Epostim 2000 IU/ml solution for intravenous and subcutaneous administration 1 ml syringe 1 pc.

Anemia in patients with chronic kidney disease, 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, non-Hodgkin's lymphomas of low malignancy, chronic lymphocytic leukemia, and in patients with rheumatoid arthritis.
Treatment and prevention of anemia in premature infants born with a birth weight of less than 1.5 kg.
Preparation of patients for surgical interventions with anticipated significant blood loss.

Treatment of anemia in patients with chronic kidney disease:

Epostim® is administered intravenously or subcutaneously. For patients undergoing hemodialysis, the drug is administered through an arteriovenous shunt at the end of the dialysis session. When changing the route of administration, the drug is given at the previous dose, and then adjusted as necessary (for subcutaneous administration of Epostim®, a dose 20-30% lower is required to achieve the same therapeutic effect as with intravenous administration). Treatment with Epostim® consists of two stages:

1. Correction stage: For subcutaneous administration of Epostim®, the initial single dose is 30 IU/kg three times a week. For intravenous administration of Epostim®, the initial single dose is 50 IU/kg. The correction period lasts until the optimal hemoglobin level (100-120 g/L in adults and 95-110 g/L in children) and hematocrit (30-35%) are achieved. These parameters should be monitored weekly. The following situations may occur:

1) Hematocrit increases by 0.5 to 1.0% per week. In this case, the dose remains unchanged until optimal levels are reached.

2) The rate of hematocrit increase is less than 0.5% per week. In this case, the single dose should be increased by 1.5 times.

3) The rate of increase is more than 1.0% per week. In this case, the single dose of the drug should be reduced by 1.5 times.

4) Hematocrit remains low or decreases. The reasons for resistance should be analyzed.

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

2. Maintenance therapy stage: To maintain hematocrit at 30-35%, the dose of Epostim® achieved during the correction stage should be reduced by 1.5 times. The maintenance dose of Epostim® is then adjusted individually based on the dynamics of hematocrit and hemoglobin. After stabilizing 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. If the serum erythropoietin concentration is less than 200 IU/L, the initial dose of Epostim® for intravenous administration is 150 IU/kg three times a week. For subcutaneous administration, the initial dose of Epostim® may be reduced to 100 IU/kg three times a week. If there is no response, the dose may be increased to 300 IU/kg three times a week. Further dose increases are not advisable. Erythropoietin is not recommended for patients with serum endogenous erythropoietin levels above 200 IU/L.

During Epostim® therapy, it is undesirable for hemoglobin levels to increase by more than 20 g/L per month or exceed 140 g/L. If hemoglobin levels increase by more than 20 g/L per month, the dose of Epostim® should be reduced by half. If hemoglobin exceeds 140 g/L, Epostim® is discontinued until hemoglobin levels drop below 120 g/L, after which treatment is resumed at a dose of 50% of the dose at which the drug was discontinued.

Prevention and treatment of anemia in patients with HIV infection:
Intravenous administration of Epostim® at a dose of 100-150 IU/kg three times a week is effective in HIV-infected patients receiving zidovudine therapy, provided that the serum endogenous erythropoietin level is less than 500 IU/L and the zidovudine dose is less than 4200 mg per week. For subcutaneous administration, the dose of Epostim® may be reduced by 1.5 times.

Prevention and treatment of anemia in patients with myeloma, low-grade non-Hodgkin's lymphomas, and chronic lymphocytic leukemia: In these patients, the appropriateness of treatment with epoetin beta is determined by inadequate synthesis of endogenous erythropoietin against the background of anemia. When hemoglobin 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 conducted weekly. If necessary, the dose of Epostim® is adjusted upwards or downwards every 3-4 weeks. If after 4 weeks the hemoglobin level increases by 10 g/L, treatment continues 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 three times a week. If after 8 weeks of Epostim® therapy the hemoglobin level has not increased by at least 10 g/L, the likelihood of response is low, and the drug should be discontinued. If during 4 weeks of therapy the hemoglobin increases by more than 20 g/L, the dose of Epostim® should be reduced by half. If hemoglobin exceeds 140 g/L, treatment with Epostim® is suspended until hemoglobin levels drop below 130 g/L, after which therapy continues at a dose equal to 50% of the dose at which therapy was suspended. In chronic lymphocytic leukemia, treatment with Epostim® continues for 4 weeks after the end of chemotherapy. The maximum dose should not exceed 300 IU/kg three times a week. Treatment should only be resumed 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, there is suppression of endogenous erythropoietin synthesis due to increased concentrations of pro-inflammatory cytokines. Anemia in these patients is treated with Epostim® administered subcutaneously at a dose of 50-75 IU/kg three times a week. If hemoglobin increases by less than 10 g/L after 4 weeks of treatment, the dose of Epostim® is increased to 150-200 IU/kg three times a week. Further dose increases are not advisable.

Treatment and prevention of anemia in premature infants born with low birth weight: For the prevention and treatment of anemia in premature newborns, 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 three times a week and continue for no more than 6 weeks. The effect of the drug in premature newborns who have already received blood transfusions is somewhat less than in those who have not received transfusions.

Preparation of patients for surgical interventions with planned significant blood loss: The recommended dose of Epostim® is 450-600 IU/kg once a week subcutaneously for 3 weeks prior to surgery (on days 21, 14, and 7 before surgery) and on the day of surgery. If it is necessary to shorten the preoperative preparation period, Epostim® may be administered at a dose of 300 IU/kg subcutaneously daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery. If hemoglobin levels in the preoperative period exceed 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 treatment course. Whenever possible, additional oral iron supplements should be provided before starting Epostim® therapy to create an iron depot in the patient's body.

One graduated syringe (1 ml) of solution for intravenous and subcutaneous administration contains:
recombinant human erythropoietin 2000 IU/ml
excipients: human albumin* - 2.50 mg, sodium citrate dihydrate - 5.80 mg, sodium chloride - 5.84 mg, citric acid - 0.057 mg, water for injections up to 1 ml.

• human albumin, sodium caprylate, acetyltryptophan

Clear colorless liquid.

Increased sensitivity to the drug or its components; partial red cell aplasia after previous therapy with any erythropoietin; uncontrolled arterial hypertension; inability to conduct adequate anticoagulant therapy; myocardial infarction and acute cerebrovascular accident within one month after the event; unstable angina or increased risk of deep vein thrombosis and thromboembolism within the framework of a pre-deposit blood collection program before surgical operations; porphyria.
With caution:
In patients with thrombocytosis; moderately severe anemia (Hb 100-130 g/L or hematocrit 30-39%, without Fe deficiency); thrombosis (in history); sickle cell anemia; malignant neoplasms; refractory anemia; epilepsy; and chronic liver failure, as well as in patients weighing less than 50 kg (to increase the volume of donor blood for subsequent autotransfusion).
Due to insufficient experience with the use of erythropoietin during pregnancy and lactation in humans, epoetin beta should be prescribed only if the expected benefits of its use outweigh the possible risks to the fetus and mother.

During treatment, it is necessary to monitor blood pressure weekly and conduct a complete blood count, including hematocrit, platelet count, and ferritin levels. In patients with uremia undergoing hemodialysis, an increase in hematocrit often requires an increase in heparin dosage; additionally, timely thrombosis prophylaxis and early shunt revision are necessary. In the pre- and postoperative periods, hemoglobin should be monitored more frequently if the baseline level was less than 140 g/L. It should be noted 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 antihypertensive and/or anticoagulant medication may be required. In the event of a hypertensive crisis, emergency medical assistance should be provided to the patient, and treatment with epoetin beta should be discontinued. When prescribing epoetin beta to patients with liver failure, a slowdown in its metabolism and a pronounced increase in erythropoiesis may occur. The safety of epoetin beta in this patient group has not been established. The possibility of epoetin beta influencing the growth of certain types of tumors, including bone marrow tumors, cannot be excluded. It should be considered that preoperative increases in hemoglobin levels may predispose to thrombotic complications. Before starting treatment, possible causes of inadequate response to the drug should be excluded (iron deficiency, folic acid deficiency, cyanocobalamin deficiency, severe Al3+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and treatment should be adjusted if necessary. In most patients with uremia, as well as in cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels should be monitored throughout the treatment course. If it is less than 100 ng/mL, oral iron replacement therapy is recommended at a dosage of 200-300 mg/day (for children 100-200 mg/day). For premature infants, oral iron therapy at a dose of 2 mg/day should be initiated as early as possible. Patients donating autologous blood and in the pre- or postoperative period should also receive adequate iron therapy at a dose of up to 200 mg/day. In patients with uremia, correction of anemia with epoetin beta may lead to improved appetite and increased absorption of potassium and proteins. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain urea, creatinine, and K+ levels within normal limits. Serum electrolyte levels should also be monitored in these patients. The use of epoetin beta in women of reproductive age may lead to the resumption of menstruation. The patient should be warned about the possibility of pregnancy and the need for reliable contraceptive methods before starting therapy. During treatment, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially dangerous activities that require increased concentration and rapid psychomotor responses due to the increased risk of elevated blood pressure at the beginning of therapy. Considering the potentially more pronounced effect of Epostim®, its dose should not exceed the dose of recombinant erythropoietin used in the previous treatment course. During the first two weeks, the dose should not be changed; the dose/response ratio should be evaluated. After that, the dose may be decreased or increased according to the scheme presented above.

The side effects listed below are categorized by frequency of occurrence according to the following gradation: common (> 1/100 to 1/1000 to 1/10000 to < 1/1000), very rare (10%), slight increase in platelet count, especially up to 12-14 days of life.

Others:
rare - skin allergic reactions to the components of the drug: rash, urticaria, itching; reactions at the injection site;
very rare - anaphylactoid reactions; flu-like symptoms (especially at the beginning of therapy) are usually mild or moderate and disappear within a few hours or a few days: fever, chills, headaches, malaise, pain in limbs or bones; formation of neutralizing antibodies to epoetin beta with or without the development of partial red cell aplasia.

In case of an overdose of Epostim®, an exacerbation of side effects may be observed. Symptomatic treatment is indicated; in cases of high hemoglobin and hematocrit levels, phlebotomy is recommended.

When used concurrently with cyclosporine, it may be necessary to adjust the dose of the latter due to increased binding to erythrocytes. Clinical experience with Epostim® has not revealed any instances of pharmacological incompatibility with other medications to date. However, to avoid possible incompatibility or reduced efficacy, Epostim® should not be mixed with solutions of other medications.

Epoetin beta is a glycoprotein that specifically stimulates erythropoiesis, activating mitosis and the maturation of erythrocytes from precursor cells in the erythroid lineage. Recombinant epoetin beta is synthesized in mammalian cells that have been genetically modified to include the gene encoding human erythropoietin. In terms of 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 tissue perfusion and heart function. The most pronounced effect of epoetin beta is observed in anemias caused by chronic kidney failure. In very rare cases, with prolonged use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin may occur, leading to partial red cell aplasia or without it.

When administered intravenously, the half-life of epoetin beta in healthy individuals and patients with uremia is 5-6 hours. When administered subcutaneously, the concentration of epoetin beta in the blood increases slowly, reaching a maximum between 12 to 18 hours after administration, with a half-life of 16-24 hours. The bioavailability of epoetin beta when given subcutaneously is 25-40%.