Eralfon,. 3000 me 0,3 ml syringe with needle protection device 6 pcs.

Epoetin alpha is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of erythrocytes from erythrocyte progenitor cells. Recombinant epoetin alfa is synthesized in mammalian cells, in which the gene encoding human erythropoietin is embedded. By its composition, biological and immunological properties epoetin alpha is identical to natural human erythropoietin.

Injection of epoetin alfa results in increase of hemoglobin and hematocrit levels, improvement of blood supply to tissues and heart work. The most pronounced effect of epoetin alfa administration is observed in anemia caused by chronic renal failure. In very rare cases with long-term use of erythropoietin for therapy of anemic conditions, formation of neutralizing antibodies to erythropoietin with development of partial red cell aplasia or without it may be observed.

Pharmacokinetics

In intravenous administration of epoetin alfa in healthy individuals and patients with uremia, T_1/2 is 5-6 hours. When epoetin alfa is administered subcutaneously its concentration in blood increases slowly and reaches a maximum from 12 to 18 hours after injection, T_1/2 – 16-24 hours. Bioavailability of epoetin alfa when administered subcutaneously is 25-40%. It does not cumulate.

Indications

Anemia

• anemia in patients with chronic renal failure, including those on hemodialysis.
• Prevention and treatment of anemia in patients with solid tumors whose anemia has resulted from antitumor therapy;
• Prevention and treatment of anemia in patients infected with human immunodeficiency virus (HIV) caused by zidovudine, with endogenous erythropoietin levels less than 500 ME/mL;
• prevention and treatment of anemia in patients with myeloma disease, non-Hodgkin’s lymphoma of low malignancy, chronic lympholeukosis, rheumatoid arthritis;
• treatment and prevention of anaemia in premature infants born with low birth weight (up to 1.5 kg);
• treatment and prevention of anaemia in premature infantsas part of a preoperative program before major surgery in patients with a hematocrit level of 33-39% to facilitate autologous blood collection and reduce risks associated with the use of allogeneic blood transfusions if the expected need for transfused blood exceeds the amount that can be obtained by autologous collection without the use of epoetin alfa;
• Before major surgery with an expected blood loss of 900-1800 ml in adult patients without anemia or with mild to moderate anemia (hemoglobin level 100-130 g/L), to reduce the need for allogeneic hemotransfusions and facilitate recovery of erythropoiesis.

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Active ingredient

Epoetin alfa

Composition

1 syringe (0.3 ml)contains:

active ingredient:

epoetin alfa (REPOETIN-SP – recombinant human erythropoietin) 3000 IU,

auxiliary substances:

albumin solution in terms of dry albumin – 1 mg;

sodium citrate pentasquihydrate – 2.32 mg or sodium citrate dihydrate – 1.9104 mg;

Sodium chloride – 2.336 mg;

Citric acid monohydrate – 0.0228 mg;

Injectable water – up to 0.4 ml.

How to take, the dosage

Treatment of anemia in patients with chronic renal failure

Adults on hemodialysis. Eralfon is administered subcutaneously or intravenously at the end of a dialysis session. When changing the method of administration the drug is administered in the same dose, then the dose is adjusted if necessary (if the drug is administered subcutaneously, to achieve the same therapeutic effect, the dose is 20-30% less than that when administered intravenously). Treatment with the drug includes two stages.

1. Correction stage: when the drug is administered subcutaneously, the initial single dose is 30 IU/kg 3 times a week. When administered intravenously, the initial single dose is 50 IU/kg 3 times weekly. The period of correction lasts until the optimal level of haemoglobin (100-120 g/l for adults and 95-110 g/l for children) and haematocrit (30-35%) are reached. These values should be monitored weekly.

The following situations are possible:

Hematocrit rises from 0.5 to 1% per week. In this case, the dose is not changed until optimal values are reached;

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

– the rate of increase more than 1% a week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times;

– hematocrit remains low or decreases. The reasons for resistance should be analyzed before increasing the dose of the drug.

The effectiveness of therapy depends on a properly selected individual treatment regimen.

2. maintenance phase of therapy: in order to maintain hematocrit at 30-35%, the drug dose used in the correction phase should be reduced by 1.5 times. Then the maintenance dose of the drug is adjusted individually, taking into account the dynamics of hematocrit and hemoglobin levels.

Children on hemodialysis. The initial dose is 50 units/kg 3 times a week. If necessary, the single dose is increased once in 4 weeks by 25 units/kg until optimal hemoglobin concentration is achieved. Maintenance dose in children with body weight less than 10 kg – 75-150 iu/kg (average 100 iu/kg) 3 times a week; 10-30 kg – 60-150 iu/kg (average 75 iu/kg) 3 times a week; over 30 kg – 30-100 iu/kg (average 33 iu/kg) 3 times a week.

Adult pre-dialysis patients. The initial dose is administered subcutaneously or intravenously 3 times 50 IU/kg per week. If necessary, the single dose is increased 1 time every 4 weeks by 25 units/kg until optimal hemoglobin concentration is achieved. Maintenance dose is 17-33 units/kg 3 times a week.

Prevention and treatment of anemia in patients with solid tumors

Before starting treatment, it is recommended that endogenous erythropoietin levels be determined. If serum erythropoietin concentration is less than 200 IU/ml, the initial dose with intravenous administration is 150 IU/kg 3 times weekly. If after 4 weeks of the treatment the hemoglobin level increases and is more than 10 g/l or the number of reticulocytes has increased by more than 40000 cells/μl over the basic level, the dose of the preparation remains the same (150 IU/kg 3 times a week).

If after 4 weeks of treatment the increase in hemoglobin is less than 10 g/l and the increase in reticulocyte count is less than 40000 cells/μL compared to baseline, the dose is increased to 300 IU/kg 3 times per week for the next 4 weeks. If after an additional 4 weeks of treatment with a 300 IU/kg dose, the hemoglobin level has increased to at least 10 g/l or the reticulocyte count has increased by more than 40,000 cells/μL, then the current dose of the drug (300 IU/kg 3 times weekly) is maintained. If after 4 weeks of 300 IU/kg treatment, the hemoglobin level has increased by less than 10 g/l and the reticulocyte count is less than 40000 cells/μL compared to the initial level, treatment should be discontinued. In case of hemoglobin level increase of more than 20 g/l within a month, the drug dose should be decreased by 25%. If hemoglobin level exceeds 140 g/l, it is necessary to suspend treatment until hemoglobin level drops below 120 g/l and then continue the drug administration at a dose 25% lower than the initial one.

The therapy with the drug should be continued for 1 month after completion of chemotherapy.

The serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with the drug. Additional iron supplementation is prescribed if necessary.

Prevention and treatment of anemia in patients with HIV infection

It is recommended that baseline serum levels of endogenous erythropoietin be determined before starting treatment with Eralfon. Studies have shown that therapy with erythropoietin at levels greater than 500 IU/ml has little effect.

The treatment with the drug includes 2 stages.

1. Correction stage: The drug is given in a dose of 100 IU/kg three times weekly subcutaneously or intravenously for 8 weeks. If after 8 weeks of therapy it was not satisfactory (for example, to decrease the necessity of hemotransfusions or increase the hemoglobin level) the dose can be gradually increased (not more often than once in 4 weeks) by 50-100 IU/kg 3 times a week. If no satisfactory effect of therapy with Eralfon at a dose of 300 IU/kg 3 times weekly has been achieved, the appearance of response to further therapy at higher doses is unlikely.

2. maintenance therapy phase: after satisfactory effect in anemia correction phase, maintenance dose should provide hematocrit level within 30-35% depending on zidovudine dose changes, presence of concomitant infectious or inflammatory diseases. If hematocrit is greater than 40%, the drug should be discontinued until hematocrit decreases to 36%. During resumption of therapy, the dose of epoetin alfa should be decreased by 25% with subsequent adjustment 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, additional iron supplementation is prescribed.

Prevention and treatment of anemia in patients with myeloma disease, non-Hodgkin’s lymphoma of low malignancy and chronic lympholeukemia

In these patients the reason of treatment with epoetin alfa is inadequate synthesis of endogenous erythropoietin with development of anemia. In hemoglobin levels below 100 g/l and serum erythropoietin levels below 100 IU/ml Eralfon is administered subcutaneously in a starting dose of 100 IU/kg 3 times a week. Laboratory control of hemodynamic parameters is carried out weekly. If necessary, the dose is adjusted upward or downward every 3-4 weeks. If at a weekly dose of 600 IU/kg increase in hemoglobin level is not observed, further administration of epoetin alfa should be discontinued as ineffective.

Prevention and treatment of anemia in patients with rheumatoid arthritis

In patients with rheumatoid arthritis there is inhibition of endogenous erythropoietin synthesis under influence of increased concentration of proinflammatory cytokines. Anemia in these patients is treated by subcutaneous administration of the drug at a dose of 50-75 IU/kg 3 times a week. If hemoglobin level increases less than 10 g/l after 4 weeks of treatment, the drug dose is increased to 150-200 IU/kg 3 times a week. Further increase of the dose seems inexpedient.

The treatment and prevention of anemia in preterm infants of low birth weight

Eralfon is administered subcutaneously in a dose of 200 IU/kg 3 times a week from the 6th day of life until the target values of hemoglobin and hematocrit are reached, but not longer than 6 weeks.

Adult patients participating in the autologous blood collection program before surgical interventions

The intravenous route of administration is recommended. Epoetin alfa should be administered at the end of the blood collection procedure.

Before prescribing the drug, all contraindications for autologous blood collection should be considered. Before surgery, Eralphon should be administered twice weekly for 3 weeks. At each visit, a blood sample is taken from the patient (if hematocrit ≥33% and/or hemoglobin level ≥110 g/l) and stored for autologous transfusion. The recommended dose of Eralphon is 600 IU/kg w/v 2 times per week.

The serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with the drug. Additional iron supplementation is prescribed if necessary.

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

Patients in the pre- and postoperative period who do not participate in the autologous blood collection program

The use of subcutaneous administration of the drug at a dose of 600 IU/kg per week during the 3 weeks preceding surgery (days 21, 14 and 7 before surgery) and on the day of surgery is recommended. If necessary, when it is medically necessary to shorten the preoperative period, Elalfon can be administered daily in a dose of 300 IU/kg during 10 days before surgery, on the day of surgery, and during 4 days after surgery. If preoperative hemoglobin levels reach 150 g/L or higher, epoetin alfa should be discontinued. Before starting therapy with epoetin alfa it is necessary to make sure that patients have no iron deficiency.

All patients should receive adequate amounts of iron (oral 200 mg/day per divalent iron) throughout the course of treatment. If possible, additional oral iron should be provided before therapy with epoetin alfa to ensure adequate iron deposition in the patient.

Interaction

Decreases the concentration of cyclosporine due to an increased degree of its binding to red blood cells (it may be necessary to adjust the dose of cyclosporine).

Pharmaceutically incompatible with other drug solutions.

Special Instructions

During treatment, BP should be monitored weekly and general blood counts (including platelets, hematocrit, and ferritin) should be performed. In pre- and postoperative period hemoglobin levels should be monitored more frequently if the initial level was

In patients with controlled arterial hypertension or thrombotic complications in the anamnesis it may be necessary to increase the dose of hypotensive drugs and/or anticoagulants respectively. When administered to patients with hepatic impairment, metabolism of epoetin alfa may be slowed and erythropoiesis may be markedly increased. The safety of using the drug in this category of patients has not been established. Although the drug stimulates erythropoiesis, the possibility of action of epoetin alpha on growth of some types of tumors, including bone marrow, cannot be completely excluded.

We should consider the possibility that preoperative hemoglobin elevation may be a predisposing factor to the development of thrombotic complications. Patients should receive adequate prophylactic antiplatelet therapy prior to elective surgery. In pre- and postoperative period the drug is not recommended to be administered to patients with a baseline hemoglobin level of more than 150 g/l.

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

We should rule out possible causes of inadequate response to the drug (deficiency of iron, folic acid, cyanocobalamin, severe aluminum salts poisoning, concomitant infections, inflammatory processes and injuries, hidden bleeding, hemolysis, bone marrow fibrosis of various etiologies) and adjust treatment if necessary.

Before treatment, iron stores in the body should be assessed. In most patients with chronic renal failure, cancer and HIV-infected patients plasma ferritin concentration decreases simultaneously with an increase in hematocrit level. Ferritin concentration should be determined during the whole course of treatment. If it is less than 100 ng/ml, oral iron replacement therapy at a rate of 200-300 mg/day (100-200 mg/day for children) is recommended. In premature infants, oral iron therapy at a dose of 2 mg/day should be administered as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate oral iron at a dose of 200 mg/day.

In patients with chronic renal insufficiency, correction of anemia may improve appetite and increase potassium and protein absorption. Periodic correction of dialysis parameters may be necessary to maintain urea, creatinine, and potassium concentrations within normal limits.

In patients with chronic renal insufficiency, serum electrolyte levels should be monitored.

The use of epoetin alfa in predialysis patients has not been reported to accelerate the progression of chronic renal failure. Due to increased hematocrit, an increased dose of heparin is often required during hemodialysis. With inadequate heparinization, occlusion of the dialysis system, vascular access thrombosis is possible, especially in patients with a tendency to hypotension or complications of arteriovenous fistula (including stenosis, aneurysm). In such patients, thrombosis prophylaxis is recommended.

When administered in women of reproductive age with anemia against a background of chronic renal insufficiency, menstruation may resume. The patient should be warned about possible pregnancy and necessity of using reliable methods of contraception prior to the beginning of therapy. No teratogenic effect was found in experimental studies on rats and rabbits when administered intravenously in doses up to 500 units/kg/day; at higher doses a weak statistically insignificant decrease of fertility was noted.

With regard to a 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 administration”).

Impact on the ability to drive vehicles and operate machinery. During the treatment period, until the optimal maintenance dose is established, patients with chronic renal insufficiency should be cautious about driving and engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions (increased risk of BP increase at the beginning of therapy).

Contraindications

• high sensitivity to Eralfon or its components;
• partial red cell aplasia after previous therapy with any erythropoietin;
• uncontrolled arterial hypertension;
• unable to adequate anticoagulant therapy;
• severe occlusive disease of the coronary, carotid, cerebral and peripheral arteries and its consequences, including acute and recent myocardial infarction and acute cerebral circulatory disorders (as part of the preoperative blood collection program before surgical procedures).

With caution: malignant neoplasms; epileptic syndrome, including history; thrombocytosis, thrombosis (history); sickle cell anemia; iron-, B₁₂– or folic deficiency states; porphyria; chronic liver failure.

Side effects

In the beginning of treatment there may be flu-like symptoms: dizziness, somnolence, feverishness, headache, myalgia, arthralgia.

Systems: dose-dependent increase of BP, worsening of arterial hypertension course (especially in patients with chronic renal failure); in single cases – hypertensive crisis, sharp increase of BP with encephalopathy symptoms (headache, mental confusion) and generalized tonic-clonic convulsions.

Hematopoietic organs: thrombocytosis, in some cases – thrombosis of shunt or arteriovenous fistula (including patients on hemodialysis with a tendency to arterial hypotension or with aneurysm, stenosis), aplasia of red blood cell generation.

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

Local reactions: hyperemia, burning, mild to moderate soreness at the injection site (more common when administered by injection).

Laboratory findings: decreased serum ferritin concentration; in uremia – hyperkalemia, hyperphosphatemia.

Others: complications associated with respiratory distress or with a decrease in BP, immune reactions (induction of antibody formation), exacerbation of porphyria.

Overdose

Symptoms: intensification of side effects.

Treatment: symptomatic therapy, with high hemoglobin levels – bloodletting.

Pregnancy use

Because there is insufficient experience with the use of erythropoietin in pregnancy and lactation in humans, epoetin alfa should only be administered if the expected benefits of its use exceed the possible risk to the fetus and mother.

It is not known whether epoetin alfa is excreted with breast milk.

Similarities

Binocrit