Neratinib

Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro , neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines.

• NERLYNX is a kinase inhibitor indicated: As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. ( 1.1 ) In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.ICD-10: C50.919

• None. None.contraindicated

Premedication for diarrhea: 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. ( 2.1 , 2.2 ) Extended adjuvant treatment of early-stage breast cancer: 240 mg (6 tablets) given orally once daily, with food, continuously until disease recurrence or for up to one year. ( 2.2 ) Advanced or metastatic breast cancer: 240 mg (6 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. ( 2.2 ) Dose escalation: A two-week dose escalation for NERLYNX may also be initiated. ( 2.2 ) Dose interruptions and/or dose reductions are recommended based on individual safety and tolerability. ( 2.3 ) Hepatic impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment. ( 2.4 ) 2.1 Premedication for Diarrhea When not using dose escalation [see Dosage and Administration ( 2.2 )], administer antidiarrheal prophylaxis during the first 56 days of treatment and initiate with the first dose of NERLYNX [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Instruct patients to take loperamide as directed in Table 1 . Titrate loperamide to 1–2 bowel movements per day.

Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis ( 2.1 , 2.2 ). 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. ( 2.3 , 5.1 ) Hepatotoxicity: 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. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Diarrhea Severe diarrhea and sequelae, such as dehydration, hypotension, and renal failure occurred during treatment with NERLYNX. Diarrhea was reported in 95% of NERLYNX-treated patients in ExteNET, a randomized placebo-controlled trial in the extended adjuvant setting who were not required to receive antidiarrheal prophylaxis. In the NERLYNX arm, Grade 3 diarrhea occurred in 40% and Grade 4 diarrhea occurred in 0.1% of patients.

The following clinically significant adverse reactions are described elsewhere in the labeling: Diarrhea [see Warnings and Precautions ( 5.1 )] Hepatotoxicity [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (reported in ≥5% of patients) were: NERLYNX as a single agent: diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection. ( 6 ) NERLYNX in combination with capecitabine: diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Lactation: Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, NERLYNX can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of neratinib to pregnant rabbits during organogenesis resulted in abortions, embryo-fetal death and fetal abnormalities in rabbits at maternal exposures (AUC) approximately 0.2 times exposures in patients at the recommended dose ( see Data ). Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In a fertility and early embryonic development study in female rats, neratinib was administered orally for 15 days before mating to Day 7 of pregnancy, which did not cause embryonic toxicity at doses up to 12 mg/kg/day in the presence of maternal toxicity. A dose of 12 mg/kg/day in rats is approximately 0.5 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis.

Metabolism

Neratinib AUC increases in less than dose proportional manner over a daily dose range of 40 to 400 mg (0.17 to 1.7 times the maximum approved recommended dosage). Absorption Peak concentrations of neratinib and major active metabolites M3, M6 and M7 are reached in the range of 2 to 8 hours after oral administration.

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. In the clinical trial setting, a limited number of patients reported 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.

• Jul 17, 2017NDANDA208051Puma Biotech

1. 1Diarrhoea1,24254%
2. 2Nausea55224%
3. 3Fatigue47121%
4. 4Off Label Use40918%
5. 5Vomiting31114%
6. 6Constipation27712%
7. 7Decreased Appetite25111%
8. 8Death1958.6%
9. 9Disease Progression1546.8%
10. 10Dehydration1466.4%
11. 11Weight Decreased1386.1%
12. 12Abdominal Pain1175.1%
13. 13Headache1165.1%
14. 14Dizziness1034.5%
15. 15Asthenia1004.4%

The 10 most recently updated of 100 ClinicalTrials.gov registrations naming Neratinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
  Recruiting · Phase 2 · Interventional · 2,900 enrolled · National Cancer Institute (NCI)
  NCT05564377updated 2026-06-12
• Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Gastroesophageal Cancer
  Active not recruiting · Phase 2 · Interventional · 8 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT06109467updated 2026-06-12
• Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
  Recruiting · Phase 2 · Interventional · 70 enrolled · National Cancer Institute (NCI)
  NCT06126276updated 2026-06-11
• Identification of Genetic Determinants for Treatment Resistance/Sensitivity and/or Toxicity in Adjuvant Setting for HER2 Positive Breast Cancer
  Recruiting · Observational · 9,000 enrolled · Centre Paul Strauss
  NCT04638725updated 2026-06-04
• Personalized Medicine for Advanced Biliary Cancer Patients
  Recruiting · Phase 3 · Interventional · 800 enrolled · UNICANCER
  NCT05615818updated 2026-05-19
• Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene
  Suspended · Phase 1 · Interventional · 33 enrolled · National Cancer Institute (NCI)
  NCT05372614updated 2026-05-18
• Niraparib and Neratinib in Advanced Solid Tumors With Expansion Cohort in Advanced Ovarian Cancer
  Active not recruiting · Phase 1 · Interventional · 18 enrolled · Virginia Commonwealth University
  NCT04502602updated 2026-05-11
• Pilot Study of [68Ga]Ga-ABY-025 Imaging in Patients Undergoing Treatment With HER2-targeted Therapy
  Recruiting · Early phase 1 · Interventional · 30 enrolled · Vanderbilt-Ingram Cancer Center
  NCT06828588updated 2026-05-08
• I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
  Recruiting · Phase 2 · Interventional · 5,000 enrolled · QuantumLeap Healthcare Collaborative
  NCT01042379updated 2026-05-06
• Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
  Recruiting · Phase 2 · Interventional · 109 enrolled · Scott R. Plotkin, MD, PhD
  NCT04374305updated 2026-05-06

Frequently asked questions

How does Neratinib work?

Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro , neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines.

What is Neratinib used for?

According to FDA labeling, Neratinib carries indications including: NERLYNX is a kinase inhibitor indicated: As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. ( 1.1 ) In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Neratinib?

Neratinib is classified as Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors, Kinase Inhibitor, Kinase Inhibitors, P-Glycoprotein Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Neratinib?

Neratinib is marketed under brand names including Nerlynx.

What are the contraindications for Neratinib?

Neratinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.