It indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen.
Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis leading to cell death. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Intravenous (Adult): Chronic lymphocytic leukaemia: 25 mg/m2 BSA daily given by bolus inj or by IV infusion over 30 minutes for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles. Oral (Adult): Chronic lymphocytic leukaemia: 40 mg/m2 BSA daily for 5 consecutive days. Courses may be repeated every 28 days, usually for up to 6 cycles. Interaction
In a clinical investigation, using Fludara in combination with pentostatin (deoxycoformycin) for the treatment of CLL, there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of Fludara in combination with pentostatin is not recommended. Dipyridamole and other inhibitors of adenosine uptake may reduce the therapeutic efficacy of Fludara. Clinical studies and in vitro experiments showed that using Fludara in combination with cytarabine may increase the intracellular concentration and intracellular exposure of Ara-CTP (active metabolite of cytarabine) in leukemic cells. Plasma concentrations of Ara-C and the elimination rate of Ara-C were not affected.
Renal impairment ,Concomitant use of live vaccines,
Fever, chills, cough, dyspnoea, pneumonia; GI disturbances, stomatitis; oedema; tumour lysis syndrome; skin rashes; haemolytic anaemia, haemorrhagic cystitis; neurological disturbances including peripheral neuropathy, agitation, confusion, visual disturbances and coma
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk
Higher than recommended doses of FLUDARA (fludarabine phosphate) have been associated
with leukoencephalopathy, acute toxic leukoencephalopathy, or posterior reversible
encephalopathy syndrome (PRES)/ reversible posterior leukoencephalopathy syndrome (RPLS).
Symptoms, which may be delayed and irreversible, may include headache, nausea and vomiting,
seizures, visual disturbances such as vision loss, altered sensorium, focal neurological deficits,
coma, and death. Additional effects may include optic neuritis, and papillitis, confusion,
somnolence, agitation, paraparesis/ quadriparesis, muscle spasticity and incontinence. High
doses are also associated with bone marrow suppression manifested by thrombocytopenia and
neutropenia.
There is no known specific antidote for FLUDARA overdosage. Treatment consists of drug
discontinuation and supportive therapy.
Injection should store below 25°C. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2 to 8°C or 8 hours at room temperature. Tablets should store between 15°C and 30°C. Do not freeze. Keep out of reach and sight of children. Leave contents in protective packaging until use.
.png&w=384&q=75)