Epoetin beta

Inappropriate use of the drug by healthy people (for example, as a doping agent) can cause a sharp increase in hematocrit, accompanied by life-threatening complications from the cardiovascular system.

Due to the possible development of anaphylactoid reactions, the first dose of the drug should be administered under the supervision of a physician.

The hematocrit should be periodically monitored until the value reaches 30-35% (Hb 100-120 g/l). In the future, these indicators need to be determined weekly.

Due to increased hematocrit, it is often necessary to increase the dose of heparin during hemodialysis. With inadequate heparinization, blockage of the dialysis system and thrombosis of shunts are possible, especially in patients with a tendency to hypotension or with complications of an arteriovenous fistula (stenosis, aneurysm, etc.). In such patients, early revision of the shunt and timely prevention of thrombosis (for example, ASA) are recommended. Before starting treatment with epoetin beta, it is necessary to exclude deficiency of cyanocobalamin and folic acid, because it reduces the effectiveness of the drug.

A sharp increase in Al3+ concentrations due to treatment of renal failure may reduce the effectiveness of epoetin beta. The decision to use the drug in patients with nephrosclerosis who are not on dialysis must be made individually, because In such patients, a more rapid deterioration of renal function cannot be ruled out. During treatment, it is recommended to periodically monitor the concentration of K+ and phosphates in the blood serum. If hyperkalemia occurs, it is necessary to temporarily discontinue the drug until the K+ concentration normalizes.

It is recommended to monitor blood pressure, incl. between dialysis sessions, with a rapid increase in hematocrit, and in cancer patients, especially at the beginning of treatment. An increase in blood pressure can be controlled with medications; if there is no effect, a temporary break in treatment with epoetin beta is necessary. When a hypertensive crisis develops, urgent measures are taken.

In cancer patients and in patients preparing for subsequent autotransfusion and receiving epoetin beta, a higher incidence of thromboembolic complications was noted, although a clear causal relationship with the drug has not been established.

In the first 8 weeks of therapy, weekly counts of blood cells (especially platelets) are necessary. If the platelet count increases by more than 150 thousand/μl from the initial value, treatment should be interrupted.

If epoetin beta is prescribed before autologous blood donation, follow the recommendations for the donation procedure: blood can only be collected from patients with a hematocrit of 33% or more (or Hb of at least 110 g/l).

Particular caution should be observed in patients weighing less than 50 kg. The volume of blood taken at one time should not exceed 12% of the patient's estimated blood volume. In most cases, simultaneously with an increase in hematocrit, the concentration of ferritin in the blood serum decreases. Therefore, all patients with anemia of renal origin and with a serum ferritin concentration of less than 100 mcg/l or transferrin saturation of less than 20% are recommended to take oral Fe supplements at a dose of 200-300 mg/day.

Patients with oncological and hematological diseases are treated with Fe preparations according to the same principles; However, patients with multiple myeloma, non-Hodgkin's lymphoma or chronic lymphocytic leukemia with transferrin saturation less than 25% can be given 100 mg Fe per week intravenously.

For premature infants, oral therapy with Fe preparations at a dose of 2 mg/day should be prescribed as early as possible (at the latest - on the 14th day of life). The dose of Fe is adjusted depending on the concentration of serum ferritin. If it persistently remains below 100 mcg/ml or there are other signs of Fe deficiency, the dose of Fe supplements should be increased to 5-10 mg/day and therapy should be continued until the signs of Fe deficiency are relieved.

In patients preparing to donate blood for subsequent autotransfusion, as well as those with indications of temporary Fe deficiency, oral therapy with Fe preparations at a dose of 300 mg/day should be started simultaneously with therapy with epoetin beta and continued until ferritin levels normalize. If, despite oral Fe replacement therapy, signs of Fe deficiency develop (ferritin concentration 20 mcg/L or less or transferrin saturation less than 20%), additional intravenous Fe supplementation should be considered.

Vero- Epoetin Epoetin beta

Types of tumors » Medicines in this group »

Pharmacotherapeutic group: Hematopoiesis stimulator. ATX code: B03ХА01. Dosage form: Lyophilisate for the preparation of a solution for intravenous and subcutaneous administration.

Composition: Recombinant human erythropoietin 1000 IU, 2000 IU, 4000 IU, 10000 IU; low molecular weight medical polyvinylpyrrolidone (povidone); citrate-phosphate buffer to obtain a solution with a pH of 6.9.

Description: Porous amorphous mass of white or almost white color.

Pharmacological action: Epoetin beta is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of erythrocytes from erythrocyte precursor cells. Recombinant epoetin beta is synthesized in mammalian cells into which the gene encoding human erythropoietin is integrated. In its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The administration of epoetin beta leads to an increase in hemoglobin and hematocrit, improving blood supply to tissues and heart function. The most pronounced effect of the use of epoetin beta is observed in anemia caused by chronic renal failure. In very rare cases, with long-term use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin with or without the development of partial red cell aplasia may be observed.

Pharmacokinetics: With intravenous administration of Vero-epoetin in healthy individuals and patients with uremia, the half-life is 5-6 hours. With subcutaneous administration of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 28 hours after administration, the half-life is 13-28 hours. When administered intravenously, the half-life is 4-12 hours. The bioavailability of Vero-epoetin when administered subcutaneously is 25-40%.

Indications:

anemia in patients with chronic renal failure, including those on hemodialysis;
prevention and treatment of anemia in patients with solid tumors, whose anemia was a consequence of antitumor therapy;
prevention and treatment of anemia in HIV-infected patients (AIDS) caused by the use of Zidovudine;
prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis;
treatment and prevention of anemia in premature babies born with low body weight up to 1.5 kg;
to reduce the volume of blood transfused during major surgical interventions and acute blood loss.

Contraindications: Hypersensitivity to the drug or its components, partial red cell aplasia after previous therapy with any erythropoietin, uncontrolled hypertension, failure to receive adequate anticoagulant therapy, myocardial infarction within a month after the event, unstable angina or increased risk of deep vein thrombosis and thromboembolism as part of a pre-deposit blood collection program before surgery, porphyria.

With caution: in patients with thrombosis (history), malignant neoplasms, sickle cell anemia, in patients with moderate anemia without iron deficiency, in patients with refractory anemia, epilepsy and chronic liver failure. Since humans do not have sufficient experience with the use of erythropoietin during pregnancy and lactation, Vero-epoetin should be prescribed only if the expected benefits from its use outweigh the possible risk to the fetus and mother.

Directions for use and doses

Intravenously and subcutaneously. A Vero-epoetin solution is prepared by adding 1 ml of physiological solution to the lyophilisate.

Treatment of anemia in patients with chronic renal failure: Vero-epoetin is administered subcutaneously or intravenously, for patients on hemodialysis - through an arteriovenous shunt at the end of the dialysis session. When changing the route of administration, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Vero-epoetin, to achieve the same therapeutic effect, a dose of 20-30% less is required than with intravenous administration). Treatment with Vero-epoetin includes two stages:

1. Correction stage.

When administering Vero-epoetin subcutaneously, the initial single dose is 30 IU/kg three times a week. When administering Vero-epoetin intravenously, the initial single dose is 50 IU/kg. The correction period lasts until the optimal level of hemoglobin (100-120 g/l in adults and 95-110 g/l in children) and hematocrit (30-35%) is achieved. These indicators must be monitored weekly. The following situations are possible:

Hematocrit increases from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved.
The rate of increase in hematocrit is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times.
Growth rate of more than 1.0% per week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times.
The hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on a correctly selected individual treatment regimen.

2. Maintenance therapy stage.

To maintain the hematocrit at a level of 30-35%, the dose of Vero-epoetin used at the correction stage should be reduced by 1.5 times. Then the maintenance dose of Vero-epoetin is selected individually, taking into account the dynamics of hematocrit and hemoglobin. After stabilization of hemodynamic parameters, it is possible to switch to the administration of Vero-epoetin once every 1-2 weeks.

Prevention and treatment of anemia in patients with solid tumors: Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of serum erythropoietin is less than 200 IU/ml, the initial dose of Vero-epoetin is 150 IU/kg for intravenous administration. When administered subcutaneously, the initial dose of Vero-epoetin can be reduced to 100 IU/kg. If there is no response, it is possible to increase the dose to 300 IU/kg, further increasing the dose seems inappropriate. It is not recommended to prescribe erythropoietin to patients with serum endogenous erythropoietin levels above 200 IU/ml.

Prevention and treatment of anemia in patients with HIV infection: Intravenous administration of epoetin beta at a dose of 100-150 IU/kg 3 times a week is effective in HIV patients receiving zidovudine therapy, provided that the patient's serum endogenous erythropoietin level is less than 500 IU /ml, and the dose of Zidovudine is less than 4200 mg/week. When administered subcutaneously, the dose of Vero-epoetin can be reduced by 1.5 times.

Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphomas and chronic lymphocytic leukemia: In these patients, the advisability of treatment with epoetin beta is determined by inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. When the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/ml, Vero-epoetin is administered subcutaneously at a starting dose of 100 IU/kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of epoetin beta is adjusted upward or downward every 3-4 weeks. If, upon reaching a weekly dose of 600 IU/kg, an increase in hemoglobin levels is not observed, further use of epoetin beta should be discontinued as ineffective.

Prevention and treatment of anemia in patients with rheumatoid arthritis: In patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Anemia in these patients is treated with Vero-epoetin when administered subcutaneously at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin level increases by less than 10 g/l after 4 weeks of treatment, the dose of Vero-epoetin is increased to 150-200 IU/kg 3 times a week. further increase in dose seems inappropriate.

Treatment and prevention of anemia in premature infants born with low body weight: Vero-epoetin is administered subcutaneously at a dose of 200 IU/kg three times a week, starting from the 6th day of life, until the target hemoglobin and hematocrit values are achieved, but not more than 6 weeks

Prevention of anemia during extensive surgery and acute blood loss: Vero-epoetin is administered intravenously or subcutaneously three times a week at a dose of 100-150 IU/kg until hematocrit and hemoglobin content normalize.

Side effects

In some cases, flu-like symptoms (dizziness, drowsiness, fever, headache, myalgia, arthralgia) are observed at the beginning of treatment.

Allergic reactions are possible, namely mild or moderate skin rash, urticaria, itching, angioedema, eczema.

On the part of the cardiovascular system, a dose-dependent increase in blood pressure, a worsening of arterial hypertension (most often in patients with uremia), in some cases a hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic symptoms may be observed. clonic convulsions.

On the part of the hematopoietic organs, thrombocytosis may be observed, and in some cases, shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or with an aneurysm, stenosis, etc.).

Local reactions may manifest themselves in the form of hyperemia, burning, mild or moderate pain at the injection site (more often occur with subcutaneous administration).

Laboratory parameters show a decrease in serum ferritin levels. Patients with uremia may experience hyperkalemia and hyperphosphatemia.

Other side effects may include complications associated with respiratory problems or changes in blood pressure, very rarely, immune reactions are possible (induction of antibody formation with or without the development of partial red cell aplasia), exacerbation of porphyria.

Overdose: In case of an overdose of Vero-epoetin, increased side effects may occur. Treatment is symptomatic, with high hemoglobin and hematocrit levels, bloodletting is indicated.

Interaction with other drugs: With simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding to erythrocytes. Experience in the clinical use of Vero-epoetin to date has not revealed any evidence of its pharmacological incompatibility with other drugs. However, to avoid possible incompatibility or decreased activity, Vero-epoetin should not be mixed with solutions of other drugs.

Special instructions: During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin.

In patients with uremia on hemodialysis, due to an increase in hematocrit, it is often necessary to increase the dose of heparin; in addition, timely prevention of thrombosis and early revision of the shunt are necessary. In the pre- and postoperative period, it should not be monitored more often if its initial level was less than 140 g/l. It must be remembered that Vero-epoetin does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled hypertension or thrombotic complications, an increase in the dose of antihypertensive and/or anticoagulant drugs may be required. If a hypertensive crisis develops, urgent measures are taken to provide medical care to the patient; treatment with Vero-epoetin should be interrupted.

When Veroepoetin is prescribed to patients with liver failure, its metabolism may slow down and erythropoiesis may be markedly increased. The safety of Vero-epoetin in this group of patients has not been established.

We also cannot exclude the possibility of interaction between Vero-epoetin and the growth of certain types of tumors, including bone marrow tumors. The possibility that a preoperative increase in Hb levels may predispose to the development of thrombotic complications should be considered.

Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamine, severe A 13+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment .

In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is less than 100 mg/ml, replacement therapy with iron preparations for oral administration is recommended at the rate of 200-300 mg/day (for children 100-200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be started as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements at a dose of up to 200 mg/day.

In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the level of urea, creatinine and K + within normal limits. Serum electrolyte levels should also be monitored in these patients.

During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy.

Given the possible more pronounced effect of epoetin beta, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first two weeks, the dose is not changed and the dose/response ratio is assessed. After this, the dose can be reduced or increased according to the scheme presented above.

Release form: Lyophilisate for the preparation of a solution for intravenous and subcutaneous administration of 1000 IU, 2000 IU, 4000 IU or 10000 IU in vials. 1, 5 or 10 bottles along with instructions for use in a cardboard pack.

Storage conditions: List B. Store in a dry place, protected from light at a temperature of 2 to 8°C. Keep out of the reach of children.

Shelf life: 2 years. Do not use after the expiration date stated on the package.

Conditions for dispensing from pharmacies: By prescription.

Epostim solution for i/v/s/c 10000 IU 1 ml N 10

pharmachologic effect

Epoetin beta is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of red blood cells from erythrocyte precursor cells.
Recombinant epoetin beta is synthesized in mammalian cells into which the gene encoding human erythropoietin is integrated. In its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The administration of epoetin beta leads to an increase in hemoglobin and hematocrit, improving blood supply to tissues and heart function. The most pronounced effect of the use of epoetin beta is observed in anemia caused by chronic renal failure. In very rare cases, with long-term use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin may be observed with or without the development of partial red cell aplasia. Pharmacokinetics When epoetin beta is administered intravenously in healthy individuals and patients with uremia, the half-life is 5-6 hours. When epoetin beta is administered subcutaneously, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 18 hours after administration, the half-life is 16-24 hours. The bioavailability of epoetin beta when administered subcutaneously is 25-40%.

Indications

Anemia in patients with chronic renal failure, including those on hemodialysis.
Prevention and treatment of anemia in patients with solid tumors resulting from antitumor therapy.
Prevention and treatment of anemia in HIV-infected patients caused by the use of zidovudine.
Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphoma, chronic lymphocytic leukemia, and in patients with rheumatoid arthritis.
Treatment and prevention of anemia in premature infants born weighing up to 1.5 kg.
Preparing patients for surgical interventions with planned large blood loss.

Contraindications

Hypersensitivity to the drug Epostim or its components,
partial red cell aplasia after previous therapy with any erythropoietin,
uncontrolled arterial hypertension,
inability to carry out adequate anticoagulant therapy,
myocardial infarction and acute cerebrovascular accident within a month after the event,
unstable angina or increased risk of deep vein thrombosis and thromboembolism as part of a pre-deposit blood collection program before surgery,
porphyria.

With caution : In patients with thrombocytosis, moderate anemia (Hb 100-130 g/l or hematocrit 30-39%, without Fe deficiency), thrombosis (history), sickle cell anemia, malignant neoplasms, refractory anemia, epilepsy and chronic hepatic insufficiency, as well as in patients weighing less than 50 kg (to increase the volume of donor blood for subsequent autotransfusion).

Since humans do not have sufficient experience with the use of erythropoietin during pregnancy and lactation, epoetin beta should be prescribed only if the expected benefits from its use outweigh the possible risk to the fetus and mother.

special instructions

During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin. In patients with uremia on hemodialysis, due to an increase in hematocrit, it is often necessary to increase the dose of heparin; in addition, timely prevention of thrombosis and early revision of the shunt are necessary. In the pre- and postoperative period, hemoglobin should be monitored more often if its initial level was less than 140 g/l. It must be remembered that epoetin beta does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled hypertension or thrombotic complications, an increase in the dose of antihypertensive and/or anticoagulant drugs may be required. If a hypertensive crisis develops, urgent measures are taken to provide medical care to the patient; treatment with epoetin beta should be interrupted.

When prescribing epoetin beta to patients with liver failure, a slowdown in its metabolism and a pronounced increase in erythropoiesis is possible. The safety of epoetin beta in this group of patients has not been established. We also cannot exclude the possibility that epoetin beta may influence the growth of certain types of tumors, including bone marrow tumors. The possibility that a preoperative increase in hemoglobin levels may predispose to the development of thrombotic complications should be considered. Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamine, severe A13+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment. In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit.

Ferritin levels must be determined throughout the course of treatment. If it is less than 100 ng/ml, replacement therapy with iron preparations for oral administration is recommended at the rate of 200-300 mg/day (for children 100-200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be started as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements at a dose of up to 200 mg/day. In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the level of urea, creatinine and K + within normal limits. Serum electrolyte levels should also be monitored in these patients.

When using epoetin beta in women of reproductive age, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy. During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy. Considering the possible more pronounced effect of Epostim, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first two weeks, the dose is not changed and the dose/response ratio is assessed. After this, the dose can be reduced or increased according to the above scheme.

Compound

active substance: recombinant human erythropoietin 10000 IU/ml,

Directions for use and doses

Treatment of anemia in patients with chronic renal failure: Epostim is administered intravenously or subcutaneously. For hemodialysis patients, the drug is administered through an arteriovenous shunt at the end of the dialysis session. When changing the method of administration, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Epostim, to achieve the same therapeutic effect, a dose of 20-30% less is required than with intravenous administration). Treatment

Epostim includes two stages: 1. Correction stage: For subcutaneous administration of Epostim, the initial single dose is 30 IU/kg 3 times a week. When Epostima is administered intravenously, the initial single dose is 50 IU/kg. The correction period lasts until the optimal level of hemoglobin (100-120 g/l in adults and 95-110 g/l in children) and hematocrit (30-35%) is achieved. These indicators must be monitored weekly. The following situations are possible: 1) Hematocrit increases from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved. 2) The rate of increase in hematocrit is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times. 3) Growth rate of more than 1.0% per week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times. 4) Hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on a correctly selected individual treatment regimen.

2. Stage of maintenance therapy: To maintain the hematocrit at the level of 30-35%, the dose of Epostim achieved at the correction stage should be reduced by 1.5 times. Then the maintenance dose of Epostim is selected individually, taking into account the dynamics of hematocrit and hemoglobin. After stabilization of hemodynamic parameters, it is possible to switch to administering Epostim once every 1-2 weeks.

Prevention and treatment of anemia in patients with solid tumors: Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of erythropoietin in the serum is less than 200 IU/l, the initial dose of Epostim is 150 IU/kg 3 times a week for intravenous administration. When administered subcutaneously, the initial dose of Epostim can be reduced to 100 IU/kg 3 times a week. If there is no response, the dose may be increased to 300 IU/kg 3 times a week. Further increase in dose seems inappropriate. It is not recommended to prescribe erythropoietin to patients with serum endogenous erythropoietin levels above 200 IU/L.

During therapy with Epostim, it is undesirable to increase the hemoglobin level by more than 20 g/l per month or above 140 g/l. If the hemoglobin level increases by more than 20 g/l per month, the dose of Epostim should be reduced by 2 times. If the hemoglobin level exceeds 140 g/L, Epostim is discontinued until the hemoglobin level decreases to ≤120 g/L, after which treatment is resumed at a dose equal to 50% of the dose at which the drug was discontinued.

Prevention and treatment of anemia in patients with HIV infection: Intravenous administration of Epostima at a dose of 100-150 IU/kg 3 times a week is effective in HIV-infected patients receiving zidovudine therapy, provided that the level of endogenous erythropoietin in the patient's serum is less than 500 IU/L, and the dose of zidovudine is less than 4200 mg per week. When administered subcutaneously, the dose of Epostim can be reduced by 1.5 times.

Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphomas and chronic lymphocytic leukemia: In these patients, the advisability of treatment with epoetin beta is determined by inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. When the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/l, Epostim is administered subcutaneously at a starting dose of 100 IU/kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of Epostim is adjusted upward or downward every 3-4 weeks. If after 4 weeks the hemoglobin level increases by 10 g/l, treatment is continued at the same dose. If after 4 weeks hemoglobin increases by less than 10 g/l, the dose may be increased to 300 IU/kg 3 times a week. If after 8 weeks of treatment with Epostim the hemoglobin level has not increased by at least 10 g/l, the development of an effect is unlikely and the drug should be discontinued.

If during 4 weeks of therapy the hemoglobin level increases by more than 20 g/l, the dose of Epostim should be reduced by 2 times. If the hemoglobin level exceeds 140 g/L, treatment with Epostim is suspended until the hemoglobin level decreases to ≤ 130 g/L, after which therapy is continued at a dose equal to 50% of the dose at which therapy was suspended.

For chronic lymphocytic leukemia, treatment with Epostim is continued for up to 4 weeks after the end of chemotherapy. The maximum dose should not exceed 300 IU/kg 3 times a week.

Treatment should only be restarted if the most likely cause of anemia is insufficient production of endogenous erythropoietin.

Prevention and treatment of anemia in patients with rheumatoid arthritis: In patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Treatment of anemia in these patients is carried out with Epostim when administered subcutaneously at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin level increases by less than 10 g/l after 4 weeks of treatment, the dose of Epostim is increased to 150-200 IU/kg 3 times a week. Further increase in dose seems inappropriate.

Treatment and prevention of anemia in premature infants born with low body weight: For the prevention and treatment of anemia in premature newborns, the administration of Epostim should begin as early as possible, preferably from the 3rd day of life at a dose of 200 IU/kg body weight intravenously or subcutaneously 3 times per week and last no more than 6 weeks. The effect of the drug in premature newborns who have already undergone blood transfusions is somewhat less than in those who have not undergone blood transfusions.

Preparing patients for surgical interventions with planned large blood loss: The recommended dose of Epostim is 450-600 IU/kg once a week subcutaneously for 3 weeks preceding surgery (21, 14 and 7 days before surgery) and on the day of surgery. If it is necessary to reduce the time of preoperative preparation, it is possible to use Epostim at a dose of 300 IU/kg subcutaneously daily 10 days before surgery, on the day of surgery and 4 days after surgery.

If the hemoglobin level in the preoperative period is ≥150 g/l, the use of Epostim should be discontinued.

All patients should receive oral iron supplements at a dose of 200 mg/day throughout the course of treatment. If possible, additional oral administration of iron supplements should be provided before starting Epostim therapy to create an iron depot in the patient's body.

Side effects

From the cardiovascular system, a dose-dependent increase in blood pressure, a worsening of arterial hypertension (most often in patients with uremia), in some cases a hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic symptoms may be observed. clonic convulsions. To correct increased blood pressure, antihypertensive drugs are prescribed or the dose of Epostim is reduced.

In patients with uremia, the development of hyperkalemia and hyperphosphatemia may occur. An appropriate diet is prescribed as therapeutic measures.

On the part of the circulatory system, thrombocytosis may be observed, and in some cases, shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or with an aneurysm, stenosis, etc.). The use of Epostim can lead to the development of high blood viscosity syndrome (acute encephalopathy, decreased efficiency of hemodialysis), increased levels of creatinine and blood urea (requires an increase in dialysis time, dialysis index - KT/Y1.4-1.6).

Allergic skin reactions to the components of the drug are rarely observed: rash, urticaria, itching, anaphylactoid reactions, reactions at the injection site. Local reactions may manifest themselves in the form of hyperemia, burning, mild or moderate pain at the injection site (more often occur with subcutaneous administration).

In rare cases, mainly at the beginning of treatment, a flu-like syndrome (fever, chills, headaches, weakness, arthralgia, myalgia) may develop. Very rarely, immune reactions are possible (induction of antibody formation with or without the development of partial red cell aplasia), exacerbation of porphyria.

Drug interactions

With simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding to erythrocytes. The experience of clinical use of Epostim to date has not revealed any evidence of its pharmacological incompatibility with other drugs. However, to avoid possible incompatibility or decreased activity, Epostim should not be mixed with solutions of other drugs.

Overdose

In case of an overdose of Epostim, increased side effects may occur. Treatment is symptomatic, with high hemoglobin and hematocrit levels, bloodletting is indicated.

Storage conditions

Store in a dry place, protected from light, at a temperature of 2 °C to 8 °C. Do not freeze. Keep out of the reach of children.

Best before date

2 years.

Conditions for dispensing from pharmacies

Dispensed with a doctor's prescription

Eralfon 12000 IU/0.3 ml No. 3 syringe with needle protection device

Content

Pharmacodynamics Indications Contraindications Side effects Interaction Method of administration and dosage Overdose Special instructions Storage conditions Shelf life

Pharmacodynamics

Epoetin alfa is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of erythrocytes from erythrocyte precursor cells. Recombinant epoetin alfa is synthesized in mammalian cells into which the gene encoding human erythropoietin is integrated. In its composition, biological and immunological properties, epoetin alfa is identical to natural human erythropoietin. Administration of epoetin alfa leads to an increase in Hb and hematocrit levels, improvement in blood supply to tissues and heart function. The most pronounced effect of the use of epoetin alfa is observed in anemia caused by chronic renal failure. In very rare cases, with long-term use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin with or without the development of partial red cell aplasia may be observed.

Indications

Are common

prevention and treatment of anemia in patients with solid tumors, whose anemia was a consequence of antitumor therapy;
prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphoma, chronic lymphocytic leukemia;
as part of a predeposit program before major surgery in patients with a hematocrit level of 33–39%, to facilitate the collection of autologous blood and reduce the risk associated with the use of allogeneic blood transfusions if the expected need for transfusion exceeds the amount that can be obtained by autologous collection without the use of epoetin alfa;
before major surgery with an expected blood loss of 900–1800 ml in adult patients without anemia or with mild to moderate anemia (Hb concentration 100–130 g/l) to reduce the need for allogeneic blood transfusions and facilitate the restoration of erythropoiesis.

Additionally for solution for intravenous and subcutaneous administration 1000, 2000, 3000, 4000, 5000, 10000, 20000 IU

anemia in patients with chronic renal failure, incl. those on hemodialysis;
prevention and treatment of anemia in patients infected with HIV caused by the use of zidovudine when the level of endogenous erythropoietin is less than 500 IU/ml.
Additionally for solution for intravenous and subcutaneous administration 1000, 2000, 4000, 10000 IU
treatment and prevention of anemia in premature babies born with low body weight up to 1.5 kg.
prevention and treatment of anemia in patients with rheumatoid arthritis.

Contraindications

hypersensitivity to the drug or its components;
partial red cell aplasia after previous therapy with any erythropoietin;
uncontrolled arterial hypertension;
inability to carry out adequate anticoagulant therapy;
severe occlusive diseases of the coronary, carotid, cerebral and peripheral arteries and their consequences, including acute and recent myocardial infarction and acute cerebrovascular accident (as part of a pre-deposit blood collection program before surgery).

Carefully:

malignant neoplasms; epileptic syndrome (including if there is a history); thrombocytosis; thrombosis (history); sickle cell anemia; iron, B12 or folate deficiency conditions; porphyria; chronic liver failure.

Use during pregnancy and breastfeeding

Since there is insufficient experience with the use of erythropoietin during pregnancy and lactation in humans, epoetin alfa should be prescribed only if the expected benefits for the mother outweigh the possible risk to the fetus. It is not known whether epoetin alfa is excreted in breast milk, therefore breastfeeding should be discontinued during treatment with Eralfon®.

Side effects

At the beginning of treatment, flu-like symptoms may be observed: dizziness, drowsiness, fever, headache, myalgia, arthralgia.
From the cardiovascular system: dose-dependent increase in blood pressure, worsening of arterial hypertension (most often in patients with chronic renal failure), in some cases - hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic clonic convulsions.
From the hematopoietic organs: thrombocytosis, in some cases - thrombosis of the shunt or arteriovenous fistula (including in patients on hemodialysis with a tendency to arterial hypotension or with an aneurysm, stenosis), aplasia of the erythrocyte lineage.
Allergic reactions: skin rash (mild or moderate), eczema, urticaria, itching, angioedema.
Local reactions: hyperemia, burning, mild or moderate pain at the injection site (more often occur with subcutaneous administration).
From the laboratory parameters: decrease in serum ferritin concentration, with uremia - hyperkalemia, hyperphosphatemia.
Other: complications associated with respiratory failure or decreased blood pressure, immune reactions (induction of antibody formation), exacerbation of porphyria.

Interaction

Reduces the concentration of cyclosporine due to an increase in the degree of its binding to red blood cells (it may be necessary to adjust the dose of cyclosporine). Pharmaceutically incompatible with solutions of other drugs.

Directions for use and doses

Intravenously, subcutaneously.

Treatment of anemia in patients with chronic renal failure

Adults on hemodialysis. Eralfon® is administered subcutaneously or intravenously at the end of the dialysis session. If the route of administration is changed, the drug is used at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of the drug, to achieve the same therapeutic effect, a dose of 20–30% less is required than with intravenous administration). Treatment with the drug includes two stages.

1. Correction stage: when administering the drug subcutaneously, the initial single dose is 30 IU/kg 3 times a week. When administered intravenously, the initial single dose is 50 IU/kg 3 times a week. The correction period lasts until the optimal level of Hb (100–120 g/l in adults and 95–110 g/l in children) and hematocrit (30–35%) is achieved. These indicators must be monitored weekly.

The following situations are possible:

hematocrit increases from 0.5 to 1% per week. In this case, the dose is not changed until optimal values are achieved;
the rate of increase in hematocrit is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times;
growth rate of more than 1% per week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times;
hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on a correctly selected individual treatment regimen.

2. Maintenance therapy stage: to maintain the hematocrit at a level of 30–35%, the dose of the drug used at the correction stage should be reduced by 1.5 times. Then the maintenance dose of the drug is selected individually, taking into account the dynamics of hematocrit and Hb levels.

Children on hemodialysis. The initial dose is 50 IU/kg 3 times a week. If necessary, the single dose is increased once every 4 weeks by 25 IU/kg until the optimal Hb concentration is achieved. Maintenance dose in children weighing less than 10 kg - 75–150 IU/kg (average 100 IU/kg) 3 times a week; 10–30 kg - 60–150 IU/kg (average 75 IU/kg) 3 times a week; more than 30 kg - 30–100 IU/kg (average 33 IU/kg) 3 times a week.

Adult predialysis patients. The initial dose is administered subcutaneously or intravenously 3 times at 50 IU/kg/week. If necessary, the single dose is increased once every 4 weeks by 25 IU/kg until the optimal Hb concentration is achieved. Maintenance dose: 17–33 IU/kg 3 times a week.

Prevention and treatment of anemia in patients with solid tumors

For the treatment of anemia in cancer patients, it is recommended to administer Eralfon® subcutaneously. The optimal Hb concentration should be 120 g/l in men and women and should not be exceeded.

The drug Eralfon® can be prescribed to patients with symptomatic anemia, for the prevention of anemia in patients receiving chemotherapy and having an initial low Hb concentration during the first course of chemotherapy (including an initial Hb content of 110–130 g/l or a decrease by more than 20 g/l with initial Hb over 130 g/l).

Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of serum erythropoietin is less than 200 IU/ml, the initial dose of the drug for intravenous administration is 150 IU/kg 3 times a week. Alternatively, the initial dose may be 40,000 IU once weekly subcutaneously. If after 4 weeks of treatment the Hb level increases and is at least 10 g/l or the reticulocyte count has increased by more than 40,000 cells/μl above the initial level, then the dose of the drug remains the same (150 IU/kg 3 times a week).

If after 4 weeks of treatment the increase in Hb level is less than 10 g/l and the increase in the number of reticulocytes is less than 40,000 cells/μl compared to the initial level, then over the next 4 weeks the dose is increased to 300 IU/kg 3 times a week. If after an additional 4 weeks of treatment at a drug dose of 300 IU/kg, the Hb level has increased and is at least 10 g/l or the reticulocyte count increases by more than 40,000 cells/μl, then maintain the existing dose of the drug (300 IU/kg 3 times a week ). If after 4 weeks of treatment at a dose of 300 IU/kg or 60,000 IU once a week, the Hb level has increased by less than 10 g/l and the increase in the reticulocyte count is less than 40,000 cells/μl compared to the initial level, treatment should be discontinued. If the Hb level increases by more than 20 g/l within a month, the dose of the drug must be reduced by 25%. If the Hb level exceeds 140 g/l, it is necessary to suspend treatment until the Hb level decreases below 120 g/l and then continue administration of the drug at a dose 25% lower than the original one.

Therapy with the drug should continue for 1 month after completion of chemotherapy.

Serum ferritin levels (or serum iron levels) should be determined in all patients before and during treatment with the drug. If necessary, additional iron intake is prescribed.

Prevention and treatment of anemia in patients with HIV infection

It is recommended to determine the initial level of endogenous erythropoietin in the blood serum before starting treatment with Eralfon®. Studies have shown that if the level of erythropoietin is more than 500 IU/ml, the effect of drug therapy is unlikely.

Treatment with the drug includes 2 stages.

1. Correction stage: the drug is prescribed at a dose of 100 IU/kg 3 times a week subcutaneously or intravenously for 8 weeks. If, after 8 weeks of therapy, it has not been possible to achieve a satisfactory effect (for example, to reduce the need for blood transfusions or to achieve an increase in Hb levels), the dose can be gradually increased (no more than once every 4 weeks) by 50-100 IU/kg 3 times a week . If it was not possible to achieve a satisfactory effect from therapy with Eralfon® at a dose of 300 IU/kg 3 times a week, then a response to further therapy at higher doses is unlikely.

2. Maintenance phase: after achieving a satisfactory effect in the anemia correction phase, the maintenance dose should ensure a hematocrit level within 30–35%, depending on changes in the dose of zidovudine, the presence of concomitant infectious or inflammatory diseases. If the hematocrit is more than 40%, the drug should be discontinued until the hematocrit decreases to 36%. When restarting therapy, the dose of epoetin alfa should be reduced by 25%, followed by adjustments to maintain the required hematocrit level. Serum ferritin levels (or serum iron levels) should be determined in all patients before and during treatment with the drug. If necessary, additional iron intake is prescribed.

Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia

In these patients, the advisability of treatment with epoetin alfa is determined by the inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. When the Hb level is below 100 g/l and serum erythropoietin is below 100 IU/ml, Eralfon® is administered subcutaneously at a starting dose of 100 IU/kg 3 times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of the drug is adjusted upward or downward every 3-4 weeks. If, upon reaching a weekly dose of 600 IU/kg, no increase in Hb levels is observed, further use of epoetin alfa should be discontinued as ineffective.

Prevention and treatment of anemia in patients with rheumatoid arthritis

In patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Anemia in these patients is treated with the drug when administered subcutaneously at a dose of 50–75 IU/kg 3 times a week. If the Hb level increases by less than 10 g/l after 4 weeks of treatment, the dose of the drug is increased to 150–200 IU/kg 3 times a week. Further increase in dose seems inappropriate.

Treatment and prevention of anemia in premature infants born with low birth weight

Eralfon® is administered subcutaneously at a dose of 200 IU/kg 3 times a week, starting from the 6th day of life until the target levels of Hb and hematocrit are achieved, but not more than 6 weeks.

Adult patients participating in a pre-surgical autologous blood collection program

It is recommended to use the intravenous route of drug administration. Epoetin alfa should be administered at the end of the blood collection procedure.

Before prescribing the drug, all contraindications to autologous blood collection should be taken into account. Before surgery, Eralfon® should be prescribed 2 times a week for 3 weeks. At each doctor's visit, a portion of blood is taken from the patient (if hematocrit ≥33% and/or Hb level ≥110 g/l) and stored for autologous transfusion. The recommended dose of Eralfon® is 600 IU/kg intravenously 2 times a week.

Serum ferritin levels (or serum iron levels) should be determined in all patients before and during treatment with the drug. If necessary, additional iron intake is prescribed.

If anemia is present, the cause should be determined before initiating epoetin alfa therapy. It is necessary to ensure adequate iron intake into the body as soon as possible by prescribing an oral iron supplement at a dose of 200 mg/day (calculated as ferrous iron), and maintain iron intake at this level throughout the entire course of therapy.

Patients in the pre- and postoperative period who are not participating in the autologous blood collection program

It is recommended to use subcutaneous administration of the drug at a dose of 600 IU/kg per week for 3 weeks preceding surgery (21, 14 and 7 days before surgery), and on the day of surgery. If necessary, when for medical reasons it is necessary to shorten the preoperative period, Eralfon® can be prescribed daily at a dose of 300 IU/kg for 10 days before surgery, on the day of surgery and for 4 days after surgery. If the preoperative Hb level reaches 150 g/L or higher, the use of epoetin alfa should be discontinued. Before initiating therapy with epoetin alfa, it is necessary to ensure that patients do not have iron deficiency.

All patients should receive adequate amounts of iron (orally 200 mg/day based on ferrous iron) throughout the course of treatment. If possible, supplemental oral iron intake should be provided prior to initiation of epoetin alfa therapy to ensure adequate iron storage in the patient.

Overdose

Symptoms: increased side effects.

Treatment: symptomatic. If Hb level is high - bloodletting.

special instructions

During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count (including platelets, hematocrit, ferritin). In the pre- and postoperative period, Hb concentration should be monitored more often if the initial concentration was less than 140 g/l. It must be remembered that epoetin alfa in the treatment of anemia does not replace blood transfusion, but reduces the need for its repeated use.

In patients with controlled arterial hypertension or a history of thrombotic complications, an increase in the dose of antihypertensive drugs and/or anticoagulants may be required, respectively.

When prescribed to patients with liver failure, a slowdown in the metabolism of epoetin alfa and a pronounced increase in erythropoiesis are possible. The safety of the drug in this category of patients has not been established.

Although the drug stimulates erythropoiesis, the possibility of epoetin alfa affecting the growth of certain types of tumors, including bone marrow.

The possibility that a preoperative increase in Hb levels may predispose to the development of thrombotic complications should be considered. Before undergoing elective surgery, patients should receive adequate prophylactic antiplatelet therapy. In the pre- and postoperative period, the drug is not recommended for use in patients with an initial Hb level of more than 150 g/l.

In adult patients with chronic renal failure, clinically significant ischemic heart disease or heart failure, the Hb concentration should not exceed 100–120 g/l.

Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamin, severe poisoning with aluminum salts, concomitant infections, inflammatory processes and injuries, hidden bleeding, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust the treatment.

Before starting treatment, iron reserves in the body should be assessed. In most patients with chronic renal failure, cancer and HIV-infected patients, plasma ferritin concentration decreases simultaneously with an increase in hematocrit level. Ferritin concentrations must be determined throughout the course of treatment. If it is less than 100 ng/ml, oral iron replacement therapy is recommended at a rate of 200–300 mg/day (100–200 mg/day for children). In premature infants, oral iron therapy at a dose of 2 mg/day should be prescribed as early as possible. Patients donating autologous blood and in the pre- or postoperative period should also receive adequate amounts of iron orally at a dose of 200 mg/day.

In patients with chronic renal failure, correction of anemia may result in improved appetite and increased absorption of potassium and protein. Periodic adjustments of dialysis parameters may be required to maintain blood urea, creatinine, and potassium concentrations within normal limits.

In patients with chronic renal failure, it is necessary to monitor the level of electrolytes in the blood serum.

According to available data, the use of epoetin alfa in predialysis patients does not accelerate the progression of chronic renal failure. Due to increased hematocrit, it is often necessary to increase the dose of heparin during hemodialysis. With inadequate heparinization, blockage of the dialysis system and thrombosis of the vascular access are possible, especially in patients with a tendency to hypotension or with complications of an arteriovenous fistula (including stenosis, aneurysm). In such patients, thrombosis prophylaxis is recommended.

When used in women of reproductive age with anemia due to chronic renal failure, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy. Experimental studies on rats and rabbits did not reveal a teratogenic effect when administered intravenously in doses up to 500 IU/kg/day; at higher doses, a weak, statistically insignificant decrease in fertility was noted.

Considering the possible more pronounced effect of the drug, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first 2 weeks, the dose is not changed, the dose/response ratio is assessed. After this, the dose can be reduced or increased (see “Dosage and Administration”).

Influence on the performance of potentially hazardous activities that require special attention and speed of reactions. During the treatment period, until the optimal maintenance dose is established, patients with chronic renal failure must be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (increased risk of increased blood pressure at the beginning of therapy).

Storage conditions

At a temperature of 2–8 °C.

Keep out of the reach of children.

Best before date

solution for intravenous and subcutaneous administration 1000 IU - 3 years.
solution for intravenous and subcutaneous administration 2000 IU - 3 years.
solution for intravenous and subcutaneous administration 3000 IU - 3 years.
solution for intravenous and subcutaneous administration 4000 IU - 3 years.
solution for intravenous and subcutaneous administration 5000 IU - 3 years.
solution for intravenous and subcutaneous administration 10,000 IU - 3 years.
solution for intravenous and subcutaneous administration 20,000 IU - 3 years.
solution for intravenous and subcutaneous administration 40,000 IU/ml - 3 years.

Do not use after the expiration date stated on the package.