indication

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

pharmacology

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.

half life

20 hours

drug interactions

Dipyridamole: Dipyridamole may decrease the effect of fludarabine.

Pentostatin: Unacceptable pulmonary toxicity

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.