Fludarabine Phosphate is indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) whose disease has not responded to, or has progressed after, treatment with at least one standard alkylating-agent–based chemotherapy regimen. The safety and effectiveness of Fludarabine Phosphate have not been established in previously untreated or non-refractory CLL patients

Fludarabine phosphate is rapidly converted to 2-fluoro-ara-A through dephosphorylation and subsequently phosphorylated داخل cells by deoxycytidine kinase to form its active metabolite, 2-fluoro-ara-ATP. This active compound inhibits key enzymes involved in DNA synthesis, including DNA polymerase alpha, ribonucleotide reductase, and DNA primase. As a result, DNA replication is disrupted, leading to cell death. The exact mechanism of action of this antimetabolite is complex and not fully understood.

Fludarabine injection: This should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. The recommended dose is 25 mg Fludarabinebine phosphate/m² body surface given daily for 5 consecutive days every 28 days by the intravenous route. Each vial is to be made up in 2 ml water for injection. Each ml of the resulting solution for injection/infusion will contain 25 mg Fludarabinebine phosphate. The required dose (calculated on the basis of the patient's body surface) is drawn up into a syringe. For intravenous bolus injection, this dose is further diluted into 10 ml of 0.9% sodium chloride. Alternatively, for infusion, the required dose drawn up in a syringe may be diluted into 100 ml 0.9% sodium chloride and infused over approximately 30 minutes. The duration of treatment depends on the treatment success and the tolerability of the drug. In CLL patients, Fludarabine should be administered up to the achievement of best response (complete or partial remission, usually 6 cycles) and then the drug should be discontinued. In patients with Lg-NHL, treatment with Fludarabine is recommended up to the achievement of best response (complete or partial remission). Two cycles of consolidation should be considered after best response has been reached. In clinical trials with Lg-NHL, the majority of patients underwent not more than 8 cycles.

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.

Clinical studies have shown that combining Fludarabine Phosphate (Fludara) with pentostatin (deoxycoformycin) in the treatment of chronic lymphocytic leukemia (CLL) resulted in a high incidence of severe and fatal lung toxicity. Therefore, this combination is not recommended. Drugs such as dipyridamole and other adenosine uptake inhibitors may reduce the therapeutic effectiveness of Fludara. Studies also indicate that when Fludarabine is used together with cytarabine, the intracellular concentration and exposure of Ara-CTP (the active metabolite of cytarabine) in leukemic cells may increase. However, the plasma concentration and elimination rate of cytarabine (Ara-C) remain unchanged.

Fludarabine Phosphate should not be used in patients with:

• Known hypersensitivity to fludarabine or any of its components
• Severe renal impairment with creatinine clearance less than 30 mL/min
• Decompensated hemolytic anemia

The following serious adverse effects may occur:

• Suppression of bone marrow function leading to reduced production of blood cells. This may impair the body’s ability to fight infections, transport oxygen, and maintain normal blood clotting, and can be life-threatening.
• Severe central nervous system complications such as blindness, coma, and death have been reported at doses significantly higher than recommended for CLL; such effects are rare at standard doses.
• Hemolytic anemia, caused by the destruction of red blood cells, which may be severe and potentially fatal.
• Pulmonary toxicity, which may lead to death, especially when used in combination with pentostatin (deoxycoformycin).

There are very limited data on the use of Fludarabine during pregnancy, particularly in the first trimester. Some cases have reported congenital abnormalities, early pregnancy loss, and premature delivery. Breastfeeding should not be started during Fludarabine treatment, and nursing mothers should discontinue breastfeeding. Although it is not definitively known whether fludarabine passes into human milk, preclinical studies suggest that the drug and its metabolites may transfer into breast milk.

Fludarabine Phosphate should only be administered under the supervision of a physician experienced in anticancer chemotherapy. Serious risks associated with fludarabine include:

• Severe bone marrow suppression, including fatal cases
• Irreversible central nervous system toxicity
• Autoimmune hemolytic anemia, which may be life-threatening

Fludarabine should not be used together with pentostatin, as this combination significantly increases the risk of fatal lung toxicity.

Renal Impairment:

• Creatinine clearance 30–70 mL/min: Dose may need to be reduced by up to 50%
• Severe renal impairment: Use should be avoided

Cytotoxic Chemotherapy

Fludarabine injection should be stored below 25°C. If not used immediately after preparation, it may be stored for up to 24 hours at 2–8°C or 8 hours at room temperature. Fludarabine tablets should be stored between 15°C and 30°C. Do not freeze. Keep the medicine in its original protective packaging and out of the reach of children.