Fludarabine Phosphate

Fludarabine Phosphate 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.

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 inhibits DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis leading to cell death.

• B-cell Chronic Lymphocytic Leukemia (CLL): Used for treatment of adult patients with CLL who have not responded to or progressed on standard alkylating-agent containing regimens.

Cytotoxic Chemotherapy

Purine Analog Antimetabolite

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 inhibits DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis leading to cell death.

Fludarabine phosphate inhibits DNA synthesis by blocking DNA polymerase alpha, ribonucleotide reductase and DNA primase, leading to cancer cell death.

Adult Dose (IV):

• 25 mg/m² IV once daily for 5 consecutive days, repeated every 28 days.
• Continue until best response achieved (complete or partial remission, usually 6 cycles).

Adult Dose (Oral):

• 40 mg/m² once daily for 5 consecutive days, repeated every 28 days.
• Continue until best response achieved (usually 6 cycles).

Renal Dose: CrCl 30-70: May reduce doses by up to 50%; CrCl <30: Avoid.

Should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Administered as IV injection or infusion.

If you miss a dose of Fludarabine Phosphate, please consult your doctor.

Serious Side Effects:

• Bone marrow suppression (may affect infection protection, oxygen carrying capacity; may be fatal)
• Central nervous system problems (blindness, coma, death at 4 times recommended dose)
• Hemolytic anemia (may be fatal)
• Lung toxicity with pentostatin combination (fatal)

Precautions:

• Administer under supervision of qualified physician experienced in antineoplastic therapy.
• Myelosuppression (including fatal cases)
• Irreversible CNS effects (including fatal cases)
• Auto-immune hemolytic anemia (including fatal cases)
• Pentostatin combination contraindicated (fatal pulmonary toxicity)

Contraindications:

• Hypersensitivity
• Creatinine clearance <30 mL/min
• Decompensated hemolytic anemia

Drug Interactions:

• Pentostatin (deoxycoformycin): Fatal pulmonary toxicity; concomitant use not recommended.
• Dipyridamole and other inhibitors of adenosine uptake: May reduce therapeutic efficacy.
• Cytarabine: May increase intracellular concentration of Ara-CTP in leukemic cells.

Food Interactions: It is not known whether it is safe to consume alcohol with Fludarabine Phosphate; consult your doctor.

Use in Pregnancy: Very limited data on use in first trimester; fetal abnormalities reported; early pregnancy loss reported.

Use in Lactation: Breastfeeding should not be initiated during treatment; nursing women should discontinue breastfeeding; fludarabine phosphate and/or metabolites transfer from maternal blood to milk.

Pediatric Use: Safety and efficacy not established.

Geriatric Use: No specific dosage adjustment is necessary for elderly patients.

Renal Impairment: CrCl 30-70: May reduce doses by up to 50%; CrCl <30: Avoid.

Hepatic Impairment: Limited information available; use with caution.

Overdose: Limited information on overdose; symptomatic treatment.

Storage: Injection: store below 25 degree C; Tablets: store between 15-30 degree C; Do not freeze; Keep out of reach and sight of children.

Fludarabine Phosphate