CLOFARABINE ACCORD 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

Clofarabine

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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 Accord and what is it used for
2. What you need to know before you use Clofarabine Accord
3. How to use Clofarabine Accord
4. Possible side effects
5. Storage of Clofarabine Accord
6. Contents of the pack and other information

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

This medicine contains the active substance clofarabine. Clofarabine belongs to a group of medicines called antineoplastic agents. It works by making it harder for abnormal white blood cells to grow, and then killing them. It works best on cells that are growing quickly, like cancer cells.

Clofarabine 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) that has not responded to or has 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 Accord

Do not use Clofarabine Accord:

• 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 above situations.If you are the parent or guardian of a child being treated with this medicine, tell the doctor if your child is in any of the above situations.

Warnings and precautions

Tell your doctor if you are in any of the situations listed below.Clofarabine Accord may not be suitable for you:

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

Tell your doctor or healthcare provider 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 (like you are about to pass out) 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 can be signs of acute kidney failure or kidney failure).

If you are the parent or guardianof a child being treated with clofarabine, tell the doctor if your child is in any of the above situations.

During treatment with Clofarabine Accord, 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.Young men and women should use effective birth control methods during and after treatment. See the section “Pregnancy and breast-feeding” below. Clofarabine can cause damage to the reproductive organs in both males and females. Ask your doctor to explain what can be done to protect you or allow you to have a family.

Using Clofarabine Accord with other medicines

Tell your doctor if you are using or have recently 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 method of birth control 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, consult your doctor immediately.

Men should also use effective birth control methods and are advised not to father a child while receiving this medicine 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 use tools or machines if you feel dizzy, lightheaded, or are going to faint.

Clofarabine Accord contains sodium

This medicine contains 70.77 mg of sodium (the main component of table/cooking salt) per vial. This is equivalent to 3.54% of the maximum recommended daily intake of sodium for an adult.

Consult your doctor or pharmacist if you need 5 or more vials per day for an extended period, especially if you have been advised to follow a low-salt diet.

3. How to use Clofarabine Accord

A qualified and experienced doctor has prescribed this medicine for you.

Your doctor will decide the right dose for youbased on your weight, height, and health. Before administration, clofarabine 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 administered.

Your doctor will give you Clofarabine Accord 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 implanted. 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 adjust the dose depending on your response to treatment. It is essential to drink plenty of water to avoid dehydration.

If you use more Clofarabine Accord than you should

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

If you miss a dose of Clofarabine Accord

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 side effects (may affect more than 1 in 10 people):

• anxiety, headache, fever, fatigue;
• nausea and vomiting, diarrhea;
• flushing, skin inflammation and itching, inflammation of the mucous membranes (wet surfaces) of the mouth and other areas of the body;
• more infections than usual because clofarabine 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 side effects (may affect up to 1 in 10 people):

• blood infections, pneumonia, herpes zoster, infections in an implant, mouth infections such as candidiasis or ulcers caused by herpes;
• changes in blood biochemistry, changes in white blood cells;
• allergic reactions;
• feeling thirsty, 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, breathing difficulties, shortness of breath, cough;
• vomiting blood, stomach pain, pain in the buttocks;
• bleeding in 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;
• chest pain or bone pain, neck or back pain, 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 status, feeling hot, cold, or feeling "strange";
• clofarabine can 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 side effects (may affect up to 1 in 100 people):

• liver inflammation (hepatitis).

Reporting of side effects

If you experience any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency at www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Clofarabine Accord

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 refers to the last day of the month stated.

Do not freeze.

Do not use this medicine if you notice any discoloration.

After dilution:

Physical and chemical stability has been demonstrated for up to 3 days at 2°C-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, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

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 Content and Additional Information

Clofarabine Accord Composition

The active ingredient is clofarabine. Each ml contains 1 mg of clofarabine. Each 20 ml vial contains 20 mg of clofarabine.

The other components are sodium chloride and water for injectable preparations.

Product Appearance and Container Size

Clofarabine Accord 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. Each box contains 1 vial,

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n, Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Pharmadox Healthcare Ltd.

KW20A

Kordin Industrial Park,

Paola, PLA3000, Malta

or

Accord Healthcare Polska Sp.z.o.o.

Ul. Lutomierska 50,

95-200, Pabianice,

Poland

This Medicinal Product isAuthorized in the Member States of the European Economic Area under the following names:

Date of Last Revision of this Leaflet: October 2023

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

Instructions for Use of Clofarabine by Healthcare Professionals

The following information is intended for healthcare professionals only:

Special Precautions for Administration

Clofarabine Accord 1 mg/ml Concentrate for Solution for Infusion must be diluted before administration. It should be passed through a sterile 0.2 microns syringe filter, and then diluted in an intravenous infusion solution with 9 mg/ml of sodium chloride (0.9%) to obtain the required total volume according to 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 syringe filter is not available, the concentrate should be pre-filtered 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 for 3 days at 2 °C to 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 normally should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless the dilution has been carried out under controlled and validated aseptic conditions. Do not freeze.

Handling Instructions

Proceed according to the recommended procedures for the proper handling of antineoplastic agents. Cytotoxic drugs should be handled with caution.

The use of disposable gloves and protective clothing is recommended when handling clofarabine. If the product comes into contact with the eyes, skin, or mucous membranes, rinse the area immediately with plenty of water.

Pregnant women should not handle clofarabine.

Disposal

Clofarabine is for single use. The disposal of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.