EVOLTRA 1 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. Evoltra 1 mg/mL concentrate for solution for infusion
   1. What is Evoltra and what is it 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

Evoltra 1 mg/mL concentrate for solution for infusion

clofarabine

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
encountered during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before using this medicine as 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If any possible side effects occur, including those not listed in this leaflet, tell 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 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 is Evoltra and what is it used for

Evoltra contains the active substance clofarabine. Clofarabine belongs to a group of medicines
called antineoplastic agents. It works by slowing the growth of abnormal white blood cells and eventually killing them.
It works best on cells that are multiplying rapidly, such as cancer cells.
Evoltra is used for the treatment of children (≥ 1 year of age), adolescents and young patients
up to 21 years of age with acute lymphoblastic leukemia (ALL) for whom previous treatments have not
worked or have stopped working. 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 allergicto clofarabine or any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding(see the “Pregnancy and breastfeeding” section 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 being treated with Evoltra tell your doctor if the child falls into any
of these conditions.
Warnings and precautions
Tell your doctor if any of these conditions apply to you.Evoltra may not be suitable for you:

• if you have developed severe reactionsafter using this medicine previously;
• if you have a kidney diseaseor have had one in the past;
• if you have a liver diseaseor have had one in the past;
• if you have a heart diseaseor have had one in the past.

Tell your doctor or healthcare professional immediatelyif you experience any of the
following, as you may need to stop treatment:

• if you have a 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, are breathing rapidly, or feel short of breath;
• if you feel that your heart rate is changing;
• if you experience dizziness (feeling lightheaded) or fainting: this may be a symptom of low blood pressure;
• if you have nausea or diarrhea;
• if your urine is darker than usual - it is important to drink plenty of water to prevent dehydration;
• if a rash develops with blisters or sores in the mouth;
• if you lose your appetite, feel unwell, have vomiting, diarrhea, dark urine, and pale stools, abdominal pain, jaundice (yellowing of the skin and eyes), or a general feeling of being unwell; these could be symptoms of liver inflammation (hepatitis) or liver damage (liver failure);
• if you pass little or no urine, or feel sleepy, have nausea, vomiting, shortness of breath, loss of appetite and/or weakness (these may be signs of acute kidney injury / kidney failure).

If you are the parentof a child being treated with Evoltra, tell your doctor if the child
falls into any of the above conditions.
During treatment with Evoltra,your doctor will take blood samples and perform
other tests at regular intervals to monitor your health. Due to the way this medicine
works, it will affect your blood 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 “Pregnancy and breastfeeding” section
below. Evoltra can damage male and female reproductive organs. Ask your doctor to
explain what you can do to protect yourself so that you can conceive.

Other medicines and Evoltra
Tell your doctor if you are taking or have recently taken:

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

Pregnancy and breastfeeding
Clofarabine should not be used during pregnancy unless it is clearly necessary.

Women who could become pregnant:must use effective contraception during
treatment with clofarabine and for 6 months after completing treatment. If used by pregnant
women, clofarabine can harm the unborn child. If you are pregnant or become pregnant
during treatment with clofarabine, tell your doctor immediately.
Men must also use effective contraception and must be warned 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 up to 2 weeks after finishing treatment.

Driving and operating machinery
Do not drive or operate tools or machinery if you feel dizzy, lightheaded, or faint.

Evoltra contains sodium
This medicine contains 72 mg of sodium (the main component of table salt) per
vial. This is equivalent to 3.6% of the recommended maximum daily intake of
salt for an adult. Talk to your doctor or pharmacist if you need 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

Treatment with Evoltra has been prescribed by a qualified doctor experienced in the treatment of
leukemia.

The doctor will calculate the right dose for youbased on your height, weight and state of health. Before it
is administered to you, Evoltra will be diluted in a sodium chloride solution (water and salt). Inform your
doctor if you are following a controlled-sodium diet because this could affect the
way the medicine is administered.

The doctor will administer Evoltra once a day for 5 daysvia infusion, through a
long, thin tube that enters a vein (drip) or a small medical device inserted
under the skin (port-a-cath), if one has been implanted in you (or the child). The infusion will be
administered over 2 hours. If you (or the child) weigh less than 20 kg, the infusion time may
be longer.
The doctor will monitor your health and may adjust the dose based on 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 believe that the medicine has been administered to you in an excessive quantity, inform your
doctor immediately.

If you forget to use Evoltra
The doctor will tell you when the medicine should be administered to you. If you believe you have missed
a dose, inform your doctor immediately.
If you have any further doubts about 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, fatigue;
• nausea and vomiting, diarrhoea;
• hot flushes, itching and inflamed skin, inflammation of the mucous membranes such as the mouth and other areas;
• infections may be more frequent than normal since Evoltra can reduce the number of certain types of blood cells present in the body;
• skin rashes which may be itchy, reddened, painful or scaling skin, even on the palms of the hands and soles of the feet, or small reddish or purplish spots under the skin.

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

• blood infections, pneumonia, herpes zoster, implant infections, mouth infections, such as candidiasis and cold sores;
• changes in blood test values, changes in white blood cells;
• allergic reactions;
• feeling thirsty and passing darker urine or less urine than normal, decreased or loss of appetite, weight loss;
• agitation, irritability or restlessness;
• feeling of numbness or weakness in the arms and legs, skin insensitivity, drowsiness, dizziness, tremor;
• hearing problems;
• fluid accumulation around the heart, rapid heartbeat;
• low blood pressure, swelling due to large bruises;
• bleeding from the smallest blood vessels (capillaries), rapid breathing, nosebleeds, difficulty breathing, shortness of breath, cough;
• vomiting blood, stomach pain, anal pain;
• brain bleeding, of the stomach, intestine or lungs, of the mouth or gums, mouth ulcers, inflammation of the oral mucosa;
• yellowing of the skin and eyes (also called jaundice) or other liver disorders;
• bruising, hair loss, changes in skin colour, increased sweating, dry skin and other skin problems;
• pain in the chest wall or bones, neck or back, pain in the limbs, muscles or joints;
• blood in the urine;
• organ failure, pain, increased muscle tension, fluid retention and swelling in some parts of the body, including the arms and legs, changes in mental status, feeling of warmth, feeling of coldness, feeling out of sorts;
• clofarabine may affect the levels of certain substances in the blood. The doctor will perform periodic blood tests to check the proper functioning of the body;
• liver damage (hepatic failure);
• little or no urine, drowsiness, nausea, vomiting, shortness of breath, loss of appetite and/or weakness (possible signs of acute renal 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, even those not listed in this leaflet, tell your doctor. You can also report side effects directly through the national reporting system indicated in Annex V .
By reporting side effects you can help to 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 bottle 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
a refrigerator (at 2-8 C).
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack 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 is
prepared and diluted before use. It is available in 20 mL glass vials. The vials
contain 20 mg of clofarabine and are packaged 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 on this medicine, contact the local representative of the Marketing
Authorisation Holder

België/Belgique/Belgien/
Sanofi Belgium
Tél/Tel: + 32 2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel. +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел: +359 (0) 2 4942 480

Česká republika
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: + 32 2 710 54 00
(Belgique/Belgien)

Magyarország
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
Sanofi B.V.
Tel: +31 20 245 4000

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Norge
sanofi-aventis Norge AS
Tlf: + 47 67 10 71 00

Eesti
Swixx Biopharma OÜ
Tel. +372 640 10 30

Österreich
sanofi-aventis GmbH
Tel: + 43 1 80 185 - 0

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 1600

Polska
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Portugal
Sanofi – Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

France
Sanofi Winthrop Industrie
Tél : 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ireland
sanofi-aventis Ireland Ltd T/A SANOFI
Tel: +353 (0) 1 4035 600

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Ísland
Vistor hf.
Sími: +354 535 7000

Suomi/Finland
Sanofi Oy
Puh/Tel: + 358 201 200 300

Italia
Sanofi S.r.l
Tel: 800536389

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

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

United Kingdom (Northern Ireland)
Sanofi-aventis Ireland Ltd. T/A SANOFI
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
because the disease is rare, it has not been possible to obtain complete information on this
medicine. The European Medicines Agency will review any new information annually.
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 {member state competent authority (link)}. Links to
other websites on rare diseases and related therapeutic treatments are also provided.
The following information is intended for healthcare professionals:
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 micrometer syringe filter and then
diluted with sodium chloride 9 mg/mL (0.9%) for intravenous infusion to reach a total
volume according to the examples reported in the following table. However, the final dilution
volume may vary depending on the patient's clinical condition and at the physician's discretion. (If a
0.2 micrometer syringe filter cannot be used, the concentrate must be pre-filtered with a 5 micrometer
filter, diluted and then administered through an in-line 0.22 micrometer filter.)

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

The diluted concentrate should be a clear and colourless solution. It should be visually inspected
for the presence of particles and colour change 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 point of
view, it should be used immediately. If not used immediately, the storage times and conditions
before use are the responsibility of the user and should normally 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.
Instructions for handling
Procedures for the correct handling of antineoplastic agents must be observed. Cytotoxic
medicines must be handled with caution.
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 plenty of water.
Evoltra should not be handled by pregnant women.
Disposal
Evoltra is for single use only. Any unused medicine or waste material should be disposed of in
accordance with local requirements.