See package insert for further information. Re-MATC H Protocol Page 76 of 106 Version: 20180628 18.8 Fludarabine phosphate Source and Pharmacology 9-b-Barabinofuanosyl-2-fluoroadenine. Fludarabine (FAMP, Fludara ®) is a synthetic purine nucleoside. While the exact mechanism of action of fludarabine has not been fully elucidated, fludarabine appears to inhibit alpha -DNA polymerase, ribonucleotide reductase, and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis. Additionally, the drug may inhibit DNA chain elongation and interfere with RNA and protein synthesis by decreasing the incorporation of uridine and leucine. Pharmacokinetics - After administration, fludarabine phosphate is rapidly dephosphorylated to fludarabine triphosphate, the cytotoxic form of the drug. Areas under the concentration-time curve for fludarabine appear to be dose related. The elimination profile of fludarabine has been reported as either biphasic or triphasic, with terminal elimination half -lives for fludarabine and fludarabine triphosphate of 8- 10 and 15 hours, respectively. Fludarabine appears to be eliminated through the kidneys. Formulation and Stability Fludarabine is supplied in a 50mg powder form, and reconstituted with 2mL of sterile water. The appropriate dose of drug i s then withdrawn and added to 100 or 125mL of D5W or 0.9% sodium chloride solution. Fludarabine contains no preservatives and should be used within 8 hours after reconstitution. Supplier Commercially available from various manufacturers.