Drug reference
Initial treatment of advanced B-cell chronic lymphocytic leukaemia (CLL) or after first line treatment in patients with sufficient bone-marrow reserves ▶BY MOUTH ▶Adult: 40 mg/m2 for 5 days every 28 days, usually given for 6 cycles ▶BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Adult: (consult product literature)
PDF page 982
Haemolytic anaemia
PDF page 982
Increased susceptibility to skin cancer. worsening of existing skin cancer CAUTIONS, FURTHER INFORMATION ▶Immunosuppression Fludarabine has a potent and prolonged immunosuppresive effect. Patients treated with fludarabine are more prone to serious bacterial, opportunistic fungal, and viral infections, and prophylactic therapy is recommended in those at risk. To prevent potentially fatal transfusion-related graft-versus-host reaction, only irradiated blood products should be administered. Prescribers should consult specialist literature when using highly immunosuppressive drugs. Co-trimoxazole is used to prevent pneumocystis infection.
PDF page 982
NICE decisions ▶Fludarabine monotherapy for the first-line treatment of chronic lymphocytic leukaemia (February 2007) NICE TA119 Fludarabine monotherapy is not recommended for the first-line treatment of chronic lymphocytic leukaemia. www.nice.org.uk/guidance/ta119 ▶Fludarabine for B-cell chronic lymphocytic leukaemia (September 2001) NICE TA29 Oral fludarabine is recommended for the second-line treatment of B-cell chronic lymphocytic leukaemia in patients who have either failed, or are intolerant of, first line chemotherapy, and who would otherwise have received combination chemotherapy of either: . cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) . cyclophosphamide, doxorubicin and prednisolone (CAP) or . cyclophosphamide, vincristine and prednisolone (CVP) Intravenous fludarabine should only be used when oral fludarabine is contra-indicated. www.nice.org.uk/guidance/ta29 Scottish Medicines Consortium (SMC) decisions SMC No. 176/05 The Scottish Medicines Consortium has advised (November 2006) that fludarabine phosphate (Fludara ®) is accepted for restricted use within NHS Scotland for the treatment of B-cell chronic lymphocytic leukaemia (CLL) in patients with sufficient bone marrow reserves. First-line treatment should only be initiated 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.
PDF page 983
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938.
PDF page 982
→Appendix 1: fludarabine
PDF page 982
GENERAL SIDE-EFFECTS ▶Common or very common Anaemia. appetite decreased. asthenia. bone marrow depression (may be cumulative). chills. cough. diarrhoea. fever. increased risk of infection . malaise. mucositis. nausea. neoplasms. nerve disorders. neutropenia. oedema. stomatitis. thrombocytopenia. vision disorders. vomiting ▶Uncommon Autoimmune disorder. confusion. dyspnoea. haemorrhage. respiratory disorders. tumour lysis syndrome ▶Rare or very rare Agitation. arrhythmia. coma. heart failure. seizure. severe cutaneous adverse reactions (SCARs) SPECIFIC SIDE-EFFECTS ▶Common or very common ▶With oral use Progressive multifocal leukoencephalopathy (PML). skin reactions. viral infection reactivation ▶With parenteral use Rash ▶Uncommon ▶With oral use Acquired haemophilia. crystalluria. electrolyte imbalance. haemolytic anaemia. hyperuricaemia. metabolic acidosis. renal failure ▶Frequency not known ▶With parenteral use Encephalopathy. intracranial haemorrhage
PDF page 982
Manufacturer advises effective contraception during and for at least 6 months after treatment in men or women.
PDF page 982
Avoid (embryotoxic and teratogenic in animal studies). See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
PDF page 982
Discontinue breast-feeding.
PDF page 982
Avoid if creatinine clearance less than 30 mL/minute. Dose adjustments Reduce dose by up to 50% if creatinine clearance 30–70 mL/minute.
PDF page 982
▶Monitor for signs of haemolysis. ▶Monitor for neurological toxicity. ▶Assess creatinine clearance in patients over 65 years before treatment initiation.
PDF page 982
Concentrate for intravenous injection or infusion must be diluted before administration (consult product literature).
PDF page 982
There can be variation in the licensing of different medicines containing the same drug. Solution for injection ▶Fludarabine phosphate (Non-proprietary) Fludarabine phosphate 25 mg per 1 ml Fludarabine phosphate 50mg/2ml concentrate for solution for injection vials | 1 vial P £155.00–£156.00 (Hospital only) Tablet ▶Fludara (Sanofi) Fludarabine phosphate 10 mg Fludara 10mg tablets | 15 tablet P £302.48 (Hospital only) | 20 tablet P £403.31 (Hospital only) Powder for solution for injection ▶Fludarabine phosphate (Non-proprietary) Fludarabine phosphate 50 mg Fludarabine phosphate 50mg powder for solution for injection vials | 1 vial P £155.00 (Hospital only) ▶Fludara (Sanofi) Fludarabine phosphate 50 mg Fludara 50mg powder for solution for injection vials | 5 vial P £735.34 (Hospital only)
PDF page 983
40 mg/m2 for 5 days every 28 days, usually given
First-line fragment. Read the complete Indications and Dose section above.
PDF page 982
(consult product literature)
First-line fragment. Read the complete Indications and Dose section above.
PDF page 982
