Neupogen - Instructions For Use, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Neupogen

Neupogen: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Neupogen

ATX code: L03AA02

Active ingredient: filgrastim (filgrastim)

Manufacturer: F. Hoffmann-La Roche Ltd. (F. Hoffmann-La Roche, Ltd.) (Switzerland)

Description and photo update: 2018-21-11

Prices in pharmacies: from 2579 rubles.

Buy

Neupogen is a stimulator of the process of leukocyte formation.

Release form and composition

• solution for subcutaneous (s / c) administration: clear liquid, colorless or slightly yellowish, with or without a faint odor (0.5 ml each in syringe tubes equipped with a sterile injection needle, 1 set in a cardboard box);
• solution for s / c and intravenous (i / v) administration: clear liquid, colorless or slightly yellowish, with or without a faint odor [1 ml (300 mcg) in vials, in a cardboard box 5 vials; 1.6 ml (480 μg) in vials, in a cardboard box 1 or 5 vials].

0.5 ml (1 syringe tube) solution for subcutaneous administration contains:

• active ingredient: filgrastim - 300 or 480 mcg;
• auxiliary ingredients: glacial acetic acid, polysorbate 80, sorbitol, sodium hydroxide, water for injection.

1 ml of solution for subcutaneous and intravenous administration contains:

• active ingredient: filgrastim - 300 mcg;
• auxiliary ingredients: glacial acetic acid, polysorbate 80, sorbitol, sodium hydroxide, water for injection.

Pharmacological properties

Pharmacodynamics

The active component of Neupogen is filgrastim, a hematopoietic growth factor, a non-glycosylated, highly purified protein of 175 amino acids, produced by Escherichia coli K12 (E. coli K12). For its production, the human G-CSF (granulocyte colony-stimulating factor) gene is introduced into the E. coli genome by genetic engineering methods.

Human G-CSF is a glycoprotein that regulates the formation of functionally active neutrophils with their subsequent release from the bone marrow into the blood. Neupogen containing recombinant G-CSF clinically significantly increases the number of neutrophils in the peripheral blood already in the first day after its administration, while the number of monocytes increases slightly. In patients with TCN (severe chronic neutropenia), the drug can also cause a slight increase in the number of circulating basophils and eosinophils.

Filgrastim dose-dependently increases the number of neutrophils with normal or increased functional activity. At the end of the course of therapy, their number in the peripheral blood flow decreases by 50% within 1–2 days, after which it returns to normal levels over the next 1–7 days. The duration of action with intravenous administration may be reduced. The clinical significance of this effect with repeated administration of filgrastim is unclear.

By significantly reducing the frequency, duration and severity of neutropenia and neutropenic fever, the drug reduces the need and duration of hospitalization for patients receiving myeloablative therapy (with further bone marrow transplantation) or cytostatic chemotherapy.

Patients receiving cytotoxic chemotherapy in combination with Neupogen require lower doses of antibiotics in comparison with those receiving exclusively cytotoxic chemotherapy.

The duration of febrile neutropenia decreases, the need for antibiotics and hospitalization during treatment with Neupogen after induction chemotherapy of acute myeloid leukemia decreases. The drug does not affect the frequency of fever and infectious complications.

Neupogen, including after chemotherapy, mobilizes the release of hemocytoblasts into the peripheral bloodstream. Allogeneic or autologous peripheral blood stem cell (PBC) transplantation is performed after taking high doses of cytostatics instead of or in addition to bone marrow transplantation. It is also possible to prescribe PSCC transplantation after myelosuppressive cytotoxic therapy in high doses. The use of PSCC mobilized with Neupogen accelerates the recovery of hematopoiesis, reduces the severity and duration of the risk of hemorrhagic complications, thrombocytopenia, and the need for platelet transfusion after myelosuppressive / myeloablative therapy.

The efficacy and safety indicators of Neupogen in adult patients and children receiving cytotoxic chemotherapy are equal.

In patients of all age groups with severe chronic neutropenia (intermittent, congenital, idiopathic), Neupogen administration steadily increases the number of neutrophils in the peripheral blood, reducing the incidence of infectious complications.

Reception of Neupogen for human immunodeficiency virus (HIV) allows you to maintain a baseline level of neutrophils and use the recommended doses of antiretroviral and other myelosuppressive treatment. In this case, there are no signs of an increase in HIV replication.

G-CSF, like other hematopoietic growth factors, stimulates human endothelial cells in vitro.

Pharmacokinetics

Filgrastim, when administered intravenously and subcutaneously, demonstrates a positive linear dependence of the concentration of the substance in the blood serum on the administered dose. Due to subcutaneous administration in therapeutic doses, the concentration of the drug exceeds 10 ng / ml for 8 to 16 hours. The volume of distribution (V _d) is 150 ml / kg.

Filgrastim elimination, regardless of the route of administration, proceeds according to the rules of kinetics of the 1st order. The half-life (T _1/2) is 3.5 hours, the clearance is 0.6 ml / min / kg.

With prolonged use after autologous bone marrow transplantation (up to 4 weeks), filgrastim does not cause cumulation and increase in T _1/2.

In end-stage renal failure, there is an increase in the maximum concentration (C _max) in the serum, an increase in the area under the concentration-time curve (AUC), a decrease in V _d and clearance in comparison with healthy volunteers, as well as patients with moderate renal failure.

Indications for use

According to the instructions, Neupogen is recommended for use in adult patients and children with the following diseases / conditions:

• neutropenia and febrile neutropenia due to intensive myelosuppressive cytotoxic chemotherapy for malignant neoplasms (except for chronic myeloid leukemia and myelodysplastic syndrome); neutropenia and its clinical manifestations during myeloablative therapy followed by allogeneic / autologous bone marrow transplantation, aggravated by an increased likelihood of developing severe prolonged neutropenia;
• mobilization of autologous PSCC, including after myelosuppressive therapy; mobilization of PSCC (allogeneic) in healthy donors;
• severe recurrent, congenital or idiopathic neutropenia in children and adults [ANC (absolute neutrophil count) ≤ 0.5 × 10 ⁹ / L] with a history of severe or recurrent infections - to increase the number of neutrophils, reduce the frequency and duration of various infectious complications;
• persistent neutropenia in patients with an advanced stage of HIV (ANC ≤ 1 × 10 ⁹ / l) - to reduce the likelihood of bacterial infection if it is impossible to use other methods of therapy;
• neutropenia in patients with acute myeloid leukemia receiving chemotherapy (induction / consolidation) - to reduce its duration and frequency, as well as to reduce the duration of clinical consequences.

Contraindications

Absolute:

• severe congenital hereditary neutropenia (childhood genetically determined agranulocytosis or Kostmann's syndrome) with cytogenetic disorders;
• simultaneous use with cytotoxic chemotherapy / radiation therapy;
• end-stage chronic renal failure;
• lactation period;
• children's age from birth to 28 days (neonatal period);
• a history of increased individual sensitivity to filgrastim or any other components of the drug.

Neupogen cannot be used to increase doses (above the recommended) of cytotoxic chemotherapy drugs.

Relative contraindications for which Neupogen should be used with caution:

• period of pregnancy;
• malignant and precancerous conditions / diseases of a myeloid nature, including primary (de novo) and secondary acute myeloid leukemia;
• combined use with high-dose chemotherapy.

Instructions for the use of Neipogen: method and dosage

The solution is administered subcutaneously or in the form of short (30 minutes) intravenous infusions on 5% dextrose solution. The method of administration of the solution is chosen depending on the clinical situation, preference is given to the subcutaneous route of administration.

The vial and syringe tube with Neupogen solution are intended solely for single use.

The solution is injected daily until the number of neutrophils passes the required minimum (nadir) and rises to the normal level.

Recommended dosage according to indications:

• cytotoxic chemotherapy (standard regimens): 5 μg (0.5 million IU) / kg once a day. The first dose of filgrastim should be administered no earlier than 1 day after completion of the course of cytotoxic chemotherapy. The duration of the course is up to 14 days. Upon completion of the induction and consolidation treatment of acute myelogenous leukemia, the duration of the course may increase up to 38 days (depending on the scheme of cytotoxic chemotherapy, its type and doses used). After 1–2 days from the start of treatment, a transient increase in the number of neutrophils is usually observed, but to achieve a stable therapeutic effect, treatment should be continued until their number exceeds the expected minimum level and reaches a normal value. It is premature and not recommended to cancel Neupogen before the neutrophil level exceeds the expected minimum. Treatment is completed when the ANC (absolute number of neutrophils) after nadir (maximum decrease in their number) reaches 1 × 10⁹ / l;
• the period after myeloablative therapy followed by autologous / allogeneic bone marrow transplantation: initial dose - 10 μg (1 million IU) / kg per day; injected intravenously (30 minutes or 24 hours) or subcutaneously by continuous infusion (24 hours). The first dose of filgrastim should be administered no earlier than 1 day after completion of the course of cytotoxic chemotherapy, and for transplantation of hematopoietic stem cells of peripheral blood - no later than 1 day after their infusion. The duration of the course is no more than 28 days. After reaching nadir, depending on the dynamics of the number of neutrophils, the daily dose is corrected. If the level of neutrophils is> 1 × 10 ⁹ / l for 3 consecutive days, the dose of Neupogen is reduced to 5 μg (0.5 million U) / kg per day; with ACN> 1 × 10 ⁹/ l for 3 consecutive days - the drug is canceled. If in the course of ARC therapy it is below 1 × 10 ⁹ / L, then the dose of filgrastim is increased again according to the scheme described above;
• mobilization of PSCC after myelosuppressive therapy followed by autologous transfusion of PSCC with / without bone marrow transplantation or in patients with myeloablative therapy and subsequent transfusion of PSCC: 10 μg (1 million U) / kg per day; administered once a day as a subcutaneous injection or continuous subcutaneous infusion (24 hours). The course duration is 6 days, on the 5th, 6th days leukapheresis is performed, two procedures are usually enough. Sometimes additional extraction of leukocytes is required, while Neupogen continues to be administered until the last leukapheresis;
• mobilization of PSCC after myelosuppressive chemotherapy: 5 μg (0.5 million units) / kg per day; injected subcutaneously by injection, daily, from the first day after completion of chemotherapy and until the steady transition of the number of neutrophils through the expected minimum and reaching normal levels. Leukapheresis is performed during the period when the ACN rises from <0.5 × 10 ⁹ / L to> 5 × 10 ⁹ / L. For patients who have not received intensive chemotherapy, one leukapheresis procedure is sufficient, in other cases additional procedures are necessary;
• mobilization of PSCC in healthy donors in order to prepare for allogeneic transplantation: 10 μg (1 million U) / kg per day; entered s / c for 4-5 days. From the 5th day, leukapheresis is performed, if necessary, prolonged until the 6th day in order to obtain CD34 + cells ≥ 4 × 10 ⁶ / kg of the recipient's body weight. In healthy donors before the age of 16 and after 60 years, the efficacy and safety of use have not been studied;
• THN: filgrastim is injected s / c daily, at a time or divided into several injections; congenital neutropenia: initial dose - 12 mcg (1.2 million units) / kg per day; idiopathic or intermittent neutropenia - 5 μg (0.5 million U) / kg per day until the neutrophil level is stable exceeded 1.5 × 10 ⁹ / l. Upon reaching a therapeutic effect, it is required to determine the minimum effective dose in order to maintain this level, which is administered daily for a long time. After 1–2 weeks, depending on the patient's response to treatment, the initial dose may be doubled or halved. Individual dose adjustment during further treatment can be done once every 1–2 weeks, maintaining the neutrophil count in the range from 1.5 to 10 × 10 ⁹/ l. For severe infections, a more intense dose escalation regimen is used. In 97% of cases, when patients responded positively to therapy, the maximum clinical effect is observed with doses up to 24 μg / kg per day. The maximum daily dose of filgrastim is 24 μg / kg;
• neutropenia in HIV infection: an initial dose of 1–4 μg (0.1–0.4 million units) / kg per day; injected s / c daily, 1 time, until the level of neutrophils normalizes, which usually occurs after 2 days. Upon reaching the therapeutic effect, a maintenance dose of 300 mcg per day is administered 2-3 times a week using an alternating regimen (every other day). Further treatment may require dose adjustment and long-term administration of the drug to maintain an average neutrophil count> 2 × 10 ⁹ / L. The maximum daily dose is 10 μg / kg.

Directions for diluting Neupogen solution:

1. The drug is allowed to be diluted with only 5% glucose solution. Dilution with 0.9% NaCl solution and dilution to a final concentration of <5 μg / ml is not allowed.
2. When diluted to a concentration of <15 μg / ml (1.5 million U / ml), human serum albumin must be added to the solution, bringing its final concentration to 2 mg / ml [for example, when the required volume of the final solution is 20 ml, the total doses of Neupogen are < 300 μg (30 million units) is injected with the addition of a 20% albumin solution in an amount of 0.2 ml].
3. The diluted preparation can be adsorbed to glass and plastics, but when diluted with 5% glucose solution, Neupogen is compatible with glass and a number of plastics, including polyvinyl chloride, polyolefin (copolymer of polypropylene and polyethylene) and polypropylene.
4. The finished solution is stored for no more than a day at a temperature of 2 to 8 ° C.

Side effects

The following scale was used for the frequency of side effects determined from clinical trials: very often - more than 10%; often - from 1 to 10%; infrequently - less than 1%; rarely - less than 0.01%.

The drug does not increase the frequency of side reactions of the body to cytotoxic chemotherapy; undesirable effects were observed with the same frequency in patients receiving Neupogen / chemotherapy and placebo / chemotherapy.

Side effects in patients with cancer:

• the body as a whole: often - general weakness, fatigue, mucositis (inflammation of the mucous membranes), anorexia; infrequently - nonspecific pain; rarely - exacerbation of rheumatoid arthritis;
• musculoskeletal system: often - bone pain (especially in bone tissue with active hematopoiesis), chest pain, muscle pain (weak or moderate - up to 10%, strong - up to 3%; in most cases, they can be stopped by conventional analgesics);
• digestive system: very often - nausea / vomiting; often constipation or diarrhea;
• cardiovascular system: extremely rarely - transient arterial hypotension (drug correction is not required); vascular disorders associated with a change in the amount of fluid in the body when receiving high doses of chemotherapy followed by bone marrow transplantation (autologous) and veno-occlusive disease (the relationship of vascular reactions with filgrastim therapy has not been established);
• respiratory system: often - sore throat, cough; rarely - interstitial pneumonia, infiltrates in the lungs, pulmonary edema, in isolated episodes with an unfavorable course - respiratory failure, respiratory distress syndrome in adults (up to death);
• skin and subcutaneous fat: often - skin rash, alopecia; rarely - acute febrile neutrophilic dermatosis (Sweet's syndrome), cutaneous vasculitis (the mechanism of development is not known);
• nervous system: often - headache;
• the immune system: rarely - hypersensitivity reactions (about half of the immune responses are associated with the introduction of the first dose, especially the intravenous dose; in some cases, resumption of therapy is accompanied by a relapse of symptoms);
• urinary system: rarely - problems with urination (most often manifest as mild to moderate dysuria);
• laboratory data: very often - an increase in the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), an increase in serum uric acid concentration (all deviations are usually dose-dependent, reversible, weak or moderate).

Side effects in patients with HIV infection:

• musculoskeletal system: very often - pain in muscles (myalgia) and bones, mostly weak or moderate (the frequency is comparable to that of cancer patients);
• hematopoietic system: often - splenomegaly (the connection with filgrastim use was detected in less than 3% of cases; in all episodes, mild to moderate splenomegaly with a favorable clinical course was observed during physical examination; hypersplenism was not recorded; splenectomy was not required in any of the cases). Splenomegaly is a fairly common concomitant condition in patients with HIV, as well as in varying degrees of severity in most patients with AIDS - its relationship with the use of Neupogen in such cases has not been established.

Side effects in healthy donors (mobilization of allogeneic PSCC):

• the body as a whole: rarely - exacerbation of rheumatoid arthritis;
• musculoskeletal system: very often - pain in muscles and bones, mostly mild or moderate;
• nervous system: very often - headache;
• respiratory system: rarely - infiltrates in the lungs, hemoptysis;
• immune system: infrequently - severe hypersensitivity reactions;
• hematopoietic system: very often - leukocytosis (> 50 × 10 ⁹ / L) (recorded in 41% of healthy donors), transient thrombocytopenia (<100 × 10 ⁹ / L) (recorded in 35% of healthy donors); often - splenomegaly (without clinically significant manifestations); infrequently - impaired spleen function;
• laboratory data: often - a transient slight increase in the activity of alkaline phosphatase, LDH; infrequently - a slight, without clinical consequences, an increase in the activity of aspartate aminotransferase (AST), hyperuricemia.

Side effects in patients with TCN (over time, the frequency of adverse reactions decreases):

• the body as a whole: often (<2%) - reactions (including pain) at the injection site, arthralgia;
• musculoskeletal system: very often - pain in bones and muscles; often (<2%) - osteoporosis;
• digestive system: often - diarrhea, mainly immediately after the start of treatment, hepatomegaly (<2%);
• skin and subcutaneous fat: often (<2%) - rash, alopecia, cutaneous vasculitis;
• nervous system: often (<2%) - headache, mainly immediately after the start of treatment;
• genitourinary system: infrequently - proteinuria, hematuria;
• hematopoietic system: very often - anemia, splenomegaly (sometimes progressive); often - thrombocytopenia; infrequently - dysfunction of the spleen, sometimes nosebleeds were observed;
• laboratory data: very often - a transient increase in the activity of alkaline phosphatase, LDH without clinical symptoms; transient moderate hypoglycemia (after eating), hyperuricemia.

Side effects according to post-registration observations:

• immune system: rarely - hypersensitivity reactions, including anaphylaxis, skin rash, urticaria (may develop at the beginning of filgrastim use or with repeated treatment); sometimes, when therapy was resumed, a relapse of symptoms was noted, suggesting a relationship between drug use and the occurrence of adverse reactions. In the event of severe allergic responses, discontinuation of therapy is required;
• hematopoietic system: individual episodes of sickle-cell crises with a possible fatal outcome are described, cases of rupture of the spleen both in patients with cancer and in healthy donors;
• skin and subcutaneous fat: rarely (from 0.01 to 0.1%) - acute febrile neutrophilic dermatosis (Sweet's syndrome); in isolated cases (with an estimated frequency of 0.001%) when filgrastim is used against the background of oncological diseases - cutaneous vasculitis;
• metabolism: in isolated cases, when filgrastim is used against the background of oncological diseases, pseudogout (chondrocalcinosis);
• laboratory data: with filgrastim therapy after cytotoxic chemotherapy - a transient (usually mild and moderate) increase in serum uric acid concentration, LDH and ALP activity without clinically significant consequences.

Overdose

Filgrastim overdose cases have not been reported.

Usually, 1–2 days after discontinuation of filgrastim, the number of neutrophils decreases by 50%, after which it returns to normal levels after 1–7 days.

special instructions

The use of Neupogen is allowed only under the supervision of an oncologist or hematologist with experience in using G-CSF, in a room equipped with everything necessary for diagnosis. Cell mobilization and apheresis should be performed at an oncology or hematology center by personnel who have experience in this area and the ability to adequately monitor hematopoietic progenitor cells.

The safety and efficacy of filgrastim in patients with myelodysplastic syndrome and chronic myeloid leukemia have not been established, and therefore its use in such patients is contraindicated. Emphasis should be placed on the differential diagnosis between the blast crisis of chronic myeloid leukemia and acute myeloid leukemia.

Human G-CSF is able to stimulate the growth of myeloid cells in vitro; similar effects in vitro can be observed in relation to some non-myeloid cells.

Cytotoxic chemotherapy

Less than 5% of patients who received filgrastim at doses of more than 3 μg (0.3 million IU) / kg per day, the concentration of leukocytes increased to 100 × 10 ⁹ / L or more. No side effects directly associated with such leukocytosis were observed. However, taking into account the possible risk associated with high leukocytosis, you should regularly determine the number of leukocytes during the use of Neupogen. When, after passing the expected minimum, this figure exceeds 50 × 10 ⁹ / l, it is required to stop using the drug. In the case of using filgrastim to mobilize PSCC, it is canceled when the concentration of leukocytes exceeds 70 × 10 ⁹ / l.

Particular care is recommended when treating patients receiving high-dose chemotherapy, since higher doses of chemotherapy have a more pronounced toxic effect, increasing skin reactions and side effects from the nervous, respiratory and cardiovascular systems.

Neupogen used as monotherapy does not prevent the anemia and thrombocytopenia associated with myelosuppressive chemotherapy. Because it allows for the use of higher doses of chemotherapy, up to full doses as prescribed, the patient may be at increased risk of anemia and thrombocytopenia. In this regard, it is recommended to regularly, twice a week, donate blood for analysis to determine the number of platelets and hematocrit. Particular care must be taken when using single-component or combined chemotherapy regimens that can cause severe thrombocytopenia.

Severe chronic neutropenia (THN)

Given the risk of transformation of TCN into leukemia or pre-leukemia, special care is required when diagnosing the disease in order to confidently differentiate TCN from other hematological pathologies, such as myeloid leukemia, myelodysplasia, and aplastic anemia. Before the start of the course, a detailed blood test should be done to determine the number of platelets and leukocyte counts, as well as to study the morphological picture of the bone marrow and karyotype.

In 3% of patients with Kostmann's syndrome (severe congenital neutropenia) who received Neupogen, leukemia and MDS (myelodysplastic syndrome) were identified, which are natural complications of the underlying disease, but their relationship with filgrastim use has not been clarified. About 12% of patients with initially normal cytogenetics showed abnormalities during re-examination, including monosomy of chromosome 7. When cytogenetic pathologies appear in a patient with Costmann's syndrome, a careful assessment of the ratio of the benefits of therapy with the risk of its continuation is required. The development of MDS or leukemia requires discontinuation of the drug. To date, the question of whether prolonged use of Neupogen in Kostmann's syndrome predisposes to the development of MDS, leukemia, and cytogenetic abnormalities remains open. Such patients are recommended to regularly (at least once a year) undergo morphological and cytogenetic examinations of the bone marrow.

Leukemia, osteoporosis, and cytogenetic disorders were found in 9.1% of patients with concomitant CNS therapy with Neupogen (more than 5 years), but their relationship with the drug intake has not been established.

The blood count must be carefully monitored, especially in the first few weeks of Neupogen therapy, 2 times a week to do a clinical blood test and determine the number of platelets. For patients in a stable condition, the procedure is then carried out once a month. When thrombocytopenia appears (platelet count is consistently below 100 × 10 ⁹ / l), the question of discontinuing the drug for a while or reducing its dose is considered. Other changes in the blood count observed during treatment, such as anemia, a transient increase in the number of myeloid progenitor cells, also require careful monitoring.

It is important to rule out a viral cause of transient neutropenia.

The increase in the size of the spleen is a direct consequence of the use of filgrastim. According to clinical studies, splenomegaly was found on palpation in 31% of patients with TCN. Radiography shows an increase in the volume of the spleen soon after the start of treatment, the process tends to stabilize. Reducing the dose of the drug slows down or stops its increase; up to 3% of patients may experience the need for splenectomy. The size of the spleen must be regularly monitored by palpation.

Some patients may develop hematuria and proteinuria, in order to monitor these indicators, urinalysis should be performed regularly.

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

Mobilization of Autologous Peripheral Blood Stem Cells (PBCS) in Patients

Bone marrow transplant patients require a blood test and platelet count 3 times a week.

Two methods are recommended for mobilization: filgrastim monotherapy or combination therapy with myelosuppressive cytotoxic chemotherapy drugs. Since no comparison has been made between these methods in the same contingent, the method of mobilization should be selected depending on the general goals and objectives of the treatment of a particular patient.

It is more difficult for patients who have received active myelosuppressive therapy in the past to achieve sufficient PSCC growth to the minimum recommended level (≥ 2 × 10 ⁶CD34 + / kg) or accelerate the normalization of platelet count. Due to their particular toxicity towards hematopoietic progenitor cells, some cytostatics can adversely affect their mobilization. The combined use of filgrastim with melphalan, carboplatin, or carmustine is effective in activating PSCC; therefore, when planning transplantation, it is recommended to start mobilizing stem cells at an early stage of treatment. Particular attention is paid to the number of progenitor cells activated prior to high-dose chemotherapy. If the results do not meet the requirements of mobilization, alternative therapies are considered that do not require the use of progenitor cells.

When assessing the amount of PSCC mobilized in patients using Neupogen, special attention is paid to the method of quantitative determination. The readings of the flow cytometric analysis of the number of CD34 + cells differ depending on the used determination methodology. Caution is required with regard to concentration recommendations based on results obtained in other laboratories.

There is a complex but stable statistical correlation between the number of CD34 + cells injected into reinfusion and the rate of normalization of platelet levels after high-dose chemotherapy. The minimum concentration of PSCC (≥ 2 × 10 ⁶ CD34 + cells / kg) leads to a satisfactory restoration of hematological characteristics.

Mobilization of allogeneic peripheral blood stem cells (PBSC) in healthy donors

Mobilization and apheresis of PSCC should be carried out in a center with experience in carrying out such procedures. It is possible to start mobilization if laboratory parameters, especially hematological parameters of the donor, meet the selection criteria.

In healthy donors, transient leukocytosis is observed in 41% with a leukocyte count of more than 50 × 10 ⁹ / L, in 2% - more than 75 × 10 ⁹ / L. Transient thrombocytopenia with a platelet count of less than 100 × 10 ⁹ / L after filgrastim with leukapheresis is observed in 35% of donors, in two cases after leukapheresis a platelet count of less than 50 × 10 ⁹ / L was noted.

If more than one leukapheresis is required, it is necessary to control the platelet count before each apheresis procedure, especially when the platelet count is less than 100 × 10 ⁹ / L. It is not recommended to carry out leukapheresis when the neutrophil level is less than 75 × 10 ⁹ / l, in conjunction with anticoagulants, or with known hemostasis disorders.

When the level of leukocytes exceeds 70 × 10 ⁹ / l, Neupogen must be canceled or its dose reduced.

Healthy donors are regularly monitored for all blood count indicators until they are normalized.

Considering the isolated cases of rupture of the spleen in healthy donors after the appointment of G-CSF, it is required to control its size by ultrasound (US) or palpation.

The process of long-term monitoring of the safety of filgrastim use in healthy donors continues. There were no reports of a violation of their hematopoiesis up to 4 years after the appointment of Neupogen. Nevertheless, the apheresis center recommends systematic monitoring of the long-term safety of the drug in healthy donors.

Recipients of allogeneic PSCCs obtained with Neupogen should take into account that the use of such a graft may be associated with an increased risk of developing an acute or chronic graft versus host reaction.

Neutropenia in HIV-infected patients

During Neupogen therapy in patients with HIV infection, it is necessary to regularly do a detailed blood test (ANC, platelets, erythrocytes, etc.): daily for the first few days, then the first 2 weeks, 2 times a week, then during maintenance treatment every week or every other week. Taking into account fluctuations in the value of ANC, blood sampling should be carried out to determine nadir immediately before the introduction of the next dose of the drug.

In patients with infectious diseases and bone marrow infiltration with infectious pathogens (Mycobacterium avium complex) or with tumor lesions of the bone marrow, Neupogen therapy is carried out simultaneously with treatment directed against these conditions.

Other special precautions

Patients with sickle cell disease require regular monitoring of the blood count, taking into account the possibility of developing splenomegaly and / or vascular thrombosis.

Patients with osteoporosis and bone pathology, who receive continuous treatment with Neupogen for more than six months, need to control the bone density.

With a significantly reduced number of myeloid progenitor cells, the effectiveness of filgrastim is unknown, since it increases the number of neutrophils by acting primarily on the precursor cells of neutrophils. Therefore, with their reduced content, for example, after intensive radiation or chemotherapy, the degree of increase in the number of neutrophils may be lower.

The sorbitol content in the preparation is 50 mg / ml, therefore, patients with hereditary fructose intolerance need to be careful.

In case of respiratory distress syndrome in adult patients, drug therapy is canceled and appropriate treatment is prescribed.

Influence on the ability to drive vehicles and complex mechanisms

The influence of Neupogen on concentration of attention and speed of psychomotor reactions was not observed.

Application during pregnancy and lactation

The safety of Neupogen for pregnant women has not been established; the passage of filgrastim through the placental barrier is possible. Studies carried out on rats and rabbits did not reveal a teratogenic effect of the drug. In rabbits, the frequency of miscarriages without fetal abnormalities increased.

The appointment of Neupogen during pregnancy is permissible after a careful assessment of the benefit to the mother / risk to the fetus ratio.

It is not known for certain whether filgrastim passes into breast milk; therefore, it is not recommended to prescribe Neupogen to nursing mothers.

Pediatric use

Neupogen is used to treat children over 28 days old (neonatal period) according to indications and in recommended doses.

When the drug was used in children with concurrent CNS and oncological diseases, its safety profile was identical to that in adult patients. Dosage for pediatric patients is the same as for adults receiving myelosuppressive cytotoxic chemotherapy treatment.

With impaired renal function

Neupogen dose adjustment is not required in patients with severe renal insufficiency, since the pharmacokinetic and pharmacodynamic parameters of filgrastim are similar to those in healthy people.

For violations of liver function

Neupogen dose adjustment is not required in patients with severe hepatic impairment, since the pharmacokinetic and pharmacodynamic parameters of filgrastim are similar to those in healthy people.

Use in the elderly

For elderly patients, there are no special recommendations for the use of Neupogen.

The safety and efficacy of the drug has not been evaluated in healthy donors over 60 years of age.

Drug interactions

The safety and efficacy of Neupogen administration on the same day as myelosuppressive cytotoxic chemotherapy drugs have not been established. However, due to the increased sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, it is not recommended to administer filgrastim 24 hours before or after these drugs.

Prescribing Neupogen along with fluorouracil may aggravate the severity of neutropenia. Potential interactions with other cytokines and hematopoietic growth factors are unknown.

Since lithium stimulates the release of neutrophils, theoretically it can enhance the effect of Neupogen in combined use, but in practice such studies have not been carried out.

An increase in the hematopoietic activity of the bone marrow in response to the use of growth factors leads to positive transient changes in bone imaging, this should be taken into account when interpreting the results.

Neupogen solution is pharmaceutically incompatible with 0.9% sodium chloride solution, therefore they cannot be mixed.

Analogs

Analogs of Neipogen are: Grasalva, Granogen, Zarcio, Immugrast, Leucita, Leucostim, Mielastra, Neipomax, Neutrostim, Tevagrastim, Filgrastim-Nanolek, Filgrastim and others.

Terms and conditions of storage

Keep out of the reach of children. Store and transport in a temperature range of 2-8 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Neipogen

According to reviews, Neupogen is a very effective drug for restoring the number of neutrophils and normalizing the blood count after chemotherapy, treatment of viral hepatitis C according to the protocol, in other cases when necessary. Of the side effects, most often noted are a decrease in blood pressure, muscle pain and dysuric disorders.

Price for Neupogen in pharmacies

The approximate price of Neipogen can be: for 1 syringe-tube (30 million U / 0.5 ml) - 4492-5208 rubles, for 5 bottles (30 million U / 0.5 ml) - 7900 rubles.

Neupogen: prices in online pharmacies

Drug name Price Pharmacy

Neupogen 30 mln IU solution for subcutaneous administration 0.5 ml 1 pc. 2579 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!