Epobiocrin solution for injection 2000 IU syringe No. 5

Instructions for use Epobiocrin solution for injection 2000 IU syringe No. 5

Composition

active ingredient: Epoetin alfa;

1 ml of solution contains recombinant human erythropoietin 1000 IU or 2000 IU, or 4000 IU, or 10,000 IU;

Excipients: human albumin, sodium citrate, sodium chloride, citric acid monohydrate; water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: transparent colorless solution.

Pharmacotherapeutic group

Drugs affecting the blood system and hematopoiesis Antianemic drugs. Other antianemic drugs. Erythropoietin.

ATX code V0ZH A01.

Pharmacological properties

Pharmacodynamics.

Recombinant human erythropoietin corresponds in biological and immunological activity to human erythropoietin - a natural glycoprotein hormone that plays the role of a factor stimulating mitosis and is a hormone that stimulates erythropoiesis, the process of formation of erythrocytes from stem cell precursors. Normally, in a healthy person, erythropoietin is synthesized by the kidneys (90%) and Kupffer cells of the liver (10%). The level of its synthesis is determined by the level of blood oxygen saturation. Erythropoietin stimulates the proliferation and differentiation of erythroid cells into mature erythrocytes. Its action is carried out in the early stages of erythropoiesis at the level of cluster-forming units-erythrocytes and colony-forming units-erythrocytes, then at the level of proerythroblast, erythroblast and reticulocyte (the sensitivity of these cells to erythropoietin is proportional to their degree of maturity). Erythropoietin normalizes hemoglobin and hematocrit levels and eliminates symptoms associated with anemia.

The molecular weight of epoetin alfa is approximately 30,600 daltons. The protein portion constitutes approximately 60% of the molecular weight and contains 165 amino acids. Four carbohydrate chains are attached to the protein by three N-glycosidic bonds and one O-glycosidic bond.

Pharmacokinetics.

Intravenous administration. When the drug is administered intravenously, the half-life in individuals with normal renal function is about 4 hours; in patients with impaired renal function - about 5 hours. The half-life in children is about 6 hours.

Subcutaneous administration. Plasma concentrations are significantly lower after subcutaneous administration than after intravenous administration. After subcutaneous administration, the concentration of the drug in the blood increases slowly and reaches a maximum 12-18 hours after administration. The maximum plasma concentration after subcutaneous administration is lower than after intravenous administration (approximately 1/20 of the value).

There is no cumulative effect, i.e. measured serum erythropoietin concentrations remain at the same level regardless of whether the drug concentration is determined 24 hours after the first injection or 24 hours after the last.

There is no data on whether recombinant human erythropoietin can penetrate the placental barrier or into breast milk, but this substance does not penetrate the blood-brain barrier.

The half-life after subcutaneous administration is about 24 hours.

The bioavailability of the drug after subcutaneous administration is significantly lower than after intravenous administration, and is approximately 20%.

Indication

Treatment of symptomatic anemia associated with chronic renal failure:

treatment of anemia associated with chronic renal failure in children and adults on hemodialysis and adult patients on peritoneal dialysis;

Treatment of severe anemia of renal origin accompanied by clinical symptoms in adult patients with renal failure who are not yet undergoing hemodialysis.

Treatment of anemia and reduction of blood transfusion requirements in adult patients receiving chemotherapy for non-myeloma, malignant lymphoma or multiple myeloma who are at increased risk of transfusion based on the patient's overall condition (including cardiovascular status, pre-existing anemia prior to chemotherapy).

Epobiocrin can be used as part of a pre-deposit program before major surgery in patients with moderate anemia (hemoglobin level 10-13 g/dL (6.2-8.1 mmol/L), no iron deficiency) to facilitate the collection of autologous blood and reduce the risk associated with the use of allogeneic blood transfusions, if the expected need for blood for transfusion exceeds the amount that can be obtained by autologous collection without the use of epoetin alfa.

Epobiocrin is used in adult patients with mild to moderate anemia (hemoglobin within 10–13 g/dL in the absence of iron deficiency) before major orthopedic surgeries with expected moderate blood loss (900–1800 ml of blood) to reduce the need for allogeneic blood transfusions and facilitate recovery of the erythropoiesis system.

Contraindication

Patients who have developed pure red cell aplasia following treatment with any erythropoietin should not receive Epobiocrin or any other erythropoietin (see section “Special warnings and precautions for use”).

Uncontrolled hypertension.

Contraindications associated with the autologous blood donation program in patients receiving epoetin alfa.

Severe coronary, peripheral arterial, carotid or cerebrovascular disease, including recent myocardial infarction or stroke, in patients scheduled for major elective orthopedic surgery who have not participated in an autologous blood donation program.

Inability to use adequate antithrombotic prophylaxis in surgical patients for any reason.

Interaction with other medicinal products and other types of interactions

There is no evidence to suggest that treatment with epoetin alfa affects the metabolism of other drugs.

Drugs that inhibit erythropoiesis may reduce the response to epoetin alfa treatment.

Since cyclosporine binds to erythrocytes, there is a possibility of drug interaction. When using Epobiocrin and cyclosporine simultaneously, the level of the latter in the blood should be monitored and the dose adjusted if the hematocrit increases.

There is no evidence of an interaction between epoetin alfa and G-CSF (granulocyte colony-stimulating factor) or G-CSF (granulocyte-macrophage colony-stimulating factor) with respect to hematological differentiation or tumor cell proliferation in a biopsy specimen in vitro.

In adult patients with metastatic breast cancer, subcutaneous administration of epoetin alfa at a dose of 40,000 U/ml concomitantly with trastuzumab at a dose of 6 mg/kg had no effect on the pharmacokinetics of trastuzumab.

Application features

In order to improve the traceability of biological medicinal products, the name and batch number of the administered erythropoiesis-stimulating agent used in the treatment should be clearly recorded in the patient's medical record.

Blood pressure should be monitored continuously in all patients during treatment with Epoetin alfa. The drug should be used with caution in patients with untreated, inadequately treated hypertension, or with inadequately controlled hypertension. Antihypertensive therapy may need to be initiated or increased during treatment with Epoetin alfa. If blood pressure is not controlled, epoetin alfa should be discontinued.

Cases of hypertensive crisis with encephalopathy and convulsions, requiring immediate medical attention and intensive care, have also been observed in patients with normal or low blood pressure at the start of treatment. Particular attention should be paid to the appearance of sudden migraine-like shooting headache, which may be an alarm signal (see section "Adverse reactions").

Epoetin alfa should be used with caution in patients with epilepsy, a history of seizures, or medical conditions that are risk factors for seizures, such as CNS infections or brain metastases.

Epoetin alfa should be used with caution in patients with chronic hepatic insufficiency. The safety of epoetin alfa in this patient population has not been established.

Patients receiving erythropoiesis-stimulating medicinal products are at increased risk of vascular events with thrombotic complications (see section 4.8), including venous and arterial thrombosis and embolism (including fatal outcomes), namely deep vein thrombosis, pulmonary embolism, retinal vein thrombosis and myocardial infarction. Cases of cerebrovascular accidents (including ischemic stroke, hemorrhagic stroke and transient ischemic attacks) have also been reported.

The reported risk of these thrombotic/vascular complications should be carefully weighed against the benefits of treatment with epoetin alfa, especially in patients with existing risk factors for thrombotic/vascular complications, including obesity and a history of thrombotic/vascular complications (e.g. deep vein thrombosis, pulmonary embolism and cerebrovascular insufficiency).

Hemoglobin levels should be closely monitored in all patients due to the potential increased risk of thromboembolic complications and fatal outcome when the medicinal product is used at haemoglobin levels higher than the target in the indications for use.

All other causes of anemia (iron, folic acid, vitamin B12 deficiency, aluminum poisoning, infection or inflammation, blood loss, hemolysis or bone marrow fibrosis of any origin) should be identified and treated before initiating therapy with epoetin alfa and before deciding to increase the dosage. In most cases, serum ferritin values decreased simultaneously with an increase in hematocrit. To ensure an optimal response to epoetin alfa treatment, it is important to ensure adequate iron levels and, if necessary, supplement iron (see section 4.2):

Patients with chronic renal failure are recommended to take iron (200–300 mg/day for adults and 100–200 mg/day for children orally in terms of elemental iron) if the serum ferritin level is below 100 ng/ml;

Patients with cancer are recommended to take iron (200–300 mg/day orally in terms of elemental iron), if transferrin saturation is below 20%;

Patients participating in an autologous blood donation program are recommended to take iron (200 mg/day orally as elemental iron) several weeks before the start of autologous blood donation in order to achieve significant iron stores in the body before the start of therapy and during the course of treatment with epoetin alfa;

Patients undergoing major elective orthopedic surgery are advised to take iron (200 mg/day orally as elemental iron) during treatment with epoetin alfa. If possible, iron should be started before starting epoetin alfa therapy to ensure adequate iron stores.

There have been very rare reports of the development or worsening of pre-existing porphyria in patients treated with epoetin alfa. Epoetin alfa should be used with caution in patients with porphyria.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported with epoetin alfa treatment (see section 4.8). More severe cases have been observed with long-acting epoetins.

Patients should be informed about the signs and symptoms of skin reactions before use and monitored closely. If signs and symptoms of skin adverse reactions develop, epoetin alfa treatment should be discontinued immediately and alternative treatments should be considered. If a patient has developed a serious skin reaction such as SJS or TEN following the use of Epobiocrin, the patient should not be restarted on this medicinal product under any circumstances.

Transferring a patient from one erythropoiesis-stimulating agent to another is possible only under the supervision of a physician.

Pure red cell aplasia (PRCA).

There have been reports of antibody-mediated pure red cell aplasia (PRCA) following months or years of subcutaneous administration of epoetin, predominantly in patients with chronic renal failure. Cases of pure red cell aplasia have also been reported in patients with hepatitis C receiving interferon and ribavirin concomitantly with erythropoiesis-stimulating agents. Epoetin alfa is not indicated for the treatment of anemia associated with hepatitis C.

Patients who experience a sudden loss of response (as evidenced by a decrease in hemoglobin of 1–2 g/dL per month) with an increase in transfusion requirements should be referred for reticulocyte count and identification of typical causes of decreased clinical response (e.g., iron, folic acid, vitamin B12 deficiency, aluminum poisoning, infection or inflammation, blood loss, hemolysis, or bone marrow fibrosis of any origin).

In case of paradoxical decrease in hemoglobin and development of severe anemia associated with low reticulocyte count, treatment with Epobiocrin should be interrupted and the presence of antibodies to erythropoietin should be determined, as well as a bone marrow examination should be performed to establish the diagnosis of pure red cell aplasia.

Patients should not be treated with other erythropoiesis-stimulating agents because of the potential for cross-reaction.

Treatment of symptomatic anemia in adult patients and children with chronic renal failure.

In patients with chronic renal failure receiving epoetin alfa, hemoglobin levels should be monitored regularly until stable, then periodically thereafter. The rate of increase in hemoglobin should be approximately 1 g/dL (0.62 mmol/L) per month and should not exceed 2 g/dL (1.25 mmol/L) per month to minimize the risk of developing hypertension.

Controlled clinical trials have not shown significant benefits of using epoetins at hemoglobin concentrations above the level necessary to ensure control of anemia symptoms and prevent blood transfusion.

Caution should be exercised when increasing the dose of Epoetin in patients with chronic renal failure, as high cumulative doses of erythropoietin may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events. In patients with an inadequate response to epoetin therapy, other options for overcoming the inadequate response should be considered (see section 4.2).

Patients with chronic renal failure receiving subcutaneous Epobiocrin should be monitored regularly for loss of efficacy, defined as a decrease or loss of response to epoetin alfa treatment in patients who previously responded to therapy. Loss of efficacy is characterized by a persistent decrease in hemoglobin levels regardless of an increase in the dose of epoetin alfa (see section 4.8).

In patients on a treatment regimen with extended dosing intervals (administration of epoetin alfa less than once a week), hemoglobin levels may decrease in some patients, and such patients may require an increase in dose. Hemoglobin levels should be monitored regularly.

Shunt thrombosis has been observed in hemodialysis patients, especially in those with a predisposition to hypotension or complications of arteriovenous fistulas (e.g. stenosis, aneurysms, etc.). Early shunt inspection and thrombosis prophylaxis, e.g. with acetylsalicylic acid, are recommended in such patients.

Hyperkalemia has been observed in isolated cases, although a causal relationship has not been established. In patients with chronic renal failure, serum electrolyte levels should be monitored. In the event of an increase in serum potassium, in addition to appropriate treatment of hyperkalemia, temporary discontinuation of Epobiocrine should be considered until the hyperkalemia has fully resolved.

Due to the increase in hematocrit, patients on hemodialysis receiving Epobiocrin often require an increase in the dose of heparin during dialysis. In case of insufficient heparinization, occlusion of the dialysis system may develop.

According to the information available to date, the use of Epobiocrin in predialysis patients does not accelerate the progression of renal failure.

Treatment of patients with chemotherapy-induced anemia.

In cancer patients treated with epoetin alfa, hemoglobin levels should be monitored regularly until a stable level is achieved, then periodically.

Epoetins are growth factors that primarily stimulate the production of red blood cells. Erythropoietin receptors have also been found on the surface of various tumor cells. As with other growth factors, the possibility that epoetins may stimulate the growth of certain types of tumors cannot be ruled out.

An effect of erythropoiesis-stimulating agents on tumour progression or reduced progression-free survival cannot be excluded. In controlled clinical trials, the use of Epobiocrin and other erythropoiesis-stimulating agents has been associated with reduced locoregional tumour control or overall survival:

reduced locoregional control in patients with advanced head and neck cancer receiving radiation therapy when used to increase hemoglobin levels above 14 g/dL (8.7 mmol/L);

reduced overall survival and increased mortality due to disease progression within 4 months in patients with metastatic breast cancer receiving chemotherapy when used to increase hemoglobin levels to 12-14 g/dL (7.5-8.7 mmol/L);

increased risk of death when used to increase hemoglobin to 12 g/dL (7.5 mmol/L) in patients with active malignant disease who are not receiving chemotherapy or radiation therapy. Erythropoiesis-stimulating drugs are contraindicated in this group of patients;

a 9% increase in the risk of disease progression or death compared to the primary analysis in the group of patients receiving epoetin alfa and standard of care, and a 15% increase in risk that cannot be statistically excluded in patients with metastatic breast cancer receiving chemotherapy when used to increase hemoglobin levels to 10-12 g/dL (6.2-7.5 mmol/L).

Cancer patients receiving chemotherapy typically show a 2–3 week delay in response (from erythropoietin administration to the appearance of erythropoietin-induced blood cells). This should be taken into account when assessing the effectiveness of therapy (especially in patients requiring transfusions).

Patients undergoing surgery and participating in an autologous blood donation program.

All special warnings and precautions associated with the autologous blood donation program, especially the procedures for restoring circulating blood volume, should be followed.

Patients undergoing major elective orthopedic surgery.

Good blood transfusion practices should always be followed in the pre- and postoperative period.

Patients undergoing major elective orthopedic surgery should receive appropriate antithrombotic prophylaxis, as thrombotic and vascular complications may occur after surgery, especially in patients with underlying cardiovascular disease. Particular caution should be exercised when treating patients with a predisposition to deep vein thrombosis. Furthermore, patients with baseline hemoglobin > 13 g/dL are at significantly higher risk of postoperative thrombotic or vascular complications associated with epoetin alfa therapy. Therefore, the use of epoetin alfa in patients with baseline hemoglobin > 13 g/dL is not recommended.

Elderly patients

The safety of epoetin alfa in this category of patients has not been established.

Important information about excipients.

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Pregnancy.

There are currently no controlled studies of the use of Epoetin alfa in pregnant women. Animal studies have shown reproductive toxicity. Therefore, Epoetin alfa should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus. The use of epoetin alfa in pregnant women participating in an autologous blood donation program is not recommended.

Breast-feeding.

It is not known whether exogenous epoetin alfa is excreted in human milk. Caution should be exercised when epoetin alfa is administered to nursing mothers. A decision on whether to continue or discontinue breast-feeding or to continue or discontinue epoetin alfa therapy should be made taking into account the benefit of breast-feeding to the child and the benefit of epoetin alfa therapy to the woman.

The use of epoetin alfa in patients participating in an autologous blood donation program is not recommended during breastfeeding.

Fertility.

No studies have been conducted on the effects of epoetin alfa on male or female fertility.

The ability to influence the reaction speed when driving or working with other mechanisms

No studies have been conducted on the effect on reaction speed when driving vehicles or other mechanisms.

Method of administration and doses

Epoetin alfa can be administered by subcutaneous and intravenous injection.

As with any parenteral medicinal product, the drug Epobiocrin should be inspected visually for visible particulate matter and discoloration of the solution prior to administration.

All other causes of anemia (iron, folic acid, vitamin B12 deficiency, aluminum poisoning, infection or inflammation, blood loss, hemolysis or bone marrow fibrosis of any etiology) should be identified and treated before initiating therapy with epoetin alfa and before deciding to increase the dosage. To achieve an optimal response to treatment with epoetin alfa, adequate iron intake should be ensured and, if necessary, additional iron preparations should be prescribed (see section "Special instructions").

Intravenous administration.

Epoetin alfa is administered by injection over 1 to 5 minutes, depending on the dose. In patients undergoing hemodialysis, a bolus injection may be administered during the procedure through a suitable venous port in the dialysis line. The drug may also be administered after the hemodialysis procedure through the catheter fistula, followed by the administration of 10 ml of isotonic sodium chloride to flush the system and ensure proper distribution of the drug in the circulation.

Slow administration is used mainly for patients with cold symptoms.

Epoetin alfa should not be administered as an intravenous infusion or mixed with other drugs.

Subcutaneous injection.

The maximum volume of subcutaneous administration of the drug in one area is 1 ml. If it is necessary to use larger volumes, subcutaneous administration is carried out in several areas.

The drug should be administered subcutaneously into the extremities or the anterior abdominal wall.

Treatment of symptomatic anemia in adult patients and children with chronic renal failure.

In patients with chronic renal failure, if intravenous administration is possible (patients on hemodialysis), this route is considered preferable. In case of difficulties with intravenous administration (patients for whom hemodialysis is not yet indicated or patients on peritoneal dialysis), epoetin alfa can be administered subcutaneously.

Anemia symptoms and complications may vary depending on age, gender, and underlying disease conditions; a physician's assessment of the patient's individual clinical course and condition is necessary.

Epobiocrin should be used to increase the haemoglobin level to no more than 12 g/dl (7.5 mmol/l). An increase in haemoglobin of more than 2 g/dl (1.25 mmol/l) over a 4-week period should be avoided. In such cases, the dose should be reduced as indicated below.

Due to individual variability, periodic hemoglobin levels in each patient may be higher or lower than the desired level.

Haemoglobin levels should be monitored by dose titration, with the aim of maintaining the haemoglobin level between 10 g/dl (6.2 mmol/l) and 12 g/dl (7.5 mmol/l). In children, the recommended optimal haemoglobin level is 9.5–11 g/dl (5.9–6.8 mmol/l).

A persistent hemoglobin level above 12 g/dL (7.5 mmol/L) should be avoided. If the hemoglobin concentration increases by at least 2 g/dL (1.25 mmol/L) per month or the persistent hemoglobin level exceeds 12 g/dL (7.5 mmol/L), the epoetin dose should be reduced by 25%. If the hemoglobin level exceeds 13 g/dL (8.1 mmol/L), treatment should be discontinued until the hemoglobin level decreases to 12 g/dL (7.5 mmol/L) and then epoetin alfa treatment should be resumed at a dose 25% lower than the previous dose.

Patients should be closely monitored to ensure that the lowest approved dose of erythropoiesis-stimulating medicinal products provides adequate control of signs of anemia.

Ferritin levels (or serum iron concentrations) should be determined in all patients before and during treatment with Epobiocrin. Iron supplements should be administered as needed. Other types of anemia (such as vitamin B12 deficiency or folate deficiency) should be excluded before initiating therapy with Epobiocrin. Failure to respond to Epobiocrin therapy requires the investigation of underlying factors such as iron, folate, or vitamin B12 deficiency, aluminum intoxication, intercurrent infections, inflammatory processes or trauma, hemolysis, and bone marrow fibrosis of any etiology.

Adult patients on hemodialysis.

For patients undergoing hemodialysis, the drug is administered intravenously.

Treatment is divided into two stages.

Correction phase.

50 IU/kg 3 times a week.

If necessary, increase the dose gradually (no more than once within 4 weeks) by 25 IU/kg 3 times a week until the optimal hemoglobin concentration is achieved (10–12 g/dL 6.2–7.5 mmol/L).

Supportive phase.

Dose adjustment to maintain desired hemoglobin (Hb) level – 10 to 12 g/dL (6.2–7.5 mmol/L).

The recommended total weekly dose is 75 to 300 IU/kg.

Patients with relatively low baseline hemoglobin levels (< 6 g/dL or < 3.75 mmol/L) may require higher doses to maintain concentrations than patients with less severe anemia (hemoglobin > 8 g/dL or > 5 mmol/L).

Children on hemodialysis.

For patients undergoing hemodialysis, the drug is administered intravenously.

Treatment is divided into two stages.

Correction phase.

50 IU/kg 3 times a week.

If a dose increase is necessary, a gradual increase (no more than once within 4 weeks) of 25 IU/kg 3 times a week can be performed until an optimal hemoglobin concentration of 9.5–11 g/dL (5.9–6.8 mmol/L) is achieved.

Supportive phase.

Adjust the dose to maintain the desired hemoglobin (Hb) level of 9.5–11 g/dL (5.9–6.8 mmol/L).

Children weighing up to 30 kg require a higher maintenance dose than adults and children weighing more than 30 kg.

Maintenance doses of epoetin alfa:

Patients with very low baseline hemoglobin levels (< 6.8 g/dL or < 4.25 mmol/L) may require higher doses to maintain concentrations compared to patients with less severe anemia (hemoglobin > 6.8 g/dL or > 4.25 mmol/L).

Adult patients with renal failure in the predialysis period.

For patients with renal failure who are in the predialysis period, if there is no access to the intravenous route of administration, the drug can be administered subcutaneously.

The treatment is divided into two stages.

Correction phase.

50 IU/kg 3 times a week.

If necessary, dose adjustment can be performed by adding 25 IU/kg 3 times a week, with an interval between increases of at least 4 weeks until a hemoglobin level of 10–12 g/dl (6.2–7.5 mmol/l) is achieved.

During the maintenance phase, Epobiocrin can be administered either 3 times a week or, in the case of subcutaneous administration, 1 time per week or 1 time per 2 weeks. The doses and intervals between administrations should be adjusted to maintain the desired hemoglobin level: (Hb) 10 to 12 g/dl (6.2 to 7.5 mmol/l). Prolonging the intervals between administrations may require an increase in the dose. The maximum dose should not exceed 150 IU/kg 3 times a week, 240 IU/kg (maximum 20,000 IU) once a week or 480 IU/kg (maximum 40,000 IU) once every 2 weeks.

Adult patients on peritoneal dialysis.

For patients on peritoneal dialysis, if there is no access to an intravenous route of administration, the drug can be administered subcutaneously.

The treatment is divided into two stages.

Correction phase.

50 IU/kg 2 times a week.

Supportive phase.

Typically, the dose to maintain the desired hemoglobin (Hb) level of 10 to 12 g/dL (6.2–7.5 mmol/L) is 25 to 50 IU/kg 2 times a week by administering two equal injections.

Treatment of patients with chemotherapy-induced anemia.

In patients with anemia (e.g., hemoglobin concentration ≤ 10 g/dL (6.2 mmol/L)), Epobiocrin should be administered subcutaneously. Symptoms of anemia and complications depend on the patient's age, gender, and underlying disease; a physician's assessment of the patient's individual clinical course and condition is necessary.

Due to individual variability, the periodic values of hemoglobin levels in each patient may be higher or lower than the desired level. The hemoglobin level should be monitored by dose adjustment, taking into account that its level should be in the range of 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l). A persistent hemoglobin level above 12 g/dl (7.5 mmol/l) should be avoided. Guidelines for dose adjustment for hemoglobin levels above 12 g/dl (7.5 mmol/l) are described below.

Epoetin alfa therapy should be continued for one month after cessation of chemotherapy.

The starting dose for the treatment of anemia in this group of patients is 150 IU/kg 3 times a week. Alternatively, epoetin alfa can be administered at a starting dose of 450 IU/kg subcutaneously once a week.

If, after 4 weeks of the initial dose, the hemoglobin level has increased by at least 1 g/dL (0.6 mmol/L) (or the reticulocyte level has increased to ≥ 40,000 cells/mL), the dose should remain at 150 IU/kg 3 times a week or 450 IU/kg subcutaneously once a week. If, after 4 weeks of the initial dose, the hemoglobin level has increased by 1 g/dL (0.62 mmol/L) or the reticulocyte level has increased to < 40,000 cells/mL, the dose should be increased to 300 IU/kg 3 times a week or 40,000 IU once a week.

If, after 4 weeks of treatment with an additional dose of 300 IU/kg 3 times a week, the hemoglobin level has increased by ≥ 1 g/dL (≥ 0.62 mmol/L) or the reticulocyte level has increased to ≥ 40,000 cells/mL, the dose should not be changed. However, if the hemoglobin level has increased by < 1 g/dL (≥ 0.62 mmol/L) or the reticulocyte level has increased to < 40,000 cells/mL, the clinical response is considered negative and treatment should be discontinued.

Recommended dosage regimen:

Patients should be closely monitored to ensure that the lowest approved dose of erythropoiesis-stimulating medicinal products provides adequate control of signs of anemia.

Dose selection to maintain the target hemoglobin level of 10 – 12 g/dl.

If the rate of increase in hemoglobin is more than 2 g/dL (1.25 mmol/L) in 1 month and the total hemoglobin level approaches 12 g/dL (7.5 mmol/L), the dose of Epobiocrine should be reduced by 25-50% depending on the rate of increase in hemoglobin. If the hemoglobin level exceeds 13 g/dL (8.1 mmol/L), therapy should be temporarily discontinued until the level decreases to 12 g/dL (7.5 mmol/L) and therapy should be resumed at a dose 25% lower than the previous dose.

Adult patients participating in an autologous blood donation program prior to surgery.

Intravenous administration should be used.

Epoetin alfa is administered after each blood sampling procedure.

Patients with moderate anemia (hematocrit 33–39%) who require ≥ 4 units of blood should be treated with epoetin alfa at a dose of 600 IU/kg twice weekly for 3 weeks prior to surgery.

All patients treated with epoetin alfa should receive adequate iron supplementation (200 mg/day orally) throughout the course of therapy. To ensure adequate iron levels in the body, the administration of iron supplements is recommended.