Package Leaflet: Information for the User

Glivec 100mg Film-Coated Tablets

Glivec 400mg Film-Coated Tablets

imatinib

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

• Keep this leaflet, as 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 others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

if they are not listed in this leaflet. See section 4.

1.What Glivec is and what it is used for

2.What you need to know before you start taking Glivec

3.How to take Glivec

4.Possible side effects

5.Storage of Glivec

6.Contents of the pack and additional information

Glivec is a medication that contains an active ingredient called imatinib. This medication acts by inhibiting the growth of abnormal cells in the following diseases, which include some types of cancer.

Glivec is a treatment for adults and children for:

• Chronic Myeloid Leukemia (CML). Leukemia is a cancer of the white blood cells. These white blood cells normally help the body fight infections. Chronic Myeloid Leukemia is a form of leukemia in which abnormal white blood cells (called myeloid cells) start to grow uncontrollably.
• Acute Lymphoblastic Leukemia with Philadelphia chromosome positive (ALL Ph-positive). Leukemia is a cancer of the white blood cells. These white blood cells normally help the body fight infections. Acute Lymphoblastic Leukemia is a form of leukemia in which abnormal white blood cells (called lymphoblasts) start to grow uncontrollably. Glivec inhibits the growth of these cells.

Glivec is also a treatment for adults for:

• Myeloproliferative/Myelodysplastic Syndromes (MPMDS). These are a group of blood disorders in which some blood cells start to grow uncontrollably. Glivec inhibits the growth of these cells in a certain subtype of these diseases.
• Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL). These are blood disorders in which some blood cells (called eosinophils) start to grow uncontrollably. Glivec inhibits the growth of these cells in a certain subtype of these diseases.
• Gastrointestinal Stromal Tumors (GIST). GIST is a cancer of the stomach and intestine. It originates from an uncontrolled growth of the supporting tissues of these organs.
• Dermatofibrosarcoma Protuberans (DFSP). DFSP is a cancer of the tissue under the skin in which some cells start to grow uncontrollably. Glivec inhibits the growth of these cells.

In the rest of this prospectus, these abbreviations are used when referring to these diseases.

If you have any questions about how Glivec works or why this medication has been prescribed to you, ask your doctor.

Only a doctor with experience in cancer medications for blood cell cancers or solid tumors will prescribe Glivec.

Follow your doctor's instructions carefully, even if they differ from the general information contained in this prospectus.

Do not take Glivec

-if you are allergic to imatinib or any of the other components of this medication (including those listed in section6).

If this applies to you,inform your doctor and do not take Glivec.

If you think you may be allergic but are not sure, ask your doctor for advice.

Warnings and precautions

Consult your doctor before starting to take Glivec:

• if you have or have had any liver, kidney, or heart problems.
• if you are taking a medication containing levotiroxine because your thyroid gland has been removed.
• if you have ever had or may currently have a hepatitis B infection. This is because Glivec may cause hepatitis B to become active again, which can be fatal in some cases. Your doctor will carefully check for signs of this infection before starting treatment.
• if while taking Glivec you experience bruising, bleeding, fever, fatigue, and confusion, please contact your doctor. This could be a sign of blood vessel damage called microangiopathic thrombosis (MAT).

If any of these cases apply to you,inform your doctor before taking Glivec.

You may become more sensitive to the sun while taking Glivec. It is essential to cover exposed skin areas and use high-protection sunscreen. These precautions also apply to children.

Inform your doctor immediately during Glivec treatmentif you experience rapid weight gain. Glivec may cause severe fluid retention in the body.

While taking Glivec, your doctor will regularly monitor the medication's effectiveness. Blood tests and regular weighing will also be performed.

Children and adolescents

Glivec is also a treatment for children with LMC. There is no experience with children with LMC under 2years of age. Experience with children with Ph-positive LLA is limited, and experience with SMD/SMP, DFSP, GIST, and SHE/LEC is very limited.

Some children and adolescents taking Glivec may experience slower-than-normal growth. Your doctor will monitor growth during regular visits.

Other medications and Glivec

Inform your doctor or pharmacist if you are using, have recently taken, or may need to take any other medication, including over-the-counter medications (such as paracetamol) and herbal medications (such as St. John's Wort). Some medications may interact with Glivec when taken together. These may increase or decrease Glivec's effect, leading to increased side effects or making Glivec less effective. Glivec may also affect other medications.

Inform your doctor if you are taking medications that prevent blood clotting.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.
• It is not recommended to use Glivec during pregnancy except when clearly necessary, as it may harm your baby. Your doctor will discuss the possible risks of taking Glivec during pregnancy with you.
• Women who may become pregnant are advised to use an effective contraceptive method during treatment and for 15days after treatment has ended.
• Do not breastfeed your baby during Glivec treatmentor for the following 15days after treatment has ended, as it may harm your baby.
• Patients concerned about their fertility while taking Glivec should consult their doctor.

Driving and operating machinery

You may experience dizziness, drowsiness, or blurred vision while taking this medication.

If you experience these symptoms, do not drive or operate tools or machinery until you feel better again.

Your doctor has prescribed Glivec because you have a serious disease. Glivec may help you fight this disease.

However, follow exactly the administration instructions for this medication indicated by your doctor or pharmacist. It is essential that you do this for the time your doctor or pharmacist tells you. In case of doubt, consult your doctor or pharmacist again.

Do not stop taking Glivec unless your doctor tells you to. If you cannot take the medication as prescribed by your doctor or think you no longer need to take it for a longer period, 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 LMC:

Depending on your situation, the usual initial dose is400mgor600mgoncea day:

• If you are being treated for GIST:

The initial dose is 400mgoncea day.

For LMC and GIST, your doctor may prescribe a higher or lower dose depending on how you respond to treatment. If your daily dose is 800mg, you should take 400mg in the morning and 400mg at night.

• If you are being treated for LLA Ph-positive:

The initial dose is 600mgoncea day.

• If you are being treated forSMD/SMP:

The initial dose is 400mgoncea day.

• If you are being treated for SHE/LEC:

The initial dose is 100mgoncea day. Your doctor may decide to increase the dose to 400mgoncea day, depending on how you respond to treatment.

• If you are being treated for DFSP:

The dose is 800mg a day, that is, 400mg in the morning and 400mg at night.

The dose of 400mg can be taken either with 1tablet of 400mg or with 4tablets of 100mg.

The dose of 600 mg can be taken with 1 tablet of 400 mg and 2 tablets of 100 mg or with 1 tablet of 400 mg plus half a tablet of 400 mg.

Tablets can be divided in half by breaking them along the score.

Use in children and adolescents

Your doctor will tell you how many Glivec tablets to administer to the child. The amount of Glivec administered will depend on the child's situation, weight, and height. The total daily dose in children should not exceed 800mg in LMC and 600mg in LLA Ph+. Treatment can be given to the child once a day or, alternatively, the dose can be divided into two doses (half in the morning and half at night).

When and how to take Glivec

• Take Glivec with food.This will help protect you from stomach problems when taking Glivec.
• Swallow the tablets with a large glass of water.

If you are unable to swallow the tablets, you can dissolve them in a glass of water without gas or apple juice:

• Use approximately 50ml for each 100mg tablet or 200ml for each 400mg tablet.
• Stir until the tablets have completely dissolved.
• Once the tablet has dissolved, drink the contents of the glass immediately. There may be remaining dissolved tablet residue at the bottom of the glass.

For how long to take Glivec

Continue taking Glivec every day for the time your doctor tells you.

If you take more Glivec than you should

If you accidentally take too many tablets, talk to your doctorimmediately. You may need medical attention. Bring the medication packaging.

If you forget to take Glivec

• If you forget to take a dose, take it as soon as you remember. However, if it is almost time for the next dose, do not take the missed dose,
• Then continue with the regular schedule.
• Do not take a double dose to compensate for the missed doses.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. These are usually mild to moderate.

Some side effects can be serious. Inform your doctor immediately if you experience any of the following:

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

• 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 in your blood, making you more susceptible to infections.
• Bleeding or unexpected bruising (when you have not had any injuries).

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

• Chest pain, irregular heart rhythm (signs of heart problems).
• Cough, difficulty breathing, or painful breathing (signs of lung problems).
• Dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Nausea, loss of appetite, dark urine, yellow skin or eyes (signs of liver problems).
• Rash, skin redness, blisters on the lips, eyes, skin, or mouth, skin peeling, fever, red or purple skin patches, itching, burning sensation, pustular rash (signs of skin problems).
• Severe abdominal pain, blood in your vomit, stool, or urine, black stool (signs of gastrointestinal problems).
• Significant decrease in urine output, feeling thirsty (signs of kidney problems).
• Nausea, diarrhea, vomiting, abdominal pain, or fever (signs of intestinal problems).
• Severe headache, weakness, or paralysis in the limbs or face, difficulty speaking, sudden loss of consciousness (signs of nervous system problems such as bleeding or swelling in the brain or skull).
• Pale skin, feeling tired, difficulty breathing, dark urine (signs of low red blood cell count).
• Eye pain or vision problems, bleeding in the eyes.
• Bone or joint pain (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Numbness or cold sensation in the feet and toes (signs of Raynaud's syndrome).
• Rapid skin swelling and redness (sign of skin infection called cellulitis).
• Difficulty hearing.
• Muscle weakness and muscle spasms, abnormal heart rhythm (signs of changes in potassium levels in the blood).
• Bruising.
• Abdominal pain with nausea.
• Muscle spasms with fever, reddish-brown urine, muscle pain or weakness (signs of muscle problems).
• Pelvic pain, sometimes with nausea and vomiting, unexpected vaginal bleeding, dizziness or fainting due to low blood pressure (signs of ovarian or uterine problems).
• Nausea, difficulty breathing, irregular heartbeat, cloudy urine, fatigue, and/or joint pain associated with abnormal laboratory test results (e.g., elevated potassium, uric acid, and calcium levels, and low phosphorus levels in the blood).
• Microangiopathic thrombosis.

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

• Combination of widespread rash, feeling unwell, fever, elevated levels of certain blood cells, or yellow skin or eyes (signs of jaundice) with difficulty breathing, chest pain, decreased urine output, 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 symptoms,inform your doctor immediately.

Other side effects may include:

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

• Headache or feeling tired
• Nausea, vomiting, diarrhea, or indigestion.
• Rash.
• Muscle cramps or pain in the muscles, joints, or bones, during treatment with Glivec or when stopping treatment.
• Inflammations such as swollen ankles or eyes.
• Weight gain.

If any of these affect you significantly,inform your doctor.

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

• Loss of appetite, weight loss, or altered sense of taste.
• Feeling tired or weak.
• Difficulty sleeping (insomnia).
• Excessive tearing of the eyes with itching, redness, and swelling (conjunctivitis), watery eyes, or blurred vision.
• Nasal bleeding.
• Abdominal pain, bloating, heartburn, or constipation.
• Itching.
• Unusual hair loss or thinning.
• Numbness in the hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin, or dry eyes.
• Decreased or increased skin sensitivity.
• Hot flashes, chills, or night sweats.

If any of these affect you significantly,consult your doctor.

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

• Red, painful bumps on the skin, skin pain, skin redness (inflammation of subcutaneous fat).
• Cough, nasal secretion or blockage, feeling of heaviness or pain when pressing the eye area or the sides of the nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe headache, like a stabbing or pulsating pain, usually on one side of the head, often accompanied by nausea, vomiting, and sensitivity to light or sound (signs of migraine).
• Symptoms similar to the flu.
• Pain or burning sensation when urinating, fever, pain in the groin or pelvis, cloudy or reddish-brown urine (signs of urinary tract infection).
• Joint pain (signs of arthralgia).
• Constant feeling of sadness and loss of interest, which interferes with the ability to lead a normal life (signs of depression).
• Feeling anxious and worried, accompanied by physical symptoms such as palpitations, sweating, tremors, dry mouth (signs of anxiety).
• Drowsiness, excessive sleepiness, or excessive sleep.
• Tremors or involuntary movements (tremor).
• Memory damage.
• Restless leg syndrome.
• Heard sounds (e.g., bells, buzzing) in the ears that do not come from the outside (tinnitus).
• High blood pressure.
• Belching or gas.
• Lip inflammation.
• Difficulty swallowing.
• Increased sweating.
• Decoloration of the skin.
• Brittle nails.
• Red, painful bumps or acne around the hair follicles, possibly with pain, itching, or burning sensation (signs of folliculitis).
• Dermatitis exfoliativa (skin rash with peeling or shedding).
• Breast growth (may occur in men or women).
• Dull, aching pain or feeling of heaviness in the testicles or lower abdomen, pain when urinating, during sex, or when ejaculating, blood in the urine (signs of testicular edema).
• Difficulty achieving or maintaining an erection (erectile dysfunction).
• Irregular or heavy menstrual periods.
• Difficulty achieving or maintaining sexual excitement.
• Decreased sex drive.
• Breast pain.
• General feeling of discomfort (general malaise)
• Herpes labialis (cold sore).
• Lower back pain due to kidney problems.
• Increased frequency of urination.
• Increased appetite.
• Pain or burning sensation in the upper abdomen and/or chest (heartburn), nausea, vomiting, acid reflux, feeling full, bloated, black stool (signs of stomach ulcer).
• Rigidity in the joints or muscles.
• Abnormal laboratory test results.
• If any of these affect you significantly,consult your doctor.

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

• Confusion.
• Yellowing of the nails.

Frequency not known(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 burning sensation.
• Painful skin lesions with blisters
• Delayed growth in children and adolescents.

If any of these affect you significantly,consult your doctor.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet.You can also report them directly through thenational reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box after CAD.
• Storage Temperature
• Glivec 100mg film-coated tablets: Do not store above30°C.
• Glivec 400mg film-coated tablets: Store below 25°C.
• Store in the original packaging to protect it from moisture.
• Do not use any packaging if you observe that it is damaged or shows signs of handling.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medication that you no longer need. This will help protect the environment.

Composition of Glivec

• The active ingredient is imatinib mesylate.
• • Each 100 mg tablet of Glivec contains 100 mg of imatinib mesylate.
  • Each 400 mg tablet of Glivec contains 400 mg of imatinib mesylate.

• The other components are microcrystalline cellulose, crospovidone, hypromellose, magnesium stearate, and anhydrous colloidal silica.
• The tablet coating is formed by red iron oxide (E172), yellow iron oxide (E172), macrogol, talc, and hypromellose.

Appearance of the product and contents of the package

Glivec 100 mg film-coated tablets are round, dark yellow to orange-brown tablets with the mark "NVR" on one side and "SA" and a score on the other.

Glivec 400 mg film-coated tablets are oval-shaped, dark yellow to orange-brown tablets with the mark "400" on one side and a score on the other with "SL" on either side of the score.

Glivec 100 mg film-coated tablets are available in packs containing 20, 60, 120, or 180 tablets.

Glivec 400 mg film-coated tablets are available in packs containing 10, 30, or 90 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Irlanda

Responsible for manufacturing

Novartis Pharmaceutical Manufacturing LLC

Verovskova Ulica 57

Ljubljana, 1000

Eslovenia

Lek d.d, PE PROIZVODNJA LENDAVA

Trimlini 2D

Lendava, 9220

Eslovenia

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nürnberg

Alemania

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Alemania

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.