Fludarabine Phosphate

What it is and how it works

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.

Indications

Fludarabine Phosphate Injection is a nucleotide metabolic inhibitor 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. Benefit in treatment-naïve or non-refractory CLL patients is not established. Indication Fludarabine Phosphate Injection is 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. The safety and effectiveness of Fludarabine Phosphate Injection in previously untreated or non-refractory patients with CLL have not been established.

Dosage and administration (summary)

The recommended adult dose is 25 mg/m 2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5 day course of treatment should commence every 28 days. Reduce dose in patients with creatinine clearance 30 to 70 mL/min/l.73 m 2 . Do not use in patients with severe renal impairment . Recommended Dose The recommended adult dose of fludarabine phosphate injection is 25 mg/m 2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5-day course of treatment should commence every 28 days. Dosage may be decreased or delayed based on evidence of hematologic or nonhematologic toxicity.

Contraindications

None None

Warnings and precautions

( see BOXED WARNINGS ) Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia. Monitor blood counts before and during treatment. Transfusion-associated graft-versus-host disease. Use only irradiated blood products for transfusions. Infections. Monitor for infection. Renal Insufficiency. Reduce dose for moderate renal impairment and monitor closely. Do not administer to patients with severe renal impairment. Tumor lysis syndrome (TLS). Take precautions for patients at high risk for TLS. Can cause fetal harm when administered to a pregnant woman.

Pregnancy

Pregnancy Based on its mechanism of action, fludarabine phosphate can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Fludarabine Phosphate Injection in pregnant women. Fludarabine phosphate was embryolethal and teratogenic in rats and rabbits.

Storage and supply

Storage Store refrigerated between 2° and 8°C (36° and 46°F). Handling and Disposal Procedures for proper handling and disposal should be considered. Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs. Several guidelines on this subject have been published.

Source: Fludarabine Phosphate (Fludarabine Phosphate) — US FDA prescribing information, 2023-01-31, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.