Neupomax (Filgrastim) ampoules 30000000 IU/ml 300 mcg/ml 5 vials, 30000000 IU/ml 480 mcg/1.6ml 5 vials,

480mcg/1.6ml – 11/2018

Release form and composition:

Solution for the on/in and s/to the introduction in the form of a transparent or slightly opalescent, colorless or slightly colored liquid.

1 FL.

filgrastim 30 million UNITS (300 micrograms)

Auxiliary substances: glacial acetic acid, sodium hydroxide, sorbitol, Polysorbate 80, water d/I.

1 ml – glass vials (5) – packing contoured PVC (1) – packs of cardboard.

Solution for the on/in and s/to the introduction in the form of a transparent or slightly opalescent, colorless or slightly colored liquid.

1 ml 1 FL.

filgrastim 30 million UNITS (300 micrograms) 48 million UNITS (480 micrograms)

Auxiliary substances: glacial acetic acid, sodium hydroxide, sorbitol, Polysorbate 80, water d/I.

1.6 ml – glass vials (5) – packing contoured PVC (1) – packs of cardboard.

Pharmacological action:

Filgrastim is a recombinant human granulocyte colony-stimulating factor (G-CSF). Has biological activity similar to endogenous human G-CSF, differing from the latter in that it is neglikolizirovanny protein with an additional N-terminal methionine residue.

Filgrastim is produced by recombinant DNA technology, extracted from the cells of the bacterium Escherichia ci, in the genetic apparatus which introduced gene coding a protein G-CSF.

Filgrastim stimulates the formation of functionally active neutrophils and their release in the peripheral blood from the bone marrow and is used in the treatment of patients with neutropenia of different origins.

Pharmacokinetics:

Suction

As the on/in and s/to the introduction of filgrastim there is a positive linear relationship to its serum concentrations are dose-related.

Distribution

Vd is approximately 150 ml/kg.

Excretion

The average value of T1/2 filgrastim from serum is about 3.5 hours, a clearance of approximately 0.6 ml/min/kg Continuous infusion with filgrastim over a period of time up to 28 days to patients after autologous bone marrow transplantation is not accompanied by signs of accumulation and increase in T1/2.

Indications:

– reducing the period of neutropenia and the frequency of febrile neutropenia resulting from myelosuppressive cytotoxic chemotherapy of malignant diseases (except chronic myeloid leukemia and myelodysplastic syndrome)

– neutropenia in myeloablative therapy followed by allogeneic or autologous bone marrow transplantation with the aim of reducing the duration of neutropenia

– mobilization of peripheral blood stem cells (pskk) in donors and patients

– severe congenital, periodic or idiopathic neutropenia (absolute number of neutrophils e500/µl) in children and adults with severe or recurrent infections in history

– resistant neutropenia (the absolute number of neutrophils e1000/µl) in patients with extended stage of HIV infection to reduce the risk of bacterial infections and the ineffectiveness of or inability to use other methods of treatment.

Dosing regimen:

Neipomax® may be administered by daily s/C injection or the daily 30-minute on/in infusions. Also, the product can be entered as in/in or n/a 24-hour infusion. The choice of route of administration should depend on the specific clinical situation, however, in most cases, preferably the p/to the introduction of the drug.

In order to avoid painful sensations at introduction should be daily to change the injection site.

The standard scheme of cytotoxic chemotherapy

The drug should be administered 5 µg/kg 1 times/day daily p/K or in/in drip for 30 min until then, until after the expected maximum decline in the level of neutrophils, their number is not restored to a normal figure. When reaching the norms of the drug can be abolished.

The first dose of Neipomax should be administered no earlier than 24 hours after the course of cytotoxic chemotherapy. Duration of therapy not more than 14 days.

After induction and consolidation therapy of acute myeloid leukemia the duration of the application of Neupomax may increase to 38 days depending on the type, dose and type of chemotherapy.

A transient increase in the number of neutrophils is observed, usually in 1-2 days after starting treatment with filgrastim. To achieve a stable therapeutic effect is not recommended to interrupt the treatment to achieve normal values of neutrophils after the expected maximum reduction of their level. When the absolute number of neutrophils gt10 000/µl treatment Neipomax stop.

Myeloablative therapy with subsequent autologous or allogeneic bone marrow transplantation

Initial dose – 10 mg/kg/day, in/in drip for 30 min or 24 h, or by 24-hour p/infusion. The first dose of Neipomax should be administered no earlier than 24 hours after the cytotoxic chemotherapy, and in bone marrow transplantation – not later than 24 hours Duration of therapy – not more than 28 days.

Daily dose of the drug also corrected depending on the dynamics of the content of neutrophils. If the absolute number of neutrophils for 3 days in a row is greater than 1000/µl, dose of Neipomax reduce to 5 mcg/kg/day, if you use this dose for the next 3 days absolute neutrophil count continues to exceed the value of 1000/µl, the introduction of Neipomax should be discontinued. If during treatment the absolute number of neutrophils decreases to less than 1000/µl, dose of Neipomax should increase again, in accordance with the above scheme.

Mobilization of peripheral blood stem cells in patients with neoplastic diseases

The drug should be used at 10 µg/kg 1 times/day n/a or enter by continuous 24-hour p/infusion for 6 days in a row. Usually spend 2 leikafereza in a row, on the 5th and 6th days. In case of additional leikafereza the introduction of Neipomax should continue until the last leukapheresis.

Mobilization of TUAC after myelosuppressive chemotherapy

The drug should be used at 5 µg/kg / day by daily p/injection, from the first day after completion of chemotherapy and until then, until the number of neutrophils did not reach normal values. Leikaferez should be carried out only when the absolute number of neutrophils exceeds the normal value (gt2000/µl).

Mobilization of TUAC in healthy donors for allogeneic transplantation

The use of the drug by 10 µg/kg/day s/C for 4-5 days and conducting 1-2 leukapheresis is usually possible to obtain CD34+gt4х106 cells/kg of body weight of the recipient.

Severe chronic neutropenia (TKHN)

Neipomax® should be used in an initial dose of 12 mcg/kg/day and in congenital neutropenia 5 mcg/kg/day in idiopathic or periodic neutropenia n/a single or by multiple injection daily until until the number of neutrophils is not consistently exceed 1500/MKL. After a therapeutic effect will determine the minimum effective dose to maintain this level. After 1-2 weeks of treatment the initial dose can be doubled or reduced by half, depending on the patient’s response to therapy.

Subsequently, every 1-2 weeks it is possible to produce individual dose adjustment to maintain the average number of neutrophils in the range 1500-10 000/µl. In patients with severe infections, you can apply a scheme with a more rapid increase in dose. Safety of filgrastim in long-term care of patients with TKHN doses over 24 mg/kg/day not established.

Neutropenia in HIV infection

The initial dose is 1-4 mcg (0.1-0.4 million IU)/kg p/to 1 times/day to normalize the number of neutrophils. The maximum daily dose should not exceed 10 µg/kg.

After a therapeutic effect, it is recommended to apply Neipomax® maintenance dose is 300 micrograms s/C every other day. Further, the dosing regimen corrected in each individual case separately to maintain the average number of neutrophils gt2000/µl.

Recommendations for dosing regime for children with those for adults. Data on the safety and effectiveness of filgrastim in healthy donors under the age of 16 do not exist.

Patients with impaired renal function and/or liver, as well as the elderly patients correction dosing regimen of Neipomax not required. Data on the safety and effectiveness of filgrastim in healthy donors older than 60 years do not exist.

Rules of preparation of solutions

When s/to the introduction of the drug is further diluted should not be. In preparing the solution for infusion as a solvent it is recommended to use only 5% dextrose solution. Breeding 0.9% solution of sodium chloride is not allowed because of incompatibilities of pharmaceutical.

Neipomax® in diluted form in a concentration of from 2 to 15 µg/ml can be adsorbed by glass and plastic materials. In this case, to prevent absorption into the solution of the drug is necessary to add human serum albumin in the required amount to achieve its concentration in the final solution 2 mg/ml For the diluted solution of Neipomax in concentrations greater than 15 mcg/ml, add albumin is not required. Do not dilute Neipomax® to a concentration less than 2 µg/ml.

Side effects:

From the side of musculoskeletal system: pain in bones, muscles and joints, osteoporosis.

From the digestive system: anorexia, diarrhea, hepatomegaly, nausea, vomiting.

On the part of the blood: neutrophilia, leukocytosis (as a consequence of the pharmacological actions of filgrastim), anemia, thrombocytopenia, enlargement, and rupture of the spleen.

The respiratory system: respiratory distress syndrome, adult, lung infiltrates.

From the side of cardiovascular system: decrease or increase in blood pressure, cutaneous vasculitis, tachycardia.

From the laboratory parameters: reversible increase in the content of LDH, ALP, GGT, uric acid, transient hypoglycemia after a meal very rarely – proteinuria, hematuria.

Allergic reactions: skin rash, hives, swelling of the face, wheezing, shortness of breath.

Other: headache, fatigue, weakness, epistaxis, petechiae, and erythema nodosum.

Filgrastim does not increase the frequency of adverse reactions of cytotoxic therapy.

Contraindications:

– severe congenital neutropenia syndrome (Kostmann) with cytogenetic abnormalities

– the use of the drug, with increasing doses of cytotoxic chemotherapy drugs that exceed recommended dose

– hypersensitivity to filgrastim or other components of the drug.

With caution should use the drug with precancerous and malignant diseases of myeloid character (including acute myelogenous leukemia), sickle-cell anemia.

Pregnancy and lactation:

Drug category C. the Safety of filgrastim in pregnancy is not established, therefore, in appointing the drug to pregnant women should be weighed the expected benefit to the mother and the potential risk to the fetus.

It is unknown whether filgrastim is excreted in breast milk. To use filgrastim in the period of breast-feeding is not recommended.

Special instructions:

Should be treated with Neipomax only under the supervision of a doctor with experience in the use of KSF and with the necessary diagnostic capabilities. Procedures for the mobilization and apheresis cells should be performed in specialized medical institutions.

The safety and effectiveness of filgrastim in patients with myelodysplastic syndrome and chronic myelogenous leukemia is not installed, therefore in these diseases to apply filgrastim is not recommended. Special attention should be paid to the differential diagnosis between acute myeloid leukemia and blast crisis of chronic myeloid leukemia.

Before assigning Neipomax paycenter with TKHN should carefully make a differential diagnosis to exclude other hematological diseases such as aplastic anemia, myelodysplasia and chronic myeloid leukemia (before starting therapy should conduct a morphological and cytogenetic analysis of the bone marrow).

With the use of filgrastim in patients with TKHN was marked by the occurrence of myelodysplastic syndrome and acute myeloid leukemia. Despite the fact that the connection between the occurrence of these diseases with the use of filgrastim is not installed, use the drug during TKHN should be used with caution under the control of morphological and cytogenetic bone marrow analysis (1 time per 12 months). With the appearance of cytogenetic anomalies in the bone marrow should carefully evaluate the risk-benefit ratio when further therapy with filgrastim. With the development of myelodysplastic syndrome or leukemia Neipomax should be abolished.

Treatment Neipomax should be under regular monitoring of complete blood count with leukocyte count and platelet count (before starting therapy and then 2 times a week with standard chemotherapy and at least 3 times a week for mobilization of TUAC with or without subsequent bone marrow transplantation). When applying Neipomax to mobilize pskk a preparation cancel, if the number of leukocytes exceeds 1х105/µl. With a stable platelet count, not exceeding 1х105/µl, it is recommended to temporarily cancel the therapy with filgrastim or to reduce the dose of the drug.

Filgrastim prevents due to myelosuppressive chemotherapy thrombocytopenia and anemia. During treatment Neipomax should regularly do a urine test (to exclude hematuria and proteinuria) and control the size of the spleen.

Filgrastim should be used with caution in patients with sickle-cell anemia in connection with a possible substantial increase in the number of sickle cells.

The safety and efficacy of the drug in patients with autoimmune neutropenia is not installed.

Patients with bone pathology and osteoporosis, and receiving continuous treatment with Neipomax more than 6 months, monitoring is required in bone density.

The effect of filgrastim on the graft versus host is not installed.

Use in Pediatrics

Recommendations for dosing regime for children with those for adults.

Data on the safety and effectiveness of filgrastim in healthy donors under the age of 16 do not exist.

The safety and efficacy of the drug in newborns is not established.

Overdose:

The effects of an Neipomax unknown.

1-2 days after drug withdrawal, the number of circulating neutrophils is usually reduced by 50%, with a return to normal in 1 -7 days.

Drug interactions:

The safety and effectiveness of the introduction of filgrastim in the same day as myelosuppressive antineoplastic agents not established.

There are separate reports on the strengthening of neutropenia together with the appointment of filgrastim and 5-fluorouracil. Data on possible interactions with other haematopoietic growth factors and cytokines currently there.

Lithium, stimulating the release of neutrophils can exacerbate the effects of filgrastim.

Pharmaceutical interaction

Breeding 0.9% solution of sodium chloride is not allowed because of incompatibilities of pharmaceutical.

Terms and conditions of storage:

List B. the Drug should be stored out of the reach of children in protected from light place at temperature not exceeding 25°C. shelf Life – 2 years.