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Updated 2 Feb 2023 | Antimetabolites


Film coated tablets containing 10mg fludarabine phosphate

Drugs List

  • FLUDARA ORAL 10mg tablets
  • fludarabine 10mg tablets
  • Therapeutic Indications


    Treatment of patients with B-cell chronic lymphocytic leukaemia (CLL) with sufficient bone marrow reserves.

    The use of oral fludarabine as a first line treatment, should only be commenced in patients with advanced disease: Rai stages III/IV (Binet stage C) or Rai stages I/II (Binet stage A/B) where the patient has disease related symptoms or evidence of progressive disease.

    Unlicensed Uses

    In children poor prognosis or relapsed acute myeloid leukaemia, relapsed acute lymphoblastic leukaemia and conditioning before bone marrow transplantation.


    Fludarabine should only be prescribed by a qualified physician experienced in the use of antineoplastic therapy.

    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.


    The recommended dose is 40mg fludarabine phosphate per square metre of body surface area (BSA) given daily for 5 consecutive days at 28 day intervals by the oral route. (This dose corresponds to 1.6 times the recommended intravenous dose.)

    The duration of treatment depends on the therapy success and tolerability. It is recommended that fludarabine is administered until the best response is achieved (complete or partial remission, usually 6 cycles) and then the drug should be discontinued.


    At present, there is limited data for the use of fludarabine in elderly persons particularly those over 75 years of age. Therefore, caution should be exercised with the administration of fludarabine in these patients.

    Manufacturers recommend creatinine clearance should be measured in patients over the age of 65 years and a reduced dose given if appropriate (see Dosage - Renal Impairment ).


    Treatment of children under 18 years with fludarabine is not recommended by the manufacturer, as its safety and effectiveness have not been established.

    Patients with Renal Impairment

    Doses should be adjusted for patients with reduced kidney function.

    The manufacturers suggest the following dose adjustments:
    Creatinine clearance is between 30 and 70ml/minute : The dose should be reduced by up to 50% and close haematological monitoring should be used to assess toxicity.
    Creatinine clearance is less than 30ml/minute : Fludarabine treatment is contraindicated.

    However, The Renal Drug Handbook suggests the following dose reductions:
    Glomerular filtration rate is between 30 and 70ml/minute: 50-75% of normal doses.
    Glomerular filtration rate is between 10 and 20ml/minute: 50-75% of normal doses. Use with care.
    Glomerular filtration rate is less than 10ml/minute: 50% of normal dose. Use with care.

    Patients with Hepatic Impairment

    There are inadequate data available concerning the use of fludarabine in patients with hepatic impairment. The manufacturer advises that fludarabine should be used with caution in these patients.

    Additional Dosage Information

    Dose adjustments for the first cycle are not recommended, except in renal impairment (see Dosage - Renal Impairment ).

    If at the start of a subsequent cycle cell numbers are too low to administer the recommended dose and there is evidence of treatment associated myelosuppression, the planned treatment cycle should be postponed until granulocyte count is above 1.0 x 10 to the power of 9 per litre and platelet count is above 100 x 10 to the power of 9 per litre.

    Treatment should be postponed for a maximum of two weeks; if granulocyte and platelet counts have not recovered after two weeks of postponement, the dose should be reduced according to the suggested dose adjustments below, unless thrombocytopenia is disease-related.

    Granulocytes 0.5-1.0 x10 to the power of 9 per litre OR platelets 50-100 x10 to the power of 9 per litre, 30mg per square metre per day of fludarabine phosphate is recommended.

    Granulocytes < 0.5 x10 to the power of 9 per litre OR platelets < 50 x10 to the power of 9 per litre, 20mg per square metre per day of fludarabine phosphate is recommended.

    If there is no response after two treatment cycles and the patient shows no or little haematological toxicity, a careful dose adjustment towards higher doses in subsequent cycles could be considered.


    For oral administration

    The tablets must be swallowed whole, not chewed or broken, with water on an empty stomach or with food.


    Standard guidelines on handling cytotoxic drugs should be followed:
    1. Trained personnel should reconstitute cytotoxics;
    2. Protective clothing (including gloves) should be worn;
    3. The eyes should be protected and means of first aid should be specified;
    4. Pregnant staff should not handle cytotoxics;
    5. Adequate care should be taken for the disposal of waste material, including syringes, containers and absorbent material.


    Renal impairment - creatinine clearance below 30ml/minute - see Dosage - Renal impairment
    Decompensated haemolytic anaemia
    Breastfeeding - see Lactation section
    Pregnancy - see Pregnancy section

    Precautions and Warnings

    Fludarabine should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.

    Whilst the doses stated are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Observe patients carefully for signs of neurological toxicity. Fludarabine has been associated with severe central nervous system toxicity at doses within the dose range for CLL (Chronic Lymphocytic Leukaemia). Side effects include coma, blindness, seizures and agitation (rare) and confusion (uncommon).

    Renal impairment requires dose adjustment. Creatinine clearance should be measured if renal impairment is clinically suspected or in patients over the age of 65 years. A dose reduction by up to 50% is suggested for creatinine clearance between 30 and 70ml/minute and close haematological monitoring should be used to assess toxicity - see Dosage - Renal impairment.

    At present, there are insufficient data available in patients with hepatic impairment. Use with caution in these patients.

    Use with caution in patients with impaired health. This applies particularly to patients with severe impairment of bone marrow function (thrombocytopenia, anaemia and/or granulocytopenia), immunodeficiency or with a history of opportunistic infection.

    Severe bone marrow depression, notably anaemia, thrombocytopenia and neutropenia has been reported in patients receiving fludarabine. In a Phase I intravenous study in patients with solid tumours, the median time to nadir counts was 13 days (range 3 to 25 days) for granulocytes and 16 days (range 2 to 32) for platelets. Most patients had haematological impairment at baseline either as a result of their disease, or previous myelosuppressive therapy.

    Administration of fludarabine requires careful haematological monitoring as cumulative myelosuppression may be seen. Chemotherapy-induced myelosuppression is often reversible. Periodic assessment of peripheral blood counts is recommended to monitor for development of anaemia, neutropenia and thrombocytopenia.

    Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in adult patients. The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year. These episodes have occurred both in previously treated or untreated patients.

    Evolution of Epstein-Barr Virus (EBV) infection/reactivation into EBV-associated lymphoproliferative disorders has been observed in immunocompromised patients.

    Caution when further haematopoietic stem sampling is required.

    Transfusion-associated graft-versus-host disease (reaction by the transfused immunocompetent lymphocytes to the host) has been observed after infusion of non-irradiated blood in patients treated with intravenous fludarabine and has a fatal outcome in a high proportion of patients. Patients requiring blood transfusion should receive irradiated blood only.

    Reversible worsening or flare-up of pre-existing skin cancer lesions has been reported during or after intravenous fludarabine treatment. New onset skin cancer has also been reported.

    Tumour lysis syndrome has uncommonly been associated with fludarabine treatment in patients with a high tumour burden. This response may be induced as early as the first week of treatment. Use with caution in patients at risk of developing tumour lysis syndrome.

    Life-threatening and sometimes fatal autoimmune phenomena have been reported during or after intravenous fludarabine, irrespective of any previous history of autoimmune process or Coombs' test status. The majority of patients experiencing haemolytic anaemia developed a recurrence after rechallenge with fludarabine. Monitor patients for signs of autoimmune haemolytic anaemia. If haemolysis occurs, discontinue treatment. Blood transfusion (with irradiated blood) and adrenocorticoid preparations are the most common treatment for autoimmune haemolytic anaemia.

    A crossover from initial treatment with fludarabine to chlorambucil for non-responders to fludarabine should be avoided. Most patients who have been resistant to fludarabine have shown resistance to chlorambucil.

    Use with caution in patients over 75 years of age as there are limited data for use in elderly patients and decline in renal function with age may require dose adjustment - see Dosage - Renal impairment.

    The safety and effectiveness of fludarabine in children under 18 years has not been established by the manufacturer. Therefore, treatment with fludarabine in children is not recommended - see Dosage - Children.

    Women of child-bearing age and men must take contraceptive precautions during and for 6 months after treatment with fludarabine. If pregnancy occurs, they should inform their physician immediately.

    Avoid vaccination with live vaccines during treatment.

    Central nervous system side effects may impair ability to drive or operate machinery. Patients experiencing such events should not drive or operate machinery.

    Some brands contain lactose. Patients with rare hereditary problems of galactose intolerance or glucose-galactose malabsorption should not take this medicine.

    Pregnancy and Lactation


    Fludarabine is contraindicated during pregnancy, and it has the potential to cause foetal harm.

    Very limited human experience supports the findings of embryotoxicity studies in animals demonstrating an embryotoxic and/or teratogenic potential at the therapeutic dose. Pre-clinical studies in rats demonstrated a transfer of fludarabine and/or metabolites across the placenta.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Licensed in pregnancy? - No

    Known human teratogen? - Unknown but animal data suggests likely


    Fludarabine is contraindicated during breastfeeding.

    Breastfeeding should be discontinued for the duration of fludarabine treatment.

    It is not known if the drug is excreted into human milk, but there is evidence from preclinical data that fludarabine or its metabolites are excreted in milk.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Drug substance licensed in infants? - No

    Effects on Ability to Drive and Operate Machinery

    Central nervous system side effects may impair ability to drive or operate machinery. Patients experiencing such events should not drive or operate machinery.


    Advise women of child-bearing age and men to take contraceptive precautions during and for 6 months after treatment with fludarabine. If pregnancy occurs, they should inform their physician immediately.

    Central nervous system side effects may impair ability to drive or operate machinery. Advise patients experiencing such events not to drive or operate machinery.

    Side Effects

    Reactivation of herpes zoster
    Reactivation of Epstein Barr virus
    Progressive multifocal leukoencephalopathy (PML)
    Lymphoproliferative disorders
    Myelodysplastic syndrome
    Autoimmune disorders
    Haemolytic anaemia
    Thrombocytopenic purpura
    Evans' syndrome
    Tumour lysis syndrome
    Metabolic acidosis
    Renal failure
    Alterations in hepatic enzymes
    Alterations in pancreatic enzymes
    Peripheral neuropathy
    Visual disturbances
    Optic neuritis
    Optic neuropathy
    Interstitial pulmonary infiltrate
    Gastro-intestinal haemorrhage
    Cardiac failure
    Haemorrhagic cystitis
    Stevens-Johnson syndrome
    Toxic epidermal necrolysis
    Flare up of pre-existing skin cancer lesions
    Skin carcinoma
    Acute myeloid leukaemia
    Acquired haemophilia
    Cerebral haemorrhage
    Pulmonary fibrosis
    Pulmonary haemorrhage
    Pulmonary toxicity
    Bone marrow hypoplasia
    Bone marrow aplasia


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Shelf Life and Storage

    Store in original packaging. This medicinal product does not require any special temperature storage conditions.

    Further Information

    Last Full Review Date: June 2012

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Summary of Product Characteristics: Fludara oral 10mg film-coated tablet. Genzyme. Revised March 2011.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    NICE Evidence Services Available at: Last accessed: 17 August 2017

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