Eralfon 5000 IU 0.3 ml syringe with needle protection device, 6 pcs.

Epoetin alpha is a glycoprotein that specifically stimulates erythropoiesis and activates cytosis 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 during long-term use of erythropoietin for therapy of anemic conditions the formation of neutralizing antibodies to erythropoietin with the 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 the elimination half-life is 5-6 hours. When administered subcutaneously epoetin alfa its concentration in blood increases slowly and achieves maximum during 12 to 18 hours after administration, the period of semi-elimination is 16-24 hours. Bioavailability of epoetin alfa when administered subcutaneously is 25-40%. It does not cumulate.

Indications

Active ingredient

Composition

How to take, the dosage

The treatment of anemia in patients with chronic renal failure

Adult patients on hemodialysis

Eralfon® is given 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% lower than that when administered intravenously). Treatment with the drug includes two stages:

1. The correction phase: When the drug is administered subcutaneously, the initial single dose is 30 IU/kg 3 times per week. When administered intravenously, the initial single dose is 50 IU/kg. The period of correcting lasts till the optimal level of hemoglobin (100-120g/l in adults and 95-110g/l in children) and hematocrit (30-35%) are reached. These values should be monitored weekly.

The following situations are possible:

1) Hematocrit increases from 0.5% to 1.0% per week. In this case, the dose is not changed until optimal values are reached.
2) Hematocrit increases less than 0.5% per week. In this case the single dose should be increased 1.5 times.
3) Increase rate is more than 1.0% a 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. The causes of resistance should be analyzed.

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

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

In children on hemodialysis the initial dose is 50 units/kg 3 times a week. If necessary, the single dose is increased 1 time 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 (mean 100 iu/kg), 10-30 kg – 60-150 iu/kg (mean 75 iu/kg), over 30 kg – 30-100 iu/kg (mean 33 iu/kg).

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

Prevention and treatment of anemia in patients with solid tumors

We recommend determination of endogenous erythropoietin levels before starting treatment. If serum erythropoietin concentrations are less than 200 IU/ml, the starting dose of the drug is 150 IU/kg three times weekly with the intravenous route of administration.

If after 4 weeks of treatment the hemoglobin level has increased to at least 10 g/l or the number of reticulocytes has increased more than 40.000 cells/μl over the initial level, the dose of the drug remains the same (150 IU/kg body weight).

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 40,000 cells/μL compared to baseline, then the dose is increased to 300 IU/kg body weight for the next 4 weeks.

If after an additional 4 weeks of treatment with a 300 IU/kg dose, the hemoglobin level is increased to at least 10 g/kg or the reticulocyte count has increased by more than 40,000 cells/μL, then the current dose (300 IU/kg body weight) is maintained.

If after 4 weeks of treatment with 300 IU/kg body weight the hemoglobin level has increased less than 10 g/l and the reticulocyte count is less than 40,000 cells/μL compared to the initial level, treatment should be stopped. If the hemoglobin level increases by more than 20 g/l within a month, the drug dose should be reduced by 25%.

If hemoglobin levels exceed 140 g/l, treatment should be stopped until hemoglobin levels fall below 120 g/l; then the drug should be continued at a dose 25% lower than the original dose.

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

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

The prevention and treatment of anemia in patients with HIV infection:

It is recommended that baseline serum levels of endogenous erythropoietin be determined prior to treatment with Eralfon®. Studies have shown that therapy with erythropoietin levels greater than 500 IU/ml is unlikely to have an effect.

1. correction stage: The drug is given in a dose of 100 IU/kg, 3 times weekly, subcutaneously or intravenously for 8 weeks. If after 8 weeks of therapy it was not possible to reach a satisfactory effect (for example, to decrease the necessity of hemotransfusions or to increase hemoglobin level) the dose can be gradually increased (not more often than once in 4 weeks) by 50-100 IU/kg 3 times per week. If it was not possible to reach satisfactory effect from the therapy with Elalfon® in dose of 300 IU/kg 3 times per week, the appearance of response to further therapy in 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 the change of zidovudine dose, presence of concomitant infectious or inflammatory diseases. If hematocrit is greater than 40%, the drug should be discontinued until hematocrit drops to 36%.

If therapy is resumed, 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.

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

In these patients the appropriateness of treatment with epoetin alfa is conditioned by inadequate synthesis of endogenous erythropoietin against 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 three times a week. Laboratory control of hemodynamic indices is carried out weekly.

If necessary, the dose of the drug is adjusted upward or downward every 3-4 weeks. If at a weekly dose of 600 IU/kg there is no increase of hemoglobin level 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 the influence of increased concentration of proinflammatory cytokines. Treatment of anemia in these patients is performed by subcutaneous administration of the drug at the dose of 50-75 IU/kg: once a week. If hemoglobin level increases less than 10 g/l after 4 weeks of treatment, the drug dose is increased up to 150-200 IU/kg 3 times a week. Further increase of the dose * seems inexpedient.

The treatment and prophylaxis of anemia in preterm infants born with low body weight.
Eralfon® is administered subcutaneously in a dose of 200 IU/kg three times a week from the 6th day of life until the target values of hemoglobin and hematocrit are achieved but not longer than 6 weeks.

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

Intravenous administration of the drug is recommended. Epoetin alfa should be administered at the end of the blood collection procedure. All contraindications for autologous blood collection should be considered before prescribing the drug. Before surgical intervention Eralfon® should be administered 2 times a week for 3 weeks. At each visit, a blood sample is taken from the patient (if hematocrit >33% and/or hemoglobin level >11C g/l) and stored for autologous transfusion. The recommended dose of Eralphon® is 600 IU/kg body weight twice weekly.

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 body weight per week for 3 weeks prior to surgery (days 21, 14 and 7 prior to surgery) and on the day of surgery is recommended. If necessary, when it is medically necessary to shorten preoperative period, Eralfon® can be administered daily in a dose of 300 IU/kg of body weight 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

Special Instructions

During treatment, blood pressure should be monitored weekly and general blood counts (including platelets, hematocrit, ferritin) should be performed. In the pre- and postoperative period hemoglobin levels should be monitored more frequently if the baseline was 140 g/l. It should be remembered that epoetin alfa in the treatment of anemia does not replace hemotransfusion, but reduces the need for its repeated use.

In patients with a history of controlled arterial hypertension or thrombotic complications 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, we cannot fully exclude the possibility of action of epoetin alpha on growth of certain types of tumors, including bone marrow.

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 the pre- and postoperative period, pregranate is not recommended for patients with baseline hemoglobin levels greater than 150 g/l. In adult patients with chronic renal insufficiency, clinically significant coronary heart disease, 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 concentrations should be determined throughout the course of treatment. If it is less than 100 ng/ml, substitution therapy with oral iron preparations 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 required 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 been reported not 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 with complications of arteriovenous fistula (stenosis, aneurysm, etc.). In such patients the prophylaxis of thrombosis is recommended.

When used in women of reproductive age with anemia against a background of chronic renal insufficiency, menstruation may resume. The patient should be warned about possibility of pregnancy and necessity of using reliable methods of contraception before 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 of body weight per day; a weak statistically insignificant decrease of fertility was noted in higher doses.

At the time of treatment, until the optimal maintenance dose is established, patients with chronic renal insufficiency should be cautious about driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions (increase: risk of increased blood pressure at the beginning of therapy).

Because of 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. For the first two weeks the dose is not changed, the dose/response ratio is evaluated. Thereafter, the dose can be decreased or increased according to the scheme described above.

Contraindications

– partial red cell aplasia after previous therapy with any erythropoietin;

– uncontrolled arterial hypertension;

– inability to perform adequate anticoagulant therapyp> – in severe occlusive diseases of coronary, carotid, cerebral and peripheral arteries and their sequelae, including acute and recently suffered myocardial infarction in acute cerebral circulation disorder (as part of the preoperative blood collection program before surgical procedures).

With caution

Malignant neoplasms, epileptic syndrome (including in the presence of thrombocytosis, thrombosis (history), sickle cell anemia, iron-, folate-deficient states, porphyria, chronic liver failure. Since there is insufficient experience with the use of erythropoietin in pregnancy and humans, epoetin alfa should be prescribed only 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.

Side effects

Overdose

Similarities