GLIVEC 400 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Glivec 100mg film-coated tablets

Glivec 400mg film-coated tablets

imatinib

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

Contents of the pack

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

1. What is Glivec and what is it used for

Glivec is a medicine that contains the active substance imatinib. This medicine works by inhibiting the growth of abnormal cells in the diseases described below. These include some types of cancer.

Glivec is a treatment for adults and children for:

• Chronic myeloid leukaemia (CML). Leukaemia is a cancer of the white blood cells. These white blood cells normally help the body to fight infections. Chronic myeloid leukaemia is a type of leukaemia in which some abnormal white blood cells (called myeloid cells) start to grow out of control.
• Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL). Leukaemia is a cancer of the white blood cells. These white blood cells normally help the body to fight infections. Acute lymphoblastic leukaemia is a type of leukaemia in which some abnormal white blood cells (called lymphoblasts) start to grow out of control. Glivec inhibits the growth of these cells.

Glivec is also a treatment for adults for:

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of blood diseases in which some blood cells start to grow out of control. Glivec inhibits the growth of these cells in a certain subtype of these diseases.
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL). These are blood diseases in which some blood cells (called eosinophils) start to grow out of control. Glivec inhibits the growth of these cells in a certain subtype of these diseases.
• Gastrointestinal stromal tumours (GIST). GIST is a cancer of the stomach and intestine. It originates from uncontrolled cell 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 out of control. Glivec inhibits the growth of these cells.

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

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

2. What you need to know before you take Glivec

Glivec will only be prescribed by a doctor who has experience in medicines used to treat blood cell cancer or solid tumours.

Follow carefully 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 any of the other ingredients of this medicine (listed in section 6).

If this applies to you, tell 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 taking Glivec:

• if you have or have had liver, kidney, or heart problems.
• if you are taking a medicine that contains levothyroxine because you have had your thyroid gland removed.
• if you have ever had or might currently have a hepatitis B virus infection. This is because Glivec could cause the hepatitis B virus to become active again, which can be life-threatening in some cases. Your doctor should check you carefully 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 thrombotic microangiopathy (TMA).

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

You may be more sensitive to the sun while taking Glivec. It is important that you cover the skin that is exposed to the sun and use a high-protection sunscreen. These precautions also apply to children.

During treatment with Glivec, tell your doctor immediatelyif you gain weight very quickly. Glivec can cause water retention in the body (severe fluid retention).

While taking Glivec, your doctor will regularly check if 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 in children with Ph+ ALL is limited, and experience in children with MDS/MPD, DFSP, GIST, and HES/CEL is very limited.

Some children and adolescents who take Glivec may have slower than normal growth. The doctor will check growth during regular visits.

Other medicines and Glivec

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription (such as paracetamol) and 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 increased risk of side effects or making Glivec less effective. Glivec may have the same effect on other medicines.

Tell your doctor if you are taking medicines that prevent blood clots from forming.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before taking this medicine.
• Glivec is not recommended during pregnancy unless clearly necessary, as it may harm your baby. Your doctor will discuss with you the potential risks of taking Glivec during pregnancy.
• Women who could become pregnant are advised to use an effective method of contraception during treatment and for 15 days after finishing treatment.
• Do not breastfeed while taking Glivec and for 15 days after finishing treatment, as it may harm your baby.
• Patients who are concerned about their fertility while taking Glivec should consult their doctor.

Driving and using machines

You may feel dizzy or drowsy or have blurred vision while taking this medicine.

If you experience this, do not drive or use tools or machines until you feel better.

3. How to take Glivec

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

However, follow your doctor's or pharmacist's instructions exactly as they tell you. It is important that you do this for the time they tell you. If you are unsure, ask your doctor or pharmacist again.

Do not stop taking Glivec unless your doctor tells you to. If you cannot take the medicine as your doctor has prescribed or think you no longer need it, contact your doctor immediately.

How much Glivec to take

Adult use

Your doctor will tell you exactly how many Glivec tablets to take.

• If you are being treated for CML:

Depending on your situation, the usual starting dose is 400mgor 600mgoncea day:

• If you are being treated for GIST:

The starting dose is 400 mg oncea day.

For CML and GIST, your doctor may prescribe a higher or lower dose depending on how you respond to treatment. If your daily dose is 800 mg, 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 oncea day.

• If you are being treated for MDS/MPD:

The starting dose is 400 mg oncea day.

• If you are being treated for HES/CEL:

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

• If you are being treated for DFSP:

The dose is 800 mg a day, which is 400 mg in the morning and 400 mg in the evening.

A dose of 400 mg can be taken as either 1 tablet of 400 mg or 4 tablets of 100 mg.

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

Tablets can be divided into two by breaking them along the score line.

Use in children and adolescents

Your doctor will tell you how many Glivec tablets to give to the child. The amount of Glivec given will depend on the child's situation, body weight, and height. The total daily dose in children should not exceed 800 mg in CML and 600 mg in Ph+ ALL. 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 in the evening).

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 still water or apple juice:

• Use approximately 50 ml for each 100 mg tablet or 200 ml for each 400 mg tablet.
• Stir with a spoon until the tablets have completely dissolved.
• Drink the whole contents of the glass immediately. There may be some residue left in the glass.

How long to take Glivec

Keep taking Glivec every day for as long as your doctor tells you.

If you take more Glivec than you should

If you accidentally take too many tablets, talk to your doctor immediately. You may need medical attention. Take the pack with you.

If you forget to take Glivec

• If you forget to take a dose, take it as soon as you remember. However, if it is nearly time for the next dose, do not take the missed dose,
• Then continue with your normal schedule.
• Do not take a double dose to make up for missed doses.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. These are usually mild to moderate.

Some adverse effects can be serious. Inform your doctor immediately if you suffer from any of the following:

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

• 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 ulcers in the mouth. Glivec may reduce the number of white blood cells in the blood, so you may suffer from infections more easily.
• Bleeding or bruising unexpectedly (when you have not suffered any injury).

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

• Chest pain, irregular heartbeat (signs of heart problems).
• Cough, with difficulty breathing or painful breathing (signs of lung problems).
• Feeling of dizziness, dizziness, or fainting (signs of low blood pressure).
• Nausea, with loss of appetite, dark-colored urine, yellowish skin or eyes (signs of liver problems).
• Rash, skin redness, with blisters on the lips, eyes, skin, or mouth, skin peeling, fever, red or purple skin spots, itching, burning sensation, rash with pus (signs of skin problems).
• Severe abdominal pain, blood in your vomit, stools, or urine, black stools (signs of gastrointestinal disorders).
• Significant decrease in urine output, feeling of thirst (signs of kidney problems).
• Nausea, with diarrhea and 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 skull/brain).
• Pale skin, feeling of tiredness, and difficulty breathing, dark-colored urine (signs of low red blood cell count in the blood).
• Pain in the eyes or vision disorders, bleeding in the eyes.
• Pain in the bones or joints (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Numbness or feeling of cold in the feet and toes (signs of Raynaud's syndrome).
• Sudden swelling and redness of the skin (sign of a skin infection called cellulitis).
• Hearing difficulties.
• Muscle weakness and muscle spasms, with an abnormal heartbeat (signs of changes in potassium levels in the blood).
• Bruising.
• Stomach pain with nausea.
• Muscle spasms with fever, reddish-brown urine, pain, or weakness in the muscles (signs of muscle problems).
• Pelvic pain, sometimes with nausea and vomiting, with unexpected vaginal bleeding, feeling of dizziness or fainting due to low blood pressure (signs of problems in the ovaries or uterus).
• Nausea, difficulty breathing, irregular heartbeat, cloudy urine, fatigue, and/or joint discomfort associated with abnormal laboratory test results (e.g., high levels of potassium, uric acid, and calcium, and low levels of phosphorus in the blood).
• Blood clots in small blood vessels (microangiopathic thrombosis).

Frequency Not Known(cannot be estimated from the available data):

• Combination of a widespread rash, feeling of discomfort, fever, high levels of certain blood cells, or yellowish skin or eyes (signs of jaundice) with difficulty breathing, chest pain, severely decreased urine production, and feeling of thirst, etc. (signs of an allergic reaction related to treatment).
• Chronic kidney failure.
• Recurrence (reactivation) of hepatitis B virus infection if you have had hepatitis B in the past (a liver infection).

If you suffer from any of the above alterations, inform your doctor immediately.

Other adverse effects may include:

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

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

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

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

• Anorexia, weight loss, or altered sense of taste.
• Feeling of tiredness or weakness.
• Difficulty sleeping (insomnia).
• Eye tearing with itching, redness, and swelling (conjunctivitis), or watery eyes or blurred vision.
• Nosebleeds.
• Pain or swelling in the abdomen, flatulence, heartburn, or constipation.
• Itching.
• Weakness or unusual hair loss.
• Numbness of the hands or feet.
• Ulcers in the mouth.
• Pain in the joints 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 importantly, consult your doctor.

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

• Painful red lumps on the skin, skin pain, skin redness (inflammation of the fatty tissue under the skin).
• Cough, secretion, or blockage in the nose, feeling of heaviness or pain when pressing the area around the eyes or to 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 pain or a 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 urinating, fever, pain in the groin or pelvis, cloudy or reddish-brown urine (signs of urinary tract infection).
• Pain and swelling of the joints (signs of arthralgia).
• A constant feeling of sadness and loss of interest, which disrupts daily life (signs of depression).
• A feeling of apprehension and worry along with physical symptoms such as palpitations, sweating, trembling, dry mouth (signs of anxiety).
• Numbness/sleepiness/excessive sleep.
• Tremors or involuntary movements (tremor).
• Memory impairment.
• Need to constantly move the legs (restless legs syndrome).
• Hearing noises (e.g., ringing, buzzing) in the ears that do not come from outside (tinnitus).
• High blood pressure (hypertension).
• Belching or gas.
• Lip inflammation.
• Difficulty swallowing.
• Increased sweating.
• Discoloration of the skin.
• Brittle nails.
• Reddish bumps or pimples around the hair root, possibly with pain, itching, or burning sensation (signs of folliculitis, also called hair follicle inflammation).
• Skin rash with peeling or skin shedding (exfoliative dermatitis).
• Breast growth (can occur in men or women).
• Dull pain and/or feeling of heaviness in the testicles or lower abdomen, pain when urinating, having sex, or ejaculating, blood in the urine (signs of testicular edema).
• Difficulty having or maintaining an erection (erectile dysfunction).
• Intense or irregular menstrual periods.
• Difficulty achieving or maintaining sexual arousal.
• Decreased sexual desire.
• Pain in the nipples.
• General feeling of discomfort (general malaise)
• Viral infections such as cold sores.
• Lower back pain due to a kidney disorder.
• 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, black stools (signs of stomach ulcer).
• Stiffness in the joints or muscles.
• Abnormal laboratory test results.

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

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

• Confusion.
• Discoloration of the nails.

Frequency Not Known(cannot be estimated from the available data):

• Redness and/or swelling of the palms of the hands and the soles of the feet that may be accompanied by a tingling sensation and burning pain.
• Painful skin lesions and/or blisters
• Delayed growth in children and adolescents.

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

Reporting of Adverse Effects

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

5. Storage of Glivec

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the box 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 in the original packaging to protect from moisture.
• Do not use any packaging if you notice it is damaged or shows signs of tampering.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Glivec Composition

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

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

Product Appearance and Package Contents

Glivec 100 mg film-coated tablets are dark yellow to orange-brown, round tablets. They have the mark «NVR» on one side and «SA» and a score line on the other.

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

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 packs may be marketed.

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 Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of the Last Revision of this Leaflet:

Other Sources of Information

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