Active substanceFilgrastimFilgrastim
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  • Dosage form: & nbspsolution for intravenous and subcutaneous administration
    Composition:

    1 ml of the solution contains:

    active substance: filgrastim (recombinant granulocyte human colony-stimulating factor) 300 mcg (30 ppm) ME);

    Excipients: mannitol 50 mg, dextran 60,000 15 mg, sodium acetate trihydrate 0.23 mg, acetic acid ice to pH 4.0, polysorbate 80 0.04 mg, water for injection up to 1 ml. Complaints on the drug should be addressed to the manufacturer.

    Description:

    A clear, colorless or slightly yellow solution.

    Pharmacotherapeutic group:leukopoiesis stimulant
    ATX: & nbsp

    L.03.A.A.02   Filgrastim

    Pharmacodynamics:

    Leucostim® (filgrastim - recombinant human granulocyte colony-stimulating factor) belongs to the group of biologically active proteins regulating cell differentiation and proliferation.

    Filgrastim is produced by a strain of bacteria Escherichia coli, in which gene of granulocyte colony-stimulating factor of a person was introduced by genetic engineering methods. Leucostim® is identical to the natural granulocyte colony-stimulating factor of a human in biological activity, differing from it by the absence of glycosylation and the presence of an additional N-terminal amino acid residue of methionine.

    Leucostim® accelerates the proliferation of granulocyte precursor cells of the neutrophilic bone marrow (CFU-G), differentiation in the direction of mature neutrophils, and their release into the peripheral blood from the bone marrow. Causes a dose-dependent increase in the number of neutrophils in peripheral blood. Neutrophils produced in response to the administration of Leukostim® have normal or increased chemotactic and phagocytic activity.

    The use of Leucostim® allows to restore the number of neutrophils in peripheral blood with neutropenia in patients receiving chemotherapy, or in patients with chronic neutropenia. The use of Leukostim® for preventive purposes can reduce the frequency, severity, and duration of neutropenia and febrile neutropenia after chemotherapy. This leads to the prevention of infectious complications, a reduction in the length of hospitalization, and adherence to the intervals prescribed in the treatment regimens between cycles of chemotherapy.

    The use of Leukostim® both after and without chemotherapy leads to the mobilization of hemopoietic progenitor cells into the peripheral blood.These cells can be collected by cytapheresis and administered to the patient after high-dose chemotherapy. The introduction of hematopoietic stem cells allows the recovery of the hematopoietic and immune systems after myeloablative chemotherapy. After mielosupressivnoy chemotherapy, the introduction of hematopoietic stem cells accelerates the recovery of hematopoiesis, reducing the incidence and severity of infectious and hemorrhagic complications.

    The efficacy and safety of Leucostim in adults and children receiving cytotoxic chemotherapy are the same.

    In children and adults with severe chronic neutropenia, Leucostim® steadily increases the number of neutrophils in peripheral blood, reducing the incidence of infectious complications.

    The administration of Leucostim® to patients with HIV infection can maintain a normal level of neutrophils and follow recommended doses of antiretroviral and / or other myelosuppressive therapy. There are no signs of an increase in HIV replication with filgrastim.

    Pharmacokinetics:

    The concentration of the drug in the blood plasma is proportional to the administered dose.The half-life of filgrastim with subcutaneous and intravenous administration is 3-4 hours. After subcutaneous administration of therapeutic doses of filgrastim, its concentration in the serum exceeds 10 ng / ml for 8-16 hours. There is a direct relationship between the concentration of filgrastim in plasma and the increase in the number of neutrophils in peripheral blood.

    Filgrastim, in general, is metabolized to peptides and only slightly excreted in the urine unchanged (less than 1% of the administered dose). Long-term use of filgrastim for up to 28 days is not accompanied by signs of cumulation and an increase in the half-life period.

    Indications:

    The drug is used to:

    - shortening the duration of grade II-IV neutropenia and reducing the frequency of febrile neutropenia in patients with non-myeloproliferative neoplasms after chemotherapy with cytostatic drugs;

    - mobilization of hematopoietic progenitor cells into peripheral blood for the purpose of their subsequent separation and transplantation after myelosuppressive chemotherapy;

    - shortening the duration of neutropenia and preventing complications associated with it in patients receiving myeloablative chemotherapy followed by bone marrow transplantation;

    - treatment of severe chronic neutropenia to increase the number of neutrophils and reduce the frequency and duration of infectious complications;

    - treatment of persistent neutropenia in patients with advanced stage of HIV infection (absolute number of neutrophils (<1.0 × 109/ l) to reduce the risk of bacterial infections;

    - mobilization of hematopoietic progenitor cells in peripheral blood in healthy donors for the purpose of their subsequent separation and allogeneic transplantation.

    Contraindications:

    Hypersensitivity to the active substance (filgrastim) or other components of the drug.

    Severe congenital neutropenia (Kostmann's syndrome) with cytogenetic disorders.

    Newborn age (immediately after birth until 28 days of life).

    Pregnancy and lactation:

    Safety filgrastim for pregnant women is not established, so its appointment to pregnant women can not be recommended. If you need filgrastim during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Leukostim® can be administered either subcutaneously or intravenously. The mode of administration and dose depend on the specific clinical situation and are determined by the attending physician.Preferably a subcutaneous route of administration. If intravenous administration is required, the required amount of the drug is injected from the syringe into a vial or plastic container with a 5% dextrose solution, followed by a 30-minute infusion of the diluted drug. Due to the increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, the use of Leukostim® is not recommended less than 24 hours before the start of chemotherapy and earlier than 24 hours after the end of chemotherapy.

    Dilution instructions:

    Leuchkam can not be diluted with 0.9% solution of sodium chloride; the preparation is bred 5% solution of dextrose. If the drug is diluted to concentration of less than 15 μg / ml (less than 1.5 million IU / ml), then the solution should be added with whey human albumin, so that the final concentration of albumin is 2 mg / ml. For example, with a final solution volume of 20 ml, the total dose of Leucostim ® is less than 300 μg (less than 30 million) ME) should be administered with the addition of 0.2 ml of a 20% solution of human albumin. You can not breed filgrastim to a final concentration of less than 2 μg / ml (less than 0.2 million IU / ml).

    Recommended doses:

    For treatment neutropenia after a course of cytotoxic chemotherapy Leucostim® is administered once a day subcutaneously or intravenously at a dose of 5.0 μg (0.5 million) ME) per 1 kg of body weight of the patient.

    In patients receiving cytotoxic chemotherapy, a transient increase in the number of neutrophils is usually observed 1-2 days after the start of treatment with Leucostim®. Daily evaluation of neutrophil count in peripheral blood is desirable to evaluate the effectiveness of treatment. To achieve a stable therapeutic effect, it is necessary to continue therapy with Leukostim® until the number of neutrophils passes the expected minimum and does not reach normal values. After reaching an absolute number of neutrophils in excess of 2.0x109/ l the drug can be canceled. If necessary, the duration of therapy can be up to 12 days, depending on the severity of the disease and the severity of neutropenia.

    After myeloablative chemotherapy followed by bone marrow transplantation Leucostim® is administered subcutaneously or intravenously at a rate of 10 μg (1.0 million) ME) per 1 kg of body weight. The first dose of Leucostim® should not be given earlier,than 24 hours after cytotoxic chemotherapy, and when bone marrow transplantation - no later than 24 hours after the infusion of the bone marrow. After the moment of the maximum decrease in the number of neutrophils passes, the daily dose is adjusted depending on the dynamics of their number. If the content of neutrophils in peripheral blood exceeds 1.0x109/ l for three consecutive days, the dose of Leucostim® is halved (to 5.0 μg (0.5 million) ME) per 1 kg of body weight). Then, if the absolute number of neutrophils exceeds 1.0x109/ l for three consecutive days, Leucostim® is canceled. In the case of a decrease in the absolute number of neutrophils during treatment, less than 1.0x09/ l, the dose of Leucostim® is again increased to 10 μg (1.0 million) ME) per 1 kg of body weight.

    For mobilization of hematopoietic stem cells Leucostim® is administered subcutaneously at a daily dose of 5.0 μg (0.5 million; ME) per 1 kg of body weight (in patients after myelosuppressive chemotherapy) or 10 μg (1.0 million) ME) per 1 kg of patient weight (in the absence of chemotherapy) for 5-7 consecutive days (the number of administrations depends on the rate of increase in the number of leukocytes in the peripheral blood and the effectiveness of separation).The day before the anticipated period of the first separation (the 4th day of Leukostim® administration) and the following days (until the last separation day), the number of leukocytes and neutrophils in the peripheral blood of the patient is estimated. Cytapheresis is performed in the case of an increase in the number of leukocytes to 5x10 / L of peripheral blood, starting from the 5th day of administration of Leucostim®. After each separation, the number of nucleated cells is counted and Cd34+ cells in a cryoconservation sample. When the number of cryopreserved Cd34+ cells, which is sufficient for transplantation (at least 2x106 per kg of patient weight), the injection of Leucostim® is stopped.

    The efficacy and safety of using Leucostim® in healthy donors under the age of 16 and older than 60 years have not been investigated.

    When severe chronic neutropenia (THC) Leukostim® should be injected daily subcutaneously until the number of neutrophils is consistently greater than 1.5 × 109/ l (with congenital neutropenia - at a dose of 12 μg (1.2 million) ME) per 1 kg of patient weight per day subcutaneously in one or more administrations; for idiopathic or intermittent neutropenia, 5.0 μg (0.5 million; ME) per 1 kg of weight per day).After achieving the therapeutic effect, it is necessary to determine the minimum effective dose to maintain this level of neutrophils. This requires a long daily administration of the drug. After 1-2 weeks of treatment, the initial dose can be doubled or halved, depending on the patient's response to therapy. Subsequently, every 1-2 weeks, dose adjustment should be performed to maintain the number of neutrophils in the range of 1.5-10 × 109/ l.

    When neutropenia associated with HIV infection: the initial dose of 1-4 μg (0.1-0.4 million; ME) per 1 kg of body weight per day once subcutaneously to normalize the number of neutrophils (> 2x109/ l). Normalization of the number of neutrophils usually occurs in 2 days. If the initial dose is not effective, it escalates to 5.0 μg (0.5 million) ME) per 1 kg of weight per day once subcutaneously. After the therapeutic effect is achieved, maintenance therapy with Leucostim® in a dose of 1-4 μg (0.1-0.4 million) ME) for 1 kg of weight per day 2-3 times a week. In the future, individual dose adjustment and long-term therapy with Leucostim® may be required to maintain the number of neutrophils more 2,0x109/ l.

    Special instructions for dosing:

    When applying filgrastim in pediatric practice in patients with severe chronic neutropenia and oncological diseases, the safety profile of filgrastim did not differ from that in adults. Recommendations for dosing for children of the same age are the same as for adults receiving myelosuppressive or cytotoxic chemotherapy.

    Correction of filgrastim dose is not required in patients with severe renal or hepatic insufficiency, since their pharmacokinetic and pharmacodynamic indices are similar to those of healthy volunteers.

    Side effects:

    Treatment with Leukostim® in recommended doses may be accompanied by pain at the injection site, pain in the bones and muscles.

    In the clinical study of the drug Leucostim® at 7.5% patients had mild to moderate musculoskeletal pain, which either did not require drug correction, or were stopped by the use of non-steroidal anti-inflammatory drugs. There were no severe pains.

    According to the literature, in rare cases, hypersensitivity reactions of a delayed type can be detected at the site of administration of the drug, accompanied by the appearance of erythema and edema.If such reactions are detected, the drug should be discontinued.

    In rare cases, with filgrastim, headache, fatigue, diarrhea, hepatomegaly, and urinary disorders (mainly mild or moderate dysuria) have been observed. There are some reports of a transient decrease in blood pressure that did not require treatment. A reversible, dose-dependent and usually mild or moderate increase in the concentrations of lactate dehydrogenase, alkaline phosphatase, serum uric acid and γ-glutamyltransferase, a decrease in the number of platelets in the peripheral blood.

    Rarely, skin rash, enlarged spleen in patients with initially not enlarged spleen, vasculitis, blood vessel thrombosis can be observed. The cases of the appearance of infiltrates in the lungs with the development of adult respiratory distress syndrome are described; These phenomena were more often observed after chemotherapy regimens including bleomycin, their connection with filgrastim is not established. Very rarely, after filgrastim, cases of proteinuria and hematuria were observed.

    Rarely, rheumatoid arthritis was exacerbated against the background of filgrastim, as well as rupture of the spleen, thrombocytopenia and anemia with prolonged use of filgrastim.With prolonged therapy with filgrastim, 2% of patients with TCH had skin vasculitis.

    Overdose:

    Filgrastim overdose cases are not noted.

    Interaction:

    Due to the high sensitivity of actively proliferating myeloid cells to antitumor cytostatic drugs, the appointment of filgrastim should be followed 24 hours before or after the administration of myelosuppressive drugs. The efficacy and safety of filgrastim administration in one day with cytotoxic chemotherapeutic agents have not been established. 5-fluorouracil reinforces the severity of neutropenia with concomitant administration with filgrastim.

    Filgrastim is not pharmaceutically compatible with 0.9% sodium chloride solution.

    When filgrastim is used to mobilize hematopoietic stem cells after chemotherapy, it should be borne in mind that when cytostatics are prescribed for a long time melphalan, carmustine (BCNU) and carboplatin, mobilization efficiency can be reduced.

    Special instructions:

    With extreme caution filgrastim should be used for acute myelogenous leukemia.

    With myelodysplastic syndrome (MDS) and chronic myeloid leukemia, the efficacy and safety of filgrastim have not been established.Patients with the abovementioned diseases, as well as with premalignant lesions of the myeloid germ of hematopoiesis, filgrastim is not recommended, since the cells of some tumors can carry a receptor to G-CSF. Because of this, special attention should be paid to a differential diagnosis between the blast crisis of chronic myelogenous leukemia and acute myeloid leukemia.

    A small number of patients (less than 5%) who received filgrastim, hyperleukocytosis was observed (an increase in the number of leukocytes in excess of 100x109/ l). Adverse events directly associated with filgrastim induced hyperleukocytosis are not described. However, given the possible risk associated with hyperleukocytosis, during treatment with filgrastim it is necessary to regularly determine the number of leukocytes. With an increase in the number of leukocytes over 50x109/ l filgrastim should be immediately canceled. If filgrastim is used to mobilize hematopoietic stem cells, the drug should be discarded when the number of leukocytes exceeds 70x109/ l.

    It should be noted that the use of filgrastim does not prevent thrombocytopenia and anemia.Because thrombocytopenia and anemia often result from the use of high doses of chemotherapy, it is recommended to regularly determine the number of platelets, as well as the number of erythrocytes or hemoglobin level during filgrastim after the chemotherapy.

    Particular attention should be given to differential diagnosis of severe chronic neutropenia from other hematological diseases, such as aplastic anemia, myelodysplasia and myeloid leukemia.

    A small number (3%) of patients with severe congenital neutropenia (Costman's syndrome) who received filgrastim, MDS and leukemia were observed.

    MDS and leukemia are natural complications of this disease; their connection with treatment with filgrastim is unclear. Approximately 12% of patients with initially normal cytogenetics had anomalies on repeated examination, including monosomy 7. If a patient with Costman's syndrome develops cytogenetic disorders, it is necessary to carefully evaluate the benefits and risk of continuing therapy with filgrastim. With the development of MDS or leukemia filgrastim should be canceled. It is not yet clear whether long-term treatment with filgrastim predisposes patients with severe congenital neutropenia (Costman's syndrome) to the development of cytogenetic abnormalities, MDS and leukemia.Patients with Costman's syndrome are recommended to perform morphological and cytogenetic studies of the bone marrow at regular intervals (approximately every 12 months).

    Effect on the ability to drive transp. cf. and fur:

    Given the mechanism of pharmacological (immunological) action filgrastim, its impact on the ability to drive vehicles and work with mechanisms is extremely unlikely.

    Form release / dosage:

    Solution for intravenous and subcutaneous administration, 300 μg / ml (30 million IU / ml).

    Packaging:

    For 0.5 ml (150 μg (15 million) ME)) or 1 ml (300 μg (30 ppm) ME)) in

    a sterile syringe made of neutral glass with a soldered injection needle covered with a protective cap elastic or rigid, sealed with a butyl rubber tip, laminated fluoropolymer equipped with a piston. For each syringe stick a label.

    For 1 or 5 filled syringes in a contiguous Instructions for use are placed in a pack of cardboard.

    Storage conditions:

    At a temperature of 2 to 8 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-0002968/10
    Date of registration:08.04.2010
    The owner of the registration certificate:BIOCAD, CJSC BIOCAD, CJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspBIOCAD CJSC BIOCAD CJSC Russia
    Information update date: & nbsp23.09.2015
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