Granocyte 34
Active material: Lenograstim
When ATH: L03AA10
CCF: Stimulator leykopoeza
ICD-10 codes (testimony): D70
When CSF: 19.01.01.01
Manufacturer: CHUGAI SANOFI-AVENTIS (France)
DOSAGE FORM, STRUCTURE AND PACKAGING
Valium for solution for the on/in and s/to the introduction as a white mass of dried or powder.
| 1 fl. | |
| lenograstim | 33.6 Million International Units (263 g) |
Excipients: D-mannitol, polysorbate 20, L-arginine, L-phenylalanine, L-methionine, hydrochloric acid (to pH 6.5).
Solvent: water d / and (1 ml).
Bottles (5) together with the solvent (amp. 5 PC.) – contoured plastic packaging (1) – packs cardboard.
Pharmacological action
Recombinant human granulocyte colony-stimulating factor (protein from a group of cytokines). Provides a stimulating and differentiating effect on cells nejtrofil'nogo series, that leads to a significant rise in the number of active neutrophil in peripheral blood already during the first 24 no. There is a direct correlation between nejtrofil'nym response and concentration of the drug in plasma. Repeated injection cause an additional increase of neutrophils in the blood. Neutrophils, produced in response to the introduction of Granocita® 34, have normal hemotaksicheskimi properties and Phagocytic activity. If® 34 stimulates proliferation of human endothelial cells.
Use Granocita® 34, as after chemotherapy, and regardless of her, causes an exit in the peripheral blood progenitor cells, gemopoaiza, that can be isolated from blood of patients, and healthy donors and/patient is entered after high-dose chemotherapy with a view to restoring damaged blood instead of bone marrow transplant or in addition thereto.
Displaying, that the introduction of the patient autologous hemopoietic progenitor cells from peripheral blood, obtained through stimulation Granocitom® 34, promotes faster recovery of blood compared to autologous bone marrow, that also significantly reduces the duration of thrombocytopenia.
Pharmacokinetics
Pharmacokinetic performance Granocita® 34 dependent on the dose of drugs and duration of its introduction.
Absorption
In reintroduce (in/in and c/a) Cmax proportional to the imposed dose. If you are using the recommended dose bioavailability is 30%. At repeated twice a drug not found its cumulation.
Distribution
The average retention time in an organism when s/to the introduction of 7 no. Vd – about 1 l / kg.
Metabolism
Lenograstim biotransformiroetsa to peptides.
Deduction
T1/2 When s/to the introduction of 3-4 no, at / in – 1-1.5 no. With urine in an unmodified form appears less 1% of the administered dose.
Testimony
-to reduce the period of neutropenia and its complications (in patients with nemieloproliferativnymi Neoplasms, mielosupressivnaja who had therapy with subsequent bone marrow transplantation, and are at increased risk of prolonged development expressed neutropenia);
-to reduce the duration of the expressed neutropenia and its complications after standard chemotherapy mielosupressivnoj;
— for mobilizing peripheral hemopoietic progenitor cells in peripheral blood.
Dosage regimen
At bone marrow transplant, When standard chemotherapy cytotoxic funds and to mobilize the hemopoietic progenitor cells in the peripheral blood after the use of drugs the drug is prescribed in doses of calculation 150 g (19.2 Million International Units)/m2 body surface, equivalent 5 g (0.64 Million International Units)/kg body weight / day. The introduction of the drug start the next day after spending a bone marrow transplant or end of chemotherapy. The drug is injected daily n/a (When bone marrow transplantation may be in the form of a 30-minute in/in infusion) until, until after the expected lowering of blood, their number will not be restored to normal indicator. Duration of use of the drug should not exceed 28 days.
To mobilization of the hemopoietic progenitor cells in peripheral blood without the use of drugs The recommended dose is 10 g (1.28 Million International Units)/kg body weight / day, daily n/a for 4-6 days.
Lejkaferez should be carried out after the restoration of the number of cells or after determining in blood CD34+-cell. Patients, who did not receive previously massive chemotherapy, often enough one MSC to get the minimum number of cells is ≥ 2 x 106 CD34+-cells/kg body weight.
In healthy donors application of n/a for 5-6 day dose 10 g (1.28 Million International Units)/kg body weight allowed get ≥ 3 x 106 CD34+-cells/kg body weight as a result of MSC in 83% cases and two lejkaferezov in 97% cases.
Special studies in the elderly not performed. In this regard, recommendations regarding changes in dosage in elderly patients no.
Terms of solution for injection
Contents 1 Ampoules of solvent (1 ml water for injection) You should add in a bottle with liofilizirovannam powder. Gently stir until complete dissolution (about 5 sec). Do not shake. Type in the required number of syringe solution and enter n/a.
The on/in the application of the resulting solution should be diluted 0.9% solution of sodium chloride or 5% solution dekstrozy to concentration of not less than 0.32 million IU/ml (2.5 ug / ml), but not more than 100 ml of the above solutions. Entered in/in drip for 30 m.
Cooked solution should be used as soon as possible.
Side effect
When applying Granocita® 34 in healthy donors the most frequently encountered side effects were headache u 30%, bone pain from 23%, lower back pain from 17%, man u 11%, abdominal pain at 6% persons. It was also reported on the development of pharyngitis have 7% and laryngitis at the 6% persons. The risk of pain was higher among persons, with high values of the number of leukocytes in the blood, especially, If the white blood cell count exceeded 50 000/l (It was noted at the 24% Donor), and aferezom-related thrombocytopenia (platelet count less 100 000/l) I observed in 42% Donor. Transient increase level of AST and/or ALT in 12%, a transient increase in the level of ALP – in 16% Donor.
Observed when bone marrow transplantation side effects such as infectious and inflammatory lesions of the oral cavity, fever, diarrhea, stomach ache, vomiting, rash, alopecia, sepsis and infection, associated with the air-conditioning modes, and not with the acquisition Granocita® 34. Impact Granocita® 34 the frequency of occurrence and severity of acute and chronic reactions “Graft-versus-host” reliably is not defined.
When applying Granocita® 34 at neutropenia, chemotherapy-induced, usually seen side effects, to receive specific drugs. More often experienced pain in the bones and reaction at the site of injection (hyperemia, puffiness). Reported sightings of infiltrates in lungs, that in a few cases have resulted in the development of pulmonary disease or distress syndrome in adults.
When a background application Granocita® 34 such symptoms, How cough, fever, breathlessness, in conjunction with the radiological changes and impaired respiratory function, you must assign appropriate therapy and consider terminating the introduction Granocita® 34.
Contraindications
- Pregnancy;
- Lactation (breast-feeding);
is the myeloid Neoplasms (except for newly identified acute mieloblastnogo leukemia);
— initially identified acute myelogenous leukemia in patients older than 55 years with favorable cytogenetic predictive signs;
-hypersensitivity to the primary active substance or other components of the drug.
Pregnancy and lactation
Contraindicated use Granocita® 34 Pregnancy.
If necessary, use during lactation should stop breastfeeding.
Cautions
Treatment Granocitom® 34 should be under the supervision of a doctor-oncologist (hematologist).
Granulocyte colony-stimulating factor (G-CSF) is able to enhance the growth of myeloid tumor cells in vitro, a similar effect can occur in vitro and on some tumor cells nemieloidnogo series.
Not installed the efficacy and safety of Granocita® 34 in mielodisplasticheskom syndrome, secondary acute myeloid leukemia or chronic mielolakose. Therefore, patients with the above-mentioned pathologies If® 34 assign should not. Special attention is required in the diagnosis of acute mieloblastnogo leukemia. This diagnosis should be clearly differentiated from the blastic crisis of chronic myeloid leukemia.
Impact Granocita® 34 the progression of mielodisplasticheskogo syndrome and its transformation in myeloid leukemia has not been. If® 34 should be used with caution when all lesions of pretumorous myeloid marrow germ. Because some tumors may, as an exception, carry g-CSF receptor, caution must be exercised in the event of unexpected of tumor recurrence after treatment of g-CSF.
None of the 174 patients, treated If® 34 dose 5 ug / kg / day (0.64 million IU/kg/day) about bone marrow transplantation, white blood cell count does not exceed the 50 000/l. Less than 5%, treated If® 34 dose 5 ug / kg / day (0.64 million IU/kg/day), After cytotoxic chemotherapy the number of leukocytes was equal to or exceeded the 70 000/l. With no side effects, directly associated with Leukocytosis, not observed.
Due to the potential risk of, associated with the emergence of pronounced Leukocytosis, during treatment Granocitom® 34 should regularly monitor the number of leukocytes in the blood. If the number of WBCs reaches 50 000/l, use Granocita® 34 should be stopped immediately.
During the application Granocita® 34 to mobilize the hemopoietic progenitor cells in peripheral blood levels of the drug should not be imposed in the event of an increase in the number of cells over 70 000/l.
Special attention when bone marrow transplantation should be given to monitoring the number of platelets in peripheral blood, tk. their level when applying Granocita® 34 may be lower, than usual.
If®34 It should not be used to reduce the prescribed intervals between courses of chemotherapy and/or to increase the doses of chemotherapy, tk. If® 34 reduces mielotoksichnost' only and does not affect the other side effects of drugs.
Due to the increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy use Granocita® 34 It is recommended that you not later than 24 h before and after 24 hours after the end of chemotherapy.
Mobilization of hemopoietic progenitor cells in peripheral blood in the application Granocita® 34 After chemotherapy, compared with using only one Granocita® 34 higher. However, the choice between the two methods of mobilization should be carried out individually for each patient taking into account all goals of treatment.
Patients, which was carried out massive mielosupressivnaja therapy, may not see enough to get the minimum number of cells mobilization of hemopoietic progenitor cells in peripheral blood, and, Consequently, adequate recovery of Hematopoiesis.
In patients with a significant reduction in the number of stem cells in the bone marrow (as a result of previous intensive radiation or chemotherapy) neitrofilny answer sometimes can be reduced, safety of Granocita in such cases is not installed.
Program transplant hemopoietic progenitor cells should be planned in the early stages of the course of treatment of patients, and particular attention should be paid to the number of mobilized hemopoietic progenitor cells in peripheral blood before applying chemotherapy high doses. If the number of cells is low, transplantation of hemopoietic progenitor cells must be replaced with other treatments.
As the results of analyses on the definition of CD34+ cell, conducted by the method of flow cytometry, vary in different laboratories, particular attention should be paid to methods of quantifying derived progenitor cells.
Recommendations on the minimum required quantity of cells (>2x106 CD34+ cells per kg body weight) based on published data on experience achieve adequate recovery of Hematopoiesis. Introduction of greater number of CD34+ cells leads to faster recovery of Hematopoiesis, including the number of platelets.
Asoljutnaja security mobilization of progenitor cells of blood from healthy donors not proven, Therefore, this procedure should be carried out in accordance with the rules of, established by the legislation.
Guaranteed mobilization of progenitor cells, gemopoaiza should only be undertaken with donors, have results of clinical and laboratory research suitable for bone marrow donation.
Lejkaferez should not be donors, who take anticoagulants or have Hemostatic disorders. If you want to conduct more than one MSC, particular attention should be paid to those donors, have the number of platelets before the MSC was 100 000/l.
In general there should be no lejkaferez when indicator number of platelets <75 000/l. If possible, you should avoid setting central venous catheter.
Efficacy and safety of Granocita® 34 in the Group of donors over 60 years have not been evaluated. In this regard, the age group of donors is not recommended If® 34 for suction of hemopoietic progenitor cells. Also worth not to carry out the procedure the mobilization of progenitor cells hematopoiesis in adolescents.
According to long-term observations (the duration to 6 years) for a small number of donor liver were observed. Despite this possible risk stimulation of malignant clone myeloid cells. It is therefore recommended to conduct systematic monitoring of these individuals with appropriate documentation maintained in holding centres, MSC.
Transplantation of allogeneic hemopoietic progenitor cells, raised Granocitom® 34, may be accompanied by an increased risk of developing a chronic reaction “Graft-versus-host”. Data for the long-term monitoring of graft are few and far between.
To date not studied the efficacy and safety of Granocita® 34 in patients with severe violations of the liver and kidney.
Overdose
Effects, occur when a drug overdose If® 34, not investigated.
People use the drug in the dose to 40 mcg/kg/day has not been accompanied by the emergence of toxic side effects, except for the pain in the bones and muscles. The increase in the number of leukocytes on the fifth day of treatment to 50 000/MCL is observed in every third patient, If the recipient® 34 to the maximum dose 40 ug / kg / day (5.12 million. IU / kg / day).
Discontinuation of treatment Granocitom® 34 typically leads to 50% reduction in the number of neutrophils in peripheral blood during 1-2 days, then the indicator returned to normal within 1-7 days.
Drug Interactions
Possible interactions Granocita® 34 with other factors, stimulating blood, and cytokines to date have not been studied in clinical trials.
Safety of Granocita® 34 in combination with anticancer drugs with a cumulative toxicity to the bone marrow or the predominant toxicity on its platelet Rostock (nitrosourea, Mitomycin c) not installed. Use Granocita® 34 may even lead to an increase in the toxicity of these substances, especially against platelets.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored at a temperature between 2° to 25° c; Do not freeze. The Stability Of Granocita® 34 not broken by brief exposure to temperatures up to 30° c vials (no more 14 days). Shelf life – 2 year. If® 34 should be restored and/or divorced no earlier than 24 hours before the introduction, Thus the solution should be stored in the refrigerator at a temperature from 2° to 8° c.
