Glivec 400 mg film-coated tablets

 

What is it and how is it used?

Glivec is a medicine containing an active substance called imatinib. This medicine works by inhibiting the growth of abnormal cells in the diseases listed 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 white blood cells. These white cells usually help the body to fight infection. Chronic myeloid leukaemia is a form of leukaemia in which certain abnormal white cells (named myeloid cells) start growing out of control.

Glivec is also a treatment for adults for:

  • Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph-positive ALL). Leukaemia is a cancer of white blood cells. These white cells usually help the body to fight infection. Acute lymphoblastic leukaemia is a form of leukaemia in which certain abnormal white cells (named lymphoblasts) start growing out of control. Glivec inhibits the growth of these cells.
  • Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of blood diseases in which some blood cells start growing 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 (named eosinophils) start growing 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 bowels. It arises from uncontrolled cell growth of the supporting tissues of these organs.
  • Dermatofibrosarcoma protuberans (DFSP). DFSP is a cancer of the tissue beneath the skin in which some cells start growing out of control. Glivec inhibits the growth of these cells. In the rest of this leaflet, we will use the abbreviations when talking about these diseases.

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

What do you have to consider before using it?

Glivec will only be prescribed to you by a doctor with experience in medicines to treat blood cancers or solid tumours.

Follow all your doctor’s instructions carefully, even if they differ from the general information contained in this leaflet.

Do not take Glivec:

  • if you are allergic (hypersensitive) to imatinib or any of the other ingredients of Glivec listed in section 6. If this applies to you, tell your doctor without taking Glivec.

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

Take special care with Glivec
Before taking Glivec, tell your doctor:

  • if you have or have ever had a liver, kidney or heart problem.
  • if you are taking the medicine levothyroxine because your thyroid has been removed. If any of these apply to you, tell your doctor before taking Glivec.

During treatment with Glivec, tell your doctor straight away if you put on weight very quickly. Glivec may cause your body to retain water (severe fluid retention).

While you are taking Glivec, your doctor will regularly check whether the medicine is working. You will also have blood tests and be weighed regularly.

Glivec is also a treatment for children with CML. There is no experience in children with CML below 2 years of age. There is limited experience in children with Ph-positive ALL. There is no experience in children with GIST.

Some children and adolescents taking Glivec may have slower than normal growth. The doctor will monitor the growth at regular visits.

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription (such as paracetamol) and including herbal medicines (such as St. John’s Wort). Some medicines can interfere with the effect of Glivec when taken together. They may increase or decrease the effect of Glivec, either leading to increased side effects or making Glivec less effective. Glivec may do the same to some other medicines.

Pregnancy and breast-feeding

  • Talk to your doctor before taking Glivec if you are pregnant, might become pregnant or are breast-feeding.
  • Glivec is not to be used during pregnancy unless clearly necessary. Your doctor will discuss with you the possible risks of taking Glivec during pregnancy.
  • Women who might become pregnantare advised to use effective contraception during treatment.
  • Do not breast-feed during the treatment with Glivec.

Driving and using machines
You may feel dizzy or get blurred vision while taking this medicine. If this happens, do not drive or use any tools or machines until you are feeling well again.

How is it used?

Your doctor has prescribed Glivec because you suffer from a serious condition. Glivec can help you to fight this condition.

However, always take Glivec exactly as your doctor has told you. It is important that you do this as long as your doctor tells you to. You should check with your doctor or pharmacist if you are not sure.

Do not stop taking Glivec unless your doctor tells you to. If you are not able to take the medicine as your doctor prescribed or you feel you do not need it anymore, contact your doctor straight away.

How much to take

Use in adults
Your doctor will tell you exactly how many tablets of Glivec to 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 one tablet once a day, 600 mg to be taken as one tablet of 400 mg plus 2 tablets of 100 mg once a day.

If you are being treated for GIST The starting dose is 400 mg, to be taken as one tablet once a day.

For CML and GIST, your doctor may prescribe a higher or lower dose depending on how you respond to the treatment. If your daily dose is 800 mg (2 tablets), you should take one tablet in the morning and a second tablet in the evening.

  • If you are being treated for Ph-positive ALL: The starting dose is 600 mg to be taken as one tablet of 400 mg plus 2 tablets of 100 mg once a day.
  • If you are being treated for MDS/MPD: The starting dose is 400 mg to be taken as one tablet once a day.
  • If you are being treated for HES/CEL: The starting dose is 100 mg, to be taken as one tablet of 100 mg once a day. Your doctor may decide to increase the dose to 400 mg, to be taken as one tablet of 400 mg once a day, depending on how you respond to treatment.
  • If you are being treated for DFSP: The dose is 800 mg per day (2 tablets), to be taken as one tablet in the morning and a second tablet in the evening.

Use in children
The doctor will tell you how many tablets of Glivec to give to your child. The amount of Glivec given will depend on your child’s condition, body weight and height. The total daily dose in children must not exceed 800 mg. The treatment can either be given to your child as a once-daily dose or alternatively the daily dose can 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 you from stomach problems when taking Glivec.
  • Swallow the tablets whole 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 about 200 ml for each 400 mg tablet.
- Stir with a spoon until the tablets have completely dissolved.
- Once the tablet has dissolved, drink everything in the glass straight away. Traces of the dissolved tablets may be left behind 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 have accidentally taken too many tablets, talk to your doctor straight away. You may require medical attention. Take 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 nearly time for the next dose, skip the missed dose.
  • Then continue with your normal schedule.
  • Do not take a double dose to make up a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

What are possible side effects?

Like all medicines, Glivec can cause side effects, although not everybody gets them. They are usually mild to moderate.

These side effects may occur with certain frequencies, which are defined as follows:

  • Very common: affects more than 1 patient in 10.
  • Common: affects 1 to 10 patients in 100.
  • Uncommon: affects 1 to 10 patients in 1,000.
  • Rare: affects 1 to 10 patients in 10,000.
  • Very rare: affects less than 1 patient in 10,000.
  • Not known: frequency cannot be estimated from the available data.

Some side effects may be serious. Tell your doctor straight away if you get any of the following:

Very common or common side effects:
- 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 can reduce the number of white blood cells, so you might get infections more easily.
- Unexpected bleeding or bruising (when you have not hurt yourself).

Uncommon or rare side effects Chest pain, irregular heart rhythm signs of heart problems. Cough, having difficulty breathing or painful breathing signs of lung problems. Feeling light-headed, dizzy or fainting signs of low blood pressure. Feeling sick nausea, with loss of appetite, light-coloured urine, yellow skin or eyes signs of liver problems. Rash, red skin with blisters on the lips, eyes, skin or mouth, peeling skin, fever, raised red or purple skin patches, itching, burning sensation, pustular eruption signs of skin problems. Severe abdominal pain, blood in your vomit, stools or urine, black stools signs of gastrointestinal disorders. Severely decreased urine output, feeling thirsty signs of kidney problems. Feeling sick nausea with diarrhoea and vomiting, abdominal pain or fever signs of bowel problems. Severe headache, weakness or paralysis of limbs or face, difficulty speaking, sudden loss of consciousness signs of nervous system problems. Pale skin, feeling tired and breathlessness and having dark urine signs of low levels of red blood cells. Eye pain or deterioration in vision. Pain in your hips or difficulty walking. Numb or cold toes and fingers signs of Raynauds syndrome. Sudden swelling and redness of the skin signs of a skin infection called cellulites. Difficulty hearing. Muscle weakness and spasms with an abnormal heart rhythm signs of changes in the amount of potassium in your blood. Bruising. Stomach pain with feeling sick nausea. Muscle spasms with a fever, red-brown urine, pain or weakness in your muscles signs of muscle problems. Pelvic pain sometimes with nausea and vomiting, with unexpected vaginal bleeding, feeling dizzy or fainting due to low blood pressure signs of problems with your ovaries or womb. Nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness andor joint discomfort associated with abnormal laboratory test results eg. high potassium, uric acid and phosphorous levels and low calcium levels in the blood. If you get any of the above, tell your doctor straight away.

Other side effects may include:

Very common side effects Headache or feeling tired. Feeling sick nausea, being sick vomiting, diarrhoea or indigestion. Rash. Muscle cramps or joint, muscle or bone pain. Swelling such as round your ankles or puffy eyes. Weight gain. If any of these affects you severely, tell your doctor.

Common side effects Anorexia, weight loss or a disturbed sense of taste. Feeling dizzy or weak. Difficulty in sleeping insomnia. Discharge from the eye with itching, redness and swelling conjunctivitis, watery eyes or having blurred vision. Nose bleeds. Pain or swelling in your abdomen, flatulence, heartburn or constipation.

Itching. Unusual hair loss or thinning. Numbness of the hands or feet. Mouth ulcers. Joint pain with swelling. Dry mouth, dry skin or dry eye. Decreased or increased skin sensitivity. Hot flushes, chills or night sweats. If any of these affects you severely, tell your doctor.

Not known:
- Reddening and/or swelling on the palms of the hands and soles of the feet which may be accompanied by tingling sensation and burning pain.
- Slowing of growth in children and adolescents.
If any of these affects you severely, tell your doctor.

If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How should it be stored?

Keep out of the reach and sight of children. Do not use after the expiry date which is stated on the carton. Do not store above 30C. Store in the original package in order to protect from moisture. Do not use any pack that is damaged or shows signs of tampering.

What is it?

Glivec is a medicine that contains the active substance imatinib. It is available as capsules (orange-yellow: 50 mg; orange: 100 mg) and dark yellow/orange tablets (round: 100 mg; oval: 400 mg).

What is it used for?

Glivec is an anticancer medicine. It is used to treat the following diseases:

  • chronic myeloid leukaemia (CML), a cancer of the white blood cells in which granulocytes (a type of white blood cell) start growing out of control. Glivec is used when the patients are ‘Philadelphia chromosome positive’ (Ph+). This means that some of their genes have re-arranged themselves to form a special chromosome called the Philadelphia chromosome. Glivec is used in adults and children who have been newly diagnosed with Ph+ CML, who are not eligible for a bone marrow transplant. It is also used in adults and children in the ‘chronic phase’ of the disease if it is not responding to interferon alpha (another anticancer medicine), and in more advanced phases of the disease (‘accelerated phase’ and ‘blast crisis’);
  • Ph+ acute lymphoblastic leukaemia (ALL), a type of cancer in which lymphocytes (another type of white blood cell) multiply too quickly. Glivec is used in combination with other anticancer medicines in adults who have been newly diagnosed with Ph+ ALL. It is also used alone to treat Ph+ ALL that has returned following previous treatment, or is not responding to other medicines.
  • myelodysplastic or myeloproliferative diseases (MD/MPD), a group of diseases in which the body produces large numbers of abnormal blood cells. Glivec is used to treat adults with MD/MPD who have re-arrangements of the gene for platelet-derived growth factor receptor (PDGFR);
  • advanced hypereosinophilic syndrome (HES) or chronic eosinophilic leukaemia (CEL), diseases in which eosinophils (another type of white blood cell) start growing out of control. Glivec is used to treat adults with HES or CEL who have a specific re-arrangement of two genes called FIP1L1 and PDGFRα;
  • gastrointestinal stromal tumours (GIST), a type of cancer (sarcoma) of the stomach and bowel, when there is uncontrolled growth of cells in the supporting tissues of these organs. Glivec is used to treat adults with GIST that cannot be removed with surgery or have spread to other parts of the body, and adults who are at risk of GIST coming back after surgical removal;
  • dermatofibrosarcoma protuberans (DFSP), a type of cancer (sarcoma) in which cells in the tissue beneath the skin divide uncontrollably. Glivec is used to treat adults with DFSP that cannot be

removed with surgery, and in adults who are not eligible for surgery when the cancer has returned after treatment or has spread to other parts of the body.
Because the number of patients with these diseases is low, they are considered ‘rare’, and Glivec was designated an ‘orphan medicine’ (a medicine used in rare diseases) on various dates (see below). The medicine can only be obtained with a prescription.

How is it used?

Glivec treatment should be started by a doctor who has experience in the treatment of patients with cancers of the blood or solid tumours. Glivec is given by mouth with a meal and a large glass of water to reduce the risk of irritation of the stomach and gut. The dose depends on the disease being treated, the age and condition of the patient, and the response to treatment, but it should not exceed 800 mg a day. For more information, see the Package Leaflet.

How does it work?

The active substance in Glivec, imatinib, is a protein-tyrosine kinase inhibitor. This means that it blocks some specific enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of cancer cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these receptors, Glivec helps to control cell division.

How has it been studied?

For CML, Glivec has been examined in four main studies involving 2,133 adults and one study of 54 children. These included a study involving 1,106 adults that compared Glivec with the combination of interferon alpha plus cytarabine (other anticancer medicines). This study measured how long the patients lived without their cancer getting worse.
For ALL, Glivec has been examined in three studies involving 456 adults, including one study comparing Glivec with standard chemotherapy (medicines used to kill cancer cells) in 55 newly-diagnosed patients.
For GIST, Glivec has been examined in two main studies. One involved 147 patients whose GIST could not be surgically removed or had spread to other parts of the body, and looked at whether the tumours shrank in size. This study did not compare Glivec with any other medicines. The other study compared Glivec with placebo (a dummy treatment) in 713 patients whose cancer had been removed with surgery. This study measured how long the patients lived without their cancer coming back. For MD/MPD (31 patients), HES and CEL (176 patients), and DFSP (18 patients), Glivec was not compared with any other medicines. These studies examined whether blood cell counts returned to normal levels, or whether the number of cancerous blood cells or the size of tumours fell.

What benefits has it shown during the studies?

Glivec was more effective than the comparator medicines. In patients with CML, the cancer had got worse in 16% of the patients taking Glivec after five years, compared with 28% of those taking interferon alpha plus cytarabine. Glivec was also better than standard chemotherapy in patients with ALL. In patients with GIST that had been removed with surgery, patients taking Glivec lived for longer than those taking placebo without their cancer coming back. In the non-comparative studies of CML, ALL and GIST, between 26 and 96% of patients showed a response to Glivec. Due to their rarity, limited data were available for the other diseases, but around two thirds of the patients showed at least a partial response to Glivec.

What is the risk associated?

The most common side effects with Glivec (seen in more than 1 in 10 patients) are weight increase, neutropenia (low levels of the white blood cells that fight infection), thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), headache, nausea (feeling sick), vomiting, diarrhoea, dyspepsia (indigestion), abdominal (tummy) pain, oedema (fluid retention), rash, muscle spasm and cramps, muscle and joint pain, and fatigue (tiredness). For the full list of all side effects reported with Glivec, see the Package Leaflet.
Glivec should not be used in people who may be hypersensitive (allergic) to imatinib or any of the other ingredients.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Glivec’s benefits are greater than its risks for the treatment of CML, ALL, MD/MPD, HES, CEL, GIST and DFSP. The Committee recommended that Glivec be given marketing authorisation.
Glivec was originally authorised under ‘Exceptional Circumstances’, because, as the diseases are rare, limited information was available at the time of the approval. As the company had supplied the additional information requested, the ‘Exceptional Circumstances’ were lifted on 13 April 2007.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Glivec to Novartis Europharm Limited on 7 November 2001. The marketing authorisation was renewed on 7 November 2006.

The summaries of opinion of the Committee for Orphan Medicinal Products for Glivec are available here (CML: 14 February 2001), here (GIST: 20 November 2001), here (ALL: 26 August 2005), here (DFSP: 26 August 2005), here (HES and CEL: 28 October 2005) and here (MD/MPD: 23 December 2005).