Leucostim
Instructions for use:
LEUCOSTIM®
Registration number:
Trade name of the drug:
Leucostim®.
International nonproprietary name:
filgrastim.
Dosage form:
solution for intravenous and subcutaneous administration.
Compound.
1 ml of solution contains:
active substance:
filgrastim (recombinant human granulocyte colony-stimulating factor) 600 mcg (60 million IU).
Excipients:
mannitol, dextran 60000, sodium acetate trihydrate, glacial acetic acid, polysorbate 80, water for injection.
Description.
Transparent, colorless solution.
Pharmacotherapeutic group.
Leukopoiesis stimulator.
ATX Code:
L03AA02.
Pharmacological properties.
Pharmacodynamics.
Filgrastim is a highly purified non-glycosylated protein consisting of 175 amino acids.
It is produced by a strain of Escherichia coli,
into the genome of which the gene for human granulocyte colony-stimulating factor (G-CSF), a glycoprotein that regulates the formation of functionally active neutrophils and their release into the blood from the bone marrow, has been introduced using genetic engineering.
Leucostim containing recombinant G-CSF significantly increases the number of neutrophils in peripheral blood within the first 24 hours after administration, with a slight increase in the number of monocytes. In
patients with severe chronic neutropenia, Leukostim® may cause a slight increase in the number of circulating eosinophils and basophils. Leucostim® dose-dependently increases the number of neutrophils with normal or increased functional activity. After treatment, the number of neutrophils in the peripheral blood decreases by 50% within 1-2 days and returns to normal levels over the next 1-7 days. The duration of action when administered intravenously may be shortened. The clinical significance of this phenomenon with repeated administration of the drug is unclear.
The use of the drug Leukostim®, both independently and after chemotherapy, mobilizes the release of hematopoietic stem cells into the peripheral bloodstream. Autologous or allogeneic peripheral blood stem cell (PBSC) transplantation is performed after therapy with large doses of cytostatics, either instead of bone marrow transplantation or in addition to it. PSCC transplantation may also be indicated after (high-dose) myelosuppressive cytotoxic therapy. The use of PSCC mobilized using the drug Leukostim® accelerates the restoration of hematopoiesis, reduces the severity and duration of thrombocytopenia, the risk of hemorrhagic complications and the need for platelet transfusion after myelosuppressive or myeloablative therapy.
The effectiveness and safety of Leukostim in adults and children receiving cytotoxic chemotherapy are the same.
In children and adults with severe chronic neutropenia (severe congenital, periodic, idiopathic neutropenia), Leucostim® consistently increases the number of neutrophils in the peripheral blood and reduces the incidence of infectious complications. Prescribing Leukostim® to patients with HIV infection allows them to maintain normal neutrophil counts and follow the recommended doses of antiretroviral and/or other myelosuppressive therapy. There were no signs of increased HIV replication when using the drug Leucostim®. Like other hematopoietic growth factors, G-CSF stimulates human endothelial cells in vitro.
Pharmacokinetics.
With intravenous and subcutaneous administration of filgrastim, a positive linear relationship is observed between the administered dose and serum concentration. After subcutaneous administration of therapeutic doses, its concentration exceeds 10 ng/ml for 8-16 hours. The volume of distribution is 150 ml/kg.
Regardless of the route of administration, the elimination of filgrastim proceeds according to the rules of 1st order kinetics. The half-life is 3.5 hours, clearance is 0.6 ml/min/kg. Long-term administration of filgrastim up to 28 days after autologous bone marrow transplantation does not lead to accumulation and an increase in the half-life. In patients with end-stage renal disease, there is an increase in maximum concentration (Cmax) and area under the curve (AUC), and a decrease in volume of distribution and clearance compared with healthy volunteers and patients with moderate renal failure.
Indications for use.
• Neutropenia, febrile neutropenia in patients receiving intensive myelosuppressive cytotoxic chemotherapy for malignant diseases (except for chronic myeloid leukemia and myelodysplastic syndrome), as well as neutropenia and its clinical consequences in patients receiving myeloablative therapy followed by allogeneic or autologous bone marrow transplantation.
• Mobilization of peripheral blood stem cells, including after myelosuppressive therapy.
• Severe congenital, recurrent or idiopathic neutropenia (absolute neutrophil count less than or equal to 0.5x109/L) in children and adults with a history of severe or recurrent infections.
• Persistent neutropenia (absolute neutrophil count less than or equal to 1.0x109/l) in patients with advanced HIV infection to reduce the risk of bacterial infections when other treatments are ineffective or impossible to use.
Contraindications.
• Hypersensitivity to filgrastim or other components of the drug.
• Severe congenital neutropenia (Kostmann's syndrome) with cytogenetic disorders.
• Use of the drug to increase doses of cytotoxic chemotherapy drugs above the recommended ones.
• Simultaneous administration with cytotoxic chemotherapy and radiation therapy.
• End-stage chronic renal failure.
• Myelodysplastic syndrome (MDS) and chronic myeloid leukemia (no data on efficacy and safety)
• Lactation.
• Newborn age (up to 28 days of life).
Carefully.
During pregnancy, malignant and precancerous diseases of a myeloid nature (including acute myeloid leukemia), sickle cell anemia, in combination with high-dose chemotherapy.
Use during pregnancy and lactation.
The safety of filgrastim in pregnant women has not been established. It is possible for the drug Leucostim to pass through the placental barrier in women. When prescribing Leucostim® to pregnant women, the expected therapeutic effect should be balanced against the possible risk to the fetus. In animal studies, filgrastim was not teratogenic. An increased rate of miscarriage was observed, but no fetal anomalies were noted.
There is no data on the penetration of filgrastim into breast milk. The use of Leucostim® in nursing mothers is not recommended.
Method of administration and dose.
Daily subcutaneously (SC) or as short intravenous (IV) infusions (30 minutes). The drug can also be administered as a 24-hour intravenous or subcutaneous infusion.
The choice of route of administration depends on the specific clinical situation. The preferred route of administration is subcutaneous.
Standard cytotoxic chemotherapy regimens.
At a dose of 5 mcg (0.5 million IU)/kg once a day daily subcutaneously or in the form of short intravenous infusions. The first dose of the drug is administered no earlier than 24 hours after the end of the course of cytotoxic chemotherapy. A transient increase in the number of neutrophils is usually observed 1-2 days after the start of treatment with Leukostim®. 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. If necessary, the duration of therapy can be up to 14 days, depending on the severity of the disease and the severity of neutropenia. After induction and consolidation therapy for acute myeloid leukemia, the duration of therapy with Leukostim® may increase to 38 days, depending on the type, dose and mode of administration of the cytotoxic drugs used.
It is not recommended to discontinue Leucostim® prematurely, before the expected minimum number of neutrophils occurs.
After myeloablative chemotherapy followed by bone marrow transplantation.
The recommended starting dose is 10 mcg (1.0 million IU)/kg, diluted in 20 ml of 5% dextrose solution, as a 30-minute or 24-hour intravenous infusion or by continuous subcutaneous infusion over 24 hours. First dose 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 infusions. The duration of therapy is no more than 28 days. After the maximum reduction in the number of neutrophils, the daily dose is adjusted depending on the dynamics of their number. If the content of neutrophils in peripheral blood exceeds 1.0 x109/l for three consecutive days, the dose of Leucostim® is reduced to 5.0 mcg (0.5 million IU)/kg; if at this dose the absolute number of neutrophils exceeds 1.0x109/l for three more days in a row, Leucostim® is discontinued. If during the treatment period the absolute number of neutrophils decreases to less than 1.0 xYue/l, the dose of Leucostim® is increased again in accordance with the above scheme.
Mobilization of peripheral blood stem cells (PBSCs) after myelosuppressive therapy followed by autologous PBSC transfusion with (or without) bone marrow transplantation or in patients with myeloablative therapy followed by PBSC transfusion.
At a dose of 10 mcg (1.0 million IU)/kg by subcutaneous injection once a day or continuous 24-hour subcutaneous infusion for 6 consecutive days, two consecutive leukapheresis procedures on the 5th, 6th are usually sufficient days. In some cases, additional leukapheresis may be performed. The prescription of Leukostim® must be continued until the last leukapheresis.
Mobilization of PSCC after myelosuppressive therapy.
At a dose of 5 mcg (0.5 million IU)/kg by daily subcutaneous injection, starting on the first day after completion of chemotherapy until the neutrophil count passes the expected minimum and reaches normal values. Leukapheresis should be performed during the period when the absolute neutrophil count rises from less than 0.5 x 109/L to more than 5.0 x 109/L. For patients who have not received intensive chemotherapy, leukapheresis alone is sufficient. In some cases, additional leukapheresis is recommended.
Mobilization of PSCCs from healthy donors for allogeneic transplantation.
At a dose of 10 mcg (1.0 million units)/kg per day subcutaneously, for 4-5 days. Leukapheresis is carried out from the 5th day and, if necessary, until the 6th day in order to obtain CD34+ cells in an amount of >4x106 cells/kg of the recipient’s body weight. The effectiveness and safety of Leucostim® in healthy donors under 16 and over 60 years of age have not been studied.
Severe chronic neutropenia (SCN).
Daily subcutaneously, once or divided into several injections. The initial dose for congenital neutropenia is 12 mcg (1.2 million IU)/kg per day, for idiopathic or periodic neutropenia - 5 mcg (0.5 million IU)/kg per day, until the number of neutrophils is stable above 1, 5x109/l. Once a therapeutic effect has been achieved, the minimum effective dose to maintain this neutrophil level should be determined. 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 can be made every 1 to 2 weeks to maintain the neutrophil count in the range of 1.5-10 x109/L.
In patients with severe infections, a more rapid dose escalation regimen may be used. In 97% of patients who responded positively to treatment, a full therapeutic effect is observed when filgrastim doses are prescribed up to 24 mcg/kg/day. The daily dose of Leucostim® should not exceed 24 mcg/kg.
Neutropenia in HIV infection.
The initial dose is 1-4 mcg (0.1-0.4 million IU)/kg per day once subcutaneously until the number of neutrophils normalizes (>2x109/l). Normalization of the number of neutrophils usually occurs after 2 days. After achieving a therapeutic effect, a maintenance dose of 300 mcg per day every other day. In the future, individual dose adjustment and long-term therapy with Leucostim® may be required to maintain the neutrophil count more than 2.0 x109/l.
Special dosage instructions.
Elderly age:
There are no special recommendations for elderly patients.
Children:
When 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.
No dosage adjustment of filgrastim is required in patients with severe renal or hepatic impairment, as their pharmacokinetic and pharmacodynamic parameters are similar to those of healthy volunteers.
Recommendations for preparing a solution for intravenous administration.
If intravenous administration of the drug Leucostim® is necessary, the required amount of the drug is injected from a syringe into a vial or plastic container with a 5% dextrose solution.
Leucostim® cannot be diluted with 0.9% sodium chloride 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. Leukostim® should not be diluted to a final concentration of less than 2 mcg/ml (less than 0.2 million IU/ml).
Leucostim®, when diluted with a 5% dextrose solution or a 5% dextrose solution and albumin, is compatible with glass and a number of plastics, including polyvinyl chloride, polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.
Syringes with Leukostim® are intended for single use only.
The prepared solution of Leucostim® is stored at a temperature of 2 to 8°C for no more than 24 hours.
Side effect.
Adverse reactions are listed according to the following gradation: very often (> 10%); often (> 1% - < 10%); infrequently (> 0.1% - < 1%); rare (>0.01% to <0.1%); very rare (<0.01%).
From the hematopoietic organs:
very often - neutrophilosis and leukocytosis (as a consequence of the pharmacological action of filgrastime), with long-term administration - anemia, splenomegaly; often - thrombocytopenia; very rarely - rupture of the spleen.
From the respiratory system:
often - cough; very rarely - infiltrates in the lungs, adult respiratory distress syndrome.
From the musculoskeletal system:
often - pain in bones, muscles, joints; often - osteoporosis; very rarely - exacerbation of rheumatoid arthritis, pseudogout (pyrophosphate arthropathy)
From the cardiovascular system:
very rarely - decreased or increased blood pressure, skin vasculitis (with long-term therapy in patients with SCN).
From the digestive system:
often – diarrhea, hepatomegaly.
From the genitourinary system:
rarely – hematuria, proteinuria; very rarely - dysuria.
From the skin and its appendages:
often – skin rash, with long-term use alopecia; rarely - Sweet's syndrome (acute febrile neutrophilic dermatosis, connection with taking filgrastim has not been established).
Allergic reactions:
very rarely - skin rash, urticaria, facial swelling, wheezing, shortness of breath, low blood pressure, tachycardia.
From the laboratory parameters:
very often - reversible, weak Moderate increase in the activity of gammaglutamyltransferase, alkaline phosphatase, lactate dehydrogenase, increase in the concentration of uric acid in the blood serum, transient hypoglycemia; rarely - increased aspartate aminotransferase activity.
Others:
often - headache, increased fatigue, general weakness, reactions at the injection site (less than 2% of patients with SCN).
Overdose.
There have been no cases of filgrastim overdose. 1-2 days after discontinuation of the drug, the number of circulating neutrophils usually decreases by 50% and returns to normal levels after 1-7 days.
Interaction with other drugs.
The effectiveness and safety of administering filgrastim on the same day as cytotoxic chemotherapy have not been established. Due to the high sensitivity of actively proliferating myeloid cells to antitumor cytotoxic drugs, it is not recommended to prescribe filgrastim 24 hours before or after the administration of these drugs. There are isolated reports of increased severity of neutropenia with simultaneous administration of filgrastim and 5-fluorouracil. There is currently no data on possible interactions with other hematopoietic growth factors and cytokines.
Given that lithium stimulates the release of neutrophils, the effect of filgrastim may be enhanced when used in combination. Interaction studies between lithium and filgrastim have not been conducted.
Filgrastim is not pharmaceutically compatible with 0.9% sodium chloride solution.
When using filgrastim to mobilize hematopoietic stem cells after chemotherapy, it should be taken into account that when cytostatics such as melphalan, carmustine and carboplatin are prescribed for a long time, the effectiveness of mobilization may be reduced.
Special instructions.
Treatment with Leukostim® should be carried out under the supervision of a physician experienced in the use of colony-stimulating factors, if the necessary diagnostic capabilities are available. Cell mobilization and apheresis procedures should be performed in specialized medical institutions.
In myelodysplastic syndrome (MDS) and chronic myeloid leukemia, the effectiveness and safety of filgrastim have not been established. For patients with the above diseases, the use of filgrastim is not indicated. Particular attention should be paid to the differential diagnosis between blast crisis of chronic myeloid leukemia and acute myeloid 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.
A small number (3%) of patients with severe congenital neutropenia (Kostmann's syndrome) treated with filgrastim have developed MDS and leukemia. MDS and leukemia are natural complications of this disease; their relationship to filgrastim treatment is unclear. In approximately 12% of patients with initially normal cytogenetics, anomalies were discovered upon re-examination, including monosomy 7. If cytogenetic abnormalities appear in a patient with Kostmann's syndrome, or if MDS or leukemia develops, filgrastim should be discontinued. It is not yet clear whether long-term treatment with filgrastim predisposes patients with Kostmann syndrome to the development of cytogenetic abnormalities, MDS and leukemia. Patients with Kostmann syndrome are recommended to undergo morphological and cytogenetic studies of the bone marrow at regular intervals (approximately every 12 months).
Cytogenetic disorders, leukemia and osteocorosis were found with long-term use of filgrastim (>5 years) in 9.1% of patients with severe chronic neutropenia. Their connection with taking the drug has not been clarified.
Treatment with filgrastim should be carried out under regular monitoring of a complete blood count with counting the leukocyte formula and platelet count (before starting therapy and then 2 times a week with standard chemotherapy and at least 3 times a week with mobilization of PSCC with or without subsequent bone marrow transplantation). If the leukocyte count increases to more than 50x109/l, filgrastim should be discontinued immediately. If filgrastim is used to mobilize hematopoietic stem cells, it must be discontinued if the leukocyte count exceeds 70 x109/l.
Filgrastim does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. It is recommended to regularly perform blood tests twice a week to determine platelet count and hematocrit while using filgrastim after chemotherapy.
Platelet counts should be carefully monitored, especially during the first few weeks of treatment with filgrastim. In case of SCN, during the first weeks of initial therapy, a clinical blood test and platelet count are determined 2 times a week, and if the patient’s condition is stable - once a month. If the patient develops thrombocytopenia (platelet count consistently below 100×10%), temporary discontinuation of the drug 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.
Causes of transient neutropenia such as viral infections should be excluded.
During treatment with filgrastim, urine tests should be performed regularly (to exclude hematuria and proteinuria) and the size of the spleen should be monitored.
The safety and effectiveness of filgrastim in neonates and patients with autoimmune neutropenia have not been established.
After bone marrow transplantation, a blood test is performed and the platelet count is determined 3 times a week.
Patients who have received active myelosuppressive therapy in the past may not have a sufficient increase in PSCC to the recommended minimum level (>2.0x106CD34+/
Kr). In this regard, in such patients, if it is necessary to undergo PSCC transplantation, it is recommended to plan their mobilization at an early stage of the course of treatment, and if, as a result of mobilization before the introduction of high-dose chemotherapy, it was not possible to obtain a sufficient number of PSCCs, then alternative types of treatment should be considered, not requiring the use of progenitor cells.
When using filgrastim-mobilized PSCC, a decrease in the severity and duration of thrombocytopenia caused by myelosuppressive or myeloablative chemotherapy is observed.
There is a complex; but a stable statistical relationship between the number of introduced CO34+ cells and the rate of normalization of the platelet count after high-dose chemotherapy.
A minimum number of PSCC equal to or exceeding 2.0 × 106 CO34+ cells/kg leads to a sufficient restoration of hematological parameters.
Mobilization of PSKs can only be considered in those healthy donors whose clinical and laboratory parameters, especially hematological parameters, meet the criteria for selecting donors for mobilization of PSKs.
Transient leukocytosis (leukocytes more than 50x109/l) is observed in 41% of healthy donors, more than 75x109/l - in 2% of healthy donors. Transient thrombocytopenia (platelet count less than 100x109/l) after administration of filgrastim and leukapheresis is observed in 35% of donors. In addition, 2 cases of thrombocytopenia less than 50 xl09/l were noted after the leukapheresis procedure.
If more than one leukapheresis is required, special care should be taken if the donor's platelet count before leukapheresis is less than 100x109/L. Leukapheresis is not recommended if the platelet count is less than 75 xl0/l, as well as in donors with impaired hemostasis or receiving anticoagulants.
Filgrastim should be discontinued or its dose reduced if the white blood cell count exceeds 70 x109/L.
In healthy donors, it is necessary to regularly monitor all blood test parameters until they normalize.
Considering isolated cases of splenic rupture after the administration of granulocyte colony-stimulating factor to healthy donors, it is recommended to monitor its size (palpation, ultrasound).
During long-term observation of the safety of filgrastim use in healthy donors up to 4 years after filgrastim administration, no cases of hematopoiesis disorders were noted. However, the risk of stimulating the emergence of a clone of malignant myeloid cells cannot be excluded, and therefore, in apheresis centers it is recommended to systematically monitor healthy stem cell donors for at least 10 years.
Special instructions for recipients of allogeneic PSCC obtained with filgrastim:
the use of allogeneic PSCC graft may be associated with an increased risk of acute or chronic graft-versus-host disease compared with bone marrow transplantation.
When treating HIV-infected patients with neutropenia with filgrastim, it is necessary to regularly conduct a complete blood count (absolute neutrophil count (ANC), red blood cells, platelets, etc.) daily for the first few days, then 2 times a week for the first 2 weeks and every week or every other week during maintenance therapy. Given fluctuations in the ANC value, to determine the true maximum reduction in ANC (nadir), blood sampling should be performed before prescribing the next dose of the drug.
In patients with infectious diseases and infiltration of the bone marrow by infectious pathogens (for example, Mycobacterium avium complex) or with tumor lesions of the bone marrow (lymphoma), filgrastim therapy is carried out simultaneously with therapy directed against these conditions.
In patients with sickle cell anemia, blood tests should be performed regularly and the possibility of splenomegaly and vascular thrombosis should be taken into account.
In patients with bone pathology and osteoporosis receiving continuous treatment with filgrastim for more than 6 months, bone density monitoring is indicated.
The effect of filgrastim in patients with a significantly reduced number of myeloid progenitor cells is not known. 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.
A history of pneumonia or pulmonary infiltrates may be risk factors for interstitial lung disease during filgrastim therapy. The appearance of cough, fever and shortness of breath associated with the appearance of infiltrates in the lungs may be the first signs of the development of adult respiratory distress syndrome. If these signs appear, filgrastim should be discontinued and appropriate treatment should be prescribed.
The effect of the drug on the ability to drive vehicles and maintain machinery.
There was no effect of filgrastim on the ability to drive vehicles and operate machinery.
Release form.
Solution for intravenous and subcutaneous administration 600 mcg/ml (60 million IU/ml). 0.8 ml of a drug with a concentration of 600 mcg/ml (60 million IU/ml), containing 480 mcg (48 million IU) of filgrastim in neutral glass syringes with soldered needles and a butyl rubber stopper laminated with a fluoropolymer, sealed with tips on pistons.
1 or 5 syringes complete with pistons (1 or 5, respectively) in a blister pack made of PVC film, along with instructions for use in a cardboard box.
Storage and transportation conditions.
At temperatures from 2 to 8 °C. Keep out of the reach of children.
Best before date.
2 years. Do not use after the expiration date stated on the package.
Conditions for dispensing from pharmacies.
Dispensed by prescription.
Manufacturer. LLC "Biocad", Petrovo-Dalneye, Moscow region.
www.biocad.ru and www.leucostim.ru
Release form and composition
Dosage form - solution for intravenous and subcutaneous administration: colorless or yellowish, transparent (150 mcg/ml - 1 ml in bottles, 1 or 5 bottles in a contour strip package, 1 package in a cardboard pack; 300 mcg/ml - 1 or 1.6 ml in vials, 1 or 5 vials in a blister pack, 1 pack in a cardboard pack; 0.5 or 1 ml in syringes with pistons and soldered needles, 1 or 5 syringes in a cardboard pack; 600 mcg/ml – 0.8 ml each in syringes with pistons and soldered needles, 1 or 5 syringes in a blister pack, 1 pack in a cardboard pack; each pack also contains instructions for using Leucostim). Active substance: filgrastim, in 1 ml of solution - 150 mcg (15 million IU), 300 mcg (30 million IU) or 600 mcg (60 million IU) (IU - international units). Auxiliary components: water for injection, glacial acetic acid, sodium acetate trihydrate, polysorbate 80, dextran 60,000, mannitol.
Side effects
Cardiovascular system: transient decrease in blood pressure; Musculoskeletal system: muscle and/or bone pain (usually mild or moderate), exacerbation of existing rheumatoid arthritis; Hematopoietic system: anemia, thrombocytopenia; Nervous system: headache, increased fatigue; Respiratory system: infiltrates in the lungs with the development of respiratory distress syndrome in adults (more often after chemotherapy regimens including bleomycin; their connection with the use of Leucostim is unclear); Digestive system: diarrhea, hepatomegaly; Laboratory indicators: decrease in the number of platelets in peripheral blood, reversible increase in the levels of lactate dehydrogenase, alkaline phosphatase, uric acid, glutamyl transpeptidase in the blood plasma; Urinary system: dysuria (usually mild or moderate); Other: pain at the injection site; rarely (more often after intravenous administration) - allergic reactions (about half of them usually occur during the first dose), skin rash, vasculitis, enlarged spleen, splenic rupture, vascular thrombosis.
special instructions
Treatment with Leukostim should only be carried out under the supervision of an oncologist or hematologist with experience in the use of such drugs. Before prescribing it, causes of transient neutropenia such as viral infections should be excluded. Particular attention must be paid to the diagnosis of severe chronic neutropenia to differentiate it from other hematological diseases such as myeloid leukemia, myelodysplasia and aplastic anemia. In chronic myeloid leukemia and myelodysplastic syndrome, the safety and effectiveness of filgrastim have not been established. For patients with these diseases and with precancerous lesions of the myeloid lineage of hematopoiesis, Leucostim is not recommended, because Some tumor cells may carry a receptor for granulocyte colony-stimulating factor. For this reason, special attention should be paid to the differential diagnosis between blast crisis of chronic myeloid leukemia and acute myeloid leukemia. During therapy, it is necessary to constantly monitor the size of the spleen (by palpation of the abdomen). According to research data, when the dose of Leucostim is reduced, the enlargement of the spleen stops or, at least, slows down. A small number (about 3%) of patients with Kostmann's syndrome treated with filgrastim experienced leukemia and myelodysplastic syndrome, natural complications of this disease, the relationship of which with the use of the drug has not been established. If these complications develop, Leucostim should be discontinued. In rare cases (less than 5%), hyperleukocytosis (increase in white blood cell count above 100x109/L) has been observed in patients undergoing treatment with filgrastim, so the white blood cell count should be determined regularly. If they increase to more than 50×109/l, Leucostim should be discontinued. If the drug is used to mobilize hematopoietic stem cells, it should be discontinued if the leukocyte count increases to more than 70 × 109/L. In approximately 12% of patients with initially normal cytogenetics, abnormalities, including monosomy 7, were detected on repeat testing. If cytogenetic abnormalities are detected in patients with severe congenital neutropenia, the benefits and possible risks of continuing therapy should be weighed. Every 12 months it is necessary to conduct cytogenetic and morphological studies of the bone marrow. It is important to consider that Leucostim does not prevent anemia and thrombocytopenia, which are often a consequence of the use of chemotherapy drugs in high doses. Therefore, during treatment after chemotherapy, the number of platelets and red blood cells, as well as the level of hemoglobin, should be regularly determined.
Impact on the ability to drive vehicles and complex mechanisms
Considering the mechanism of pharmacological action of filgrastim, its effect on the speed of psychomotor reactions and the ability to concentrate seems extremely unlikely.
Drug interactions
Leucostim is pharmaceutically incompatible with sodium chloride solution 0.9%. Given the increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, it is not recommended to use Leucostim 24 hours before the start of a chemotherapy course and at least 24 hours after its completion. The safety and effectiveness of administering filgrastim on the same day as cytotoxic chemotherapy have not been established. It is known that 5-fluorouracil, when used simultaneously with filgrastim, increases the severity of neutropenia. When using Leukostim to mobilize hematopoietic stem cells after chemotherapy, it should be taken into account that long-term use of cytostatics, such as carboplatin, melphalan, carmustine (BCNU), may reduce the effectiveness of mobilization.
