GRASALVA
Active material: Filgrastim
When ATH: L03AA02
CCF: Stimulator leykopoeza
ICD-10 codes (testimony): D70
When CSF: 19.01.01.01
Manufacturer: TEVA Pharmaceutical Industries Ltd. (Israel)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
The solution for I / O and p / to the introduction clear, colorless.
| 1 syringe (1 ml) | |
| filgrastim | 30 Million International Units (300 g) |
Excipients: acetic acid, Sodium hydroxide, sorbitol, polysorbate 80, water d / and.
1 ml – Disposable glass syringes (1) – packings Valium planimetric (1) complete with a sterile needle in a blister – packs cardboard.
The solution for I / O and p / to the introduction clear, colorless.
| 1 syringe (0.8 ml) | |
| filgrastim | 48 Million International Units (480 g) |
Excipients: acetic acid, Sodium hydroxide, sorbitol, polysorbate 80, water d / and.
0.8 ml – Disposable glass syringes (1) – packings Valium planimetric (1) complete with a sterile needle in a blister – packs cardboard.
Pharmacological action
Recombinant human G-CXF. Philgrastim has the same biological activity, Like the endogenous human G-CXF, And the latter differs only, What is a non-glycosylated protein with an additional N-conte residue of methionine. Filgrastim, obtained by recombinant DNA technology, separated from cells of the bacterium Escherichia coli, a part of the genetic apparatus which introduced gene, g-CSF protein.
Human G-CXF – glycoprotein, regulating the formation of functionally active neutrophils and their exit to the blood from the bone marrow. Filgrastim, with the activity of G-CXF, significantly increases the number of neutrophils in peripheral blood already in the first 24 h after introduction with a slight increase in the number of monocytes. With severe chronic neutropenia, in some cases, phylgratim can also cause a slight increase in the number of circulating eosinophils and basophils compared to the initial values.
In the interval of recommended doses of Philgrastim, a dose -dependent increase in the number of neutrophils with normal or increased chemotactic and phagocytic activity is observed. After the treatment is completed, the number of neutrophils in peripheral blood decreases by 50% during 1-2 days and returns to the normal level during subsequent 1-7 days.
Philgrastim significantly reduces the frequency, severity and duration of neutropenia and febrile neutropenia after cytotoxic chemotherapy.
Philgrastim significantly reduces the duration of febrile neutropenia, The duration of antibiotic therapy and hospitalization after induction chemotherapy in acute myelocosis, And also after myeloablative therapy, followed by bone marrow transplantation, without affecting the frequency of fever and infectious complications and without reducing the duration of the febrile period in patients after myeloablative therapy, followed by bone marrow transplantation.
The use of phylgrastim as independently, and after chemotherapy, the exit of hematopoietic stem cells into peripheral blood flow mobilizes. Autological or allogene transplantation of peripheral blood stem cells (TUAC) can be carried out after highly treated treatment with cytostatics or instead of bone marrow transplantation, or in addition to it. PSKK transplantation accelerates the restoration of blood formation, Reducing the danger of hemorrhagic complications and the need for transfusion of platelet mass.
The use of phylgrastim in recipients of mobilized allogeneous PSKKs leads to a faster normalization of hematological indicators in comparison with transplantation of allogene bone marrow. The normal number of platelets is restored and the need to control thrombocytopenia disappears.
The appointment of healthy donors of Philgrastim by 10 mcg/kg/day n/k daily during 4-5 days usually allows you to get the number of PSKK when conducting two lecaferes, equal or exceeding 4×106 CD34+-cells/kg of body weight of the recipient.
In children and adults with severe chronic neutropenia (congenital, periodic or idiopathic) Philgrastim stably increases the amount of neutrophils in peripheral blood, reduces the frequency of infections and related complications. The appointment of phylgrastim to patients with HIV infection allows you to support the normal level of neutrophils, which contributes to the systematic antiviral and/or myelosupressive therapy. There were no signs of an increase in HIV replication in the treatment of phylgrastim.
Like other hematopoietic growth factors, Philgrastim stimulates in vitro proliferation of human endothelial cells.
Pharmacokinetics
As with the/in, and with the p/c administration of the drug, Philgrastim is displayed in accordance with the 1st order kinetics. The average value of T1/2 philgrastim from blood serum is about 3.5 no, The clearance is equal 0.6 ml / min / kg. With prolonged use of philgrastim before 28 days after autological bone marrow transplantation, there were no signs of cumulation and increase t1/2.
With V/V and P/c the introduction of Philgrastim, a positive linear dependence between the dose and the concentration in the blood serum is observed. After the p/to the introduction of Philgrastim in therapeutic doses, its concentration in the blood serum exceeds 10 ng / ml for 8-16 no. Vd is about 150 ml / kg.
Testimony
As a preventive and medical agent:
- to reduce the duration of neutropenia and reduce the frequency of febrile neutropenia in patients, receiving cytotoxic chemotherapy for malignant diseases (with the exception of chronic myeloid leukemia and mielodisplastičeskogo syndrome);
- to reduce the duration of neutropenia in patients, receiving myeloablative therapy with subsequent bone marrow transplantation;
- to mobilize peripheral stem cells of the blood in patients;
- with the aim of prolonged therapy to increase the number of neutrophils and reduce the frequency and the duration of infectious complications in children and adults with severe chronic congenital, periodic or idiopathic neutropenia (Absolute number of neutrophils ≤0.5x109/l) and severe or recurrent history infections;
- to reduce the risk of bacterial infections with persistent neutropenia (Absolute number of neutrophils ≤1×109/l) In patients with a detailed stage of HIV infection with the ineffectiveness of other means of control of neutropenia;
- to mobilize PSKK in healthy donors for allogene transplantation PSKK.
Dosage regimen
Patients, receiving cytotoxic chemotherapy for malignant diseases
The recommended dose – 0.5 million. ME (5 g)/kg body weight 1 time / day. The first dose should be entered no earlier, than 24 hours after completion of the course, cytotoxic chemotherapy. Grassalva can be introduced by daily injections or daily short (30-Minute) c/in infusion in 5% dextrose (Glucose). Preferred the Path of Introduction, with iv, the introduction of the action of philgrastim can shorten.
Grassalva is introduced daily until then, until the number of neutrophils exceeds the expected minimum (Nadir) and will not reach the range of normal values. Patients, receiving cytotoxic chemotherapy for solid tumors, lymphoma and lympholecosis, Duration of therapy before 14 days. After induction and consolidation therapy of acute myelolecosis the duration of the use of grasalva can increase to 38 days. The duration of treatment with the drug grasalva is depending on the type, doses and used cytotoxic chemotherapy scheme.
Usually a transient increase in the number of neutrophils is observed through 1-2 Day after the start of the treatment of Grassalva. To achieve a stable therapeutic effect, it is necessary to continue therapy for the gracealova until then, until the number of neutrophils exceeds the expected minimum (Nadir) and will not reach the normal level. It is not recommended to cancel the treatment of premature, to the transition of the number of neutrophils through Nadir.
Patients, receiving myeloablative therapy followed by bone marrow transplantation
The starting dose – 1 million. ME (10 g)/kg body weight per day – Assigned in the form of a 30-minute or continuous 24-hour iv infusion or continuous 24-hour p/to infusion. For iv and p/to infusion, grasalva is diluted 20 ml 5% dextrose (Glucose).
The first dose of Grassalva should be entered no earlier, than 24 h after chemotherapy and no later, than 24 h after bone marrow transplantation.
After, How will the moment of maximum decrease in the number of neutrophils pass, The daily dose should be adjusted depending on the dynamics of the content of neutrophils as follows:
| The number of neutrophils | Dose of gracealva |
| More 1 x 109/l during 3 days in a row | Reduce to 0.5 million. ME (5 g)/kg / Sut |
| More 1 x 109/l during subsequent 3 days in a row | Grassalva is canceled |
If during treatment the absolute amount of neutrophils decreases to less than a level 1 x 109/l, The dose of the drug is increased again in accordance with the above scheme.
PSKK mobilization in patients, receiving myelosuppressive or myeloblative therapy with subsequent autological transfusion of the PSKK
To mobilization of PSKK, as independent therapy, the drug is prescribed in a dose 1 million. ME (10 g)/kg/day in the form of a continuous 24-hour p/to infusion or by injection 1 times / day for 5-7 days in a row. For infusion, grasalva is bred 20 ml 5% dextrose (Glucose). Typically, one or two lecaferes on the 5th or 6th days is enough. In the case of additional lecaferes, the appointment of grasalva in the same dose must be continued until finishing lecaferes.
To mobilization of PSKK after myelosupressive chemotherapy appointed 0.5 million. ME (5 g)/kg/day by daily injections, starting from the first day after chemotherapy completion and until, until the number of neutrophils passes through the expected minimum and does not reach normal values. Leicaphazes should be carried out during the period of increasing the number of neutrophils with 0.5 X109/l to >5 x109/l. Patients, not receiving intensive chemotherapy, one lecaferes is enough. In some cases, it is recommended to carry out additional leicapheres.
Patients with severe chronic neutropenia (PIU)
At congenital neutropenia Grassalva is prescribed in the initial dose 1.2 million. ME (12 g)/kg/day by p/to injections once or divided into several introductions.
At idiopathic or periodic neutropenia the drug is prescribed in an initial dose 0.5 million. ME (5 g)/kg/day s/k once or by several introduction.
Dose adjustment: Grassalva is introduced daily to a stable excess of the number of neutrophils 1.5x109/l. After therapeutic effect defines the minimum effective dose to maintain this level of. To maintain the right number of neutrophils, a long -term daily administration of the drug is required. Through 1-2 The initial dose of treatment can be doubled or half reduced, Depending on the effect of therapy. Subsequently every 1-2 weeks are carried out by an individual dose correction to maintain an average number of neutrophils in the range from 1.5x109/l up to 10×109/l. In patients with severe infections, you can apply a scheme with a more rapid increase in dose. The safety of the use of grasalva with prolonged treatment of patients with TKH doses of more 2.4 million. ME (24 g)/kg/day is not installed.
Patients with HIV infection
To restoration of the number of neutrophils the initial dose – 0.1 million. ME (1 g)/kg/day daily by one -time p/to injection, With an increase in the dose as much as possible to 0.4 million. ME (4 g)/kg / Sut – to normalize the number of neutrophils (more than 2×109/l).
To maintaining a normal number of neutrophils: At the end of neutropenia, the minimum effective dose of the drug is determined to maintain the normal number of neutrophils. It is recommended to start with the introduction 30 million. ME (300 g) (regardless of body weight) P/k every other day. It is necessary to maintain the number of neutrophils more than 2.0×109/l, Therefore, subsequently, an individual dose correction may be required depending on the level of neutrophils in the patient. Usually this dose is just injected 3 times a week, Sometimes to maintain the number of neutrophils >2.0x109/l requires a long -term prescription of the drug.
Mobilization of PSKK in healthy donors for allogeneous transplantation PSKK
The recommended dose – 1 million. ME (10 g)/kg/day by 24-hour p/to infusion or p/to injection 1 times / day for 4-5 days in a row. The leicaphazes are carried out from the 5th day and, if necessary, until the 6th day in order to get 4×106 CD34+-cells/kg of body weight of the recipient.
Security and efficiency of using philgrastim in donors younger 16 and older 60 leT no.
In children with TKHN and oncological diseases Grasalva is used in the same doses, in adults, receiving myelosupressive cytotoxic chemotherapy.
To elderly patients special recommendations are not established due to insufficient research.
Rules for the preparation and administration of infusion solutions
Grassalva is only bred 5% dextrose (Glucose), Divorce is not allowed 0.9% sodium chloride solution.
The drug after breeding can be adsorbed by glass and plastics.
If Grassalva is divorced to a concentration of less 1.5 million. ME (15 g) in 1 ml, To prevent adsorption, it is necessary to add serum albumin in the amount, so that the ultimate concentration of albumin is 2 mg / ml. For Example, When breeding a total dose of grasalva less 30 million. ME (300 g) to the final volume of the solution 20 ml should be added 0.2 ml 20% Albumin solution. Grasalva cannot be diluted to a concentration of less 0.2 million. ME (2 g)/ml.
Properly diluted 5% dextrose (Glucose) or 5% dextrose (Glucose)with Albumin Grassalva compatible with glass and near plastics, incl. polyvinyl chloride, polyolefin (Copolymer of polypropylene and polyethylene) and polypropylene.
The diluted solution of gracealva can be stored at a temperature of 2 ° C to 8 ° C no more 24 no.
After use, the syringe with the remainder of the solution is destroyed.
The drug should be administered daily at the same time. In order to avoid pain, it is best to change the place of introduction daily.
Side effect
Patients with cancer
On the part of the musculoskeletal system: often – pain in the bones and muscles, usually, Weak or moderate (10%), However, sometimes strong (3%), In most cases, they are stopped by ordinary analgesics.
From the urinary system: urination disorders (mainly, Weak or moderate dysuria).
Metabolism: obratimoe, dose -dependent and usually weak or moderate increase in LDH content, Alkaline phosphatase, serum content of uric acid, GGT, respectively, 50%, 35%, 25% and 10% patients.
Cardio-vascular system: rarely – transient reduction in blood pressure, not requiring treatment.
Dermatological reactions: in some cases – kozhnыy vasculitis, whose mechanism is unclear.
The respiratory system: in some patients noted the formation of infiltrates in the lungs, led to the development of pulmonary failure or respiratory distress syndrome of adults, which can end death.
Allergic reactions: rare cases of symptoms are described, indicating an allergic type reactions, Moreover, about half of them were associated with the introduction of the first dose. There were more such reactions after the use of the drug. Sometimes the renewal of treatment was accompanied by relapse of symptoms.
Other: in some cases – Exacerbation of rheumatoid arthritis.
According to randomized placebo-controlled clinical studies, Philgrastim did not increase the frequency of adverse reactions to cytotoxic chemotherapy. Adverse events, with the same frequency observed in patients, treated with filgrastim / chemotherapy and placebo / chemotherapy, They turned on nausea, vomiting, alopecia, diarrhea, slackness, general weakness, anorexia, mucositis, Headache, cough, each eruption, chest pain, sore throat, constipation and non -specific pain (without instructions diagnosis).
Sometimes in patients, receiving high -type chemotherapy, followed by autological bone marrow transplantation, Vascular violations were noted, eg, Veno-o-clusion disease and disorders of water metabolism. Their causal connection with Philgrastim was not established.
Cases of Svit syndrome were noted (acute febrile neutrophilic dermatosis). The causal connection with Philgrastim in these cases is not known, tk. A significant part of them belonged to patients with leukemia, And the Syndrome of the Svit is characteristic of this disease.
Patients with TKHN
On the part of the musculoskeletal system: common – pain in the bones and muscles; less 2% – joint pain, osteoporosis.
From the digestive system: It is possible to increase the spleen, which in a small number of patients can progress; less 10% – diarrhea shortly after the start of treatment with Philgrastim; less 2% – enlargement of the liver.
From the hematopoietic system: Possible thrombocytopenia; less 10% – anemia and nasal bleeding after prolonged treatment.
CNS: less 10% – Headaches shortly after the start of treatment with Philgrastim; less 2% – headaches with subsequent therapy.
Metabolism: perhaps a transient and asymptomatic increase in the serum content of uric acid, LDG and SHF ACTIVITIES, a transient moderate decrease in blood glucose after eating.
Dermatological reactions: less 2% – alopecia, skin rash; 2% – Skin vasculitis with prolonged therapy.
From the urinary system: very rarely with a long therapy – Proteinuria and/or hematuria.
Other: less 2% – reactions at the injection site.
The frequency of the aforementioned symptoms in some patients with TKHN decreased over time.
HIV-infected patients
On the part of the musculoskeletal system: common – pain in the bones and muscles, usually, Weak or moderate. The frequency of symptoms is about the same, like oncological patients.
From the digestive system: less 3% – a small or average increase in the spleen with a favorable clinical course; Hypersplenism, Like splenectomy, None of the patients had. Unnecessarily. With HIV infection and AIDS, the spleen is usually increased, the connection of this phenomenon with the reception of Philgrastim remains unexplained.
Healthy donors for mobilization of PSKK
On the part of the musculoskeletal system: common – weak or moderate pain in bones and muscles; in some cases – Symptoms of exacerbation of arthritis.
From the hematopoietic system: 41% – leukocytosis (more than 50×109/l); 35% – After the introduction of phylgrastim and lecapheresis, transient thrombocytopenia was observed (The number of platelets is less than 100x109/l).
Metabolism: in some cases – asymptomatic increase in the activity of the SCF, LDH, AST and uric acid content.
CNS: headache.
From the digestive system: in a few cases – splenic rupture.
Other: rarely – severe allergic reactions.
Contraindications
- chronic myelolecosis and myelodesplastic syndrome;
-severe congenital neutropenia (Kostmann syndrome) with cytogenetic disorders;
- use in order to increase doses of cytotoxic chemotherapeutic drugs above the recommended;
- Lactation (breast-feeding);
- Hypersensitivity to the drug.
Pregnancy and lactation
Filgrastim safety in pregnant women has not been established. There are literary data on the penetration of Philgrastim through the placental barrier. The appointment of grasalva during pregnancy is not recommended, However, if it is necessary to use the drug, it is necessary to carefully evaluate the expected benefit of therapy for the mother and the possible risk to the fetus.
IN experimental studies on rats and rabbits of data on teratogenicity of Philgrastim was not obtained. The rabbits had an increased frequency of miscarriages, However, no developmental abnormalities were noted.
It is not recommended to use grasalva during lactation (breast-feeding).
Cautions
Grassalva treatment should only be carried out in cooperation with the oncology center, have specialists with experience in the treatment of patients with hematological diseases and in the presence of the necessary diagnostic capabilities.
Mobilization and cells of cells should be carried out in cooperation with the oncological or hematological center, have specialists with sufficient experience in this area and the possibilities of adequate monitoring of hematopoiesis predecessors.
Philgrastim can cause the growth of myeloid cells in vitro. Similar effects can be observed in vitro and on some non -iloid cells.
Safety and efficacy of Filgrastim in patients with mielodisplastičeskim syndrome and chronic myelogenous leukemia is not installed, Therefore, with these diseases, grasalva cannot be prescribed. Particular attention should be paid to the differential diagnosis between the blast crisis of chronic myelolecosis and acute myelolecosis.
The safety and efficiency of the use of phylgrastim in patients with secondary acute myelocosis has not been studied sufficiently, Therefore, grasalva should be appointed to them with caution.
The safety and efficiency of the use of phylgrastim with De Novo in acute myelolecosis in patients younger have not been established 55 years in cases of prognostically favorable cytogenetic factors t(8;21), t(15;17) and Inv(16).
Patients with concomitant bone pathology and osteoporosis, receiving continuous treatment of gracealva during more 6 Months, Control of bone density is shown.
In patients with impaired renal function or dose correction, no dose correction is required.
In the treatment of philgrastim, the development of a respiratory distress syndrome of adults is possible, The first signs of which can be a cough, fever and shortness of breath. Also possible education in light infiltrates are possible, identified radiologically, and respiratory disorder. In this case, grasalva should be canceled and prescribed the necessary treatment.
Special precautions in patients with malignant diseases
Leukocytosis
Patients, receiving chemotherapy with cytotoxic agents, Given the possible risk, highly leukocytosis, During the treatment of Grazalva, the amount of leukocytes should be regularly monitored. First 2-3 the day of treatment is recommended to determine the number of neutrophils daily, then for the first two weeks of therapy – at least 2 once a week, and during supporting treatment – at least, 1 once a week or after a week. If the number of leukocytes after passing the expected minimum exceeds 50×109/l, Grassalva treatment should be canceled immediately. However, if philgrastim is used to mobilize PSKK, The drug is canceled or reduced by the dose when exceeding the number of leukocytes 70x109/l.
Risk, associated with high-dose chemotherapy
Particular caution should be manifested in the treatment of patients, receiving high-dose chemotherapy, since in these cases improvement of the outcome of a malignant neoplasm has not been established, while chemotherapeutic drugs in increased doses have more pronounced toxicity with the development of heart, lung, neurological and dermatological reactions.
Monotherapy filgrastim not prevent thrombocytopenia and anemia, due to myelosuppressive chemotherapy. Because of the possibility of using higher doses of chemotherapy (eg, full doses in accordance with the schemes) the patient may be at greater risk of developing thrombocytopenia and anemia, Therefore, it is recommended to regularly determine the amount of platelets and hematocrit.
Particular caution should be taken when using one -component or combined chemotherapeutic schemes, It is known for its ability to cause severe thrombocytopenia.
Application of PSKK, mobilized using Philgrastim, reduces the severity and duration of thrombocytopenia after myelosuppressive or myeloblative chemotherapy.
Other precautions
The effect of phylgrastim in patients with a significantly reduced number of myeloid cell cells was not studied. The drug increases the number of neutrophils by exposure, primarily, On the predecessors of neutrophils. Therefore, in patients with a reduced content of predecessor cells (eg, exposed intensive radiation therapy or chemotherapy, as well as with tumor bone marrow infiltration) The degree of increase in the number of neutrophils can be reduced.
Sorbitol in the amount 50 MG/ml should not have a negative effect on patients with hereditary fructose intolerance. However, grasalva should be used in such patients with caution.
Special precautions in patients, passing on the mobilization of the PSKK
Mobilization
Prospective randomized studies in comparison 2 Recommended mobilization methods (only philgrastim or in combination with myelosupressive chemotherapy) On the same contingent patients were not carried out. The individual characteristics of patients in various studies and the degree of discrepancy between the results of the laboratory determination of the number of CD34+cells make it difficult to compare the results of these studies. Therefore, the optimal method is difficult to recommend. The choice of mobilization method should be carried out depending on the treatment of this patient.
Before the appointment of cytotoxic agents
Patients, which in the past received active myelosupressive therapy, there may not be sufficient activation of the PSKK to the recommended minimum level (> 2 X106 CD34+-cells/kg) or acceleration of normalization of the number of platelets.
Some cytostatics have special toxicity in relation to cells- hemopoiesis predecessors and can negatively affect their mobilization. Such funds, Like Melfalan, Karmustin and carboplatin, If they were assigned for a long time before attempts to mobilize stem cells, can reduce its effectiveness. However, the use of Melfalan, Karboplatin or Karmustin, together with Philgrastim, turned out to be effective in activating stem cells. If it is planned to transplant PSKK, It is recommended to plan mobilization of stem cells at an early stage of treatment. Particular attention should be paid to the number of stem cells, activated in such patients to highly dose chemotherapy. If the results of mobilization in accordance with the above criteria are insufficient, alternative types of treatment should be considered, not requiring the use of predecessor cells.
Assessment of the number of mobilized peripheral stem cells of the blood
Assessing the number of PSKK, mobilized in patients using phylgrastim, special attention should be paid to the method of quantitative determination. The results of a prototal citometric analysis of the number of SB34+cells differ depending on the specific methodology, Therefore, you need to be careful about the recommendations for their number, based on research, in other laboratories.
The speed of normalization of the number of platelets after highly dosage chemotherapy depends on the number of CD34+cells introduced into the reinfusion. The recommended minimum number of PSKK is > 2 X106 CD34+-cells/kg. The number of predecessor cells, superior to this value, apparently, accompanied by faster normalization, Whereas the amount of less than the specified – a slower normalization of blood composition.
Special precautions in healthy donors, passing on the mobilization of the PSKK
Donors are not indifferent to their health for their health and is used only before the transplantation of allogeneous predecessor cells.
Donors can mobilize PSKK only in case of compliance with ordinary clinical and laboratory criteria for donation of hematopoiesis predecessors, Especially paying attention to hematological indicators and the presence of infectious diseases.
Safety and effectiveness of the use of phylgrastim in healthy donors under the age of younger 16 and older 60 years have not been evaluated.
If necessary, conducting more than one lecapheresis, special attention should be paid to donors, in which the number of platelets to lecaferes is less than 100x109/l.
Conducting lecapheresis is not recommended, If the number of platelets is less than 75×109/l, When prescribing anticoagulants or known gymostasis disorders.
Grasalva should be canceled or reduced by the dose, If the number of leukocytes is more than 70×109/l.
The period of observation of the donor should be long for assessing the safety of the drug. Donors, taking philgrastim for mobilization of PSKK, should be under observation until the normalization of hematological indicators.
Besides, The risk of stimulating a malignant myeloid clone is not excluded. The centers of AFERISE is recommended to register and monitor the Donovs of the PSKK to ensure further data collection on the use of the drug.
After the use of Philgrastim in healthy donors, a spleen rupture is possible. In this regard, it is recommended to control the size of the spleen (palpation, US). It should be borne in mind the possibility of breaking the spleen when complaints about pain in the upper left side of the abdomen or in the left shoulder.
Special precautions in recipients of allogeneous PSKKs, mobilized by Philgrastim
Literary data indicate, that the immunological interaction of allogeneous PSKC and the recipient is characterized by a greater degree of risk of developing an acute reaction of the transplant against the owner in comparison with the bone marrow transplantation.
Special precautions in patients with TKHN
The study of the composition of the blood
It is necessary to carefully monitor the number of platelets, especially during the first few weeks of treatment with phylgrastim. If the patient manifests thrombocytopenia (The number of platelets is steadily below 100x109/l), The issue of temporary cancellation of the drug or dose reduction should be considered. Other changes in the blood formula may be observed, requiring its thorough control, Including anemia and a transient increase in the number of myeloid predecessor cells.
Transformation into leukemia or myelodesplastic syndrome
Particular caution should be shown in the case of diagnosis of severe chronic neutropenies, It is necessary to differentiate them from other hematological diseases, such as aplastic anemia, myelodysplasia and myeloid leukemia. Prior to the start of treatment, a full clinical blood test should be carried out with the determination of the leukocyte formula and the number of platelets, and also to investigate the morphological picture of the bone marrow and karyotype.
If patients with TKHN have cytogenetic disorders, it is necessary to carefully assess the advantages and risk of continuing therapy. With the development of myelodisplastic syndrome (MDC) or leukemia grasalva should be canceled. It is currently not clear, Does prolonged treatment with philgrastim of patients with severe chronic neutropenia to the development of cytogenetic abnormalities predispose, MDS and leukemia. Such patients are recommended regularly (Approximately each 12 Months) conduct morphological and cytogenetic studies of bone marrow.
Other cases
Such causes of transitional neutropenies should be excluded, as viral infections.
An increase in the spleen is a direct consequence of the treatment of phylgrastim, Dose reduction slows down or stops an increase in the size of the spleen. The sizes of the spleen must be controlled by regularly, To detect an abnormal increase in the volume of the spleen, it is enough to palpate the abdomen.
In a small number of patients, hematuria and/or proteinuria were detected, To control them, laboratory study of urine should be regularly carried out.
The safety and effectiveness of the use of the drug in newborns and patients with autoimmune neutropenia have not been established.
Special precautions for HIV infection
Blood cell examination
The number of neutrophils should be carefully monitored, especially during the first few weeks of treatment with phylgrastim. In some patients, after the first injection, the therapeutic effect is very quickly manifested and the number of neutrophils increases significantly. It is recommended to control the number of neutrophils in the first 2-3 Day of treatment with Philgrastim daily, Then in the first two weeks of treatment – at least 2 once a week, and during supporting treatment – at least 1 once a week or in 2 of the week.
If a dose 30 million. ME (300 g) The patient is not introduced into the patient not daily, After a while, strong fluctuations in the number of neutrophils begin to observe. To determine a decrease in the number of neutrophils or their true minimum level (Nadir) It is recommended to take to analyze samples of the patient’s blood directly before the introduction of the next dose of the drug.
Risk in connection with highly awarded myelosupressive therapy
Monotherapy filgrastim not prevent thrombocytopenia and anemia, due to myelosuppressive chemotherapy. Due to the possibility of using more chemotherapy or their high doses together with philgrastim, the patient may be at greater risk of developing thrombocytopenia and anemia, In this connection, it is recommended to regularly determine the number of blood cells, as stated above.
Infections and malignant neoplasms, causing myelosuppression
In patients with neutropenia, caused by bone marrow infiltration by infectious pathogens (eg, With a dissected infection, the bacteria of the group Mycobacterium avium) or tumor lesion of bone marrow (lymphoma), In addition to the purpose of philgrastim, specific treatment should be applied. The effect of phylgrastim on neutropenia, caused by infectious pathogens or malignant bone marrow tumors, It is not investigated enough.
Special precautions in patients with sickle cell anemia
The literature published data on, that a large number of leukocytes in the case of sickle cell anemia is a prognostically unfavorable factor. Therefore, patients with sickle cell anemia philgrastim should be prescribed with caution, and during therapy, carefully monitor the corresponding clinical and laboratory indicators, Paying special attention to the possible increase in the spleen and the development of thrombosis of blood vessels.
Impact on the ability to drive transport and management of mechanisms
The impact on the ability to drive vehicles or work with mechanisms has not been established.
Overdose
The action of the gracealva during an overdose has not been established. After the drug is canceled, the number of circulating neutrophils usually is usually reduced first and then returns to the norm.
Drug Interactions
The safety and efficacy of filgrastim administration in the same day, that myelosupressive antitumor drugs have not been installed. Due to the sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapeutic drugs, It is not recommended to introduce philgrasty during 24 h to their use or earlier than through 24 H after the administration of these drugs.
There are separate reports on the strengthening of the severity of neutropenia while the prescription of phylgrastim and 5-fluoruracyl.
Data on the possible interaction with other hematopoietic growth factors and cytokines are absent.
Lithium, stimulating neutrophil output, It may exacerbate the effects of Filgrastim. This interaction has not been investigated, But there is no information about its undesirable consequences.
Pharmaceutical interaction
Grassalva drug is pharmaceutically incompatible with 0.9% sodium chloride solution.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C . Shelf life – 2 year.
