Expiration date: 11/2025

Composition and form of release:

Solution for intravenous and subcutaneous administration 1 ampoule, vials or syringe:

recombinant human erythropoietin 1000 IU/ml, 2000 IU/ml, 4000 IU/ml, 5000 IU/ml, 10000 IU/ml

excipients: plasbumin 20* - 2, 5 mg sodium citrate dihydrate-5, 8 mg sodium chloride-5, 84 mg citric acid-0, 057 mg water for injection-up to 1 ml

*human albumin, sodium caprylate, acetyltryptophan

in ampoules, vials or syringes of 1 ml (1000 IU, 2000 IU, 4000 IU, 5000 IU, 10000 IU) in a pack of cardboard 5 or 10 ampoules 1 or 5 vials 1 or 3 syringes.

Description of the dosage form:

Transparent colorless liquid.

Pharmacokinetics:

When intravenous administration of epoetin beta in healthy individuals and patients with uremia T1 / 2-5-6 hours — When n / a introduction of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 18 hours after administration, T1 / 2-16-24 hours. Bioavailability of epoetin beta with n / a administration — 25-40%.

Description of pharmacological action:

Epoetin beta-a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of red blood cells from erythrocyte progenitor cells. Recombinant epoetin beta is synthesized in mammalian cells, in which the gene encoding human erythropoietin is embedded. According to its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The introduction 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, long-term use of erythropoietin for the treatment of anemic conditions may result in the formation of neutralizing antibodies to erythropoietin with or without the development of partial red cell aplasia.

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 myeloma, low-grade non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and patients with rheumatoid arthritis
• treatment and prevention of anemia in premature babies born with a body weight of up to 1, 5 kg
• preparing patients for surgery with planned major blood loss.

Contraindications:

• hypersensitivity to the drug or its components
• partial red cell aplasia after previous therapy with any erythropoietin
• uncontrolled hypertension
• inability to conduct 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-exposure blood collection program before surgery
• porphyria.

With caution:

• 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
• chronic liver failure
• patients with a body weight <50 kg (to increase the volume of donated blood for subsequent autotransfusion).

Use during pregnancy and lactation:

Since there is no sufficient experience of using erythropoietin during pregnancy and lactation, epoetin beta should be prescribed only if the expected benefits from its use exceed the possible risk to the fetus and mother.

Side effect:

From the cardiovascular system: there may be a dose-dependent increase in blood PRESSURE, 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-clonic convulsions. For correction of blood pressure increase prescribed antihypertensive drugs or reducing the dose Apostila.

Patients with uremia may develop hyperkalemia, hyperphosphatemia. As therapeutic measures, an appropriate diet is prescribed.

On the part of the circulatory system: thrombocytosis may be observed, in some cases — shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or with aneurysm, stenosis, etc.). the Use of Epostin may lead to the development of high blood viscosity syndrome (acute encephalopathy, decreased hemodialysis efficiency), increased blood creatinine and urea (requires an increase in the time of dialysis, dialysis index-KT/Y 1, 4-1, 6). Rarely there are skin allergic reactions to the components of the drug-rash, urticaria, itching, anaphylactoid reactions, reactions at the injection site. Local reactions may occur in the form of hyperemia, burning, mild or moderate soreness at the site of administration (more often occur with p / C administration).

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

Drug interaction:

With simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding by red blood cells. The experience of clinical use of Epostin to date has not revealed any facts of its pharmacological incompatibility with other drugs. However, to avoid potential incompatibility or loss of activity, Apostil cannot be mixed with solutions of other drugs.

Dosage and administration:

intravenous, subcutaneous.

Treatment of anemia in patients with chronic renal failure: intravenous, subcutaneous. Patients on hemodialysis are given the drug via an arteriovenous shunt at the end of the dialysis session. When changing the method of administration, the drug is administered in the same dose, then the dose is adjusted if necessary (with the n / a method of administration of Epostin to achieve the same therapeutic effect, a dose of 20-30% less than with the I/V introduction). Treatment Epistimon includes two stages.

1. stage of correction: with the introduction of Epostin, the initial single dose is 30 IU/kg 3 times a week. With the IV introduction of Epostin, 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 reached. These indicators should be monitored on a weekly basis. The following situations are possible:

1. Hematocrit increases from 0, 5 to 1% per week. In this case, the dose is not changed until optimal parameters are reached.

2. The rate of increase in hematocrit is <0, 5% per week. In this case, it is necessary to increase the single dose by 1, 5 times.

3. The rate of growth of >1% in a week. In this case, it is necessary to reduce the single dose of the drug by 1, 5 times.

4. The hematocrit is low or reduced. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on the correct individual treatment regimen.

2. Phase of maintenance therapy: to maintain a hematocrit level of 30-35% dose Apostila reached at the stage of correction, decrease in 1, 5 times. Then Apostila maintenance dose is selected individually taking into account the dynamics of hematocrit and hemoglobin. After stabilization of hemodynamic parameters, it is possible to switch to the introduction of Epostin1 time in 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 <200 IU/l, the initial dose of Epostin is 150 IU / kg 3 times a week with an intravenous method of administration. With the n / a method of administration, the initial dose of Epostin can be reduced to 100 IU / kg 3 times a week. If there is no response, it is possible to increase the dose to 300 IU / kg 3 times a week. A further increase in the dose seems impractical. It is not recommended to prescribe erythropoietin to patients with endogenous serum erythropoietin >200 IU/l.

During Epostin therapy, 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 Epostin dose should be reduced by 2 times. If the hemoglobin level exceeds 140 g / l, Epostin is canceled until the hemoglobin level drops to &le120 g / l, after which treatment is resumed at a dose of 50% of the dose at which the drug was canceled.

Prevention and treatment of anemia in patients with HIV infection: IV administration of Epostin 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 <500 IU/l, and the dose of zidovudine is <4200 mg per week. With p / C administration, the dose of Epostin can be reduced by 1, 5 times.

Prevention and treatment of anemia in patients with myeloma, low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia: in these patients, the feasibility of treatment with epoetin beta is due to inadequate synthesis of endogenous erythropoietin against the background of anemia. If the hemoglobin content is <100 g/l and serum erythropoietin <100 IU/l, Epostin is administered 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 Apostila correct in the direction of increase or decrease every 3-4 weeks. If after 4 weeks the level of hemoglobin increases by 10 g / l, treatment is continued at the same dose. If after 4 weeks the hemoglobin increases by less than 10 g/l, it is possible to increase the dose to 300 IU/kg 3 times a week. If after 8 weeks of Epostin therapy, the hemoglobin level has not increased by at least 10 g/l, it is unlikely that the effect will develop, the drug should be discontinued. If the hemoglobin level increases by more than 20 g/l during 4 weeks of therapy, the Epostin dose should be reduced by 2 times. If the hemoglobin level exceeds 140 g / l, treatment with Epostin is suspended until the hemoglobin level drops to &le130 g / l, after which the therapy continues at a dose equal to 50% of the one at which the therapy was suspended.

In chronic lymphocytic leukemia, Epostin treatment 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 be resumed only 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, the synthesis of endogenous erythropoietin is suppressed under the influence of an increased concentration of Pro-inflammatory cytokines. Treatment of anemia in these patients is carried out with Epostin when administered at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin content increases by less than 10 g/l after 4 weeks of treatment, The Epostin  dose is increased to 150-200 IU/kg 3 times a week. Further increase in the dose seems impractical.

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

Preparation of patients for surgery with planned major blood loss: the recommended dose of Epostin is 450-600 IU / kg once a week for 3 weeks prior to the operation (21, 14 and 7 days before the operation) and on the day of the operation. If you need to reduce the time of preoperative preparation, you can use Epostin at a dose of 300 IU / kg p / K daily for 10 days before surgery, on the day of surgery and 4 days after surgery.

If the level of hemoglobin in the preoperative period &ge150 g/l, the use of Epostin should be discontinued.

All patients should receive oral iron supplements at a dose of 200 mg / day throughout the course of treatment. If possible, you should provide additional oral administration of iron preparations until the start of therapy Apostila to create a depot of iron in the body of the patient.

Overdose:

Symptoms: there may be increased side effects.

Treatment: symptomatic, with high levels of hemoglobin and hematocrit, bloodletting is indicated.

Special instruction:

During treatment, it is necessary to monitor blood PRESSURE weekly and conduct a General blood test, including the determination of hematocrit, platelets and ferritin. In patients with uremia who are 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 is necessary. In the pre - and postoperative period, hemoglobin should be monitored more often if its initial level was <140 g / l. It should be remembered that epoetin beta does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled arterial hypertension or with thrombotic complications, it may be necessary to increase the dose of hypotensive and / or anticoagulant drugs. When developing a hypertensive crisis, urgent measures are taken to provide medical care to the patient, treatment with epoetin beta should be interrupted. When assigning epoetin beta to patients with hepatic insufficiency, its metabolism may slow down and a pronounced increase in erythropoiesis. The safety of the use of epoetin beta in this group of patients has not been established. It is also impossible to exclude the possibility of the influence of epoetin beta on the growth of certain types of tumors, including bone marrow tumors. It is necessary to take into account the possibility that a preoperative increase in hemoglobin may serve as a predisposing factor to the development of thrombotic complications. Before starting treatment, possible causes of an inadequate response to the drug should be excluded (iron deficiency, folic acid, cyanocobalamin, severe AL3 + 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, the level of ferritin in the plasma decreases simultaneously with an increase in hematocrit. The level of ferritin should be determined throughout the course of treatment. If it is <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). Preterm children should receive oral iron therapy at a dose of 2 mg/day as early as possible. Patients who donate autologous blood and are in the pre-or postoperative period should also receive adequate therapy with iron preparations at a dose of up to 200 mg / day. In patients with uremia, correction of anemia with epoetin beta can cause improved appetite and increased absorption of potassium and proteins. In this regard, it may be necessary to periodically adjust the parameters of hemodialysis to maintain the level of urea, creatinine and K+ within the normal range. In these patients, it is also necessary to monitor the level of electrolytes in the blood serum. 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 treatment until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions, because of the increased risk of increased blood PRESSURE at the beginning of therapy. Given the potential for a more pronounced effect Aposteme, 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 evaluated. After this, the dose can be reduced or increased according to the above scheme.