Index of drugs

It is indicated to reduce the duration of neutropenia and to reduce the incidence of febrile neutropenia in patients undergoing cytotoxic chemotherapy for malignancies (with the exception of chronic myeloid leukemia and myelodysplastic syndromes) and to reduce the duration of neutropenia in patients undergoing myeloablative chemotherapy followed by bone marrow transplantation exposed to prolonged severe neutropenia. The safety and efficacy of treatment with the product are similar in adults and in children undergoing cytotoxic chemotherapy. The preparation is indicated for the mobilization of peripheral blood progenitor cells (PBPC). In patients, both children and adults with severe congenital, cyclical or idiopathic neutropenia with absolute neutrophil count (ANC) ≤ 0.5 x 10⁹/ l, with a history of severe or recurrent infections, long-term administration of the drug is indicated to increase the number of neutrophils and to reduce the incidence and duration of infectious complications. The preparation is indicated for the treatment of persistent neutropenia (ANC ≤11,0 x 10⁹/ l) in patients with advanced HIV infection to reduce the risk of bacterial infections if other treatments for neutropenia can not be used.

1 vial contains 300 μg (30 million IU) of filgrastim in 1 ml solution for injection. 1 pre-filled syringe contains 300 μg (30 million IU) or 480 μg (48 million IU) of filgrastim in 0.5 ml solution for injection. The drug contains sorbitol.

Human growth factor for granulocyte colonies (G-CSF), a glycoprotein regulating the maturation and release of mature neutrophils from the bone marrow. The preparation contains recombinant methionylated G-CSF (r-metHuG-CSF), which causes a significant increase in peripheral blood neutrophil counts within 24 hours of administration and a small increase in 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. Based on studies of chemotactic and phagocytic activity, it was shown that neutrophilic granulocytes 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. T_0,5 is about 3.5 h. Following intravenous or subcutaneous administration of filgrastim, there is a positive linear relationship between the dose and the concentration of the drug in the blood.

Hypersensitivity to filgrastim or other ingredients of the preparation.

The use of filgrastim in cancer patients and healthy donors is associated with the risk of capillary leak syndrome (CLS) - patients should be carefully observed for the occurrence of CLS symptoms, such as: generalized edema with swelling (which may be associated with less frequent urination), difficulty breathing, abdominal swelling or feeling of fullness, fatigue, hypotension, hypoalbuminemia and blood thickening; if they occur, standard symptomatic treatment should be started immediately, which may include intensive medical care. Do not administer the preparation to increase the doses of cytostatics beyond the established dosing schedule. It should not be used in patients with severe congenital neutropenia who have or have had leukemia. Use cautiously in patients with recent inflammatory infiltration in the lungs or with previous pneumonia - 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 adult type of acute adult respiratory distress syndrome (ARDS) - in this case it is recommended to discontinue filgrastim administration. Filgrastim in conditionsin vitro it can stimulate the growth of myeloid cells, including cancer cells. It should not be used in patients with myelodysplastic syndrome and chronic myelogenous leukemia - the safety and efficacy of the medicine have not been established in these patient groups. Use with caution in patients with secondary acute myelogenous leukemia. The safety and efficacy of the medicine have not been established in patients with acute myelogenous leukemiade novo aged <55 years with favorable cytogenetic tests - t (8; 21), t (15; 17) and inv (16). Special care should be taken when treating patients receiving high-dose chemotherapy. Due to the possibility of increasing the dose of chemotherapy, the patient may be at increased risk of thrombocytopenia and anemia. Particular care should be taken when using cytostatics, either as monotherapy or in combination therapy, with a known effect of causing severe thrombocytopenia. The effects of the preparation have not been studied in patients with a significantly reduced number of myeloid progenitor cells. In patients with a reduced number of neutrophil precursors (e.g., those receiving intensive radiotherapy or chemotherapy, or those with tumor infiltration in the bone marrow), the neutrophil response may be reduced. 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 before filgrastim administration may reduce the number of progenitor cells obtained - because the use of these drugs in combination with filgrastim allows effective mobilization of progenitor cells, it is recommended to plan the procedure of mobilization of stem cells at an early stage of treatment . The safety and efficacy of filgrastim in healthy donors undergoing PBPC mobilization <16 years and> 60 years have not been evaluated. In patients with severe chronic neutropenia who develop cytogenetic changes during treatment with the preparation, the benefits and risks of continuing filgrastim should be carefully considered, due to the risk of myeloblastic syndrome or leukemia. The safety and efficacy of the preparation in neonates and in patients with autoimmune neutropenia has not been established. In patients who have been diagnosed with an infection or cancer that causes bone marrow infiltration, appropriate treatment of the underlying disease should be considered in addition to filgrastim therapy for neutropenia. In patients with sickle cell anemia, use only after careful consideration of the potential risks and benefits due to the risk of a disease breakthrough, sometimes with fatal outcome. In patients receiving G-CSF products after allogeneic bone marrow transplantation, cases of graft-versus-host disease (GvHD) have been reported, including fatal cases. Do not use the drug in patients with congenital fructose intolerance (the preparation contains sorbitol).

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.

In patients treated for cancer - very common: nausea or vomiting, increased GGTP activity, alkaline phosphatase, lactate dehydrogenase, increased uric acid concentration; often: fatigue, weakness, constipation, anorexia, headache, diarrhea, mucositis, chest pain, bone and muscle pain, cough, sore throat and larynx, alopecia, rash; uncommon: pain; rare: angiopathy; very rare: abnormal urinalysis results. In addition: vasculitis, Swet's syndrome (acute febrile dermatosis), exacerbation of rheumatoid arthritis, alleged gout, hypersensitivity reactions (including anaphylaxis, rash, urticaria, angioneurotic edema, dyspnea, hypotension), urination disorders.Respiratory adverse reactions have also been observed (including interstitial pneumonitis, pulmonary edema and lung infiltrates, respiratory failure or adult-type respiratory failure syndrome that may be fatal) and in patients with allogeneic bone marrow transplantation - graft-versus-disease host (GvHD), including fatal cases. Occasionally, a reduction in blood pressure was observed that did not require treatment. In patients with sickle cell disease, isolated cases of breakthrough disease have been reported.In healthy donors undergoing PBPC mobilization - very common: headache, leukocytosis, thrombocytopenia, bone and muscle pain; often: increased alkaline phosphatase and lactate dehydrogenase; uncommon: spleen disorders, increased AST, increased uric acid, exacerbation of rheumatoid arthritis. In addition: side effects in the lungs (haemoptysis, pulmonary haemorrhage, inflammatory infiltrates in the lungs, dyspnoea, hypoxia), cases of anaphylaxis, splenic rupture. The occurrence of capillary leak syndrome (CLS) (including fatal cases) has been reported in patients undergoing chemotherapy and in healthy donors undergoing peripheral blood progenitor cell mobilization with filgrastim; these events were generally found in patients with advanced cancer, sepsis, repeated chemotherapy or apheresis.In patients with severe chronic neutropenia - very common: anemia, enlarged spleen, decreased blood Glucose, increased alkaline phosphatase, lactate dehydrogenase, increased uric acid, bone and muscle pain, nose bleeds; common: headache, diarrhea, thrombocytopenia, hepatomegaly, osteoporosis, alopecia, vasculitis, pain at the injection site, rash; uncommon: spleen disorders, hematuria, proteinuria. Myeloblastic syndromes or leukemias have also been observed (these side effects are a natural complication of severe congenital neutropenia and their association with filgrastim is uncertain).In patients with HIV - very often; bone and muscle pain; common: spleen abnormalities - the association with filgrastim is uncertain (splenomegaly is common in HIV and most AIDS patients).

Treatment should only be carried out in cooperation with a specialist oncology center.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. The drug should be administered daily until the expected neutrophil nadir is over and returns to the normal value.Patients undergoing myeloablative therapy followed by bone marrow transplantation: initially 1 million IU (10 μg) / kg / day as a 30-minute or 24-hour infusion or 24-hour subcutaneous infusion. The preparation should be diluted in 20 ml of 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 IU / 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/ l, the dose should be increased again according to the above diagram.Mobilization of PBPC in patients undergoing myelosuppressive or myeloablative therapy followed by transplantation of autologous progenitor cells: monotherapy 1 million IU (10 μg) / kg / day in a 24-hour subcutaneous infusion (after dilution in 20 ml of a 5% glucose solution) 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.The administration of filgrastim should be maintained until the last leukapheresis. However, after myelosuppressive chemotherapy: 0.5 million IU (5 μg) / kg / day in daily subcutaneous injections from the first day after completion of chemotherapy to passing the expected neutrophil nadir and returning to the normal value. 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 prior to transplantation of allogeneic peripheral blood progenitor cells: 10 μg / kg / day subcutaneously for 4-5 consecutive days. Carrying out leukeptides should begin on day 5 and continue, if necessary, by day 6, so as to collect 4 x 10⁶ CD34 cells⁺/ kg body recipient.Severe chronic neutropenia: 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 preparation should be administered daily until the neutrophil count is increased and maintained at a level higher than 1.5 x 10⁹/ L. After obtaining a therapeutic response, a minimum effective dose, sufficient to maintain this number of neutrophils, should be established. In order to maintain an adequate 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 an 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 infection. The safety of long-term use in doses higher than 24 μg / kg / day in patients with severe chronic neutropenia has not been established.Patients infected with HIV: for the withdrawal of neutropenia - the recommended starting dose is 0.1 million IU (1 μg) / kg / day administered daily under the skin. The initial dose can be gradually increased to a maximum value of 0.4 million. IU (4 μg) / kg / day until normal neutrophil counts are obtained and maintained (ANC> 2.0 x 10⁹/ L); in order to maintain a normal neutrophil count - after obtaining the correct number of neutrophils, a minimum dose should be set to maintain the effect of treatment. It is recommended to increase the initial dose to 30 million IU. (300 μg) / day administered subcutaneously every other day, long-term administration of the drug may be necessary.In children(with severe chronic neutropenia and cancer) - dosing as in adults receiving myelosuppressive chemotherapy. 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.