Evoltra 1 mg/ml concentrate for solution for infusion

Evoltra is used to treat children, teenagers and young adults up to 21 years old with acute lymphoblastic leukaemia (ALL) when previous treatments have not worked or have stopped working. Acute lymphoblastic leukaemia is caused by abnormal growth of some types of white blood cells. Clofarabine is one of a family of medicines called cytotoxic medicines. It works by hindering the growth of these abnormal white blood cells, and eventually kills them. It works best against cells which are multiplying quickly ? such as cancer cells.

Do not use Evoltra:

• if you are allergic (hypersensitive) to clofarabine or any of the other ingredients of Evoltra;
• if you are breast-feeding (please read the section ?Pregnancy and breast-feeding? below);
• if you have severe kidney or liver problems.

Tell your doctor if any of these conditions apply to you. If you are the parent of a child who is being treated with Evoltra, tell the doctor if any of them apply to your child.

Take special care with Evoltra:

• if you have suffered a severe reaction after previously using this medicine;
• if you have kidney disease, or used to have it;
• if you have liver disease, or used to have it;
• if you have heart disease, or used to have it.

Tell your doctor if any of these apply to you. Evoltra may not be suitable for you.

Tell your doctor or carer immediately if you experience any of the following as you may need to stop treatment:

• If you get a fever or high temperature ? because clofarabine reduces the number of blood cells made in the bone marrow, you may be more likely to catch infections;
• If you have breathing difficulties, rapid breathing, or breathlessness;
• If you feel a change in your heart rate;
• If you suffer from dizziness (light-headedness) or fainting ? it may be a symptom of low blood pressure;
• If you feel sick or have diarrhoea (loose bowels);
• If your urine is darker than usual ? it is important to drink plenty of water to avoid dehydration.

If you are the parent of a child who is being treated with Evoltra, tell the doctor if any of the above conditions apply to your child.

During treatment with Evoltra, your doctor will carry out regular blood tests and other tests to monitor your health. Because of the way this medicine works, it will affect your blood and other organs.

Talk to your doctor about contraception. Young men and women must use effective contraception during and after treatment. See the section ?Pregnancy and breast-feeding? below. Evoltra may harm both male and female reproductive organs. Ask your doctor to explain what can be done to protect you or allow you to have a family.

Taking other medicines
Please tell your doctor if you are taking or have recently taken:

• medicines for heart disease;
• any medicine that changes your blood pressure;
• medicines that affect your liver or kidneys;
• any other medicines including those obtained without a prescription.

Pregnancy and breast-feeding

Clofarabine should not be used during pregnancy unless clearly necessary.
Women who are able to get pregnant: you must use effective contraception during treatment with clofarabine. Clofarabine may cause harm to unborn babies when used by pregnant women. If you are pregnant or you become pregnant during treatment with clofarabine, get medical advice immediately.

Men must also use effective contraception while they or their partner are treated with clofarabine.

If you are breast-feeding, you must stop breast-feeding before starting the treatment, and must not breast-feed either during or after your treatment.

Driving and using machines
Do not drive or use any tools or machines if you feel dizzy, light-headed or faint.

Evoltra contains salt

Each vial contains 180 mg of salt (sodium chloride). This is equivalent to 3.08 mmol (or 70.77 mg) of sodium. You need to allow for this if you are on a controlled sodium diet.

Your treatment with Evoltra has been prescribed by a qualified doctor experienced in treating leukaemia.

Your doctor will work out the dose that is right for you depending on your height, weight and how well you are. Before Evoltra is given to you, it will be diluted in a sodium chloride solution (salt and water). Tell your doctor if you are on a controlled sodium diet as it could affect how you will be given your medicine.

Your doctor will give you Evoltra once every day for 5 days. It will be given to you as an infusion through a long thin tube which goes into a vein (a drip), or into a small medical appliance that is inserted under the skin (port-a-cath) if you (or your child) have one implanted. The infusion will be given over 2 hours. If you (or your child) weigh less than 20 kg, the infusion time may be longer.

Your doctor will monitor your health and may change your dose depending on your response to the treatment. It is important to drink plenty of water to avoid dehydration.

If you use more Evoltra than you should
If you think you may have been given too much medicine, tell your doctor straight away.

If you forget to use Evoltra
Your doctor will tell you when you need to be given this medicine. If you think that you have missed a dose, tell your doctor straight away.

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

Like all medicines, Evoltra can cause side effects.

Very common side effects

These are likely to affect more than 1 in 10 patients:

• anxiety, headache, fever, tiredness;
• feeling and being sick, diarrhoea (loose bowels);
• flushing, itching and inflamed skin, inflammation of mucus (moist) linings such as the mouth and other areas;
• you may have more infections than normal because Evoltra can lower the number of certain types of blood cells in your body;
• skin rashes which may be itchy, red, painful or peeling skin including palms of the hands and soles of the feet, or small reddish or purple spots underneath the skin.

Common side effects

These are likely to affect more than 1 in every 100 people:

• infections of the blood, pneumonia, shingles, implant infections, infections of the mouth such as thrush and cold sores;
• changes in blood chemistry, changes in white blood cells;
• allergic reactions;
• feeling thirsty and producing darker or less urine than normal, decreased or loss of appetite, weight loss;
• agitation, irritability, or restlessness;
• feeling numb or weak in the arms and legs, numbness of the skin, sleepiness, dizziness, tremor;
• hearing problems;
• water collecting around the heart, fast heartbeat;
• low blood pressure, lump due to bad bruising;
• leaking from tiny blood vessels, rapid breathing, nosebleeds, breathing difficulties, breathlessness, cough;
• vomiting blood, stomach ache, pain in the bottom;
• bleeding mouth or gums, mouth ulcers, inflamed mouth lining;
• yellowing of the skin and eyes (also called jaundice), or other liver disorders;
• bruising, hair loss, changes to skin colour, increased sweating, dry skin, or other skin problems;
• pain in the chest wall or bones, neck or back pain, pain in limbs, muscles, or joints;
• blood in urine;
• failure of organs, pain, increased muscle tension, waterretention and swelling in parts of the body, including the arms and legs, changes in mental state, feeling hot, cold or abnormal;
• clofarabine may affect the levels of certain substances in the blood. Your doctor will carry out regular blood tests to check whether your body is working properly.

Talk to your doctor if you are concerned about any of these side effects or if there is anything you do not understand.

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

Keep out of the reach and sight of children.

Do not use Evoltra after the expiry date which is stated on the vial label and box after EXP. The expiry date refers to the last day of that month.

Do not freeze. Once prepared and diluted, Evoltra should be used straight away or within 24 hours if stored in a refrigerator (at 2 oC to 8 oC).

Any unused medicine should be destroyed by your doctor.

What Evoltra contains
The active substance is clofarabine. Each ml contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine.The other ingredients are sodium chloride and water for injections.

What Evoltra looks like and contents of the pack
Evoltra is a concentrate for solution for infusion . It is a clear, almost colourless solution that is prepared and diluted before it is used. It is supplied in 20 ml glass vials. The vials contain 20 mg of clofarabine and are packaged in a box. Each box contains 1, 3, 4, 10 or 20 vials, but not all pack sizes may be marketed.

Marketing Authorisation Holder

Genzyme Europe B.V.
Gooimeer 10
1411DD Naarden
The Netherlands
Tel: +31 (0)35 699 12 00
Fax: +31 (0) 35 694 32 14

Manufacturer
Pharmachemie B.V. (PCH)
Swensweg 5
Haarlem
The Netherlands

Genzyme Limited
37 Hollands Road
Haverhill
Suffolk
CB9 8PU
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

ItaliaMalta Genzyme Srl ItaliaItalja Tel 39 059 349811 BelgiëBelgiqueBelgien LuxemburgLuxembourg Genzyme Belgium N.V. TelTél 32 2 714 17 11

Magyarország Genzyme Europe B.V. Képviselet Tel 36 1 310 7440 Genzyme CEE GmbH 359 2 971 1001

Nederland Genzyme Europe B.V. Tel 31 35 6991200 eská RepublikaSlovenská RepublikaSlovenija Genzyme Czech, s.r.o. Tel 420 221 772 511

Österreich Genzyme Austria GmbH Tel 43 1 774 65 38 DanmarkNorgeSverigeSuomiFinland Ísland Genzyme AS DanmarkTanskaDanmörk TlfPuh.Sími 45 32712600

Deutschland Genzyme GmbH Tel 49 610236740 PolskaEestiLatvijaLietuva Genzyme Polska Sp. z o.o. PoolaPolijaLenkija Tel 48 22 24 60 900

Genzyme Hellas Ltd. 30 210 99 49 270 Portugal Genzyme Portugal S.A. Tel 351 21 422 0100

España Genzyme S.L.U. Tel 34 91 6591670 România Genzyme Biopharma SRL Tel 40 21 24 34 228

France Genzyme S.A.S. Tél 33 0 825 825 863 United KingdomIreland Genzyme Therapeutics Ltd.United Kingdom Tel 44 1865 405200

This leaflet was last approved in

This medicine has been authorised under ?Exceptional Circumstances?. This means that because of the rarity of this disease it has been impossible to get complete information on this medicine. The European Medicines Agency will review any new information on the medicine every year and this leaflet will be updated as necessary.