Index of drugs

Reduction in the duration of neutropenia and reduction in the incidence of febrile neutropenia in patients receiving chemotherapy with cytotoxic agents due to established malignancy (except chronic myeloid leukemia and myelodysplastic syndromes) and shorter duration of neutropenia in patients undergoing myeloablative therapy prior to bone marrow transplantation who are at increased risk prolonged severe neutropenia. The safety and efficacy of filgrastim are similar in adults and children receiving chemotherapy with cytotoxic agents. Mobilization of peripheral blood progenitor cells (PBPC). In children and adults with severe congenital, cyclical or idiopathic neutropenia with absolute neutrophil count (ANC) ≤ 0.5 x 10⁹/ l and history of severe or recurrent infections, long-term administration of filgrastim is indicated to increase the number of neutrophils and to reduce the frequency and duration of symptoms associated with infection. Treatment of chronic neutropenia (ANC ≤ 1.0 x 10⁹/ l) in patients with advanced HIV infection to reduce the risk of bacterial infections when other treatments for neutropenia can not be used.

1 pre-filled syringe (0.5 ml) contains 300 μg (30 million units) or 480 μg (48 million units) filgrastim. The preparation contains sorbitol.

Human granulocyte colony growth factor (G-CSF) - a glycoprotein that regulates the production and release of neutrophils from the bone marrow. The preparation contains a recombinant, methionylated human granulocyte colony growth factor (r-metHuG-CSF), produced byE. coli recombinant DNA technology. It causes a significant increase in the number of neutrophils in the peripheral blood within 24 hours after administration, with a small increase in the number of monocytes. The increase in the number of neutrophils depends on the dose of the drug. In some patients with severe chronic neutropenia, filgrastim also induces, to a lesser extent, an increase in circulating eosinophilic and basophilic granulocytes compared to baseline values. Neutrophils produced after administration of filgrastim have normal or increased activity. After completion of treatment, the number of circulating neutrophils decreases by 50% within 1-2 days and returns to the normal range within 1-7 days. After subcutaneous administration of a single dose of filgrastim, C_max occurred after 4.5 +/- 0.9 h. After intravenous or subcutaneous administration, a positive linear relationship between the dose and the concentration of the drug in the blood is found. T_0,5 after a single subcutaneous dose is 2.7 h (1.0 MU / kg) to 5.7 h (0.25 MU / kg) and prolongs after 7 days of administration to 8, 5-14 hours

Hypersensitivity to filgrastim or any of the ingredients.

During the treatment, a general urine test should be performed regularly and the blood morphological image should be monitored. Patients should be monitored for lung side effects; cough, fever and shortness of breath, occurring together with radiological signs of inflammatory infiltration in the lungs, deterioration of respiratory function may be indicative of an acute adult respiratory distress syndrome (ARDS) - in this case it is recommended to discontinue filgrastim administration. Use with caution in patients with recent inflammatory infiltrations in the lungs or with a history of pneumonia. The size of the spleen (eg medical examination, ultrasound) should be checked regularly - consideration should be given to diagnosing a spleen rupture, if there is pain in the left upper abdomen or on the top of the shoulder. Patients who develop symptoms of capillary permeability syndrome (hypotension, hypoalbuminaemia, edema and blood thrombosis) should be closely monitored and provided with standard symptomatic treatment, which may include intensive care; cases of occurrence of capillary permeability syndrome mainly concerned patients with advanced cancer, sepsis, repeated chemotherapy, or patients with apheresis.In patients with osteoporosis treated with filgrastim for more than 6 months, bone density monitoring is indicated. In patients with sickle cell disease before the use of filgrastim, the benefit-risk ratio should be evaluated (Sickle-cell carcinomas that sometimes lead to death have been reported). Filgrastim should not be used to increase the dose of chemotherapy with cytotoxic agents beyond the established dosage regimen. Do not administer to patients with severe congenital neutropenia who will develop leukemia or show signs of leukemia.Chemotherapy with cytotoxic drugs. G-CSF can stimulatein vitro growth of myeloid cells and some extramedullary cells. Filgrastim is not recommended in patients with myelodysplastic syndrome or chronic myelogenous leukemia; particular attention should be paid to the differentiation of blast transformation in chronic myeloid leukemia from blast transformation in acute myeloid leukemia. Caution should be exercised in patients with secondary acute myelogenous leukemia. The safety and efficacy of filgrastim administration in patients <55 years with acute myelogenous leukemia has not been establishedde novo and promising cytogenetic changes: t (8; 21), t (15; 17) and inv (16). Considering the risk associated with severe leukocytosis, the number of white blood cells should be regularly measured during treatment with filgrastim. If the leukocyte count is> 50 x 10⁹/ l after the occurrence of the expected nadir, filgrastim administration should be stopped immediately. However, during the administration of filgrastim for PBPC mobilization, the drug should be discontinued or the dose reduced if the leukocyte count is> 70 x 10⁹/ L. Special care should be taken when treating patients receiving high-dose chemotherapy. It is recommended to check the number of platelets and hematocrit regularly. Special care should be taken when monotherapy or combination therapy with chemotherapeutics known to induce severe thrombocytopenia. In patients with a reduced number of neutrophil precursors (eg in patients receiving intensive radiotherapy or chemotherapy, or in patients with bone marrow cancer infiltrates), the response to treatment may be weaker.Mobilization of PBPC. Patients who have undergone very extensive myelosuppressive therapy may not have sufficient PBPC mobilization to achieve the recommended minimum number of cells (≥ 2.0 x 10⁶ CD34 cells⁺/ kg) or accelerate the regeneration of platelets, to the same extent as patients less intensively treated. Some cytotoxic drugs (including melphalan, carmustine, carboplatin) used for a long time before attempts to mobilize progenitor cells, may reduce the number of these cells - because the use of these drugs in combination with filgrastim allows effective mobilization of progenitor cells, it is recommended to plan the mobilization procedure stem cells at an early stage of treatment. In these patients, particular attention should be paid to the number of mobilized progenitor cells before high-dose chemotherapy. If the yield of progenitor cells is insufficient, according to the above criteria, alternative treatment methods should be considered without progenitor cells. When assessing the number of progenitor cells collected in patients treated with filgrastim, particular attention should be paid to the method of quantification. Results of the analysis of the number of CD34 cells⁺ Flow cytometry differs depending on the accuracy of the cell counting method, and therefore cell count recommendations based on test results obtained in other laboratories should be interpreted with caution. Recommended minimum yield ≥2.0 x 10⁶ CD34 cells⁺/ kg was formulated on the basis of published results of experiments describing satisfactory haematological reconstitution. Obtaining a larger number of cells seems to correlate with faster regeneration, and a smaller number - with slower regeneration. PBPC mobilization does not provide direct clinical benefit to healthy donors and should only be considered for allogeneic stem cell transplantation. PBPC mobilization should only be considered in donors who meet normal clinical and laboratory criteria for stem cell donors, paying particular attention to the results of haematological tests and infectious diseases.The safety and efficacy of filgrastim have not been evaluated in healthy donors <16 years or> 60 years. If more than one leukapheresis is required, pay special attention to donors with platelet counts <100 x 10⁹/ l before performing leukapheresis; basically, leukapheresis should not be performed if the platelet count is <75 x10⁹/ L. Leukapheresis should not be given to donors who are taking anticoagulants or who have been diagnosed with hemostasis. Filgrastim administration should be discontinued or its dosage should be reduced if the number of white blood cells increases to> 70 x10⁹/ L. Donors receiving G-CSF for PBPC mobilization should be monitored until the hematological parameters return to normal. The risk of promoting a malignant myeloid clone in healthy donors can not be ruled out - it is recommended that the apheresis center conduct systematic observation of stem cell donors for at least 10 years to ensure long-term safety monitoring.Severe chronic neutropenia (SCN). The number of platelets should be closely monitored, especially in the first few weeks of filgrastim therapy. If the patient develops thrombocytopenia, i.e. a persistent reduction in platelet count to <100 x 10⁹/ l should be considered temporarily discontinuation of filgrastim administration or reduction of its dose. There are also other changes in blood cells, including anemia and a transient increase in the number of myeloid progenitor cells, which necessitates close quantitative monitoring. Special care should be taken when diagnosing severe chronic neutropenia, differentiating it from other hematopoietic disorders such as aplastic anemia, myelodysplasia and myeloid leukemia. Before the treatment, a full blood count should be performed with a smear and platelet count, and a myelogram and a karyotype should be performed. It is currently unclear whether long-term treatment of SCN patients predisposes to cytogenetic anomalies, MDS transitions or leukemia. Regular morphological and cytogenetic bone marrow tests are recommended (approximately every 12 months). The urine should be checked regularly (hematuria and proteinuria are observed). The safety and efficacy of the drug in newborns and patients with autoimmune neutropenia have not been established.HIV infection. During the first few weeks of treatment with filgrastim, absolute neutrophil counts (ANC) should be monitored regularly - ANC is recommended every day for the first 2-3 days of treatment, at least 2 times a week for the first 2 weeks of treatment and then once a week. or every second week during maintenance treatment - blood sampling is recommended immediately prior to administration of the planned dose of filgrastim. It is recommended to regularly monitor blood counts (risk of anemia and thrombocytopenia). Neutropenia may be due to bone marrow infiltration by infections with opportunistic microbes, such asMycobacterium avium or by malignant tumors, such as lymphomas. In patients with bone marrow infiltration infections or malignancies, the use of appropriate treatment for underlying disease should be considered in addition to filgrastim in the treatment of neutropenia. The effect of filgrastim on neutropenia due to infections or malignancies infiltrating the bone marrow has not been well defined. Due to the sorbitol content, the drug should not be used in patients with rare hereditary fructose intolerance. Needle cover in amp-syringe. contains dry, natural rubber (a derivative of latex), which can cause allergic reactions.

In pregnancy, it is allowed to be used only if the anticipated benefits outweigh the potential risk to the fetus. Do not use during breast-feeding.

Patients with malignant tumor. Very common: increased uric acid in the blood, increased lactate dehydrogenase in the blood, decreased appetite, headache, pain in the mouth and throat, cough, shortness of breath, diarrhea, vomiting, constipation, nausea, increased GGT, increase in alkaline phosphatase in blood, rash, alopecia, musculoskeletal pain, weakness, fatigue, mucositis. Common: hypersensitivity reactions, hypotension, hemoptysis, pain during urination, chest pain.Uncommon: splenic rupture, splenomegaly, sickle cell breakthrough, graft versus host disease (in patients with allogeneic bone marrow transplantation), pseudoarthrosis, veno-thrombotic disease of veins, disturbances in fluid volume, capillary leak syndrome, acute syndrome respiratory failure, respiratory failure, pulmonary edema, interstitial lung disease, pulmonary infiltrates, pulmonary haemorrhage, Sweet's syndrome, inflammation of the skin's blood vessels, worsening of rheumatoid arthritis, abnormal urine parameters, pain.Healthy donors subjected to PBPC mobilization. Very common: thrombocytopenia, leukocytosis, headache, musculoskeletal pain. Common: splenomegaly, increased blood lactate dehydrogenase activity, dyspnoea, increased alkaline phosphatase in the blood. Uncommon: splenic rupture, anaphylactic reaction, hyperuricemia, capillary leak syndrome, pulmonary haemorrhage, haemoptysis, pulmonary infiltrates, hypoxia, increased AST, and worsening of rheumatoid arthritis.Patients with SCN. Very common: splenomegaly, anemia, hyperuricemia, decreased blood Glucose, increased blood lactate dehydrogenase, headache, nosebleeds, diarrhea, hepatomegaly, increased alkaline phosphatase in the blood, rash, musculoskeletal pain, pain joints. Common: splenic rupture, thrombocytopenia, vasculitis of the skin, alopecia, osteoporosis, hematuria, injection site reaction. Uncommon: proteinuria.Patients with HIV. Very common: musculoskeletal pain. Common: enlargement of the spleen.

Cytotoxic chemotherapy: 0.5 million IU (5 μg) / kg / day in the form of subcutaneous injections (preferred route of administration) or, after prior dilution in 5% glucose, by 30 minutes intravenous infusion. The first dose of the drug should not be administered before 24 hours after the end of the administration of cytotoxic drugs. It should be given daily until the expected neutrophil nadir has been resolved and returned to normal. After chemotherapy used to treat solid tumors, lymphomas and lymphatic leukemias, it is expected that the duration of treatment that meets the above criteria will be up to 14 days. After the induction and consolidation of treatment of acute myeloid leukemia, the duration of treatment can be significantly longer (up to 38 days).Patients undergoing myeloablative therapy followed by bone marrow transplantation: Initially 1 million U (10 μg) / kg / day as a 30-minute or 24-hour infusion or 24-hour subcutaneous infusion. The preparation should be diluted in a 5% Glucose solution. The first dose should not be administered within 24 hours of the end of cytotoxic chemotherapy and within 24 hours of bone marrow transplantation. The Next doses are adjusted to the absolute neutrophil count (ANC), i.e. if the ANC is> 1.0 x 10⁹/ l for 3 consecutive days - the dose is reduced to 0.5 million joules (5 μg) / kg / day; if the ANC exceeds 1.0 x 10⁹/ l for 3 consecutive days - the drug should be discontinued. If during ANC treatment it decreases to <1.0 x 10⁹, the dose should be increased again according to the diagram above.Mobilization of PBPC in patients undergoing myelosuppressive or myeloablative therapy followed by transplantation of autologous peripheral blood progenitor cells: in monotherapy, 1 MU (10 μg) / kg / day in a 24-hour subcutaneous infusion (after dilution in 5% glucose) or as a single subcutaneous injection for 5-7 consecutive days. It is often sufficient to perform one or two leukapheresis on days 5 and 6 of treatment. In special cases, it may be necessary to perform additional leukapheres. Filgrastim administration should continue until the last leukapheresis. However, after myelosuppressive chemotherapy, the recommended dose of filgrastim is 0.5 MU (5 μg) / kg / day in daily subcutaneous injections from the first day after chemotherapy to the expected neutrophil nadir and return to normal. Leukapesis should be carried out during the increase of ANC from <0.5 x 10⁹/ l to> 5.0 x 10⁹/ L.In patients who have not undergone intensive chemotherapy in the past, it is often enough to perform one leukapheresis; in other cases, it is recommended to perform additional leukapheres.Mobilization of PBPC in healthy donors before transplantation of allogeneic peripheral blood progenitor cells: 1 million U (10 μg) / kg / day in the form of subcutaneous injections for 4-5 consecutive days. Carrying out leukeptides should begin on the 5th day and continue, if necessary, by day 6, so as to collect 4 x 10⁶ CD34 cells⁺/ kg body recipient.Severe chronic neutropenia (SCN): congenital neutropenia - 1.2 million IU (12 μg) / kg / day subcutaneously in a single dose or divided doses; neutropenia idiopathic or cyclic - initially 0.5 million IU (5 μg) / kg / day subcutaneously in a single dose or in divided doses. The product should be administered daily until the neutrophil count increases and> 1.5 x 10⁹/ L. After receiving a response to treatment, a minimum effective dose, sufficient to maintain this number of neutrophils, should be established. In order to maintain the appropriate number of neutrophils, long-term daily administration of the drug is necessary. After 1-2 weeks, the starting dose can be doubled or halved depending on the patient's response. The dose can then be individually adjusted every 1-2 weeks to maintain the average neutrophil count in the 1.5 x 10 range.⁹-10 x 10⁹/ L. Faster dose escalation should be considered in patients with severe infections. The safety of long-term use of filgrastim in doses> 2.4 MU (24 μg) / kg / day in patients with SCN has not been established.Patients infected with HIV. For the reversal of neutropenia, the recommended initial dose is 0.1 million IU (1 μg) / kg / day given daily in the form of subcutaneous injections, which can be gradually increased to a maximum value of 0.4 million. j. (4 μg) / kg / day until the correct number of neutrophils is obtained and maintained (ANC> 2.0 x 10⁹/ L). In order to maintain normal neutrophil counts - after reversing neutropenia, a minimum effective dose should be set to maintain the normal neutrophil count; initial dose adjustment and administration of 30 million IU (300 μg) / day subcutaneously every 2 hours is recommended; long-term administration may be necessary.Special groups of patients. In children - dosage as in adults. There is no need to change the dosage in patients with impaired liver or kidney function. No specific dosage recommendations have been set for elderly patients.