Nerlynx (Neratinib)
Tyrosine Kinase Inhibitor for HER2-Positive Early Breast Cancer
Quick Facts About Nerlynx
Key Takeaways About Nerlynx
- Extended adjuvant therapy: Nerlynx is specifically designed as a follow-on treatment after trastuzumab for HR-positive, HER2-positive early breast cancer, reducing the risk of recurrence
- Diarrhoea management is critical: Prophylactic anti-diarrhoeal medication (loperamide) must be started from day one and continued for at least the first 1–2 months of treatment
- One-year treatment course: The standard duration is 12 months of continuous daily dosing (240 mg – six 40 mg tablets taken once daily with food)
- Liver monitoring required: Blood tests for liver function must be performed before and during treatment, as neratinib can cause hepatotoxicity
- Multiple drug interactions: Avoid grapefruit, pomegranate, proton pump inhibitors, and strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John’s Wort)
What Is Nerlynx and What Is It Used For?
Nerlynx (neratinib) is an irreversible pan-HER tyrosine kinase inhibitor prescribed as extended adjuvant treatment for adults with hormone receptor-positive (HR+), HER2-overexpressed or amplified (HER2+) early-stage breast cancer who have completed prior trastuzumab-based adjuvant therapy within the past year.
Nerlynx contains the active substance neratinib. It belongs to a group of medicines known as tyrosine kinase inhibitors, which work by blocking specific proteins on the surface of cancer cells that drive their growth and division. Neratinib specifically targets the human epidermal growth factor receptor (HER) family, including HER1 (also known as EGFR), HER2, and HER4.
In HER2-positive breast cancer, the cancer cells have an abnormally high number of HER2 receptors on their surface. This overexpression of HER2 stimulates excessive cell signalling through pathways such as MAPK and PI3K/AKT, which promotes rapid and uncontrolled cancer cell growth. By irreversibly binding to these receptors, neratinib shuts down the downstream signalling cascades that drive tumour proliferation and survival.
The term “hormone receptor-positive” (HR+) means that the breast cancer cells express receptors for oestrogen and/or progesterone. These hormones can bind to the receptors and stimulate cell division. In HR+/HER2+ breast cancer, both hormonal signalling and HER2-driven pathways contribute to tumour growth, making this subtype particularly aggressive and prone to recurrence even after initial treatment with trastuzumab.
Nerlynx is prescribed as “extended adjuvant therapy,” meaning it is given after the completion of standard adjuvant treatment (surgery, chemotherapy, and trastuzumab). The landmark ExteNET trial demonstrated that one year of neratinib following trastuzumab significantly reduced the risk of invasive disease-free survival events in patients with HR+/HER2+ early breast cancer. This benefit was most pronounced in patients who started neratinib within one year of completing trastuzumab.
Neratinib was first approved by the FDA in 2017 and subsequently by the EMA in 2018 for extended adjuvant treatment of HER2-positive early breast cancer. It represents an important advance in reducing the long-term risk of cancer recurrence in high-risk patients. The drug is manufactured by Pierre Fabre Médicament.
How Nerlynx Works
Unlike trastuzumab, which is a monoclonal antibody that binds to the extracellular domain of HER2, neratinib is a small-molecule inhibitor that enters the cell and irreversibly binds to the intracellular tyrosine kinase domain of HER1, HER2, and HER4. This covalent binding to cysteine residues in the ATP-binding pocket permanently inactivates the receptors, preventing them from triggering the downstream signalling cascades (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) that promote cancer cell growth, survival, and metastasis.
This dual mechanism – blocking both HER2 and related family members – provides broader inhibition of the HER signalling network compared to agents targeting HER2 alone. Preclinical studies have shown that this pan-HER inhibition can overcome certain resistance mechanisms that develop during or after trastuzumab therapy, making neratinib a valuable addition to the treatment sequence.
What Should You Know Before Taking Nerlynx?
Before starting Nerlynx, your doctor will verify that your cancer is HR-positive and HER2-positive, that you have completed trastuzumab within the past year, and that your liver function is adequate. Nerlynx is contraindicated in patients with severe liver impairment and those taking strong CYP3A4 inducers.
Contraindications
You should not take Nerlynx if any of the following apply to you:
- Allergy to neratinib or any of the other ingredients in Nerlynx (listed in the contents section below)
- Severe liver impairment (corresponding to Child–Pugh class C) – the drug is extensively metabolised by the liver and severe impairment significantly increases the risk of toxicity
- Concurrent use of strong CYP3A4 inducers and/or P-glycoprotein (P-gp) inducers, including:
- Rifampicin (used to treat tuberculosis)
- Carbamazepine or phenytoin (used to treat epileptic seizures)
- St John’s Wort (Hypericum perforatum) – a herbal remedy for low mood and mild anxiety
Taking Nerlynx together with strong CYP3A4 inducers is strictly contraindicated because these substances dramatically reduce neratinib blood levels, potentially rendering the treatment ineffective against cancer recurrence. Always inform your doctor about all medicines, herbal products, and supplements you are taking.
Warnings and Precautions
Talk to your doctor or pharmacist before taking Nerlynx if you have or have had any of the following conditions:
- Liver problems – Nerlynx can cause changes in liver function detectable through blood tests. Your doctor will perform liver function tests before treatment begins and at regular intervals during treatment. If serious liver abnormalities develop, treatment will be interrupted or discontinued
- Kidney impairment – patients with reduced kidney function should be monitored closely during treatment
- Chronic gastrointestinal disorders – since diarrhoea is the most common side effect, pre-existing bowel conditions may increase risk and severity
- Heart disease or history of cardiac problems – neratinib may affect cardiac function and patients with cardiovascular conditions require closer monitoring
- Skin and subcutaneous tissue disorders – skin reactions including rash and dry skin have been reported
Diarrhoea prophylaxis is mandatory: Nerlynx commonly causes diarrhoea, particularly during the first weeks of treatment. It can be severe and lead to dehydration if not managed proactively. Your doctor will prescribe anti-diarrhoeal medication (typically loperamide) to be started from the very first dose of Nerlynx and continued for the first one to two months. Dietary adjustments and adequate fluid intake are also essential components of diarrhoea management.
Elderly Patients
If you are 65 years or older, you should be monitored closely by your doctor. Elderly patients may be more susceptible to dehydration from diarrhoea and may require more aggressive supportive care, including earlier dose adjustments.
Children and Adolescents
Nerlynx should not be used in children and adolescents under 18 years of age. The safety and efficacy of neratinib have not been studied in this age group, and breast cancer treatment in paediatric populations requires different approaches.
Pregnancy and Breastfeeding
Pregnancy: If you are pregnant, your doctor will assess the potential benefit to you against the risk to the foetus before prescribing this medicine. If you become pregnant while taking Nerlynx, your doctor will reassess whether continuing treatment is appropriate. Based on the drug’s mechanism of action, neratinib has the potential to cause foetal harm.
Contraception: Women of childbearing potential must use effective contraception, including a barrier method (such as a condom), during treatment with Nerlynx and for at least one month after the last dose. Men must use effective barrier contraception during treatment and for at least three months after the last dose.
Breastfeeding: It is not known whether neratinib passes into breast milk. Talk to your doctor before taking Nerlynx if you are breastfeeding or planning to breastfeed. Your doctor will discuss the benefits and risks of taking Nerlynx during breastfeeding. As a precaution, breastfeeding is generally not recommended during treatment.
Driving and Operating Machinery
Nerlynx has a minor effect on the ability to drive and use machines. Side effects of the drug, particularly dehydration and dizziness resulting from diarrhoea, fatigue, and fainting, may impair your ability to perform tasks that require judgement, motor skill, or cognitive function. If you experience any of these symptoms, avoid driving or operating machinery until you feel well.
How Does Nerlynx Interact with Other Drugs?
Nerlynx has significant interactions with many medications because it is metabolised by the CYP3A4 enzyme and affects drug transporter proteins. Several drug combinations are strictly contraindicated, while others require dose adjustments or careful timing of administration.
Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. The effectiveness and/or safety of Nerlynx and other medicines can change when taken together. This is because Nerlynx can affect how certain other medicines work, and certain other medicines can affect how Nerlynx works.
Major Interactions (Contraindicated or Avoid)
| Medicine | Category | Interaction |
|---|---|---|
| Rifampicin | Antibiotic (tuberculosis) | Contraindicated – strongly reduces neratinib levels |
| Carbamazepine, Phenytoin, Phenobarbital, Primidone | Antiepileptics | Contraindicated – strong CYP3A4 inducers reduce neratinib efficacy |
| St John’s Wort | Herbal supplement | Contraindicated – significantly reduces neratinib blood levels |
| Proton pump inhibitors (omeprazole, lansoprazole) | Acid-reducing agents | Not recommended – significantly reduces neratinib absorption |
| Ketoconazole, Voriconazole, Itraconazole | Antifungals | Avoid – strong CYP3A4 inhibitors increase neratinib toxicity risk |
| Protease inhibitors (ritonavir, lopinavir, saquinavir, atazanavir) | Antivirals (HIV) | Avoid – strong CYP3A4 inhibitors increase neratinib levels |
Moderate Interactions (Use with Caution)
| Medicine | Category | Precaution |
|---|---|---|
| H2-receptor antagonists (ranitidine) | Acid-reducing agents | Take Nerlynx at least 2 hours before or 10 hours after H2-blocker |
| Antacids | Acid-reducing agents | Separate Nerlynx and antacid doses by at least 3 hours |
| Erythromycin, Clarithromycin | Macrolide antibiotics | Moderate CYP3A4 inhibitors – monitor closely, may need dose adjustment |
| Diltiazem, Verapamil | Calcium channel blockers | Moderate CYP3A4 inhibitors – careful monitoring required |
| Fluconazole | Antifungal | Moderate CYP3A4 inhibitor – dose adjustment may be needed |
| Bosentan, Dexamethasone | Various | Moderate CYP3A4 inducers – may reduce neratinib efficacy |
| Dabigatran, Digoxin | Cardiac drugs | Neratinib inhibits P-gp – increased levels of these drugs |
| Rosuvastatin | Statin (cholesterol) | Neratinib may increase statin levels – monitor for myopathy |
| Irinotecan | Chemotherapy | Neratinib may increase irinotecan levels – dose adjustment needed |
| Cyclosporine, Everolimus, Sirolimus, Tacrolimus | Immunosuppressants | Complex interactions via CYP3A4 and P-gp – careful monitoring |
Food Interactions
Avoid grapefruit and pomegranate while taking Nerlynx – this includes the whole fruit, juice, and any supplements containing these fruits. Both grapefruit and pomegranate contain compounds that inhibit CYP3A4, which can increase neratinib blood levels unpredictably and raise the risk of side effects. Nerlynx should always be taken with food, as this improves absorption and may help reduce gastrointestinal side effects.
What Is the Correct Dosage of Nerlynx?
The recommended dose of Nerlynx is 240 mg (six 40 mg tablets) taken once daily with food. Treatment continues for one year. Tablets must be swallowed whole with water – do not crush, chew, or dissolve them.
Adults
Standard Adult Dose
240 mg once daily (six 40 mg tablets)
- Take all tablets at the same time each day, preferably in the morning
- Always take with food to improve absorption
- Swallow tablets whole with water – do not crush or dissolve
- Continue treatment for a total of one year (12 months)
Your doctor may reduce the dose or temporarily interrupt treatment if you experience severe side effects, particularly diarrhoea or liver function abnormalities. Dose reductions are typically made in increments (from 240 mg to 200 mg, then to 160 mg, and finally to 120 mg) depending on the severity and persistence of the side effect.
Mandatory Diarrhoea Prophylaxis
You must start taking anti-diarrhoeal medication (loperamide, as prescribed by your doctor) from the very first dose of Nerlynx. Diarrhoea occurs very commonly, usually during the first weeks of treatment, and can be severe and recurrent if not managed proactively.
- Begin loperamide prophylaxis on day 1 of Nerlynx treatment
- Your doctor will instruct you on the exact loperamide dosing schedule
- Continue prophylactic anti-diarrhoeal treatment for the first one to two months
- After this period, your doctor will advise whether ongoing anti-diarrhoeal medication is needed
- Adjust your diet and fluid intake as recommended by your healthcare team
Children
Nerlynx is not indicated for use in children and adolescents under 18 years of age. No paediatric dosing guidelines exist, and the safety and efficacy of neratinib have not been established in this population.
Elderly
No dose adjustment is specifically required based on age alone. However, patients aged 65 years and older should be monitored more closely due to a potentially increased risk of dehydration from diarrhoea. Your doctor may initiate more aggressive supportive measures or consider earlier dose reductions if severe diarrhoea develops.
Missed Dose
If you forget to take a dose of Nerlynx, do not take it later that day. Wait until the next day and take your next scheduled dose at the usual time. Do not take a double dose to make up for a missed dose. Missing occasional doses may reduce the effectiveness of treatment, so try to take Nerlynx consistently at the same time each day.
Overdose
If you take more Nerlynx than prescribed, contact your doctor or go to a hospital emergency department immediately. Bring the medicine packaging with you. Symptoms associated with overdose may include diarrhoea, nausea, vomiting, and dehydration. Treatment is supportive, as there is no specific antidote for neratinib overdose.
Do not stop taking Nerlynx without first consulting your doctor. Discontinuing treatment prematurely may reduce its protective benefit against cancer recurrence. If you are experiencing side effects, your doctor can adjust the dose or provide additional supportive care.
What Are the Side Effects of Nerlynx?
Like all medicines, Nerlynx can cause side effects, although not everyone gets them. The most significant side effect is diarrhoea, which affects the majority of patients and requires proactive management from day one. Liver function changes, skin reactions, and fatigue are also reported.
Diarrhoea
Diarrhoea is the most common and clinically significant side effect of Nerlynx. It typically occurs early in treatment, often within the first month, and can be severe and recurrent. Without prophylactic anti-diarrhoeal treatment, diarrhoea can lead to dehydration, electrolyte imbalances, and potentially serious complications. See the dosage section above for mandatory diarrhoea prophylaxis instructions.
Contact your doctor if your diarrhoea does not improve despite anti-diarrhoeal medication, or if you feel dizzy or weak. If your doctor is unavailable, seek hospital attention immediately, as severe dehydration can be dangerous.
Liver Problems
Nerlynx can cause changes in liver function that are detectable through blood tests. You may or may not notice signs or symptoms of liver problems, which can include yellowing of the skin and/or eyes (jaundice), dark urine, or pale stools. Your doctor will monitor your liver function with regular blood tests throughout treatment and will stop Nerlynx if serious liver abnormalities develop.
Side Effect Frequency Overview
Very Common
May affect more than 1 in 10 people
- Diarrhoea
- Abdominal pain, nausea, vomiting
- Decreased appetite
- Inflammation of the mouth lining (stomatitis), including blisters and mouth ulcers
- Skin rash
- Muscle cramps (spasms)
- Severe fatigue
Common
May affect up to 1 in 10 people
- Urinary tract infection (burning sensation during urination, frequent or urgent need to urinate)
- Dehydration
- Fainting (syncope)
- Nosebleed (epistaxis)
- Bloating, indigestion (dyspepsia)
- Dry mouth
- Elevated liver enzymes (ALT and AST) in blood tests
- Nail problems (cracking, discolouration)
- Dry skin, including cracked skin
- Changes in kidney function tests
- Weight loss
Uncommon
May affect up to 1 in 100 people
- Kidney failure (renal failure)
- Elevated bilirubin in blood tests (indicator of liver function)
If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance.
Contact your doctor or go to a hospital immediately if you experience severe diarrhoea with signs of dehydration (dizziness, weakness, dry mouth, reduced urination), yellowing of the skin or eyes (jaundice), unusually dark urine, severe abdominal pain, or persistent vomiting that prevents you from keeping food or liquids down.
How Should You Store Nerlynx?
Keep Nerlynx out of the sight and reach of children. Store with the container tightly closed to protect from moisture. Do not use after the expiry date printed on the bottle and carton.
Nerlynx does not require any special temperature storage conditions. The film-coated tablets are packaged in a white, round, high-density polyethylene (HDPE) bottle with a child-resistant polypropylene closure and an inner foil safety seal. Each bottle contains 180 film-coated tablets along with a desiccant canister containing 1 g of silica gel.
- Keep the bottle tightly closed at all times to protect from moisture
- Do not swallow the desiccant canister – keep it inside the bottle with the tablets
- Check the expiry date (marked “EXP”) before taking any tablets – the expiry date refers to the last day of the stated month
- Do not use Nerlynx if the packaging appears damaged or if there are signs of tampering (e.g., broken inner seal)
Do not flush unused tablets down the toilet or throw them in household waste. Return any unused or expired medication to your pharmacy for safe disposal. These measures help protect the environment from pharmaceutical contamination.
What Does Nerlynx Contain?
Each Nerlynx film-coated tablet contains neratinib maleate equivalent to 40 mg of neratinib, along with inactive ingredients necessary for tablet manufacture. The tablets are red, oval-shaped, and imprinted with “W104” on one side.
Active Ingredient
The active substance is neratinib. Each film-coated tablet contains neratinib maleate equivalent to 40 mg of neratinib. Neratinib maleate is the salt form used to optimise the drug’s solubility and bioavailability.
Inactive Ingredients (Excipients)
The other ingredients are:
- Tablet core: mannitol (E421), microcrystalline cellulose, crospovidone, povidone, colloidal anhydrous silica, magnesium stearate
- Film coating: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, red iron oxide (E172)
Tablet Appearance and Packaging
Nerlynx tablets are red, oval-shaped film-coated tablets imprinted with “W104” on one side and plain on the other. They are supplied in a white round HDPE bottle with a child-resistant polypropylene closure containing 180 tablets. A desiccant canister (1 g silica gel) is included in each bottle – do not swallow the desiccant.
Marketing Authorisation Holder
Pierre Fabre Médicament, Les Cauquillous, 81500 Lavaur, France. The tablets are manufactured by Pierre Fabre Médicament Production at the Cahors site in France.
Frequently Asked Questions About Nerlynx
Nerlynx (neratinib) is used as extended adjuvant treatment for adults with hormone receptor-positive, HER2-overexpressed or amplified early-stage breast cancer. It is prescribed after completion of prior trastuzumab-based adjuvant therapy (within the past year) to reduce the risk of cancer recurrence. By irreversibly blocking HER2 signalling, Nerlynx provides continued protection beyond the initial trastuzumab treatment.
Diarrhoea is caused by neratinib’s inhibition of HER receptors in the gastrointestinal tract, which disrupts normal fluid absorption. It is the most common side effect, occurring in the majority of patients and typically starting within the first month. Management requires prophylactic loperamide from the first dose, continued for 1–2 months. Dietary adjustments, adequate hydration, and dose reductions may also be necessary. Contact your doctor if diarrhoea persists or becomes severe.
The standard course of treatment with Nerlynx is one year (12 months) of continuous daily dosing. You take 240 mg (six 40 mg tablets) once daily with food. The full treatment duration is important for maximum benefit in reducing cancer recurrence risk. Do not stop treatment early without consulting your oncologist, even if you feel well.
Proton pump inhibitors (PPIs) such as omeprazole and lansoprazole are not recommended with Nerlynx because they significantly reduce neratinib absorption by raising stomach pH. H2-receptor antagonists (such as ranitidine or famotidine) should be taken at least 2 hours before or 10 hours after Nerlynx. Antacids must be separated from Nerlynx by at least 3 hours. Always discuss any acid-reducing medications with your oncologist before starting Nerlynx.
Yes, Nerlynx can cause changes in liver function that are detectable through routine blood tests (elevated ALT, AST, and bilirubin). Your doctor will check liver function before starting treatment and at regular intervals throughout the treatment year. If serious abnormalities are detected, your dose may be reduced or treatment may be stopped. Report any symptoms such as yellowing of the skin or eyes, dark urine, or unusual fatigue to your doctor immediately.
While taking Nerlynx, you should avoid grapefruit and pomegranate (fruit, juice, or supplements) as they can increase neratinib blood levels unpredictably. Avoid strong CYP3A4 inducers including rifampicin, carbamazepine, phenytoin, and St John’s Wort, which are contraindicated. Proton pump inhibitors should also be avoided. Women of childbearing potential must use effective contraception during treatment and for one month after, and men must use barrier contraception for three months after the last dose.
References
This article is based on the following international medical guidelines and peer-reviewed sources. All medical claims have evidence level 1A, the highest quality of evidence based on systematic reviews of randomised controlled trials.
- Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2017;18(12):1688–1700. doi:10.1016/S1470-2045(17)30717-9
- Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): updated efficacy analysis. The Lancet Oncology. 2021;22(6):743–755.
- European Medicines Agency (EMA). Nerlynx (neratinib) – Summary of Product Characteristics. EMA product information database. Updated 2025.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2025.
- European Society for Medical Oncology (ESMO). Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2024;35(2):159–182.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd list. Geneva: WHO; 2023.
- Barcenas CH, Hurvitz SA, Di Palma JA, et al. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Annals of Oncology. 2020;31(9):1223–1230.
- British National Formulary (BNF). Neratinib. NICE BNF monograph. Accessed December 2025.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, a group of licensed specialist physicians with expertise in oncology, clinical pharmacology, and breast cancer treatment.
Medical Writers
Board-certified physicians specialising in medical oncology and clinical pharmacology with documented academic and clinical experience in breast cancer treatment.
Medical Reviewers
Independent review board ensuring clinical accuracy, adherence to international guidelines (ESMO, ASCO, NCCN, WHO), and evidence level 1A standards.
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