Evoltra

Package leaflet: Information for the user

Evoltra 1 mg/mL concentrate for solution for infusion

clofarabine
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please 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 questions, ask your doctor.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any possible side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

1. What Evoltra is and what it is used for
2. What you need to know before using 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 belongs to a group of medicines called antineoplastic agents. It works by slowing down the growth of abnormal white blood cells and eventually kills them. It is most effective against cells that are multiplying rapidly, such as cancer cells.
Evoltra is used to treat children (≥ 1 year of age), adolescents, and young patients up to 21 years of age with acute lymphoblastic leukemia (ALL) when previous treatments have failed or are no longer effective. Acute lymphoblastic leukemia is caused by the abnormal growth of certain types of white blood cells.

2. What you need to know before using Evoltra

Do not use Evoltra

• if you are allergic to clofarabine or to any of the excipients of this medicine (listed in section 6);
• if you are breastfeeding (see the section “Pregnancy and breastfeeding” below);
• if you have severe kidney or liver problems.

Tell your doctor if any of the following apply to you. If you are the parent of
a child being treated with Evoltra, inform the doctor if the child meets any of these conditions.
Warnings and precautions
Tell your doctor if any of the following apply to you. Evoltra may not be suitable for you:

• if you have previously experienced severe reactions after using this medicine;
• if you have a kidney disease or have had one in the past;
• if you have a liver disease or have had one in the past;
• if you have a heart condition or have had one in the past.

Tell your doctor or healthcare professional immediately if you experience any of the following, as treatment may need to be stopped:

• if you have fever or high temperature; because clofarabine reduces the number of blood cells produced by the bone marrow, you may be more likely to develop an infection;
• if you have difficulty breathing, breathe rapidly, or feel short of breath;
• if you notice changes in your heart rate;
• if you experience dizziness (a feeling of emptiness in the head) or fainting: this could be a sign of low blood pressure;
• if you have nausea or diarrhea;
• if your urine is darker than normal – it is important to drink plenty of water to prevent dehydration;
• if you develop a rash with blisters or mouth ulcers;
• if you lose your appetite, have nausea (feeling unwell), vomiting, diarrhea, dark urine and pale stools, stomach pain, jaundice (yellowing of the skin and eyes), or feel generally unwell; these could be symptoms of liver inflammation (hepatitis) or liver damage (liver failure);
• if you urinate less than usual or not at all, or if you experience drowsiness, nausea, vomiting, shortness of breath, loss of appetite and/or weakness (these could be signs of acute kidney failure / kidney impairment).

If you are the parent of a child being treated with Evoltra, inform the doctor if the child experiences any of the above conditions.
During treatment with Evoltra, your doctor will regularly take blood samples and perform other tests to monitor your health. Due to its mechanism of action, this medicine may affect blood parameters and other organs.
Talk to your doctor about contraception. Men and women of childbearing age must use effective contraceptive methods during and after treatment. See the section “Pregnance and breastfeeding” below. Evoltra may damage male and female reproductive organs. Ask your doctor to explain what can be done to preserve your fertility.
Other medicines and Evoltra
Inform your doctor if you are currently using or have recently used:

• medicines for heart conditions;
• any medicine that affects blood pressure;
• medicines that affect the liver or kidneys;
• any other medicines, including those without a prescription.

Pregnancy and breastfeeding
Clofarabine must not be used during pregnancy unless clearly necessary.
Women of childbearing potential: you must use effective contraception during treatment with clofarabine and for 6 months after completing treatment. Clofarabine may harm the unborn child if used during pregnancy. If you are pregnant or become pregnant during treatment with clofarabine, contact your doctor immediately.
Men must also use effective contraception and must be advised not to father a child during treatment with clofarabine and for 3 months after completing treatment.
If you are breastfeeding, you must stop breastfeeding before starting treatment and must not breastfeed during treatment or for at least 2 weeks after stopping treatment.
Driving and using machines
Do not drive or operate tools or machinery if you experience dizziness, a feeling of emptiness in the head, or feel faint.
Evoltra contains sodium
This medicine contains 72 mg of sodium (a key component of table salt) per vial. This corresponds to 3.6% of the maximum daily recommended dietary intake of sodium for an adult. Talk to your doctor or pharmacist if you require 5 or more vials per day during your treatment cycle for a prolonged period, especially if you have been advised to follow a low-sodium diet.

3. How to use Evoltra

Your treatment with Evoltra has been prescribed by a qualified doctor experienced in the treatment of leukaemia.
Your doctor will calculate the correct dose for you based on your height, weight, and general health status. Before administration, Evoltra will be diluted in a sodium chloride solution (salt and water). Inform your doctor if you are following a sodium-controlled diet, as this may affect the way the medicine is administered.
Your doctor will administer Evoltra once daily for 5 days by infusion, through a thin tube inserted into a vein (intravenous drip) or through a small medical device implanted under the skin (port-a-cath), if one has been implanted in you (or in the child). The infusion will be given over a period of 2 hours. If you (or the child) weigh less than 20 kg, the infusion time may be longer.
Your doctor will monitor your health condition and may adjust the dose according to your response to treatment. It is important to drink plenty of water to avoid dehydration.
If you use more Evoltra than you should
If you think the medicine has been administered in excess, inform your doctor immediately.
If you forget to use Evoltra
Your doctor will inform you when the medicine should be administered. If you think you have missed a dose, inform your doctor immediately.
If you have any further questions about the use of this medicine, consult 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, fatigue;
• nausea and vomiting, diarrhoea;
• hot flushes, itching and inflamed skin, inflammation of mucous membranes such as the mouth and other areas;
• infections may occur more frequently than normal, as Evoltra can reduce the number of certain types of blood cells in the body;
• skin rashes, possibly itchy, red, painful or peeling skin, including on the palms of the hands and soles of the feet, or small reddish or purple spots under the skin.

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

• blood infections, pneumonia, shingles (herpes zoster), catheter-related infections, mouth infections such as candidiasis and cold sores (herpes labialis);
• changes in blood chemistry values, changes in white blood cells;
• allergic reactions;
• feeling thirsty, producing darker urine or less urine than normal, reduced or loss of appetite, weight loss;
• restlessness, irritability or agitation;
• numbness or weakness in arms and legs, skin numbness, drowsiness, dizziness, tremor;
• hearing problems;
• fluid accumulation around the heart, rapid heartbeat;
• low blood pressure, swelling due to large bruises;
• bleeding from small blood vessels (capillaries), rapid breathing, nosebleeds, difficulty breathing, shortness of breath, cough;
• vomiting blood, stomach pain, anal pain;
• bleeding in the brain, stomach, intestines or lungs, mouth or gums, mouth ulcers, inflammation of the mucous membrane of the mouth;
• yellowing of the skin and eyes (also known as jaundice) or other liver problems;
• bruising, hair loss, skin colour changes, increased sweating, dry skin and other skin problems;
• chest wall, bone, neck or back pain, limb, muscle or joint pain;
• blood in the urine;
• organ failure, pain, increased muscle tension, fluid retention and swelling in parts of the body, including arms and legs, changes in mental state, feeling hot, feeling cold, feeling out of tune;
• clofarabine may affect levels of certain substances in the blood. Your doctor will perform periodic blood tests to monitor your body’s proper functioning;
• liver damage (hepatic failure);
• little or no urine, drowsiness, nausea, vomiting, shortness of breath, loss of appetite and/or weakness (possible signs of acute kidney injury 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, including any not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V.
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 stated on the vial after "Exp". The expiry date refers to the last day of that month.
Do not freeze.
Once prepared and diluted, Evoltra must be used immediately or within 24 hours if stored in the refrigerator (at 2-8°C).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

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 excipients are sodium chloride and water for injections.

Description of the appearance of Evoltra and contents of the pack
Evoltra is a concentrate for solution for infusion. It is a clear, almost colourless solution, which must be prepared and diluted before use. It is available in 20 mL glass vials. The vials contain 20 mg of clofarabine and are supplied in a carton. Each carton contains 1, 3, 4, 10 or 20 vials, but not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanofi B.V.
Paasheuvelweg 25
1105 BP Amsterdam
The Netherlands

Manufacturer
SANOFI WINTHROP INDUSTRIE
30-36, avenue Gustave Eiffel
37100 Tours
France

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien / Lietuva
Sanofi Belgium Swixx Biopharma UAB
Tél/Tel: + 32 2 710 54 00 Tel. +370 5 236 91 40

България / Luxembourg/Luxemburg
Swixx Biopharma EOOD Sanofi Belgium
Tел: +359 (0) 2 4942 480 Tél/Tel: + 32 2 710 54 00
(Belgique/Belgien)

Česká republika / Magyarország
sanofi-aventis, s.r.o. sanofi-aventis Zrt.
Tel: +420 233 086 111 Tel: +36 1 505 0050

Malta
Sanofi S.r.l
Tel: +39 02 39394275

Danmark / Nederland
Sanofi A/S Sanofi B.V.
Tlf: +45 45 16 70 00 Tel: +31 20 245 4000

Deutschland
Sanofi-Aventis Deutschland GmbH / Norge
Tel.: 0800 52 52 010 sanofi-aventis Norge AS
Tel. aus dem Ausland: +49 69 305 21 131 Tlf: + 47 67 10 71 00

Eesti / Österreich
Swixx Biopharma OÜ sanofi-aventis GmbH
Tel. +372 640 10 30 Tel: + 43 1 80 185 - 0

Ελλάδα / Polska
Sanofi-Aventis Μονοπρόσωπη AEBE sanofi-aventis Sp. z o.o.
Τηλ: +30 210 900 1600 Tel.: +48 22 280 00 00

España / Portugal
sanofi-aventis, S.A. Sanofi – Produtos Farmacêuticos, Lda.
Tel: +34 93 485 94 00 Tel: +351 21 35 89 400

France / România
Sanofi Winthrop Industrie Sanofi Romania SRL
Tél : 0 800 222 555 Tel: +40 (0) 21 317 31 36
Appel depuis l’étranger : +33 1 57 63 23 23

Hrvatska / Slovenija
Swixx Biopharma d.o.o. Swixx Biopharma d.o.o.
Tel: +385 1 2078 500 Tel: +386 1 235 51 00

Ireland / Slovenská republika
sanofi-aventis Ireland Ltd T/A SANOFI Swixx Biopharma s.r.o.
Tel: +353 (0) 1 4035 600 Tel: +421 2 208 33 600

Ísland / Suomi/Finland
Vistor hf. Sanofi Oy
Sími: +354 535 7000 Puh/Tel: + 358 201 200 300

Italia / Sverige
Sanofi S.r.l Sanofi AB
Tel: 800536389 Tel: +46 (0)8 634 50 00

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Latvija / United Kingdom (Northern Ireland)
Swixx Biopharma SIA Sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6 616 47 50 Tel: +44 (0) 800 035 2525

This leaflet was last updated on
The marketing authorisation for this medicine has been granted under "exceptional circumstances". This means that, due to the rarity of the disease, complete information about this medicine could not be obtained. The European Medicines Agency will review any new information on the medicine annually, and this patient information leaflet will be updated if necessary.

More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ and on the website of {name of Member State agency (link)}. In addition, links to other websites on rare diseases and their treatments are provided.

The following information is intended for healthcare professionals only:

Special precautions for administration
Evoltra 1 mg/mL concentrate for solution for infusion must be diluted before administration. It must be filtered through a sterile 0.2 micrometre syringe filter and then diluted with sodium chloride 9 mg/mL (0.9%) for intravenous infusion to achieve a total volume according to the examples shown in the table below. However, the final dilution volume may vary depending on the patient's clinical condition and at the physician's discretion. (If a 0.2 micrometre syringe filter cannot be used, the concentrate must be pre-filtered with a 5 micrometre filter, diluted, and then administered through an in-line 0.22 micrometre filter.)

The diluted concentrate should be a clear, colourless solution. It must be visually inspected for the presence of particles and discoloration before administration.
The diluted concentrate is chemically and physically stable for 3 days at a temperature between 2°C and 8°C and at room temperature (up to 25°C). From a microbiological standpoint, it should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, unless the dilution has taken place under controlled and validated aseptic conditions. Do not freeze.
Handling instructions
Procedures for the proper handling of antineoplastic agents must be observed. Cytotoxic medicinal products must be handled with care.
The use of disposable gloves and protective clothing 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 must not be handled by pregnant women.
Disposal
Evoltra is for single use only. Any unused medicinal product or waste material must be disposed of in accordance with local requirements.