NERLYNX 40 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Nerlynx 40mg film-coated tablets

neratinib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Nerlynx and what is it used for

What is Nerlynx

Nerlynx contains the active substance «neratinib». It belongs to a group of medicines called «tyrosine kinase inhibitors», which are used to block cancer cells and treat breast cancer.

What Nerlynx is used for

Nerlynx is used in patients with early-stage breast cancer who:

• have positive hormonal receptors (HR-positive) and overexpressed/amplified human epidermal growth factor receptor 2 (HER2-positive), and

have been previously treated with trastuzumab-based therapy that ended less than a year ago.

The «HER2 receptor» is a protein found on the surface of body cells that helps control the growth of normal breast cells. In HER2-positive breast cancer, cancer cells have more HER2 receptors on their surface. This makes the cancer cells divide and grow faster.

«Hormone receptors» are also proteins expressed within the cells of some specific tissues. Estrogen and progesterone bind to these proteins and regulate cell activity. In HR-positive breast cancer, estrogen and/or progesterone may promote the division and growth of tumor cells.

Before using Nerlynx, it is necessary to analyze your cancer to confirm that it is HR-positive and HER2 overexpressed/amplified. Additionally, you should have received prior treatment with trastuzumab-based therapy.

How Nerlynx works

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

2. What you need to know before you take Nerlynx

Do not take Nerlynx

• 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 Child-Pugh class C),
• if you are taking a medicine that strongly induces liver enzymes (CYP3A4) and/or the drug transporter (P-gp) such as:
• rifampicin (a medicine for tuberculosis (TB)),
• carbamazepine or phenytoin (medicines for seizures),
• St. John's Wort or hypericum (a herbal medicine for depression).

Warnings and precautions

Consult your doctor or pharmacist before starting Nerlynx.

When you start treatment with Nerlynx, you will need to take a medicine for diarrhea

Nerlynx may cause diarrhea at the beginning of treatment. It can occur more than once. You should take a medicine for diarrhea that your doctor has recommended so that the diarrhea does not worsen and to avoid dehydration during treatment with Nerlynx. Changes in diet (including adapted fluid intake) and appropriate dose adjustments of Nerlynx may be necessary to manage diarrhea.

Tests and checks to detect liver problems

Nerlynx may cause changes in liver function, which are detected in blood tests. Your doctor will perform blood tests before and during treatment with Nerlynx and will interrupt treatment with Nerlynx if liver tests show severe problems.

Your doctor should closely monitor you if you have:

• Reduced kidney function
• Chronic gastrointestinal disorder
• Heart problems or history of heart disease
• Skin and subcutaneous tissue disorders

Elderly patients:

If you are 65 years or older, your doctor should closely monitor you.

Children and adolescents

Nerlynx should not be used in children and adolescents under 18 years. The safety and efficacy of Nerlynx in this age group have not been studied.

Other medicines and Nerlynx

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 may be affected when taken together. This is because Nerlynx may affect the way other medicines work. Additionally, some medicines may affect the way Nerlynx works.

In some cases, your doctor may make dose adjustments or close monitoring.

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

• rifampicin, a medicine for tuberculosis (TB)
• carbamazepine, phenobarbital, phenytoin, or primidone, medicines for seizures
• St. John's Wort, a herbal medicine for depression
• ketoconazole, voriconazole, itraconazole, or fluconazole, medicines for fungal infections
• erythromycin, clarithromycin, troleandomycin, or ciprofloxacin, medicines for bacterial infections
• protease inhibitors (such as ritonavir, lopinavir, saquinavir, nelfinavir, atazanavir, indinavir, efavirenz, etravirine) or medicines used in combination with antiretroviral therapy for HIV (cobicistat), antiviral medicines
• nefazodone, a medicine for depression
• diltiazem or verapamil, medicines for high blood pressure and chest pain
• bosentan, a medicine for high blood pressure in the pulmonary artery
• dabigatran or digoxin, medicines for heart problems
• statin medicines (such as rosuvastatin), a medicine for high cholesterol
• dexamethasone, an anti-inflammatory medicine (corticosteroid)
• colchicine, an anti-inflammatory medicine used for gout
• irinotecan, a medicine used for colorectal cancer
• sulfasalazine, an anti-inflammatory intestinal medicine
• cyclosporin, everolimus, sirolimus, and tacrolimus: immunosuppressant medicines
• fluvoxamine, a medicine used to treat depressive states and obsessive-compulsive disorders
• medicines for stomach problems:
• proton pump inhibitors or PPIs whose use is not recommended (such as lansoprazole, omeprazol)
• "H2 receptor antagonists" (such as ranitidine). Neratinib should be taken at least 2 hours before or 10 hours after taking the H2 receptor antagonist.
• antacids, the intake of these medicines and Nerlynx should be spaced at least 3 hours apart.

If any of the above applies to you (or if you have any doubts), consult your doctor or pharmacist before taking Nerlynx.

Taking Nerlynx with food and drinks

Do not take grapefruit or pomegranate while taking Nerlynx; this includes eating it, drinking its juice, or taking supplements that may contain it. The reason is that these fruits may interact with Nerlynx and affect its functioning.

Pregnancy

If you are pregnant, your doctor will assess the potential benefits for you and the risks for the fetus before prescribing this medicine. If you become pregnant while taking this medicine, your doctor will assess the potential benefits for you and the risks for the fetus from continuing treatment with this medicine.

Contraception

Women who may become pregnant must use an effective contraceptive method, including a barrier method:

• while taking Nerlynx and
• for one month after finishing treatment.

Men must use an effective barrier contraceptive method, such as a condom:

• while taking Nerlynx and
• for three months after finishing treatment.

Breast-feeding

Consult your doctor before taking Nerlynx if you are breast-feeding or plan to breast-feed, as it is unknown whether small amounts of this medicine can pass into breast milk. Your doctor will explain the benefits and risks of taking Nerlynx during this period.

Driving and using machines

Nerlynx has a minor influence on the ability to drive and use machines. The side effects of Nerlynx (e.g., dehydration and dizziness due to diarrhea, fatigue, and fainting) may affect the way tasks that require judgment and motor or cognitive skills are performed.

3. How to take Nerlynx

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

How much Nerlynx should you take

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 the tablets.
• Take all the tablets with water, approximately at the same time each day, preferably in the morning.

The duration of treatment is one year.

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

When you start treatment with Nerlynx, you will need to take a medicine for diarrhea

Nerlynx may cause diarrhea at the beginning of treatment unless an anti-diarrheal medicine is used to prevent or reduce diarrhea. Diarrhea usually occurs at the beginning of treatment with Nerlynx and can be severe and recurrent, causing dehydration. Your doctor will advise you on how to adapt your diet and fluid intake.

• Start taking the anti-diarrheal medicine prescribed by your doctor with the first dose of Nerlynx.
• Your doctor will tell you how to take the anti-diarrheal medicine.
• Continue taking the anti-diarrheal medicine during the first month or the first two months of treatment with Nerlynx. Your doctor will tell you if you need to continue taking it after the first two months.
• Your doctor will also tell you if you need to change the dose of Nerlynx due to diarrhea.

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

Some side effects that may occur if you take more Nerlynx than you should are: diarrhea, nausea, vomiting, and dehydration.

If you forget to take Nerlynx

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

If you stop taking Nerlynx

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may occur with this medicine:

Diarrhea

Nerlynx may cause diarrhea (an increase in the number per day and/or a change in the consistency of the stool) at the beginning of treatment unless anti-diarrheal medicines are used to prevent or reduce diarrhea. Diarrhea can be severe and cause dehydration. See section 3 for more information on the anti-diarrheal medicine you should take at the same time as Nerlynx.

Tell your doctor if:

• diarrhea does not go away; your doctor may give you advice on how to control diarrhea.
• you feel weak or dizzy due to diarrhea; if your doctor is not available, go to the hospital immediately.

Liver problems

Nerlynx may cause changes in liver function, which are detected in blood tests. You may or may not have signs or symptoms of liver problems (e.g., yellowing of the skin or eyes, dark urine, or light-colored stools). Your doctor will perform blood tests before and during treatment with Nerlynx and will interrupt treatment with Nerlynx if liver tests show severe problems.

Other side effects

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

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

• diarrhea
• stomach pain, nausea, vomiting, decreased appetite
• inflammation of the mouth mucosa, with blisters or sores in the mouth
• rash
• muscle spasms or cramps
• extreme fatigue

Common(may affect up to 1 in 10 people)

• burning sensation while urinating, frequent and urgent need to urinate (may be symptoms of urinary tract infection)
• dehydration
• fainting
• nosebleeds
• mild stomach discomfort (bloating, indigestion)
• dry mouth
• changes in blood test results that measure liver function (the enzymes called alanine aminotransferase and aspartate aminotransferase increase)
• nail problems, such as brittle or discolored nails
• dry skin, including cracked skin
• changes in kidney function tests
• weight loss

Uncommon(may affect up to 1 in 100 people)

• kidney failure
• changes in blood test results that measure liver function (i.e., elevated bilirubin in the blood)

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible that the side effects are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Nerlynx

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage temperature.

Keep the bottle tightly closed to protect it from moisture.

Do not use Nerlynx if you notice signs of damage to the packaging or if there are signs of tampering (e.g., if the inner seal is broken).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Nerlynx

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

Appearance of the product and pack contents

The film-coated tablets are red, oval with «W104» engraved on one side and smooth on the other side.

Nerlynx film-coated tablets are presented in a white high-density polyethylene (HDPE) round bottle with a child-resistant closure made of polypropylene and an inner aluminum induction seal. Each bottle contains 180 film-coated tablets.

A desiccant bag made of HDPE with 1 g of silica gel is included with the tablets in each bottle. Do not ingest the desiccant. Keep it inside the bottle.

Marketing authorization holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Manufacturer

Pierre Fabre Médicament Production – Cahors

Site de Cahors

Le Payrat

46000 Cahors

France

Date of last revision of this leaflet: MM/AAAA

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.