Nerlynx 40 mg film-coated tablets

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Nerlynx is and what it is used for
2. What you need to know before you take Nerlynx
3. How to take Nerlynx
4. Possible side effects
5. How to store Nerlynx
6. Contents of the pack and other information

Nerlynx contains the active substance ‘neratinib’. It belongs to a group of medicines called ‘tyrosine kinase inhibitors’ used to block cancer cells and treat breast cancer.

Nerlynx is used for patients who have early stage breast cancer which:

• is hormone receptor positive (HR-positive) and human epidermal growth factor receptor 2-positive (HER2) overexpressed/amplified (HER2-positive), and
• has previously been treated with trastuzumab based therapy that ended less than one year ago.

The ‘HER2 receptor’ is a protein found on the surface of cells in the body. It helps control how a healthy breast cell grows. In HER2-overexpressed/amplified breast cancer, the cancer cells have an increased amount of HER2 receptors on their surface. This results in the cancer cells dividing and growing faster.

‘Hormone receptors’ are also proteins expressed inside the cells of some specific tissues. Estrogens and progesterone bind to these proteins and regulate cell activity. In HR-positive breast cancer, tumor cell division and growth can be enhanced by estrogens and/or progesterone.

Before Nerlynx is used, your cancer must have been tested to show it is HR-positive and HER2-overexpressed/amplified. You must also have previously been treated with trastuzumab based therapy.

Nerlynx works by blocking the HER2 receptors on the cancer cells. This helps to stop the cells from dividing and growing.

• if you are allergic to neratinib or any of the other ingredients of this medicine (listed in section 6),
• if you have a severe liver problem (corresponding to class C on the Child-Pugh score),
• if you are taking a medicine that strongly induces liver enzymes (CYP3A4) and/or drugs transporter (P-gp) such as:
  • rifampicin (a medicine for tuberculosis (TB)),
  • carbamazepine or phenytoin (medicines for seizures),
  • St. John’s wort (herbal product for depression).

Talk to your doctor or pharmacist before taking Nerlynx.

Nerlynx can cause diarrhoea early during treatment. It can appear more than one time. You should take an anti-diarrhoea medicine that your doctor has recommended so that your diarrhoea does not become severe, and to prevent you from getting dehydrated during treatment with Nerlynx. Dietary changes (including adapted fluid intake) and appropriate dose modifications of Nerlynx might be needed for diarrhoea management.

Nerlynx can cause changes in liver function – these are shown in blood tests. Your doctor will do blood tests before and during your treatment with Nerlynx. Your doctor will stop your treatment with Nerlynx if your liver tests show severe problems.

You should be closely monitored by your doctor if you suffer from:

• Reduced kidney function
• Chronic gastrointestinal disorder
• Cardiac disorders or if you have history of heart disease
• Skin and subcutaneous tissue disorders.

If you are 65 or over you should be closely monitored by your doctor.

Do not use in children and adolescents under 18 years of age. The safety of Nerlynx and how effective it is has not been studied in this age group.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. The efficacy and/or safety of Nerlynx and/or other medicines might be modified when taken concomitantly. This is because Nerlynx can affect the way some other medicines work. Also some other medicines can affect the way Nerlynx works.

In some cases, dose modifications or close monitoring can be done by your doctor.

In particular tell your doctor or pharmacist if you are taking any of the following medicines:

• rifampicin - a medicine for tuberculosis
• carbamazepine, phenobarbital, phenytoin or primidone - medicines for seizures
• St John’s wort - an herbal product for depression
• ketoconazole, voriconazole, itraconazole or fluconazole - medicines for fungal infections
• erythromycin, clarithromycin, troleandomycin or ciprofloxacine - medicines for bacterial infections
• protease inhibitors (such as ritonavir, lopinavir, saquinavir, nelfinavir, atazanavir, indinavir, efavirenz, etravirine) or medicine used in combination with antiretroviral therapy in HIV (cobicistat) - antiviral medicines
• nefazodone - a medicine to treat depression
• diltiazem or verapamil - medicines for high blood pressure and chest pain
• bosentan - a medicine for high blood pressure in pulmonary arteria
• dabigatran or digoxin - a medicine for heart problems
• Statin medicine (such as rosuvastatin) - a medicine to treat high cholesterolemia
• doxamethasone - an anti inflammatory medicine (corticosteroids)
• colchicine - an anti inflammatory medicine used in gout
• irinotecan - a medicine used in colorectal cancers
• sulfasalazine - an anti-inflammatory intestinal medicine
• cyclosporine, everolimus, sirolimus and tacrolimus - immunosuppressant medicine
• fluvoxamine - a drug used to treat depressive states and obsessive-compulse disorders
• medicines for stomach problems:
  • proton pump inhibitors’ or PPIs are not recommended (such as lansoprazole, omeprazole)
  • “H2 receptor antagonists” (such as ranitidine). Nerlynx should be taken at least 2 hours before or 10 hours after the intake of the H2-receptor antagonist.
  • antacid medicines. The dose of these medicines and Nerlynx should be separated by at least 3 hours.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking Nerlynx.

Do not take grapefruit or pomegranate while you are taking Nerlynx – this includes eating them, drinking the juice or taking a supplement that might contain them. This is because these fruits may interact with Nerlynx and affect how the medicine works.

If you are pregnant, the doctor will assess the potential benefit to you and the risk to the foetus before giving this medicine to you. If you become pregnant while taking this medicine, the doctor will assess the potential benefit to you and the risk to the foetus, of continuing treatment with this medicine.

Women who can become pregnant must use an effective method of contraception, including a barrier method:

• while taking Nerlynx and
• for one month after treatment has finished.

Men must use an effective barrier method of contraception such as a condom:

• while taking Nerlynx and
• for three months after treatment has finished.

Talk to your doctor before taking Nerlynx if you are breast-feeding or plan to breast-feed because it is unknown if small amounts of this medicine may pass into your breast milk. Your doctor will discuss with you the benefits and risks of taking Nerlynx during this time.

Nerlynx has minor influence on the ability to drive and use machines. The side effects of Nerlynx (for example, dehydration and dizziness resulting from diarrhoea, fatigue, and fainting) may affect how tasks that require judgment, motor or cognitive skills are carried out.

The recommended dose of Nerlynx is 6 tablets once a day (a total of 240 mg).

• Take the tablets with food. Do not crush or dissolve them.
• Take all the tablets with water, at about the same time each day, preferably in the morning.

The course of treatment is one year.

If you get side effects, your doctor may adjust the dose or stop treatment temporarily or permanently.

Nerlynx can cause diarrhoea early during treatment unless anti-diarrhoea medicine is taken to prevent or reduce diarrhoea. Diarrhoea usually happens early in treatment with Nerlynx and may be severe and recurrent, causing you to get dehydrated. Your doctor will tell you how to adapt your diet and fluid intake.

• Start taking the anti-diarrhoea medicine prescribed by your doctor with the first dose of Nerlynx.
• Your doctor will tell you how to take the anti-diarrhoea medicine.
• Keep taking anti-diarrhoea medicine during the first one to two months of Nerlynx treatment. Your doctor will tell you if you need to keep taking anti-diarrhoea medicine after the first two months to control your diarrhoea.
• Your doctor will also tell you if you need to change the dose of Nerlynx because of diarrhoea.

If you take more Nerlynx than you should, contact a doctor or a hospital straight away. Take the medicine pack with you.

Some side effects associated with taking more Nerlynx than you should are: diarrhoea, nausea, vomiting and dehydration.

• If you forget a dose, wait until the next day before you take the next dose.
• Do not take a double dose to make up for a forgotten dose.

• Do not stop taking Nerlynx without talking to your doctor.

Nerlynx can cause diarrhoea (increase in number per day and/or change in stool consistency) early during treatment unless anti-diarrhoeal medicines are taken to prevent or reduce diarrhoea. The diarrhoea may be severe, and you may get dehydrated. See section 3 for more information about the anti-diarrhoea treatment you need to take at the same time as Nerlynx.

Talk to your doctor if:

• you are having diarrhoea that does not go away - they can advise how to control your diarrhoea.
• you feel dizzy or weak from diarrhoea. If your doctor is not available go to the hospital immediately.

Nerlynx can cause changes in liver function - these are shown in blood tests. You may or may not have signs or symptoms of liver problems (e.g., yellow skin and/or eyes, dark urine, or light-colour stools). Your doctor will do blood tests before and during your treatment with Nerlynx. Your doctor will stop your treatment with Nerlynx if your liver tests show severe problems.

Tell your doctor or pharmacist if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people):

• diarrhoea
• stomach pain, feeling sick (nausea), being sick (vomiting), decreased appetite
• inflammation of the lining of the mouth, including blisters or mouth ulcers
• rash
• muscle spasms or cramps
• feeling very tired

Common (may affect up to 1 in 10 people):

• burning sensation during urination, frequent and urgent need to urinate, (may be symptoms of urinary tract infection)
• dehydration
• fainting
• nosebleed
• mild stomach upset (bloating, indigestion)
• dry mouth
• changes in liver blood test results (enzymes named alanine aminotransferase and aspartate aminotransferase increased)
• nail problems including nail splitting or colour change
• dry skin including cracked skin
• changes in kidney function test
• weight loss

Uncommon (may affect up to 1 in 100 people):

• kidney failure
• changes in liver blood test results (i.e., blood bilirubin increased)

Tell your doctor or pharmacist if you notice any of the side effects above.

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is neratinib. Each film-coated tablet contains neratinib maleate, equivalent to 40 mg neratinib.
• The other ingredients are:
  • Tablet core: mannitol (E421), microcrystalline cellulose, crospovidone, povidone, colloidal anhydrous silica, magnesium stearate
  • Tablet coating: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, iron oxide red (E172)

The film-coated tablets are red oval shaped and debossed with ‘W104’ on one side and plain on the other side.

Nerlynx film-coated tablets are packaged in a white, high-density polyethylene (HDPE) round bottle with child-resistant, polypropylene closure, and foil induction inner seal for a tamper-evident seal. Each bottle contains 180 film-coated tablets.

An HDPE desiccant canister with 1 g silica gel is enclosed with the tablets in each bottle. Do not swallow the desiccant. Keep it inside the bottle.