Epostim 2000IU-Ml 1 Piece Solution for Intravenous and Subcutaneous Administration

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

pharmachologic effect

Recombinant human erythropoietin (purified glycoprotein), which is a hematopoietic growth factor. Obtained by genetic engineering. Increases the number of red blood cells, reticulocytes, stimulates hemoglobin synthesis in cells. Does not affect leukopoiesis. It is believed that erythropoietin interacts with specific erythropoietin receptors on the surface of cells.

Composition and release form Epostim 2000 IU/ml 1 pc. solution for intravenous and subcutaneous administration

Solution - 1 ml: epoetin beta 2000 IU.

1 ml - ampoules (1) - cardboard packs.

Directions for use and doses

Doses, regimen and duration of treatment are determined individually and depend on the severity of anemia, the severity of the patient’s condition, and the nature of the disease. Injected subcutaneously and intravenously. Initial doses are 50-150 IU/kg, frequency of administration is an average of 3 times a week.

Pharmacokinetics

After subcutaneous administration, Cmax in plasma is achieved after 12-28 hours. T1/2 in the final phase is 13-28 hours.

After intravenous administration, T1/2 of the active substance is 4-12 hours.

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

Severe anemia occurring against the background of chronic renal failure.

Anemia due to bone marrow lesions and some chronic diseases (including aplastic anemia, anemia due to myelodysplastic diseases, chronic inflammatory diseases, AIDS, cancer).

Prevention of anemia in premature newborns born with a body weight of 750-1500 g before the 34th week of pregnancy.

To increase the volume of donor blood intended for subsequent autotransfusion in order to avoid blood transfusions.

Contraindications

Uncontrolled arterial hypertension, myocardial infarction or cerebral stroke within the previous month, unstable angina, history of thromboembolism, hypersensitivity to epoetin beta.

Application Epostim 2000IU/ml 1 pc. solution for intravenous and subcutaneous administration during pregnancy and lactation

During pregnancy and lactation, epoetin beta is used only when the expected benefit of treatment for the mother outweighs the potential risk of side effects in both the mother and the fetus or child.

No teratogenic effects were detected in experimental studies.

special instructions

Use with caution for epilepsy, thrombocytosis, liver failure, vascular insufficiency, and malignant neoplasms; in patients with nephrosclerosis not receiving hemodialysis, since a more rapid deterioration of renal function is possible.

The effectiveness of treatment decreases with iron deficiency in the body, with infectious and inflammatory diseases, and hemolysis.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, you should refrain from activities that require increased attention and speed of psychomotor reactions.

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

From the cardiovascular system: arterial hypertension, hypertensive crisis are possible.

From the side of the central nervous system: possible encephalopathy (usually during hypertensive crises), headache, confusion.

From the blood coagulation system: rarely - thrombocytosis, thrombotic complications.

Metabolic disorders: rarely - hyperkalemia.

Allergic reactions: rarely - skin rash, anaphylactoid reactions.

Drug interactions

With the simultaneous use of drugs that affect hematopoiesis (for example, iron supplements), the stimulating effect of epoetin beta may be enhanced.

Epostim, d/in solution IV s/c 2 thousand IU/ml amp 1 ml No. 10

Composition and release form.


recombinant human erythropoietin	1000 IU/ml
2000 IU/ml
4000 IU/ml
5000 IU/ml
10000 IU/ml
excipients: plasmbumin 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 cardboard pack 5 or 10 ampoules; 1 or 5 bottles; 1 or 3 syringes.

Description of the dosage form.

Transparent colorless liquid.
Pharmachologic effect. Erythropoietic.

Pharmacodynamics.

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 with or without the development of partial red cell aplasia may be observed.

Pharmacokinetics.

With intravenous administration of epoetin beta in healthy individuals and patients with uremia, T1/2 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 18 hours after administration, T1 /2 - 16-24 hours. Bioavailability of epoetin beta with subcutaneous administration is 25-40%.

Indications.

● anemia in patients with chronic renal failure, incl. 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's lymphoma, chronic lymphocytic leukemia, and in patients with rheumatoid arthritis;

● treatment and prevention of anemia in premature babies born weighing up to 1.5 kg;

● preparing patients for surgical interventions with planned large blood loss.

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;

● 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-surgical blood collection program;

● porphyria.

Carefully:

● 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 body weight <50 kg (to increase the volume of donor blood for subsequent autotransfusion).

Use during pregnancy and breastfeeding.

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.

Side effects.

From the cardiovascular system:

There may be 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-clonic convulsions. To correct the increase in blood pressure, antihypertensive drugs are prescribed or the dose of Epostima® is reduced.

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

From 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 Epostima® 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/Y 1.4–1.6). 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.

Interaction.

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® has not yet 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.

Method of administration and dose.

IV, s.c.

Treatment of anemia in patients with chronic renal failure:

i.v. or s.c. For hemodialysis patients, the drug is administered through an arteriovenous shunt at the end of the dialysis session. If the route of administration is changed, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Epostima®, to achieve the same therapeutic effect, a dose of 20–30% less is required than with intravenous administration). Treatment with Epostim® includes two stages.

1. Correction stage:

with subcutaneous administration of Epostima®, the initial single dose is 30 IU/kg 3 times a week. For intravenous administration of Epostima®, 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% per week. In this case, the dose is not changed until optimal values are achieved.

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. Growth rate >1% 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. Maintenance therapy stage:

to maintain the hematocrit at the level of 30–35%, the dose of Epostima® 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 the administration of 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 concentration of erythropoietin in the serum is <200 IU/l, the initial dose of Epostima® is 150 IU/kg 3 times a week for intravenous administration. With the subcutaneous route of administration, the initial dose of Epostima® 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 >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® must 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:

IV 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 <500 IU/l and the dose of zidovudine is <4200 mg per week. With subcutaneous administration, the dose of Epostima® 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 the inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. If the hemoglobin content is <100 g/l and serum erythropoietin <100 IU/l, Epostim® 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 Epostima® is adjusted up or down 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 therapy 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 within 4 weeks of therapy the hemoglobin level increases by more than 20 g/l, the dose of Epostima® 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 one 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® with subcutaneous administration 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 Epostima® 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:

for the prevention and treatment of anemia in premature newborns, the administration of Epostima® should begin as early as possible, preferably from the 3rd day of life at a dose of 200 IU/kg body weight IV or SC 3 times a 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 Epostima® 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 Epostima® 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.

Overdose.

Symptoms:

increased side effects may occur.

Treatment:

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

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 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 are necessary. In the pre- and postoperative period, hemoglobin should be monitored more often if its initial level was <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 arterial hypertension or with 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 of epoetin beta influencing the growth of certain types of tumors, incl. 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, it is necessary to exclude possible causes of an inadequate reaction to the drug (deficiency of iron, 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, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is <100 ng/ml, oral iron replacement therapy is recommended at a 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 prescribed 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 in 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 2 weeks, the dose is not changed, the dose/response ratio is assessed. After this, the dose can be reduced or increased according to the scheme presented above.

Epostim®