Fludara oral 10 mg film-coated tablet

• 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 symptoms 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.

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

• if you are allergic to fludarabine phosphate or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding.
• if you have severe kidney problems.
• if your red blood cell count is low, because of a type of anaemia (decompensated haemolytic anaemia). Your doctor will have told you if you have this condition.

Tell your doctor, before taking Fludara oral if you think any of these may apply to you.

Talk to your doctor before taking Fludara oral.

Take special care with Fludara oral:

• if your bone marrow is not working properly or if you have a poorly functioning or depressed immune system or a history of serious infections.
  • Your doctor may decide to not give you this medicine, or may take precautions.
• if you feel very unwell, notice any unusual bruising, more bleeding than usual after injury, or if you seem to be catching a lot of infections.
• if during treatment you have a red to brownish urine, or have a rash or any blisters on your skin.
  • Tell your doctor immediately.

These may be signs of a reduction in the number of your blood cells, which may be caused either by the disease itself or the treatment. It can last for up to a year, independent of whether or not you had treatment with Fludara oral before. During treatment with Fludara oral also your immune system may attack different parts of your body, or your red blood cells (called ‘autoimmune disorders’). These conditions can be life-threatening.

If this occurs your doctor will stop your treatment and you may receive further medication such as transfusion of irradiated blood (see below) and adrenocorticoids.

You will have regular blood tests during treatment and you will be closely monitored while you are being treated with Fludara oral.

• if you notice any unusual symptoms of your nervous system such as disturbed vision, headache, confusion, seizures.

If Fludara oral is used for a long time, its effects on the central nervous system are not known. However, patients treated with the recommended dose for up to 26 courses of treatment were able to tolerate it.

When Fludara is used at the recommended dose, following the treatment with some other medications or at the same time as some other medications, the following adverse events have been reported:

neurological disorders manifested by headache, feeling sick (nausea) and vomiting, seizures, visual disturbances including vision loss, changes in mental status (thinking abnormal, confusion, altered consciousness) and occasionally neuromuscular disorders manifested by muscle weakness in your limbs (including irreversible partial or complete paralysis) (symptoms of leukoencephalopathy, acute toxic leukoencephalopathy or posterior reversible leukoencephalopathy syndrome (RPLS)).

In patients on doses four times greater than recommended blindness, coma and death have been reported. Some of these symptoms appeared delayed around 60 days or more after treatment had been stopped. In some patients receiving Fludara doses higher than the recommended dose, leukoencephalopathy (LE), acute toxic leukoencephalopathy (ATL) or posterior reversible leukoencephalopathy syndrome (RPLS) have also been reported. Same symptoms of LE, ATL or RPLS as above described could occur. LE, ATL, and RPLS may be irreversible, life-threatening, or fatal.

Whenever LE, ATL or RPLS is suspected, your treatment will Fludara will be stopped for further investigations. If the diagnosis of LE, ATL, or RPLS is confirmed, you doctor will permanently discontinue your treatment with Fludara.

• if you notice any pain in your side, blood in your urine or reduced amount of urine.

When your disease is very severe, your body may not be able to clear all the waste products from the cells destroyed by Fludara oral. This is called tumour lysis syndrome and can cause kidney failure and heart problems from the first week of treatment. Your doctor will be aware of this and may give you other medicines to help prevent it. He/she may decide that you should start your treatment in hospital.

• if you need to have stem cells collected and you are being treated with Fludara oral (or have been).
• if you need a blood transfusion and you are being treated with Fludara oral (or have been).

In case you need a blood transfusion your doctor will ensure that you only receive blood that has been treated by irradiation. There have been severe complications and even death, from transfusions of non-irradiated blood.

• if you notice any changes to your skin either while you are receiving this medicine or after you have finished the treatment.
• if you have or have had skin cancer it may worsen or flare up again while you take Fludara oral or afterwards. You may develop skin cancer during or after Fludara oral treatment.

• Fludara oral must not be taken if you are pregnant unless clearly indicated by your doctor.
• Females: you must not become pregnant during treatment with Fludara oral and must use an effective method of contraception during and for 6 months after end of treatment, because Fludara oral may be harmful for the unborn baby. If pregnancy occurs during your treatment, you must immediately inform your doctor. Your doctor will decide with you whether you should carry on taking Fludara.
• Males: you are advised not to father a child and must use an effective method of contraception during and at least for 3 months after end of treatment. You should seek advice on conservation of sperm prior to treatment because Fludara oral may alter male fertility.
• You must not breast-feed while you are treated with Fludara oral.
• if you need a vaccination, check with your doctor, because live vaccinations should be avoided during and after treatment with Fludara oral.
• if you have kidney problems or if you are over 65, you will have regular blood and/or laboratory tests to check your kidney function. If your kidney problems are severe, you will not be prescribed this medicine at all (see sections 2 and 3).
• Fludara oral tablets may cause more vomiting and nausea (being or feeling sick) than Fludara given intravenously. If this is a problem, your doctor will consider switching your treatment to the intravenous Fludara.

The safety and effectiveness of Fludara oral in children below the age of 18 years has not been established. Therefore, Fludara oral is not recommended for use in children.

People over 65 will have regular tests for kidney function (see section 3. How to take Fludara oral).

People over 75 will be monitored especially closely.

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

It is especially important to tell your doctor about:

• pentostatin (deoxycoformycin), also used to treat B-CLL. Taking these two drugs together can lead to severe lung problems.
• dipyridamole, used to prevent excessive blood clotting or other similar drugs. They may reduce the effectiveness of Fludara oral.
• cytarabine (Ara-C) used to treat chronic lymphatic leukaemia. If Fludara oral is combined with cytarabine, levels of the active form of Fludara in leukaemic cells may rise. However, the overall levels in the blood and its elimination from the blood were not shown to have changed.

Pregnancy

Females: you must not become pregnant during treatment with Fludara oral because animal studies and very limited experience in humans have shown a possible risk of abnormalities in the unborn baby as well as early pregnancy loss or premature delivery. If pregnancy occurs during your treatment, you must immediately inform your doctor. Your doctor will decide with you whether you should carry on taking Fludara.

Breast-feeding:

You must not breast-feed while you are treated with Fludara.

Fertility in males and females

Females: you must use an effective method of contraception during and for 6 months after end of treatment, because Fludara oral may be harmful for the unborn baby.

Males: You are advised not to father a child and must use an effective method of contraception during and at least for 3 months after end of treatment. You should seek advice on conservation of sperm prior to treatment because Fludara oral may alter male fertility.

Both men and women who are planning to have a child after treatment are advised to talk to a doctor before start of Fludara treatment.

Some people get tired, feel weak, have disturbed vision, become confused, or agitated or have seizures while they are treated with Fludara oral. Do not try to drive or operate machines until you are sure that you are not affected.

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

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

The dose you should take depends on your body surface area. This is measured in square metres (m²) and is worked out by the doctor from your height and weight.

The recommended dose is 40 mg fludarabine phosphate/m² body surface area, once a day. The usual dose is between 3 to 10 tablets once a day. The exact number of tablets you should take is calculated by your doctor.

Swallow the tablet whole with water. Do not break or chew the tablets. You can take Fludara oral either on an empty stomach or together with food.

Take the dose worked out by your doctor once a day for 5 consecutive days.

This 5-day-course of treatment will be repeated every 28 days until your doctor has decided that the best effect has been achieved (usually after 6 courses).

How long the treatment lasts depends on how successful your treatment is and how well you tolerate Fludara oral. The repeat course may be delayed if side effects are a problem.

You will have blood tests after every treatment. Your individual dose will be carefully adjusted according to the number of your blood cells and your response to the treatment. If the number of your blood cells is too low, your next treatment cycle may be postponed for up to two weeks or your dose may be decreased. The dosage may also be decreased if side effects are a problem.

If you have been treated for two courses and you did not respond to the treatment but you also showed few symptoms of a reduced blood cell count, your doctor may decide to increase your dose.

If you have kidney problems or if you are over the age of 65, you will have regular tests to check your kidney function. If your kidneys do not work properly your doctor may prescribe a lower dose. If your kidney function is severely reduced you will not be prescribed this medicine at all (see section 2).

Tell your doctor immediately if you took too many Fludara oral tablets

High doses can lead to a severely reduced number of blood cells.

For Fludara given intravenously it has been reported, that overdose can cause delayed blindness, coma and even death.

Talk to your doctor as soon as possible if you think you may have missed a dose or vomit after tablet taking.

Do not take a double dose to make up for the forgotten tablets.

Do not stop taking Fludara oral without advice from your doctor.

You and your doctor may decide to stop your treatment with Fludara oral, if the side effects are becoming too severe.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is fludarabine phosphate. Each film-coated tablet of Fludara oral contains 10 mg fludarabine phosphate.
• The other ingredients are
  • in the tablet core: cellulose (microcrystalline), lactose (monohydrate), silica (colloidal anhydrous), croscarmellose sodium, magnesium stearate;
  • in the film-coat: hypromellose, talc, titanium dioxide (E171), ferric oxide pigment (yellow (E172)), ferric oxide pigment (red (E172)).

Fludara oral are salmon-pink, capsule-shaped film-coated tablets, marked with ‘LN’ in a regular hexagon on one side. The tablets are provided in blisters of 5 tablets each. The blisters are of polyamide/aluminium/poly-propylene thermoformable foil with a lidding foil of aluminium. The blisters are packed in a polyethylene tablet container with a child-resistent polypropylene screw cap.

Fludara oral is available in packs containing:

• 15 tablets in 3 blisters in a child-resistant bottle.
• 20 tablets in 4 blisters in a child-resistant bottle.

Not all pack sizes may be marketed.

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