EVOLTRA 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Evoltra 1 mg/ml concentrate for solution for infusion

clofarabine

This medicinal product is subject to additional monitoring, which 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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Evoltra and what is it used for
2. What you need to know before you use Evoltra
3. How to use Evoltra
4. Possible side effects
5. Storage of 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 making it harder for abnormal white blood cells to grow, and then killing them. It works best on cells that are growing quickly, such as cancer cells.

Evoltra is used to treat children (from 1 year of age), adolescents and young adults up to 21 years of age with acute lymphoblastic leukaemia (ALL) that has not responded to, or has responded to, previous treatments. Acute lymphoblastic leukaemia is caused by the abnormal growth of some types of white blood cells.

2. What you need to know before you use Evoltra

Do not 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 (see the section “Pregnancy and breast-feeding” below);
• if you have severe kidney or liver problems.

Tell your doctor if you are in any of the situations listed above.If you are the parent of a child being treated with Evoltra, tell the doctor if your child is in any of these situations.

Warnings and precautions

Tell your doctor if you are in any of the situations listed below.Evoltra may not be a suitable treatment for you:

• if you have had a severe reaction in the past after using this medicine;
• if you have had kidney problems in the past;
• if you have had liver problems in the past;
• if you have had heart problems in the past.

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

• if you have a fever or high temperature: clofarabine can make your bone marrow produce fewer blood cells, so you may get infections more easily;
• if you have difficulty breathing, feel short of breath or need to breathe more quickly;
• if you notice any changes in your heart rate;
• if you feel dizzy (like you are about to faint) or faint: this could be a sign that your blood pressure is too low;
• if you have nausea or diarrhoea;
• 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, feel sick (nausea), are sick (vomiting), have diarrhoea, dark urine and pale stools, stomach pain, yellowing of the skin and eyes (jaundice), or if you generally do not feel well, these can be symptoms of liver inflammation (hepatitis) or liver damage (liver failure).
• if you produce little or no urine, or if you experience drowsiness, nausea, vomiting, difficulty breathing, loss of appetite and/or weakness (these can be signs of acute kidney failure or kidney failure).

If you are the parentof a child being treated with Evoltra, tell the doctor if your child is in any of the situations listed above.

During treatment with Evoltra, your doctor will regularly take blood samples and do other tests to check your health. Because of the way this medicine works, it will have effects on your blood and on other organs.

Talk to your doctor about birth control.Young men and women should use effective birth control during and after treatment. See the section “Pregnancy and breast-feeding” below. Evoltra can cause damage to the reproductive organs in both males and females. Ask your doctor what can be done to protect you or allow you to have a family.

Using Evoltra with other medicines

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

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

Pregnancy and breast-feeding

Clofarabine is not recommended during pregnancy unless clearly necessary.

Women of childbearing age:you must use effective birth control during treatment with clofarabine and for 6 months after the end of treatment. If you are pregnant or become pregnant during treatment with clofarabine, consult your doctor immediately.

Men must also use effective birth control and be advised not to try to father a child while receiving clofarabine and for 3 months after the end of treatment.

If you are breast-feeding, you must stop before starting treatment and not start again until 2 weeks after the end of treatment.

Driving and using machines

Do not drive or use tools or machines if you feel dizzy, faint or are going to faint.

Evoltra contains sodium

This medicine contains 72 mg of sodium (the main component of cooking/table salt) per vial. This is equivalent to 3.6% of the maximum recommended daily intake of sodium for an adult. Consult 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-salt diet.

3. How to use Evoltra

Evoltra has been prescribed for you by a doctor who is qualified and experienced in treating leukaemia.

Your doctor will decide the right dose for youbased on your weight, height and health. Before it is given to you, Evoltra must be mixed with a salt solution (salt and water). Tell your doctor if you are on a low-sodium diet, as this may affect how the medicine is given to you.

Your doctor will give you Evoltra once a day for 5 days.It will be given to you as an infusion into a vein, either through a drip or through a small medical device inserted under the skin (a port-a-cath), if you (or your child) have one. The infusion will be given over a period of 2 hours. If you (or your child) weigh less than 20 kg, the infusion time may be longer.

Your doctor will check your health and may change the dose depending on how you respond 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 miss a dose of Evoltra

Your doctor will tell you when you need to be given this medicine. If you think 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 side effects (may affect more than 1 in 10 people):

• anxiety, headache, fever, tiredness;
• nausea and vomiting, diarrhoea;
• flushing, skin inflammation and itching, inflammation of the mucous membranes (wet parts) of the mouth and other parts of the body;
• more infections than usual because Evoltra can reduce the number of certain types of blood cells in your body;
• skin rashes that may itch, redness, pain or peeling of the skin that also affects the palms of the hands and soles of the feet, or small red or purple spots under the skin surface.

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

• blood infections, pneumonia, shingles, infections in an implant, mouth infections such as thrush or cold sores;
• changes in blood biochemistry, changes in white blood cells;
• allergic reactions;
• feeling thirsty and dark urine or less urine than usual, decreased or lost appetite, weight loss;
• agitation, irritability or restlessness;
• numbness or weakness in legs and arms, numbness of the skin, drowsiness, dizziness, shaking;
• hearing problems;
• fluid build-up around the heart, fast heart rate;
• low blood pressure, bruising;
• bleeding from small blood vessels, fast breathing, nosebleeds, breathing difficulties, shortness of breath, cough;
• vomiting blood, stomach pain, pain in the buttocks;
• bleeding in the head, stomach, intestine or lungs, mouth or gums, mouth ulcers, inflammation of the mouth lining;
• yellowing of the skin and eyes (also called jaundice) or other liver disorders;
• bruising, hair loss, changes in skin colour, increased sweating, dry skin or other skin problems;
• chest pain or bone pain or neck pain or back pain, pain in the limbs, muscles or joints;
• blood in the urine;
• organ failure, pain, increased muscle tone, fluid retention and swelling of some parts of the body including the arms and legs, changes in mental status, feeling hot, cold or feeling “funny”;
• clofarabine may affect the levels of certain substances in your blood. Your doctor will regularly take blood samples to check that your body is working properly.
• liver damage (liver failure).
• little or no urine, drowsiness, nausea, vomiting, difficulty breathing, 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):

• liver inflammation (hepatitis).

Reporting of side effects

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

5. Storage of 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 carton after EXP. The expiry date refers to the last day of that month.

Do not freeze.

Once prepared and diluted, Evoltra should be used immediately or within 24 hours if stored in the refrigerator (between 2°C and 8°C).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container contents and additional information

Evoltra composition

The active ingredient is clofarabine. Each ml contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine.

The other components are sodium chloride and water for injectable preparations.

Product appearance and packaging size

Evoltra is a concentrate for solution for infusion. It is a clear and almost colorless solution that is prepared and diluted before use. It is supplied in 20 ml glass vials. The vials contain 20 mg of clofarabine and are supplied packaged in a box. Each box contains 1, 3, 4, 10, or 20 vials, but only some packaging sizes may be marketed.

Marketing authorization holder

Sanofi B.V.

Paasheuvelweg 25

1105 BP Amsterdam

Netherlands

Manufacturer

SANOFI WINTHROP INDUSTRIE

30-36, avenue Gustave Eiffel

37100 Tours

France

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this prospectus:

This medicinal product has been authorized under "exceptional circumstances".

This authorization means that, due to the rarity of the disease, it has not been possible to obtain complete information on this medicinal product.

The European Medicines Agency will review any new information on the medicinal product that may become available annually, and this prospectus will be updated as necessary.

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu/ and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/. It also provides links to other websites on rare diseases and orphan medicines.

The following information is intended for healthcare professionals only:

Special precautions for administration

Evoltra 1 mg/ml concentrate for solution for infusion should be diluted before administration. It should be passed through a sterile 0.2 microns filter for syringe, and then diluted in an intravenous infusion solution with 9 mg/ml of sodium chloride (0.9%) to obtain the necessary total volume according to the examples provided in the table below. However, the final dilution volume may vary depending on the patient's clinical condition and the physician's judgment. (If a 0.2 microns syringe filter is not available, the concentrate should be prefiltered through a 5 microns filter, diluted, and then administered through a 0.22 microns filter integrated into the administration line).

The diluted concentrate should be a clear and colorless solution. It should be visually inspected before administration to rule out the presence of particles or signs of discoloration.

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, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless the dilution has been performed under controlled and validated aseptic conditions. Do not freeze.

Handling instructions

Procedures recommended for the proper handling of antineoplastic agents should be followed. Cytotoxic drugs should be handled with caution.

The use of disposable gloves and protective clothing is recommended when handling Evoltra. If the product comes into contact with the eyes, skin, or mucous membranes, the area should be rinsed immediately with plenty of water.

Pregnant women should not handle Evoltra.

Disposal

Evoltra is for single use. The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.