Characteristic

Immunological and biological properties. recombinant erythropoietin of the person on biological and immunological activity corresponds to erythropoietin of the person (epo) — to the natural glycoprotein hormone stimulating an erythrogenesis. normal at the healthy person epo it is synthesized by kidneys (90%) and kupferovsky cells of a liver (10%). level of its synthesis is defined by blood saturation level oxygen. epo stimulates proliferation and differentiation of erythroidal cells in mature erythrocytes. its action is shown at early stages of an erythrogenesis at the level of burstobrazuyushchy erythroidal units and colony-forming erythroidal units, further — at the level of a proerythroblast, an erythroblast and a reticulocyte (the sensitivity of these cells to epo is proportional to degree of their maturity). epo normalizes the level of hemoglobin and a hematocrit and eliminates the symptoms connected with anemia.

Pharmacological properties

Pharmacokinetics. at in in administration of the medicament t½ at persons with normal function of kidneys makes about 4 h; patients with a renal failure have about 5 h

At p / to introduction the concentration of medicament in blood increases slowly and reaches a maximum during from 12 to 18 h after introduction. T _½ makes 24 h

Drug has no cumulative properties.

Indication

• Anemia at patients with an uraemic stage hpn, receiving therapy by a chronic hemodialysis (hg) and a constant out-patient peritoneal hemodialysis (papd); anemia at pregnant women (ііі a pregnancy trimester) and at women in labor with the reduced level of hemoglobin and a hematocrit; early anemia at newborn premature children; late anemia at the newborns with a hemolytic disease who transferred the pre-natal packed red cells transfusion or post-natal replaceable and fractional blood transfusions which are characterized inadequately low (concerning anemia degree) products of erythropoietin; stimulation of an erythrogenesis in late hyporegenerative anemia at newborns with a hemolytic disease; the anemia caused by deficiency of erythropoietin in patients with hpn; the anemias connected with khimio- and radiotheraphy of tumors; anemias at patients about the HIV caused by use of a zidovudine; epo-dependent anemias (not myeloid tumors, pseudorheumatism, etc.); for reduction of volumes of the transfused blood at considerable surgical interventions and sharp blood losses.

Use

Drug is administered p / to or in / century duration in/in an injection — 1–2 min.

For infusions do not use drug.

Anemia at patients with an uraemic stage of HPN. The patient who is on a hemodialysis (State Duma), the medicament is administered p / to or in/in in a dose 200 Me/kg/ned after the hemodialysis session. It is recommended a week dose (200 Me/kg/ned) to divide into 3 introductions for a week (after each session of a hemodialysis). The maximum dose should not exceed 200 ME/kg 3 times a week. P / to medicament enter in a dose of 100 ME/kg once a week.

Patient who is on PAPD, the medicament is administered p / to in a dose of 75 ME/kg once a week. The course of treatment makes 8 weeks

In/in Epobiokrin's introduction allows to reach the C _max medicament in blood for the first hour, with its decrease to basic level by the end of the first day after introduction. P / to Epobiokrin's introduction allows to reach irrespective of a type of dialysis the C _max medicament in blood for 8–24 h (with its decrease to basic level by the end of second day after introduction).

P / to a route of administration of Epobiokrin it is reasonable for planned therapy of the patients who are on haemo - and peritoneal dialysis as he demands a smaller starting dose.

Anemia at pregnant women and women in labor. To pregnant women (ІІІ a pregnancy trimester) and to women in labor with anemia the medicament is administered p / to in a dose 450 Me/kg/ned (for 6 days) in a complex with adequate saturation of an organism iron in combination with group B vitamins (B ₁ , by B ₆ , B ₁₂ and folic acid). In the first day the medicament is administered in a dose of 150 ME/kg, the following 5 injections carry out in a dose of 60 ME/kg.

needs to be carried out by

in case of resistance to therapy early detection of the factors inhibiting an erythrogenesis, such as deficiency of iron, the masked infection, hypoproteinemia and, whenever possible, their correction.

Anemia at newborn children. For prevention and treatment of early anemia at newborn premature children, treatment of late anemia at the newborns with a hemolytic disease who transferred the pre-natal packed red cells transfusion or post-natal replaceable and fractional blood transfusions which are characterized inadequately low (concerning anemia degree) products of erythropoietin; for stimulation of an erythrogenesis in late hyporegenerative anemia at newborn children with a hemolytic disease the medicament is administered p / to in a dose of 200 ME/kg by 3 times a week. The course of treatment makes 10 injections. In a complex with therapy by Epobiokrin appoint iron preparations of 2-3 mg/kg/days (on elementary iron), folic acid — 50 mkg/days and vitamin E — 5 mg/days

Anemia at patients with HPN. The initial dose of Epobiokrin makes 30–75 ME/kg 3 times a week. The period of correction lasts until achievement of optimum level of hemoglobin (110–125 g/l), a hematocrit (30–35%). These indicators need to be controlled weekly.

following situations Are possible

:

1) the hematocrit raises from 0.5 to 2.0% a week. In that case the dose is not changed before achievement of optimum indicators;

2) the reduced answer to EPO (speed of gain of a hematocrit less than 0.5% a week). It is necessary to raise a single dose on 25 ME/kg. The maximum dose — 300 ME/kg 3 times a week;

3) the raised answer to EPO (speed of gain of a hematocrit more than 2.0% for 2 weeks). It is necessary to lower a single dose of medicament by 1.5 times;

4) the hematocrit remains low or decreases. It is necessary to analyze the resistance reasons.

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

Period of maintenance therapy. The previous dose of the correctional period decreases by 25–30% and is supported at such level that indicators of a hematocrit were in range of 30-35%, and concentration of hemoglobin made 110–125 g/l. As a rule, the maintenance dose makes 50–60 ME/kg 3 times a week. For therapy during the supporting period it is recommended p / to a method of administration (as the most economic and safe).

Anemia at patients after khimio- and radiotheraphy of tumors. Before an initiation of treatment it is recommended to carry out determination of level of endogenous erythropoietin. At concentration of EPO lower than 200 ME/ml the initial dose makes 150 ME/kg. In the absence of the answer the increase in a dose to 300 ME/kg in 8 weeks from an initiation of treatment is possible. Further increase in a dose is represented inexpedient. Epobiokrin to patients with the content of endogenous erythropoietin in blood plasma is not recommended to appoint higher than 200 ME/ml.

Anemia at patients about the HIV caused by use of a zidovudine. Epobiokrin's introduction in a dose of 100 ME/kg 3 times a week is effective at patients from the HIV receiving therapy by a zidovudine provided that the level of serumal endogenous erythropoietin of the patient is lower than 500 ME/ml, and the dose of a zidovudine makes less than 4200 mg/week

Surgery. Preparation for extensive surgical interventions. Epobiokrin apply in a dose of 100-300 ME/kg every other day, in 10 days prior to surgical intervention and within 4–6 days after operation.

General diseases. Pseudorheumatism. The initial dose of Epobiokrin makes 50–75 ME/kg 3 times a week. In the absence of the answer in 4 weeks of treatment it is recommended to raise a dose to 150–200 ME/kg 3 times a week. Further increase in a dose is represented inexpedient.

After achievement of optimum levels of a hematocrit and hemoglobin of a dose and frequency rate of introduction of Epobiokrin have to be selected individually for each patient. At treatment by Epobiokrin it is necessary to remember that the dose should be raised not more often than once a month. Normal level of the answer — gain of a hematocrit from 0.5 to 2.0% for 2 weeks. At a speed of gain of a hematocrit more than 2% for 2 weeks a dose should be lowered by 1.5 times.

Replacement of other erythropoietins on Epobiokrin. Proceeding from possible more significant effect of Epobiokrin, his dose should not exceed a dose of recombinant erythropoietin which was used in the previous course of treatment. During the first 2 weeks the dose is not changed, estimating a ratio the dose/answer. After that the dose can be reduced or raised according to the above-stated scheme.

Contraindication

Necontroliruyemaya ag. hypersensitivity to an epoetin an alpha.

Also use of medicament is contraindicated to

:

• before carrying out extensive surgery not within the predeposit program with use of autologous blood;
• in heavy pathology of vessels (including coronary, sleepy, cerebral, peripheral);
• at recently postponed myocardial infarction, an acute disorder of cerebral circulation.

Side effects

Grippopodobny syndrome. dizzinesses, drowsiness, a feverish state, a headache, joint and muscles pain are possible (mainly in an initiation of treatment).

from a cardiovascular system: are possible dose-dependent increase in the ABP; deterioration in a course of the available AG (most often at patients with chronic kidney disease); in some cases — hypertensive crises, malignant AG with encephalopathy symptoms (headache, confusion of consciousness) and symptoms of generalized toniko-clonic spasms.

from the system of a hemopoiesis: seldom — a thrombocytosis.

from the system of fibrillation: in some cases — shunt fibrinferments at patients with tendency to hypotension (being on a hemodialysis) or in the presence at them are stenoses, aneurysms.

from an urinary system: the hyperpotassemia, a hyperphosphatemia, increase in concentration of urea, creatinine, uric acid in blood plasma are possible (at patients with chronic kidney disease).

Allergic reactions: in some cases — it is weak or skin rash, eczema, a small tortoiseshell, an itching, a Quincke's edema are moderate. Seldom there are anaphylactic reactions: potentially serious complications connected with disturbance of breath or with decrease in the ABP, immune responses (has the minimum ability to induce antibody formation).

Local reactions: hyperaemia of integuments, burning sensation, weak or moderate morbidity in the injection site (arise at hypodermic introduction more often).

Special instructions

Drug cannot be used at disturbance of integrity, marking, physical properties, a period of storage.

Drug with care is used at patients with convulsive reactions in the anamnesis; patients with the increased risk of developing thrombosis or other vascular complications. Careful medical control is required.

With care is applied in gout.

should be convinced by

Prior to use that patients with AG receive effective antihypertensive therapy.

during use of medicament needs to control the ABP level, paying attention to emergence or strengthening of an unusual headache. At the same time correction of the carried-out therapy or prescribing of antihypertensive medicaments can be required. If despite adequate therapy, the ABP does not decrease, Epobiokrin it is necessary to cancel.

Prior to Epobiokrin's use should estimate a condition of depot of iron in an organism. At most of patients with chronic kidney disease, at oncological and HIV-positive patients the ferritin level in blood plasma snizhtsya along with increase in a hematocrit. Level of ferritin needs to be determined during all course of treatment. If it makes less than 100 ng/ml, replacement therapy is recommended by iron preparations. The patients taking an autologous blood test and patients in before - or the postoperative period, also have to receive in addition adequate amount of iron.

during use should control hemoglobin level, before achievement of stable level at least once a week, then is more rare. In before - and the postoperative period the level of hemoglobin should be checked more often if initial level was less than 14 g/dl. It is necessary to control hematocrit level also regularly. During the first 8 weeks of therapy it is regularly necessary to control quantity of thrombocytes as Epobiokrin can cause moderate dose-dependent increase in their number (which returns to normal independently during a therapy course); the thrombocytosis develops seldom.

Should consider

that preoperative increase in level of hemoglobin can serve as the contributing factor to development of trombotichesky complications. Before performing planned surgical intervention the patients have to receive adequate preventive antitrombotichesky therapy.

B before - and the postoperative period does not recommend to apply Epobiokrin at the initial level of hemoglobin more than 15 g/dl.

With care should be applied at patients with a porphyria. In chronic kidney disease against the background of therapy by Epobiokrin the aggravation of a porphyria is possible.

Correction of anemia can be followed by improvement of appetite and increase in absorption of potassium and proteins. It must be kept in mind possible need of periodic correction of parameters of dialysis for maintenance of level of urea, creatinine and potassium within norm. At patients with chronic kidney disease it is necessary to control the level of electrolytes in blood plasma. Epobiokrin's use by predialysis patients does not accelerate progressing of a renal failure.

to

to the Patients who are on a hemodialysis against the background of therapy by Epobiokrin, as a rule, needs increase in a dose of heparin during dialysis (because of increase in a hematocrit). At an inadequate dose of heparin the occlusion of a dialysis system is possible.

At patients with chronic kidney disease and a clinically apparent ischemic heart disease or stagnant heart failure the supporting concentration of hemoglobin should not exceed an upper limit of the optimum recommended concentration (adults have no more than 10-12 g/dl).

At use for patients with abnormal liver functions the delay of biotransformation of Epobiokrin and the significant strengthening of an erythrogenesis is possible

. Safety of use of Epobiokrin for this category of patients is not established.

Cannot exclude completely a possibility of influence of Epobiokrin on growth of some types of tumors, especially on malignant new growths of marrow.

Should observe all special preventions and precautionary measures connected with the program of collecting autologous blood (it extends to all patients receiving Epobiokrin).

Therapeutic effectiveness of Epobiokrin can decrease at deficiency of iron, folic acid, _{12 vitamin B} , intoxications aluminum, intercurrent diseases, the concealed hemorrhage, hemolysis, marrow fibrosis.

Use during pregnancy and feeding by a breast. Safety of use of Epobiokrin at pregnancy and in the period of a lactation is not established.

Influence on ability of control of vehicles. Does not affect ability of control of vehicles.

Interaction

Action of an epobiokrin can amplify at simultaneous administration of blood preparations.

At simultaneous use of Epobiokrin with cyclosporine the decrease in concentration of the last in plasma because of increase in extent of its linking with erythrocytes is possible

(at use of this combination it is necessary to control concentration of cyclosporine in plasma and, if necessary, to raise its dose).

Incompatibility. Epobiokrin it is impossible to mix with solutions of other medicines.

Overdose

Is possible

at incorrectly picked up individual scheme of treatment. about overdose symptoms, measures of their prevention and elimination see in sections: side effects and special instructions.

Storage conditions

B the dry, protected from light place at a temperature of 2-8 °C. not to freeze. not to stir up.

Translation of the instruction Mose