CLOFARABINE 1 mg /Ml Concentrate

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Clofarabine Vivanta, 1 mg/ml, concentrate for solution for infusion
   1. You should read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Clofarabine Vivanta and what is it used for
4. Important information before using Clofarabine Vivanta
   1. When not to use Clofarabine Vivanta:
   2. Warnings and precautions
   3. Clofarabine Vivanta and other medicines
   4. Pregnancy and breastfeeding
   5. Driving and using machines
   6. Clofarabine Vivanta contains sodium
5. How to use Clofarabine Vivanta
   1. Using a higher dose of Clofarabine Vivanta than recommended
   2. Missing a dose of Clofarabine Vivanta
6. 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
7. How to store Clofarabine Vivanta
8. Contents of the packaging and other information
   1. What Clofarabine Vivanta contains
   2. What Clofarabine Vivanta looks like and contents of the pack
   3. Marketing authorization holder:
   4. Importer:
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet: 08/2024
   8. Instructions for use for healthcare professionals

Leaflet accompanying the packaging: information for the user

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

Clofarabine

You should read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should 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 as yours.
• If the patient experiences any side effects, including any possible 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 Vivanta and what is it used for
• 2. Important information before using Clofarabine Vivanta
• 3. How to use Clofarabine Vivanta
• 4. Possible side effects
• 5. How to store Clofarabine Vivanta
• 6. Contents of the packaging and other information

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

The active substance of Clofarabine Vivanta is clofarabine. Clofarabine belongs to a family of cytotoxic 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 quickly - such as cancer cells.
Clofarabine Vivanta 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 Vivanta

When not to use Clofarabine Vivanta:

• -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 (see the section "Pregnancy and breastfeeding" below);
• if the patient has severe kidney or liver disease.

The patient should inform their doctor if any of these diseases apply to them. The parent of a child taking Clofarabine Vivanta should inform the doctor if any of these diseases apply to their child.

Warnings and precautions

The patient should inform their doctor if any of these diseases apply to them. Clofarabine Vivanta 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 kidney disease in the past;
• -if the patient has liver disease or has had liver disease in the past;
• -if the patient has heart disease or has had heart disease in the past.

The patient or their parent should immediately inform the doctor or caregiver if 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 prone to infections;
• if the patient has difficulty breathing, breathes quickly 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 vomits or has diarrhea (loose stools);
• if the patient's urine is darker than usual - the patient should 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, vomits, has diarrhea, has darker than usual urine, has lighter than usual stool, abdominal pain, jaundice (visible yellowing of the skin and eyes) or feels unwell, these may be signs of liver inflammation or damage (liver failure);
• if the patient urinates very little or not at all, or feels sleepy, nauseous, vomits, has shortness of breath, has no appetite and (or) feels weak (these may be signs of acute kidney failure or kidney failure).

The parent of a child taking Clofarabine Vivanta should inform the doctor if any of these symptoms occur in their child.
During treatment with Clofarabine Vivanta, 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.
The patient should consult their doctor about contraception. Young men and women must use effective contraception during and after treatment. See the section "Pregnancy and breastfeeding" below. Clofarabine Vivanta may damage male and female reproductive organs. The patient should ask their doctor what can be done to protect them or their ability to have children in the future.

Clofarabine Vivanta and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, such as:

• medicines used for heart diseases;
• 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 absolutely necessary.
Women of childbearing age: the patient must use effective contraceptive measures during treatment with clofarabine and for 6 months after the end of treatment. Clofarabine taken by pregnant women may be harmful to the fetus. If the patient is pregnant or becomes pregnant during treatment with clofarabine, they should immediately consult their doctor.
Men must also use effective contraception and should be informed not to father a child during treatment with clofarabine and for 3 months after the end of treatment.
If the patient is breastfeeding, they should stop breastfeeding before starting treatment and should not breastfeed during treatment and for 2 weeks after its end.

Driving and using machines

The patient should not drive or operate machinery if they experience dizziness, feeling of emptiness in the head, or fainting.

Clofarabine Vivanta contains sodium

One vial of this medicine contains 71 mg of sodium (the main component of common salt). This corresponds to 3.5% of the recommended maximum daily intake of sodium for an adult. If the patient takes 5 or more vials per day for a long time, patients, especially those controlling their salt (sodium) intake, should contact their pharmacist or doctor.

3. How to use Clofarabine Vivanta

Clofarabine Vivanta is 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 Vivanta will be diluted with a sodium chloride solution (a solution of salt and water). The patient should inform their doctor if they are on a low-salt diet, as this may affect the administration of the medicine.
The doctor will administer Clofarabine Vivanta 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 central venous catheter), 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.
The patient should remember to drink plenty of water to avoid dehydration.

Using a higher dose of Clofarabine Vivanta than recommended

The patient should immediately inform their doctor if they think they have been given a higher dose of Clofarabine Vivanta than recommended.

Missing a dose of Clofarabine Vivanta

The doctor will inform the patient when the medicine will be administered. The patient should immediately inform their doctor if they think they have missed a dose of the medicine.
In case of doubts about the use of the medicine, the patient should consult their doctor.

4. Possible side effects

Like all medicines, Clofarabine Vivanta 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 and skin inflammation with itching, inflammation of the mucous membranes, e.g., in the mouth or other areas;
• more frequent than usual infections, as clofarabine 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 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 biochemistry test results, changes in white blood cells;
• allergic reactions;
• feeling thirsty and darker or reduced urine, reduced or no appetite, weight loss;
• agitation, irritability, or restlessness;
• feeling numbness or weakness in the arms and legs, numbness of the skin, sleepiness, dizziness, trembling;
• 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, cough;
• bloody vomiting, stomach pain, anal pain;
• bleeding in the head, stomach, intestines, or lungs, from the mouth or gums, mouth sores, inflammation of the mucous membranes of the mouth;
• yellowing of the skin and eyes (also known as jaundice) or other liver function disorders;
• bruises, hair loss, changes in skin color, increased sweating, dry skin, or other skin problems;
• chest pain or bone pain, neck or back pain, limb, muscle, or joint pain;
• blood in the urine;
• organ failure, pain, increased muscle tension, fluid retention and swelling of body parts, including arms and legs, changes in mental state, feeling hot, cold, or unwell;
• clofarabine 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 very little or no urine, sleepiness, nausea, vomiting, shortness of breath, no appetite, and (or) weakness (possible signs of acute kidney failure or kidney failure).

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

• hepatitis.

Reporting side effects

If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor. 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 181C, 02-222 Warsaw, tel.: +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 representative of the marketing authorization holder.
By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Clofarabine Vivanta

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the vial and on the carton after "Expiry date (EXP)". The expiry date refers to the last day of the month stated.
There are no special precautions for storage.
Storage instructions after dilution:
After preparation and dilution, Clofarabine Vivanta 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).
The diluted concentrate should be a clear, colorless solution. Before administration, it should be visually inspected for the presence of particles and changes in color.
The diluted concentrate shows chemical and physical stability for 3 days at a temperature of 2°C to 8°C and at room temperature (up to 25°C). From a microbiological point of view, the product should be used immediately. If not used immediately, the time and conditions of storage before use are the responsibility of the user. This time should not be longer than 24 hours at a temperature of 2°C to 8°C, unless the dilution took place in controlled and validated aseptic conditions. Do not freeze.
Medicines should not be disposed of via wastewater. The patient should ask their 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 Vivanta contains

• The active substance is clofarabine. Each ml contains 1 mg of clofarabine. Each vial of 20 ml contains 20 mg of clofarabine.
• The other ingredients are sodium chloride and water for injections.

What Clofarabine Vivanta looks like and contents of the pack

Clofarabine Vivanta 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 vials of 20 ml. The vials contain 20 mg of clofarabine and are placed in cartons. Each carton contains 1, 3, 4, 10, or 20 vials, but not all pack sizes may be marketed.

Marketing authorization holder:

Vivanta Generics s.r.o.
Třtinová 260/1, Čakovice
196 00 Prague 9
Czech Republic
tel.: (+48) 699 711 147

Importer:

Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Portugal:
Clofarabina Vivanta 1 mg/ml de concentrado para solução para perfusão
Czech Republic:
Clofarabine Vivanta
Hungary:
Clofarabine Vivanta 1 mg/ml koncentrátum oldatos infúzióhoz
Poland:
Clofarabine Vivanta
Romania:
Clofarabine Vivanta 1 mg/ml concentraat voor oplossing voor infusie
Netherlands:
Clofarabine Vivanta 1 mg/ml concentrat pentru soluţie perfuzabilă

Date of last revision of the leaflet: 08/2024

Clofarabine Vivanta contains the same active substance and works in the same way as the "reference medicine" already authorized in EU countries. The reference medicine for Clofarabine Vivanta was authorized under "exceptional circumstances". This means that due to the rare occurrence of this disease, it was not possible to obtain full information about the reference medicine.
The European Medicines Agency reviews all new information about the reference medicine every year, and any updates to the reference medicine are also included in the relevant information for Clofarabine Vivanta, such as this leaflet.

Instructions for use for healthcare professionals

Handling clofarabine
Information intended exclusively for healthcare professionals:
Special precautions for the preparation of the medicinal product for administration
Before administering Clofarabine Vivanta 1 mg/ml concentrate for solution for infusion, it should be diluted. It should be filtered through a sterile syringe filter with a pore size of 0.2 micrometers, 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 the dilution may be different, depending on the patient's clinical condition and the doctor's decision. (If it is not possible to use a syringe filter with a pore size of 0.2 micrometers, the concentrate should be pre-filtered through a filter with a pore size of 5 micrometers, diluted, and then administered through a built-in filter with a pore size of 0.22 micrometers.)
The diluted concentrate should be a clear, colorless solution. Before administration, it should be visually inspected for the presence of particles and changes in color.
The diluted concentrate shows chemical and physical stability for 3 days at a temperature of 2°C to 8°C and at room temperature (up to 25°C). From a microbiological point of view, the product should be used immediately. If not used immediately, the time and conditions of storage before use are the responsibility of the user. This time should not be longer than 24 hours at a temperature of 2°C to 8°C, unless the dilution took place in controlled and validated aseptic conditions. Do not freeze.
Administration instructions
Proper handling procedures for anticancer medicines should be followed. Caution should be exercised when handling cytotoxic medicines.
When handling the medicinal product containing clofarabine, it is recommended to wear single-use gloves and protective clothing. In case of contact with the eyes, skin, or mucous membranes, the area should be rinsed immediately with plenty of water.

Pregnant women should not come into contact with clofarabine.
Disposal of unused product
Clofarabine is intended for single use only. Any unused product or waste should be disposed of in accordance with local regulations.