Composition, form of production and packaging
The solution for IV and IV administration is clear, colorless or slightly yellowish, odorless or with a faint odor.
1 f.
filgrastim 30 million AD (300 Ојg)
Excipients: glacial acetic acid - 0.6 mg, 1 N sodium hydroxide solution - qs to pH 4, sorbitol - 50 mg, polysorbate 80 - 0.04 mg, water d / and - up to 1 ml.
1 ml - bottles (5) - packs cardboard.
The solution for the sc administration is clear, colorless or slightly yellowish, odorless or with a faint odor.
1 syringe tube
filgrastim 30 million AD (300 Ојg)
Excipients: glacial acetic acid 0.3 mg, 1 N sodium hydroxide solution qs to pH 4, sorbitol 25 mg, polysorbate 80 0.02 mg, water d / and up to 0.5 ml.
0.5 ml - syringe tubes (1) complete with sterile needle d / u - packs cardboard.
The solution for the sc administration is clear, colorless or slightly yellowish, odorless or with a faint odor.
1 syringe tube
filgrastim 48 million AD (480 Ојg)
Excipients: glacial acetic acid 0.3 mg, 1 N sodium hydroxide solution qs to pH 4, sorbitol 25 mg, polysorbate 80 0.02 mg, water d / and up to 0.5 ml.
0.5 ml - syringe tubes (1) complete with sterile needle d / u - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Recombinant human G-CSF. Hematopoietic growth factor - filgrastim - highly purified non-glycosylated protein, consisting of 175 amino acids. It is produced by the strain K12 Escherichia coli, the genome of which was introduced into the genome by genetic engineering methods of the granulocyte colony-stimulating factor (G-CSF) of a human.
Human G-CSF is a glycoprotein that regulates the formation of functionally active neutrophils and their release into the blood from the bone marrow. Neupogen В®significantly increases the number of neutrophils in the peripheral blood in the first 24 hours after administration with a slight increase in the number of monocytes. In patients with severe chronic neutropenia (TCN), Neupogen В® may cause a slight increase in the number of circulating eosinophils and basophils. Some of these patients may experience eosinophilia or basophilia before starting therapy.
Neupogen В® dose-dependently increases the number of neutrophils with normal or increased functional activity, which was detected by determining the chemotactic and phagocytic activity of neutrophils. After the end of treatment, the number of neutrophils in peripheral blood is reduced by 50% within 1-2 days and returns to normal level during the next 1-7 days.
Neupogen В® significantly reduces the frequency, severity and duration of neutropenia and febrile neutropenia, reducing the need and duration of inpatient treatment in patients receiving chemotherapy with cytostatics or myeloablative therapy followed by bone marrow transplantation.
Patients receiving Neupogen В® and cytotoxic chemotherapy require smaller doses of antibiotics compared to patients receiving only cytotoxic chemotherapy.
Treatment with Neupogen В® significantly reduces the duration of febrile neutropenia, the need for antibiotic therapy and hospitalization after induction chemotherapy for acute myelogenous leukemia, without affecting the incidence of fever and infectious complications.
The use of Neupogen В® both alone and after chemotherapy, mobilizes the release of hematopoietic stem cells into the peripheral bloodstream. Transplantation of autologous peripheral blood stem cells (PSKK) is carried out 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 Neupogen В® , accelerates the recovery of hematopoiesis, reduces the risk of hemorrhagic complications and the need for transfusion of platelet mass. In children and adults with TCN (severe congenital, periodic, idiopathic neutropenia), Neupogen В® stably increases the number of neutrophils in peripheral blood, reduces the incidence of infectious complications.
The administration of Neupogen В® to patients with HIV infection allows maintaining a normal level of neutrophils and following recommended doses of antiviral and / or other myelosuppressive therapy. There were no signs of an increase in HIV replication with Neupogen В® .
Like other hematopoietic growth factors, G-CSF stimulates human endothelial cells in vitro.
Preclinical safety data
The carcinogenic properties of filgrastim have not been studied. Filgrastim did not cause mutations in the genome of bacteria, regardless of the presence of the enzyme system necessary for the metabolism of the drug.
It was found that some malignant cells have on their surface receptors for G-CSF. The likelihood that filgrastim can serve as a growth factor for various types of tumors can not be ruled out.
In studies on rats of both sexes, no effect was found on fertility and pregnancy with filgrastim at doses up to 500 Ојg / kg.
In studies on rats and rabbits, filgrastim did not have a teratogenic effect. Rabbits had an increased incidence of miscarriages, but there was no abnormality of fetal development.
PHARMACOKINETICS
Suction
After sc administration, filgrastim is rapidly absorbed and after 2-8 hours reaches its C max in serum. T 1/2 after IV or SC administration is usually between 2 and 4 hours. Clearance and T 1/2 depend on the dose of the drug and the number of neutrophils. Considering the dependence of the clearance on the number of neutrophils, its saturation with increasing filgrastim concentration and a decrease in neutropenia, we can speak of the predominance of the linear nature of clearance and the linear nature of the pharmacokinetics. Absolute bioavailability after SC administration is 62% at a dose of 375 μg and 72% at a dose of 750 μg. After the termination of the administration of filgrastim, its concentration is reduced to endogenous values ​​within 24 hours.
In healthy volunteers and patients with oncological diseases, a reduction in the plasma concentration of filgrastim after repeated administration was shown before chemotherapy. The increased clearance of filgrastim in this case is dose-dependent, and the extent of this increase may depend on the degree of neutrophilia in the recipients, which is consistent with the data on the increase in neutrophil-dependent clearance with increasing neutrophil pool. In patients receiving filgrastim after chemotherapy, the concentration of the drug in the plasma remained at the same level until the beginning of the restoration of hemopoiesis.
Distribution
With iv and n / k administration of filgrastim a positive linear relationship between the administered dose and serum concentration is observed. After sc administration of therapeutic doses, its concentration exceeds 10 ng / ml for 8-16 hours. The volume of distribution is 150 ml / kg.
Excretion
Long-term administration of filgrastim (up to 28 days) after autologous bone marrow transplantation does not lead to cumulation and a change in half-life.
Regardless of the mode of administration, the elimination of filgrastim proceeds according to the rules of kinetics of the first order. T 1/2 - 3.5 h, the clearance is 0.6 ml / min / kg.
Pharmacokinetics in special patient groups
In children after chemotherapy, the pharmacokinetics of filgrastim is similar to that in adult patients receiving the same dose of the drug, taking into account the mass of the body, which allows us to conclude that the pharmacokinetics of filgrastim are independent of age.
Pharmacokinetic data in patients older than 65 years are absent.
In studies on the use of filgrastim, it was shown that pharmacodynamics and pharmacokinetics in patients with severe impairment of renal or hepatic functions are similar to those in healthy subjects. Therefore, in these cases, there is no need for dose adjustment.
Patients with end-stage renal failure tended to increase the systemic exposure of filgrastim compared with healthy volunteers and patients with creatinine clearance of 30-60 ml / min.
INDICATIONS
Adults and children
- neutropenia, febrile neutropenia in patients receiving intensive myelosuppressive cytotoxic chemotherapy for malignant diseases (with the exception of chronic myeloid leukemia and myelodysplastic syndrome), as well as neutropenia and its clinical consequences in patients receiving myeloablative therapy followed by allogeneic or autologous bone marrow transplantation, with increased risk of developing prolonged and severe neutropenia;
- mobilization of autologous peripheral blood stem cells (autologous PSKK), incl. after mielosupressivnoy therapy, as well as mobilization of peripheral blood stem cells in healthy donors (allogeneic PSKK);
- severe congenital, periodic or idiopathic neutropenia (absolute number of neutrophils (ACHN) ≥ 0.5 × 10 9 / L) in children and adults with severe or recurrent infections in history to increase the number of neutrophils, and to reduce the frequency and duration of infectious complications;
- persistent neutropenia (AChN 1.0 Г— 10 9 / L) in patients with developed stage of HIV infection to reduce the risk of bacterial infections when other methods of treatment are not possible;
- neutropenia in patients with acute myelogenous leukemia, receiving induction or consolidation chemotherapy, to reduce its duration and clinical consequences.
DOSING MODE
Adults and children
Daily SC or as short IV infusions (30-minute) on a 5% glucose solution until the number of neutrophils passes the expected minimum (nadir) and returns to the normal range. Preferably after the route of administration.
Standard schemes of cytotoxic chemotherapy
For 0.5 million units (5 Ојg) / kg 1 time / day every day or in the form of short intravenous infusions (30-minute) in a 5% solution of glucose. In most cases, the route of administration is preferred. There is evidence that with IV injection of the drug, the duration of the effect is shortened. However, the clinical relevance of these data remains unclear. The choice of route of administration should depend on the individual characteristics of the patient and the clinical picture of the disease. The first dose of Neupogen В® is administered no earlier than 24 hours after the end of the course of cytotoxic chemotherapy. Daily administration of Neupogen В® should be continued until the number of neutrophils exceeds the expected minimum and does not reach normal values. After the course of chemotherapy (standard regimens) for the treatment of solid tumors, lymphoma and lymphoid leukemia, the duration of therapy to achieve the desired effect is usually up to 14 days. After induction and consolidation therapy of acute myelogenous leukemia, the duration of application of Neupogen В® can be increased up to 38 days depending on the type, doses and the used scheme of cytotoxic chemotherapy.
A transient increase in the number of neutrophils is usually observed 1-2 days after the onset of treatment with Neupogen В® . To achieve a stable therapeutic effect, it is necessary to continue therapy with Neupogen В® until the number of neutrophils exceeds the expected minimum and reaches normal values. It is not recommended to abolish Neupogen В® prematurely, until the number of neutrophils passes through the expected minimum.
After myeloablative therapy followed by bone marrow transplantation
Daily n / k or IV in the form of infusion in 20 ml of 5% glucose solution. The initial dose is 1.0 million ED (10 Ојg) / kg / day drip for 30 minutes or 24 hours, or by continuous infusion for 24 hours. The first dose of Neupogen В® should be administered no earlier than 24 hours after cytotoxic chemotherapy, and with bone marrow transplantation - no later than 24 hours after the infusion of the bone marrow. The duration of therapy is not more than 28 days (efficacy and safety of therapy lasting more than 28 days are not established).
After the maximum reduction in the number of neutrophils (nadir), the daily dose is corrected depending on the dynamics of the neutrophil content. If the neutrophil count exceeds 1.0 Г— 10 9 / L for three consecutive days, the dose of Neupogen В® is reduced to 0.5 million units per kg per day; then, if the ACN exceeds 1.0 Г— 10 9 / L for 3 consecutive days, Neupogen В® is canceled. If during the treatment period, the AFN decreases less than 1.0 Г— 10 9 / L, the dose of Neupogen В® should be increased again, in accordance with the above scheme.
Mobilization of peripheral blood stem cells (SBSC) in patients receiving myelosuppressive or myeloablative therapy followed by autologous transfusion of PSKK with or without bone marrow transplantation
For the mobilization of PSKK, 1.0 million ED (10 Ојg) / kg / day by injection 1 time / day or continuous 24 hour infusion (in 20 ml of 5% glucose solution) for 5-7 days in a row, usually 1-2 procedures of leukapheresis are sufficient in a row on the 5th, 6th days. In some cases, additional leukapheresis is possible. The administration of Neupogen В® should be continued until the last leukapheresis.
To mobilize PSKK after mielosupressivnoy chemotherapy - for 0.5 million units (5 mcg) / kg / day by daily injections, starting from the first day after completion of chemotherapy and until the amount of neutrophils passes through the expected minimum and will not reach normal values. Leukapheresis should be carried out during the period when ACN rises from less than 0.5 Г— 10 9 / L to more than 5.0 Г— 10 9 / L. Patients who did not receive intensive chemotherapy, it is enough to have one leukapheresis. In some cases, additional leukapheresis is recommended.
Mobilization of PSKC in healthy donors for allogeneic transplantation
For 1 million units (10 Ојg) / kg / day for 4 to 5 days. Leukapheresis is carried out from 5 days and if necessary up to 6 days in order to get CD34 +? 4 Г— 10 6 cells / kg body weight of the recipient. The effectiveness and safety of the Neupogen В® preparation for mobilizing PSKC in healthy donors under the age of 16 and older than 60 years has not been investigated.
Severe chronic neutropenia (THC)
Daily, c / o, once or divided into several introductions. With congenital neutropenia: the initial dose is 1.2 million units (12 Ојg) / kg / day; with idiopathic or intermittent neutropenia: 0.5 million ED (5 Ојg) / kg / day until the neutrophil count exceeds 1.5 Г— 10 9 / L. After achieving a therapeutic effect, the minimum effective dose should be determined to maintain this level. To maintain the required number of neutrophils requires a long daily administration of the drug. After 1-2 weeks of treatment, depending on the response of the patient to therapy, the initial dose can be doubled or halved. Subsequently, every 1-2 weeks, individual dose adjustments can be made to maintain the number of neutrophils in the range of 1.5-10 Г— 10 9 / L. In patients with severe infections, a scheme with a faster increase in dose can be used. In 97% of patients who responded positively to treatment, the full therapeutic effect is observed with the appointment of doses up to 24 mcg / kg per day. The safety of prolonged administration of Neupogen В® in doses over 24 mcg / kg per day in patients with TCN is not established.
Neutropenia in HIV infection
The initial dose is 0.1-0.4 million ED (1-4 mcg) / kg per day once before and to maintain a normal neutrophil count (more than 2.0 Г— 10 9 / L). In more than 90% of patients who responded positively to treatment, the normalization of the number of neutrophils usually occurs in 2 days. A small number of patients (less than 10%) required a dose of 1.0 million ED (10 Ојg) / kg / day (maximum daily dose of not more than 10 Ојg / kg) to achieve a normal neutrophil count. After achieving the therapeutic effect, it is necessary to administer the minimum effective dose to maintain a normal number of neutrophils. The recommended maintenance dose of 300 mcg per day is p / k an average of 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 neutrophil count> 2.0 Г— 10 9 / L.
Use in children
Standard cytotoxic chemotherapy regimens : the safety and efficacy profiles of Neupogen В® in children receiving cytotoxic chemotherapy did not differ from those in adults.
Patients after myelosuppressive or myeloablative therapy followed by autologous transfusion of PSKK: the safety and efficacy of Neupogen В® in healthy donors under 16 years of age have not been evaluated.
Patients with TCN and oncological diseases : the efficacy and safety of Neupogen В® in newborns suffering from TCN are not established.
Severe congenital, periodic or idiopathic neutropenia (AFN less than or equal to 0.5 Г— 10 9 / L) is an indication for prolonged use of Neupogen В® in children with severe or recurrent infections in history to increase the number of neutrophils, and to reduce the frequency and duration of complications, related infections.
In clinical trials, efficacy was proven Neupogen В® in patients under the age of 18 years with TXH and cancer. The safety profile of the drug in children for the treatment of TXH not differ from that in adults.
Dosing recommendations for pediatric patients are the same as for adults receiving myelosuppressive cytotoxic chemotherapy.
Old age
The study involved a small number of elderly patients, special studies in this group of patients was conducted. Specific recommendations for elderly patients are missing.
Evaluation of the safety and efficacy of Neupogen В®older than 60 years has not been evaluated in healthy donors.
Patients with renal or hepatic impairment
No dose adjustment is required in patients with severe renal or hepatic insufficiency, since pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.
Instructions for breeding
Neupogen В® diluted only 5% glucose solution. When this is not permitted dilution of 0.9% sodium chloride solution. It introduced the drug to final concentrations of less than 5 micrograms in 1 ml.
If Neupogen В®diluted to a concentration of less than 1.5 million. ED (15 ug) in 1 ml, the solution should be added to human serum albumin in an amount that the final concentration of albumin was 2 mg / ml. For example, in a final volume of 20 ml, total doses of less than 30 filgrastim Mill. ED (300 mg) to be administered with the addition of 0.2 ml of 20% albumin solution.
Single Neupogen В® can adsorb to glass and plastics. However Neupogen В® at a dilution of 5% glucose solution is compatible with glass and a number of plastics, including polyvinyl chloride, polyolefin (copolymer of polypropylene and polyethylene) and polypropylene.
Ready solution Neupogen В® stored at 2 В° to 8 В° C is not more than a day.
SIDE EFFECT
These clinical studies
Determination of the frequency of adverse reactions: very often (> 10%), frequent (1-10%), rare (<1%), rare (<0.01%).
Patients with cancer
Neupogen В® does not increase the incidence of adverse reactions to cytotoxic chemotherapy. Adverse events were observed with similar frequency in patients receiving Neupogen В® / placebo chemotherapy and / chemotherapy.
On the part of the body as a whole : often - fatigue, generalized weakness, inflammation of mucous membranes (mucositis), anorexia; infrequently - nonspecific pain; rarely - worsening of rheumatoid arthritis.
On the part of the musculoskeletal system:often - chest pain, bone pain (particularly bone active hematopoiesis) and muscle (weak or moderate (10%), sometimes strong (3%), which in most cases are stopped conventional analgesics).
From the digestive system: very often - nausea, vomiting; often - constipation, diarrhea.
Cardio-vascular system : in rare cases - transient hypotension, not requiring medical correction, vascular disorders (venookklyuzionnaya disease, disorders associated with a change in fluid content in the body, in patients treated with high-dose chemotherapy followed by autologous bone marrow transplantation; Feedback from receiving Neupogen В® is not installed).
The respiratory system:often - cough, sore throat; rarely - pulmonary infiltrates, interstitial pneumonia, pulmonary edema, in rare cases with poor outcome in the form of respiratory failure or adult respiratory distress syndrome (may be fatal).
Skin and subcutaneous tissue: often - alopecia, skin rash; rarely - Sweet's syndrome (acute febrile dermatosis, cutaneous vasculitis (the development of a mechanism in patients receiving Neupogen В® , is not known).
From the nervous system: often - headache.
On the part of the immune system:rare - allergic reactions. About half of allergic reactions associated with administration of the first dose, more often - after / in the drug. Sometimes resumption of treatment is accompanied by a relapse of symptoms.
From the urinary system: rarely - a violation of urination (dysuria generally mild to moderate).
Laboratory findings: very often - increasing the activity of LDH, alkaline phosphatase, GGT, increase in serum uric acid concentration (reversible dose-related changes are usually mild to moderate).
Patients with HIV infection
From the musculoskeletal system: very often - pain in bones and muscles (myalgia), mainly mild to moderate (incidence is similar to that in patients with cancer).
From the hematopoietic system: often - splenomegaly (linked to the drug intake of less than 3% of the cases, in all cases, physical examination, there was a slight to moderate splenomegaly with a favorable clinical course, been no cases of hypersplenism, splenectomy was not carried out in any case). Splenomegaly is quite common in patients with HIV infection, as well as varying degrees of symptoms occurs in the majority of patients with AIDS; in such cases the connection with the reception of Neupogen В® has not been established.
Healthy donor (allogeneic PBSC mobilization)
On the part of the body as a whole : rarely - worsening of rheumatoid arthritis.
On the part of the musculoskeletal system:very often - pain in bones and muscles, mainly mild to moderate.
Respiratory system: rare - hemoptysis, pulmonary infiltrates.
From the nervous system: very often - headache.
Immune system: rarely - severe allergic reactions.
From the hematopoietic system: very often - leukocytosis (more than 50 x 10 9 / l) was observed in 41% of healthy donors transient thrombocytopenia (less than 100 x 10 9 / l) was seen in 35% of healthy donors; often - splenomegaly (without clinical manifestations); seldom - disorders of the spleen function.
From the laboratory parameters:often - transient slight increase in LDH, alkaline phosphatase; infrequently - a slight increase in AST activity (no clinical sequelae), hyperuricemia.
Patients with TXH
incidence of adverse events when taking the drug Neupogen В® patients with TXH decreases with time.
From the sides of the body as a whole: often - reactions (including pain) at the injection site (<2%), arthralgia (<2%).
On the part of the musculoskeletal system: very often - pain in bones and muscles; often - osteoporosis (<2%).
From the digestive system: often - diarrhea (usually after the start of therapy), hepatomegaly (<2%).
Skin and subcutaneous tissue:often - alopecia (<2%), rash (<2%), cutaneous vasculitis (2%).
From the nervous system: often - headache (<2%, usually after the beginning of therapy).
From hemopoiesis system: very often - anemia, splenomegaly (may progress in some cases); often - thrombocytopenia; seldom - disorders of the spleen function. Also identified cases of epistaxis.
Genito-urinary system: rarely - hematuria, proteinuria.
From the laboratory parameters: often - transient increase in LDH, alkaline phosphatase, without clinical manifestations, moderate transient hypoglycemia after eating, hyperuricemia.
Postmarketing use of the drug
Immune system:in rare cases - allergic reactions, including anaphylaxis, skin rash, urticaria, which can develop at the beginning of therapy or during subsequent treatment of filgrastim. In some cases, accompanied by resumption of treatment relapse of symptoms, which suggests a relationship between the drug and undesirable. With the development of a serious allergic reaction filgrastim therapy should be discontinued.
From hemopoiesis system: while taking filgrastim separate cases of sickle cell crises, some - with fatal consequences. In patients receiving G-CSF (filgrastim) describes individual cases splenic rupture in healthy donors and patients with cancer.
Skin and subcutaneous tissue:In rare cases (0.01% and <0.1%?) - Sweet's syndrome (acute febrile dermatosis). In patients with cancer in the application cases of cutaneous vasculitis (estimated frequency communications 0.001%) described filgrastim.
Metabolism: patients with cancer in patients receiving filgrastim individual cases described development pseudogout (chondrocalcinosis).
From the laboratory parameters: in patients receiving filgrastim after cytotoxic chemotherapy, there was a reversible increase in the concentration of uric acid in serum, activity of ALP and LDH without clinical manifestations (usually mild or moderate).
CONTRAINDICATIONS
- severe congenital neutropenia (Kostmann syndrome) with cytogenetic disorders;
- application to increase the doses of cytotoxic chemotherapy drugs recommended above;
- co-administration of cytotoxic chemotherapy and radiotherapy;
- Hypersensitivity to the components of the drug.
PREGNANCY AND LACTATION
Category C
Safety Neupogen В® during pregnancy has not been established. Perhaps the passage of filgrastim the placenta in women. In animal studies, reproductive toxicity was identified. When administering the drug Neupogen В® pregnant should correlate expected therapeutic effect with the possible risk to the fetus.
In studies in rats of both sexes were not observed any influence on the fertility and pregnancy when applying filgrastim at doses up to 500 .mu.g / kg.
In studies on rats and rabbits Neupogen В® is not teratogenic. In rabbits, there was an increased incidence of miscarriage, but fetal abnormalities were noted.
It is not known whether allocated fligrastim breast milk. Not recommended for use Neupogen В® in nursing mothers.
APPLICATION FOR FUNCTIONS OF THE LIVER
No dose adjustment is required in patients with severe renal insufficiency, because of their 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 their pharmacokinetic and pharmacodynamic parameters were similar to those of healthy volunteers.
APPLICATION FOR CHILDREN
Perhaps the use of indications and at the recommended doses.
APPLICATION IN ELDERLY PATIENTS
The study involved a small number of elderly patients, special studies in this group of patients was conducted. Specific recommendations for elderly patients are missing.
Evaluation of safety and efficacy of the drug Neupogen in donors aged over 60 years has not been evaluated.
SPECIAL INSTRUCTIONS
Treatment with Neupogen В® 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.
The growth of malignant cells
Safety and efficacy of Neupogen В® in patients with myelodysplastic syndrome, and chronic myelogenous leukemia have not been established, so it is not shown in these diseases. Particular attention should be paid to the differential diagnosis between acute myeloid leukemia and blast crisis of chronic myeloid leukemia.
Human G-CSF can promote growth of myeloid cells in vitro. Similar effects can be observed in vitro and in respect of certain non-myeloid cells.
It should be used with caution Neupogen В® patients with secondary acute myeloid leukemia, due to the limited data on the safety and effectiveness in the present case.
Safety and efficacy of Neupogen В® patients with acute myeloid leukemia de novo under 55 years in cases of cytogenetic favorable prognostic factors (translocation t (8; 21), t (15; 17), inv (16)) is established.
Patients receiving cytotoxic chemotherapy
Leukocytosis: less than 5% of patients receiving Neupogen В®at doses more than 0.3 million units (3 ug / kg / day), the number of leukocytes was increased to 100 x 10 9 / L or more. Any adverse events directly linked with leukocytosis, is not described. However, given the potential risks associated with high leukocytosis, during treatment with Neupogen В® should regularly (eg, 2-3 times a week) to determine the number of leukocytes. If, after passing the minimum expected number of cells exceeds 50 Г— 10 9 / L, Neupogen В® should be discontinued immediately. If Neupogen В® is used for PBSC mobilization, the dose should be reduced or completely canceled in the case where the white blood cell count exceeds 70 x 10 9 / L.
Risks associated with high-dose chemotherapy: caution should be exercised in patients receiving high dose chemotherapy because of improving the outcome of cancer is not observed while higher doses of chemotherapeutic agents exhibit more pronounced toxicity, including skin reactions and side effects of cardiovascular, nervous and respiratory systems.
Monotherapy drug Neupogen В®It does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. Because of the potential application of higher doses of chemotherapy (eg full doses in accordance with the schemes), the patient may be at greater risk of thrombocytopenia and anemia. It is recommended to conduct regular blood tests and to determine platelet count and hematocrit. Particular caution should be exercised when applying single-component or combination chemotherapeutic regimens known to cause severe thrombocytopenia.
It has been shown that the use of Neupogen В® for mobilization of PBSC reduces the extent and duration of thrombocytopenia which developed due myeloablative or myelosuppressive chemotherapy.
Patients with TXH
transformation to leukemia or predleykoz (myelodysplastic syndrome): caution should be exercised in the diagnosis TXH and differentiate it from other hematologic disorders such as aplastic anemia, myelodysplasia, and myeloid leukemia. Prior to treatment should be carried out with the full blood count and determination of leukocyte platelet counts, as well as explore morphologic picture of bone marrow and karyotype.
A small percentage (3%) patients with severe congenital neutropenia (Kostmann syndrome) receiving Neupogen В® , was observed myelodysplastic syndrome and leukemia. Myelodysplastic syndrome and leukemia - natural complications of the disease. Their connection with the treatment of drug Neupogen В®unclear. Approximately 12% of patients with normal cytogenetics when re-examination detected anomalies, including monosomy 7. If the patient with the syndrome Kostmann cytogenetic abnormalities appear, it is necessary to carefully evaluate the benefits and risks of continuing therapy with Neupogen В® . With the development of myelodysplastic syndrome or leukemia Neupogen В® should be discontinued. It is not yet clear whether long-term treatment predisposes drug Neupogen В®patients with severe congenital neutropenia (Kostmann's syndrome) to the development of cytogenetic abnormalities, myelodysplastic syndrome and leukemia. Patients with the syndrome Kostmann is recommended at regular intervals (approximately every 12 months.) To carry out the morphological and cytogenetic bone marrow examinations.
Cytogenetic abnormalities, leukemia and osteoporosis have been found long-term use prepa
