• When not using dose escalation, initiate loperamide with the first dose of Nerlynx and continue during the first 56 days of treatment. After day 56, use loperamide to maintain 1–2 bowel movements per day.

Recommended Dosage: 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 also be initiated.

Hepatic impairment:

• Reduce starting dose to 80 mg in patients with severe hepatic impairment.

Administration

• Take Nerlynx exactly as your healthcare provider tells you to take it.
• Your healthcare provider may change your dose of Nerlynx if needed.
• Take Nerlynx with food.
• Take Nerlynx at about the same time each day.
• Swallow Nerlynx tablets whole. Do not chew, crush, or split Nerlynx tablets.
• If you take an antacid medicine, take Nerlynx 3 hours after the antacid medicine.
• If you take an acid reducer (H 2 receptor blocker), Nerlynx should be taken at least 2 hours before or 10 hours after you take these medicines.
• If you miss a dose of Nerlynx, skip that dose and take your next dose at your regular scheduled time.
• If you take too much Nerlynx, call your healthcare provider right away or go to the nearest hospital emergency room.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 40 mg

This medicine is available in fallowing brand namesː

• Nerlynx

What side effects can this medication cause?

The most common side effects of Nerlynx when used alone include:

• diarrhea
• nausea
• stomach-area (abdomen) pain
• tiredness
• vomiting
• rash
• dry or inflamed mouth, or mouth sores
• decreased appetite
• muscle spasms
• upset stomach
• nail problems including color change
• dry skin
• swelling of your stomach-area
• nosebleed
• weight loss
• urinary tract infection

The most common side effects of Nerlynx when used with capecitabine include:

• diarrhea
• nausea
• vomiting
• decreased appetite
• constipation
• tiredness/weakness
• weight loss
• dizziness
• back pain
• joint pain
• urinary tract infection
• upper respiratory tract infection
• swelling of your stomach-area
• kidney problems
• muscle spasms

Nerlynx may cause serious side effects, including:

• Liver problems
• Diarrhea

What special precautions should I follow?

• Manage diarrhea through either Nerlynx dose escalation or loperamide prophylaxis . If diarrhea occurs despite recommended prophylaxis, treat with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold Nerlynx in patients experiencing severe and/or persistent diarrhea. Permanently discontinue Nerlynx in patients experiencing Grade 4 diarrhea or Grade ≥2 diarrhea that occurs after maximal dose reduction.
• Nerlynx has been associated with hepatotoxicity characterized by increased liver enzymes. Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold Nerlynx in patients experiencing Grade 3 liver abnormalities and permanently discontinue Nerlynx in patients experiencing Grade 4 liver abnormalities.
• Nerlynx can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

What to do in case of emergency/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.

Management for overdosage:

• 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.

Can this medicine be used in pregnancy?

• Nerlynx can cause fetal harm when administered to a pregnant woman.
• There are no available data in pregnant women to inform the drug-associated risk.

Can this medicine be used in children?

• The safety and efficacy of Nerlynx in pediatric patients has not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: neratinib
• Inactive ingredients: Tablet Core: colloidal silicon dioxide, mannitol, microcrystalline cellulose, crospovidone, povidone, magnesium stearate, and purified water. Coating: red film coat: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide red.

Who manufactures and distributes this medicine?

• Manufactured for: Puma Biotechnology, Inc. 10880 Wilshire Blvd., Suite 2150 Los Angeles

What should I know about storage and disposal of this medication?

• Store Nerlynx at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Nerlynx and all medicines out of the reach of children.

• Dailymed label info on Neratinib
• FDA Neratinib

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