Clofarabine accord

Package leaflet: Information for the user

Clofarabine Accord, 1 mg/ml, concentrate for solution for infusion
Clofarabinum
Please read the entire leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform the doctor immediately. See section 4.

Table of contents

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

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

The active substance in Clofarabine Accord is clofarabine. Clofarabine belongs to a family of cytotoxic medicines. It works by inhibiting the growth of abnormal white blood cells, ultimately leading to their death. It is most effective against rapidly dividing cells – such as cancer cells.
Clofarabine Accord is used to treat children (≥ 1 year of age), adolescents, and young adults up to 21 years of age with acute lymphoblastic leukaemia (ALL), when previous treatments have been ineffective or have stopped being effective. Acute lymphoblastic leukaemia is caused by abnormal development of a certain type of white blood cells.

2. Important information before using Clofarabine Accord

When not to use Clofarabine Accord:

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

Tell the doctor if any of the conditions listed above apply to the patient.
The parent of a child receiving Clofarabine Accord should inform the doctor if
any of the above conditions apply to their child.
Warnings and precautions
Tell the doctor if any of the following conditions apply to the patient. Clofarabine Accord may not be suitable for the patient:

• if the patient has experienced a serious reaction after previous use of this medicine;
• if the patient has or has had kidney disease in the past;
• if the patient has or has had liver disease in the past;
• if the patient has or has had heart disease in the past.

Contact the doctor or caregiver immediately if the patient experiences any of the following symptoms:

• if the patient develops fever or elevated temperature – clofarabine reduces the number of blood cells produced by the bone marrow, making the patient more susceptible to infections;
• if the patient experiences difficulty breathing, breathes rapidly, or has shortness of breath;
• if the patient feels changes in heart rhythm;
• if the patient experiences dizziness (a feeling of emptiness in the head) or fainting – this may be a sign of low blood pressure;
• if the patient vomits or has diarrhoea (loose stools);
• if the patient's urine is darker than usual – remember to drink plenty of fluids to avoid dehydration;
• if the patient develops blistering rash or mouth ulcers;
• if the patient loses appetite, feels nauseous, vomits, has diarrhoea, urine is darker than usual, stools are paler than usual, experiences abdominal pain, develops jaundice (yellowing of the skin and whites of the eyes), or feels generally unwell – these may be signs of liver inflammation or damage (liver failure);
• if the patient passes little or no urine, feels drowsy, nauseous, vomits, feels short of breath, has no appetite and/or feels weak – these may be symptoms of acute kidney failure.

The parent of a child receiving Clofarabine Accord should inform the doctor if
any of the above symptoms occur in their child.
While receiving Clofarabine Accord, the doctor will perform regular blood tests and other examinations to monitor the patient's health. The medicine's mechanism of action affects the patient's blood and other organs.
Consult the doctor regarding contraception. Young men and women must use effective contraception during treatment and after treatment has ended. See the section below entitled "Pregnancy and breastfeeding". Clofarabine Accord may damage male and female reproductive organs. Ask the doctor to explain what can be done to protect the patient or preserve the possibility of having children in the future.
Clofarabine Accord and other medicines
Tell the doctor about all medicines the patient is currently taking or has recently taken, including:

• heart medications;
• any medicines affecting blood pressure;
• medicines affecting the liver or kidneys;
• any other medicines, including those available without a prescription.

Pregnancy and breastfeeding
Clofarabine should not be used during pregnancy, except when clearly necessary.
Women of childbearing potential: the patient must use effective contraception during treatment with clofarabine and for 6 months after treatment ends. Clofarabine taken during pregnancy may harm the unborn baby. If the patient is pregnant or becomes pregnant during treatment with clofarabine, seek immediate medical advice.
Men must also use effective contraception and should be advised not to father a child during treatment with Clofarabine Accord and for 3 months after treatment ends.
If the patient is breastfeeding, breastfeeding must be stopped before starting treatment and must not be resumed during treatment and for 2 weeks after treatment ends.
Driving and using machines
Do not drive or operate machinery if the patient experiences dizziness, a feeling of emptiness in the head, or fainting.
Clofarabine Accord contains sodium
This medicine contains 70.77 mg of sodium (the main component of table salt) per vial. This corresponds to 3.54% of the recommended maximum daily dietary sodium intake for adults. Consult a doctor or pharmacist if the patient requires 5 or more vials per day during a prolonged treatment cycle, especially if the patient has been advised to follow a low-salt (low-sodium) diet.

3. How to use Clofarabine Accord

Clofarabine Accord should be administered by a qualified doctor experienced in the treatment of leukemias.
The doctor will determine the appropriate dose for the patient based on height, body weight, and health status. Before administration, Clofarabine Accord will be diluted with sodium chloride solution (a solution of salt and water). Patients should inform their doctor if they are on a diet restricting salt intake, as this may affect the way the medicine is administered.
The doctor will administer the medicine to the patient daily for 5 days. The medicine will be given as an intravenous infusion through a long, thin tube inserted into a vein (intravenous drip) or through a small device implanted under the skin (an implanted venous access device), if one has been placed in the patient (or child). The infusion will last 2 hours. If the patient's (or child's) body weight is less than 20 kg, the infusion duration may be extended.
The doctor will monitor the patient's health condition and may adjust the dose depending on the response to treatment. It is important to drink plenty of fluids to avoid dehydration.
Use of a higher than recommended dose of Clofarabine Accord
Patients should immediately inform their doctor if they believe they have received more than the recommended dose of the medicine.
Missed dose of Clofarabine Accord
The doctor will inform the patient when the medicine will be administered. Patients should immediately notify their doctor if they believe a dose has been missed.
If in doubt about the use of this medicine, patients should consult their treating physician.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will get them.

Very common (may affect more than 1 in 10 patients):

• anxiety, headache, fever, fatigue;
• nausea and vomiting, diarrhoea (loose stools);
• sudden flushing and skin inflammation with itching, mucositis (e.g. in the mouth or other areas);
• increased frequency of infections, as Clofarabine Accord may reduce the number of certain types of blood cells in the patient's body;
• skin rashes which may cause itching, red, painful or peeling skin on the hands and feet, or red or purplish spots under the skin.

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

• blood infections, pneumonia, shingles, infections of implants, oral infections such as candidiasis or herpes labialis;
• changes in blood biochemical test results, changes in white blood cells;
• allergic reactions;
• feeling thirsty, dark-coloured urine or reduced urine volume compared to usual, decreased or loss of appetite, weight loss;
• agitation, irritability or restlessness;
• sensation of numbness or weakness in arms and legs, skin numbness, drowsiness, dizziness, tremor;
• hearing disorders;
• fluid accumulation around the heart, rapid heartbeat;
• low blood pressure, hardening associated with bruising;
• leakage from small blood vessels, rapid breathing, nosebleeds, breathing difficulties, shortness of breath, cough;
• vomiting blood, stomach pain, rectal pain;
• bleeding inside the head, stomach, intestines or lungs, from the mouth or gums, mouth ulcers, oral mucositis;
• yellowing of the skin and eyes (also known as jaundice) or other liver function abnormalities;
• skin rashes which may cause itching, red, painful or peeling skin on the hands and feet, or red or purplish spots under the skin;
• bruising, hair loss, skin colour changes, increased sweating, dry skin or other skin problems;
• chest wall, bone, neck or back pain, limb, 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 generally unwell;
• clofarabine may affect levels of certain substances in the blood. Your doctor will perform regular blood tests to monitor whether your body is functioning properly;
• liver damage (liver failure);
• passing small amounts of urine or no urine at all, drowsiness, nausea, vomiting, shortness of breath, loss of appetite and (or) weakness (possible symptoms of acute kidney injury or kidney failure).

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

• hepatitis.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Clofarabine Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the
carton after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Do not freeze.
Do not use this medicine if changes in the colour of the solution are visible.
After dilution:
The diluted concentrate remains 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, the product should be used immediately. If the product is
not used immediately, the user is responsible for the storage period and conditions prior to use.
Storage should usually not exceed 24 hours at 2°C to 8°C, provided that dilution was carried out
under controlled and validated aseptic conditions.
Medicines must not be disposed of via wastewater. Ask your pharmacist how to dispose of
medicines no longer required. These measures will help protect the environment.

6. Contents of the pack 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 pack
Clofarabine Accord is a concentrate for solution for infusion. It is a clear, practically colourless solution which must be prepared and diluted before use. The medicine is supplied in 20 ml vials. The vials contain 20 mg of clofarabine and are presented in cardboard boxes.
One cardboard box contains 1 vial.

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

Manufacturer / Importer
Pharmadox Healthcare Ltd.
KW20AKordin Industrial Park
Paola, PLA3000
Malta
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland

Clofarabine Accord contains the same active substance and works in the same way as the reference medicinal product authorised in the EU. The reference medicinal product for Clofarabine Accord was authorised under "exceptional circumstances". This means that, due to the rarity of the disease, it was not possible to obtain full information on the reference medicinal product. The European Medicines Agency reviews all new information on the reference medicinal product annually, and any updates to the information on the reference medicinal product will also be incorporated into the patient information materials for Clofarabine Accord, such as this leaflet.

Instructions for use for healthcare professionals

Handling of clofarabine
Information intended solely for healthcare professionals:

Special precautions for the preparation of the medicinal product for administration
Before administration, Clofarabine Accord 1 mg/ml concentrate for solution for infusion must be diluted. It should be filtered through a sterile syringe filter with a pore size of 0.2 micrometres and then diluted with sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a total volume according to the example provided in the table below. However, the final volume of dilution may vary depending on the patient's clinical condition and the physician's decision. (If it is not possible to use a syringe filter with a pore size of 0.2 micrometres, the concentrate should first be filtered through a filter with a pore size of 5 micrometres, then diluted, and subsequently administered through an in-line filter with a pore size of 0.22 micrometres.)

The diluted concentrate should be a clear, colourless solution. It should be inspected visually for particulate matter and discoloration prior to administration.
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 standpoint, the medicinal product should be used immediately. If not used immediately, the responsibility for the storage conditions and duration prior to use lies with the user. This time should not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution has taken place under controlled and validated aseptic conditions. Do not freeze.
Administration instructions
Procedures for the safe handling of cytotoxic anticancer drugs must be observed.
Caution must be exercised when handling cytotoxic agents.
When handling Clofarabine Accord medicinal product, it is recommended to wear disposable gloves and protective clothing. In case of contact with eyes, skin or mucous membranes, the affected area should be immediately flushed with copious amounts of water.
Pregnant women should avoid contact with the Clofarabine Accord medicinal product.
Disposal of unused product
Clofarabine Accord is intended for single use only. Any unused residues of the medicinal product or waste materials must be disposed of in accordance with local regulations.