TYVERB 250 mg FILM-COATED TABLETS

2. What you need to know before you take Tyverb

Do not take Tyverb

• if you are allergic to lapatinib or any of the other ingredients of this medicine (listed in section 6).

Be cautious with Tyverb

Your doctor will perform tests to check that your heart is working properlybefore and during treatment with Tyverb.

Before taking Tyverb, tell your doctor if you have any heart problems.

Before starting Tyverb, your doctor also needs to know:

• if you have any lung disease
• if you have lung inflammation
• if you have any liver problems
• if you have any kidney problems.
• if you have diarrhea (see section 4)

Your doctor will perform tests to check that your liver is working properlybefore and during treatment with Tyverb.

Tell your doctorif you are in any of these situations.

Severe skin reactions

Severe skin reactions have been observed with the use of Tyverb. Symptoms may include skin rash, blisters, and skin peeling.

Tell your doctor as soon as possible if you experience any of these symptoms.

Other medicines and Tyverb

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.This includes herbal medicines and medicines obtained without a prescription.

It is especially important that you tell your doctorif you are using or have recently used any of the following medicines. Some medicines may affect how Tyverb works or Tyverb may affect how other medicines work. These medicines include medicines from the following groups:

• St. John's Wort – a herbal extract used for the treatment of depression

• erythromycin, ketoconazole, itraconazole, posaconazole, voriconazole, rifabutin, rifampicin, telithromycin – medicines used for the treatment of infections
• cyclosporin – a medicine used to suppress the immune system, for example, after organ transplantation
• ritonavir, saquinavir – medicines used for the treatment of HIV
• phenytoin, carbamazepine – medicines used for the treatment of epileptic seizures
• cisapride – a medicine used for the treatment of some digestive system problems
• pimozide – a medicine used for the treatment of some mental health problems
• quinidine, digoxin – medicines used for the treatment of some heart problems
• repaglinide – a medicine used for the treatment of diabetes
• verapamil – a medicine used for the treatment of high blood pressureor heart problems(angina pectoris)
• nefazodone – a medicine used for the treatment of depression
• topotecan, paclitaxel, irinotecan, docetaxel – medicines used for the treatment of some types of cancer
• rosuvastatin – a medicine for the treatment of high cholesterol
• medicines that reduce stomach acidity - used for the treatment of stomach ulcersor indigestion.

Tell your doctorif you are using or have recently used any of these medicines.

Your doctor will review the medicines you are taking to ensure that you are not taking any medicine that should not be taken with Tyverb. Your doctor will advise you if there is an alternative available.

Taking Tyverb with food and drink

Do not drink grapefruit juice while you are being treated with Tyverb.It may affect how this medicine works.

Pregnancy and breastfeeding

Tyverb should not be used during pregnancy unless your doctor specifically recommends it.

• Tell your doctor if you are pregnantor planning to become pregnant.
• Use an effective method of contraceptionto prevent pregnancy while you are taking Tyverb and for at least 5 days after the last dose.
• Tell your doctor if you become pregnantduring treatment with Tyverb.

It is not known if Tyverb passes into breast milk. Do not breastfeed while you are taking Tyverb and for at least 5 days after the last dose.

• Tell your doctor if you are breastfeedingor planning to breastfeed.

If you are unsure, consult your doctor or pharmacistbefore taking Tyverb.

Driving and using machines

You are responsible for deciding whether you are able to drive a vehicle or perform tasks that require high concentration. Due to the possible side effects of Tyverb, your ability to drive or operate machinery may be affected. These effects are described in section 4, "Possible side effects".

Tyverb contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is, essentially "sodium-free".

3. How to take Tyverb

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

Your doctor will decide the correct dose of Tyverb depending on the type of breast cancer being treated.

If you are prescribed Tyverb in combination with capecitabine, the usual dose is 5 Tyverb tablets per day, in a single dose.

If you are prescribed Tyverb in combination with trastuzumab, the usual dose is 4 Tyverb tablets per day, in a single dose.

If you are prescribed Tyverb in combination with an aromatase inhibitor, the usual dose is 6 Tyverb tablets per day, in a single dose.

Take the dose that has been prescribed for you every day for the time that your doctor indicates.

Your doctor will inform you about the dose of the other anticancer medicine and how to take it.

Taking the tablets

• Swallow the tablets whole with water, one after the other, at the same time every day.
• Take Tyverb at least one hour before or one hour after food.Take Tyverb every day at the same time in relation to meals, for example, you can take the tablets every day one hour before breakfast.

While taking Tyverb

• Depending on the side effects you experience, your doctor may recommend reducing the dose or temporarily stopping treatment.
• Your doctor will perform tests to check the functioning of your heart and liver before and during treatment with Tyverb.

If you take more Tyverb than you should

Contact your doctor or pharmacist immediately. If possible, show them the pack.

If you forget to take Tyverb

Do not take a double doseto make up for forgotten doses. Take the next dose at the scheduled time.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

A severe allergic reaction is a rare side effectthat may affect up to 1 in 1,000 people and may appear rapidly.

Symptoms may include:

• skin rash (including itching, presence of papules)
• unusual wheezing or difficulty breathing
• swollen eyelids, lips, or tongue
• muscle or joint pain
• collapse or fainting.

Tell your doctor immediatelyif you have any of these symptoms. Do not take any more tablets.

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

• diarrhea (which can cause dehydration and lead to more serious complications)

Tell your doctor immediately if you have any sign of diarrhea, as it is very important that diarrhea is treated immediately. Also, tell your doctor immediately if diarrhea worsens.You can find more advice on how to reduce the risk of diarrhea at the end of section 4.

• rash, dry skin, itching

Tell your doctor if you have a skin rash.You can find more advice on how to reduce the risk of skin rash in section 4.

Other very common side effects:

• loss of appetite
• nausea
• vomiting
• fatigue, weakness
• indigestion
• constipation
• mouth inflammation/ulcers in the mouth
• stomach pain
• sleeping problems
• back pain
• pain in hands and feet
• pain in joints and back
• a skin reaction on the palms of the hands or soles of the feet (including tingling, numbness, pain, swelling, or redness)
• cough, difficulty breathing
• headache
• nasal bleeding
• hot flushes
• unusual hair loss or fragility.

Tell your doctorif any of these side effects become serious or troublesome.

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

• an effect on the functioning of your heart.

In most cases, the effect on your heart will not have any symptoms. If you experience symptoms associated with this side effect, they are likely to include irregular heartbeat and difficult breathing.

• liver problems, which can cause itching, yellow eyes or skin (jaundice), dark urine, or pain or discomfort in the upper right part of the stomach

• nail changes, such as a tendency to develop infection and inflammation of the cuticles
• skin fissures (deep cracks in the skin or cracked skin)

Tell your doctor if you have any of these symptoms.

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

• treatment-induced lung inflammation, which can cause shortness of breath or cough.

Tell your doctor immediately if you have any of these symptoms.

Other uncommon side effects include:

• blood test results showing changes in liver function (usually mild and temporary)

Rare side effects(may affect up to 1 in 1,000 people):

• severe allergic reactions (see the beginning of section 4)

Frequency not known (cannot be estimated from the available data):

• irregular heartbeat (change in the electrical activity of the heart)
• a severe skin reaction that can include: rash, skin redness, blisters on the lips, eyes, or mouth, skin dryness, fever, or any combination of these.
• pulmonary arterial hypertension (high blood pressure in the arteries (blood vessels) that go to the lungs)

If you have other side effects

Tell your doctor or pharmacistif you notice any side effects not mentioned in this leaflet.

Reducing the risk of diarrhea and skin rash

Tyverb can cause severe diarrhea

If you experience diarrhea while taking Tyverb:

• drink plenty of fluids (8-10 glasses a day), such as water, sports drinks, or other clear drinks
• eat low-fat, high-protein foods instead of fatty or spicy foods
• eat cooked vegetables instead of raw vegetables and remove the skin from fruits before eating them
• avoid milk and dairy products (including ice cream)
• avoid herbal supplements (some may cause diarrhea).

Tell your doctorif your diarrhea continues.

Tyverb can cause skin rash

Your doctor will perform skin checks before and during treatment.

To care for sensitive skin:

• wash with a soap-free product
• use hypoallergenic, fragrance-free beauty products
• use sunscreens (sun protection factor (SPF) 30 or higher).

Tell your doctorif you have a skin rash.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible that they 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 Tyverb

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 blister or carton.

Do not store above 30°C.

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

6. Package Contents and Additional Information

Tyverb Composition

• The active ingredient of Tyverb is lapatinib. Each film-coated tablet contains lapatinib ditosylate monohydrate, equivalent to 250 mg of lapatinib.
• The other ingredients are: microcrystalline cellulose, povidone (K30), sodium carboxymethyl starch (Type A), magnesium stearate, hypromellose, titanium dioxide (E171), macrogol (400), polysorbate 80, yellow iron oxide (E172) and red iron oxide (E172).

Product Appearance and Package Contents

Tyverb film-coated tablets are oval, biconvex, yellow, film-coated, with “GS XJG” engraved on one side.

Tyverb is supplied in blister packs or bottles:

Blister Packs

Each Tyverb package contains 70 or 84 tablets in an aluminum blister pack of 10 or 12 tablets. Each blister pack has a perforation in the middle that allows them to be divided into two blister packs of 5 or 6 tablets, depending on the package size.

Tyverb is also available in multiple packs with 140 tablets, which contain 2 boxes of 70 tablets.

Bottles

Tyverb is also available in plastic bottles containing 70, 84, 105, or 140 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Lek Pharmaceuticals d.d.

Verovškova 57

1526 Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovškova ulica 57

1000 Ljubljana

Slovenia

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Glaxo Wellcome, S.A.

Avda. Extremadura, 3

09400 Aranda de Duero, Burgos

Spain

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Sandoz S.R.L.

Str. Livezeni nr. 7A

540472 Targu Mures

Romania

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.