Pharmacological properties of the drug Filgrastim
filgrastim is a human granulocyte colony-stimulating factor (G-CSF). It is a highly purified non-glycosylated protein that consists of 175 amino acids. It is produced by a laboratory strain of the bacterium Escherichia coli , into which the human granulocyte colony-stimulating factor gene has been introduced using genetic engineering methods. Human granulocyte colony-stimulating factor (glycoprotein) regulates the maturation of functionally active neutrophil granulocytes and their release into the blood from the bone marrow. Filgrastim significantly increases the number of neutrophil granulocytes in peripheral blood within the first 24 hours after administration and simultaneously causes a slight increase in the number of monocytes. The increase in the number of neutrophil granulocytes with filgrastim is dose-dependent within the recommended dose range. Their functional properties are identical to normal or enhanced, as evidenced by the results of studies of chemotaxis and phagocytosis. After treatment with the drug, the number of neutrophil granulocytes in the peripheral blood decreases by 50% over 1–2 days and normalizes over 1–7 days. The use of filgrastim significantly reduces the frequency, severity and duration of neutropenia in patients after chemotherapy with cytostatics or myeloablative therapy followed by bone marrow transplantation. The use of filgrastim, both primary and after chemotherapy, activates peripheral blood hemocyte progenitor cells (PHPCs). These autologous PHPCs can be obtained from the patient and administered to him after treatment with cytotoxic drugs in high doses or instead of bone marrow transplantation, or as an addition to it. The introduction of PHPC accelerates the restoration of hematopoiesis, reduces the risk of hemorrhagic complications and the need for platelet transfusion. In children and adults with severe chronic neutropenia, filgrastim consistently increases the number of neutrophil granulocytes in the peripheral blood and reduces the incidence of infectious complications. With both intravenous and subcutaneous administration of filgrastim, a positive linear dependence of its concentration in the blood plasma on the dose is observed. After subcutaneous administration in standard doses, the concentration in the blood serum exceeds 10 ng/ml for 8–16 hours; the volume of distribution is approximately 150 ml/kg. Both after subcutaneous and intravenous administration, the elimination of filgrastim from the body corresponds to first-order kinetics. The mean half-life of filgrastim is approximately 3.5 hours and clearance is approximately 0.6 ml/min/kg. Continuous administration by intravenous infusion for 28 days to patients after autologous bone marrow transplantation was not accompanied by signs of accumulation and an increase in the half-life of filgrastim.
Indications for use of the drug Filgrastim
To reduce the duration and incidence of febrile neutropenia in patients receiving chemotherapy with cytotoxic agents for non-myeloid malignant diseases, as well as to reduce the duration of the clinical consequences of neutropenia in patients receiving myeloablative therapy followed by bone marrow transplantation. Mobilization of autologous AGEPCs, including after myelosuppressive therapy, to accelerate the recovery of hematopoiesis by introducing these cells after myelosuppression or myeloablation. Long-term therapy aimed at increasing the number of neutrophil granulocytes, reducing the frequency and duration of infectious complications in children and adults with severe congenital, periodic or malignant neutropenia (absolute number of neutrophil granulocytes ≤500 in 1 mm3) and a history of severe or recurrent infections
Use of the drug Filgrastim
The dosage regimen for adults and children is determined individually depending on the patient's condition. When carrying out cytotoxic chemotherapy according to standard regimens, the drug is prescribed at a dose of 500,000 units (5 mcg) per 1 kg of body weight once a day. Filgrastim can be administered daily by subcutaneous injection at a dose of 5–12 mcg per 1 kg of body weight or short (30 min) intravenous drip infusion in a 5% glucose solution at a dose of 5–10 mcg/kg body weight. Filgrastim can be administered daily until the neutrophil granulocyte count reaches the expected normal range. The duration of treatment can be up to 14 days depending on the type, dose and regimen of cytotoxic chemotherapy. During cytotoxic chemotherapy, an increase in the number of neutrophil granulocytes is usually observed 1–2 days after the start of treatment with filgrastim. However, to achieve a stable therapeutic effect, it is necessary to continue therapy until the number of neutrophil granulocytes reaches normal values. It is not recommended to discontinue filgrastim prematurely, before reaching the required minimum value of the number of neutrophil granulocytes. For myeloablative therapy followed by bone marrow transplantation, an initial dose of 1,000,000 units (10 mcg) per 1 kg of body weight per day is administered intravenously over 30 minutes or 24 hours, or 1,000,000 units (10 mcg) per 1 kg body weight per day by continuous subcutaneous infusion for 24 hours. Filgrastim must be diluted in 20 ml of 5% glucose solution; The first dose should be administered no earlier than 24 hours after cytotoxic chemotherapy or bone marrow transplant. The effectiveness and safety of using filgrastim for more than 28 days in patients after bone marrow transplantation and in patients receiving cytotoxic chemotherapy have not been established. After the moment of maximum decrease in the number of neutrophil granulocytes has passed, the daily dose should be adjusted taking into account the dynamics of their number: if the number of neutrophil granulocytes exceeds 1000 per 1 mm3 for 3 consecutive days, the dose of filgrastim is reduced to 500,000 units (5 mcg) per 1 kg body weight per day; if the absolute number of neutrophil granulocytes exceeds 1000 per 1 mm3 also for 3 days, treatment with filgrastim is stopped. If during treatment the absolute number of neutrophil granulocytes decreases to ≤1000 per 1 mm3, the dose of filgrastim should be increased again in accordance with the given scheme. To activate PHCP, which is carried out as an independent therapy, 1,000,000 units (10 mcg) per 1 kg of body weight per day is administered by continuous 24-hour IV infusion or subcutaneous injection once a day for 6 days in a row. (for infusion, filgrastim is diluted in 20 ml of 5% glucose solution). It is recommended to carry out three leukapheresis in a row - for 5; 6th and 7th days. To mobilize AGEPC after myelosuppressive chemotherapy, administer 500,000 units (5 mcg) per 1 kg of body weight per day by daily injections starting on the 1st day after completion of chemotherapy until the number of neutrophil granulocytes passes the expected minimum and reaches normal values . Leukapheresis should be carried out during the period when the absolute number of neutrophil granulocytes increases from ≤500 to 5000 per 1 mm3. For patients who have not undergone intensive chemotherapy, leukapheresis alone is sufficient. In other cases, additional leukapheresis is recommended. For congenital neutropenia, filgrastim is administered at an initial dose of 1,200,000 units (12 mcg) per 1 kg of body weight per day subcutaneously, once or dividing the daily dose into several administrations. For idiopathic or periodic neutropenia - 500,000 units (5 mcg) per 1 kg of body weight per day subcutaneously once or in several injections. In patients with severe chronic neutropenia, filgrastim should be administered daily subcutaneously until the number of neutrophil granulocytes consistently exceeds 1500 per 1 mm3. After achieving a therapeutic effect, the minimum effective maintenance dose should be determined. To maintain the required number of neutrophil granulocytes, prolonged daily administration of the drug is required. After 1–2 weeks of treatment, the initial dose can be doubled or halved depending on the patient's response to therapy. In the future, individual dose adjustments can be made every 1–2 weeks to maintain the average number of neutrophil granulocytes in the range of 1500–10,000 per 1 mm3. In patients with severe infections, a more rapid dose escalation regimen may be used. In clinical studies, in 97% of patients who responded positively to treatment, a full therapeutic effect was observed when using the drug in doses of up to 24 mcg/kg/day. The safety of using filgrastim in the long-term treatment of patients with severe chronic neutropenia at doses exceeding 24 mcg/kg/day has not been established.
Filgrastim
It is not recommended for use in patients with severely impaired renal or liver function, because the effectiveness and safety of filgrastim in this category of patients has not been studied.
In patients with concomitant bone pathology and osteoporosis receiving filgrastim continuously for more than 6 months, monitoring of bone density is recommended.
The effectiveness of filgrastim in patients with significantly reduced numbers of myeloid progenitor cells has not been studied. Filgrastim increases the number of neutrophils by acting primarily on neutrophil precursor cells. Therefore, in patients with a reduced number of progenitor cells (for example, those who have undergone intensive radiation therapy or chemotherapy), the degree of increase in the number of neutrophils may be lower.
Human granulocyte colony-stimulating factor can induce the growth of myeloid cells in vitro. Similar effects may be observed in vivo in some non-myeloid cells. The safety and effectiveness of filgrastim in patients with myelodysplastic syndrome and chronic myeloid leukemia have not been established, so it is not indicated for these diseases. The differential diagnosis between blast transformation of chronic myeloid leukemia and acute myeloid leukemia should be especially carefully carried out.
During treatment, it is necessary to regularly determine the number of leukocytes. If, after passing the expected minimum, it exceeds 50,000/µl, filgrastim should be discontinued immediately. If filgrastim is used to mobilize peripheral blood hematopoietic progenitor cells, it should be discontinued when the leukocyte count exceeds 100,000/µl.
Use with extreme caution in patients receiving high-dose cytotoxic chemotherapy.
Filgrastim monotherapy does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. It is recommended to regularly determine the platelet count and hematocrit. Particular caution should be exercised when using single or combination chemotherapy regimens known to cause severe thrombocytopenia.
Before using filgrastim for severe chronic neutropenia, a differential diagnosis with other hematological diseases, such as aplastic anemia, myelodysplasia and myeloid leukemia, should be especially carefully carried out. Before starting treatment, a detailed blood test should be performed to determine the leukocyte formula and platelet count, as well as examine the morphological picture of the bone marrow and karyotype.
The blood picture should be carefully monitored, incl. platelet count, especially during the first few weeks of treatment with filgrastim. In case of thrombocytopenia (platelet count consistently below 100,000/μl), temporary discontinuation of filgrastim or dose reduction should be considered. There are also other changes in the blood count that require careful monitoring, incl. anemia and a transient increase in the number of myeloid progenitor cells.
During treatment, the size of the spleen should be regularly monitored and a urine test should be performed.
When assessing the number of progenitor cells mobilized in patients with filgrastim, special attention should be paid to the quantification method. The results of flow cytometric analysis of CD34+ cell counts vary depending on the specific methodology, and caution should be exercised in making cell count recommendations based on studies performed in other laboratories.
There have been no specific studies of the effectiveness and safety of filgrastim in elderly patients.
The safety and effectiveness of use in newborns and patients with autoimmune neutropenia have not been established.
Contraindications to the use of the drug Filgrastim
In patients receiving cytotoxic chemotherapy, treatment with filgrastim is often accompanied by bone and muscle pain. In most cases, pain is eliminated by taking non-narcotic analgesics. There is often a reversible, dose-dependent and, as a rule, mild or moderate increase in the concentration of LDH, alkaline phosphatase, uric acid and γ-glutamyltransferase in the blood. In isolated cases, urinary disturbances and decreased blood pressure occur. A leukocyte count of 100,000 per mm3 or higher was observed in less than 5% of patients who received filgrastim in doses exceeding 300,000 units (3 mcg) per day. No adverse effects directly related to this high leukocytosis have been reported. Filgrastim did not increase the incidence of side effects during cytotoxic chemotherapy. Side effects such as nausea, vomiting, alopecia, diarrhea, anorexia, inflammation of the mucous membranes, headache, cough, skin rash, general weakness, sore throat, constipation were observed with equal frequency in patients who received filgrastim and chemotherapy or placebo and chemotherapy. Vascular disorders (venous thrombosis and fluid and electrolyte imbalance) were sometimes observed in patients who received high-dose chemotherapy followed by autologous bone marrow transplantation, but their connection with the use of filgrastim has not been established. There are isolated cases of allergic reactions, half of which occurred during the first dose. These cases were more often observed after intravenous administration of the drug. In patients with severe chronic neutropenia, side effects have been described when using filgrastim. The most common symptoms were bone pain and generalized musculoskeletal pain, splenomegaly, and thrombocytopenia; headache and diarrhea at the beginning of treatment with filgrastim and anemia and nosebleeds with prolonged use of the drug. Adverse effects possibly related to filgrastim use were reported in less than 2% of patients with severe chronic neutropenia and included injection site reactions, hepatomegaly, arthralgia, hair loss, osteoporosis, skin rash, vasculitis, proteinuria and hematuria.
Side effects of the drug Filgrastim
Human granulocyte colony-stimulating factor promotes the growth of myeloid cells in vitro . A similar effect in vitro can be observed for some non-myeloid cells. The safety and effectiveness of filgrastim in patients with myelodysplasia, acute and chronic myeloid leukemia has not been established. Due to the possibility of potentiating tumor growth, filgrastim should be used with caution in malignant myeloid diseases and in any myeloproliferative disease. During treatment with filgrastim, it is necessary to regularly monitor the number of leukocytes: if it exceeds 50,000 per 1 mm3, treatment with the drug should be stopped immediately; if the drug is used to mobilize AGEPCs, treatment is stopped when the number of leukocytes exceeds 100,000 per 1 mm3. Particular care should be taken when treating patients receiving high-dose chemotherapy. Monotherapy with filgrastim does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy, however, it makes it possible to use higher doses of chemotherapy, as a result of which the patient has a high risk of developing thrombocytopenia and anemia. It is recommended to regularly determine the platelet count and hematocrit. Particular caution should be exercised when using single-component regimens that can cause severe thrombocytopenia. Particular attention should be paid to the diagnosis of severe forms of chronic neutropenia. Before treatment, a detailed blood test is indicated with calculation of the leukocyte formula and platelet count, as well as a study of the morphological composition of the bone marrow and karyotype. If cytogenetic abnormalities are detected in patients with Costner's syndrome, the risks and benefits of continuing filgrastim therapy should be carefully weighed; If myelodysplastic syndrome or leukemia is detected, treatment with the drug should be discontinued. Patients with Costner syndrome are recommended to undergo morphological and cytogenetic studies of the bone marrow every 12 months. It is necessary to monitor the platelet count in peripheral blood, especially during the first weeks of treatment with filgrastim. If the patient has thrombocytopenia (platelet count is consistently below 100,000 per 1 mm3), the issue of temporarily stopping treatment or reducing the dose should be decided. Splenomegaly is a direct consequence of treatment with filgrastim, so it is necessary to regularly palpate the abdomen. When the dose of the drug is reduced, splenomegaly stops progressing; 3% of patients required splenectomy. In a small number of cases, patients were found to have hematuria and proteinuria. To monitor them, it is necessary to regularly conduct laboratory urine tests. The safety and effectiveness of the drug in newborns and patients with autoimmune neutropenia have not been established. Patients who have received active myelosuppressive therapy in the past may not sufficiently activate AGEPCs to the recommended level (2 x 106 CD34-positive cells/kg) or accelerate platelet count normalization. Some cytostatics are particularly toxic to AGEPCs and may adversely affect their mobilization. Drugs such as melphalan, carmustine, and carboplatin, if prescribed for an extended period of time before attempting to mobilize CPPC, may reduce its effectiveness. However, the use of melphalan, carmustine and carboplatin together with filgrastim was effective in activating AGEPCs. If transplantation of PHCC is planned, it is recommended to mobilize stem cells at the beginning of the course of treatment. Particular attention should be paid to the number of progenitor cells activated in such patients before the use of high-dose chemotherapy. If mobilization results according to the above criteria are insufficient, alternative treatments that do not require the use of progenitor cells should be considered. Patients with osteoporosis and concomitant skeletal pathology who receive continuous treatment with filgrastim for 6 months or more are advised to undergo densitometric monitoring of bone tissue. Studies on the use of filgrastim in patients with severely impaired renal or hepatic function have not been conducted, so it is not recommended to prescribe it for the treatment of this group of patients. The effect of filgrastim in patients with a significantly reduced number of meloid progenitor cells has not been studied. Filgrastim increases the number of neutrophil granulocytes by acting primarily on their precursor cells. Therefore, in patients with a reduced content of progenitor cells (for example, those who have received intensive radiation and chemotherapy), the degree of increase in the number of neutrophil granulocytes may be lower. The effect of filgrastim on graft-versus-host disease has not been established. The safety of filgrastim during pregnancy has not been established, so the expected therapeutic effect for the expectant mother should be weighed against the potential risk to the fetus. It is unknown whether filgrastim passes into breast milk, so its use during breastfeeding is not recommended.
Filgrastimum
Filgrastim therapy should only be carried out under the supervision of an oncologist or hematologist with experience in the use of such drugs.
Growth of malignant cells. G-CSF can induce the growth of myeloid cells in vitro. Similar effects may be observed in vitro in some non-myeloid cells. The safety and effectiveness of filgrastim in patients with myelodysplastic syndrome and chronic myeloid leukemia have not been established, therefore it is not indicated for these diseases. Particular attention should be paid to the differential diagnosis between blastotransformation of chronic myeloid leukemia and acute myeloid leukemia.
Leukocytosis. Given the possible risk associated with severe leukocytosis, the leukocyte count should be regularly monitored during treatment with filgrastim: if it exceeds 50,000 cells/mm3, the drug should be discontinued. When filgrastim is used to mobilize peripheral blood stem cells, it is discontinued if the white blood cell count exceeds 100,000/mm3.
Risks associated with high-dose chemotherapy. Particular caution should be exercised when treating patients receiving high-dose chemotherapy as there has been no evidence of improvement in cancer outcome, while higher doses of chemotherapy are associated with greater toxicity, including cardiac, pulmonary, neurological and dermatological reactions. Filgrastim monotherapy does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. Due to the possibility of using higher doses of chemotherapy drugs (eg, full doses according to regimens), the patient may be at greater risk of thrombocytopenia and anemia. It is recommended to regularly monitor the platelet count and hematocrit. Particular caution should be exercised when using single or combination chemotherapy regimens known to cause severe thrombocytopenia.
Transformation into leukemia or pre-leukemia. Particular care should be taken when diagnosing severe chronic neutropenia to differentiate it from other hematological diseases such as aplastic anemia, myelodysplasia and myeloid leukemia. Before starting treatment, a detailed blood test should be performed to determine the leukocyte formula and platelet count, as well as examine the morphological picture of the bone marrow and karyotype. If a patient with Kostmann's syndrome develops cytogenetic abnormalities, the risks and benefits of continuing therapy must be carefully assessed. If myelodysplastic syndrome or leukemia develops, the drug should be discontinued. It is unclear whether long-term treatment with filgrastim predisposes patients with severe congenital neutropenia (Kostmann syndrome) to the development of cytogenetic abnormalities, myelodysplasia and leukemia. Patients with hereditary neutropenia should undergo regular (every 12 months) morphological and cytogenetic studies of the bone marrow.
Blood formula. During treatment, especially during the first few weeks, the platelet count must be carefully monitored. If thrombocytopenia occurs (platelet count is stable <100,000 cells/mm3), dose reduction or temporary discontinuation of the drug should be considered. Other changes in the blood count that require careful monitoring are also observed, including anemia and a transient increase in the number of myeloid progenitor cells.
Before prescribing, causes of transient neutropenia such as viral infections should be excluded.
When treating with filgrastim, it is necessary to regularly monitor the size of the spleen (palpation of the abdomen). Reducing the dose of filgrastim slowed or stopped spleen enlargement in studies.
Drug interactions Filgrastim
Diluted filgrastim can be adsorbed to glass and plastics; however, when diluted as recommended, the product is compatible with glass and some plastics, including polyvinyl chloride, polyolefin (polypropylene-polyethylene copolymer), and polypropylene. If filgrastim is diluted to a concentration of less than 1,500,000 units (15 mcg) in 1 ml, then human plasma albumin should be added to the solution so that the final concentration is 2 mg/ml. For example, with a final solution volume of 20 ml, total doses of filgrastim less than 30,000 00 IU (300 mcg) should be administered with the addition of 0.2 ml of human plasma albumin solution. In no case is it recommended to dilute the drug to a final concentration of less than 200,000 units (2 mcg) per 1 ml. The safety and effectiveness of administering filgrastim on the same day with myelosuppressive cytotoxic chemotherapy has not been established. Given the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, administration of filgrastim within 24 hours before and after administration of these drugs is not recommended.
LEUCOSTIM
Directions for use and doses
Leukostim® can be administered both subcutaneously and intravenously.
The route of administration and dose depend on the specific clinical situation and are determined by the attending physician. The preferred route of administration is subcutaneous. If intravenous administration is necessary, the required amount of the drug is injected from a syringe into a vial or plastic container with a 5% dextrose solution, then a 30-minute infusion of the diluted drug is performed. Due to the increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, the use of Leucostim® is not recommended less than 24 hours before the start of chemotherapy and earlier than 24 hours after the end of chemotherapy. Breeding instructions:
Leucostim cannot be diluted with 0.9% sodium chloride solution; the drug is diluted with a 5% dextrose solution. If the drug is diluted to a concentration of less than 15 mcg/ml (less than 1.5 million IU/ml), then human serum albumin should be added to the solution so that the final albumin concentration is 2 mg/ml. For example, with a final solution volume of 20 ml, a total dose of Leucostim® less than 300 mcg (less than 30 million IU) should be administered with the addition of 0.2 ml of a 20% solution of human albumin. Filgrastim should not be diluted to a final concentration of less than 2 mcg/ml (less than 0.2 million IU/ml).
Recommended doses:
For the treatment of neutropenia after a course of cytotoxic chemotherapy
Leucostim® is administered once a day subcutaneously or intravenously at a dose of 5.0 mcg (0.5 million IU) per 1 kg of patient body weight.
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 Leukostim®. To assess the effectiveness of treatment, daily counting of the number of neutrophils in peripheral blood is desirable. To achieve a stable therapeutic effect, it is necessary to continue therapy with Leucostim® until the number of neutrophils passes the expected minimum and reaches normal values. Once the absolute neutrophil count exceeds 2.0×109/L, the drug can be discontinued. 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 transplant
Leucostim® is administered subcutaneously or intravenously at the rate of 10 mcg (1.0 million IU) per 1 kg of body weight. The first dose of Leucostim® should be administered no earlier than 24 hours after cytotoxic chemotherapy, and in case of bone marrow transplantation - no later than 24 hours after bone marrow infusion. After the moment of maximum decrease in the number of neutrophils has passed, the daily dose is adjusted depending on the dynamics of their number. If the content of neutrophils in peripheral blood exceeds 1.0 × 109/l for three consecutive days, the dose of Leucostim® is reduced by half (to 5.0 mcg (0.5 million IU) per 1 kg of body weight). Then, if the absolute neutrophil count exceeds 1.0×109/l for three consecutive days, Leucostim® is discontinued. If the absolute number of neutrophils decreases during treatment below 1.0x09/l, the dose of Leucostim® is again increased to 10 mcg (1.0 million IU) per 1 kg of body weight.
To mobilize hematopoietic stem cells
Leucostim® is administered subcutaneously at a daily dose of 5.0 mcg (0.5 million IU) per 1 kg of body weight (in patients after myelosuppressive chemotherapy) or 10 mcg (1.0 million IU) per 1 kg of patient weight (in the absence of chemotherapy) for 5-7 consecutive days (the number of injections depends on the rate of increase in the number of leukocytes in the peripheral blood and the effectiveness of separation). The day before the expected date of the first separation (4th day of administration of the drug Leukostim®) and on the following days (before the day of the last separation), the number of leukocytes and neutrophils in the patient’s peripheral blood is assessed. Cytapheresis is carried out if the number of leukocytes increases to 5×10/l of peripheral blood, starting from the 5th day of administration of the drug Leukostim®. After each separation, the number of nucleated cells and CD34+ cells in the sample intended for cryopreservation is counted. When the number of cryopreserved CD34+ cells is reached, which is sufficient for transplantation (at least 2 × 106 per kg of patient weight), the administration of Leukostim® is stopped.
The effectiveness and safety of Leucostim® in healthy donors under 16 and over 60 years of age have not been studied.
For severe chronic neutropenia (SCN)
Leukostim® should be administered subcutaneously daily until the number of neutrophils stably exceeds 1.5x109/l (for congenital neutropenia - at a dose of 12 mcg (1.2 million IU) per 1 kg of patient weight per day subcutaneously in one or several injections; for idiopathic or periodic neutropenia - 5.0 mcg (0.5 million IU) per 1 kg of body weight per day). After achieving a therapeutic effect, the minimum effective dose to maintain this level of neutrophils must be determined. This requires long-term 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, dose adjustments should be made every 1-2 weeks to maintain the neutrophil count in the range of 1.5-10x109/L.
For
neutropenia associated with HIV infection
: initial dose of 1-4 mcg (0.1-0.4 million IU) per 1 kg of body weight per day, once subcutaneously until the number of neutrophils normalizes (>2 × 109/l). Normalization of the number of neutrophils usually occurs after 2 days. If the initial dose is ineffective, it is escalated to 5.0 mcg (0.5 million IU) per 1 kg of body weight per day once subcutaneously. After achieving a therapeutic effect, maintenance therapy with Leukostim® is carried out at a dose of 1-4 mcg (0.1-0.4 million IU) per 1 kg of body weight per day 2-3 times a week. In the future, individual dose adjustment and long-term therapy with Leukostim® may be required to maintain the neutrophil count more than 2.0 × 109/l.
Special dosage instructions
:
When filgrastim was used in pediatric practice in patients with severe chronic neutropenia and cancer, the safety profile of filgrastim did not differ from that in adults. Dosing recommendations for pediatric patients are the same as for adults receiving myelosuppressive or cytotoxic chemotherapy.
Dose adjustment of filgrastim is not required in patients with severe renal or hepatic impairment, since their pharmacokinetic and pharmacodynamic parameters are similar to those in healthy volunteers.
