Эральфон®

General characteristics. Structure:

Epoetin an alpha (erythropoetin of the person recombinant) 3000 ME or 5000 ME contains 1 syringe (0,3 ml) in quality of active agent
1 syringe (0,5 or 0,6 ml) Epoetin an alpha (erythropoetin of the person recombinant) contains in quality of active agent 20 000 ME
Excipients: albumine solution, citrate sodium pentasexivihydrat or citrate sodium a dihydrate, sodium chloride, citric acid monohydrate, water for injections.
Description: transparent colourless liquid.

Pharmacological properties:

Pharmacodynamics. Epoetin an alpha - the glycoprotein which is specifically stimulating an erythrogenesis activates a mitosis and maturing of erythrocytes from progenitors of an erythrocyte row. Recombinant эпоэтин the alpha is synthesized in cells of mammals which the gene coding human erythropoetin is built in. On the structure, biological and immunological properties эпоэтин an alpha it is identical to natural erythropoetin of the person. The alpha leads introduction of an epoetin to increase in levels of hemoglobin and a hematocrit, improvement of blood supply of fabrics and cardiac performances. The most expressed effect of use of an epoetin an alpha is observed at the anemias caused by a chronic renal failure. Seldom or never, at prolonged use of erythropoetin for therapy of anemic states formation of neutralized antibodies to erythropoetin with development of a partial krasnokletochny aplasia or without it can be observed.

Pharmacokinetics. At intravenous administration of an epoetin the alpha at healthy faces and patients with uraemia an elimination half-life makes 5-6 h. At hypodermic introduction of an epoetin an alpha its concentration in blood increases slowly and reaches a maximum during from 12 to 18 h after introduction, the elimination half-life makes 16-24 hours. Bioavailability of an epoetin the alpha at hypodermic introduction makes 25-40%. Does not kumulirut.

Indications to use:

Anemia at patients with a chronic renal failure, including, being on a hemodialysis;
- prevention and treatment of anemias at patients with solid tumors at which anemia turned out to be consequence of performing antineoplastic therapy;
- prevention and treatment of anemias at the patients infected with the human immunodeficiency virus (HIV), called by use of a zidovudine at concentration of endogenous erythropoetin less than 500 ME/ml;
- prevention and treatment of anemias at patients with a multiple myeloma, nekhodzhskinsky lymphoma of low degree of a zlokachestvennost, a chronic lymphoid leukosis;
- within the predepozitny program before extensive surgical intervention at patients with the level of a hematocrit, equal 33-39%, for simplification of collecting autologous blood and reduction of the risk connected with use of allogenic hemotransfusions if the expected need for the transfused blood exceeds quantity which can be received by method of autologous collecting without use of an epoetin an alpha;
- before carrying out extensive operation with the expected blood loss of 900-1800 ml at the adult patients who do not have anemia or with easy and average degree of anemia (concentration of hemoglobin of 100-130 g/l) for reduction of need for allogenic hemotransfusions and simplification of recovery of an erythrogenesis.

Use at pregnancy and during breastfeeding.

As the person has no sufficient experience of use of erythropoetin at pregnancy and a lactation, эпоэтин an alpha it is necessary to appoint only if the expected advantages of its use exceed possible risk for a fruit and mother. It is unknown whether the alpha with breast milk therefore at treatment by the drug Eralfon® it is necessary to stop breastfeeding is allocated эпоэтин.

Route of administration and doses:

Treatment of anemia at patients with a chronic renal failure

The adult patients who are on a hemodialysis

Эральфон® enter subcutaneously or intravenously at the end of dialysis session. At change of a way of introduction the drug is administered in a former dose, then, the dose is adjusted if necessary (at a hypodermic way of administration of drug, achievement of identical therapeutic effect requires a dose 20-30% less, than at intravenous administration). Treatment by drug includes two stages:

1. Correction stage: at hypodermic administration of drug the initial single dose makes 30 ME/kg 3 times a week. At intravenous administration of drug the initial single dose makes 50 ME/kg. The period of correction lasts until achievement of an optimum hemoglobin content (adults have 100-120 g/l and children have 95-110 g/l) and a hematocrit (30-35%). These indicators need to be controlled weekly.

The following situations are possible:
1. The hematocrit raises from 0,5 to 1,0% a week. In this case the dose is not changed before achievement of optimum indicators.
2. Hematocrit gain speed less than 0,5% a week. In this case increase in a single dose by 1,5 times is necessary.
3. Speed of a gain is more than 1,0% a week. In this case it is necessary to lower a single dose of drug by 1,5 times.
4. The hematocrit remains low or decreases. It is necessary to analyze the resistance reasons.

Efficiency of therapy depends on correctly picked up individual scheme of treatment.

2. Stage of a maintenance therapy: for maintenance of a hematocrit at the level of 30-35% the drug dose applied at a stage of correction should be reduced by 1,5 times. Then the maintenance dose of drug is selected individually, taking into account dynamics of indicators of a hematocrit and hemoglobin.

At the children who are on a hemodialysis, the initial single dose makes 50 ME/kg 3 times a week subcutaneously or intravenously. If necessary the single dose is raised 1 time in 4 weeks on 25 ME/kg to achievement of optimum concentration of hemoglobin. The supporting single dose at children with body weight less than 10 kg - 75-150 ME/kg (on average 100 ME/kg), 10-30 kg - 60-150 ME/kg (on average 75 ME/kg), more than 30 kg - 30-100 ME/kg (on average 33 ME/kg) 3 times a week.

To adult predialysis patients the initial dose is entered subcutaneously or intravenously 3 times on 50 ME/kg a week. If necessary the single dose is increased once in 4 weeks by 25 ME/kg before achievement of optimum concentration of hemoglobin. A maintenance dose - 17-33 ME/kg 3 times a week subcutaneously or intravenously.

Prevention and treatment of anemia at patients with solid tumors

Before an initiation of treatment it is recommended to carry out definition of concentration of endogenous erythropoetin. At concentration of erythropoetin in blood serum less than 200 ME/ml, an initial single dose of drug make at an intravenous way of introduction of 150 ME/kg 3 times a week. If in 4 weeks of treatment concentration of hemoglobin increased and makes not less than 10 g/l or the quantity of reticulocytes increased more than by 40 000 cells / мкл over a reference value, then the dose of drug remains former (150 ME/kg of body weight). If in 4 weeks of treatment increase in concentration of hemoglobin makes less than 10 g/l and increase in quantity of reticulocytes makes less than 40 000 cells / мкл in comparison with initial, then within the next 4 weeks the dose is increased to 300 ME/kg of body weight. If after additional 4 weeks of treatment at a dose of drug of 300 ME/kg concentration of hemoglobin increased and makes not less than 10 g/l or the quantity of reticulocytes increased more than by 40 000 cells / мкл, then keep the existing drug dose (300 ME/kg of body weight). If in 4 weeks of treatment in a dose of 300 ME/kg of body weight concentration of hemoglobin increases less than on 10 g/l and increase in quantity of reticulocytes makes less than 40 000 cells / мкл in comparison with initial, treatment should be stopped. In case of increase in concentration of hemoglobin more than on 20 g/l within a month, the dose of drug needs to be reduced by 25%. If concentration of hemoglobin exceeds 140 g/l, it is necessary to suspend treatment before decrease in concentration lower than 120 g/l and then to continue administration of drug in a dose 25% lower initial.

Therapy by drug has to continue within one month after the termination of a course of chemotherapy.

Content of ferritin of serum needs to be determined at all patients prior to the beginning of and in the course of treatment by drug. If necessary iron preparation is in addition appointed.

Prevention and treatment of anemia at patients with HIV infection

It is recommended by the drug Eralfon® to determine prior to treatment the initial content of endogenous erythropoetin in blood serum. The conducted researches show that at the content of erythropoetin more than 500 ME/ml the effect of therapy by drug is improbable.

1. Correction stage: drug is appointed in a single dose of 100 ME/kg 3 times a week subcutaneously or intravenously within 8 weeks. If after 8 weeks of therapy it was not succeeded to reach satisfactory effect (for example, to reduce the need for hemotransfusions or to achieve increase in concentration of hemoglobin), the dose can increase step by step (not more often than 1 time in 4 weeks) on 50-100 ME/kg 3 times a week. If it was not succeeded to reach satisfactory effect of therapy by the drug Eralfon® in a single dose of 300 ME/kg 3 times a week, then emergence of the response to further therapy in higher doses is improbable.

2. Stage of a maintenance therapy: after achievement of satisfactory effect in a phase of correction of anemia the maintenance dose has to provide a hematocrit within 30-35% depending on change of a dose of a zidovudine, existence of the accompanying infectious or inflammatory diseases. At a hematocrit more than 40%, it is necessary to stop administration of drug before decrease in a hematocrit to 36%. When resuming therapy a dose of an epoetin the alpha has to be lowered by 25% with the subsequent adjustment for maintenance of a required hematocrit. Content of ferritin of serum needs to be determined at all patients prior to the beginning of and in the course of treatment by drug. If necessary iron preparation is in addition appointed.

Prevention and treatment of anemia at patients with a multiple myeloma, nekhodzhskinsky lymphoma of low degree of a zlokachestvennost and with a chronic lymphoid leukosis

These patients have an expediency of treatment epoetiny the alpha is caused by inadequate synthesis of endogenous erythropoetin against the background of development of anemia. At concentration of hemoglobin it is lower than 100 g/l and contents of erythropoetin in blood serum enter lower than 100 ME/ml Eralfon® subcutaneously in a starting single dose of 100 ME/kg three times a week. Laboratory control of hemodynamic indicators is carried out weekly. If necessary the dose of drug is adjusted towards increase or reduction by each 3-4 weeks. If at achievement of a week dose of 600 ME/kg increase in concentration of hemoglobin is not observed, further use of an epoetin an alpha should be cancelled as inefficient.

The adult patients participating in the program of collecting autologous blood before surgical interventions

It is recommended to use intravenous administration of drug. Epoetin an alpha it is necessary to enter upon termination of the procedure of collecting blood. Before purpose of drug it is necessary to consider all contraindications to collecting autologous blood. Before surgical intervention of Eralfon® it is necessary to appoint 2 times a week within 3 weeks. At each visit of the doctor take away a portion of blood from the patient (if a hematocrit of ≥33% and/or concentration of hemoglobin of ≥110 g/l) and keep for an autologous transfusion. The recommended single dose of the drug Eralfon® - 600 ME/kg of body weight 2 times a week.

Content of ferritin of serum needs to be determined at all patients prior to the beginning of and in the course of treatment by drug. If necessary iron preparation is in addition appointed.

In the presence of anemia its reason has to be established prior to therapy epoetiny an alpha. It is necessary to provide in the shortest possible time adequate intake of iron in an organism, having appointed iron preparation in a dose of 200 mg/days (at the rate on elementary iron) and to support intake of iron at this level during all course of therapy.

Patients in before - and the postoperative period, not participating in the program of collecting autologous blood

It is recommended to use hypodermic administration of drug in a dose of 600 ME/kg of body weight in a week within 3 weeks preceding operation (the 21st, 14th and 7th days before operation), and in day of operation. If necessary, when on medical indications it is necessary to reduce the preoperative period, Eralfon® can appoint daily in a dose of 300 ME/kg of body weight within 10 days before operation, in day of operation and within 4 days after operation. If concentration of hemoglobin in the preoperative period reaches 150 g/l and above, use of an epoetin an alpha should be stopped. Prior to therapy epoetiny an alpha it is necessary to be convinced of absence at patients of deficit of iron. All patients have to receive adequate amount of iron (200 mg/days at the rate on elementary iron) throughout all course of treatment. Whenever possible it is necessary to provide additional intake of iron prior to therapy epoetiny an alpha for providing adequate depot of iron in the patient's organism.

Features of use:

During treatment it is necessary to control weekly arterial pressure and to carry out the general blood test (including calculation of thrombocytes), definition of a hematocrit and content of ferritin in blood serum. In before - and the postoperative period concentration of hemoglobin should be controlled more often if initial concentration made less than 140 g/l. It is necessary to remember that эпоэтин the alpha at treatment of anemia does not replace a hemotransfusion, but reduces need of its repeated use.

At patients with controlled arterial hypertension or trombotichesky complications in the anamnesis increase in a dose of hypotensive medicines and/or anticoagulants respectively can be required.

At appointment to patients with a liver failure delay of metabolism of an epoetin an alpha and the expressed strengthening of an erythrogenesis is possible. Safety of use of drug for this category of patients is not established.

Though drug stimulates an erythrogenesis, it is impossible to exclude completely a possibility of influence of an epoetin an alpha on growth of some types of tumors, including marrow.

It is necessary to consider an opportunity that preoperative increase in concentration of hemoglobin can serve as the contributing factor to development of trombotichesky complications. Before carrying out planned surgical intervention patients have to receive adequate preventive antiagregantny therapy. In before - and the postoperative period drug is not recommended to appoint to patients with the initial level of hemoglobin more than 150 g/l.

At adult patients with the chronic renal failure which is clinically expressed by coronary heart disease or chronic heart failure concentration of hemoglobin should not exceed 100-120 g/l.

Before an initiation of treatment it is necessary to exclude the possible reasons of inadequate reaction to drug (the deficit of iron, folic acid, cyanocobalamine, a serious poisoning aluminum salts accompanying an infection, inflammatory processes and injuries, the concealed hemorrhages, hemolysis, fibrosis of marrow of various etiology) and if necessary to correct treatment.

Prior to treatment it is necessary to estimate iron reserves in an organism. At most of patients with a chronic renal failure, at oncological and HIV-positive patients concentration of ferritin in plasma decreases along with increase in level of a hematocrit. Concentration of ferritin needs to be defined during all course of treatment. If it makes less than 100 ng/ml, replacement therapy by iron preparations for intake at the rate of 200-300 mg/days is recommended (100-200 mg/days for children). To premature children peroral therapy by iron preparations in a dose of 2 mg/days has to be appointed as soon as possible. The patients taking an autologous blood test and being in before - or the postoperative period, have to receive also adequate amount of iron inside in a dose of 200 mg/days.

With a chronic renal failure correction of anemia can cause improvement of appetite and increase in absorption of potassium and proteins in patients. Periodic correction of parameters of dialysis for maintenance of concentration of urea, creatinine and potassium within norm can be required.

At patients with a chronic renal failure it is necessary to control the content of electrolytes in blood serum.

According to the available data, use of an epoetin the alpha at predialysis patients can prevent progressing of a chronic renal failure. Because of increase in a hematocrit often it is required to increase a heparin dose during a hemodialysis. At an inadequate geparinization obstruction of dialysis system, fibrinferments of vascular access, especially at patients with a tendency to hypotension or with complications of an arteriovenous fistula are possible (a stenosis, aneurism, etc.). At such patients prevention of thromboses is recommended.

At use for women of reproductive age with anemia against the background of a chronic renal failure resuming of periods is possible. The patient should be warned about a possibility of approach of pregnancy and need of use of reliable methods of contraception prior to therapy. In pilot studies on rats and rabbits teratogenic action at intravenous administration in doses to 500 PIECES/kg of body weight a day is not revealed; in higher doses weak, statistically insignificant decrease in fertility is noted.

During treatment, before establishment of an optimum maintenance dose, to patients with a chronic renal failure, it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (increase in risk of increase in arterial pressure at the beginning of therapy).

Considering the possible more expressed effect of drug, its dose should not exceed a dose of the recombinant erythropoetin used in the previous course of treatment. Within the first two weeks the dose is not changed, estimate a ratio the dose/answer. After that the dose can be reduced or increased (see the section "Route of Administration and Doses").

Release form

Solution for intravenous and hypodermic administration of 3000 ME, 5000 ME or 20 000 ME. On 0,3 ml 3000 ME, on 0,3 ml 5000 ME, on 0,5 ml or on 0,6 ml of 20 000 ME in syringes with the additional automatic or non-automatic device for protection of a needle after use of the syringe or without it.

On 3 syringes on 3000 ME, 5000 ME or 20000 ME or on 1 syringe on 20000 ME in a blister strip packaging with a covering.

1 or 2 blister strip packagings on 3 syringes or 1 planimetric cell to packaging on 1 syringe on 20000 ME together with the application instruction place in a pack from a cardboard with stickers for opening control.

Side effects:

In an initiation of treatment the grippopodobny symptomatology can be noted: dizziness, drowsiness, feverish state, headache, mialgiya, arthralgia.

From cardiovascular system: dozozavisimy increase in arterial pressure, deterioration in a course of arterial hypertension (most often at patients with a chronic renal failure), in some cases - hypertensive crisis, sharp increase in arterial pressure with encephalopathy symptoms (a headache, confusion of consciousness) and generalized toniko-clonic spasms.

From bodies of a hemopoiesis: a thrombocytosis, in some cases - fibrinferments of the shunt or an arteriovenous fistula (at patients on a hemodialysis with tendency to arterial hypotension or with aneurism, a stenosis, etc.), a partial krasnokletochny aplasia. Allergic reactions: skin rash (poorly or moderately expressed), eczema, urticaria, an itch, a Quincke's disease.

Local reactions: a hyperemia, burning, weak or moderate morbidity in an injection site (arise at hypodermic introduction more often).

From laboratory indicators: decrease in concentration of ferritin in serum, at uraemias - hyperpotassemia, a hyperphosphatemia.

Others: the complications connected with disturbance of breath or with a lowering of arterial pressure, immune responses (induction of antibody formation), a porphyria aggravation.

Interaction with other medicines:

Reduces concentration of cyclosporine because of increase in extent of binding it with erythrocytes (there can be a need for cyclosporine dose adjustment). Pharmaceutical it is incompatible with solutions of other medicines.

Contraindications:

Hypersensitivity to drug or its components;
partial krasnokletochny aplasia after earlier carried out therapy by any erythropoetin;
uncontrollable arterial hypertension;
impossibility of performing adequate anticoagulating therapy;
at a serious occlusal illness of coronary, carotid, brain and peripheral arteries and their effects, including the acute and recently postponed myocardial infarction and an acute disorder of cerebral circulation (within the predepozitny program of collecting blood before surgeries).

With care

Malignant new growths, epileptic syndrome (including in the presence in the anamnesis), a thrombocytosis, thrombosis (in the anamnesis), a sickemia, iron-, B12-or foliyevodefitsitny states, a porphyria, a chronic liver failure.

Overdose:

Symptoms: strengthening of side effects. Treatment: symptomatic. At high concentration of hemoglobin – bloodletting.

Storage conditions:

Period of validity: 2 years. Not to use after the period of validity specified on packaging. At a temperature from 2 to 8 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and hypodermic administration of 3000 ME, 5000 ME or 20 000 ME. On 0,3 ml 3000 ME, on 0,3 ml 5000 ME, on 0,5 ml or on 0,6 ml of 20 000 ME in syringes with the additional automatic or non-automatic device for protection of a needle after use of the syringe or without it.

On 3 syringes on 3000 ME, 5000 ME or 20000 ME or on 1 syringe on 20000 ME in a blister strip packaging with a covering.

1 or 2 blister strip packagings on 3 syringes or 1 planimetric cell to packaging on 1 syringe on 20000 ME together with the application instruction place in a pack from a cardboard with stickers for opening control.