Neratinib

Neratinib is a prescription medication used for the treatment of Breast Cancer.

• Neratinib is available under the following different brand names: Nerlynx.

Common side effects of Neratinib 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 the stomach-area
• Nosebleed
• Weight loss
• Urinary tract infection

Serious side effects of Neratinib include:

• Dehydration, 
• Low blood pressure (hypotension), 
• Kidney failure.

Rare side effects of Neratinib include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 40 mg (equivalent to 48.31mg neratinib maleate)

Breast Cancer

Adult dosage

• Early-stage breast cancer
  • 240 mg (6 tablets) orally once a day continuously for 1 year.
  • Consider a two-week dose escalation instead of starting at the 240-mg daily dose to minimize severe diarrhea if not using antidiarrheal prophylaxis
• Advanced or metastatic breast cancer
  • Consider a two-week dose escalation instead of starting at the 240-mg daily dose to minimize severe diarrhea if not using antidiarrheal prophylaxis
  • Each cycle is 21 days.
    • Days 1-21: 240 mg orally once a day PLUS
    • Days 1-14: Capecitabine 750 mg/m2 orally two times a day
    • Continue until disease progression or unacceptable toxicities.
  • Dose escalation regimen
    • Days 1 to 7: 120 mg orally once a day
    • Days 8 to 14: 160 mg orally once a day
    • Day 15 and thereafter: 240 mg orally once a day; continue for up to 1 year.
    • If diarrhea occurs, treat it with antidiarrheal medications, fluids, and electrolytes as clinically warranted.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Neratinib has severe interactions with no other drugs.
• Neratinib has serious interactions with at least 96 other drugs.
• Neratinib has moderate interactions with the following drugs:
  • aluminum hydroxide
  • aspirin/citric acid/sodium bicarbonate
  • berotralstat
  • calcium carbonate
  • clonidine
  • dabigatran
  • dengue vaccine
  • digoxin
  • duvelisib
  • fexofenadine
  • magnesium oxide
  • siponimod
  • sodium zirconium cyclosilicate
  • talazoparib
• Neratinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Neratinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Neratinib?”

Cautions

• No clinically relevant effect on the QTc intervals
• Hepatoxicity reported with therapy; monitor liver function test at baseline, once monthly for the first 3 months, followed by every 3 months while on treatment and as clinically indicated; discontinue and do not restart therapy if patients experience severe changes in liver function tests
• Animal studies have shown therapy can severely affect organ growth and maturation during early postnatal development; safety and effectiveness in pediatric patients not established
• Can cause fetal harm when administered to a pregnant woman.
• Diarrhea
  • Severe diarrhea and sequelae (e.g., dehydration, hypotension, renal failure) occurred.
  • Diarrhea was reported in patients treated with neratinib plus capecitabine in NALA, a randomized placebo-controlled trial in the metastatic breast cancer setting who were required to receive anti-diarrheal prophylaxis in the first cycle.
  • Antidiarrheal prophylaxis has been shown to lower the incidence and severity of diarrhea.
  • Consider adding other agents to loperamide as clinically indicated.
  • Alternatively, consider a 2-week dose escalation approach before initiation of the treatment regimen for diarrhea management.
  • Median time to first onset of Grade above 3 diarrhea was 45 days (range, 15-132) and the median cumulative duration of Grade above 3 diarrhea was 2.5 days (range, 1-6)
  • Monitor for diarrhea and treat with additional antidiarrheals as needed.
  • When severe diarrhea with dehydration occurs, administer fluid and electrolytes as needed, interrupt therapy, and reduce subsequent doses.
  • 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)
• Drug interaction overview
• Neratinib is a CYP3A4 substrate and inhibits P-glycoprotein (P-gp) transporters.
• P-gp substrates
  • Coadministration with digoxin, a P-gp substrate, increased digoxin concentrations
  • Increased concentrations of digoxin may lead to an increased risk of adverse reactions including cardiac toxicity.
  • Caution if using concomitant P-gp substrates; monitor substrate for necessary dosage adjustments.
• Strong and moderate CYP3A4 inhibitors
  • Coadministration with strong CYP3A4 inhibitors (.g, ketoconazole, ritonavir, clarithromycin, grapefruit juice) may increase neratinib serum levels
  • Avoid coadministration.
• Strong and moderate CYP3A4 inducers
  • CYP3A4 inducers (.g, rifampin, carbamazepine) decrease neratinib serum levels
  • Avoid coadministration.
• Drugs that increase gastric pH
  • Concomitant use of neratinib with a PPI (. g, lansoprazole) decreased neratinib Cmax by 71% and AUC by 65%, which may reduce the efficacy.
  • Avoid concomitant use with drugs that raise gastric pH (.e, PPIs, H2-receptor antagonists)
  • Consider short-acting antacids in place of PPIs and H2-receptor antagonists
  • Separate antacid and neratinib dosing by 3 hours

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women
• Females of reproductive potential should have a pregnancy test before starting treatment.
• If used during pregnancy, or becomes pregnant while taking the drug, advise of the potential hazard to the fetus.
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 1 month after the last dose.
  • Males with females of reproductive potential: Use effective contraception during treatment and for 3 months after the last dose.
• Lactation
  • Unknown if distributed in human breast milk.
  • Owing to the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking neratinib and for at least 1 month after the last dose.