Clofarabine Accord

Package Leaflet: Information for the User

Clofarabine Accord, 1 mg/ml, Concentrate for Solution for Infusion

Clofarabine

Read the Package Leaflet Carefully Before Using the Medicinal Product

• Keep this Package Leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicinal product has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this Package Leaflet. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Clofarabine Accord and What is it Used For
• 2. Before You Use Clofarabine Accord
• 3. How to Use Clofarabine Accord
• 4. Possible Side Effects
• 5. How to Store Clofarabine Accord
• 6. Contents of the Package and Other Information

1. What is Clofarabine Accord and What is it Used For

The active substance of Clofarabine Accord is clofarabine. Clofarabine belongs to a group of cytotoxic medicines. It works by inhibiting the growth of abnormal white blood cells and consequently leading to their death. It works best on rapidly dividing cells, such as cancer cells.
Clofarabine Accord is used to treat children (from 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. Before You Use Clofarabine Accord

When Not to Use Clofarabine Accord:

• If you are allergicto clofarabine or any of the other ingredients of this medicinal product (listed in section 6);
• If you are breastfeeding(see the section on "Pregnancy and Breastfeeding");
• If you have severe liver or kidney disease.

Tell Your Doctor if Any of the Above Applies to You.

A parent of a child using Clofarabine Accord should tell the doctor if any of the above applies to their child.

Warnings and Precautions

Tell your doctor if any of these conditions apply to you.Clofarabine Accord may not be suitable for you:

• If you have had a severe reactionto this medicinal product in the past;
• If you have kidney diseaseor have had kidney disease in the past;
• If you have liver diseaseor have had liver disease in the past;
• If you have heart diseaseor have had heart disease in the past.

Tell your doctor or nurse immediatelyif you experience any of the following symptoms:

• if you have a fever or high temperature - clofarabine reduces the number of blood cells produced by the bone marrow and as a result, you are more prone to infections;
• if you have difficulty breathing, breathe quickly, or have shortness of breath;
• if you experience changes in heart rhythm;
• if you feel dizzy (a feeling of emptiness in the head) or faint - this may be a sign of low blood pressure;
• if you vomit or have diarrhea (loose stools);
• if your urine is darker than usual - remember to drink plenty of water to avoid dehydration;
• if you experience a blistering rash or mouth ulcers;
• if you lose your appetite, feel nauseous, vomit, have diarrhea, your urine is darker than usual, your stool is lighter than usual, you experience abdominal pain, you have jaundice (a yellowing of the skin and whites of the eyes), or if you feel unwell, these may be signs of liver inflammation or damage (liver failure);
• if you pass little or no urine, or feel sleepy, nauseous, vomit, have shortness of breath, have no appetite, and/or feel weak (these may be signs of acute kidney failure or kidney failure).

A parent of a childusing Clofarabine Accord should tell the doctor if any of the above symptoms occur in their child.
During treatment with Clofarabine Accord, your doctor will perform regular blood tests and other tests to monitor your health. The mechanism of action of the medicinal product affects your blood and other organs.
Ask your doctor about contraception.Young men and women must use effective contraception during and after treatment. See the section on "Pregnancy and Breastfeeding". Clofarabine Accord may damage male and female reproductive organs.
You should ask your doctor to explain what you can do to protect yourself or the possibility of having children in the future.

Clofarabine Accord and Other Medicinal Products

Tell your doctor about all the medicinal products you are taking or have recently taken, such as:

• cardiac glycosides;
• any medicinal products that affect blood pressure;
• medicinal products that affect the liver or kidneys;
• any other medicinal products, 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:you 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 you are pregnant or become pregnant during treatment with clofarabine, you should seek medical advice immediately.
Men must also use effective contraception and should be informed not to father a child during treatment with Clofarabine Accord and for 3 months after the end of treatment.
If you are breastfeeding, you should stop breastfeeding before starting treatment and should not breastfeed during treatment and for 2 weeks after the end of treatment.

Driving and Using Machines

You should not drive or operate machinery if you experience dizziness, a feeling of emptiness in the head, or fainting.

Clofarabine Accord Contains Sodium

The medicinal product contains 70.77 mg of sodium (the main component of common salt) per vial. This corresponds to 3.54% of the recommended maximum daily intake of sodium in the diet for adults. You should consult your doctor or pharmacist if you need 5 or more vials per day during a treatment cycle for a long time, especially if you have been advised to follow a low-sodium diet.

3. How to Use Clofarabine Accord

Clofarabine Accord is prescribed by a qualified doctor with experience in the treatment of leukemia.
Your doctor will decide on the dose that is right for youbased on your height, weight, and health status. Before administration, Clofarabine Accord will be diluted with a sodium chloride solution (a solution of salt and water). You should tell your doctor if you are on a low-sodium diet, as this may affect the administration of the medicinal product.
Your doctor will administer the medicinal product to you every day for 5 days.The medicinal product will be administered as an infusion using a long, thin tube leading to a vein (drip) or into a small device placed under the skin (a central venous catheter), if one has been implanted in you (or your child). The duration of the infusion is 2 hours. If your weight (or your child's weight) is less than 20 kg, the infusion time may be extended.
Your doctor will monitor your health and may adjust the dose based on your response to treatment. Remember to drink plenty of water to avoid dehydration.

Using More Than the Recommended Dose of Clofarabine Accord

You should tell your doctor immediately if you think you have been given more than the recommended dose of the medicinal product.

Missing a Dose of Clofarabine Accord

Your doctor will tell you when the medicinal product will be administered. You should tell your doctor immediately if you think you have missed a dose of the medicinal product.
In case of doubt about the use of the medicinal product, you should consult your doctor.

4. Possible Side Effects

Like all medicines, this medicinal product 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, mucositis (e.g., in the mouth or other areas);
• more frequent than usual infections, because Clofarabine Accord may reduce the number of certain types of blood cells in your body;
• skin rashes, which may cause itching, redness, pain, or peeling of the skin on the palms of the hands and soles of the 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 dark or reduced urine, reduced or no appetite, weight loss;
• agitation, irritability, or restlessness;
• feeling numb or weak 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 ulcers, mucositis;
• yellowing of the skin and eyes (also known as jaundice) or other liver function disorders;
• skin rashes, which may cause itching, redness, pain, or peeling of the skin on the palms of the hands and soles of the feet or red or purple spots under the skin;
• bruising, hair loss, changes in skin color, 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 status, feeling hot, cold, or unwell;
• clofarabine may affect the levels of certain substances in the blood. Your doctor will perform regular blood tests to check if your body is functioning properly;
• liver damage (liver failure);
• passing little or no urine, sleepiness, nausea, vomiting, shortness of breath, loss of 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 you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this Package Leaflet. You can also report side effects 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
You can also report side effects to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicinal product.

5. How to Store Clofarabine Accord

Keep this medicinal product out of the sight and reach of children.
Do not use this medicinal product after the expiry date which is stated on the label of the vial and on the carton after "EXP". The expiry date refers to the last day of that month.
Do not freeze.
Do not use this medicinal product if you notice changes in the color of the solution.
After dilution:

The diluted concentrate is chemically and physically stable 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 user is responsible for the storage conditions and duration before use. This storage should not exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution has been performed 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. These measures will help protect the environment.

6. Contents of the Package and Other Information

What Clofarabine Accord Contains

The active substance is clofarabine. One 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 Accord Looks Like and Contents of the Package

Clofarabine Accord is a concentrate for solution for infusion. It is a clear, practically colorless solution, which is prepared and diluted before use. The medicinal product is supplied in 20 ml vials. The vials contain 20 mg of clofarabine and are placed in cartons.
One carton contains 1 vial.

Marketing Authorization Holder

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: + 48 22 577 28 00

Manufacturer / Importer

Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA3000
Malta
Accord Healthcare Polska Sp.z.o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland

Date of Last Revision of the Package Leaflet: October 2023

Clofarabine Accord contains the same active substance and works in the same way as a reference medicinal product authorized in the EU. The reference medicinal product for Clofarabine Accord was authorized in "exceptional circumstances". This means that due to the rarity of the disease, it was not possible to obtain full information about the reference medicinal product.
The European Medicines Agency will review all new information about the reference medicinal product every year and any updates to the information about the reference medicinal product will also be included in the information leaflets for Clofarabine Accord, such as this Package Leaflet.

Instructions for Use for Healthcare Professionals

Handling of Clofarabine

Information intended for healthcare professionals only:

Special Precautions for the Preparation of the Medicinal Product for Administration

Before administration of Clofarabine Accord, 1 mg/ml, concentrate for solution for infusion, it must be diluted. It should be filtered through a sterile filter needle 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 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 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 is chemically and physically stable 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 medicinal product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration before use. This storage should not exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution has been performed in controlled and validated aseptic conditions. Do not freeze.

Administration Instructions

Follow the procedures for the proper handling of anticancer medicinal products.
Be careful when handling cytotoxic medicinal products.
When handling Clofarabine Accord, 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 Accord.

Disposal of Unused Product

Clofarabine Accord is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.