Zarcio, 30 million units /0.5 ml 0.5 ml syringes 5 pcs

Phylgrastim is a highly purified non-glycosylated protein consisting of 175 amino acids, or recombinant human granulocytic colony-stimulating factor (r-h G-CSF). It is produced by Escherichia coli strain K12, which has been genetically engineered to contain the human granulocytic colony-stimulating factor (G-CSF) gene. Human G-CSF regulates the production and release of neutrophils from the bone marrow into the peripheral blood.

Philgrastim administration is accompanied by a significant increase in the number of neutrophils in the vascular bed within 24 hours, as well as a slight increase in the number of monocytes. In some cases, an increase in eosinophil and basophil counts is also noted, but eosinophilia and basophilia may be present in some patients before the start of treatment. The increase in neutrophil counts with filgrastim in the recommended dose range is dose-dependent.

Released neutrophils have normal or increased functional activity as confirmed by chemotaxis and phagocytosis tests. At the end of therapy the number of neutrophils in peripheral blood decreases by 50% within 1-2 days and returns to the normal value during the following 1-7 days. Just like other factors of hemopoiesis stimulation, in in vitro studies it has been shown that G-CSF has the ability to stimulate endothelial cells, as they have specific receptors for G-CSF. At the same time, it was found that G-CSF is an inducer of angiogenesis of vascular endothelial cells and accelerates neutrophil transport through the vascular endothelium.

The use of filgrastim in patients receiving cytotoxic drugs is accompanied by a significant reduction in the frequency, severity and duration of neutropenia and febrile neutropenia and allows the use of antibiotics at lower doses compared to patients receiving only cytotoxic chemotherapy. Reduces the need and duration of hospital treatment in patients after induction chemotherapy for myeloleukosis or myeloablative therapy with subsequent bone marrow transplantation. The incidence of body temperature did not decrease in patients after myeloablative therapy followed by bone marrow transplantation.

The use of Zarcio both in monotherapy and after chemotherapy mobilizes the output of hematopoietic stem cells into the peripheral blood stream. Autologous or allogeneic transplantation of peripheral blood stem cells (PBSCs) is performed after therapy with high doses of cytostatics either instead of or in addition to bone marrow transplantation. PSCC transplantation can also be prescribed after (high-dose) myelosuppressive cytotoxic therapy.

The use of PRBCs mobilized with Zarsio accelerates hematopoiesis recovery, reduces the severity and duration of thrombocytopenia, reduces the risk of hemorrhagic complications and the need for platelet transfusions after myelosuppressive or myeloablative therapy.

The use of Zarsio in children and adults with severe congenital neutropenia (recurrent, idiopathic) promotes a steady increase of the number of active neutrophils in peripheral blood and reduces the incidence of infectious and other complications.

The use of Zarsio in patients with HIV infection maintains the number of neutrophils within normal values, which allows to observe the necessary dosing regime of antiretroviral drugs and means of myelosuppressive therapy. There are no signs of increased HIV replication when using Zarsio.

Indications

Reduction of neutropenia duration and frequency of febrile neutropenia in patients receiving cytotoxic chemotherapy for malignancy (except for chronic myeloleukosis and myelodysplastic syndromes) as well as reduction of neutropenia duration in patients receiving myeloablative therapy followed by bone marrow transplantation, which is considered to be an increased risk factor for long-term severe neutropenia. The efficacy and safety of filgrastim are comparable in cytotoxic chemotherapy in children and adults;

Mobilization of peripheral stem cells (PSCs), including after myelosuppressive therapy, as well as mobilization of peripheral stem cells from healthy donors (allogeneic PSCC);

hereditary recurrent or idiopathic neutropenia in adults and children (with an absolute neutrophil count of 0.5-10⁹/L or less), with a history of severe recurrent infections, long-term treatment with filgrastim is indicated to increase neutrophil counts and to reduce the frequency and duration of adverse effects associated with infectious complications;

Prevention of bacterial infections and treatment of persistent neutropenia (absolute neutrophil count of 1-10⁹/L or less) in patients with advanced HIV infection when other treatments have failed.

Active ingredient

Filgrastim

Composition

Interaction

The safety and efficacy of Zarzio administration on the same day as myelosuppressive cytotoxic chemotherapy have not been established. Because of the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, administration of Zarsio 24 hours before or after the administration of these drugs is not recommended.

In concomitant administration of Zarsio and fluorouracil, the severity of neutropenia may increase. Possible interaction with other hematopoietic growth factors and cytokines is unknown. Given that lithium stimulates neutrophil release, it is possible that the effects of Zarcio may be enhanced when combined, but such studies have not been conducted.

We should not mix Zarsio with 0.9% sodium chloride solution because of pharmacological incompatibilities.

Directions for use

Intravenously, by injection.

The therapy with Zarsio can be performed in collaboration with oncology center physicians who have experience with G-CSF and also experience treating patients with hematologic diseases at a facility with the necessary diagnostic equipment.

The mobilization and apheresis procedures must be performed in collaboration with specialists from the Oncology-Hematology Center who have adequate experience in this area and the ability to monitor hematopoietic progenitor cells as needed.

The drug Zarsio is available in the following dosages: 30 million IU/0.5 ml (0.3 mg) and 48 million IU/0.5 ml (0.48 mg).

Cytotoxic chemotherapy. The recommended daily dose of Zarsio is 0.5 million IU/kg (0.005 mg/kg).

The first dose of the drug should not be administered earlier than 24 hours after a course of cytotoxic chemotherapy.

The drug Zarsio is administered daily until the total neutrophil count in the clinical blood count exceeds the expected nadir and reaches normal values. After chemotherapy for solid tumors, lymphoma, and lymph leukemia, the duration of treatment is up to 14 days until these values are reached. After induction and consolidation therapy for acute myeloid leukemia the treatment period may be significantly longer (up to 38 days) and be determined depending on the type, dose and scheme of cytotoxic chemotherapy used.

In patients receiving cytotoxic chemotherapy, a transient increase in neutrophil counts is usually observed 1-2 days after the start of treatment with Zarcio. Nevertheless, in order to achieve a stable therapeutic effect, it is necessary to continue Zarzio therapy until neutrophil counts exceed the expected nadir and reach normal values. Premature termination of treatment with the drug before the neutrophil count has crossed the nadir is not recommended.

Patients receiving myeloablative therapy followed by a bone marrow transplant The recommended starting dose of Zarsio is 1 million IU/kg (0.010 mg)/day.

The first dose of Zarsio should be given no earlier than 24 hours after cytotoxic chemotherapy and no later than 24 hours after bone marrow transplantation.

Dose adjustment. After a maximum decrease in neutrophil count (nadir), the daily dose of Zarcio should be adjusted according to the change in neutrophil count as follows.

The dose of Zarzio should be adjusted in response to reaching nadir. If ACH>1-10⁹/l for 3 consecutive days, the dose should be reduced to 0.5 million units/kg/day (0.005 mg/kg/day); if ACH>1-10⁹/l for 3 consecutive days, the drug should be withdrawn. If, during treatment, the AFR decreases to <1-10⁹/l, the dose of Zarcio is increased again according to the above scheme.

PSCC mobilization. Patients receiving myelosuppressive or myeloablative therapy followed by autologous HSCC transplantation. For HSCC mobilization when using Zarsio as monotherapy the recommended dose is 1 million units/kg (0.010 mg/kg)/day during 5-7 consecutive days. There are 1-2 sessions of leukapheresis on days 5 and 6. In some cases, 1 additional session of leukapheresis is carried out. The dose of Zarcio drug should not be changed before the final leukapheresis.

To mobilize PSCC after myelosuppressive chemotherapy, the recommended dose of Zarcio is 0.5 million IU/kg (0.005 mg/kg)/day daily, starting on the first day after completion of chemotherapy and until neutrophil counts have passed the expected nadir and have reached normal. Leukapheresis should be performed during the period of increasing ACH from <0.5-10⁹/l to >5-10⁹/l. Patients who have not received intensive chemotherapy receive 1 session of leukapheresis. Additional leukapheresis sessions are recommended in individual cases.

Healthy donors before allogeneic HSCC transplantation. For HSCT mobilization before allogeneic HSCT transplantation in healthy donors the recommended dose of Zarcio is 1 million units/kg (0.010 mg/kg)/day by p/day for 4-5 consecutive days. Leukapheresis is performed from day 5 and, if necessary, continues until day 6 in order to obtain 4-10⁶ CD34+ cells/kg.

Severe chronic neutropenia (TCN). The recommended starting dose is 1.2 million IU/kg (0.012 mg/kg)/day once or in fractional doses.

Idiopathic and recurrent neutropenia. The recommended starting dose is 0.5 million IU/kg (0.005 mg/kg)/day in a single or divided dose.

Pick up the dose of the drug. Zarsio is administered daily until the neutrophil count reaches and stably exceeds 1.5-10%. After therapeutic effect is achieved, the minimum effective dose to maintain this level is determined. To maintain the required neutrophil count, prolonged daily administration of the drug is required. After 1-2 weeks of treatment, the initial dose may be doubled or halved depending on the therapy efficiency. Subsequently, every 1-2 weeks an individual dose adjustment is carried out to maintain an average neutrophil count in a range of 1.5-10⁹/l to 10-10⁹/l. In patients with severe infections, a regimen with more rapid dose increases can be used. In 97% of patients who responded positively to treatment, full therapeutic effect is observed when doses up to 24 mcg/kg/day are administered. The daily dose of Zarsio should not exceed 24 mcg/kg/day.

HIV infection

Reconstitution of neutrophil counts. The recommended initial dose of Zarcio is 0.1 million units/kg (0.001 mg/kg)/day with increasing the dose to a maximum of 0.4 million units/kg (0.004 mg/kg) until neutrophil count normalization (ACH >2-10⁹/l). Normalization of neutrophil counts usually occurs after 2 days. In rare cases (<10% of patients) for restoration of neutrophil count the drug dose can be increased up to 1 million units/kg (0.010 mg/kg)/day.

The maintenance of normal neutrophil counts. After achieving therapeutic effect, the maintenance dose is 0.3 mg/day 2-3 times a week on an alternating schedule (every other day). Subsequently, individual dose adjustment and long-term administration of the drug may be required to maintain an average neutrophil count >2-10⁹/l.

Particular categories of patients

Patients with impaired renal/liver function. Dose adjustment is not required in patients with severe renal or hepatic impairment because their pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.

Children with TCH and malignancies. When used in pediatric patients with TCN and cancer, the safety profile of Zarsio did not differ from that of adults. Dosing recommendations for pediatric patients are the same as for adults receiving myelosuppressive cytotoxic chemotherapy.

Elderly patients. Because of the limited number of elderly patients in clinical trials, there are no specific recommendations for the use of Zarsio in elderly patients. No additional studies have been performed in this category of patients.

Means of administration

Cytotoxic chemotherapy. Zarsio is given as a pelvic injection or intravenous infusion for 30 minutes once a day. Additional information on dilution in 5% (50 mg/ml) dextrose solution for IV administration is provided under “Special Precautions”. In most cases, the p/k route of administration is preferable. The duration of effect may be shortened if a single dose is administered by injection. The clinical significance of these data with regard to the use of multiple doses of the drug has not been established. The choice of route of administration depends on the characteristics of the individual clinical situation and is determined for each patient individually.

Patients receiving myeloablative therapy followed by bone marrow transplant: Zarsio is diluted in 20 ml of 5% (50 mg/ml) dextrose solution and given as a short intravenous infusion over 30 minutes or as a long term p/v or intravenous infusion over 24 hours. For additional instructions on dilution of the drug in 5% (50 mg/ml) dextrose solution for IV infusion, see section “Special Precautions”.

PVC mobilization

PVC administration. For mobilization of HSCT in patients undergoing myelosuppressive or myeloablative therapy followed by autologous HSCT transplantation, Zarcio may also be administered as a prolonged p/c infusion for 24 hours. Before infusion, the drug is diluted in 20 ml of 5% (50 mg/ml) dextrose solution. For additional instructions on dilution of the drug in 5% (50 mg/ml) dextrose solution for infusion, see section “Special notes”.

TCHN/HIV infection

Introduction by injection. The initial dose is 0.1-0.4 million IU (0.001-0.004 mg/kg) once, until neutrophil count normalizes (usually within 2 days). After therapeutic effect is achieved, the maintenance dose is 30 million IU (0.3 mg)/day every other day. Further individual dose adjustment and long-term therapy with Zarzio may be required to maintain neutrophil count >2-10⁹/l.

Special Instructions

Treatment with Zarcio should only be performed under the supervision of an oncologist or hematologist experienced in the use of G-CSF, with the necessary diagnostic capabilities. Cell mobilization and apheresis procedures should be performed in an oncology or hematology center with experience in this field and the ability to adequately monitor hematopoietic progenitor cells.

Cytotoxic chemotherapy

The growth of malignant cells. Because G-CSF can stimulate growth of myeloid cells in vitro, it is advisable to consider the following information:

The safety and efficacy of Zarcio in patients with myelodysplastic syndrome (MDS) and chronic myeloleukemia have not been established. Therefore, the use of Zarsio is not indicated in these diseases. Particular care is needed in the differential diagnosis between blast-transforming chronic myeloleukemia and acute myeloleukemia;

As data about the safety and efficacy of Zarsio in patients with secondary acute myelocytic leukemia (ALL) are limited, Zarsio should be used with caution.

The safety and efficacy of Zarcio, first prescribed in patients with OSL under 55 years of age without pathogenetic abnormalities [t(8; 21), t(15; 17), and inv(16)], have not been established.

Leukocytosis. Blood leukocyte counts reached or exceeded 100-10⁹/L in less than 5% of patients who received a daily dose of Zarcio greater than 0.3 million units/kg (0.0003 mg/kg). There are no reports of any adverse effects directly attributable to the development of leukocytosis of this severity. However, given the possible risks associated with severe leukocytosis, the leukocyte count should be monitored regularly during treatment with Zarsio. If the leukocyte count exceeds 50-10⁹/L after reaching the expected nadir, the drug should be stopped immediately. If Zarsio is used to mobilize PSCC, the drug should be discontinued or the dose reduced when the white blood cell count increases to >70-10⁹/L.

The risk associated with increasing the dose of ongoing chemotherapy. Particular caution should be exercised when treating patients with malignant tumors who receive high doses of chemotherapy drugs, because a significant additional effect of high doses on disease outcome has not been confirmed, but there is a high possibility of more pronounced toxic effects on the CPS, respiratory system, nervous system and skin (see instructions for medical use of chemotherapy drugs used).

Monotherapy with Zarsio does not prevent thrombocytopenia and anemia associated with myelosuppressive chemotherapy. If higher doses of chemotherapy (e.g., full doses according to prescribed regimens) are used, the risk of severe thrombocytopenia and anemia increases. Regular monitoring of clinical blood counts such as hematocrit and platelet counts is recommended. Particular caution should be exercised when using single-component or combined chemotherapeutic agents that may cause severe thrombocytopenia.

The severity and duration of thrombocytopenia due to myelosuppressive or myeloablative chemotherapy has been shown to decrease when Zarsio is used to mobilize PSCC.

Other precautions. The efficacy of Zarsio in patients with significantly reduced myeloid progenitor cell counts has not been studied. Zarsio increases neutrophil counts by acting primarily on neutrophil progenitor cells. Therefore, patients with decreased numbers of progenitor cells (e.g., as a result of intensive radiation or chemotherapy treatment or bone marrow infiltration by tumor cells) may have lower numbers of neutrophils produced.

There is evidence of graft vs. host reaction (Graft vs. Host) and death in patients treated with G-CSF after allogeneic bone marrow transplantation.

PSCC mobilization

Pre-treatment with cytotoxic agents. Patients who have previously received intensive myelosuppressive therapy may not have an increase in the number of PSCCs sufficient to the recommended minimum level (>2-10⁶CD34+ cells/kg) or an increase in platelet recovery rate when Zarcio is used to mobilize PSCCs.

Some cytotoxic agents are particularly toxic to hematopoietic progenitor cells and may have adverse effects on their mobilization. Prolonged use of drugs such as melphalan, carboplatin or carmustine before progenitor cell mobilization can lead to poorer results. However, simultaneous use of melphalan, carboplatin or carmustine with filgrastim is effective in mobilizing PSCC.

If PSCC transplantation is planned, it is recommended to perform stem cell mobilization early in the patient’s treatment. Particular attention should be paid to the number of progenitor cells activated in such patients prior to the use of high-dose chemotherapy drugs. If the results of mobilization according to the above criteria are insufficient, alternative therapies that do not require the use of progenitor cells should be considered.

The evaluation of the number of PSCCs. When assessing the number of PSCs mobilized in patients against the background of Zarzio drug, special attention should be paid to the method of quantification. The results of flow cytometric analysis for CD34+ cell counts vary depending on the method chosen, and therefore results obtained in different laboratories should be interpreted with caution.

Statistical analysis has shown that there is a complex but consistent relationship between the number of CD34+ cells injected in reinfusion and the rate of platelet count recovery after high-dose chemotherapy drugs. A minimum number(>2-10⁶ CD34+ cells/kg) results in sufficient recovery of hematological parameters and is recommended based on published data. A CD34+ cell count exceeding this value is accompanied by a more rapid normalization; if the cell count does not reach this level, the recovery of blood parameters is slower.

Healthy donors before allogeneic PSCC transplantation. PSCC mobilization has no immediate clinical outcome for healthy donors and can be performed solely for the purpose of allogeneic stem cell transplantation.

PSCC mobilization can only be administered to donors who meet standard clinical and laboratory criteria for stem cell donation, with special attention to hematological parameters and the presence of infectious diseases.

The safety and efficacy of Zarcio in healthy donors under the age of 16 years and over 60 years has not been studied.

Transient thrombocytopenia (platelet count < 100-10⁹/l) after administration of Zarcio and leukapheresis was observed in 35% of donors. Among them, 2 cases of thrombocytopenia with platelet count < 50-10⁹/l after leukapheresis were observed. If more than one session of leukapheresis is required, donors with platelet counts less than 100-10⁹/L should be particularly closely monitored; as a rule, apheresis is not recommended for neutrophil counts below 75-10⁹/L.

Leukapheresis should not be performed on donors who are taking anticoagulants or who have hemostasis disorders.

The dose of Zarsio should be withdrawn or reduced if the white blood cell count increases >70-10⁹/l.

In donors receiving G-CSF for PSCC mobilization, all clinical blood counts should be monitored regularly until they normalize.

In healthy donors treated with G-CSF, transient cytogenetic changes have been reported. The significance of these manifestations is unknown.

The safety of Zarsio in healthy donors is still being monitored. At this time, the risk of malignant myeloid clone development in donors cannot be excluded. Medical centers performing apheresis procedures are advised to systematically monitor stem cell donors for a minimum of 10 years to monitor the safety of Zarcio in the long-term.

There are reports of frequent, mostly asymptomatic cases of splenomegaly, as well as very rare cases of spleen rupture in healthy donors and patients receiving G-CSF. Some cases of spleen rupture have been fatal. Therefore, the size of the spleen should be carefully monitored (clinical examination and ultrasound). The risk of spleen rupture in donors and/or patients with upper left abdominal or upper arm pain should be considered.

In the post-marketing period, very rare cases of adverse respiratory effects (hemoptysis, pulmonary hemorrhage, pulmonary infiltrative changes, dyspnea and hypoxia) have been reported in healthy donors. If the presence of the above symptoms is suspected, the appropriateness of further use of the drug and the need for appropriate treatment should be considered.

Recipients of allogeneic PSCC derived from Zarcio-stimulated mobilization

The immunologic interaction of allogeneic PSCC grafts has been reported to be associated with a higher risk of acute and chronic RCT when compared to bone marrow transplantation.

TXN

The number of blood cells. Platelet counts should be strictly monitored, especially during the first weeks of therapy with the drug. If a patient is found to have thrombocytopenia and the platelet count is less than 100000/mm³ over a long period of time, consideration should be given to short-term withdrawal of Zarsio or reduction of its dose.

There may be other changes in blood counts that require close monitoring, including anemia and a transient increase in myeloid progenitor cells.

The development of acute leukemia or MDS. Timely diagnosis of TCH and differentiation from other hematopoietic disorders, such as aplastic anemia, MDS and myeloleukemia, should be made. Prior to treatment, a complete clinical work-up with determination of the white blood cell count and platelet count, bone marrow morphology and karyotype should be performed.

In clinical studies, a small number (approximately 3%) of patients with TCH who received filgrastim have seen MDS or leukemia. These results were only observed in patients with congenital neutropenia. MDS and leukemia are the most frequent complications of TCH, and their association with filgrastim therapy has not been determined. Approximately 12% of patients with initially unchanged cytogenetic parameters were found to have changes, including monosomia in the 7th chromosome pair, when re-examined. If a patient with TCH exhibits cytogenetic abnormalities, the risk-benefit ratio of continuing Zarsio therapy should be carefully evaluated; the drug should be discontinued if MDS or leukemia develops. It is currently unclear whether long-term use of Zarsio induces cytogenetic abnormalities, MDS, or leukemia in patients with TCN. It is recommended that morphologic and cytogenetic studies of the bone marrow be performed regularly (approximately every 12 months).

Other precautions. Causes of transient neutropenia such as viral infections must be excluded.

Enlargement of the spleen is a probable effect associated with treatment with Zarcio. During clinical studies, 31% of patients showed splenomegaly on palpation. On radiography, an increase in spleen size was detected soon after the start of filgrastim treatment and tended to stabilize. It has been noted that decreasing the dose of Zarcio slows or stops the increase in spleen size; splenectomy may be necessary in 3% of patients. Spleen size should be monitored regularly by clinical examination.

A small number of patients have had hematuria/proteinuria. To exclude these manifestations, regular monitoring of general urinalysis should be performed. The safety and efficacy of the drug in neonates and patients with autoimmune neutropenia have not been established.

HIV infection

The number of blood cells. The AFN should be monitored closely, especially during the first weeks of therapy with Zarcio. Some patients may experience a very rapid and significant increase in BUN at the initial dose of Zarcio. During the first 2-3 days of using the drug, it is recommended to measure ACH daily. Subsequently, the ACH should be checked at least twice a week during the first 2 weeks and then every week or every other week during the whole course of maintenance therapy. If Zarcio is interrupted at a dose of 30 million IU/day (0.3 mg/day), the patient may experience significant fluctuations in the ACN during treatment. In order to determine the minimum ACN (nadir), it is recommended to monitor the total blood count before each administration of Zarzio.

The risk due to the use of high doses of myelosuppressive drugs. Zarsio monotherapy is not indicated to prevent thrombocytopenia and anemia with myelosuppressive drugs. In case of using higher doses or simultaneously several myelosuppressive drugs in combination with Zarxio therapy, the risk of thrombocytopenia and anemia increases. Regular monitoring of gross blood counts is recommended.

The development of myelosuppression due to infections or tumor growths. Neutropenia may be due to bone marrow lesions in opportunistic infections caused by pathogens such as Mycobacterium avium complex or by malignant neoplasms such as lymphoma. If infiltrative bone marrow lesions of inflammatory origin or malignant neoplasms are detected, simultaneously with the use of Zarsio for treatment of neutropenia, the appropriate therapy of the diagnosed diseases must be prescribed. The efficacy of Zarsio use in treatment of neutropenia caused by bone marrow lesions of infectious origin or tumor neoplasms has not been established.

Other precautions. There have been reports of rare cases of adverse effects on the respiratory organs, particularly the development of interstitial pneumonia with G-CSF. Patients who have recently had infiltrative lung disease or pneumonia may be at high risk. The appearance of symptoms such as cough, fever and dyspnea, combined with the detected infiltrative lung lesion on radiological examination and signs of progressive respiratory failure, suggest the presence of adult respiratory distress syndrome (ARDS). If RDSD is detected, Zarsio should be discontinued and appropriate treatment administered.

Patients with concomitant bone disease and osteoporosis during long-term (more than 6 months) use of Zarsio are recommended to have regular monitoring of bone density.

In patients with sickle cell disease there have been cases of acute hemolytic crisis (increased number of altered cells), sometimes with fatal outcome. Patients with sickle cell disease should prescribe Zarsio with caution.

Bone tissue radiography revealed an increase in bone marrow hematopoietic activity in response to growth factor therapy. These data should be considered when analyzing the results of bone radiography.

Pre-application Advice

Pre-application of the drug requires visual inspection of the contents in the pre-filled syringe. The solution should be clear with no visible particles. The product contains no preservatives. To avoid microbial contamination, please note that Zarsio in a pre-filled syringe is for single use only.

Recommendations for dilution

Zarcio may be administered diluted in 5% (50 mg/ml) dextrose solution. Dilution is carried out immediately prior to administration, but dilution to a concentration of less than 0.2 million units/ml (0.002 mg/ml) is not recommended. When diluting to a concentration of 1.5 million units/ml (0.015 mg/ml), additional human albumin should be added to reach a concentration of 2 mg/ml. For example, to reach a solution volume of 20 ml and a total dose of Zarcio of 30 million units (0.3 mg), additional addition of albumin solution of 200 mg/ml (20% solution) is required.

When diluted in dextrose solution, the drug is not absorbed by glass and other materials used for infusion.

Do not use sodium chloride solution to dilute Zarsio!

The drug can be stored at a temperature not exceeding 25 °C for 72 hours during its shelf life.

After dilution, use within 24 hours.

Impact on the ability to drive vehicles and machinery. There have been no known cases of adverse effects of the drug Zarsio on the speed of psychomotor reactions; no effect of the drug on the ability to drive vehicles and operate machinery has been established.

Contraindications

Her history of hypersensitivity to the drug or its components;

a history of hypersensitivity to albumin and blood components when albumin is added to intravenous infusion solutions;

hereditary intolerance to fructose (contains sorbitol);

severe hereditary neutropenia (Kostmann syndrome) with cytogenetic abnormalities and autoimmune neutropenia;

use to increase doses of cytotoxic chemotherapy drugs above the recommended doses;

concurrent radiation or chemotherapy;

terminal stage of chronic renal failure (CKF);

the period of newborn.

With caution: Myelodysplastic syndrome; chronic myeloleukemia; secondary acute myeloblastic leukemia (patients under age 55, without cytogenetic abnormalities); Excess nadir (white blood cell count >50-10⁹/L, for PSCC mobilization, >70-10⁹/L); patients who receive high doses of chemotherapy drugs for malignancies (risk of increased toxic effects); simultaneous use of single-component or combined chemotherapy drugs (risk of severe thrombocytopenia and anemia); patients with significantly reduced myeloid progenitor cell count (less than 2-10⁶ CD34+ cells/kg – use not well studied); thrombocytopenia (platelet count in blood tests is less than 100000/mm³); splenomegaly (risk of spleen rupture) infiltrative lung disease (risk of development/progression of infiltrative pneumonia); sickle cell disease, neutropenia due to bone marrow lesions of infectious genesis or tumor neoplasms (lymphoma) (effectiveness of monotherapy is not established).

Side effects

The side effects shown below are categorized according to organ and system classification and frequency of occurrence: Very common (≥1/10); common (≥1/100 to < 1/10); infrequent (≥1/1000 to < 1/100); rare (≥1/10000 to < 1/1000); very rare (< 1/10000), frequency unknown (cannot be estimated based on available data).

Immune system disorders: very rare (in patients) and infrequent (in donors before PSCC mobilization) – hypersensitivity reactions, including anaphylactic reactions, skin rash, urticaria, angioedema, dyspnea and decreased BP.

Hematopoietic organs: Very common – anemia, splenomegaly (progressive in some cases), in donors before PSCC mobilization – leukocytosis (>50-10⁹/l) and transient thrombocytopenia (<100-10⁹/l) as a consequence of the pharmacological action of filgrastim; frequently, thrombocytopenia, splenomegaly (asymptomatic, in donors and patients); infrequently, disorders of spleen function; very rarely, rupture of the spleen.

Nervous system disorders: very common – headache.

System disorders: infrequent – transient decrease of BP; rare – vascular disorders, including veno-occlusive disease and increase of circulatory blood volume.

Respiratory system disorders: very common – nasal bleeding; very rare – pulmonary edema, interstitial pneumonia, lung infiltrates; in donors – hemoptysis, pulmonary bleeding, dyspnea, hypoxemia.

The skin and its appendages: often – vasculitis (with long-term use), alopecia, rash; very rare – Sweet’s syndrome (acute febrile dermatosis, relationship with taking filgrastim is not established).

Muscular system disorders: very common – pain in bones, joints and muscles (mild to moderate, in donors – transient); common – pain in bones, joints and muscles (severe), osteoporosis, arthralgia; infrequent (in donors) and very rare (in patients) – exacerbation of rheumatoid arthritis.

Digestive system disorders: frequently – diarrhea, hepatomegaly.

Urogenital system: infrequent – hematuria, proteinuria; very rare – dysuria.

Laboratory parameters: very common (in patients) and common (in donors) – reversible, dose-dependent, weak or moderate increase of ALP activity, LDH, in patients – glutamyltransferase, hyperuricemia, decrease of blood glucose concentration (moderate, reversible); uncommon in donors – reversible, weak increase of AST and uric acid activity.

Others: often – pain at the injection site, increased fatigue, reactions at the injection site (less than 2% of patients with TCH.

Overdose

Symptoms of filgrastim overdose have not been established.