EVOLTRA 1 MG / ML CONCENTRATION FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

Evoltra 1 mg/ml concentrate for solution for infusion

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start using 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.
• 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. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Evoltra is and what it is used for

• 2. What you need to know before you use Evoltra

• 3. How to use Evoltra

• 4. Possible side effects

• 5. How to store Evoltra

• 6. Contents of the pack and other information

1. what evoltra is and what it is used for

Evoltra contains the active substance clofarabine. Clofarabine is one of a family of medicines called anticancer medicines. It works by hindering the growth of abnormal white blood cells, and eventually kills them. It works best against cells which are multiplying quickly – such as cancer cells.

Evoltra is used to treat children (> 1 year old), 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.

2. what you need to know before you use evoltra- if you are allergic to clofarabine or any of the other ingredients of this medicine (listed in section 6);

• - 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.

Warnings and precautions

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

• - 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.

30

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 get a rash with blisters or mouth ulcers;

• – if you lose your appetite, have nausea (feeling sick), vomiting, diarrhea, dark-colored urine and light-coloured stools, stomach pain, jaundice (yellowing of the skin and eyes), or if you feel generally unwell, these could be symptoms of an inflammation of the liver (hepatitis), or liver damage (hepatic failure);

• – if you pass little or no urine, or experience drowsiness, nausea, vomiting, breathlessness, loss of appetite and / or weakness (these may be signs of acute kidney failure / kidney failure).

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.

Other medicines and Evoltra

Tell your doctor if you are using or have recently used:

• – 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 during your treatment and within 3 months after completion of 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 sodium

This medicine contains 72 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 3.6 % of the recommended maximum daily dietary intake of sodium for an adult. Talk to

31 your pharmacist or doctor if you need 5 or more vials daily during your treatment cycle for a prolonged period, especially if you have been advised to follow a low salt (sodium) diet.

3. how to use evoltra

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.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• – 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 (may affect up to 1 in 10 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;

32

• – leaking from tiny blood vessels, rapid breathing, nosebleeds, breathing difficulties, breathlessnes­s, cough;

• – vomiting blood, stomach ache, pain in the bottom;

• – bleeding inside the head, stomach, intestine or lungs, 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, water retention 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;

• – liver damage (liver failure).

• – little or no urine, drowsiness, nausea, vomiting, breathlessness, loss of appetite and /or weakness (possible signs of acute kidney failure or kidney failure).

Uncommon side effects (may affect up to 1 in 100 people):

• – inflammation of the liver (hepatitis).

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store evoltra

Keep this medicine out of the sight and reach of children.

Do not use this medicine 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 8oC).

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other informationthe 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.

33

Marketing Authorisation Holder

Genzyme Europe B.V.

Paasheuvelweg 251105 BP Amsterdam The Netherlands

Manufacturer

SANOFI WINTHROP INDUSTRIE

30–36, avenue Gustave Eiffel

37100 Tours

France

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

Belgie/Belgiqu­e/Belgien/ Sanofi Belgium Tel/Tel: + 32 2 710 54 00	Lietuva UAB”SANOFI-AVENTIS LIETUVA” Tel. +370 5 275 5224
Efcnrapun SANOFI BULGARIA EOOD Ten: +359 (0) 2 9705300	Luxembourg/Lu­xemburg Sanofi Belgium Tel/Tel: + 32 2 710 54 00 (Belgique/Belgien)
Ceska republika sanofi-aventis, s.r.o. Tel: +420 233 086 111	Magyarorszag sanofi-aventis Zrt. Tel: +36 1 505 0050
	Malta Sanofi S.r.l Tel: +39 02 39394275
Danmark Sanofi A/S Tlf: +45 45 16 70 00	Nederland Genzyme Europe B.V. Tel: +31 20 245 4000
Deutschland Sanofi-Aventis Deutschland GmbH Tel.: 0800 04 36 996 Tel. aus dem Ausland: +49 69 305 70 13	Norge sanofi-aventis Norge AS Tlf: + 47 67 10 71 00
Eesti sanofi-aventis Estonia OU Tel. +372 6 273 488	Osterreich sanofi-aventis GmbH Tel: + 43 1 80 185 – 0
EZZaSa sanofi-aventis AEBE Tip/ +30 210 900 1600	Polska sanofi-aventis Sp. z o.o. Tel.: +48 22 280 00 00
Espana sanofi-aventis, S.A. Tel: +34 93 485 94 00	Portugal Sanofi – Produtos Farmaceuticos, Lda. Tel: +351 21 35 89 400

34

France                                    Romania

sanofi-aventis France Sanofi Romania SRL

Tel : 0 800 222 555 Tel: +40 (0) 21 317 31 36

Appel depuis 1’etranger : +33 1 57 63 23 23

Hrvatska

sanofi-aventis Croatia d.o.o.

Tel: +385 1 600 34 00

Ireland

sanofi-aventis Ireland Ltd T/A SANOFI

Tel: +353 (0) 1 4035 600

^sland

Vistor hf.

Sum: +354 535 7000

Italia

Sanofi S.r.l

Tel: 800536389

Kvnpog

sanofi-aventis Cyprus Ltd.

Tql: +357 22 871600

Latvija

sanofi-aventis Latvia SIA

Tel: +371 67 33 24 51

This leaflet was last revised 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.

Detailed information on this medicine is available on the European Medicines Agency web site: and on the website of {name of Member State Agency (link)}>. There are also links to other websites about rare diseases and treatments.

The following information is intended for healthcare professionals only:

Special precautions for administration

< Product Name> 1 mg/ml concentrate for solution for infusion must be diluted prior to administration. It should be filtered through a sterile 0.2 micrometre syringe filter and then diluted with sodium chloride 9 mg/ml (0.9%) intravenous infusion to produce a total volume according to the examples given in the table below. However, the final dilution volume may vary depending on the patient’s clinical status and physician discretion. (If the use of a 0.2 micrometre syringe filter is not feasible, the concentrate should be pre-filtered with a 5 micrometre filter, diluted and then administered through a 0.22 micrometre inline filter.)

35

Suggested dilution schedule based on the recommended dosage of 52 mg/m2/day clofarabine
Body surface area (m2)	Concentrate (ml)*	Total diluted volume
< 1.44	< 74.9	100 ml
1.45 to 2.40	75.4 to 124.8	150 ml
2.41 to 2.50	125.3 to 130.0	200 ml
*Each ml of concentrate contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine. Therefore, for patients with a body surface area < 0.38 m2, the partial contents of a single vial will be required to produce the recommended daily dosage of clofarabine. However, for patients with a body surface area > 0.38 m2, the contents of between 1 to 7 vials will be required to produce the recommended daily dosage of clofarabine.

The diluted concentrate should be a clear, colourless solution. It should be visually inspected for particulate matter and discolouration prior to administration.

The diluted concentrate is chemically and physically stable for 3 days at 2°C to 8°C and at room temperature (up to 25°C). From a microbiological point of view, it should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C unless dilution has taken place under controlled and validated aseptic conditions. Do not freeze.

Instructions for handling

Procedures for proper handling of antineoplastic agents should be observed. Cytotoxic medicinal products should be handled with caution.

The use of disposable gloves and protective garments is recommended when handling Evoltra. If the product comes into contact with eyes, skin or mucous membranes, rinse immediately with copious amounts of water.

Evoltra should not be handled by pregnant women.

Disposal

Evoltra is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

36

VV-REG-1190026 1.0