Index of drugs

Initial treatment of patients with B-cell chronic lymphocytic leukemia and patients with chronic B-cell lymphocytic leukemia who have not been improved after treatment or progression of the disease during or after the treatment of at least one standard treatment cycle containing an alkylating medication this treatment.

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 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 in patients with poor general condition after considering risk and expected benefits - especially in patients with severe myelosuppression (thrombocytopenia, anemia, granulocytopenia), immunodeficiency or history of opportunistic infections. Due to the strong immunosuppressive activity of the preparation and the risk of opportunistic infections (e.g.Pneumocystis carinii, virusesherpes) appropriate prophylaxis is recommended. No data regarding treatment with patients with liver damage - the drug should be used with caution when the benefits outweigh the potential risk. Patients undergoing fludarabine treatment who have or will be given a blood transfusion should only receive irradiated blood to avoid graft versus host disease. Patients who have experienced autoimmune haemolytic anemia (AIHA) in the past with purine analogues should be expected to experience AIHA recurrence after administration of fludarabine, including severe course. Special care should be taken in patients at risk of tumor disintegration. Use with caution in patients with moderate renal impairment (creatinine clearance 30-70 ml / min) and in elderly patients (over 75 years). During or after the treatment, vaccination with live organisms should be avoided. In the absence of response to fludarabine therapy, the use of chlorambucil should be avoided (the use of chlorambucil in most patients with fludarabine resistance is also ineffective). Caution should be exercised when using the drug if you are planning to collect blood stem cells. The safety and efficacy of the preparation in children have not been established.

The drug is contraindicated during pregnancy and breastfeeding. Women and men of childbearing potential must use effective contraception during therapy and for at least 6 months after treatment.

Often, general symptoms: fever, chills, infection, malaise, weakness, tiredness.Bone marrow suppression (escalating during subsequent courses of treatment): neutropenia, thrombocytopenia, anemia. Increased risk of opportunistic infections, including reactivation of latent viruses (eg progressive multifocal leukoencephalopathy, shingles). The occurrence of myelodysplastic syndrome after treatment with fludarabine has been rarely reported. Tumor disruption syndrome (lumbar pains, haematuria, hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, hematuria, urine urine, renal failure). Edema is often observed. Changes in the activity of aminotransferases and pancreatic enzymes are uncommon. On the part of the nervous system, it was observed: rarely - coma, agitation and seizures, uncommon - confusion, often - cases of peripheral neuropathy. Visual impairment is often observed; optic neuritis, optic neuropathy, and loss of vision have been reported rarely. There is often pneumonia, hypersensitivity reactions (infiltration in the lung tissue, alveolitis, fibrosis) manifesting in cough and dyspnea. Gastrointestinal disorders were frequently observed: nausea, vomiting, lack of appetite, diarrhea, stomatitis and gastrointestinal bleeding. Rare circulatory failure and arrhythmias. The symptoms of hemorrhagic cystitis have been rare. Skin rashes were frequently observed, in rare cases Stevens-Johnson syndrome or toxic epidermal necrolysis. In patients treated with fludarabine and receiving blood transfusions that were not irradiated, the graft-versus-host reaction was observed (if this complication occurs, death may occur). In some patients, during or after treatment with the preparation transient worsening or recurrence of pre-existing neoplastic lesions within the skin was found. During or after treatment with the preparation, life-threatening or fatal autoimmune reactions (autoimmune anemia, autoimmune thrombocytopenia, thrombocytopenic purpura, pemphigus, Evans syndrome) have been observed.

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 dose of the drug should be adjusted in case of haematological toxicity. The necessary dose of the preparation should be taken into the syringe. For intravenous (bolus) administration, the dose should be diluted in 10 ml of 0.9% NaCl solution. It is also possible to dilute the total dose in 100 ml of 0.9% NaCl solution and infuse into a vein over approximately 30 minutes. The duration of therapy depends on the effectiveness and tolerance of the drug. In patients with B-cell chronic lymphocytic leukemia, it is recommended to administer the preparation until the best response is obtained (usually 6 cycles), and then the drug should be discontinued.
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.