10 mg film-coated tablets
fludarabine phosphate

1. What Fludara is and what it is used for

Fludara contains the active substance fludarabine phosphate, which stops the growth of new cancer cells. All cells in the body produce new copies of themselves through division Fludara is taken up by the cancer cells and stops their division.

In cancer of the white blood cells (such as chronic lymphocytic leukemia ), the body produces many abnormal white blood cells ( lymphocytes ) and the lymph nodes in different parts of the body begin to grow. The abnormal white blood cells are unable to perform their normal disease-fighting functions. If there are too many of these abnormal white blood cells, they displace the healthy blood cells, which can lead to infection, decreased red blood cell count anemia ), bruising, heavy bleeding or the body’s organs may even stop functioning.

Fludara is used to treat chronic B-type (B- CLL ) lymphocytic leukemia in patients with adequate production of healthy blood cells.

The first treatment for chronic lymphocytic leukemia with Fludara should only be started in patients with advanced disease with disease-related symptoms or signs of disease progression.

2. What you need to know before taking Fludara

Do not take Fludara:

  • 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 renal impairment
  • if you have a certain type of anemia (uncompensated hemolytic anemia ) that causes a decrease in the number of red blood cells. If you have this type of anemia, your doctor has told you about it.

If you think any of these apply to you, tell your doctor before using Fludara.

Warnings and cautions

Talk to your doctor before taking Fludara.

Take special care with Fludara:

  • if your bone marrow is not working properly or if you have a malfunctioning or weakened immune system or a history of serious infection.
  • Your doctor may decide not to give you this medicine or take precautions.
  • if you feel very bad, notice that you get abnormally many bruises or that wounds bleed more than usual, or if you seem to get many infections.
  • if you get red to brownish urine during treatment, or if you get a rash or blisters on the skin.
  • Tell your doctor immediately.

These symptoms may be signs of decreased blood cell count, which may be caused either by the disease itself or by the treatment. It can last for up to a year, regardless of whether you have been treated with Fludara before or not. During treatment with Fludara, your immune system can also attack different parts of the body or the red blood cells (so-called “autoimmune conditions”). These conditions can be life-threatening. If this happens, your doctor will stop the treatment and you may receive other treatments, e.g. blood transfusion with irradiated blood (see below) and corticosteroids.

You will be given blood tests regularly during treatment and you will be closely monitored during your treatment with Fludara.

  • if you notice any unusual symptoms from the nervous system such as visual disturbances, headaches, confusion, seizures.

If Fludara is used for a long time, its long-term effects on the central nervous system are not known. However, patients treated with the recommended dose of one with up to 26 treatment regimens could tolerate it.

When Fludara is given at the recommended dose, after treatment with other medicines or at the same time as other medicines, the following side effects have been reported:

neurological problems which manifest themselves as headache, nausea and vomiting, convulsions, visual disturbances including vision loss, altered state of mind (abnormal thoughts, confusion, altered consciousness), and sometimes neuromuscular disorders which manifest as muscle weakness in arms and legs (including persistent incomplete or complete paralysis ) (symptoms of leukoencephalopathyacute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome ).

In patients who have received a dose four times higher than the recommended dose, blindness, coma and death have been reported. Some of these symptoms were delayed by about 60 days or more after discontinuation of treatment. In some patients who have received a higher dose of Fludara than the recommended dose, leukoencephalopathy, acute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome have also been reported. The same symptoms as described above for these diseases can occur.

Leukoencephalopathy, acute toxic leukoencephalopathy, or reversible posterior leukoencephalopathy syndrome can be persistent, life-threatening, or cause death.

If any of these diseases are suspected, treatment with Fludara will be discontinued for further investigation. If the diagnosis of leukoencephalopathy, acute toxic leukoencephalopathy, or reversible posterior leukoencephalopathy syndrome is confirmed, your doctor will stop your treatment with Fludara permanently.

  • if you get side pain, blood in the urine,e or decreased urine volume.
    If your disease is very severe, your body may not be able to get rid of all the waste products from the cells destroyed by Fludara. This is called tumor lysis syndrome and can cause kidney failure and heart problems from the first week of treatment. Your doctor is aware of this and may give you other medicines to prevent it. He/she may consider that you should start your hospital treatment.
  • if you are undergoing stem cell collection and you are being treated (or have been treated) with Fludara.
  • if you need a blood transfusion and you are being treated (or have been treated) with Fludara.
    Your doctor will make sure that you only receive blood that has been treated with radiation. Serious complications, and even death, have occurred after transfusion of unirradiated blood.
  • if you notice any skin changes while receiving this medicine or after stopping treatment.
  • if you have (or have had) skin cancer, it may worsen or flare up again during or after treatment with Fludara. You may develop skin cancer during or after treatment with Fludara.

What you should also keep in mind when you are treated with Fludara:

  • Men and women of child-bearing age must use effective contraception during treatment and for at least 6 months after treatment. It cannot be ruled out that Fludara may harm the unborn baby. Your doctor will carefully weigh the benefits of your treatment against the possible risks to the unborn baby. If you are pregnant, you will only be treated with Fludara if necessary.
  • you should not breast-feed or start breast-feeding during treatment with Fludara.
  • If you need to get vaccinated, tell your doctor, as live vaccines should be avoided during and after treatment with Fludara.
  • if you have kidney problems or are older than 65 years, you will be regularly given blood tests and/or other tests to check your kidney function, if your kidney function is severely impaired, you will not receive this medicine at all (see sections 2 and 3).
  • Fludara tablets may cause more vomiting and nausea than when fludarabine is given intravenously. If this is difficult, your doctor may consider switching treatment to intravenous fludarabine.

Children and young people

The safety and efficacy of Fludara in children under 18 years of age have not been established. Fludara is therefore not recommended for use in children.

Older and Fludara

People over the age of 65 will be given regular tests to check their kidney function (see section 3, “How to take Fludara”).

People over the age of 75 will be followed very closely

Fludara with food, drink, and alcohol

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

You must tell your doctor about:

  • pentostatin ( deoxicoformycin ), which is also used to treat chronic B-cell lymphocytic leukemia, as concomitant use of these two drugs can lead to serious lung complications.
  • dipyridamole, which is used to prevent coagulation of the blood or other similar substances. They may reduce the effect of Fludara.
  • cytarabine ( Ara-C ), which is used to treat chronic lymphocytic leukemia. If Fludara is combined with cytarabine, the levels of the active form of Fludara in leukemia cells may rise. However, the total levels in the blood and elimination from the blood have not been shown to change.

Pregnancy, breastfeeding, and fertility

Pregnancy

Fludara should not be given to pregnant women, as animal studies and very limited human experience have shown a possible risk of abnormalities in the unborn child as well as premature miscarriage or premature birth.

If you are pregnant or think you may be pregnant, tell your doctor immediately.

Your doctor will carefully weigh the benefits of your treatment against the possible risks to the unborn baby. If you are pregnant, you will only be treated with Fludara, if necessary.

Breast-feeding

You must not start or continue breast-feeding during treatment with Fludara, as this medicine may affect the growth and development of your baby.

Fertility

Men and women of childbearing potential must use effective contraception during treatment and for at least 6 months after stopping treatment.

Driving and using machines

Some people get tired, feel weak, have visual disturbances, become confused or upset, or have seizures when treated with Fludara. Do not drive or use machines until you are sure you are not affected.

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of a drug due to its effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.

Fludara contains lactose

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 medicine.

Fludara contains sodium

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

How to take Fludara

Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.

Dose one is based on the body surface area which is measured in square meters and is calculated by the doctor based on your height and weight.

The recommended dose is 40 mg fludarabine phosphate / m 2 body surface area once daily. The daily dose can vary between 3 and 10 tablets. Your doctor will calculate the exact number of tablets you should take.

How to take Fludara tablets

The tablets must be swallowed whole with water and must not be chewed or broken. Fludara can be taken either on an empty stomach or with a meal.

How long to take Fludara

Take the dose that your doctor calculated once a day for 5 consecutive days.

This 5-day course of treatment is repeated every 28 days until the doctor assesses that the best effect has been achieved (usually after 6 rounds).

The duration of the treatment depends on how successful the treatment is and how well you tolerate Fludara. The repeated rounds of treatment can be postponed if you experience problems in the form of side effects.

You will be given blood samples regularly during treatment. Your individual dose will be carefully adjusted depending on the number of blood cells and how you respond to the treatment. If the blood cell count is too low, your next course of treatment may be delayed for up to two weeks or your dose may be reduced. The dose can also be reduced if you experience problems in the form of side effects.

If you have been treated in two rounds and have not responded to treatment, but have shown some symptoms of decreased blood cell count, your doctor may decide to increase your dose.

If you have kidney problems or are older than 65 years, you will be regularly given samples to check your kidney function. If you find that your kidneys are not working properly, your doctor may prescribe a lower dose. If your kidney function is severely impaired, you will not receive this medicine at all (see section 2).

If you take more Fludara than you should

Tell your doctor immediately if you have taken too many Fludara tablets.
High doses can cause a sharp decrease in the number of blood cells.
For Fludara given intravenously, overdose has been reported to cause delayed blindness, coma, and even death.

If you forget to take Fludara

Talk to your doctor as soon as possible if you think you may have missed a dose or have vomited after taking tablets.
Do not take a double dose to make up for a forgotten tablet.

If you stop taking Fludara

Do not stop taking Fludara without consulting your doctor.
If the side effects become too severe, your doctor may decide in consultation with you to stop taking Fludara.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you are not sure what the following side effects are, ask your doctor to explain them to you.

Some serious side effects can be life-threatening. Tell a doctor immediately:

  • if you have difficulty breathing, coughing, or chest pain with or without fever. This may be a sign of infection in the lungs.
  • if you notice abnormally many bruises, that wounds bleed more than usual or if it seems like you are getting many infections. This can be caused by a decreased number of blood cells. This can also lead to an increased risk of (serious) infections, caused by organisms that do not usually cause disease in healthy people (opportunistic infections ), including the recurrence of a virus, e.g. herpes zoster.
  • if you get side pain, blood in the urine, or decreased urine output, tell your doctor immediately. This may be a sign of tumor lysis syndrome (see section 2).
  • if you notice any skin and/or mucous membrane reactions with redness, inflammation, blisters, or tissue degradation. This may be a sign of a severe allergic reaction ( Lyell’s syndrome, Stevens-Johnson syndrome ).
  • if you get palpitations (if you suddenly feel your heart beating) or chest pain. This may be a sign of heart problems.

Listed below are possible side effects grouped by how common they are from what is known from intravenous use of Fludara.

A very common side effect is (can occur in more than 1 in 10):

  • the infection you (some serious)
  • the infection you because of the impaired immune system ( opportunistic infection s )
  • pneumonia ( pneumonia i) with symptoms such as difficulty breathing and/or coughing with or without fever
  • bruising and bleeding caused by decreased platelet count ( thrombocytopenia )
  • decreased white blood cell count ( neutropenia )
  • decreased number of red blood cells ( anemia )
  • cough
  • vomiting, diarrhea, nausea
  • fever
  • fatigue
  • weakness

Common side effects are (may affect up to 1 in 10)

  • other forms of blood cancermyelodysplastic syndrome, acute myeloid leukemia ). Most patients with these conditions had previously, concomitantly or at a later time been treated with other cancer drugs ( alkylating agents, topoisomerase inhibitors ) or radiation
  • reduced formation of various types of cell s by the influence of the bone marrow a (myelosuppression)
  • severe loss of appetite leading to weight loss anorexia )
  • numbness or weakness in the arms and legs ( peripheral neuropathy )
  • visual disturbances
  • inflammation of the mouth ( stomatitis )
  • rash
  • swelling due to heavy fluid retention ( edema )
  • inflammation of the mucous membranes of the digestive tract from the mouth to the anal opening ( mucositis )
  • frostbite
  • general malaise

Less common side effects are (may affect up to 1 in 100)

  • autoimmune diseases (see section 2)
  • tumor lysis syndrome (see section 2)
  • confusion
  • harmful effects on the lungs, scarring of the lungs  ( pulmonary fibrosis ), pneumonia  ( pneumonitis ), shortness of breath  ( dyspnoea )
  • bleeding in the stomach and intestines
  • abnormal levels of liver or pancreatic enzymes

Rare side effects are (may affect up to 1 in 1000)

  • diseases of the lymphatic system due to a viral infection ( EBV associated lymphoproliferative disease)
  • coma
  • seizures
  • indignation
  • blindness
  • inflammation or damage to the optic nerve ( optic neuritis; optic neuropathy )
  • heart failure
  • irregular heartbeat ( arrhythmia )
  • skin cancer
  • reactions in the skin and/or mucous membranes with redness, inflammation, blistering, or discharge ( Lyell’s syndrome, Stevens-Johnson syndrome )

No known frequency (cannot be calculated from the available data)

  • cerebral hemorrhage
  • neurological problems which manifest themselves as headache, nausea and vomiting, convulsions, visual disturbances including vision loss, altered state of mind (abnormal thoughts, confusion, altered consciousness), and sometimes neuromuscular disorders which manifest as muscle weakness in arms and legs (including persistent incomplete or complete paralysis ) (symptoms of leukoencephalopathyacute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome ).
  • bleeding in the lungs
  • inflammation of the bladder, which can lead to pain when urinating and blood urination (hemorrhagic cystitis ).

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 can label and on the blister after EXP.
The expiration date is the last day of the specified month.

Fludara is a cytotoxic drug ( cytostatics ). It must always be stored in the childproof original packaging.

No special temperature instructions.

Store in the original package. Moisture sensitive.

The medicine 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 to protect the environment.

Return unused or discarded tablets to your doctor or pharmacist. They ensure that Fludara is discarded according to current instructions for chemotherapy.

6. Contents of the packaging and other information

Content declaration:

  • The active substance is fludarabine phosphate. A film-coated tablet Fludara contains 10 mg of fludarabine phosphate.
  • Other ingredients are
    • in the tablet core:  cellulose (microcrystalline), lactose (monohydrate), silica ( colloidal anhydrous), croscarmellose sodium, magnesium stearate
    • in the film coating: hypromellose, talc, titanium dioxide (E171), and iron oxide (red and yellow, E172).

What it looks like and the contents of the pack:

Fludara is salmon pink, oblong film-coated tablets, marked with the letters “LN” in a regular hexagon on one side.

The tablets are packed in blisters with five tablets each. The blister packs are made of thermoformed foil of polyamide/aluminum/polypropylene with a sealing foil of aluminum.

The blister packs are packed in a polyethylene jar with a child-resistant polypropylene screw cap.

Fludara is available in packs containing:

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

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Genzyme Europe BV
Paasheuvelweg 25
1105 BP Amsterdam The
Netherlands

Manufacturer:

Genzyme Ltd.

37 Hollands Road

Haverhill

CB9 8PU

UK

or

Sanofi Winthrop Industrie
30-36, avenue Gustave Eiffel
37100 Tours
France


This medicinal product is authorized under the European Economic Area under the names:

Austria Fludara
Denmark Fludara
Finland Fludara
France Fludara
Iceland Fludara
Greece Fludara
Ireland Fludara
Italy Fludara
Luxembourg Fludara
Netherlands Fludara
Norway Fludara
Spain Benefits
UK Fludara

Muhammad Nadeem

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