Tevagrastim
Tevagrastim: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Tevagrastim
ATX code: L03AA02
Active ingredient: filgrastim (Filgrastim)
Manufacturer: Lemery, S. A. de S. V. (Lemery, SA de CV) (Mexico)
Description and photo update: 2020-28-01
Prices in pharmacies: from 1650 rubles.
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Tevagrastim - a leukopoiesis stimulant; a drug used to treat neutropenia.
Release form and composition
Tevagrastim is produced in the form of a solution for intravenous (i / v) and subcutaneous (s / c) administration: colorless transparent liquid [0.5 ml - 30 million IU (international units) (filgrastim - at a dose of 300 mcg) or 0.8 ml - 48 million IU (filgrastim - at a dose of 480 μg) in a glass graduated syringe (scale divisions 0.1 ml) with a fixed needle covered with a cap, equipped with or without an additional needle safety device; 1, 5 or 10 syringes with a solution in a cardboard holder or plastic blister strip (all types of syringes can be sealed in transparent blisters); in a cardboard box 1 cardboard holder or 1 plastic bag with 1, 5 or 10 syringes, or 10 syringes in 2 holders / packages of 5 pcs. Each pack also contains instructions for the use of Tevagrastim).
1 ml of the preparation contains:
- active substance: filgrastim - 60 million IU (equivalent to 600 μg);
- auxiliary components: glacial acetic acid, polysorbate-80, sorbitol, sodium hydroxide, water for injection.
Pharmacological properties
Pharmacodynamics
Tevagrastim, a stimulant of leukopoiesis, its active ingredient is filgrastim, is a highly purified protein in a non-glycosylated form, consisting of 175 amino acids. It is produced by a strain of Escherichia coli, in the genome of which, with the help of genetic engineering, the gene for the human granulocyte colony-stimulating factor (G-CSF) is included - a glycoprotein that regulates the formation of active neutrophils and their release into the blood from the bone marrow. The active ingredient containing recombinant G-CSF already in the first 24 hours after administration provides a significant increase in the number of neutrophils in the peripheral blood, and a slight increase in the number of monocytes. In the presence of severe chronic neutropenia, the drug may lead to a slight increase in the number of circulating basophils and eosinophils.
Tevagrastim dose-dependently increases the number of neutrophils with normal / increased functional activity. After completion of therapy in the peripheral blood, the number of neutrophils decreases by 50% for 1-2 days, and in the next 1-7 days - returns to normal. With intravenous administration, the duration of the effect may be shortened. Filgrastim significantly reduces the frequency, duration, and severity of neutropenia and febrile neutropenia. This, in turn, reduces the need and duration of inpatient treatment for patients receiving cytostatic chemotherapy or conditioning (myeloablative) therapy followed by bone marrow transplantation.
With filgrastim and cytotoxic chemotherapy, lower antibiotic doses are required when compared to patients not receiving Tevagrastim. The use of the drug also significantly reduces the duration of febrile neutropenia, the need for antibiotic treatment and hospitalization after induction chemotherapy for acute myeloid leukemia (AML), does not affect the incidence of fever and infectious complications.
Both during independent use of filgrastim and after chemotherapy, the release of hematopoietic stem cells (hemocytoblasts) into the peripheral bloodstream is mobilized. Allogeneic / autologous transplantation of peripheral blood stem cells (PSCC) is performed after treatment with cytostatics in high doses, or instead of bone marrow transplantation, or in addition to it. PSCC transplant can also be prescribed after myelosuppressive high-dose cytotoxic therapy. The use of PSCC mobilized with the help of filgrastim provides accelerated recovery of hematopoiesis, a decrease in the severity and duration of thrombocytopenia, a decrease in the risk of hemorrhagic complications and the need for platelet transfusion after the implementation of myelosuppressive / myeloablative therapy.
In adults and children receiving chemotherapy, the safety and effectiveness of Tevagrastim are identical. In severe congenital / idiopathic / intermittent neutropenia, the drug stably increases the number of neutrophils in the peripheral blood, reduces the incidence of infections and associated complications. The use of filgrastim in patients infected with the human immunodeficiency virus (HIV) contributes to the maintenance of normal levels of neutrophils in the blood and the conduct of antiviral and / or myelosuppressive therapy. There were no signs of increased HIV replication during treatment with Tevagrastim.
G-CSF, like other hematopoietic growth factors, stimulates human endothelial cells in vitro.
Pharmacokinetics
A positive linear relationship between the serum concentration in the blood and the administered dose is observed both with intravenous and subcutaneous administration of filgrastim. After s / c injections of Tevagrastim in therapeutic doses for 8-16 hours, its concentration exceeds 10 ng / ml. The volume of distribution (V d) is 150 ml / kg. The elimination of the active substance, regardless of the method of its administration, proceeds according to the rules of first-order kinetics. The half-life (T 1/2) is 3.5 hours, the clearance is 0.6 ml / min / kg. With long-term use of filgrastim (up to 28 days), after autologous bone marrow transplantation, there was no accumulation or increase in T 1/2.
In patients with severe renal / hepatic insufficiency, the pharmacodynamic and pharmacokinetic parameters of Tevagrastim are similar to those in healthy people.
Indications for use
Tevagrastim must be used strictly as directed by a physician to stimulate the formation of leukocytes in the following diseases / conditions:
- neutropenia and febrile neutropenia in individuals receiving intense myelosuppressive cytotoxic chemotherapy for malignant lesions other than myelodysplastic syndrome (MDS) and chronic myeloid leukemia; neutropenia and its clinical consequences in persons receiving myeloablative therapy followed by allogeneic / autologous bone marrow transplantation, with an increased risk of severe and prolonged neutropenia;
- severe congenital, idiopathic or intermittent neutropenia, with an absolute neutrophil count (ANC) ≤ 0.5 × 10 9 / L, in patients with a history of recurrent or severe infections, to increase the number of neutrophils and reduce the duration and frequency of infectious complications;
- neutropenia in patients with acute leukemia receiving induction / consolidation chemotherapy in order to reduce its duration and clinical consequences;
- mobilization of PSCC, including after myelosuppressive therapy, as well as in healthy donors;
- persistent neutropenia (ANC ≤ 1 × 10 9 / l) in patients with an advanced stage of HIV infection in order to reduce the threat of bacterial infections in case of impossibility of using other methods of treatment.
Contraindications
Absolute:
- severe congenital neutropenia (Kostmann syndrome) with cytogenetic disorders;
- end-stage chronic renal failure (CRF);
- simultaneous use with cytotoxic chemotherapy and radiation therapy;
- neonatal period (up to 28 days of life);
- breast-feeding;
- use of Tevagrastim in order to increase the doses of cytotoxic drugs for chemotherapy;
- hypersensitivity to any component of the product.
Relative (the drug should be prescribed with caution):
- malignant and precancerous myeloid diseases, including AML;
- pathology of bone tissue, including osteoporosis (monitoring of bone density is necessary against the background of a continuous course of treatment with Tevagrastim for more than 6 months);
- sickle cell anemia (it is required to regularly do a blood test and take into account the threat of splenomegaly and vascular thrombosis);
- combined use with high-dose chemotherapy (large doses of chemotherapy show more pronounced toxicity, including dermatological reactions, disorders of the nervous, cardiovascular and respiratory systems);
- hereditary fructose intolerance (the product contains sorbitol);
- pregnancy.
Tevagrastim, instructions for use: method and dosage
Tevagrastim solution is administered subcutaneously or in the form of short (30 minutes) intravenous infusions in 5% dextrose solution.
The drug should be administered daily until the neutrophil count crosses the expected minimum (nadir) and reaches normal levels. The route of administration is determined depending on the specific clinical data of the patient, however, s / c injections are more preferred. If necessary, intravenous administration, the prescribed amount of the drug is injected from a pre-filled syringe into a vial or plastic container with 5% dextrose solution, and then the diluted drug is infused for 30 minutes.
Syringes are intended solely for a single injection of the solution. Tevagrastim needs to be diluted with only 5% dextrose solution; 0.9% sodium chloride solution cannot be used for these purposes. The prepared solution can be adsorbed to plastics and glass. In the case when the drug is diluted to a concentration below 15 μg / ml (below 1.5 million IU / ml), it is recommended to add human serum albumin to the solution so that the final albumin content is 2 mg / ml. In particular, with a final volume of the solution of 20 ml, the total dose of Tevagrastim below 300 μg (below 30 million IU) must be administered with the addition of a solution of human albumin 20% - 0.2 ml. It is prohibited to dilute the drug to a final concentration below 2 μg / ml (below 0.2 million IU / ml).
Standard Cytotoxic Chemotherapy Regimens
Tevagrastim solution is used 1 time / day daily at a dose of 5 μg / kg (0.5 million IU / kg) s / c or i / v by short 30-minute infusions in 5% dextrose solution. The first dose is administered no earlier than 24 hours after the completion of the course of cytotoxic chemotherapy.
The course lasts up to 14 days, depending on the severity of neutropenia and the severity of the disease. After induction and consolidation treatment for AML, the duration of use of the drug can reach 38 days, taking into account the type, dose and the chemotherapy regimen used.
After the start of Tevagrastim use, a temporary increase in the number of neutrophils is noted, as a rule, after 1–2 days. To achieve a stable effect, it is necessary to carry out drug therapy until the number of neutrophils exceeds the expected minimum and reaches a normal level. It is not recommended to prematurely stop the administration of the solution before the transition of the neutrophil content through the expected minimum limit. Therapy should be canceled when the ANC after nadir is 1 × 10 9 / L.
The period after myeloablative therapy with further bone marrow transplantation
Tevagrastim is administered sc or intravenously by infusion after dilution in 20 ml of 5% dextrose solution. The initial dose is 10 μg / kg (1 million IU / kg) IV drip over 30 minutes or over 24 hours, or by continuous 24-hour SC infusion. It is recommended to administer the first dose no earlier than 24 hours after cytotoxic chemotherapy, and for bone marrow transplantation - no later than 24 hours after bone marrow infusion. The course is no more than 28 days. After the limiting decrease in the number of neutrophils (nadir), the daily dose is adjusted taking into account the dynamics of their number.
If the number of neutrophils in the peripheral blood exceeds 1 × 10 9 / l for 3 consecutive days, the dose of the drug is reduced to 5 μg / kg (0.5 million IU / kg); further, with ANC exceeding 1 × 10 9 / l for 3 consecutive days, drug therapy is canceled. In the case when, during treatment, ANC decreases to less than 1 × 10 9 / l, the dose of Tevagrastim is increased again in accordance with the above scheme.
Mobilization of the PSKK
After myelosuppressive therapy followed by autologous transfusion of PSCC, with or without bone marrow transplantation, or in patients with myeloablative therapy with further transfusion of PSCC, the solution is used at a dose of 10 μg / kg (1 million IU / kg) 1 time / day by means of p / by injection or for 6 consecutive days by continuous s / c 24-hour infusion. As a rule, in this case, 2 leukapheresis procedures in a row on the 5th and 6th days are sufficient. Sometimes it is possible to prescribe an additional leukapheresis, while Tevagrastim should be used before the final session.
After myelosuppressive therapy to mobilize PSCC, Tevagrastim solution is started to be administered in the form of daily subcutaneous injections from the first day after the end of chemotherapy at a dose of 5 μg / kg (0.5 million IU / kg) until normal neutrophil counts are reached. Leukapheresis is required to be performed during the period when ANC increases from less than 0.5 × 10 9 / l to more than 5 × 10 9 / l. For patients who have not received intensive chemotherapy, sometimes 1 leukapheresis procedure is sufficient, in some cases additional sessions may be required.
In healthy donors for allogeneic transplantation, in order to mobilize PSCC, the solution is injected s / c for 4–5 days at a dose of 10 μg / kg (1 million U / kg) per day. Leukapheresis is prescribed from day 5 and, if necessary, up to day 6 in order to obtain hematopoietic stem cells CD34 + in an amount of at least 4 × 10 6 per 1 kg of the recipient's body weight. In healthy donors under the age of 16 and after 60 years, the safety and efficacy of Tevagrastim have not been studied.
Severe chronic neutropenia (THN)
Tevagrastim is used s / c daily, once or divided into several injections. The initial dose for congenital neutropenia is 12 μg / kg (1.2 million IU / kg) per day, for idiopathic / periodic neutropenia, 5 μg / kg (0.5 million IU / kg) per day is used, until a stable excess of the number is observed neutrophils 1.5 × 10 9 / l. After the desired level is reached, the minimum effective dose is set to maintain this neutrophil count. After 7-14 days of the course, the initial dose can be increased or decreased by 2 times, depending on the patient's response to therapy. In the future, every 7-14 days, you can adjust the dose to maintain the number of neutrophils in the range from 1.5 × 10 9 / L to 10 × 10 9 / L.
For patients with severe infections, a faster dose escalation regimen may be prescribed. The maximum daily dose of Tevagrastim is 24 μg / kg. When using doses less than 24 μg / kg per day, the full therapeutic effect was observed in 97% of patients with a positive response to therapy.
Neutropenia associated with HIV infection
In patients with HIV infection, filgrastim is used sc once at an initial dose of 1-4 μg / kg (0.1-0.4 million IU / kg) per day until a neutrophil concentration of at least 2 × 10 9 / L is achieved, usually the normalization of their number is noted after 2 days.
When a sufficient therapeutic effect is obtained in a maintenance daily dose of 300 mcg, injections are made 2-3 times a week every other day. Subsequently, to maintain the level of neutrophils exceeding 2 × 10 9 / l, it may be necessary to carry out dose adjustment and long-term treatment with Tevagrastim.
Side effects
The use of Tevagrastim in patients with oncological diseases contributed to the development of the following side effects:
- metabolism and nutrition: very often - an increase in the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), an increase in the plasma level of uric acid;
- immune system: extremely rare - allergic reactions;
- blood vessels: infrequently - syndrome of increased capillary permeability; rarely - angiopathy, vascular disorders;
- liver and biliary tract: very often - an increase in the activity of gamma-glutamyltransferase (GGT);
- nervous system: often - headache;
- digestive tract: very often - vomiting, nausea; often - constipation, anorexia, mucositis, diarrhea;
- respiratory system: often - sore throat, cough; extremely rare - infiltrates in the lungs;
- musculoskeletal system: often - musculoskeletal pain, chest pain; extremely rare - exacerbation of rheumatoid arthritis;
- urinary system: very rarely - urination disorder;
- skin and subcutaneous fat: often - skin rash, alopecia; extremely rare - cutaneous vasculitis, Sweet's syndrome;
- others: often - general weakness, fatigue; infrequently - nonspecific pain.
The most common adverse events associated with the use of Tevagrastim at the recommended dose were mild / moderate (10%) and severe (3%) musculoskeletal pain, which were usually relieved with standard analgesic therapy. Urinary disturbances (mainly mild to moderate dysuria) were less frequent. Filgrastim did not increase the incidence of side effects associated with cytotoxic chemotherapy. Adverse manifestations were observed with the same frequency in patients using filgrastim and placebo in combination with chemotherapy, including disorders such as alopecia, nausea, vomiting, constipation, diarrhea, lack of appetite, fatigue, general weakness, mucositis, headache, cough, chest pain, sore throat, skin rash, nonspecific pain.
The increase in LDH, ALP, uric acid levels, and plasma GGT activity was, as a rule, reversible, dose-dependent, mild / moderate.
There have been reports of graft versus host disease and death in patients receiving G-CSF following allogeneic bone marrow transplantation.
Rare episodes of interstitial pneumonia, pulmonary edema and pulmonary infiltrates were recorded, in some cases with an unfavorable outcome - respiratory failure or adult respiratory distress syndrome (ARDS), including death. The first signs of ARDS may be shortness of breath, cough, increased body temperature against the background of infiltrates in the lungs, detected during an X-ray examination. In the event of ARDS, the use of Tevagrastim is discontinued and adequate treatment is prescribed.
In the case of the use of Tevagrastim in healthy donors during the mobilization of PSKK, the following negative side reactions were noted:
- immune system: infrequently - severe allergic reactions;
- nervous system: very often - headache;
- musculoskeletal system: very often - musculoskeletal pain (transient, weak / moderate); infrequently - exacerbation of rheumatoid arthritis;
- vessels: infrequently - syndrome of increased capillary permeability;
- metabolism and nutrition: often - increased activity of LDH, ALP; infrequently - an increase in the activity of aspartate aminotransferase (ACT) (these violations were minor and transient, without clinical consequences);
- blood and lymphatic system: very often - thrombocytopenia, leukocytosis; infrequently - dysfunctions of the spleen.
Predominantly asymptomatic, frequent cases of splenomegaly and very rare cases of ruptured spleen (sometimes fatal) have been reported after administration of G-CSF. As a result, it is required to carefully monitor the size of the spleen through ultrasound (ultrasound) and clinical examination (palpation). When patients complain of pain in the upper left abdomen or in the upper left shoulder, the likelihood of rupture of the spleen should be considered.
In the post-registration period, side effects from the respiratory system were very rarely observed - shortness of breath, hypoxia, pulmonary hemorrhage, hemoptysis, infiltrates in the lungs. If you suspect the presence of these symptoms, you should decide on the advisability of further treatment with Tevagrastim and conduct appropriate therapy. Also, in the post-registration period, cases were recorded against the background of the use of G-CSF, the appearance of a syndrome of increased capillary permeability, which, if untimely treatment, can lead to the death of the patient. This complication was predominantly observed in people with sepsis, progressive malignant disease, receiving several chemotherapy drugs at the same time, or undergoing apheresis. After the introduction of G-CSF infrequently (> 1/1000 to <1/100), this syndrome was recorded in healthy donors upon mobilization of PSCC.
In patients with concurrent CNS, the use of filgrastim contributed to the appearance of such side effects from the side of systems and organs:
- respiratory system: very often - nosebleeds;
- nervous system: often - headache;
- metabolism and nutrition: very often - a decrease in blood glucose (transient, moderate), a temporary increase in the level of LDH, ALP; hyperuricemia;
- digestive system: often - diarrhea, hepatomegaly;
- blood and lymphatic system: very often - splenomegaly, anemia; often - thrombocytopenia; infrequently - dysfunction of the spleen;
- kidneys and urinary tract: infrequently - proteinuria, hematuria;
- skin and subcutaneous tissue: often - alopecia, skin rash, pain at the injection site, cutaneous vasculitis;
- musculoskeletal system: very often - pain in bones and muscles; often osteoporosis.
The frequency of the development of side effects caused by the treatment of Tevagrastim in patients with concomitant CNS tended to decrease over time. The most common disorders associated with the use of the drug were pain in the bones and muscles. There was also an increase in the spleen, in some cases - progressive. Diarrhea and headache were predominantly noted shortly after the start of the course in less than 10% of patients.
Side effects observed in the treatment of patients with HIV infection:
- musculoskeletal system: very often - musculoskeletal pain;
- blood and lymphatic system: often - dysfunction of the spleen.
Mild / moderate musculoskeletal pain and myalgia were the persistent negative effects observed during treatment with Tevagrastim in HIV-infected patients. The frequency of their occurrence was similar to that in oncological diseases. Spleen enlargement caused by filgrastim was recorded in less than 3% of patients. On physical examination, mild / moderate splenomegaly with a favorable course was noted. The development of hypersplenism and splenectomy was not identified.
Overdose
No cases of filgrastim overdose have been reported. After discontinuation of Tevagrastim after 1–2 days, the number of circulating neutrophils in most cases decreases by 50% and returns to normal concentration after 1–7 days.
special instructions
Tevagrastim therapy should be carried out only under the supervision of a hematologist or oncologist who have experience in the use of G-CSF, as well as with the necessary diagnostic capabilities. Cell mobilization and apheresis procedures should be performed in an oncology / hematology center with sufficient experience in this area and the ability to adequately monitor hematopoietic progenitor cells.
An additional safety device that can be equipped with a syringe containing the drug is designed to prevent injections and injuries after using the solution and does not require any special precautions. To inject Tevagrastim, slowly and smoothly push the syringe plunger. Continue pressure on the plunger until the prescribed dose is administered and the needle is removed. Dispose of used syringes according to the instructions of the medical institution or specialist.
In patients with chronic myeloid leukemia and MDS, the efficacy and safety of filgrastim treatment has not been determined. The use of the drug is not indicated in the presence of the above diseases and precancerous lesions of the myeloid line of hematopoiesis. Special attention should be paid to the differential diagnosis between AML and blast crisis of chronic myeloid leukemia. It is recommended to be especially careful when using Tevagrastim in patients with secondary myelocytic leukemia, since information on the safety and effectiveness of therapy is limited.
Chronic neutropenia of severe course
Caution is required in the diagnosis of TCN in order to differentiate it from hematological lesions such as aplastic anemia, myeloid leukemia, and myelodysplasia.
In the course of studies, 3% of patients with Kostmann's syndrome (severe congenital neutropenia) who used filgrastim had MDS and leukemia, which are natural complications of this disease; however, their association with drug therapy has not been identified. If cytogenetic disorders appear, or the development of leukemia or MDS in patients with severe congenital neutropenia, Tevagrastim should be canceled. At present, it has not been established whether long-term filgrastim therapy in patients from this group leads to the appearance of cytogenetic abnormalities, MDS, and leukemia. Nevertheless, such patients should, on average, every 12 months undergo cytogenetic and morphological studies of the bone marrow.
Cytogenetic abnormalities, osteoporosis and leukemia were established in 9.1% of individuals with concomitant CNS treatment with filgrastim for more than 5 years, but no association with Tevagrastim was found.
Patients with cancer
Less than 5% of patients from the filgrastim group who received it in doses of more than 3 μg / kg (0.3 million IU / kg) per day had hyperleukocytosis - an increase in the number of leukocytes of more than 100 × 10 9 / L. No adverse effects directly associated with filgrastim-induced hyperleukocytosis have not been reported. Given the potential risk due to a significant increase in the number of leukocytes, during the period of therapy, it is necessary to regularly determine their number, and if it exceeds 50 × 10 9 / l after passing the expected minimum, urgently cancel filgrastim. But in the case of using Tevagrastim for the mobilization of hematopoietic stem cells, its use should be discontinued when the leukocyte level is more than 70 × 10 9 / l.
Monotherapy with Tevagrastim does not prevent the anemia and thrombocytopenia caused by myelosuppressive chemotherapy. Due to the possibility of administering higher doses of chemotherapy drugs (full doses according to the schemes), the risk of developing these complications is exacerbated. It is recommended to conduct a blood test regularly 2 times a week, to determine the platelet count and hematocrit during the use of filgrastim after chemotherapy. The use of single-component / combined chemotherapy regimens, which can provoke severe thrombocytopenia, requires special care.
During the period of Tevagrastim use, careful monitoring of the platelet count is necessary, especially during the first few weeks of the course. With the development of thrombocytopenia in patients with TCN, when the platelet count is consistently less than 100 × 10 9 / l, the question of temporarily withdrawing the drug or reducing the dose should be decided.
Mobilization of the PSKK
After a bone marrow transplant, a blood test and platelet count should be done 3 times a week.
Patients who have previously undergone active myelosuppressive therapy may not show a sufficient increase in the number of PSCCs to the recommended minimum content (at least 2 × 10 6 CD34 + cells / kg) or rapid normalization of platelet levels.
Some cytostatics exhibit particular toxicity towards hematopoietic progenitor cells and can have a negative effect on their mobilization. If transplantation of PSCC is planned, it is necessary to plan their mobilization at the earliest period of treatment. If an insufficient amount of PSCC is received from mobilization, alternative therapies that do not require the use of progenitor cells should be considered.
When assessing the number of PSCCs mobilized in patients with filgrastim, special attention should be paid to the method of quantification. A complex but stable statistical dependence of the rate of recovery of platelet count after high-dose chemotherapy on the number of injected CD34 + cells was revealed. A minimum PSCC level equal to or greater than 2 × 10 6 CD34 + cells / kg provides sufficient recovery of hematological parameters.
Mobilization of PSCC in healthy donors
The mobilization of PSCC is allowed only if the donor's laboratory parameters, primarily the main hematological parameters, meet the selection criteria.
Transient leukocytosis - the content of leukocytes above 50 × 10 9 / l, was observed in 41% of healthy donors, more than 75 × 10 9 / l - in 2%. Transient thrombocytopenia (platelet count below 100 × 10 9 / L) after filgrastim and leukapheresis was observed in 35% of donors. Also, after leukapheresis, 2 cases of thrombocytopenia less than 50 × 10 9 / L were reported.
If it is necessary to conduct more than 1 session of leukapheresis, the number of platelets should be monitored before the appointment of each apheresis procedure, especially if the number of platelets does not reach 100 × 10 9 / L. Leukapheresis is not recommended when the platelet count is below 75 × 10 9 / l, the use of anticoagulants or identified hemostasis disorders. It is required to cancel Tevagrastim or reduce its dose if the leukocyte count exceeds 70 × 10 9 / l.
In healthy donors, all blood test parameters should be systematically monitored until they are normalized. There is no information on cases of hematopoietic disorders up to 4 years after the use of filgrastim in healthy donors.
With allogeneic PSCC transplantation, the risk of an acute / chronic graft versus host reaction is higher than with allogeneic bone marrow transplantation.
Neutropenia associated with HIV infection
During therapy with filgrastim, patients with HIV infection should regularly carry out a detailed blood test (ANC, platelet count, erythrocyte count, etc.) during the first few days - daily, the first 2 weeks - 2 times a week, and during the further maintenance therapy - once a week or every other week.
To establish a true maximum decrease in ANC (nadir), it is necessary to draw blood before the next dose of Tevagrastim is prescribed. In case of concomitant infectious diseases and infiltration of the bone marrow with infectious agents (Mycobacterium avium complex) or with tumor lesions of the bone marrow (lymphoma), drug treatment is carried out in combination with therapy designed to eliminate these conditions.
Influence on the ability to drive vehicles and complex mechanisms
There was no effect of the drug on the ability to drive vehicles and control complex equipment.
Application during pregnancy and lactation
In pregnant women, the safety of Tevagrastim therapy has not been established. It is assumed that filgrastim can cross the placenta. When prescribing the drug during pregnancy, it is required to correlate the intended therapeutic effect with a possible threat to the fetus.
There is no data on the excretion of filgrastim in breast milk, therefore, the use of Tevagrastim during breastfeeding is contraindicated.
Pediatric use
During the neonatal period (first 28 days of life), the use of Tevagrastim is contraindicated.
In children with oncological lesions and TCN, the safety profile of the drug is similar to that in adults. For children, the dosage recommendations for the drug are identical to those for adults receiving myelosuppressive cytotoxic chemotherapy.
With impaired renal function
In patients with end-stage renal failure, there was an increase in the maximum concentration (C max) of filgrastim and the area under the concentration-time curve (AUC), as well as a decrease in Vd and clearance compared with healthy people and patients with moderate severity of renal failure.
In the presence of end-stage chronic renal failure, the use of filgrastim is contraindicated. For patients with severe renal impairment, no change in Tevagrastim dose is required.
For violations of liver function
In patients with severe hepatic impairment, dose adjustment of Tevagrastim is not required.
Use in the elderly
For elderly patients, there are no special recommendations for dosing Tevagrastim.
Drug interactions
- cytotoxic chemotherapy drugs: the safety and efficacy of filgrastim use on the same day with these drugs has not been established; since actively proliferating myeloid cells are highly sensitive to cytotoxins, it is not recommended to use filgrastim 24 hours before or after their administration;
- fluorouracil: there was an increase in the severity of neutropenia caused by it;
- other hematopoietic growth factors and cytokines: the possibility of interaction with filgrastim has not been established;
- sodium chloride solution 0.9%: incompatibility of this solution with Tevagrastim solution was revealed;
- lithium preparations: it is possible to enhance the therapeutic effect of filgrastim, since lithium activates the release of neutrophils, but there are no studies of such interaction;
- carmustine, melphalan, carboplatin (with prolonged use): the effectiveness of filgrastim may decrease if administered after chemotherapy to mobilize hematopoietic stem cells.
Analogs
Granogen, Zarsio, Granocrin, Leucita, Grasalva, Neupogen, Leucostim, Neipomax, Neutrostim, Filgrastim-Nanolek are analogues of Tevagrastim.
Terms and conditions of storage
Store at a temperature of 2–8 ° C, out of the reach of children, protected from light.
The shelf life is 2.5 years.
The finished solution can be stored for 24 hours at a temperature of 2 to 8 ° C
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Tevagrastim
According to rare reviews of Tevagrastim, left by patients, it is an effective agent used to restore the number of neutrophils after receiving intensive myelosuppressive chemotherapy, or to normalize the blood count against the background of other serious diseases.
The most common side effects are muscle and bone pain. Sometimes they indicate the absence of Tevagrastim on sale, and its high cost is also attributed to its disadvantages.
Price for Tevagrastim in pharmacies
The price of Tevagrastim in the form of a solution for intravenous and subcutaneous administration (60 million IU / ml) can be 2,200 rubles. for 1 syringe with a volume of 0.5 ml; 2400 RUB - for 1 syringe with a volume of 0.8 ml.
Tevagrastim: prices in online pharmacies
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Drug name Price Pharmacy |
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Tevagrastim 60 mlnIU / ml solution for intravenous and subcutaneous administration 0.5 ml 1 pc. 1650 RUB Buy |
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Tevagrastim 60 mlnIU / ml solution for intravenous and subcutaneous administration 0.8 ml 1 pc. 2230 RUB Buy |
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Tevagrastim i.v. and s.c. solution 60mln.iu / ml 0.5ml n1 2253 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!