Fludara

Package Leaflet: Information for the User

Fludara, 10 mg, coated tablets

Fludarabine phosphate

Read all of this leaflet carefully before taking 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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1 .
What Fludara is and what it is used for

• 2. Important information before taking Fludara 3 .How to take Fludara
• 4. Possible side effects
• 5. How to store Fludara
• 6. Contents of the pack and other information

1. What Fludara is and what it is used for

Fludara is used to treat chronic lymphocytic leukaemia (CLL). This is a type of cancer of the white blood cells called lymphocytes. In this disease, too many immature or abnormal lymphocytes are produced. These cells are not able to work properly and can crowd out healthy blood cells in the bone marrow, where they are normally produced. If the number of abnormal cells is too high, they can spill over into the bloodstream and may cause problems such as infections, anaemia, bruising, bleeding, or even organ failure.
All cells in the body, both normal and cancerous, divide to make new cells. To do this, the genetic material (DNA) in each cell must be copied and reproduced. Fludara works by blocking the production of new DNA. As a result, after Fludara is taken up by the cancer cells, the production of new cancer cells is stopped.

Indications for use

Fludara is indicated for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) of B-cell type. It is also indicated for patients with CLL of B-cell type who have not responded to or have progressed after treatment with at least one standard chemotherapy regimen containing an alkylating agent.

2. Important information before taking Fludara

When not to take Fludara

• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or breastfeeding;
• if you have severe kidney problems, with a creatinine clearance of less than 30 ml/min;
• if you have a low red blood cell count due to haemolytic anaemia. Your doctor will inform you about this condition. Before starting treatment, you must inform your doctorif you think any of these contraindications apply to you.

Warnings and precautions

Before starting treatment with Fludara, you should discuss this with your doctor.

• in patients with kidney problems, the dose of Fludara should be reduced;
• in patients with liver problems or poor general condition, Fludara should be used with caution;
• men and women of childbearing age should use effective contraception during treatment and for at least 6 months after treatment;
• you should discuss with your doctor the need for vaccinations, as live vaccines should not be given during or after treatment with Fludara;
• if you need a blood transfusion or bone marrow harvest, you should inform your doctor that you are being treated with Fludara;
• if you have a history of skin cancer, your skin condition may worsen during or after treatment with Fludara. You should inform your doctor if you notice any changes in your skin.

You should inform your doctor if you notice any unusual bruising, bleeding, or signs of infection. In these cases, your blood cell count may be low, and regular monitoring of your blood count may be necessary.
You should inform your doctor if you experience any of the following symptoms: headache, nausea, vomiting, seizures, visual disturbances, or loss of vision, optic neuritis, disorientation, somnolence, agitation, weakness, or incontinence. These symptoms may indicate life-threatening complications and require close medical attention.
Some patients treated with Fludara have reported nausea and vomiting more frequently after oral administration than after intravenous administration. If these symptoms are a significant clinical problem, intravenous administration of Fludara is recommended.
Fludara should not be taken during pregnancy, unless explicitly recommended by your doctor.

Women of childbearing age

Women must use effective contraceptionduring treatment with Fludara and for 6 months after treatment, as Fludara may harm the unborn child. If you become pregnant during treatment, you should inform your doctor immediately. Your doctor will decide with you whether to continue treatment with Fludara.

Men

Men must use effective contraceptionand should be advised not to father a childduring treatment with Fludara and for at least 3 months after treatment. Before starting treatment, men should seek advice on sperm freezing, as Fludara may affect fertility.
Fludara should not be taken during breastfeeding.

Children

The safety and efficacy of Fludara in children have not been established.

Fludara and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Ask your doctor for advice before taking any medicine.
Fludara should not be taken with pentostatin (deoxycoformycin), as this may lead to severe lung disease.
Certain medicines, such as dipyradamole, may reduce the effectiveness of Fludara.
If you are unsure about taking other medicines with Fludara, consult your doctor or pharmacist before starting treatment.

Elderly patients and Fludara

Caution should be exercised when administering Fludara to patients over 75 years of age, due to limited data on the use of Fludara in this age group.

Pregnancy and breastfeeding

Pregnancy
Women should not become pregnant during treatment with Fludara, as animal studies and limited human experience have shown a possible risk of birth defects or miscarriage. If you become pregnant during treatment, you should inform your doctor immediately. Your doctor will decide with you whether to continue treatment with Fludara.
Breastfeeding
Fludara should not be taken during breastfeeding.
Fertility in men and women
Women must use effective contraception during treatment with Fludara and for 6 months after treatment, as Fludara may harm the unborn child.
Men must use effective contraception and should be advised not to father a childduring treatment with Fludara and for at least 3 months after treatment. Before starting treatment, men should seek advice on sperm freezing, as Fludara may affect fertility.
Couples planning to have a child after treatment with Fludara should consult their doctor before starting treatment.

Driving and using machines

Some patients treated with Fludara have reported fatigue, weakness, visual disturbances, disorientation, agitation, or seizures. You should not drive or operate machinery until you are sure that you are not experiencing any of these symptoms. Your reaction time may be slowed due to insufficient sleep, sensitivity to the medicine, or dosing.

Fludara contains lactose

Fludara Oral contains lactose (a type of sugar). If you have been told that you have an intolerance to some sugars, you should contact your doctor before taking this medicine.

Fludara contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which is essentially 'sodium-free'.

3. How to take Fludara

This medicine should always be taken exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist.

How to take Fludara tablets

Swallow the tablet whole with water. Do not break or chew the tablets. Fludara can be taken on an empty stomach or with food.

How many tablets to take

The dose you take depends on your body surface area. This is measured in square metres (m²) and is calculated by your doctor based on your height and weight.
The recommended doseis 40 mg per square metre of body surface area. It is taken once a day for 5 consecutive days, in cycles of 28 days. The exact number of tablets you take is calculated by your doctor.

How long to take Fludara

Take the dose calculated by your doctor once a day for 5 consecutive days. Your doctor will tell you how many tablets to take each day.
This 5-day treatment cycle will be repeated every 28 days, until your doctor decides that the best response to treatment has been achieved (complete or partial remission, usually after 6 cycles).
The duration of treatment depends on the success of treatment and your tolerance to Fludara. If you experience side effects, your doctor may reduce the dose or extend the intervals between cycles.

Patients with kidney or liver problems

In patients with kidney problems, the dose of Fludara should be adjusted individually. If the creatinine clearance is between 30-70 ml/min, the dose should be reduced by 50% and regular haematological monitoring should be performed to assess toxicity.
Fludara is contraindicated in patients with a creatinine clearance of less than 30 ml/min.
There is no experience with the use of Fludara in patients with liver problems. In this group of patients, Fludara should be used with caution and only when the expected benefits outweigh the potential risks.

Taking too much Fludara

Tell your doctor immediatelyif you take too many Fludara tablets. After taking high doses of Fludara, the following have been observed: headache, nausea, vomiting, seizures, visual disturbances including loss of vision, optic neuritis, disorientation, somnolence, agitation, weakness, and incontinence. Additionally, the following may occur: optic neuritis, papillitis, disorientation, somnolence, agitation, weakness, and incontinence. Irreversible changes in the central nervous system, which can cause delayed loss of vision (not immediately after administration), coma, and death, have also been reported. High doses can also cause severe thrombocytopenia and neutropenia due to bone marrow suppression. There is no specific antidote in case of overdose. If you have taken more tablets than your doctor prescribed, seek medical attention immediately: call your doctor or go to the nearest hospital. Always take the packaging and any remaining tablets with you.

Missing a dose of Fludara

Tell your doctor as soon as possibleif you miss a dose or vomit after taking a tablet. Your doctor will advise you on a fixed time for taking Fludara.
Do not take a double dose to make up for a missed tablet.

Stopping treatment with Fludara

Do not stop taking Fludara without consulting your doctor.
If side effects become too severe, you and your doctor may decide to stop treatment with Fludara.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Fludara can cause side effects, although not everybody gets them.
Based on experience with Fludara, the most common side effects are: bone marrow suppression (neutropenia, thrombocytopenia, anaemia), infections (including pneumonia, cough, fever), fatigue, weakness, nausea, vomiting, and diarrhoea. Other common side effects include: chills, oedema, malaise, peripheral neuropathy, visual disturbances, anorexia, mucositis, and skin rash. Severe opportunistic infections have been reported in patients treated with Fludara. Fatal outcomes have been reported due to severe side effects.
The following is a list of possible side effects, grouped by frequency:

Very common (affecting more than 1 in 10 people):

• infections (some severe);
• infections due to a weakened immune system (opportunistic infections), e.g. herpes virus, Epstein-Barr virus, progressive multifocal leukoencephalopathy (a condition affecting the brain);
• pneumonia with symptoms such as difficulty breathing and (or) cough with or without fever;
• low platelet count (thrombocytopenia) with bruising and bleeding;
• low white blood cell count (neutropenia);
• low red blood cell count (anaemia);
• cough;
• vomiting, diarrhoea, nausea;
• fever;
• fatigue;
• weakness.

Common (affecting less than 1 in 10 people):

• other blood cancers (myelodysplastic syndrome, acute myeloid leukaemia); most patients with these conditions had previously, concurrently, or later been treated with other anti-cancer medicines (alkylating agents, topoisomerase inhibitors) or radiotherapy;
• bone marrow suppression (myelosuppression);
• severe loss of appetite leading to weight loss;
• numbness or weakness of the limbs (peripheral neuropathy);
• visual disturbances;
• mouth inflammation;
• skin rash;
• swelling due to excess fluid;
• mucositis;
• chills;
• general malaise.

Uncommon (affecting less than 1 in 100 people):

• autoimmune disorders, where the body attacks its own cells and tissues, including: autoimmune haemolytic anaemia, thrombocytopenic purpura, pemphigus, Evans syndrome (a condition affecting the blood), acquired haemophilia (a bleeding disorder);
• tumour lysis syndrome, including: kidney damage, high potassium levels in the blood, metabolic acidosis, blood in the urine, crystals in the urine, high uric acid levels in the blood, high phosphate levels in the blood, low calcium levels in the blood;
• bleeding in the digestive tract;
• disorientation (confusion);
• toxic effects on the lungs, pulmonary fibrosis, pneumonia, shortness of breath;
• changes in liver or pancreas enzyme activity.

Rare (affecting less than 1 in 1000 people):

• lymphoproliferative disorders associated with Epstein-Barr virus infection;
• coma;
• seizures;
• agitation;
• blindness;
• optic neuritis or optic nerve damage;
• heart failure;
• abnormal heart rhythm (arrhythmia);
• skin cancer;
• skin and mucous membrane reactions, including redness, inflammation, blistering, or tissue damage (Lyell's syndrome, Stevens-Johnson syndrome).

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. You can also report side effects directly to the national reporting system via the Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card Scheme (www.mhra.gov.uk/yellowcard). By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Fludara

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 carton and blister after EXP. The expiry date refers to the last day of that month.
Store below 25°C. Do not store in a refrigerator. Store in the original package.
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 pack and other information

What Fludara contains

• The active substance isfludarabine phosphate. Each Fludara tablet contains 10 mg of fludarabine phosphate.
• The other ingredients are:
• microcrystalline cellulose, lactose monohydrate, colloidal silicon dioxide, sodium croscarmellose, magnesium stearate;
• tablet coating: hypromellose, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172).

What Fludara looks like and contents of the pack

Fludara is a salmon-pink, coated tablet in a capsule shape, marked with the letters "LN" in a hexagon on one side.
The immediate packaging is a blister pack containing 5 coated tablets. To protect against children, the blisters are packaged in a child-resistant container.
Fludara is available in packs containing:

• 15 tablets in 3 blisters, packaged in a child-resistant container.
• 20 tablets in 4 blisters, packaged in a child-resistant container.

Container in a cardboard box.

Marketing Authorisation Holder

Sanofi B.V.
Paasheuvelweg 25
1105 BP Amsterdam
Netherlands

Manufacturer

SANOFI WINTHROP INDUSTRIE
30-36, avenue Gustave Eiffel
37100 Tours
France
To obtain more detailed information, contact the local representative of the Marketing Authorisation Holder:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warszawa
Tel.: 022 280 00 00

Date of last revision of the leaflet: