Clofarabine Medac

Patient Information Leaflet

Clofarabine medac 1 mg/ml concentrate for solution for infusion

Generic medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, talk to your doctor. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Clofarabina medac is and what it is used for

Clofarabina medac contains the active substance clofarabine. Clofarabine belongs to a group of
medicines called antineoplastic agents. It works by slowing down the growth of abnormal white blood cells and
ultimately kills them. It is most effective against cells that are rapidly multiplying, such as cancer cells.
Clofarabina medac is used to treat children (≥ 1 year of age), adolescents, and young patients up to 21 years of age with acute lymphoblastic leukemia (ALL) for whom previous treatments have not worked or have stopped being effective. Acute lymphoblastic leukemia is
caused by the abnormal growth of certain types of white blood cells.

2. What you need to know before using Clofarabina medac

Do not use Clofarabina medac

• if you are allergic to clofarabine or to any of the excipients of this medicine (listed in section 6);
• if you are breastfeeding (see the section “Pregnancy and breastfeeding” below);
• if you have severe kidney or liver problems.

Inform your doctor if any of the following conditions apply to you. If you are the parent of
a child being treated with Clofarabina medac, inform your doctor if any of these conditions apply to your child.
Warnings and precautions
Talk to your doctor before using Clofarabina medac.
Inform your doctor if any of the following conditions apply to you. Clofarabina medac may not be suitable for you:

• if you have had severe reactions after using this medicine previously;
• if you have kidney disease or have had it in the past;
• if you have liver disease or have had it in the past;
• if you have heart disease or have had it in the past.

Inform your doctor or healthcare provider immediately if you experience any of the following, as treatment may need to be stopped:

• if you have fever or high temperature – since clofarabine reduces the number of blood cells produced by the bone marrow, you may be more likely to develop an infection;
• if you have difficulty breathing, breathe rapidly, or feel short of breath;
• if you notice changes in your heart rate;
• if you experience dizziness (a feeling of emptiness in the head) or fainting: these may be symptoms of low blood pressure;
• if you have nausea or diarrhoea (loose stools);
• if your urine becomes darker than normal – it is important to drink plenty of water to prevent dehydration;
• if you develop a rash with blisters or mouth ulcers;
• if you lose your appetite, feel nauseous (feeling unwell), vomit, have diarrhoea, dark urine and pale stools, stomach pain, jaundice (yellowing of the skin and eyes), or feel generally unwell; these may be symptoms of liver inflammation (hepatitis) or liver damage (liver failure);
• if you urinate less than usual or not at all, or if you feel drowsy, nauseous, vomit, are short of breath, lose your appetite and/or feel weak (these may be signs of acute kidney failure / renal failure).

If you are the parent of a child being treated with Clofarabina medac, inform your doctor if any of the above conditions apply to your child.
During treatment with Clofarabina medac, your doctor will perform regular blood tests and other examinations to monitor your health status. Due to its mechanism of action, this medicine may affect blood parameters and other organs.
Talk to your doctor about contraception. Men and women of reproductive age must use effective contraceptive methods during and after treatment. See the section “Pregnancy and breastfeeding” below. Clofarabina medac may damage male and female reproductive organs. Ask your doctor to explain what can be done to protect your fertility.
Children
Safe and effective dosing recommendations for children under 1 year of age have not been established.
Other medicines and Clofarabina medac
Inform your doctor if you are currently using or have recently used:

• medicines for heart conditions;
• any medicine that affects blood pressure;
• medicines that affect the liver or kidneys;
• any other medicines, including those without a prescription.

Pregnancy and breastfeeding
Clofarabine must not be used during pregnancy unless clearly necessary.
Women of childbearing potential: you must use effective contraception during treatment with clofarabine. Clofarabine may harm the unborn baby if used during pregnancy. If you are pregnant or become pregnant during treatment with clofarabine, contact your doctor immediately.
Men must also use effective contraception when they or their partner are undergoing treatment with clofarabine.
If you are breastfeeding, you must stop breastfeeding before starting treatment and must not breastfeed during treatment or for 3 months after the end of treatment.
Driving and use of machines
Do not drive or operate tools or machinery if you experience dizziness, a feeling of emptiness in the head, or feel faint.
Clofarabina medac contains sodium salt
Each vial contains 180 mg of salt (sodium chloride), equivalent to 3.08 mmol (or 70.77 mg) of sodium. If you are on a controlled-sodium diet, you should take this into account.

3. How to use Clofarabina medac

Clofarabina medac has been prescribed for you by a qualified physician experienced in the
treatment of leukemia.
Your doctor will calculate the correct dose for you based on your height, weight, and overall health status. Before administration, Clofarabina medac will be diluted in a sodium chloride solution (water and salt). Inform your doctor if you are following a sodium-restricted diet, as this may affect the way the medicine is administered.
Your doctor will administer Clofarabina medac once daily for 5 days by intravenous infusion, through a thin tube inserted into a vein (intravenous line) or through a small medical device implanted under the skin (port-a-cath), if such a device has been implanted in you (or the child). The infusion will be given over a period of 2 hours. If you (or the child) weigh less than 20 kg, the infusion time may be longer.
Your doctor will monitor your health condition and may adjust the dose according to your response to treatment. It is important to drink plenty of fluids to avoid dehydration.
If you use more Clofarabina medac than you should
If you think you have been given too much of the medicine, inform your doctor immediately.
If you forget to use Clofarabina medac
Your doctor will inform you of the exact timing for administration of the medicine. If you think a dose has been missed, inform your doctor immediately.
If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

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

• anxiety, headache, fever, fatigue;
• nausea and vomiting, diarrhoea, (loose stools);
• hot flushes, itching and inflamed skin, inflammation of mucous membranes such as the mouth and other areas;
• infections may occur more frequently than normal, as Clofarabina medac may reduce the number of certain types of blood cells in the body;
• skin rashes, possibly itchy, red, painful or peeling skin, including on the palms of the hands and soles of the feet, or small reddish or purplish spots under the skin.

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

• blood infections, pneumonia, shingles, catheter-related infections, mouth infections such as candidiasis and cold sores;
• changes in blood chemistry values, changes in white blood cells;
• allergic reactions;
• feeling thirsty, passing darker urine or producing less urine than normal, reduced or loss of appetite, weight loss;
• restlessness, irritability or agitation;
• tingling or weakness in arms and legs, numbness, drowsiness, dizziness, tremor;
• hearing problems;
• fluid accumulation around the heart, rapid heartbeat;
• low blood pressure, swelling due to large bruises;
• bleeding from small blood vessels (capillaries), rapid breathing, nosebleeds, difficulty breathing, shortness of breath, cough;
• vomiting blood, stomach pain, anal pain;
• bleeding in the brain, stomach, intestines or lungs, mouth or gums, mouth ulcers, inflammation of the mouth mucosa;
• yellowing of the skin and eyes (also known as jaundice) or other liver problems;
• bruising, hair loss, skin colour changes, increased sweating, dry skin and 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 in parts of the body, including arms and legs, changes in mental state, feeling of warmth, feeling of cold, feeling unwell;
• clofarabine may affect levels of certain substances in the blood. Your doctor will perform periodic blood tests to monitor your body’s proper functioning;
• liver damage (hepatic failure);
• little or no urine, drowsiness, nausea, vomiting, shortness of breath, loss of appetite and/or weakness (possible signs of acute kidney injury or kidney failure).

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

• inflammation of the liver (hepatitis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Clofarabina medac

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 label of the vial and on the
box after EXP. The expiry date refers to the last day of that month.
Do not freeze.
The diluted concentrate is chemically and physically stable in PVC bags for 3 days at 2-8 °C and at
room temperature (up to 25°C). From a microbiological standpoint, the product should be used
immediately. If not used immediately, the in-use storage duration and conditions prior to use are the
responsibility of the user and normally should not exceed 24 hours at 2 to 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Clofarabina medac 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, hydrochloric acid (for pH adjustment), and water for injections.

Description of the appearance of Clofarabina medac and package contents
Clofarabina medac is a concentrate for solution for infusion. It is a clear, almost colourless solution, which must be prepared and diluted before use. It is available in 20 ml glass vials. The vials contain 20 mg of clofarabine and are packed in a box. The vials may or may not be wrapped in a protective pouch. Each box contains 4 vials, although not all pack sizes may be marketed.

Marketing Authorization Holder
medac pharma s.r.l.
via Viggiano 90
00178 Rome
Italy

Manufacturer
S.C. SINDAN-PHARMA S.R.L.
11th Ion Mihalache Boulevard
Bucharest 1
Romania

This medicinal product has been granted a marketing authorization under "exceptional circumstances".
This means that, due to the rarity of the disease, complete information on this medicinal product could not be obtained.
The information on this medicinal product and this package leaflet will be updated as necessary.

The following information is intended for healthcare professionals only:

Special administration precautions
Clofarabine medac 1 mg/ml concentrate for solution for infusion must be diluted prior to
administration. It must be filtered through a sterile 0.2 micrometer syringe filter and then diluted with
sodium chloride 9 mg/ml (0.9%) for intravenous infusion to achieve a total volume according to the
examples reported in the table below. However, the final dilution volume may vary depending on the
patient's clinical condition and at the physician's discretion. (If a 0.2 micrometer syringe filter is not
available, the concentrate must be pre-filtered with a 5 micrometer filter, diluted, and then administered
through a 0.22 micrometer in-line filter).

The diluted concentrate should be a clear, colourless solution. It must be inspected visually for the presence of particles and discoloration prior to administration.
The diluted concentrate is chemically and physically stable for 3 days at a temperature of 2–8 °C and at room temperature (up to 25°C). From a microbiological standpoint, it should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours between 2–8 °C, unless dilution has taken place under controlled and validated aseptic conditions. Do not freeze.
Handling instructions
Procedures for the proper handling of antineoplastic agents must be observed. Cytotoxic medicinal products must be handled with caution.
Use of disposable gloves and protective clothing is recommended when handling clofarabine. If the product comes into contact with eyes, skin, or mucous membranes, immediately rinse thoroughly with abundant water.
Clofarabine should not be handled by pregnant women.
Disposal
Clofarabine is for single use only.
Any unused medicinal product or waste material must be disposed of in accordance with local requirements.