Eralfon solution 10000IU 1ml syringe, 1pc

Composition

1 syringe (1 ml) contains: Active ingredient: Epoetin alfa (REPOETIN-SP — recombinant human erythropoietin) 10000 IU, excipients: albumin solution in terms of dry albumin-1 mg; sodium citrate pentasequihydrate-2.32 mg or sodium citrate dihydrate-1.9104 mg; sodium chloride-2.336 mg; citric acid monohydrate-0.0228 mg; water for injection-up to 0.4 ml

Pharmacological action

Epoetin alfa is a glycoprotein that specifically stimulates erythropoiesis and activates mitosis and maturation of red blood cells from erythrocyte progenitor cells.

Recombinant Epoetin alfa is synthesized in mammalian cells that contain the gene encoding human erythropoietin. By its composition, biological and immunological properties, Epoetin alfa is identical to natural human erythropoietin. The introduction of epoetin alfa leads to an increase in hemoglobin and hematocrit levels, an 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 prolonged use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin may occur with or without the development of partial red cell aplasia.

Indications

• anemia in patients with chronic renal failure, including hemodialysis;
• prevention and treatment of anemia in patients with solid tumors, anemia which was the result of antitumor therapy;
• prevention and treatment of anemia in patients infected with human immunodeficiency virus (HIV), caused by the use of zidovudine, while endogenous erythropoietin level less than 500 IU/ml;
• prevention and treatment of anemia in patients with multiple myeloma, non-Hodgkin’s lymphoma, low-grade, chronic lymphocytic leukemia, rheumatoid arthritis;
• treatment and prevention of anemia in premature infants, born with low body weight (1.5 kg);
• within predeposit programs before extensive surgery in patients with a hematocrit level equal to 33-39%, to facilitate autologous blood collection and reduce the risk associated with the use of allogenic blood transfusions if the expected need for transfused blood exceeds the number which can be obtained by the method of autologous collection without the use of Epoetin alfa;
• before performing extensive surgery with an anticipated blood loss 900-1800 ml in adult patients with no anemia or with mild-to-moderate anemia (hemoglobin level 100-130 g/l), to reduce the need for allogenic blood transfusions and facilitate the recovery of erythropoiesis.

Contraindications

• hypersensitivity to drug or its components Eralfon;
• partial red cell aplasia after previous treatment with any erythropoietin;
• uncontrolled hypertension;
• the impossibility of adequate anticoagulant therapy;
• severe occlusive disease of coronary, carotid, cerebral and peripheral arteries and their consequences, including acute and recent myocardial infarction and acute ischemic stroke (within predeposit collection programs of the blood before the surgery).

With caution:  malignant neoplasms; epileptic syndrome, including in the anamnesis; thrombocytosis, thrombosis (in the anamnesis); sickle cell anemia; iron -, _B12-or folate-deficient conditions; porphyria; chronic liver failure.

Side effects

At the beginning of treatment, flu-like symptoms may occur: dizziness, drowsiness, fever, headache, myalgia, arthralgia.

From the CCC side:  dose-dependent increase in blood pressure, worsening of the course of arterial hypertension (most often in patients with chronic renal failure), in some cases — a hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic seizures.

From the side of hematopoietic organs:  thrombocytosis, in some cases — thrombosis of the shunt or arteriovenous fistula (including patients on hemodialysis with a tendency to hypotension or with aneurysm, stenosis), aplasia of the erythrocyte germ.

Allergic reactions:  skin rash (mild to moderate), eczema, urticaria, pruritus, angioedema.

Local reactions:  hyperemia, burning sensation, mild or moderate soreness at the injection site (more often occur with subcutaneous use).

From the side of laboratory parameters:  decreased serum ferritin concentration, with uremia-hyperkalemia, hyperphosphatemia.

Other services:  complications associated with respiratory disorders or with a decrease in 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).

Pharmacologically incompatible with solutions of other drugs.

How to take, course of use and dosage

Treatment of anemia in patients with chronic renal failure

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

1. Correction stage:  with subcutaneous use of the drug, the initial single dose is 30 IU / kg 3 times a week. With intravenous use of the drug, the initial single dose is 50 IU / kg 3 times a week. 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 weekly.

The following situations are possible: :

– the hematocrit increases from 0.5 to 1% per week. In this case, the dose is not changed until optimal indicators are reached;

– the rate of hematocrit increase is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times;

– the 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;

– the hematocrit remains low or decreases. It is necessary to analyze the causes of resistance before increasing the dose of the drug.

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

2. Maintenance therapy stage:  to maintain the hematocrit at the 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 hemoglobin levels.

Children undergoing hemodialysis. The initial dose is 50 U / kg 3 times a week. If necessary, a single dose is increased 1 time in 4 weeks by 25 U / kg until the optimal hemoglobin concentration is reached. Maintenance dose in children weighing less than 10 kg-75-150 U/kg (average 100 U/kg) 3 times a week; 10-30 kg-60-150 U/kg (average 75 U/kg) 3 times a week; more than 30 kg-30-100 U/kg (average 33 U/kg) 3 times a week.

Adult predialysis patients. The initial dose is administered subcutaneously or intravenously 3 times at 50 U / kg per week. If necessary, a single dose is increased 1 time in 4 weeks by 25 U / kg until the optimal hemoglobin concentration is reached. The maintenance dose is 17-33 U / kg 3 times a week.

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 the drug is 150 IU/kg 3 times a week with intravenous use. If after 4 weeks of treatment the hemoglobin level increases and is not less than 10 g / l or the number of reticulocytes 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 hemoglobin 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 for 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 dose of 300 IU/kg, the hemoglobin level has increased and is not less than 10 g / l or the number of reticulocytes increases by more than 40,000 cells/µl, then the existing dose of the drug is maintained (300 IU/kg 3 times a week). If after 4 weeks of treatment at a dose of 300 IU/kg, the hemoglobin level has increased by 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, treatment should be discontinued. If the hemoglobin level increases by more than 20 g / l within a month, the dose of the drug should be reduced by 25%. If the hemoglobin level exceeds 140 g / l, it is necessary to suspend treatment until the hemoglobin level drops below 120 g/l and then continue the drug use at a dose 25% lower than the initial one.

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

Serum ferritin levels (or serum iron levels) should be determined in all patients before and during treatment with the drug. If necessary, an 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 exceeds 500 IU/ml, the effect of drug therapy is unlikely.

Treatment with the drug includes 2 stages.

1. Correction stage: the drug is administered at a dose of 100 IU/kg 3 times a week subcutaneously or intravenously for 8 weeks. If after 8 weeks of therapy it was not possible to achieve a satisfactory effect (for example, to reduce the need for blood transfusions or to increase the level of hemoglobin), 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 the appearance of a response to further therapy in higher doses is unlikely.

2. Maintenance therapy stage: after achieving a satisfactory effect in the anemia correction phase, the maintenance dose should provide a hematocrit level in the range of 30-35%, depending on the change in the dose of zidovudine, the presence of concomitant infectious or inflammatory diseases. If the hematocrit exceeds 40%, the drug should be discontinued until the hematocrit decreases to 36%. When resuming 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, an additional iron intake is prescribed.

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

In these patients, the expediency of treatment with epoetin alfa is due to inadequate synthesis of endogenous erythropoietin against the background of anemia. When the level of hemoglobin 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 to increase or decrease every 3-4 weeks. If no increase in hemoglobin levels is observed after reaching the weekly dose of 600 IU/kg, 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, the synthesis of endogenous erythropoietin is suppressed under the influence of an increased concentration of proinflammatory cytokines. Treatment of anemia in these patients is carried out with the drug with subcutaneous use 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 the drug is increased to 150-200 IU/kg 3 times a week. A further increase in the dose does not seem appropriate.

Treatment and prevention of anemia in preterm children born with low body 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 hemoglobin and hematocrit levels are reached, but not more than 6 weeks.

Adult patients participating in an autologous blood collection program before surgery

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

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

If anemia is present, its cause should be determined before starting therapy with epoetin alfa. It is necessary to ensure adequate iron intake in the body as soon as possible by prescribing an oral iron preparation at a dose of 200 mg/day (based on divalent iron), and maintain iron intake at this level throughout the entire course of therapy.

Pre – and postoperative patients who do not participate in the autologous blood collection program

It is recommended to use subcutaneous use of the drug at a dose of 600 IU / kg per week for 3 weeks preceding the operation (21,14 and 7 days before the operation), and on the day of the operation. 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 level of hemoglobin in the preoperative period reaches 150 g/l or higher, the use of epoetin alfa should be discontinued. Before starting therapy with epoetin alfa, it is necessary to make sure that patients do not have iron deficiency.

All patients should receive an adequate amount of iron (oral 200 mg / day based on bivalent iron) throughout the course of treatment. If possible, additional oral iron intake should be provided prior to initiation of epoetin alfa therapy to ensure adequate iron storage in the patient’s body.

Overdose

Symptoms: increased side effects. Treatment: conduct symptomatic therapy, with a high level of hemoglobin – bloodletting.

Special instructions

During treatment, it is necessary to monitor blood pressure weekly and perform a general blood test (including platelets, hematocrit, ferritin). In the pre – and postoperative period, the hemoglobin level should be monitored more often if the initial level was

Patients with a history of controlled arterial hypertension or thrombotic complications may need to increase the dose of antihypertensive drugs and/or anticoagulants, respectively. When prescribed to patients with hepatic insufficiency, it is possible to slow down the metabolism of epoetin alfa and a pronounced increase in erythropoiesis. The safety of using the drug in this category of patients has not been established. Although the drug stimulates erythropoiesis, it is impossible to completely exclude the possibility of the effect of epoetin alfa on the growth of certain types of tumors, including bone marrow.

It is necessary to consider the possibility that a preoperative increase in hemoglobin levels may serve as a predisposing factor to the development of thrombotic complications. Patients should receive adequate preventive antiplatelet therapy prior to elective surgery. In the pre-and postoperative period, the drug is not recommended for patients with an initial hemoglobin level of more than 150 g/l.

In adult patients with chronic renal failure, clinically expressed CHD or chronic heart failure, the hemoglobin level should not exceed 100-120 g/l.

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

Before starting treatment, you should evaluate the iron reserves in the body. In most patients with chronic renal failure, cancer and HIV-infected patients, the concentration of ferritin in plasma decreases simultaneously with an increase in the level of hematocrit. Ferritin concentration should be determined during the entire course of treatment. If it is less than 100 ng / ml, oral iron replacement therapy is recommended at the rate of 200-300 mg / day (100-200 mg / day for children). 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 an adequate amount of iron orally at a dose of 200 mg / day.

In patients with chronic renal failure, correction of anemia can lead to an improvement in appetite and an increase in the absorption of potassium and protein. Periodic adjustments to dialysis parameters may be required to maintain normal urea, creatinine, and potassium concentrations.

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 vascular access thrombosis are possible, especially in patients with a tendency to hypotension or complications of arteriovenous fistula (including stenosis, aneurysm). In such patients, prevention of thrombosis is recommended.

When used in women of reproductive age with anemia on the background of chronic renal failure, it is possible to resume menstruation. The patient should be warned about the possibility of pregnancy and the need for reliable methods of contraception before starting therapy. In experimental studies on rats and rabbits, no teratogenic effect was found when administered intravenously at doses up to 500 U/kg/day; at higher doses, a weak, statistically insignificant decrease in fertility was noted.

Given 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 evaluated. After that, the dose can be reduced or increased (see “Dosage and use”).

Influence on the ability to drive vehicles and work with mechanisms. During the treatment period, until the optimal maintenance dose is established, patients with chronic renal failure should be careful when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions (an increased risk of increased blood pressure at the beginning of therapy).

Storage conditions

At a temperature of 2-8 °C

Shelf life

2 years

Active ingredient

Epoetin alfa

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion