GLIVEC

Package leaflet: Information for the user

Glivec 100 mg hard capsules

imatinib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Glivec is and what it is used for

Glivec is a medicine containing an active substance called imatinib. In the diseases listed below,
this medicine works by inhibiting the growth of abnormal cells. These include certain types of
cancer.
Glivec is indicated in adult and pediatric patients for the treatment of:

• Chronic myeloid leukemia (CML). Leukemia is a cancer of the white blood cells. White blood cells normally help the body fight infections. Chronic myeloid leukemia is a type of leukemia in which certain abnormal white blood cells (called myeloid cells) begin to grow uncontrollably.
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Leukemia is a cancer of the white blood cells. White blood cells normally help the body fight infections. Acute lymphoblastic leukemia is a type of leukemia in which certain abnormal white blood cells (called lymphoblasts) begin to grow uncontrollably. Glivec inhibits the growth of these cells.

Glivec is also indicated in adult patients for the treatment of:

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of hematological disorders in which certain blood cells begin to grow uncontrollably. Glivec inhibits the growth of these cells in certain subtypes of these diseases.
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL). These are blood disorders in which certain blood cells (called eosinophils) begin to grow uncontrollably. Glivec inhibits the growth of these cells in a specific subtype of these diseases.
• Malignant gastrointestinal stromal tumors (GIST). GIST is a neoplasm of the stomach and intestine. It arises from the uncontrolled growth of cells supporting the tissues of these organs.
• Dermatofibrosarcoma protuberans (DFSP). DFSP is a tumor of the subcutaneous tissue in which certain cells begin to grow uncontrollably. Glivec inhibits the growth of these cells.

In the remainder of this patient information leaflet, abbreviations will be used when referring to these diseases.
If you have any questions about how Glivec works or why Glivec has been prescribed for you,
please consult your doctor.

2. What you need to know before taking Glivec

Glivec will only be prescribed by doctors experienced in the use of medicines for the treatment of blood cancers and solid tumors.
Carefully follow all your doctor's instructions, even if they differ from the information contained in this leaflet.
Do not take Glivec

• if you are allergic to imatinib or to any of the other ingredients of this medicine (listed in section 6). If this applies to you, consult your doctor before taking Glivec.

If you think you may be allergic but are unsure, ask your doctor for advice.
Warnings and precautions
Talk to your doctor before taking Glivec:

• if you have or have had liver, kidney, or heart problems.
• if you are taking the medicine levothyroxine because your thyroid gland has been removed.
• if you have ever had or may currently have hepatitis B infection. This is because Glivec can cause reactivation of hepatitis B, which in some cases may be fatal. Your doctor will carefully monitor you for signs of this infection before starting treatment.
• if you develop bruising, bleeding, fever, fatigue, or confusion while taking Glivec, contact your doctor. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA). If you are in any of these situations, consult your doctor before taking Glivec.

During treatment with Glivec, you may become more sensitive to sunlight. It is important to cover areas of skin exposed to the sun and to use sunscreen with a high sun protection factor (SPF).
These precautions also apply to children.
During treatment with Glivec, inform your doctor immediately if you gain weight rapidly. Glivec may cause your body to retain fluid (severe fluid retention).
While you are taking Glivec, your doctor will need to regularly check whether the medicine is working.
You will also have regular blood tests and be weighed regularly.
Children and adolescents
Glivec is also a treatment for children with CML. There is no experience in children with CML under 2 years of age. Experience is limited in children with Ph+ ALL and very limited in children with MDS/MPD, DFSP, GIST, and HES/LEC.
Some children and adolescents taking Glivec may have slower than normal growth. Your doctor will monitor growth at regular intervals.
Other medicines and Glivec
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription (such as paracetamol), and including herbal remedies (such as St. John’s wort). Some medicines may interfere with the effect of Glivec when taken together. They may increase or decrease the effect of Glivec, leading to an increase in side effects or making Glivec less effective. Glivec may have the same effect on other medicines.
Inform your doctor if you are using medicines that prevent blood clots.
Pregnancy, breastfeeding, and fertility

• If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
• Glivec is not recommended during pregnancy unless strictly necessary, as it may harm the unborn child. Your doctor will discuss with you the potential risks of taking Glivec during pregnancy.
• Women who could become pregnant are advised to use effective contraception during treatment and for 15 days after stopping treatment.
• Do not breastfeed during treatment with Glivec and for 15 days after stopping treatment, as it may harm the infant.
• Patients concerned about fertility during treatment with Glivec are advised to consult their doctor.

Driving and using machines
Dizziness, drowsiness, or blurred vision may occur while taking this medicine. If this happens, do not drive or operate tools or machinery until you feel well again.

3. How to take Glivec

Your doctor has prescribed Glivec because you suffer from a serious condition. Glivec can help you
fight this condition.
However, take this medicine exactly as instructed by your doctor or pharmacist. It is important that you do so until your doctor or pharmacist tells you otherwise. If you have any doubts, consult your doctor or pharmacist.
Do not stop taking Glivec unless your doctor tells you to. If you are unable to take the medicine as prescribed or feel you no longer need it, contact your doctor immediately.

How much Glivec to take
Use in adults
Your doctor will tell you exactly how many Glivec capsules you should take.

• If you are being treated for CML: Depending on your condition, the usual starting dose is either 400 mg or 600 mg:
  • 400 mg to be taken as 4 capsules once daily
  • 600 mg to be taken as 6 capsules once daily.
• If you are being treated for GIST: The starting dose is 400 mg, taken as 4 capsules once daily.

For both CML and GIST, your doctor may adjust your dose higher or lower depending on your response to treatment. If your daily dose is 800 mg (8 capsules), you should take 4 capsules in the morning and 4 capsules in the evening.

• If you are being treated for Ph+ ALL: The starting dose is 600 mg, taken as 6 capsules once daily.
• If you are being treated for MDS/MPD: The starting dose is 400 mg, taken as 4 capsules once daily.
• If you are being treated for HES/CEL: The starting dose is 100 mg, taken as one capsule once daily. Your doctor may decide to increase the dose to 400 mg (4 capsules once daily) based on your response to treatment.
• If you are being treated for DFSP: The dose is 800 mg daily (8 capsules), taken as 4 capsules in the morning and 4 capsules in the evening.

Use in children and adolescents
Your doctor will tell you how many Glivec capsules should be given to the child. The amount of Glivec administered will depend on the child's condition, weight, and height. The total daily dose must not exceed 800 mg in children with CML and 600 mg in children with Ph+ ALL. Treatment may be given to the child as a single daily dose or, alternatively, the daily dose may be divided into two administrations (half in the morning and half in the evening).

When and how to take Glivec

• Take Glivec with food. This will help protect your stomach when taking Glivec.
• Swallow the capsules whole with a large glass of water. Do not open or break the capsules unless you have difficulty swallowing (e.g., in children).
• If you are unable to swallow the capsules, you may open them and pour the powder into a glass of still water or apple juice.
• If you are pregnant or could become pregnant and need to open the capsules, handle the contents with caution to avoid contact with skin or eyes, or inhalation. Wash your hands immediately after opening the capsules.

How long to take Glivec
Continue taking Glivec every day for as long as your doctor tells you to.

If you take more Glivec than you should
If you have accidentally taken too many capsules, contact your doctor immediately. You may need medical attention. Bring the medicine pack with you.

If you forget to take Glivec

• If you forget a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
• Then continue with your regular dosing schedule.
• Do not take a double dose to make up for the missed one.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. These are generally mild to moderate.
Some side effects may be serious. Inform your doctor immediately if you experience
any of the following:

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

• Rapid weight gain. Glivec may cause your body to retain water (severe fluid retention).
• Signs of infection such as fever, severe chills, sore throat, or mouth ulcers. Glivec may reduce the number of white blood cells, making you more susceptible to infections.
• Unexpected bleeding or bruising (when you have not injured yourself).

Uncommon (may affect up to 1 in 100 people) or rare (may affect up to 1 in 1,000):

• Chest pain, irregular heartbeat (signs of heart problems).
• Cough, difficulty breathing or painful breathing (signs of lung problems).
• Feeling of dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Feeling unwell (nausea), with loss of appetite, dark-coloured urine, yellowing of the skin or eyes (signs of liver problems).
• Skin rash, redness with blisters on the lips, eyes, skin, or mouth, skin peeling, fever, raised red or purple spots on the skin, itching, burning sensation, pustular rash (signs of skin problems).
• Severe abdominal pain, presence of blood in vomit, stools, or urine, black stools (signs of gastrointestinal disorders).
• Marked decrease in urine output, feeling thirsty (signs of kidney problems).
• Feeling unwell (nausea) with diarrhoea and vomiting, abdominal pain, or fever (signs of intestinal problems).
• Severe headache, weakness or paralysis of limbs or face, difficulty speaking, sudden loss of consciousness (signs of nervous system problems such as bleeding or swelling in the skull/brain).
• Paleness, feeling tired and short of breath, dark-coloured urine (signs of low red blood cell levels).
• Eye pain or vision deterioration, bleeding in the eyes.
• Bone or joint pain (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Numbness or coldness in fingers or toes (signs of Raynaud's syndrome).
• Sudden swelling and redness of the skin (signs of a skin infection called cellulitis).
• Hearing problems.
• Muscle weakness and muscle spasms with abnormal heartbeat (signs of changes in blood potassium levels).
• Bruising (contusions).
• Stomach pain with feeling unwell (nausea).
• Muscle spasms with fever, red-brown urine, muscle pain or weakness (signs of muscle problems).
• Pelvic pain sometimes with nausea and vomiting, vaginal bleeding, feeling dizzy or fainting due to low blood pressure (signs of problems with ovaries and uterus).
• Nausea, shortness of breath, irregular heartbeat, cloudy urine, fatigue and/or joint problems associated with abnormal laboratory test results (e.g. high levels of potassium, uric acid and calcium, low levels of phosphorus in the blood).
• Blood clots in small blood vessels (thrombotic microangiopathy).

Not known (frequency cannot be estimated from available data):

• Combination of a widespread severe skin reaction, feeling unwell, fever, increased number of certain types of white blood cells or yellowing of the skin or eyes (signs of jaundice, i.e. liver problems) with shortness of breath, chest pain/discomfort, marked decrease in urine production and feeling thirsty, etc. (signs of an allergic reaction related to treatment).
• Chronic kidney failure.
• Reactivation of hepatitis B infection if you have had hepatitis B in the past (a liver infection).

If you experience any of the above effects, inform your doctor immediately.
Other side effects may include:
Very common (may affect more than 1 in 10 people):

• Headache or feeling tired.
• Feeling unwell (nausea), vomiting, diarrhoea or indigestion.
• Skin rash.
• Muscle cramps or joint, muscle or bone pain during treatment with Glivec or after stopping Glivec.
• Swelling, for example around the ankles or puffy eyes.
• Weight gain. If any of these effects become severe, inform your doctor.

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

• Loss of appetite, weight loss or taste disturbances.
• Feeling dizzy or weak.
• Sleep disturbances (insomnia).
• Eye discharge with itching, redness and swelling (conjunctivitis), increased tear production or blurred vision.
• Nosebleeds.
• Abdominal pain or bloating, flatulence, heartburn or constipation.
• Itching.
• Unusual hair loss or thinning.
• Numbness in hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin or dry eyes.
• Reduced or increased skin sensitivity.
• Hot flushes, chills or night sweats. If any of these effects become severe, inform your doctor.

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

• Painful red nodules on the skin, skin pain, skin redness (inflammation of subcutaneous fat tissue).
• Cough, runny or stuffy nose, feeling of heaviness or pain when pressing the area above the eyes or on the sides of the nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe headache felt as a pulsating pain or throbbing sensation, usually on one side of the head and often accompanied by nausea, vomiting, and sensitivity to light or sound (signs of migraine).
• Flu-like symptoms (influenza).
• Pain or burning sensation during urination, increased body temperature, groin or pelvic pain, red, brown or cloudy urine (signs of urinary tract infection).
• Pain and swelling in joints (signs of arthralgia).
• Persistent feeling of sadness and loss of interest, preventing you from carrying out your normal activities (signs of depression).
• A feeling of apprehension and worry together with physical symptoms such as palpitations, sweating, trembling, dry mouth (signs of anxiety).
• Drowsiness/lethargy/excessive sleepiness.
• Tremor or shaky movements (tremor).
• Memory disturbances.
• Uncontrollable urge to move legs (restless legs syndrome).
• Hearing noises in the ears (e.g. ringing, buzzing) that have no external source (tinnitus).
• High blood pressure (hypertension).
• Belching.
• Inflammation of the lips.
• Difficulty swallowing.
• Increased sweating.
• Change in skin colour.
• Brittle nails.
• Red bumps or pustules with white tips around hair roots, possibly with pain, itching or burning sensation (signs of inflammation of hair follicles, also called folliculitis).
• Skin rash with peeling or shedding (exfoliative dermatitis).
• Breast enlargement (can occur in men or women).
• Dull and/or heavy feeling in testicles or lower abdomen, pain during urination, sexual intercourse or ejaculation, blood in urine (signs of testicular oedema).
• Inability to achieve or maintain an erection (erectile dysfunction).
• Heavy or irregular menstrual periods.
• Difficulty achieving/maintaining sexual arousal.
• Decreased sexual desire.
• Nipple pain.
• General feeling of being unwell (malaise).
• Viral infection such as cold sores (herpes labialis).
• Lower back pain due to kidney disease.
• Increased frequency of urination.
• Increased appetite.
• Pain or burning sensation in the upper abdomen and/or chest (heartburn), nausea, vomiting, acid reflux, feeling of fullness and bloating, dark-coloured stools (signs of stomach ulcer).
• Stiffness of joints and muscles.
• Abnormal laboratory test results. If any of these effects become severe, inform your doctor.

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

• Confusion.
• An episode of seizure(s) and reduced consciousness (convulsions).
• Change in nail colour.

Not known (frequency cannot be estimated from available data):

• Redness and/or swelling of the palms of the hands and soles of the feet, which may be accompanied by tingling and painful burning sensations.
• Painful skin lesions and/or blister formation.
• Slowed growth in children and adolescents. If any of these effects become severe, inform your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glivec

• 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 carton after Exp.
• Do not store above 30 °C.
• Store in the original packaging to protect the medicine from moisture.
• Do not use if the packaging is damaged or shows signs of tampering.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Glivec contains

• The active substance is imatinib mesilate. Each Glivec capsule contains 100 mg of imatinib (as mesilate).
• The other components are microcrystalline cellulose, crospovidone, magnesium stearate and anhydrous colloidal silica. The capsule shell is composed of gelatin, iron oxide red (E172), iron oxide yellow (E172) and titanium dioxide (E171). The printing ink consists of iron oxide red (E172) and shellac.

Description of the appearance of Glivec and contents of the pack
The 100 mg Glivec capsules are orange to greyish-orange in colour and marked with the inscription
“NVR SI”. They contain a white to yellowish powder.
They are supplied in packs of 24, 48, 96, 120 or 180 capsules, although not all pack sizes may be available in your country.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Sandoz S.R.L.
Str. Livezeni nr. 7A
540472, Targu Mures
Romania
Novartis Pharma GmbH
Roonstrasse 25
D-90429 Nuremberg
Germany
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 555

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Instructions for the user: package leaflet

Glivec 100 mg film-coated tablets, 400 mg film-coated tablets

imatinib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Glivec is and what it is used for

Glivec is a medicine containing an active substance called imatinib. In the diseases listed below, this medicine works by inhibiting the growth of abnormal cells, including certain types of cancer.
Glivec is indicated in adult and pediatric patients for the treatment of:

• Chronic myeloid leukemia (CML). Leukemia is a cancer of white blood cells. White blood cells normally help the body fight infections. Chronic myeloid leukemia is a form of leukemia in which certain abnormal white blood cells (called myeloid cells) begin to grow uncontrollably.
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Leukemia is a cancer of white blood cells. White blood cells normally help the body fight infections. Acute lymphoblastic leukemia is a form of leukemia in which certain abnormal white blood cells (called lymphoblasts) begin to grow uncontrollably. Glivec inhibits the growth of these cells.

Glivec is also indicated in adult patients for the treatment of:

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of hematological disorders in which certain blood cells begin to grow uncontrollably. Glivec inhibits the growth of these cells in certain subtypes of these diseases.
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL). These are blood disorders in which certain blood cells (called eosinophils) begin to grow uncontrollably. Glivec inhibits the growth of these cells in a specific subtype of these diseases.
• Malignant gastrointestinal stromal tumors (GIST). GIST is a tumor of the stomach and intestine. It arises from the uncontrolled growth of cells supporting the tissues of these organs.
• Dermatofibrosarcoma protuberans (DFSP). DFSP is a tumor of the subcutaneous tissue in which certain cells begin to grow uncontrollably. Glivec inhibits the growth of these cells. In the remainder of this patient information leaflet, abbreviations will be used when referring to these diseases.

If you have any questions about how Glivec works or why it has been prescribed for you, please consult your doctor.

2. What you should know before taking Glivec

Glivec will only be prescribed by doctors experienced in medications for the treatment of blood cancers and solid tumors.
Carefully follow all instructions given by your doctor, even if they differ from the general information contained in this leaflet.
Do not take Glivec

• if you are allergic to imatinib or to any of the other ingredients of this medicine (listed in section 6). If this applies to you, consult your doctor before taking Glivec.

If you think you might be allergic but are unsure, please seek advice from your doctor.
Warnings and precautions
Talk to your doctor before taking Glivec:

• if you have or have had liver, kidney, or heart problems.
• if you are taking levothyroxine because your thyroid gland has been removed.
• if you have ever had or may currently have a hepatitis B infection. This is because Glivec can cause reactivation of hepatitis B, which in some cases can be fatal. Your doctor will carefully monitor you for signs of this infection before starting treatment.
• if you develop bruising, bleeding, fever, fatigue, or confusion while taking Glivec, contact your doctor immediately. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA). If you are in any of these situations, consult your doctor before taking Glivec.

During treatment with Glivec, you may become more sensitive to sunlight. It is important to cover skin areas exposed to the sun and to use a sunscreen with a high sun protection factor (SPF).
These precautions also apply to children.
During treatment with Glivec, inform your doctor immediately if you gain weight rapidly. Glivec may cause your body to retain fluid (severe fluid retention).
While you are taking Glivec, your doctor will regularly monitor whether the medicine is working.
You will also have regular blood tests and be weighed regularly.
Children and adolescents
Glivec is also a treatment for children with CML. There is no experience with Glivec in children with CML under 2 years of age. Experience is limited in children with Ph+ ALL and very limited in children with MDS/MPD, DFSP, GIST, and HES/LEC.
Some children and adolescents taking Glivec may experience slower than normal growth.
Your doctor will monitor growth at regular intervals.
Other medicines and Glivec
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription (such as paracetamol), and including herbal medicines (such as St. John’s wort). Some medicines may interfere with the effect of Glivec when taken together. They may increase or decrease the effect of Glivec, leading to an increase in side effects or making Glivec less effective. Glivec may have similar effects on other medicines.
Inform your doctor if you are taking medicines that prevent blood clots.
Pregnancy, breastfeeding and fertility

• If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
• Glivec is not recommended during pregnancy unless strictly necessary, as it may harm the unborn baby. Your doctor will discuss with you the potential risks of taking Glivec during pregnancy.
• Women of childbearing potential are advised to use effective contraception during treatment and for 15 days after stopping treatment.
• Do not breastfeed during treatment with Glivec and for 15 days after stopping treatment, as it may harm the baby.
• Patients concerned about fertility during treatment with Glivec are advised to consult their doctor.

Driving and using machines
Dizziness, drowsiness, or blurred vision may occur while taking this medicine. If this happens, do not drive or operate tools or machinery until you feel well again.

3. How to take Glivec

Your doctor has prescribed Glivec because you suffer from a serious condition. Glivec can help you
fight this condition.
However, take this medicine exactly as instructed by your doctor or pharmacist. It is important that you do so
until your doctor or pharmacist tells you otherwise. If you have any doubts, consult your doctor or pharmacist.
Do not stop taking Glivec unless your doctor tells you to. If you are unable to take the medicine as prescribed
or feel you no longer need it, contact your doctor immediately.

How much Glivec to take
Use in adults
Your doctor will tell you exactly how many Glivec tablets you should take.

• If you are being treated for CML: Depending on your condition, the usual starting dose is 400 mg or 600 mg taken once daily.
• If you are being treated for GIST: The starting dose is 400 mg, taken once daily.

For both CML and GIST, your doctor may prescribe a higher or lower dose depending on your response
to treatment. If the daily dose is 800 mg, you will take 400 mg in the morning and 400 mg in the evening.

• If you are being treated for Ph+ ALL: The starting dose is 600 mg, taken once daily.
• If you are being treated for MDS/MPD: The starting dose is 400 mg, taken once daily.
• If you are being treated for HES/CEL: The starting dose is 100 mg, taken once daily. Your doctor may decide to increase the dose to 400 mg, taken once daily, based on your response to treatment.
• If you are being treated for DFSP: The dose is 800 mg per day, taken as 400 mg in the morning and 400 mg in the evening.

A dose of 400 mg can be taken as one 400 mg tablet or four 100 mg tablets.
A dose of 600 mg can be taken as one 400 mg tablet plus two 100 mg tablets, or as one 400 mg tablet plus half of another 400 mg tablet.
The tablets can be divided in half by breaking them along the break line.

Use in children and adolescents
Your doctor will tell you how many Glivec tablets should be given to the child. The amount of Glivec given
will depend on the child's condition, weight, and height. The total daily dose must not exceed 800 mg in children with CML and 600 mg in children with Ph+ ALL. The treatment may be given to the child as a single daily dose or, alternatively, the daily dose may be split into two administrations (half in the morning and half in the evening).

When and how to take Glivec

• Take Glivec with a meal. This will help protect your stomach when taking Glivec.
• Swallow the tablets whole with a large glass of water.

If you are unable to swallow the tablets, you may dissolve them in a glass of still water or apple juice:

• Use about 50 ml for each 100 mg tablet or 200 ml for each 400 mg tablet.
• Stir with a spoon until the tablets are completely dissolved.
• Once the tablet has dissolved, drink the entire contents of the glass immediately. Residual particles from the dissolved tablets may remain in the glass.

How long to take Glivec
Continue taking Glivec every day for as long as your doctor tells you to.

If you take more Glivec than you should
If you have accidentally taken too many tablets, contact your doctor immediately. You may need
medical attention. Bring the medicine pack with you.

If you forget to take Glivec

• If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
• Then continue with your regular dosing schedule.
• Do not take a double dose to make up for the missed dose.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them. These are generally mild to moderate.
Some side effects can be serious. Contact your doctor immediately if you experience
any of the following:

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

• Rapid weight gain. Glivec may cause your body to retain water (severe fluid retention).
• Signs of infection such as fever, severe chills, sore throat, or mouth ulcers. Glivec may reduce the number of white blood cells, making you more susceptible to infections.
• Unexpected bleeding or bruising (when you have not injured yourself).

Uncommon (may affect up to 1 in 100 people) or rare (may affect up to 1 in 1,000 people):

• Chest pain, irregular heartbeat (signs of heart problems).
• Cough, difficulty breathing or painful breathing (signs of lung problems).
• Feeling of dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Feeling unwell (nausea), with loss of appetite, dark urine, yellowing of the skin or eyes (signs of liver problems).
• Skin rash, redness with blisters on the lips, eyes, skin, or mouth, skin peeling, fever, raised red or purple spots on the skin, itching, burning sensation, pustular rash (signs of skin problems).
• Severe abdominal pain, presence of blood in vomit, stools, or urine, black stools (signs of gastrointestinal disorders).
• Marked decrease in urine output, feeling thirsty (signs of kidney problems).
• Feeling unwell (nausea) with diarrhoea and vomiting, abdominal pain, or fever (signs of intestinal problems).
• Severe headache, weakness or paralysis of limbs or face, difficulty speaking, sudden loss of consciousness (signs of nervous system problems such as bleeding or swelling in the brain).
• Paleness, feeling tired and short of breath, dark-coloured urine (signs of low red blood cell levels).
• Eye pain or worsening vision, bleeding in the eyes.
• Bone or joint pain (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Numbness or coldness in fingers or toes (signs of Raynaud's syndrome).
• Sudden swelling and redness of the skin (signs of a skin infection called cellulitis).
• Hearing problems.
• Muscle weakness and muscle spasms with an abnormal heartbeat (signs of changes in blood potassium levels).
• Bruising.
• Stomach pain with feeling unwell (nausea).
• Muscle cramps with fever, red-brown urine, muscle pain or weakness (signs of muscle problems).
• Pelvic pain sometimes with nausea and vomiting, vaginal bleeding, dizziness or fainting due to low blood pressure (signs of problems with ovaries and uterus).
• Nausea, shortness of breath, irregular heartbeat, cloudy urine, fatigue and/or joint problems associated with abnormal laboratory test results (e.g. high levels of potassium, uric acid and calcium, low levels of phosphorus in the blood).
• Blood clots in small blood vessels (thrombotic microangiopathy).

Not known (frequency cannot be estimated from available data):

• A combination of widespread severe skin reaction, feeling unwell, fever, increased number of certain types of white blood cells or yellowing of the skin or eyes (signs of jaundice, i.e. liver problems), with shortness of breath, chest pain/discomfort, marked decrease in urine production, and feeling thirsty, etc. (signs of a treatment-related allergic reaction).
• Chronic kidney failure.
• Reactivation of hepatitis B infection if you have previously had hepatitis B (a liver infection).

If you experience any of the above effects, contact your doctor immediately.
Other side effects may include:

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

• Headache or feeling tired.
• Feeling unwell (nausea), vomiting, diarrhoea, or indigestion.
• Skin rash.
• Muscle cramps or joint, muscle, or bone pain during treatment with Glivec or after stopping Glivec.
• Swelling, for example around the ankles or puffy eyes.
• Weight gain. If any of these effects are severe, contact your doctor.

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

• Loss of appetite, weight loss, or taste disturbances.
• Feeling dizzy or weak.
• Sleep disturbances (insomnia).
• Eye discharge with itching, redness, and swelling (conjunctivitis), increased tearing, or blurred vision.
• Nosebleeds.
• Abdominal pain or bloating, flatulence, heartburn, or constipation.
• Itching.
• Unusual hair loss or thinning.
• Numbness in hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin, or dry eyes.
• Reduced or increased skin sensitivity.
• Hot flushes, chills, or night sweats. If any of these effects are severe, contact your doctor.

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

• Painful red nodules on the skin, skin pain, skin redness (inflammation of subcutaneous fatty tissue).
• Cough, runny or stuffy nose, feeling of heaviness or pain when pressing the area above the eyes or sides of the nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe headache felt as a pulsating pain or throbbing sensation, usually on one side of the head and often accompanied by nausea, vomiting, and sensitivity to light or sound (signs of migraine).
• Flu-like symptoms (influenza).
• Pain or burning sensation when passing urine, increased body temperature, groin or pelvic pain, red, brown, or cloudy urine (signs of urinary tract infection).
• Pain and swelling of joints (signs of arthralgia).
• Persistent feeling of sadness and loss of interest, preventing you from carrying out your normal activities (signs of depression).
• A feeling of apprehension and worry together with physical symptoms such as palpitations, sweating, trembling, dry mouth (signs of anxiety).
• Drowsiness/lethargy/excessive sleepiness.
• Tremor or shaky movements (tremor).
• Memory problems.
• Uncontrollable urge to move the legs (restless legs syndrome).
• Hearing noises in the ears (e.g. ringing, buzzing) that have no external source (tinnitus).
• High blood pressure (hypertension).
• Belching.
• Inflammation of the lips.
• Difficulty swallowing.
• Increased sweating.
• Change in skin colour.
• Brittle nails.
• Red bumps or white-headed pimples around hair roots, possibly with pain, itching, or burning sensation (signs of inflammation of hair follicles, also called folliculitis).
• Skin rash with peeling or shedding (exfoliative dermatitis).
• Breast enlargement (can occur in men or women).
• Dull and/or heavy feeling in the testicles or lower abdomen, pain when passing urine, during sexual intercourse or ejaculation, blood in the urine (signs of testicular swelling).
• Inability to achieve or maintain an erection (erectile dysfunction).
• Heavy or irregular menstrual periods.
• Difficulty achieving/maintaining sexual arousal.
• Decreased sexual desire.
• Nipple pain.
• General feeling of being unwell (malaise).
• Viral infection such as cold sores (herpes labialis).
• Lower back pain due to kidney disease.
• Increased frequency of urination.
• Increased appetite.
• Pain or burning sensation in the upper abdomen and/or chest (heartburn), nausea, vomiting, acid reflux, feeling of fullness and bloating, dark stools (signs of stomach ulcer).
• Stiffness of joints and muscles.
• Abnormal laboratory test results. If any of these effects are severe, contact your doctor.

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

• Confusion.
• An episode of seizure(s) and reduced consciousness (convulsions).
• Change in nail colour.

Not known (frequency cannot be estimated from available data):

• Redness and/or swelling of the palms of the hands and soles of the feet, which may be accompanied by tingling and painful burning.
• Painful skin lesions and/or blistering.
• Slowed growth in children and adolescents. If any of these effects are severe, contact your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glivec

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton after "Exp".
• Storage temperature
• Glivec 100 mg film-coated tablets: Do not store above 30 °C.
• Glivec 400 mg film-coated tablets: Store below 25 °C.
• Keep the medicine in the original packaging to protect it from moisture.
• Do not use if the packaging is damaged or shows signs of tampering.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Glivec contains

• The active substance is imatinib mesilate.
• Each 100 mg Glivec tablet contains 100 mg of imatinib (as mesilate).
• Each 400 mg Glivec tablet contains 400 mg of imatinib (as mesilate).
• The other ingredients are microcrystalline cellulose, crospovidone, hypromellose, magnesium stearate and anhydrous colloidal silicon dioxide.
• The tablet coating consists of iron oxide red (E172), iron oxide yellow (E172), macrogol, talc and hypromellose.

Description of the appearance of Glivec and package contents
The 100 mg Glivec film-coated tablets are round-shaped tablets ranging in colour from very dark yellow to brownish-orange. They are marked with "NVR" on one side and "SA" and a breakline on the other side.
The 400 mg Glivec film-coated tablets are oval-shaped tablets ranging in colour from very dark yellow to brownish-orange. They are marked with "400" on one side and a breakline on the other side, with "SL" on each side of the breakline.
The 100 mg Glivec film-coated tablets are supplied in packs of 20, 60, 120 or 180 tablets.
The 400 mg Glivec film-coated tablets are supplied in packs of 10, 30 or 90 tablets.
Not all pack sizes may be available in your country.

Marketing Authorization Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Pharmaceutical Manufacturing LLC
Verovskova Ulica 57
Ljubljana, 1000
Slovenia
Lek d.d, PE PROIZVODNJA LENDAVA
Trimlini 2D
Lendava, 9220
Slovenia
Novartis Pharma GmbH
Roonstrasse 25
D-90429 Nuremberg
Germany
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 555

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu