Index of drugs

Treatment of B-cell chronic lymphocytic leukemia in patients with sufficient bone marrow reserve. First-line treatment should only be undertaken in cases of advanced disease in III / IV according to the Raja classification (Bineta C classification) or I / II grade according to the Raja classification (Bineta A / B classification), if the patient has symptoms dependent on the disease or features of disease progression.

1 vial contains 50 mg fludarabine phosphate.

An antimetabolite cytostat - a fluorinated nucleotide analogue of widarabine, a drug with antiviral activity - 9-beta-D-arabinofuranosyladenine (ara-A). Phudarabine phosphate is rapidly dephosphorylated to 2F-ara-A, which is taken up by the body's cells and then intracellularly phosphorylated by deoxycytidine kinase to the active 2-fluoro-ara-ATP triphosphate. This metabolite inhibits ribonucleotide reductase, DNA polymerase, priming and DNA ligase, leading to inhibition of DNA synthesis. In addition, it partially inhibits RNA polymerase II, thereby reducing protein synthesis. As a result of the inhibition of DNA, RNA and protein synthesis, cell growth stops. After administration of the product as an infusion in a single dose of 25 mg / m² after reaching the maximum, the concentration of 2F-ara-A decreased in the three phases of elimination: initial with T_0,5 approx. 5 min, indirect with T_0,5 1-2 h and final - T_0.5 approximately 20 h. The drug is excreted mainly in the urine (40-60% of the administered dose). Fludarabine is actively transported to leukemic cells where it undergoes phosphorylation successively to mono-, di- and triphosphate, the highest concentration of which in leukemic cells is reached after 4 hours, and T_0,5 drug from the cell is 15-23 hours.

Hypersensitivity to fludarabine phosphate or other components of the preparation. Renal impairment with creatinine clearance below 30 ml / min. Unstable hemolytic anemia. Pregnancy and breastfeeding.

Caution should be exercised when using fludarabine if bone marrow biopsies are considered. Notwithstanding the history of autoimmune disorders and the Coombs test results, life-threatening or sometimes fatal autoimmune events have been observed in patients during or after termination of fludarabine therapy. In the majority of patients with hemolytic anemia, re-administration of fludarabine resulted in a recurrent hemolytic process. Patients should be monitored for haemolysis - discontinuation of fludarabine therapy is recommended if this occurs. Caution is advised in patients with large tumors due to the possibility of tumor lysis syndrome. In order to minimize the risk of graft-versus-host disease associated with transfusion, patients requiring blood transfusion who are or have been treated with fludarabine should only receive irradiated blood. Caution should be exercised in patients with poor health - use after considering the benefit / risk ratio, especially in patients with severe bone marrow abnormalities, immunodeficiency or history of opportunistic infections. In patients with impaired renal or hepatic function and in the elderly, fludarabine should be administered with caution; In patients with hepatic impairment, the drug should be administered when the expected benefit outweighs the potential risk. Fludarabine should not be used in children. During or after the treatment, vaccination with live organisms should be avoided. The replacement of initial treatment with fludarabine with chlorambucil should be avoided in patients resistant to fludarabine, as most patients resistant to fludarabine also show resistance to chlorambucil. Each vial contains less than 1 mmol sodium (23 mg / ml), hence the medicine is considered free of sodium.

The drug should not be used during pregnancy unless it is absolutely necessary. Fludarabine can cause fetal damage.Both women of childbearing age and sexually active men should use effective methods of contraception during treatment, as well as up to 6 months after its completion. In animals, unfavorable effects of fludarabine on the reproductive system of males have been demonstrated. Fludarabine should not be used in women who are breastfeeding, due to the possibility of serious side effects.

Very common: opportunistic infections / infections (including reactivation of the dormant virus, e.g. progressive multifocal leukoencephalopathy, shingles, Epstein-Barr virus), pneumonia; neutropenia, anemia, thrombocytopenia; cough; vomiting, diarrhea, nausea; fever, fatigue, weakness. Common: myelodysplatics syndrome and acute myelogenous leukemia (mainly associated with earlier, simultaneous or later treatment with alkylating agents, topoisomerase inhibitors or irradiation); bone marrow suppression; anorexia; peripheral neuropathy; blurred vision; gastritis; rash; swelling, inflammation of the mucous membranes, chills, malaise. Uncommon: autoimmune disorders (including autoimmunohemolytic anemia, Evans syndrome, thrombotic thrombocytopenic purpura, acquired haemophilia, pemphigus); tumor lysis syndrome (including renal failure, metabolic acidosis, hyperkalemia, hypocalcaemia, hyperuricemia, hematuria, excretion of urate crystals, hyperphosphatemia); entanglement; pulmonary toxicity (including pulmonary fibrosis, pneumonia, dyspnea); bleeding from the gastrointestinal tract, changes in pancreatic enzyme activity; changes in liver enzymes. Rare: lymphoproliferative disorders (associated with EBV); coma, fits, agitation; blindness, optic neuritis, neuropathy of the optic nerve, heart failure, arrhythmias; skin cancer, toxic epidermal necrolysis, Stevens-Johnson syndrome. Not known: brain haemorrhage; stroke into the lungs; hemorrhagic cystitis. Patients treated with fludarabine report deaths due to serious adverse reactions.

The drug should be used under the supervision of a qualified doctor experienced in conducting anti-cancer therapies.
Only intravenously. Adults: the recommended daily dose is 25 mg / m² pc. for 5 consecutive days in cycles repeated every 28 days. The required dose should be drawn into a syringe and diluted for a single intravenous bolus injection in 10 ml of 0.9% NaCl solution. It is also possible to dilute the required dose in 100 ml of 0.9% NaCl solution and infusion into a vein over approximately 30 minutes. The duration of therapy depends on the effectiveness and tolerance of the drug, it is recommended to administer the drug until a response is obtained (usually 6 courses).
In patients with impaired renal function, the dose should be adjusted appropriately: at a creatinine clearance of 30-70 ml / min, the dose should be reduced to 50% and blood tests should be performed to assess toxicity.