CLOFARABINE 1 mg /Ml Concentrate

Contents of the leaflet

1. PATIENT INFORMATION LEAFLET
2. Leaflet accompanying the packaging: information for the user
3. Clofarabine Norameda, 1 mg/ml, concentrate for solution for infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
4. What is Clofarabine Norameda and what is it used for
5. Important information before using Clofarabine Norameda
   1. When not to use Clofarabine Norameda:
   2. Tell your doctor if any of the above conditions apply to the patient.
   3. Warnings and precautions
   4. Clofarabine Norameda and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Clofarabine Norameda contains sodium
6. How to use Clofarabine Norameda
   1. Using more than the recommended dose of Clofarabine Norameda
   2. Missing a dose of Clofarabine Norameda
7. Possible side effects
   1. Very common (may affect more than 1 in 10 people):
   2. Common (may affect up to 1 in 10 people):
   3. Uncommon (may affect up to 1 in 100 people):
   4. Reporting side effects
8. How to store Clofarabine Norameda
9. Contents of the packaging and other information
   1. What Clofarabine Norameda contains
   2. What Clofarabine Norameda looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: information for the user

Clofarabine Norameda, 1 mg/ml, concentrate for solution for infusion

Clofarabine

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor. See section 4.

Table of contents of the leaflet

• 1. What is Clofarabine Norameda and what is it used for
• 2. Important information before using Clofarabine Norameda
• 3. How to use Clofarabine Norameda
• 4. Possible side effects
• 5. How to store Clofarabine Norameda
• 6. Contents of the packaging and other information

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

The active substance of Clofarabine Norameda is clofarabine. Clofarabine belongs to a family of medicines called anticancer medicines. The medicine works by inhibiting the growth of abnormal white blood cells and consequently leading to their death. It works best on cells that multiply rapidly - such as cancer cells.
Clofarabine Norameda is used to treat children (≥ 1 year of age), adolescents, and young adults up to 21 years of age with acute lymphoblastic leukemia (ALL), when previous therapies have not been effective or have stopped being effective. Acute lymphoblastic leukemia is caused by the abnormal development of a certain type of white blood cell.

2. Important information before using Clofarabine Norameda

When not to use Clofarabine Norameda:

• -if the patient is allergic to clofarabine or any of the other ingredients of this medicine (listed in section 6);
• -if the patient is breastfeeding (read the section "Pregnancy and breastfeeding" below);
• if the patient has severe liver or kidney disease.

Tell your doctor if any of the above conditions apply to the patient.

The parent of a child taking Clofarabine Norameda should tell the doctor if any of the above conditions apply to their child.

Warnings and precautions

Before starting treatment with Clofarabine Norameda, discuss it with your doctor.
Tell your doctor if any of these conditions apply to the patient.
Clofarabine Norameda may not be suitable for the patient:

• -if the patient has had a severe reaction to this medicine in the past;
• -if the patient has kidney disease or has had it in the past;
• -if the patient has liver disease or has had it in the past;
• -if the patient has heart disease or has had it in the past.

Tell your doctor or caregiver immediatelyif the patient experiences any of the following symptoms:

• if the patient has a fever or elevated temperature - clofarabine reduces the number of blood cells produced by the bone marrow, and the patient is more susceptible to infections;
• if the patient has difficulty breathing, breathes rapidly, or has shortness of breath;
• if the patient experiences changes in heart rhythm;
• if the patient experiences dizziness (feeling of emptiness in the head) or fainting - this may be a sign of low blood pressure;
• if the patient has nausea or diarrhea (loose stools);
• if the patient's urine is darker than usual - remember to drink plenty of water to avoid dehydration;
• if the patient experiences a blistering rash or mouth sores;
• if the patient loses appetite, feels nauseous (feels unwell), vomits, has diarrhea, their urine is darker than usual, their stool is lighter than usual, they experience abdominal pain, they have jaundice (visible yellowing of the skin and whites of the eyes), or if they feel unwell, these may be symptoms of liver inflammation or damage (liver failure);
• if the patient urinates little or not at all, or experiences drowsiness, nausea, vomiting, shortness of breath, loss of appetite, and (or) weakness (possible symptoms of acute kidney failure or kidney failure). The parent of a childtaking Clofarabine Norameda should tell the doctor if any of the above symptoms occur in their child.During treatment with Clofarabine Norameda, the doctor will perform regular blood tests and other tests to monitor the patient's health. The mechanism of action of the medicine affects the patient's blood and other organs.

Consult your doctor about contraception. Young men and women must use effective contraception during and after treatment. See the section "Pregnancy and breastfeeding" below. Clofarabine Norameda may damage male and female reproductive organs. Ask your doctor to explain what can be done to protect the patient or the possibility of having children in the future.

Clofarabine Norameda and other medicines

Tell your doctor about all medicines the patient is taking or has taken recently, such as:

• heart medicines;
• any medicines that affect 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 of childbearing age:the patient must use effective contraceptive measures during treatment with clofarabine. Clofarabine taken by women during pregnancy may be harmful to the fetus. If the patient is pregnant or becomes pregnant during treatment with clofarabine, they should consult their doctor immediately.
Men must also use effective contraception during treatment or if their partners are treated with clofarabine.
If the patient is breastfeeding, they should stop breastfeeding before starting treatmentand not breastfeed during treatment and for 3 months after its completion.

Driving and using machines

Do not drive or operate machinery if the patient experiences dizziness, feeling of emptiness in the head, or fainting.

Clofarabine Norameda contains sodium

This medicine contains 71 mg of sodium (the main component of table salt) in each vial. This corresponds to 4% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Clofarabine Norameda

The use of Clofarabine Norameda has been prescribed by a qualified doctor with experience in treating leukemia.
The doctor will determine the dose suitable for the patient based on their height, weight, and health condition. Before administration, Clofarabine Norameda will be diluted with a sodium chloride solution (a solution of salt and water). Tell your doctor if the patient is on a low-salt diet, as this may affect the administration of the medicine.
The doctor will administer the medicine to the patient daily for 5 days.The medicine will be administered as an infusion using a long, thin tube leading to a vein (drip) or to a small device placed under the skin (a venous access device), if it has been implanted in the patient (or child). The duration of the infusion is 2 hours. If the patient's (or child's) weight is less than 20 kg, the infusion time may be extended.
The doctor will monitor the patient's health and may change the dose depending on the response to treatment. Remember to drink plenty of water to avoid dehydration.

Using more than the recommended dose of Clofarabine Norameda

Tell your doctor immediately if the patient thinks they have been given more than the recommended dose of the medicine.

Missing a dose of Clofarabine Norameda

The doctor will inform the patient when the medicine will be administered. Tell your doctor immediately if the patient thinks they have missed a dose of the medicine.
In case of doubts about the use of the medicine, consult the doctor who prescribed it.

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 (loose stools)
• sudden flushing of the face, itching, skin inflammation, mucous membrane inflammation, e.g., in the mouth or other areas
• more frequent than usual infections, as Clofarabine Norameda may reduce the number of certain types of blood cells in the patient's body
• skin rashes, which may cause itching, redness, pain, or peeling of the skin on the hands and feet or small red or purple spots under the skin.

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

• blood infections, pneumonia, shingles, implant infections, mouth infections, e.g., thrush or cold sores
• changes in blood biochemical test results, changes in white blood cells
• allergic reactions
• feeling thirsty and darker or reduced urine output, reduced or no appetite, weight loss
• agitation, irritability, or restlessness
• feeling numbness or weakness in the arms and legs, numbness of the skin, drowsiness, dizziness, tremors
• hearing disorders
• fluid accumulation around the heart, rapid heart rate
• low blood pressure, hardening in connection with bruising
• leakage from small blood vessels, rapid breathing, nosebleeds, difficulty breathing, shortness of breath, coughing
• bloody vomiting, stomach pain, anal pain
• bleeding inside the head, stomach, intestines, or lungs, from the mouth or gums, mouth sores, mucous membrane inflammation of the mouth
• yellowing of the skin and eyes (also called jaundice) or other liver function disorders
• bruises, hair loss, skin color changes, increased sweating, dry skin, or other skin problems
• chest pain or bone pain, neck or back pain, limb pain, muscle or joint pain
• blood in the urine
• organ failure, pain, increased muscle tension, fluid retention and swelling of parts of the body, including arms and legs, changes in mental state, feeling hot, cold, or unwell
• Clofarabine Norameda may affect the levels of certain substances in the blood. The doctor will perform regular blood tests to check if the patient's body is functioning properly
• liver damage (liver failure)
• passing little or no urine, drowsiness, nausea, vomiting, shortness of breath, loss of appetite, and (or) weakness (possible symptoms of acute kidney failure or kidney failure).

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

Hepatitis.

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, tell your doctor or pharmacist or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Clofarabine Norameda

Store the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and carton after "EXP". The first two digits indicate the month, and the last four digits indicate the year of the expiry date.
Do not freeze.
After preparation and dilution, Clofarabine Norameda should be used immediately or within 24 hours if the medicine was stored in the refrigerator (at a temperature of 2°C to 8°C).
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Clofarabine Norameda contains

The 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 Clofarabine Norameda looks like and contents of the pack

Clofarabine Norameda is a concentrate for solution for infusion. It is a clear, practically colorless solution that is prepared and diluted before use. The medicine is supplied in 20 ml vials. The vials contain 20 mg of clofarabine and are placed in cartons. One carton contains 1, 3, 4, 10, or 20 vials.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

UAB Norameda
Meistrų G. 8A
02189 Vilnius
Lithuania

Manufacturer

Synthon BV
Microweg 22
6545CM Nijmegen
Netherlands
Synthon Hispania S.L.
C/Castelló n°1
Pol. Las Salinas
08830 Sant Boi de Llobregat
Spain
Synthon s.r.o.
Brněnská 32/c.p.597
678 01 Blansko
Czech Republic
Date of last revision of the leaflet:01/2021
Information intended for healthcare professionals only:
Special precautions for the preparation of the medicinal product for use
Before administering the Clofarabine Norameda 1 mg/ml concentrate for solution for infusion, it should be diluted. It should be filtered through a sterile filter needle with a pore size of 0.2 microns, and then diluted with a sodium chloride solution 9 mg/ml (0.9%) for injections to obtain a total volume in accordance with the example given in the table below. However, the final volume of dilution may vary depending on the patient's clinical condition and the doctor's decision. (If it is not possible to use a filter needle with a pore size of 0.2 microns, the concentrate should be pre-filtered through a filter with a pore size of 5 microns, diluted, and then administered through a filter with a pore size of 0.22 microns in the infusion set.)
The diluted concentrate should be a clear and colorless solution. Before administration, it should be visually inspected for the presence of particles and changes in color.
The diluted concentrate is physically and chemically stable for 3 days at a temperature of 2°C - 8°C and at room temperature (up to 25°C).
From a microbiological point of view, the medicine should be used immediately after dilution. If the medicine is not used immediately, the responsibility for the storage time and conditions before use lies with the user. This period should not exceed 24 hours at a temperature of 2°C - 8°C, unless the dilution is performed in controlled and validated aseptic conditions.
Do not freeze.
Administration instructions
Follow the procedures for proper handling of anticancer medicines.
Handle cytotoxic medicines with caution.
When handling the Clofarabine Norameda medicinal product, it is recommended to wear single-use gloves and protective clothing. In case of contact with the eyes, skin, or mucous membranes, the affected area should be rinsed immediately with a large amount of water.
Pregnant women should not come into contact with the Clofarabine Norameda medicinal product.
Disposal of unused product

The Clofarabine Norameda medicinal product is intended for single use. Any unused medicinal product or waste should be disposed of in accordance with local regulations.