Introduction
Fludarabine is a chemotherapeutic agent used in the treatment of hematological malignancies.
Uses
Fludarabine is a purine analog antimetabolite that inhibits DNA synthesis.
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
Associated Conditions
Pharmacodynamics
Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.
Mechanism of Action
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. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Absorption
Bioavailability is 55% following oral administration.
Protein Binding
19-29%
Half Life
20 hours
Clearance
- 117-145 mL/min [patients with B-cell CLL receiving IV administration of a single dose of 40 mg/m^2.
Food Interactions
- Take with or without food. Administration with food delays absorption, but not to a clinically significant extent.
Dosage
Fludarabine tablet: The usual starting dose of Fludarabine tablets is 40 mg/m2 of Fludarabinebine phosphate administered once daily for five consecutive days every 28 days. The duration of treatment depends on the treatment success and the tolerability of the drug. Fludarabine oral should be administered until the achievement of a maximal response (complete or partial remission, usually 6 cycles) and then the drug should be discontinued.