How does it work?

Glivec tablets contain the active ingredient imatinib mesilate,which is a type of anticancer medicine called a protein tyrosine kinaseinhibitor. It is mainly used to treat cancer of the blood cells (leukaemia),but is also used to treat a rare cancer of the stomach and intestine and a typeof skin cancer.

Imatinib works by interfering with the pathways that signalcertain types of cancer cells to grow.

Leukaemia is a type of cancer that occurs when a cancerouschange in a white blood cell is produced. Chronic myeloid leukaemia (CML)affects white blood cells called granulocytes. Acute lymphoblastic leukaemia(ALL) affects white blood cells called lymphocytes. In both these types ofleukaemia, the cancerous change often involves an abnormal rearrangement of thechromosomes (genetic material) in the white blood cells. Leukaemic blood cellsoften have an abnormal chromosome called the Philadelphia chromosome (namedafter the place it was discovered), as well as other abnormal chromosomalarrangements.

The abnormal chromosomes disturb the normal control of the waythe blood cells divide and multiply. They cause an abnormal protein to beproduced on the blood cells, called Bcr-Abl tyrosine kinase. This protein makesthe white blood cells multiply without restraint and dramatically increases thenumber produced by the bone marrow.

Imatinib works by targeting this abnormal protein produced bythe abnormal Philadelphia chromosome. Imatinib blocks the action of thisprotein, which stops the cancerous cells from multiplying. The cancerous cellsthen die.

Imatinib is also used to treat a rare kind of cancer that occursin the wall of the stomach and small intestine. This cancer is called agastrointestinal stromal tumour (GIST).

This type of tumour is also caused by an abnormal protein thatmakes the cells grow and multiply abnormally. In this case the abnormal proteinis also a tyrosine kinase, called c-kit. Imatinib blocks the action of thisprotein, which stops the cancerous cells from multiplying uncontrollably. Thecancerous cells then die.

Imatinib is also used to treat a type of skin cancer calleddermatofibrosarcoma protuberans (DFSP) and works in a similar way here.

Imatinib only acts on cancerous cells because these are the onlycells that carry the abnormal tyrosine kinase. This means imatinib stops thegrowth of the abnormal cancerous cells, while having little effect on thegrowth of normal healthy cells.

What is it used for?

• Cancer of the blood affecting a type of white blood cell called granulocytes (Philadelphia chromosome positive chronic myeloid leukaemia or CML) in adults and children.
• Cancer of the blood affecting a type of white blood cell called lymphocytes (Philadelphia chromosome positive acute lymphoblastic leukaemia or ALL) in adults.
• A group of blood diseases in which some blood cells start growing out of control (myelodysplastic/myeloproliferative diseases, MDS/MPD) in adults.
• Blood diseases in which blood cells called eosinophils start growing out of control (hypereosinophilic syndrome, HES and/or chronic eosinophilic leukaemia, CEL) in adults.
• A rare cancer that occurs in the wall of the stomach and small intestine (gastrointestinal stromal tumours or GIST) in adults.
• A type of skin cancer called dermatofibrosarcoma protuberans (DFSP) in adults.

Warning!

• Glivec tablets should be taken with food and a large glass of water in order to minimise irritation to the gut. For people unable to swallow the tablets, they may be dispersed in a glass of mineral water or apple juice. The required number of tablets should be placed in the appropriate volume of drink (approximately 50 ml for a 100 mg tablet, and 200 ml for a 400 mg tablet) and stirred with a spoon. The suspension should be drunk immediately after the tablets have disintegrated.
• This medicine may cause dizziness and blurred vision. If affected, caution is required when driving or operating machinery.
• This medicine may sometimes cause a decrease in the normal amounts of healthy blood cells in the blood. For this reason you should consult your doctor immediately if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.
• This medicine can sometimes cause liver problems. Consult your doctor promptly if you develop unexplained itching, nausea and vomiting, abdominal pains, loss of appetite, flu-like symptoms, unusually dark urine, or yellowing of the skin or whites of the eyes (jaundice) while taking this medicine.
• While taking this medicine you should have regular blood tests to allow your doctor to monitor your liver function and the number of blood cells in your blood.
• It is recommended that people taking this medicine are weighed regularly. Any unexpected and rapid increases in weight should be investigated by your doctor. This is because imatinib can sometimes cause severe fluid retention.
• This medicine may potentially be harmful to an unborn baby. Women who could get pregnant should use a reliable method of contraception to prevent pregnancy while taking this medicine.
• The manufacturer of this medicine states that they have no clinical experience with this medicine in children with CML under two years of age and only limited experience in children with ALL. There is no experience in children or adolescents with GIST or HES/CEL and very limited experience in children with MDS/MPD and DFSP.

Use with caution in

• Children.
• Elderly people.
• Decreased liver function.
• Decreased kidney function.
• History of heart disease, eg heart failure.

Not to be used in

• Breastfeeding.

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such anallergy.If you feel you haveexperienced an allergic reaction, stop using this medicine and inform yourdoctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• The safety of this medicine during pregnancy has not been established. For this reason, it should not be used during pregnancy unless considered essential by your doctor, and only if the potential benefit to the mother outweighs any risks to the developing baby. Women who could get pregnant should use a reliable method of contraception to avoid getting pregnant while taking this medicine. Consult your doctor for further information.
• It is not known whether this medicine passes into breast milk. Mothers who need to take this medicine should not breastfeed. Seek medical advice from your doctor.

Label warnings

• Take this medication with or after food.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Because a side effect is statedhere, it does not mean that all people using this medicine will experience thator any side effect.

• Disturbances of the gut such as diarrhoea, nausea, vomiting, indigestion or abdominal pain
• Excessive fluid retention in the body tissues, resulting in swelling (oedema)
• Fatigue
• Pain in the muscles or joints
• Rash or itching
• Headache
• Disturbance in the normal numbers of blood cells in the blood
• Loss of appetite
• Alteration in taste
• Dizziness
• Pins and needles sensations (paraesthesia)
• Difficulty in sleeping (insomnia)
• Blurred vision
• Inflammation of the lining of the eye, causing pain and redness (conjunctivitis)
• Nosebleeds (epistaxis)
• Shortness of breath
• Dry skin
• Hair loss (alopecia)
• Night sweats
• Liver disorders
• Depression
• Sexual problems
• Bleeding from the stomach or intestines

The side effects listed above may not include all of the sideeffects reported by the drug'smanufacturer.For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

Imatinib can prevent the breakdown of paracetamol by the liver.You should not take paracetamol with this medicine without first checking withyour doctor or pharmacist.

The following medicines may decrease the blood level ofimatinib, which may make it less effective:

• dexamethasone
• phenytoin
• carbamazepine
• rifampicin
• phenobarbital (phenobarbitone)
• the herbal remedy St John's wort (hypericum perforatum).

The following medicines may increase the blood level ofimatinib, which could increase the risk of side effects:

• antifungals such as ketoconazole, itraconazole, miconazole
• the antibiotics erythromycin or clarithromycin.

Imatinib may increase the blood levels of the followingmedicines, which may increase the risk of their side effects:

• ciclosporin
• pimozide
• statins, eg simvastatin
• certain calcium channel blockers, eg nifedipine
• benzodiazepines, eg alprazolam, triazolam.

Imatinib may alter the anti-blood-clotting effect of warfarin.For this reason, warfarin is not recommended in combination with this medicine.People who need a medicine to prevent blood clots should instead be prescribeda heparin.

There may be an increased risk of side effects on the liver orblood cells if imatinib is used in combination with chemotherapy medicines thatcan have side effects on these areas.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK thatcontain imatinib as the active ingredient.