Composition, form of production and packaging
A solution for intravenous and n / a administration is colorless or yellowish in color, transparent.
1 syringe (0.5 ml)
filgrastim 30,000,000 units (300 Ојg)
- "- 48 000 000 units (480 mcg)
Excipients: glutamic acid - 0.736 mg, sorbitol - 25 mg, polysorbate 80 - 0.02 mg, sodium hydroxide - qs up to pH, water d / u - up to 0.5 ml.
0.5 ml - colorless glass syringes with a capacity of 1 ml (1) - blisters (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Filgrastim is a highly purified non-glycosylated protein consisting of 175 amino acids, or a recombinant human granulocyte colony-stimulating factor (r-h G-CSF). It is produced by the strain K12 Escherichia coli, into the genome of which gene of granulocyte colony-stimulating factor (G-CSF) of man has been introduced into the genome by genetic engineering.
Human G-CSF regulates the production and release of neutrophils from the bone marrow to 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 small increase in the number of monocytes. In some cases, there is an increase in the number of eosinophils and basophils, however, in some patients, eosinophilia and basophilia may be present before treatment begins. The increase in the number of neutrophils in the application of filgrastim in the recommended dose range is dose-dependent. Released neutrophils have normal or increased functional activity, which is confirmed by the tests of chemotaxis and phagocytosis. At the end of therapy, the number of neutrophils in peripheral blood is reduced by 50% within 1-2 days and returns to normal within the next 1-7 days. As well as other factors stimulating 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 established that G-CSF is the inducer of angiogenesis of vascular endothelial cells and accelerates the transport of neutrophils through the endothelium of the vessels.
The use of filgrastim in patients receiving cytotoxic drugs is accompanied by a significant decrease 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 inpatient treatment in patients after induction chemotherapy with myeloleukemia or myeloablative therapy followed by bone marrow transplantation. The frequency of cases of body temperature increase did not decrease in patients after myeloablative therapy with subsequent bone marrow transplantation.
The use of Zarcio in both monotherapy and after chemotherapy, mobilizes the release of hematopoietic stem cells into the peripheral bloodstream. Autologous or allogeneic transplantation of peripheral blood stem cells (PSKK) is performed after therapy with large doses of cytostatics, or instead of bone marrow transplantation, or in addition to it. Transplantation of PSKK can also be administered after (high-dose) myelosuppressive cytotoxic therapy. The use of PSKC, mobilized with Zarcio, accelerates the recovery of hematopoiesis, reduces the severity and duration of thrombocytopenia, reduces the risk of hemorrhagic complications and the need for transfusion of platelet mass after myelosuppressive or myeloablative therapy.
The use of Zarcio in children and adults with severe congenital neutropenia (periodic, idiopathic) stimulates a steady increase in the number of active neutrophils in peripheral blood and a reduction in the incidence of infectious and other complications.
The use of Zarsio in patients with HIV infection supports the number of neutrophils within normal limits, which allows to observe the necessary dosage regimen of antiretroviral drugs and myelosuppressive therapy. There are no signs of an increase in HIV replication with the use of Zarcio.
PHARMACOKINETICS
Distribution
V d in the systemic circulation is about 150 ml / kg. With n / k and / in the introduction of the recommended doses, the concentration of filgrastim in the blood plasma remains above 10 ng / ml for 8-16 hours. A direct linear relationship between the administered dose of filgrastim and its concentration in the blood plasma was noted.
Excretion
The withdrawal of filgrastim has no linear dependence, the rate of excretion of the drug decreases with an increase in the dose of the drug. The main way of deducing filgrastim is carried out with the participation of neutrophils, while the clearance increases at higher doses of the drug. The release rate of filgrastim increases with repeated use of the drug as long as the number of neutrophils increases. T 1/2 filgrastim after a single SC administration is from 2.7 parts (1 million units / kg, 10 Ојg / kg) to 5.7 hours (0.25 million units / kg, 2.5 Ојg / kg) and after 7 days application is 8.5-14 hours, respectively.
Long-term therapy with filgrastim for more than 28 days in patients after autologous bone marrow transplantation was not accompanied by cumulation of the drug, and had comparable values ​​of T 1/2 .
INDICATIONS
- reduction in the duration of neutropenia and febrile neutropenia in patients receiving cytotoxic chemotherapy for malignant neoplasm (with the exception of chronic myelogenous leukemia and myelodysplastic syndromes), and a reduction in the duration of neutropenia in patients receiving myeloablative therapy followed by bone marrow transplantation, which is considered a risk factor prolonged severe neutropenia. The efficacy and safety of filgrastim are comparable in the conduct of cytotoxic chemotherapy in children and adults;
- Mobilization of peripheral stem cells (PSCC), incl. after mielosupressivnoy therapy, as well as the mobilization of peripheral stem cells in healthy donors (allogeneic PSKK);
- hereditary periodic or idiopathic neutropenia in adults and children with an absolute neutrophil count of 0.5? 10 9 / l or less, with a history of severe recurrent infections, prolonged treatment with filgrastim is indicated for increasing the number of neutrophils and for reducing the frequency and duration of adverse effects associated with infectious complications;
- prevention of bacterial infections and treatment of persistent neutropenia (absolute number of neutrophils is equal to 1 Г— 10 9 / L and less) in patients with developed stage of HIV infection with ineffectiveness of other methods of treatment.
DOSING MODE
Zarcio therapy can be performed by interacting with cancer center physicians who have experience in using a granulocyte colony-stimulating factor (G-CSF) preparation, as well as experience in treating patients with hematological diseases in a medical facility that has the necessary diagnostic equipment.
Mobilization and apheresis procedures should be carried out in cooperation with specialists of the oncology-hematology center, who have appropriate experience in this field and the possibility of the necessary monitoring of hematopoietic progenitor cells.
Zarcio is available in the following doses: 30 million units / 0.5 ml (0.3 mg) and 48 million units / 0.5 ml (0.48 mg).
Cytotoxic chemotherapy
The recommended daily dose of Zarcio is 0.5 million units / 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.
The drug Zarcio is administered daily until the total number of neutrophils in the clinical blood test exceeds the expected nadir and reaches normal values. After chemotherapy for solid tumors, lymphomas and lymphocytic leukemia, the duration of treatment before reaching these values ​​is up to 14 days. After induction and consolidation therapy of acute myeloid leukemia, the treatment time can be significantly increased (up to 38 days) and determined depending on the type, dose and scheme of the cytotoxic chemotherapy used.
In patients receiving cytotoxic chemotherapy, a transient increase in the number of neutrophils is usually observed 1-2 days after starting treatment with Zarcio.Nevertheless, in order to achieve a stable therapeutic effect, it is necessary to continue therapy with Zarcio until the number of neutrophils exceeds the expected nadir and reaches normal values. It is not recommended to abolish prematurely drug treatment before the transition of neutrophils through the nadir.
Patients receiving myeloablative therapy with subsequent bone marrow transplantation : the recommended initial dose of Zarcio is 1 million units / kg (0.01 mg) of body weight / day.
The first dose of Zarcio 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 Zarcio should be adjusted depending on the change in the number of neutrophils as follows.
Table 1. Selection of the dose of Zarcio in response to the nadir
Absolute number of neutrophils (ASC) Correction of dose of Zarsio
ACHN> 1 Г— 10 9 / L for 3 consecutive days. Dose reduction to 0.5 million units / kg (0.005 mg / kg) of body weight / day
ACHN> 1 Г— 10 9 / l for the next 3 days in a row.
If, during treatment, ASC decreases to <1 Г— 10 9 / L, the dose of Zarcio is increased again according to the above scheme
Mobilization of peripheral blood stem cells (PSSC)
Patients receiving myelosuppressive or myeloablative therapy with subsequent autologous transplantation of PSKK
To mobilize PSKK when using Zarcio as a monotherapy, the recommended dose is 1 million units / 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 day. In some cases, one additional leukapheresis session is performed. Do not change the dose of Zarsio until the final leukapheresis.
To mobilize PSKC after mielosupressivnoy chemotherapy, the recommended dose of Zarcio is 0.5 million ED / kg (0.005 mg / kg) of body weight per day, starting from the first day after completion of the course of chemotherapy and until the number of neutrophils passes the expected nadir and will not reach the norm.Leukapheresis should be carried out during the period of an increase in ACHN from <0.5 Г— 10 9 / L to> 5? 10 9 / l. Patients who did not receive intensive chemotherapy, undergo 1 session of leukapheresis. In some cases, additional sessions of leukapheresis are recommended.
Healthy donors before allogeneic transplantation of PSKK
To mobilize PSKK before the allogeneic transplantation of PSKC in healthy donors, the recommended dose of Zarcio is 1 million ED / kg (0.01 mg / kg) of body weight per day for 4-5 consecutive days. Leukapheresis is carried out from the 5th day and, if necessary, continues until the 6th day in order to obtain 4? 10 6 CD34 + cells / kg body weight of the recipient.
Severe chronic neutropenia (THC)
Congenital neutropenia
The recommended initial dose is 1.2 million units / kg (0.012 mg / kg) of body weight / day once or in divided doses.
Idiopathic and periodic neutropenia
The recommended initial dose is 0.5 million units / kg (0.005 mg / kg) of body weight / day once or in divided doses.
Selection of the dose of the drug
The drug Zarsio injected daily until the achievement and stable exceedance of the number of neutrophils 1.5? 10 9 . Once the therapeutic effect is achieved, the minimum effective dose is determined to maintain this level. To maintain the right amount of neutrophils requires a long daily administration of the drug. After 1-2 weeks of treatment, the initial dose can be doubled or halved, depending on the effectiveness of the therapy. Subsequently, an individual dose adjustment is performed every 1-2 weeks to maintain the average number of neutrophils in the range of 1.5? 10 9 to 10? 10 9 . In patients with severe infections, a scheme with a faster increase in dose can be used. In 97% of patients who responded positively to the treatment, the full therapeutic effect is observed with the appointment of doses up to 24 mcg / kg / day. The daily dose of Zarcio should not exceed 24 mcg / kg.
HIV infection
Recovery of the number of neutrophils
The recommended initial dose of Zarcio is 0.1 million units / kg (0.001 mg / kg) of body weight / day, with a dose increase of up to 0.4 million units / kg (0.004 mg / kg) of body weight to normalize the number of neutrophils (ACHN> 2? 10 9 ). Normalization of the number of neutrophils usually occurs in 2 days. In rare cases (<10% of patients) to restore the number of neutrophils, the dose of the drug can be increased to 1 million units / kg (0.01 mg / kg) of body weight / day.
Maintaining the normal number of neutrophils
After reaching the therapeutic effect, a maintenance dose of 0.3 mg / day 2-3 times a week, according to the alternating schedule (every other day). Subsequently, individual dose adjustment and long-term administration of the drug may be required to maintain an average number of neutrophils> 2? 10 9 / l.
Special categories of patients
Patients with impaired renal / hepatic function
Dose adjustments are not required in patients with severe renal or hepatic insufficiency, their pharmacokinetic and pharmacodynamic parameters turned out to be 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 oncological diseases, the safety profile of Zarcio did not differ from that in adults. Recommendations for dosing for children of the same age 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 Zarcio in elderly patients. There were no additional studies in this category of patients.
Method of administration
Cytotoxic chemotherapy
The drug Zarcio is used in the form of SC injections or IV infusions for 30 minutes 1 time / day. Additional guidance on the dilution of the drug in a 5% solution (50 mg / ml) of dextrose for iv administration is given in the section "Special instructions". In most cases, the route of administration is preferred. With intravenous administration of a single dose, the duration of the effect of the drug may decrease. The clinical significance of these data regarding the use of multiple doses of the drug has not been established. The choice of the method of administration depends on the specific clinical situation and is determined for each patient individually.
Patients receiving myeloablative therapy followed by bone marrow transplantation
Zarcio preparation is diluted in 20 ml of 5% (50 mg / ml) of dextrose solution and used in the form of a short IV infusion for 30 minutes, or a prolonged SC or IV infusion for 24 hours. Additional instructions for dilution of the drug in a 5% solution (50 mg / ml) of dextrose for intravenous infusions are given in the section "Special instructions".
Mobilization of PSKK .
To mobilize PSKK, patients who undergo myelosuppressive or myeloablative therapy followed by autologous transplantation of PSKK, Zarcio can also be administered as a long-term infusion for 24 hours. Before infusion, the drug is diluted in 20 ml of 5% (50 mg / ml) solution dextrose. Additional guidance on dilution of the drug in a 5% solution (50 mg / ml) of dextrose for infusions is given in the section "Special instructions".
CTC / HIV infection
The initial dose of 0.1-0.4 million units (0.001-0.004 mg / kg) once before the normalization of the number of neutrophils (usually within 2 days). After achieving the therapeutic effect, the maintenance dose is 30 million units (0.3 mg) / day every other day. In the future, individual dose adjustment and prolonged therapy with Zarcio may be required to maintain the neutrophil count> 2-10%.
SIDE EFFECT
The following side effects are distributed according to the classification of organs and systems and the frequency of occurrence: very often (? 1/10); often (? 1/100 - <1/10); infrequently (? 1/1000 - <1/100); rarely (? 1/10 000 - <1/1000); very rarely (<1/10 000), the frequency is unknown (can not be estimated from the available data).
On the part of the immune system: very rarely (in patients) and infrequently (in donors before mobilization of PSKK) - hypersensitivity reactions, including anaphylactic reactions, skin rashes, hives, angioedema, dyspnea and BP.
On the part of the organs of hematopoiesis: very often anemia, splenomegaly (progressing in a number of cases), in donors before mobilization PSKK - leukocytosis (> 50 Г— 10 9 / l) and transient thrombocytopenia (<100 Г— 10 9 / l) - as a consequence of pharmacological filgrastim action; often - thrombocytopenia, splenomegaly (asymptomatic, in donors and patients); infrequently - a violation of the function of the spleen; very rarely - rupture of the spleen.
From the nervous system: very often - a headache.
From the side of the cardiovascular system: infrequently - transient decrease in blood pressure; rarely - vascular disorders, incl. vein-occlusive disease and an increase in bcc.
On the part of the respiratory system: very often - nosebleeds; very rarely - pulmonary edema, interstitial pneumonia, pulmonary infiltrates; donors - hemoptysis, pulmonary hemorrhage, dyspnea, hypoxemia.
Of the skin and its appendages: often - vasculitis (during long-term use), alopecia, rash; very rarely - Sweet's syndrome (acute febrile dermatosis, communications with the reception filgrastim not installed).
On the part of the musculoskeletal system: very often - pain in the bones, joints and muscles (weak or moderate, donors - transient); often - pain in the bones, joints and muscles (severe), osteoporosis, arthralgia; infrequent donors and very rarely in patients - the exacerbation of rheumatoid arthritis.
From the digestive system:often - diarrhea, hepatomegaly.
With the genitourinary system: rarely - hematuria, proteinuria; very rarely - dysuria.
From the laboratory parameters: often in patients and often donors - reversible, dose-dependent, mild or moderate increase in the activity of alkaline phosphatase, LDH, patients - GGT, hyperuricemia, a decrease in the concentration of glucose in the blood (a moderate, reversible); infrequent donors - reversible slight increase of AST and uric acid.
Other: often - pain at the injection site, fatigue, injection site reactions (less than 2% of patients with TXH).
CONTRAINDICATIONS
- hereditary fructose intolerance (containing sorbitol);
- severe hereditary neutropenia (Kostmann syndrome) with cytogenetic disorders and autoimmune neutropenia;
- the drug must not be used to increase the doses of cytotoxic chemotherapy drugs recommended above;
- simultaneous radiotherapy or chemotherapy;
- end-stage chronic renal failure (CRF);
- the neonatal period.
- increased sensitivity to the drug or its components in history;
- increased sensitivity to albumin and blood components in the history in cases of adding albumin solutions in / infusion.
With caution
Myelodysplastic syndrome, chronic myelogenous leukemia, secondary acute myeloid leukemia (patients under the age of 55 years, without cytogenetic abnormalities), exceeding the nadir (the number of leukocytes in a blood test> 50 10? 9 / L, to mobilize PBSC -> 70 10? 9 / l) in patients receiving high doses of chemotherapy drugs for malignant neoplasms (risk of increased toxicity), the simultaneous use of one-component or combination of chemotherapeutic agents (risk of severe thrombocytopenia and anemia), y bo ial with a significantly reduced amount of myeloid progenitor cells (less than 2 Г— 10 6CD34 + cells / kg - application poorly understood), thrombocytopenia (with the number of thrombocytes in a blood test at least 100,000 / mm 3 ), splenomegaly (risk splenic rupture), infiltrative pulmonary disease (risk of development / progression infiltrative pneumonia), sickle cell disease, neutropenia, caused by bone marrow tumor or infectious origin neoplasms (lymphoma) (monotherapy is not installed).
PREGNANCY AND LACTATION
Data on the use of filgrastim in pregnancy are limited. There are indications suggesting a possible passage of filgrastim through the placental barrier. In animal studies, the use of filgrastim is not accompanied by a teratogenic effect. An increased incidence of miscarriage, but fetal abnormalities were noted.
When assigning pregnant filgrastim should be carefully weighed against the benefit-risk, comparing the expected therapeutic effect for the mother and the possible risk to the fetus.
Not known whether filgrastim passes into breast milk. Therefore, if necessary, the appointment during lactation should stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindications to the terminal stage of chronic renal failure (CRF).
No dose adjustment is required in patients with severe renal insufficiency, because pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
No dose adjustment is required in patients with severe hepatic insufficiency, since pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.
APPLICATION FOR CHILDREN
When used in pediatric practice in patients with cancer and TXH safety profile ZARS not differ from that in adults. Dosing recommendations for pediatric patients are the same as for adults receiving myelosuppressive cytotoxic chemotherapy.
Contraindicated in the neonatal period.
APPLICATION IN ELDERLY PATIENTS
Due to the limited number of elderly patients in clinical studies, specific recommendations for use of the drug ZARS elderly patients are missing. Additional studies in these patients has not been conducted.
SPECIAL INSTRUCTIONS
Treatment with ZARS should only be done under the supervision of an oncologist or hematologist with experience in the use of G-CSF, with the necessary diagnostic capabilities. Mobilization and apheresis procedures should be performed in the cell oncology and hematology center with experience in this field and the possibility of adequate monitoring of hematopoietic progenitor cells.
Cytotoxic chemotherapy
of malignant cell growth
Due to the fact that G-CSF can promote growth of myeloid cells in vitro, it is advisable to consider the following information.
Safety and effectiveness of the drug in patients ZARS with mielodistplasticheskim syndrome (MDS) or chronic myeloid leukemia is not installed. Therefore, when these diseases ZARS application of the drug is not shown. Particular attention should be in the differential diagnosis between the blast transformation of chronic myeloid leukemia and acute myeloid leukemia.
Since the data on the safety and efficacy ZARS for patients with secondary acute myelocytic leukemia (AML) are limited, ZARS drug should be used with caution.
The safety and efficacy of the drug ZARS first appointment of patients with AML before the age of 55 years without cytogenetic abnormalities [t (8; 21), t (15; 17) and inv (16)] have not been established.
leukocytosis
White blood cell count reaches or exceeds 100? 10 9 / l in less than 5% of patients receiving daily dose ZARS more than 0.3 million. U / kg (0.0003 mg / kg) of body weight. There is no information about any side effects that are directly caused by the development of leukocytosis such severity. However, given the potential risks associated with severe leukocytosis, during treatment with the drug ZARS should regularly monitor the number of white blood cells. If leukocyte counts exceed 50? 10 9 / l after the expected nadir should immediately stop the drug. ZARS if the drug is used for PBSC mobilization, it is necessary to cancel or reduce the dose by increasing the number of white blood cells to> 70? 10 9 / l.
The risk associated with increasing doses of chemotherapy
should be particularly careful in the treatment of patients with malignancies who receive high doses of chemotherapy drugs, since significant additional effect of high-dose on outcome is not certified, but likely more pronounced toxic effects on cardiovascular system, respiratory system, skin and nervous system (see. for medical application instructions used chemotherapeutic drugs) .
Monotherapy ZARS not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. In the case of higher doses of chemotherapeutic agents (e.g., full doses in accordance with the designated circuits) the risk of severe thrombocytopenia and anemia increases. It is recommended to regularly monitor such indicators CBC as hematocrit, and platelet count. Particular caution should be observed when using one-component or combination of chemotherapeutic agents that can cause severe thrombocytopenia.
In applying the drug ZARS PBSC mobilization was observed decrease the severity and duration of thrombocytopenia caused by myelosuppressive or myeloablative chemotherapy.
Other Precautions
ZARS effectiveness of the drug in patients with severely reduced the number of myeloid progenitors have not been studied. ZARS drug increases the number of neutrophils by acting primarily on precursor cells of neutrophils. Therefore in patients with reduced number of progenitor cells (e.g., as a result of an intensive treatment by radiotherapy or chemotherapy, or as a consequence of bone marrow infiltration of the tumor cells) the number of neutrophils can be formed below. There is evidence of the development of the reaction "graft versus host disease" (GvHD) and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation.
Mobilization of peripheral blood stem cells (PBSC)
Previous treatment with cytotoxic drugs
Patients who have previously conducted intensive myelosuppressive therapy on the background of the drug ZARS to mobilize PBSC can not increase the number of PBSC be sufficient to recommended minimum level (? 2 x 10 6 CD34 + cells / kg) or enhance platelet recovery rate.
Some cytotoxic agents exhibit particular toxicity to hematopoietic progenitor cells and may have a negative impact on their mobilization. Long term use of these medications like melphalan, carboplatin, carmustine or to mobilization of progenitor cells may lead to a deterioration in results. However, the simultaneous use of melphalan, carboplatin, carmustine or with filgrastim effective in mobilizing PSCC.
If you plan to PBSC transplantation, it is recommended to mobilize the stem cells in the early stages of treatment of the patient. Particular attention should be paid to the number of progenitor cells activated in such patients before the chemotherapy drugs in high doses. If the results of the mobilization in accordance with the above criteria are not sufficient to consider the use of alternative methods of treatment, not requiring the use of progenitor cells.
Estimating the number of peripheral blood stem cells
In assessing the number of PBSC mobilized by patients during treatment with the drug ZARS, special attention should be paid to the method of quantitation. The results of flow cytometry analysis of CD34 + cell number differ depending on the selected method, and therefore it is necessary to carefully interpret results obtained in studies in different laboratories.
Statistical analysis showed that there is a complex, yet stable relationship between the number entered in the reinfusion CD34 + cells and platelet recovery rate after high doses of chemotherapy drugs. The minimum number of> 2 Г— 10 6CD34 + cells / kg leads to a sufficient recovery of hematological parameters and recommended on the basis of published data. Number of CD34 + cells exceeding a specified value, accompanied by a more rapid normalization; if the number of cells does not reach this level, recovery of blood counts is slower.
Healthy donors prior to allogeneic PBSC
mobilization of PBSC is no direct clinical outcome for healthy donors and can be conducted solely to allogeneic stem cell transplantation.
The mobilization of PBSC may be assigned only donors that correspond to standard clinical and laboratory criteria for a donor stem cells, with emphasis on the presence of hematological indicators, and infectious diseases.
Safety and effectiveness of ZARS drug in healthy volunteers aged 16 years and older than 60 years have not been studied.
Transient thrombocytopenia (platelet count <100 Г— 10 9 / L) following the appointment of ZARS and leukapheresis observed in 35% of donors. Among them, 2 cases of thrombocytopenia with platelet counts <50? 10 9/ l after leukapheresis. If you want to conduct more than one leukapheresis session, particular care should monitor the status of donors with platelet counts less than 100? 10 9 / l; As a rule, when the number of neutrophils and 75? 10 9 / l apheresis is not recommended.
Leukapheresis should not be performed donors receiving anticoagulants or who have hemostasis disturbances.
It is necessary to cancel or reduce the applied dose of the drug ZARS, if the number of white blood cells increases> 70? 10 9 / l.
Donors who receive G-CSF for mobilization of PBSC, should regularly monitor all indicators of clinical blood tests before their normalization.
In healthy donors who have used G-CSF, there were cases of transient cytogenetic changes. The significance of these manifestations is not known.
Security monitoring applications ZARS drug in healthy donors is ongoing. At the present time we can not exclude the risk of a malignant myeloid clone donors. Medical centers conducting apheresis procedure, it is recommended to carry out systematic monitoring of the state of the stem cell donors for at least 10 years with the aim of monitoring the safety of the use of the drug in the ZARS remote period.
There is evidence of frequent, mostly asymptomatic cases of splenomegaly and very rare cases of splenic rupture in healthy donors and patients treated with G-CSF. Some cases of splenic rupture were accompanied by deaths. In this connection it is necessary to carefully monitor the size of the spleen (by clinical examination and ultrasound method). It is necessary to consider the risk of splenic rupture in donors and / or patients if they have pain in the upper left part of the abdomen or upper arm.
In post-marketing period from healthy donors very rare cases of adverse effects on the respiratory system (haemoptysis, pulmonary haemorrhage, infiltrative changes in the lungs, shortness of breath and hypoxia). Suspicion of the following symptoms must consider whether further use of the preparation and necessity of appropriate treatment.
Recipients of allogeneic PBSC obtained by mobilization stimulated drug ZARS
available data, immunological reaction of transplant allogeneic PBSC may be associated with a higher risk of developing acute and chronic reaction "graft versus host" disease (GVHD) when compared to bone marrow transplantation.
Severe chronic neutropenia (TXH)
The number of blood cells
It is necessary to strictly control the number of platelets, especially during the first weeks of drug therapy. If the patient revealed thrombocytopenia, and platelet count over a long period of time is less than 100,000 / mm 3 , should consider short-term cancellation ZARS or reducing its dose.
There may be other changes in blood counts, requiring careful control, including anemia and transient increase in the number of myeloid progenitor cells.
The development of acute leukemia or myelodysplastic syndrome (MDS)
is necessary to carry out timely diagnosis and TXH
