Leucostim is a drug used in neutropenia.
Release form and composition
Leukostim is produced in the form of a solution for subcutaneous and intravenous administration:
- 150 mcg: in 1 ml bottles, 5 bottles in a carton box;
- 300 mcg: in bottles of 1 or 1.6 ml, 5 bottles in a carton box, or 1 or 5 bottles in plastic packaging, 1 pack in a carton box;
- In glass syringes with needles of 0.5 or 1 ml, 1 or 5 syringes in a carton box;
- 600 mcg: in syringes, 0.8 ml, 1 or 5 syringes in blister packs, 1 pack in a carton box).
The composition of 1 ml contains the active substance: filgrastim - 150, 300 or 600 μg.
Indications for use
- Neutropenia (including in patients receiving cytotoxic drugs in the treatment of non-myeloid malignant neoplasms);
- Persistent neutropenia in patients with advanced HIV infection (with an absolute neutrophil count of 1000 cells / µL and less);
- Neutropenia (hereditary, idiopathic or intermittent with neutrophil count less than or equal to 500 cells / µl) and severe or recurrent infections (in history) during the last 12 months.
Leucostim is also used to reduce the duration of neutropenia and its clinical consequences in patients who are preparing for bone marrow transplantation and for mobilizing peripheral stem cells (including after conducting myelosuppressive therapy).
- Increasing doses (higher than recommended) of cytotoxic chemotherapeutic drugs;
- Severe congenital neutropenia with abnormal cytogenetics (Kostmann syndrome);
- Renal and / or liver failure;
- Age up to 1 year;
- Hypersensitivity to the drug.
Dosing and Administration
Leukostim is administered subcutaneously (preferably) or intravenously. If necessary, intravenous administration of the drug, the required amount of Leucostim with a 5% dextrose solution should be injected from a syringe into a vial or plastic container, then infusion should be performed within 30 minutes. The drug should not be diluted with 0.9% sodium chloride solution. Also, do not dilute filgrastim to a final concentration of less than 2 μg / ml (0.2 million IU / ml).
The use of the drug is not recommended less than 24 hours before the start and earlier than 24 hours after the end of the course of chemotherapy.
Doses and route of administration are determined by the specific clinical situation.
With neutropenia, Leucostimus should be administered 1 time per day intravenously or subcutaneously in a dose of 5 µg per kg of the patient’s body weight after a course of cytotoxic chemotherapy.
In patients receiving cytotoxic chemotherapy, a transient increase in the number of neutrophils is usually observed 1-2 days after the start of therapy. To assess the effectiveness of the treatment, it is desirable to daily count the number of neutrophils in the peripheral blood. Therapy is recommended until the number of neutrophils reaches normal values. Leukostim can be canceled after reaching an absolute neutrophil count exceeding 2.0x109 / l. If necessary, the duration of the treatment course can be up to 12 days.
After performing myeloablative chemotherapy followed by bone marrow transplantation, Leucostim should be administered intravenously or subcutaneously at the rate of 10 μg per 1 kg of body weight. The first dose should be administered no earlier than 24 hours after cytotoxic chemotherapy, for bone marrow transplantation - no later than 24 hours after the infusion of the bone marrow. The daily dose of Leucostim is adjusted after the moment of maximum reduction in the number of neutrophils. In cases when the content of neutrophils in the peripheral blood is higher than 1.0x109 / l for three days in a row, the dose of Leucostim is reduced by 2 times (to 5 μg per 1 kg of body weight). Then, if for three consecutive days the absolute number of neutrophils exceeds 1.0x109 / l, Leucostim is canceled. When the absolute number of neutrophils decreases during therapy below 1.0x109 / l, the dose is again increased to 10 μg per 1 kg of body weight.
When using Leucostim to mobilize hematopoietic stem cells, subcutaneous administration is recommended in a daily dose of 5 μg (in patients after myelosuppressive chemotherapy) or 10 μg per 1 kg of patient’s mass (in the absence of chemotherapy) for 5-7 consecutive days (the number of injections is determined by the separation performance and the rate of increase in the number of leukocytes in the peripheral blood). The day before the first separation (on the fourth day of Leukostim administration) and the following days before the last separation day, the number of neutrophils and leukocytes in the patient’s peripheral blood should be evaluated. Cytapheresis is carried out in cases of an increase in the number of leukocytes to 5x109 / l of peripheral blood, starting from the fifth day of Leukostim administration. After each separation, it is necessary to count the number of CD34 + cells and nucleated cells in the sample intended for cryopreservation. Leukostim administration is stopped when the number of cryopreserved CD34 + cells is sufficient for transplantation (not less than 2x106 per 1 kg of patient weight).
The safety and efficacy of Leucostim in healthy donors younger than 16 and older than 60 years have not been studied.
In the treatment of severe chronic neutropenia (TCN), Leucostim must be administered subcutaneously daily. The use of the drug is stopped after the number of neutrophils will consistently exceed 1.5x109 / l (for congenital neutropenia - at a dose of 12 µg per 1 kg of patient weight per day subcutaneously in one or more injections; for periodic or idiopathic neutropenia - 5 µg per 1 kg mass per day). To maintain this level of neutrophils determine the minimum effective dose. This requires daily prolonged administration of the drug. Depending on the response of the patient after 7-14 days of therapy, the initial dose can be increased or decreased by 2 times. In the future, every 7-14 days you need to adjust the dose to maintain the number of neutrophils in the range of 1.5-10x109 / l.
In the treatment of HIV-associated neutropenia, leucostim is administered subcutaneously once in an initial dose of 1–4 μg per 1 kg of body weight per day until the number of neutrophils is normalized (more than 2 × 109 / l). As a rule, the normalization of the number of neutrophils occurs after 2 days. With the ineffectiveness of therapy, the dose is escalated to 5 μg per 1 kg of weight per day once subcutaneously. After reaching a therapeutic effect, they switch to maintenance therapy - 2-3 times a week, 1-4 μg per 1 kg of weight per day. In the future, individual dose adjustment is possible.
The use of Leucostim may be accompanied by pain in the muscles and bones, as well as soreness at the injection site.
In 7.5% of patients, moderate or weak musculoskeletal pains were noted, which did not require drug correction or were stopped by non-steroidal anti-inflammatory drugs. No severe pain was noted during therapy.
In rare cases, at the injection site, delayed-type hypersensitivity reactions may develop, accompanied by the appearance of edema and erythema (if they develop, the use of Leucostim should be discontinued).
In some cases, the use of the drug was observed hepatomegaly, fatigue, headache, diarrhea, urination disorders (mainly moderate or weak dysuria). There were separate reports of transient lowering of blood pressure (treatment was not required). It is also possible to develop a reversible, dose-dependent and usually weak or moderate increase in the concentrations of alkaline phosphatase, lactate dehydrogenase, serum uric acid and gamma glutamyl transferase, a decrease in the number of platelets in the peripheral blood.
Rarely, skin rashes, vascular thrombosis, vasculitis, and an enlarged spleen may occur in patients with initially spleen that is not enlarged. Lung infiltrates may appear with the development of adult respiratory distress syndrome. Such phenomena often occurred after the use of chemotherapy regimens, including bleomycin, their relationship with the admission of Leucostim has not been established. Very rarely after the use of the drug were observed cases of hematuria and proteinuria.
Exceptionally rarely, when using the drug, rheumatoid arthritis has worsened, with prolonged use, spleen rupture, anemia, thrombocytopenia, and skin vasculitis may occur in patients with severe chronic neutropenia.
During the use of Leucostim, a blood test should be performed regularly.
It is necessary to observe the interval of 24 hours (before or after) while applying Leucostim with myelosuppressive drugs.
The safety and efficacy of administering filgrastim in one day with cytotoxic chemotherapy has not been established.
Pharmaceutical Leukostim is not compatible with 0.9% sodium chloride solution.
When administered simultaneously with filgrastim, 5-fluorouracil may increase the severity of neutropenia.
When using the drug to mobilize hematopoietic stem cells after chemotherapy, it must be borne in mind that when prescribing cytotoxic drugs such as carboplatin, carmustine (BCNU) and melphalan for a long time, the effectiveness of mobilization can be reduced.
Terms and conditions of storage
Store in a dark, dry, out of reach of children at a temperature of 2-8 ° C.
Shelf life - 2 years.