Treatment of B-cell chronic lymphocytic leukemia in patients with sufficient bone marrow function. First-line treatment with the preparation should only be used in patients with advanced disease, stage III / IV Rai disease (stage C according to the Binet scale), or stage I / II according to the Rai scale (Bin / A stage A / B), if symptoms of the disease or symptoms indicating the progression of the disease are visible.
Composition:
1 vial contains 50 mg fludarabine phosphate.
Action:
Antineoplastic agent - widarabine's fluoridated nucleotide analogue - 9-β-D-arabinofuranosyloadenine (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 activity, DNA polymerase, priming and DNA ligase, leading to inhibition of DNA synthesis. As a result, the RNA polymerase II activity is partially inhibited and, as a consequence, the protein synthesis is reduced. 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 T0,5 approx. 5 min, indirect with T0,5 1-2 h and final - T0.5 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 refluhorylation to mono-, di- and triphosphate, the highest concentration of which in leukemic cells is reached after 4 hours, and T0,5 drug from the cell is 23 hours.
Contraindications:
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.
Precautions:
Use cautiously in patients with poor overall condition after considering the risk-benefit ratio - especially in patients with severe bone marrow disorders (thrombocytopenia, anemia, granulocytopenia), immunodeficiency or history of opportunistic infections. In patients with hepatic insufficiency - the drug should be used with caution, because it can cause hepatotoxicity, the drug administered when the benefits outweigh the potential risk. Caution should be exercised in patients using fludarabine phosphate, if stem cell treatment is considered in the further course of treatment. Patients undergoing fludarabine treatment who will receive a blood transfusion should only receive irradiated blood to avoid graft-versus-host disease. Special care should be taken in patients at risk of tumor disintegration. In patients who have autoimmune haemolytic anemia (AIHA) in the past due to the use of fludarabine phosphate, AIHA recurrence after fludarabine should be expected. During or after the treatment, vaccination with live organisms should be avoided. In the absence of response to fludarabine treatment, the use of chlorambucil should be avoided (in patients with fludarabine resistance, chlorambucil use is also ineffective). Use with caution in patients with moderate renal impairment (creatinine clearance 30-70 ml / min) and in elderly patients (over 75 years). The safety and efficacy of the preparation in children and adolescents have not been established.
Pregnancy and lactation:
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.
Side effects:
Very common: haematological symptoms (neutropenia, thrombocytopenia, anemia). Common: peripheral neuropathy; vision disorder; nausea and vomiting, diarrhea, stomatitis, lack of appetite; skin rash; edema; infections, pneumonia; fever, fatigue, weakness, unwellness and chills.Uncommon: autoimmune disorders (autoimmune hemolytic anemia, autoimmune thrombocytopenia, thrombocytopenic purpura, Evans syndrome); entanglement; pleural hypersensitivity reactions (pulmonary infiltrates, pneumonia, fibrosis), associated with symptoms of dyspnea and cough; gastrointestinal bleeding, mainly due to thrombocytopenia, changes in the concentration of pancreatic enzymes; pemphigus; acute tumor breakdown syndrome (complications may include hyperuricemia, hyperphosphatemia, hypocalcaemia, metabolic acidosis, hyperkalemia, haematuria, crystalluria, renal failure, and the promise of acute myocardial syndrome is hip and side pain and haematuria); changes in liver enzymes. Rarely: heart failure and arrhythmia; myelodysplastic syndrome; coma, agitation, epileptic seizures; optic neuritis, neuropathy of the optic nerve, blindness; hemorrhagic cystitis; Stevens-Johnson syndrome, toxic epidermal necrolysis.
Dosage:
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 modified in the event 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.
(C)
