Glivec 400 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Glivec 100 mg film-coated tablets

Glivec 400 mg film-coated tablets

imatinib

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

Contents of the 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 that contains an active substance called imatinib. This medicine works by inhibiting the growth of abnormal cells in the diseases described below. These include certain 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 fight infections. Chronic myeloid leukaemia is a form of leukaemia in which abnormal white blood cells (called myeloid cells) begin to grow uncontrollably.
• 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 fight infections. Acute lymphoblastic leukaemia is a form of leukaemia in which abnormal white blood cells (called lymphoblasts) begin to grow uncontrollably. 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 certain blood cells begin to grow uncontrollably. Glivec inhibits the growth of these cells in a specific subtype of these diseases.
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL). These are blood diseases 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.
• Gastrointestinal stromal tumours (GIST). GIST is a cancer of the stomach and intestine. It arises from uncontrolled cell growth in the supportive tissues of these organs.
• Dermatofibrosarcoma protuberans (DFSP). DFSP is a cancer of the tissue beneath the skin in which certain cells begin to grow uncontrollably. Glivec inhibits the growth of these cells.

In the remainder 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, please ask your doctor.

2. What you need to know before taking Glivec

Glivec will only be prescribed by a doctor experienced in using medicines to treat blood cell cancers or solid tumours.

Carefully follow all instructions given by your doctor, even if they differ from the information provided 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, inform your doctor and do not take Glivec.

If you think you may be allergic but are unsure, consult your doctor for advice.

Warnings and precautions

Talk to your doctor before starting to take Glivec:

• if you have or have had any liver, kidney or heart problems.
• if you are taking a medicine containing levothyroxine because your thyroid gland has been removed.
• if you have ever had, or may currently have, an infection with hepatitis B virus. This is because Glivec could cause hepatitis B to become active again, which may be fatal in some cases. Your doctor must carefully check for signs of this infection before starting treatment.
• if you develop bruising, bleeding, fever, fatigue, or confusion while taking Glivec, please contact your doctor immediately. These symptoms could be a sign of damage to blood vessels called thrombotic microangiopathy (TMA).

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

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

During treatment with Glivec, inform your doctor immediately if you gain weight rapidly. Glivec can cause fluid retention in the body (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 children under 2 years of age with CML. Experience in children with Ph-positive ALL is limited, and experience in children with MDS/MPN, DFSP, GIST, and HES/CEL is very limited.

Some children and adolescents taking Glivec may have slower than normal growth. Your doctor will monitor growth during periodic visits.

Other medicines and Glivec

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription (such as paracetamol) and even herbal medicines (such as St. John’s wort). Some medicines may interfere with the effect of Glivec when taken together. These may increase or decrease the effect of Glivec, leading to an increase in side effects or making Glivec less effective. Glivec may also have similar effects on other medicines.

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

Pregnancy, breast-feeding and fertility

• If you are pregnant or breast-feeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.
• Use of Glivec during pregnancy is not recommended unless clearly necessary, as it may harm your unborn baby. Your doctor will discuss with you the possible risks of taking Glivec during pregnancy.
• Women who could become pregnant should use an effective method of contraception during treatment and for 15 days after stopping treatment.
• Do not breast-feed during treatment with Glivec and for the following 15 days after treatment has ended, as it may harm your baby.
• Patients concerned about fertility while taking Glivec should discuss this with their doctor.

Driving and using machines

You may experience dizziness, drowsiness or blurred vision while taking this medicine. If you experience these symptoms, 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 disease. Glivec can help you fight this disease.

However, follow exactly the administration instructions for this medicine given by your doctor or pharmacist. It is important that you do so for the length of time indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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

What dose to take of Glivec

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 situation, the usual initial dose is 400 mg or 600 mg once daily:

• If you are being treated for GIST:

The initial dose is 400 mg once daily.

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, you should take 400 mg in the morning and 400 mg in the evening.

• If you are being treated for Ph+ ALL:

The initial dose is 600 mg once daily.

• If you are being treated for MDS/MPN:

The initial dose is 400 mg once daily.

• If you are being treated for HES/CEL:

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

• If you are being treated for DFSP:

The dose is 800 mg daily, i.e., 400 mg in the morning and 400 mg in the evening.

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

The 600 mg dose 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.

The tablets may be divided in half 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 administered will depend on the child's condition, body weight, and height. The total daily dose in children must not exceed 800 mg in CML and 600 mg in Ph+ ALL. The treatment may be given to the child once daily or, alternatively, the dose may 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 may 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.
• Once the tablet has dissolved, drink the entire contents of the glass immediately. There may be remnants of the dissolved tablet at the bottom of the glass.

How long to take Glivec

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

If you take more Glivec than you should

If you have accidentally taken too many tablets, speak with your doctor immediately. You may require medical attention. Bring the medicine packaging 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 almost time for your next dose, do not take the missed dose.
• Then continue with your normal dosing schedule.
• Do not take a double dose to make up for missed doses.

If you have any further 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 everyone gets them. These are usually mild to moderate.

Some adverse effects may be serious. Inform your doctor immediately if you experience 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 mouth ulcers. Glivec may reduce the number of white blood cells in your blood, so you may be more prone to infections.
• Unexpected bleeding or bruising (when you have not suffered an 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).
• Dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Nausea, with loss of appetite, dark-colored urine, or yellowing of the skin or eyes (signs of liver problems).
• Rash, redness of the skin, blisters on the lips, eyes, skin, or mouth, skin peeling, fever, red or purple skin spots, itching, burning sensation, rash with pustules (signs of skin problems).
• Severe abdominal pain, blood in your vomit, stools, or urine, black stools (signs of gastrointestinal disturbances).
• Marked 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 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 tired and short of breath, dark-colored urine (signs of low red blood cell count).
• Eye pain or vision disturbances, 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 fingers (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 blood potassium levels).
• Bruising.
• Stomach pain with nausea.
• Muscle cramps with fever, red-brownish 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 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. elevated levels of potassium, uric acid, and calcium, and low levels of phosphorus in the blood).
• Blood clots in small blood vessels (thrombotic microangiopathy).

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

• Combination of widespread rash, feeling unwell, fever, elevated levels of certain blood cells or yellowing of the skin or eyes (signs of jaundice), together with difficulty breathing, chest pain/discomfort, severely reduced urine output, and feeling thirsty, etc. (signs of an allergic reaction related to treatment).
• Chronic kidney failure.
• Reactivation of hepatitis B virus infection if you have had hepatitis B in the past (a liver infection).

If you experience any of the above, inform your doctor immediately.

Other adverse effects may include:

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

• Headache or feeling tired.
• Nausea, vomiting, diarrhea, or indigestion.
• Rash.
• Muscle cramps or pain in 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 significantly, inform your doctor.

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

• Loss of appetite, weight loss, or altered sense of taste.
• Feeling tired or weak.
• Difficulty sleeping (insomnia).
• Watery, itchy, red, and swollen eyes (conjunctivitis), watery eyes, or blurred vision.
• Nosebleeds.
• Pain or swelling in the abdomen, flatulence, heartburn, or constipation.
• Itching.
• Unusual thinning or loss of hair.
• Numbness in hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin, or dry eyes.
• Decreased or increased skin sensitivity.
• Hot flushes, chills, or night sweats.

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

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

• Painful red lumps on the skin, skin pain, redness of the skin (inflammation of the fatty tissue beneath the skin).
• Cough, runny or stuffy nose, feeling of heaviness or pain when pressing the area around the eyes or sides of the nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe, stabbing, or throbbing headache, 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 in the joints (signs of arthralgia).
• Persistent feeling of sadness and loss of interest, interfering with normal life (signs of depression).
• Feeling of apprehension and worry along with physical symptoms such as palpitations, sweating, trembling, dry mouth (signs of anxiety).
• Numbness/drowsiness/excessive sleepiness.
• Tremors or involuntary movements (tremor).
• Memory impairment.
• Urge to keep moving legs (restless legs syndrome).
• Hearing noises (e.g. ringing, buzzing) in the ears not coming from outside (tinnitus).
• High blood pressure (hypertension).
• Belching or gas.
• Swelling of the lips.
• Difficulty swallowing.
• Increased sweating.
• Skin discoloration.
• Brittle nails.
• Red pimples or acne around the hair roots, possibly with pain, itching, or burning sensation (signs of inflammation of hair follicles, also called folliculitis).
• Skin rash with peeling or shedding of the skin (exfoliative dermatitis).
• Breast enlargement (can occur in men or women).
• Dull pain and/or heaviness in the testicles or lower abdomen, pain when urinating, during sexual intercourse, or ejaculation, blood in the urine (signs of testicular edema).
• Inability to get or maintain an erection (erectile dysfunction).
• Heavy or irregular menstrual periods.
• Difficulty achieving/maintaining sexual arousal.
• Decreased sexual desire.
• Nipple pain.
• General feeling of discomfort (malaise).
• Viral infections such as cold sores (herpes labialis).
• 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 joints or muscles.
• Abnormal laboratory test results.

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

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

• Confusion.
• Episode(s) of spasms and decreased level of consciousness (seizures).
• Discoloration 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 pain.
• Painful and/or blistering skin lesions.
• Delayed growth in children and adolescents.

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide 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 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 in the original packaging to protect from moisture.
• Do not use any container if it appears damaged or shows signs of tampering.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Glivec

• The active substance is imatinib mesilate.

• Each 100 mg Glivec tablet contains 100 mg of imatinib mesilate.

• Each 400 mg Glivec tablet contains 400 mg of imatinib mesilate.

• The other components are microcrystalline cellulose, crospovidone, hypromellose, magnesium stearate and colloidal anhydrous silica.

• The tablet coating consists of iron oxide red (E172), iron oxide yellow (E172), macrogol, talc and hypromellose.

Appearance of the product and contents of the pack

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

Glivec 400 mg film-coated tablets are oval, very dark yellow to brown-orange in colour. They are marked with «400» on one side and a score line on the other, with “SL” on each 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 pack sizes 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

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

Other sources of information

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