Granocyte 34
Instructions for use:
- 1. Release form and composition
- 2. Indications for use
- 3. Contraindications
- 4. Method of application and dosage
- 5. Side effects
- 6. Special instructions
- 7. Drug interactions
- 8. Analogs
- 9. Terms and conditions of storage
- 10. Terms of dispensing from pharmacies
Granocyte 34 is a drug with leukopoietic action.
Release form and composition
The dosage form of Granocyte 34 is a lyophilisate for the preparation of a solution for intravenous (i / v) and subcutaneous (s / c) administration: white (in colorless glass vials, solvent - in colorless neutral glass ampoules; in contoured plastic packaging, 5 vials with lyophilisate and 5 ampoules with solvent, in a cardboard box 1 package).
Composition of 1 bottle:
- active substance: lenograstim - 0.263 mg [33.6 million IU (international units)];
- auxiliary components: polysorbate 20 - 0.1 mg; D-Mannitol (Mannitol) 25 mg L-Phenylalanine (Phenylalanine) 10 mg L-Arginine (Arginine) 10 mg L-methionine (methionine) - 1 mg; hydrochloric acid - up to pH 6.5.
Supplied solvent: water for injection.
Indications for use
- neutropenia in order to reduce the duration of the disease in a pronounced course and associated complications after standard myelosuppressive chemotherapy;
- neutropenia in order to reduce the period of illness and associated complications in patients with nonmyeloproliferative neoplasms who have undergone myelosuppressive therapy with further bone marrow transplantation, and in patients at increased risk of prolonged severe neutropenia;
- mobilization of peripheral precursor cells of hematopoiesis in peripheral blood.
Contraindications
Absolute:
- myeloid neoplasms (except for the primary identified acute myeloid leukemia);
- first identified acute myeloid leukemia in patients under 55 years of age and / or in cases of the presence of favorable cytogenetic prognostic signs [translocations t (15; 17), t (8; 21), inv (16)];
- combination with cytotoxic chemotherapy;
- period of breastfeeding;
- individual intolerance to the components of the drug.
Relative (diseases / conditions in which Granocyte 34 is prescribed under medical supervision):
- precancerous lesions of the myeloid lineage of the bone marrow;
- splenomegaly (having an increased risk of ruptured spleen);
- recent infiltrative lung disease or pneumonia (the presence of an increased risk of respiratory distress syndrome);
- the period of pregnancy (it is first necessary to correlate the expected benefit with the possible risk, which is associated with the lack of necessary clinical data).
In children under 2 years of age, there is no data on the safety / efficacy of the drug in bone marrow transplantation. There is also no safety profile for Granocyte 34 for patients with severe functional impairment of the kidneys, liver, lungs and heart.
Method of administration and dosage
The route of administration of Granocyte 34 is s / c or i / v drip for 30 minutes.
The daily dose chemotherapy with standard cytotoxic agents, and bone marrow transplantation, to mobilize hematopoietic progenitor cells into the peripheral blood after administration of cytostatics - 0.15 mg (19.2 million IU) / m 2, equivalent to 0.005 mg (0.64 million IU) / kg. The administration of the drug should begin the day after the bone marrow transplantation or the end of chemotherapy. The drug is injected daily subcutaneously (with bone marrow transplantation, intravenous infusion is possible for 30 minutes) until, after the expected decrease in the level of leukocytes, their number is restored to the normal level, after which Granocyte 34 can be canceled. The maximum duration of the course with daily use is 28 days.
If cytostatics are not used to mobilize hematopoietic progenitor cells in the peripheral blood, the daily dose is 0.01 mg (1.28 million IU) / kg, the drug is administered subcutaneously daily for 4 to 6 days.
Leukapheresis should be performed after restoration of the number of leukocytes or after determination of CD34 + cells in the blood, using generally accepted methods to determine these parameters. In patients who have not previously received massive chemotherapy, in most cases, leukapheresis alone is sufficient to obtain the minimum required number of cells (≥ 2 × 10 6 CD34 + cells / kg).
Method of solution preparation (depending on the method of administration):
- s / c: the contents of 1 bottle must be dissolved in 1 ml of the supplied solvent and gently, without shaking too much, mix for 5 seconds;
- i / v: the solution obtained for s / c administration must be additionally diluted with 0.9% sodium chloride solution or 5% dextrose solution to a concentration of not less than 0.32 million IU / ml (0.0025 mg / ml); the maximum volume of the above solutions is 100 ml.
After reconstitution, the solution is recommended to be used as soon as possible; it can be stored for 24 hours at a temperature of 2–8 ° C.
Side effects
The most common disorders: nausea, asthenia, bone and back pain, headache, fever, increased activity of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase. The likelihood of developing pain is higher in patients who have an increased number of leukocytes in the blood, especially in cases where the number of leukocytes is more than 50 x 10 9 cells / l. Leukocytosis ≥ 50 x 10 9 cells / l was observed in 24% of donors, thrombocytopenia associated with apheresis (platelet count <100 x 10 9 cells / l) - in 42%.
During bone marrow transplantation, the development of side effects is most likely associated with conditioning regimens, and not with the use of Granocyte 34. The following disorders were most often noted: infectious and inflammatory lesions of the oral cavity, fever, diarrhea, rash, abdominal pain, nausea, vomiting, alopecia, sepsis, headache. The effect of therapy on the severity / frequency of the graft versus host reaction in acute and chronic course has not been reliably determined.
In bone marrow transplantation, special attention should be paid to controlling the number of platelets in the peripheral blood, since their number with the use of Granocyte 34 may be lower than usual. When treating neutropenia associated with chemotherapy, the side effects that occur are usually similar to those that occur when taking cytostatics. The development of bone pain and reactions at the injection site (in the form of swelling and redness) was noted more often. There is rare information about the development of infiltrates in the lungs, which in some cases in adults led to the development of respiratory distress syndrome or pulmonary insufficiency. If symptoms such as cough, shortness of breath, or fever occur in combination with respiratory impairment and radiological changes,you need to prescribe appropriate treatment and consider discontinuing the use of Granocyte 34.
In very rare cases, the development of various allergic reactions was noted, extremely rarely - in combination with the development of anaphylactic shock. There is also evidence of an extremely rare occurrence of Lyell's syndrome, vasculitis, pyoderma, erythema nodosum.
There is also evidence of common but mostly asymptomatic cases of enlarged spleen and very rare cases of ruptured spleen.
During post-marketing observations, the following adverse reactions were recorded (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rarely; with an unknown frequency - in cases where it is impossible to reliably estimate the incidence of the disorder):
- skin and subcutaneous tissue: infrequently - skin rash; very rarely - erythema nodosum, acute febrile neutrophilic dermatosis, pyoderma, cutaneous vasculitis, Lyell's syndrome;
- respiratory system: rarely - pulmonary infiltrates, deterioration of the functional state of the lungs (including shortness of breath, cough, fever, hypoxemia, symptoms of interstitial lung disease, pulmonary edema, acute respiratory distress syndrome), sometimes with the onset of respiratory failure up to death;
- cardiovascular system: infrequently - a syndrome of increased capillary permeability (most often when combined with chemotherapy, in the absence of appropriate treatment, it can be life-threatening; characterized by symptoms such as hypoalbuminemia, hypotension, hemoconcentration, edema);
- nervous system: very often - headache;
- lymphatic system and blood: very often - leukocytosis, thrombocytopenia; often - splenomegaly; very rarely - rupture of the spleen;
- liver and biliary tract: very often - liver dysfunction, increased activity of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase;
- musculoskeletal and connective tissue: very often - pain in the back and bones;
- immune system: very rarely - hypersensitivity reactions, anaphylactic shock;
- general disorders and local reactions: often - an increase in body temperature, reactions at the injection site; infrequently - malaise.
special instructions
It is possible to use Granocyte 34 only under the supervision of an experienced physician.
During the period of therapy, it is possible to increase the growth of myeloid cells, and therefore, caution is required when prescribing the drug to patients with myeloid leukemia with an insufficient decrease in blast cells in the bone marrow, or in cases where blast cells are present in the peripheral blood, since the number of blast cells can increase.
The efficacy / safety of Granocyte 34 in patients with myelodysplastic syndrome, secondary acute myeloid leukemia, or chronic myeloid leukemia has not been established. Patients need special attention during the diagnosis of acute myeloid leukemia, since this diagnosis must be accurately differentiated from the blast crisis of chronic myeloid leukemia.
The influence of Granocyte 34 on the progression of myelodysplastic syndrome and its transformation into acute myeloid leukemia has not been established. Therapy should be carried out with caution in all precancerous lesions of the myeloid bone marrow lineage.
During the period of therapy, the number of leukocytes in the blood should be regularly monitored, which will allow, if necessary, to promptly stop using the drug.
If symptoms such as cough, dyspnea or fever appear in combination with radiological changes (pulmonary infiltrates), as well as respiratory failure, it is necessary to take into account the likelihood of developing acute respiratory distress syndrome, which requires the cancellation of Granocyte 34 and appropriate treatment.
Granocyte 34 cannot be used to increase the doses of cytostatic drugs (which are not provided for by the established dosage regimen), which is associated with a decrease in myelotoxicity, but not the general toxicity of cytostatic drugs.
The administration of Granocyte 34 may increase the toxicity of anticancer drugs with cumulative bone marrow toxicity or predominant toxicity to platelets, in particular to platelets.
During the period of therapy, it is necessary to control changes in hematological tests.
The choice between the use of Granocyte 34 as monotherapy or as part of a combined treatment after chemotherapy is made individually, taking into account all the goals of treatment.
In patients with a significant decrease in the number of stem cells in the bone marrow (due to previous intensive radiation or chemotherapy), sometimes the neutrophilic response may be reduced, the effectiveness of the administration of Granocyte 34 in these cases has not been established.
A hematopoietic progenitor cell transplant program should be planned early in treatment. Before using high-dose chemotherapy, it is necessary to assess the number of mobilized peripheral blood stem cells. If the number of cells obtained is small, peripheral blood stem cell transplantation should be replaced with other therapies.
Particular attention should be paid to methods for the quantitative determination of the resulting progenitor cells. For adequate and faster recovery of hematopoiesis (including platelets), it is recommended to achieve the minimum required amount of ≥ 2.0 x 10 6 CD34 + cells / kg in the graft. Recovery of hematopoiesis with fewer cells usually occurs more slowly.
The efficacy / safety of the use of Granocyte 34 in the group of healthy donors under 18 and over 60 years of age has not been studied, and therefore it is not recommended to use the drug in these age groups of donors for the purpose of collecting hematopoietic progenitor cells.
The procedure for mobilizing hematopoietic progenitor cells should only be performed from donors who, according to laboratory / clinical studies, are suitable for bone marrow donation. Leukapheresis should not be performed on donors taking anticoagulants or having hemostatic disorders.
It is recommended to avoid placement of a central venous catheter whenever possible.
Transplantation of allogeneic peripheral blood stem cells mobilized by Granocyte 34 may be associated with an increased risk of chronic graft versus host disease. Long-term follow-up data on graft function are scarce.
After the introduction of Granocyte 34, there were cases of enlargement of the spleen and, in extremely rare cases, its rupture, in this regard, it is recommended to carefully monitor the hematological parameters and size of the spleen (for example, physical examination, ultrasound). If pain appears in the upper left half of the abdominal cavity and under the scapula, it is necessary to exclude the possibility of rupture of the spleen. In cases of an increase in the size of the spleen during the use of the drug, appropriate therapeutic measures are required, including the complete cancellation of Granocyte 34.
There is evidence of the development of a syndrome of increased capillary permeability after drug administration. Typical symptoms: hypotension, hypoalbuminemia, edema, hemoconcentration. If you suspect the development of this syndrome, the drug is discontinued and appropriate symptomatic treatment is prescribed, which, if necessary, may include intensive therapy.
The preparation of Granocyte 34 contains phenylalanine, which is harmful for patients with phenylketonuria.
Drug interactions
The use of Granocyte 34 later than 24 hours before and not earlier than 24 hours after the end of chemotherapy is not recommended, which is associated with an increased sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.
Analogs
The analogues of Granocyte 34 are: Grastim, Granogen, Filstim, Neupogen and others.
Terms and conditions of storage
Store at 2-25 ° C. Keep out of the reach of children. Do not freeze.
Shelf life is 2 years.
Short-term (up to 14 days) storage at temperatures up to 30 ° C does not affect the stability of Granocyte 34.
The drug remains stable for 24 hours after its dilution to a concentration of not less than 0.32 IU / ml (0.0025 mg / ml) at a storage temperature of 5-25 ° C.
Terms of dispensing from pharmacies
Dispensed by prescription.
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
