Zarsio solution 48ml/0.5ml syringe, 5pcs

Composition

Active ingredient: filgrastim 48 million Units (0.480 mg); Excipients: glutamic acid 0.736 mg, sorbitol 25,000 mg, polysorbate-80 0.020 mg, sodium hydroxide q. s. up to pH, water for injection up to 0.5 ml

Pharmacological action

Filgrastim is a highly purified non-glycosylated protein consisting of 175 amino acids, or recombinant human granulocyte colony stimulating factor (r-h G-CSF). It is produced by the K12 strain of Escherichia coli, which has been genetically engineered to contain the human granulocyte colony stimulating factor (G-CSF) gene.

Human G-CSF regulates the production and release of neutrophils from the bone marrow into the peripheral blood. The use of filgrastim 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, there is also an increase in the number of eosinophils and basophils, but in some patients, eosinophilia and basophilia may be present before the start of treatment. The increase in the number of neutrophils when using filgrastim in the recommended dose range is dose-dependent. Released neutrophils have normal or increased functional activity, which is confirmed by chemotaxis and phagocytosis tests.

At the end of therapy, the number of neutrophils in the peripheral blood decreases by 50% within 1-2 days and returns to normal values within the next 1-7 days. Just like other factors that stimulate hematopoiesis, in vitro studies have shown that G-CSF has the ability to stimulate endothelial cells, since 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 the transport of neutrophils 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 in lower doses compared to patients receiving only cytotoxic chemotherapy.

Reduces the need and duration of inpatient treatment in patients after induction chemotherapy for myeloid leukemia or myeloablative therapy followed by bone marrow transplantation. The incidence of elevated body temperature did not decrease in patients after myeloablative therapy followed by bone marrow transplantation.

The use of Zarsio both in monotherapy and after chemotherapy mobilizes the release of hematopoietic stem cells into the peripheral bloodstream. Autologous or allogeneic peripheral blood stem cell transplantation (PSCC) is performed after therapy with high doses of cytostatics, either instead of bone marrow transplantation, or in addition to it.

PSCC transplantation can also be prescribed after (high-dose) myelosuppressive cytotoxic therapy. The use of PSCs mobilized with Zarsio accelerates the restoration of hematopoiesis, reduces the severity and duration of thrombocytopenia, reduces the risk of hemorrhagic complications and the need for platelet transfusion after myelosuppressive or myeloablative therapy.

The use of Zarsio in children and adults with severe congenital neutropenia (periodic, idiopathic) stimulates a steady increase in the number of active neutrophils in the peripheral blood and a decrease in the frequency of infectious and other complications.

The use of Zarsio in patients with HIV infection keeps the number of neutrophils within normal values, which allows you to observe the necessary dosage regimen of antiretroviral drugs and myelosuppressive therapy. There were no signs of increased HIV replication with Zarsio.

Indications

-reduction of the duration of neutropenia and frequency of febrile neutropenia in patients receiving cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes), as well as reduction of the duration of neutropenia in patients receiving myeloablative therapy followed by bone marrow transplantation, which is considered an increased risk factor for long-term severe neutropenia.

The efficacy and safety of filgrastim comparable when carrying out cytotoxic chemotherapy in children and adults;

— mobilization of peripheral blood stem cells (PSCC), including after myelosuppressive therapy, and mobilization of peripheral stem cells from a healthy donor (allogeneic TUAC);

— periodic hereditary or idiopathic neutropenia in adults and children with an absolute neutrophil count of 0.5 × 109/l or less, indicating a history of severe recurrent infections, long-term treatment with filgrastim shown to increase the number of neutrophils and reduce the frequency and duration of adverse effects associated with infectious complications;

— prevention of bacterial infections and treatment of persistent neutropenia (absolute neutrophil count is equal to 1 × 109/l or less) in patients with extensive-stage HIV infection after failure of other treatments.

Recommendations for use

Before using the drug, a visual inspection of the contents in a pre-filled syringe is carried out. The solution should be clear, without visible particles. The product does not contain preservatives. To avoid microbial contamination, it should be noted that the drug Zarsio in a pre-filled syringe is intended for single use only.

Recommendations for dilution of the drug

The drug Zarsio can be administered in a diluted form in a 5% (50 mg/ml) dextrose solution. Dilution of the drug is carried out immediately before use, but it is diluted to a concentration of less than 0.2 million mg. U / ml (0.002 mg / ml) not recommended.

When diluted at a concentration of 1.5 million mg. U / ml (0.015 mg / ml) additional human albumin should be added until a concentration of 2 mg/ml is reached. For example, to achieve a solution volume of 20 ml and a total dose of Zarsio 30 million mg. U (0.300 mg), an additional addition of an albumin solution in the volume 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.

It is forbidden to use a solution of sodium chloride to dilute the drug Zarsio!

Once during the shelf life, the drug can be stored at a temperature of no more than 25°C for 72 hours.

After dilution, use for 24 hours.

Contraindications

— hereditary fructose intolerance (contains sorbitol);

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

the drug should not be used with the aim of increasing doses of cytotoxic chemotherapeutic drugs higher than recommended;

— simultaneous radiotherapy or chemotherapy;

— end-stage chronic renal failure (CRF);

— the neonatal period.

— hypersensitivity to the drug or its components in the anamnesis—

– hypersensitivity to albumin and blood components in the anamnesis in cases of adding albumin to solutions for intravenous infusions.

With caution

Myelodysplastic syndrome, chronic myeloid leukemia, secondary acute myeloblastic leukemia (in patients under 55 years of age, without cytogenetic abnormalities), nadir excess (the number of white blood cells in the blood test >50 × 109/l, for PSC mobilization – >>70 × 109/L), in patients who receive high doses of chemotherapy drugs for malignant neoplasms (risk of increased toxic effects), simultaneous use of single-component or combined chemotherapy drugs (risk of severe thrombocytopenia and anemia), in patients with a significantly reduced number of myeloid progenitor cells (less than 2 × 106 CD34+ cells/kg – use is not well understood), thrombocytopenia (with a platelet count in the blood test of less than 100,000/mm3), splenomegaly (risk of rupture of the spleen), infiltrative lung damage (risk of development/progression of infiltrative pneumonia), sickle cell disease, neutropenia, due to bone marrow damage of infectious origin or tumor neoplasms (lymphoma) (the effectiveness of monotherapy has not been established).

Side effects

The following side effects are distributed according to the classification of organs and systems and frequency of occurrence: very common (≥1/10); common (≥1/100 – <1/10); uncommon (≥1/1000 – <1/100); rare (≥1/10 000 – <1/1000); very rare (

From the immune system:  hypersensitivity reactions, including anaphylactic reactions, skin rash, urticaria, angioedema, shortness of breath, and a decrease in blood pressure, are very rare (in patients) and infrequently (in donors before PSCC mobilization).

From the side of hematopoietic organs:  very often – anemia, splenomegaly (progressive in some cases), in donors before PSCC mobilization-leukocytosis (> 50 × 109/L) and transient thrombocytopenia (>

Nervous system disorders:  very often – a headache.

From the cardiovascular system:  infrequently-a transient decrease in blood pressure; rarely-vascular disorders, including:veno-occlusive disease and increased BCC.

Respiratory system disorders: very often – nosebleeds; very rarely-pulmonary edema, interstitial pneumonia, infiltrates in the lungs; donors-hemoptysis, pulmonary bleeding, shortness of breath, hypoxemia.

From the side of the skin and its appendages: often – vasculitis (with prolonged use), alopecia, rash; very rarely-Sweet’s syndrome (acute febrile dermatosis, the relationship with filgrastim intake has not been established).

Musculoskeletal disorders: very often – pain in bones, joints and muscles (mild or moderate, in donors-transient); often – pain in bones, joints and muscles (severe), osteoporosis, arthralgia; infrequently in donors and very rarely in patients-exacerbation of rheumatoid arthritis.

From the digestive system: often – diarrhea, hepatomegaly.

From the genitourinary system: infrequently-hematuria, proteinuria; very rarely-dysuria.

From the side of laboratory parameters: very often in patients and often in donors – reversible, dose-dependent, weak or moderate increase in the activity of ALP, LDH, in patients-GGT, hyperuricemia, a decrease in the concentration of glucose in the blood (moderate, reversible); infrequently in donors – reversible, weak increase in the activity of AST and uric acid.

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

Interaction

The safety and efficacy of Zarsio use on the same day as myelosuppressive cytotoxic chemotherapy drugs have not been established. Due to the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, it is not recommended to prescribe Zarsio at an interval of 24 hours before or after the use of these drugs.

When Zarsio and fluorouracil are co-administered, the severity of neutropenia may increase.

Possible interactions with other hematopoietic growth factors and cytokines are unknown.

Given that lithium stimulates the release of neutrophils, it is possible to increase the effect of Zarsio with combined use, but such studies have not been conducted.

Due to pharmaceutical incompatibilities, Zarsio should not be mixed with 0.9% sodium chloride solution.

How to take, course of use and dosage

Therapy with Zarsio can be carried out in cooperation with doctors of the cancer center who have experience in using a drug containing granulocyte colony-stimulating factor (G-CSF), as well as experience in treating patients with hematological diseases, in a medical institution where the necessary diagnostic equipment is available.

Mobilization and apheresis procedures should be carried out in cooperation with specialists of the Center of oncology-hematology who have the appropriate experience in this field and the ability to monitor hematopoiesis progenitor cells as necessary.

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

Cytotoxic chemotherapy

The recommended daily dose of Zarsio is 0.5 million mg. U/kg (0.005 mg / kg) of body weight.

The first dose of the drug should be administered no earlier than 24 hours after the course of cytotoxic chemotherapy.

Zarsio is administered daily until the total number of neutrophils in a clinical blood test exceeds the expected nadir and reaches normal values.

After chemotherapy for solid tumors, lymphomas and lymphocytic leukemia, the duration of treatment until these values are reached is up to 14 days. After induction and consolidation therapy of acute myeloid leukemia, the duration of treatment can be significantly increased (up to 38 days) and is determined depending on the type, dose and scheme of cytotoxic chemotherapy used.

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 Zarsio. However, to achieve a stable therapeutic effect, it is necessary to continue therapy with Zarsio until the neutrophil count exceeds the expected nadir and reaches normal values. It is not recommended to prematurely cancel treatment with the drug before the number of neutrophils passes the nadir.

Patients receiving myeloablative therapy followed by bone marrow transplantation: the recommended initial dose of Zarsio is 1 million mg. U /kg (0.01 mg) of body weight/day.

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

Dose adjustment: after the maximum reduction in the number of neutrophils (nadir), the daily dose of Zarsio should be adjusted depending on the change in the number of neutrophils as follows.

Table 1. Selection of the dose of Zarsio in response to nadir achievement

Mobilisation of peripheral blood stem cells (PSCs)

Patients receiving myelosuppressive or myeloablative therapy followed by autologous PSCC transplantation

For the mobilization of PSCs when using Zarsio as monotherapy, the recommended dose is 1 million mg. U/kg (0.01 mg/kg) of body weight/day for 5-7 consecutive days. Conduct 1-2 sessions of leukapheresis on the 5th and 6th days. In some cases, an additional 1 session of leukapheresis is performed. Do not change the dose of Zarsio before the end of leukapheresis.

The recommended dose of Zarsio is 0.5 million mg for the mobilization of PSCs after myelosuppressive chemotherapy. U/kg (0.005 mg / kg) of body weight per day daily, starting from the first day after the end of chemotherapy and until the number of neutrophils passes the expected nadir and reaches normal.

Leukapheresis should be performed during the period of increasing APN from <0.5 ×109/L to >5 × 109/l. Patients who have not received intensive chemotherapy are given 1 session of leukapheresis. In some cases, it is recommended to conduct additional sessions of leukapheresis.

Healthy donors before allogeneic PSCC transplantation

To mobilize PSCs before allogeneic PSCs transplantation in healthy donors, the recommended dose of Zarsio is 1 million mg. U/kg (0.01 mg / kg) of body weight per day subcutaneously for 4-5 consecutive days. Leukapheresis is performed from the 5th day and, if necessary, continued until the 6th day in order to obtain 4 × 106 CD34+ cells/kg of body weight of the recipient.

Severe chronic neutropenia (TCN)

Congenital neutropenia

The recommended starting dose is 1.2 million mg. U/kg (0.012 mg / kg) of body weight/day in single or fractional doses.

Idiopathic and recurrent neutropenia

The recommended starting dose is 0.5 million mg. U/kg (0.005 mg / kg) of body weight/day in single or fractional doses.

Selection of the drug dose

The drug Zarsio is administered daily until the neutrophil count indicator 1.5 × 109 is reached and consistently exceeded. After the therapeutic effect is achieved, the minimum effective dose is determined to maintain this level. Long-term daily use of the drug is required to maintain the required number of neutrophils.

After 1-2 weeks of treatment, the initial dose can be doubled or halved, depending on the effectiveness of therapy. Subsequently, an individual dose adjustment is made every 1-2 weeks to maintain the average neutrophil count in the range from 1.5 x 109 to 10 x 109. In patients with severe infections, a scheme with a faster dose increase can be used.

In 97% of patients who responded positively to treatment, a complete therapeutic effect is observed when doses up to 24 micrograms/kg/day are prescribed. The daily dose of Zarsio should not exceed 24 mcg/kg.

HIV infection

Neutrophil count recovery

The recommended initial dose of Zarsio is 0.1 million mg. U/kg (0.001 mg/kg) of body weight / day with an increase in the dose to a maximum of 0.4 million mg / kg. U/kg (0.004 mg / kg) of body weight before normalization of the neutrophil count (APN > 2 × 109). Normalization of the neutrophil count usually occurs after 2 days. In rare cases ( U/kg (0.01 mg / kg) of body weight/day.

Maintaining a normal neutrophil count

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

Special categories of patients

Patients with impaired renal/hepatic function

No dose adjustment is required in patients with severe renal or hepatic insufficiency, as their pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.

Children with severe chronic neutropenia (TCN) and malignant neoplasms

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

Elderly patients

Due to 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 were conducted in this category of patients.

Method of use

Cytotoxic chemotherapy

The drug Zarsio is used in the form of subcutaneous injections or intravenous infusions for 30 minutes 1 time / day. Additional instructions for diluting the drug in a 5% solution (50 mg/ml) of dextrose for intravenous use are given in the section “Special instructions”. In most cases, the subcutaneous route of use is preferred.

With intravenous use of a single dose, the duration of the drug’s effect may be reduced. The clinical significance of these data in relation to the use of multiple doses of the drug has not been established. The choice of the method of use depends on the specific clinical situation and is determined for each patient individually.

Patients receiving myeloablative therapy followed by bone marrow transplantation

The drug Zarsio is diluted in 20 ml of a 5% (50 mg/ml) dextrose solution and used as a short intravenous infusion for 30 minutes, or a long subcutaneous or intravenous infusion for 24 hours. Additional instructions for diluting the drug in 5% dextrose solution (50 mg/ml) for intravenous infusions are given in the section “Special instructions”.

UCC mobilization.

Zarsio can also be administered as a long-term subcutaneous infusion for 24 hours to mobilize PSCs in patients undergoing myelosuppressive or myeloablative therapy followed by autologous PSCs transplantation. Before the infusion, the drug is diluted in 20 ml of a 5% (50 mg/ml) dextrose solution. Additional instructions for diluting the drug in 5% dextrose solution (50 mg/ml) for infusions are given in the section “Special instructions”.

ESRD / HIV infection

The initial dose is 0.1-0.4 million mg. UNITS (0.001-0.004 mg / kg) once subcutaneously until the neutrophil count normalizes (usually within 2 days). After the therapeutic effect is achieved, the maintenance dose is 30 million mg. UNITS (0.3 mg) / day every other day. In the future, individual dose adjustment and long-term therapy with Zarsio may be required to maintain the neutrophil count > 2 × 10%.

Overdose

Symptoms of filgrastim overdose have not been established.

Description

Clear colorless or yellowish solution

Special instructions

Treatment with Zarsio should only be carried out under the supervision of an oncologist or hematologist with experience in the use of G-CSF, if the necessary diagnostic capabilities are available. Cell mobilization and apheresis procedures should be performed in an oncology or hematology center that has experience in this area and is able to adequately monitor hematopoiesis progenitor cells.

Cytotoxic chemotherapy

Growth of malignant cells

Due to the fact that G-CSF can stimulate the growth of myeloid cells in vitro, it is recommended to consider the following information.

The safety and efficacy of Zarsio in patients with myelodystplastic syndrome (MDS) and chronic myeloid leukemia have not been established. Therefore, the use of Zarsio is not indicated for these diseases. Special attention should be paid to the differential diagnosis between blast transformation of chronic myeloid leukemia and acute myeloid leukemia.

Since data on the safety and efficacy of Zarsio in patients with secondary acute myelocytic leukemia (AML) are limited, Zarsio should be administered with caution.

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

Leukocytosis

The number of leukocytes in the blood reaches or exceeds 100 × 109/l in less than 5% of patients who received a daily dose of Zarsio more than 0.3 million mg. U/kg (0.0003 mg / kg) of body weight. There are no reports of any side effects directly related to the development of leukocytosis of this severity. However, given the possible risk associated with severe leukocytosis, it is necessary to regularly monitor the number of white blood cells during treatment with Zarsio. If the number of white blood cells exceeds 50 × 109/l after reaching the expected nadir, the drug should be discontinued immediately. If the drug Zarsio is used to mobilize PSCs, it should be discontinued or the dose should be reduced if the number of white blood cells increases to >70 × 109/l.

Risk associated with increasing the dose of chemotherapy

Special care should be taken when treating patients with malignancies who receive high doses of chemotherapy drugs, since the significant additional effect of high doses on the outcome of the disease has not been confirmed, but there is a high probability of more pronounced toxic effects on the cardiovascular system, respiratory organs, nervous system and skin (see instructions for medical use of the chemotherapeutic drugs used).

Monotherapy with Zarsio does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. The risk of severe thrombocytopenia and anemia increases if higher doses of chemotherapy are used (for example, full doses according to prescribed regimens). It is recommended to regularly monitor such indicators of a clinical blood test as hematocrit and platelet count. Special care should be taken when using single-component or combined chemotherapy drugs that can cause severe thrombocytopenia.

A reduction in the severity and duration of thrombocytopenia caused by myelosuppressive or myeloablative chemotherapy was found when Zarsio was used to mobilize the PSCs.

Other safety measures

The efficacy of Zarsio in patients with a significantly reduced number of myeloid progenitor cells has not been studied. The drug Zarsio increases the number of neutrophils by acting primarily on neutrophil progenitor cells. Therefore, in patients with a reduced number of progenitor cells (for example, as a result of treatment with intensive radiation therapy or chemotherapy, or due to infiltration of the bone marrow with tumor cells), the number of neutrophils produced may be lower. There are data on the development of a graft-versus-host reaction (GVHD) and fatal outcomes in patients receiving G-CSF after allogeneic bone marrow transplantation.

Mobilisation of peripheral blood stem cells (PSCs)

Previous treatment with cytotoxic agents

Patients who have previously received intensive myelosuppressive therapy may not experience an increase in the number of PSCs sufficient to reach the recommended minimum level (≥2 × 106 CD34+ cells/kg) or an increase in the rate of platelet recovery when using Zarsio to mobilize PSCs.

Some cytotoxic agents are particularly toxic to hematopoiesis progenitor cells and may have a negative effect on their mobilization. Long-term use of medications such as melphalan, carboplatin, or carmustine before progenitor cell mobilization can lead to poor results. However, concomitant use of melphalan, carboplatin, or carmustine with filgrastim is effective in mobilizing PSCs.

If PSCC transplantation is planned, it is recommended to mobilize stem cells at an early stage of treatment of the patient. Particular attention should be paid to the number of progenitor cells activated in such patients before the use of high-dose chemotherapy drugs. If the results of mobilization in accordance with the above criteria are insufficient, the use of alternative treatment methods that do not require the use of progenitor cells should be considered.

Assessment of the number of peripheral blood stem cells

When assessing the number of PSCs mobilized in patients treated with Zarsio, special attention should be paid to the method of quantitative determination. The results of flow cytometric analysis for the number of CD34+ cells differ depending on the chosen method, and therefore it is necessary to carefully interpret the results obtained during research in different laboratories.

Statistical analysis showed that there is a complex but stable relationship between the number of CD34+ cells reinfused and the rate of platelet count recovery after high-dose chemotherapy. A minimum amount of >2 × 106 CD34+ cells / kg leads to sufficient recovery of hematological parameters and is recommended based on published data. The number of CD34+ cells exceeding the specified value is accompanied by faster normalization; if the number of cells does not reach this level, the recovery of blood parameters is slower.

Healthy donors before undergoing allogeneic PSCC transplantation

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

PSCC mobilization can only be assigned 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 Zarsio in healthy donors under 16 years of age and over 60 years of age have not been studied.

Transient thrombocytopenia (platelet countAmong them,2 cases of thrombocytopenia with platelet count were noted If more than one session of leukapheresis is required, the condition of donors with platelet counts less than 100 × 109/l should be monitored especially carefully; as a rule, if the number of neutrophils is up to 75 × 109/L, apheresis is not recommended.

Leukapheresis should not be performed for donors who are taking anticoagulants or have hemostatic disorders.

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

In donors receiving G-CSF to mobilize PSCs, all clinical blood counts should be regularly monitored until they normalize.

In healthy donors treated with G-CSF, there were cases of transient cytogenetic changes. The significance of these manifestations is not known.

Monitoring of the safety of using Zarsio in healthy donors continues. Currently, the risk of developing a malignant myeloid clone in donors cannot be excluded. Medical centers that perform apheresis procedures are recommended to carry out systematic monitoring of the condition of stem cell donors for at least 10 years in order to monitor the safety of using Zarsio in the long-term period.

There are reports of frequent, mostly asymptomatic cases of splenomegaly, as well as very rare cases of spleen rupture in healthy donors and patients treated with G-CSF. Some cases of rupture of the spleen were accompanied by fatal outcomes. In this regard, it is necessary to carefully monitor the size of the spleen (during clinical examination and ultrasound). The risk of spleen rupture in donors and/or patients with pain in the upper left abdominal cavity or upper shoulder should be considered.

In the post-marketing period, very rare cases of adverse effects on the respiratory system (hemoptysis, pulmonary hemorrhage, infiltrative changes in the lungs, shortness of breath and hypoxia) were noted in healthy donors. If the presence of these symptoms is suspected, it is necessary to consider the feasibility of further use of the drug and the need for appropriate treatment.

Recipients of allogeneic PSCs obtained during mobilization stimulated by Zarsio

According to the available data, the immunological interaction of allogeneic graft PSCC may be associated with a higher risk of acute and chronic graft-versus-host reaction (GVHD). when compared with bone marrow transplantation.

Severe Chronic Neutropenia (TCN)

Blood cell count

It is necessary to strictly monitor the platelet count, especially during the first weeks of therapy with the drug. If a patient is diagnosed with thrombocytopenia and the platelet count is less than 100,000 / mm3 for a long time, consideration should be given to discontinuing Zarsio for a short time or reducing its dose.

There may be other changes in the blood formula that require careful monitoring, including anemia and a transient increase in the number of myeloid progenitor cells.

Development of acute leukemia or myelodysplastic syndrome (MDS)

It is necessary to carry out timely diagnosis of TCH and differentiate this diagnosis from other disorders of the hematopoietic system, such as aplastic anemia, MDS and myeloid leukemia. Before starting treatment, a general clinical analysis should be performed with the determination of the leukocyte formula and platelet count, bone marrow morphology and karyotype should be determined.

During clinical trials, a small number (approximately 3%) of patients with TCN treated with filgrastim experienced MDS or leukemia. These results were obtained only in patients with congenital neutropenia. MDS and leukemia are the most common complications of TCH, and their association with filgrastim therapy has not been determined. In approximately 12% of patients with initially unchanged cytogenetic parameters, repeated examination revealed changes, including monosomy in the 7th pair of chromosomes. If a patient with TCH exhibits cytogenetic disorders, the risk-benefit ratio of continuing therapy with Zarsio should be carefully evaluated; the drug should be discontinued if MDS or leukemia develops. Currently, it is not clear whether long-term use of Zarsio provokes the development of cytogenetic disorders, MDS, or leukemia in patients with TCH. It is recommended that morphological and cytogenetic studies of the bone marrow be performed regularly (approximately every 12 months).

Other safety measures

It is necessary to exclude such causes of transient neutropenia as viral infections.

Enlargement of the spleen is a likely effect associated with treatment with Zarsio. During clinical studies, splenomegaly was detected on palpation in 31% of patients. Radiography reveals an increase in the size of the spleen shortly after the start of treatment with filgrastim and tends to stabilize. It was noted that reducing the dose of Zarsio slows or stops the increase in spleen size; in 3% of patients, splenectomy may be necessary. It is necessary to regularly monitor the size of the spleen during a clinical examination.

Hematuria / proteinuria was observed in a small number of patients. To exclude these manifestations, a general urinalysis should be monitored regularly.

The safety and efficacy of the drug in newborns and patients with autoimmune neutropenia have not been established.

HIV infection

Number of blood cells

Absolute neutrophil counts (APN) should be strictly monitored, especially during the first weeks of Zarsio therapy. Some patients may experience a very rapid and significant increase in APN at the initial dose of Zarsio. During the first 2-3 days of using the drug, it is recommended to measure APN daily. Subsequently, the APN should be checked at least twice a week for the first 2 weeks and then every week or every other week throughout the course of maintenance therapy. With a break in the use of the drug Zarsio in a dose of 30 million mg. U/day (0.300 mg / day) the patient may experience significant fluctuations in APN during treatment. In order to determine the minimum APN (nadir), it is recommended to monitor a general blood test before each use of Zarsio.

Risk associated with high-dose myelosuppressive medications

Monotherapy with Zarsio is not used to prevent the development of thrombocytopenia and anemia while taking myelosuppressive drugs. If higher doses or multiple myelosuppressive medications are used simultaneously in combination with Zarsio therapy, the risk of thrombocytopenia and anemia increases. Regular monitoring of a detailed blood test is recommended.

Development of myelosuppression due to infections or tumors

Neutropenia can be caused by bone marrow damage in opportunistic infections that are caused by pathogens such as Mycobacterium avium complex, or malignancies such as lymphoma. If an infiltrative bone marrow lesion of inflammatory origin or a malignant neoplasm is detected, along with the use of the drug Zarsio for the treatment of neutropenia, it is necessary to prescribe appropriate therapy for the diagnosed diseases. The effectiveness of Zarsio in the treatment of neutropenia caused by bone marrow lesions of infectious origin or tumor neoplasms has not been established.

Other safety measures

There are reports of rare cases of adverse effects on the respiratory system, in particular, the development of interstitial pneumonia with the use of G-CSF. Patients who have recently had infiltrative lung disease or pneumonia may be at high risk. The appearance of symptoms such as coughing, fever and shortness of breath, combined with the detected infiltrative lung damage on X-ray examination and signs of progressive respiratory failure, suggest the presence of adult respiratory distress syndrome (RDSS). If RDSV is detected, the use of Zarsio is discontinued and appropriate treatment is prescribed.

Patients with concomitant bone pathology and osteoporosis, with prolonged (more than 6 months) use of the drug Zarsio is recommended to regularly monitor bone density.

In patients with sickle cell disease, there are cases of acute hemolytic crisis (an increase in the number of altered cells), sometimes with a fatal outcome. Patients with sickle cell disease should be prescribed Zarsio with caution.

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

Storage conditions

The drug should be administered out of the reach of children at a temperature of 2° to 8°C.

Expiration date

2.5 years old.

Active ingredient

Filgrastim

Conditions of release from pharmacies

Prescription