CLOFARABINE TEVA 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet:information for the user

Clofarabine Teva 1 mg/ml concentrate for solution for infusion EFG

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.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Clofarabine Teva and what is it used for
2. What you need to know before you use Clofarabine Teva
3. How to use Clofarabine Teva
4. Possible side effects
5. Storing Clofarabine Teva
6. Contents of the pack and other information

1. What is Clofarabine Teva and what is it used for

Clofarabine Teva contains the active substance clofarabine. Clofarabine belongs to a family of medicines called antineoplastic agents. It works by making it harder for abnormal white blood cells to grow, and then kills them. It works best on cells that multiply quickly, such as cancer cells.

Clofarabine Teva is used to treat children (≥ 1 year of age), adolescents, and young adults up to 21 years of age with acute lymphoblastic leukemia (ALL) who have not responded to or have stopped responding to previous treatments. Acute lymphoblastic leukemia is caused by the abnormal growth of some types of white blood cells.

2. What you need to know before you use Clofarabine Teva

Do not use Clofarabine Teva

• if you are allergicto 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 described above.If you are the parent of a child being treated with Clofarabine Teva, tell the doctor if your child is in any of these situations.

Warnings and precautions

Talk to your doctor before you start using Clofarabine Teva.

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

• if you have had a severe reactionin the past after using this medicine;
• if you have kidney diseaseor have had it in the past;
• if you have liver diseaseor have had it in the past;
• if you have heart diseaseor have had it in the past.

Tell your doctor 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, making you more prone to infections;
• 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 or faint - this could be a sign that your blood pressure is too low;
• if you have nausea or diarrhea;
• if your urine is darker than usual - it is essential to drink plenty of water to avoid dehydration;
• if you develop a rash with blisters or mouth ulcers.
• if you lose your appetite, feel nauseous, vomit, have diarrhea, dark-colored urine, and light-colored stools, stomach pain, yellowing of the skin and eyes (jaundice), or if you generally do not feel well, these may 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 may be signs of acute kidney failure or kidney failure).

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

During treatment with Clofarabine Teva, your doctor will perform regular blood tests and other checks to monitor your health. Due to its mechanism of action, this medicine will have effects on your blood and other organs.

Talk to your doctor about birth control measures.Men and women who may become pregnant should use effective birth control methods during and after treatment. See the section “Pregnancy and breast-feeding” below. Clofarabine Teva may 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.

Children

A safe and effective dosage recommendation has not been established for patients under 1 year of age.

Using Clofarabine Teva with other medicines

Tell your doctor if you are taking/using or have recently taken/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 an effective birth control method during treatment with clofarabine and for 6 months after the end of treatment. Administration of clofarabine to pregnant women may cause harm to the fetus. If you are pregnant or become pregnant during treatment with clofarabine, consultyour doctor immediately.

Men should also use effective birth control methods and be advised not to attempt to conceive 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 breast-feed during treatment and for 2 weeks after the end of treatment.

Driving and using machines

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

Clofarabine Teva contains sodium

This medicine contains 70.8 mg of sodium (the main component of cooking/table salt) in each 20 ml vial. This is equivalent to 3.54% of the maximum recommended daily intake of sodium for an adult.

3. How to use Clofarabine Teva

A qualified and experienced doctor in the treatment of leukemia has prescribed Clofarabine Teva for you.

Your doctor will decide the right dose for youbased on your weight, height, and health. Before administration, Clofarabine Teva must be diluted in a sodium chloride 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 Clofarabine Teva once a day for 5 days.It will be given as an infusion through a long, thin tube inserted into a vein (a drip) or into a small medical device inserted under the skin (port-a-cath), if you (or your child) have one. The infusion will be given over a 2-hour period. 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 the dose depending on your response to treatment. It is essential to drink plenty of water to avoid dehydration.

If you use more Clofarabine Teva than you should

If you think you may have been given too much medicine, tell your doctor immediately.

In case of overdose or accidental ingestion, contact the Toxicology Information Service (91) 562 04 20; or consult your doctor as soon as possible after ingestion of the medicine or contact the Emergency Department of the nearest hospital.

If you miss a dose of Clofarabine Teva

Your doctor will tell you when you need to be given this medicine. If you think you have missed a dose, tell your doctor immediately.

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, fatigue;
• nausea and vomiting, diarrhea;
• redness, inflamed skin, and itching, inflammation of the mucous membranes (wet surfaces) of the mouth and other areas of the body;
• more infections than usual because Clofarabine Teva 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 (may affect up to 1 in 10 people)

• blood infections, pneumonia, shingles, infections in an implant, mouth infections such as ulcers and cold sores;
• changes in blood biochemistry, changes in white blood cells;
• allergic reactions;
• feeling thirsty and dark-colored 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, tremors;
• hearing problems;
• fluid accumulation around the heart, rapid heartbeat;
• low blood pressure, bruising;
• bleeding from small blood vessels, rapid breathing, nosebleeds, difficulty breathing, shortness of breath, cough;
• vomiting blood, stomach pain, pain in the buttocks;
• bleeding inside the head, stomach, intestine, or lungs, mouth or gums, mouth ulcers, inflammation of the mouth lining;
• yellowing of the skin and eyes (jaundice) or other liver disorders;
• bruising, hair loss, changes in skin color, increased sweating, dry skin, or other skin problems;
• pain in the chest wall or bones, pain in the neck or back, pain in the limbs, muscles, or joints;
• blood in the urine;
• organ failure, pain, increased muscle tension, fluid retention, and swelling of some parts of the body, including the arms and legs, changes in mental state, feeling hot, cold, or feeling “strange”;
• clofarabine may alter the levels of certain substances in your blood. Your doctor will perform regular blood tests to check if 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 (may affect up to 1 in 100 people)

• liver inflammation (hepatitis).

Frequency not known (cannot be estimated from the available data)

• intestinal inflammation;
• inflammation of the pancreas (pancreatitis);
• rash with blisters on the skin and mucous membranes of the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome or toxic epidermal necrolysis).

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency's Pharmacovigilance System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Clofarabine Teva

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 is the last day of the month stated.

Do not freeze.

The diluted concentrate is chemically and physically stable in PVC bags 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 must be used immediately. If not, the in-use storage times and conditions are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has been made in controlled and validated aseptic conditions. Do not freeze.

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

6. Container contents and additional information

Clofarabine Teva composition

• The active substance is clofarabine. Each ml of concentrate contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine.
• The other components are sodium chloride, hydrochloric acid (for pH adjustment), and water for injectable preparations.

Product appearance and container contents

Clofarabine Teva 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. The vials may or may not be wrapped in a protective sleeve.

Each box contains 1 or 4 vials.

Only certain pack sizes may be marketed.

Marketing authorization holder

Teva Pharma, S.L.U.

C/ Anabel Segura, 11. Edificio Albatros B, 1ª planta.

28108 Alcobendas, Madrid

Spain

Manufacturer

S.C. SINDAN-PHARMA S.R.L.

11th Ion Mihalache Boulevard

Bucharest 1

011171

Romania

This medicinal product is authorized in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Austria Clofarabin Actavis 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Germany Clofarabin-ratiopharm 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Spain Clofarabina Teva 1 mg/ml concentrate for solution for infusion EFG

Italy Clofarabina Teva

United Kingdom Clofarabine Teva 1 mg/ml Concentrate for solution for infusion

(Northern Ireland)

Romania Clofarabina Teva 1 mg/ml concentrat pentru solutie perfuzabila

Date of last revision of thisleaflet:November 2023

The reference medicinal product containing clofarabine has been authorized under "exceptional circumstances". This type of approval 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 leaflet will be updated as necessary.

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

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This information is intended only for healthcare professionals:

Special precautions for administration

Clofarabine Teva 1 mg/ml concentrate for solution for infusion must be diluted before administration. It should be passed through a sterile 0.2 microns filter needle, and then diluted in an intravenous infusion solution with 9 mg/ml of sodium chloride (0.9%) to obtain a total volume in accordance with 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 filter needle 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 in PVC bags 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 in-use storage times and conditions are the responsibility of the user and should not normally 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 Clofarabine Teva. 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 Clofarabine Teva.

Disposal

Clofarabine Teva is for single use.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations for cytotoxics.