Эральфон®

General characteristics. Structure:

1 syringe (1,0 ml) Epoetin an alpha (erythropoetin of the person recombinant) contains in quality of active agent 40 000 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:

- 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 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.

Route of administration and doses:

For treatment of anemia at oncological patients it is recommended to enter Eralfon® subcutaneously.

Optimum concentration of hemoglobin has to make 120 g/l at men and women and should not be exceeded.

Эральфон® it can be appointed the patient with symptomatic anemia, for prevention of anemia at the patients who are receiving chemotherapy and having initial low concentration of hemoglobin during the first course of chemotherapy (for example, an initial hemoglobin content of 110-130 g/l or decrease more than to 20 g/l at initial hemoglobin over 130 g/l).

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 subcutaneously. As an alternative the initial dose can make 40 000 ME once a week subcutaneously.

If after four 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 initial quantity, the dose of Eralfona® remains former.

If after four 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 quantity, then within the next four weeks the dose is increased to 300 ME/kg of body weight by three times a week or to 60 000 ME once a week.

If after additional four weeks of treatment at a dose of Эральфона® 300 ME/kg 3 times a week or 60 000 ME once a week concentration of hemoglobin raised 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 dose of Eralfona®.

If after four weeks of treatment in a dose of 300 ME/kg of body weight or 60 000 ME once week 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 quantity, treatment should be stopped.

In case of increase in concentration of hemoglobin more than on 20 g/l within a month or achievement of concentration of hemoglobin of 120 g/l, the dose of drug needs to be reduced by 25%. If the hemoglobin content exceeds 120 g/l, it is necessary to suspend treatment before decrease in concentration of hemoglobin lower than 120 g/l and then to continue introduction of Eralfona® in a dose 25% lower initial.

Therapy of Eralfonom® has to continue within one month after the termination of a course of chemotherapy.

Serum ferritin level (or the level of serumal iron) needs to be determined at all patients prior to the beginning of and in the course of treatment of Eralfonom®. If necessary additional administration of drugs of iron is 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 or once a week a week dose. 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 an intravenous way of administration of drug. Epoetin an alpha it is necessary to enter upon termination of the procedure of collecting blood.

Before purpose of Eralfona® it is necessary to consider all contraindications to collecting autologous blood. Before surgical intervention of Eralfon® it is necessary to appoint two times a week within three weeks. At each visit of the doctor take away a portion of blood from the patient (if a hematocrit of ≥33% and/or level of hemoglobin of ≥110 g/l) and keep for an autologous transfusion. The recommended dose of Eralfona® – 600 ME/kg of body weight intravenously two times a week. Serum ferritin level (or the level of serumal iron) needs to be determined at all patients prior to the beginning of and in the course of treatment of Eralfonom®. If necessary additional reception of iron is appointed.

In the presence of anemia its reason has to be established prior to therapy of Eralfonom®. 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 a hypodermic way of administration of drug in a dose of 600 ME/kg of body weight in a week for three weeks preceding operation (21, 14 and 7 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 during 4-x days after operation. If the hemoglobin content in the preoperative period reaches 150 g/l and above, use of an epoetin 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 with the drug Eralfon® 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 thrombocytes, a hematocrit, ferritin). 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 level 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 chronic renal недостаточночтью, clinically expressed 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 level of electrolytes in blood serum.

According to the available data, use of an epoetin the alpha at predialysis patients does not accelerate 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").

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.), an aplasia of an erythrocyte sprout.

 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.

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 to mother from its use exceed possible risk for a fruit. 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.

Overdose:

Symptoms: strengthening of side effects. Treatment: symptomatic. At the high level 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 40 000 ME.

 On 1,0 ml of 40 000 ME in the syringe with the additional automatic or non-automatic device for protection of a needle after use of the syringe or without it.

 On 1, 2 or 3 syringes in a blister strip packaging with a covering.

 1 blister strip packaging on 1, 2 or 3 syringes or 2 blister strip packagings on 2 or 3 syringes together with the application instruction is placed in a pack from a cardboard with stickers for opening control.