Binocrit solution 2000IU/1ml syringes, 6 pcs

Pharmacological action

Erythropoietin is a glycoprotein that stimulates erythropoiesis, activates mitosis and maturation of red blood cells from erythrocyte progenitor cells.

The molecular weight of erythropoietin is about 32,000-40,000 daltons. The protein fraction is about 58% of the molecular weight and includes 165 amino acids. The four hydrocarbon chains are linked to the protein by three N-glycosidic bonds and one O-glycosidic bond. Epoetin alfa, obtained using genetically engineered technology, is a purified glycoprotein, which is identical in its amino acid and carbohydrate composition to human erythropoietin isolated from the urine of patients with anemia.

Binocrit® it has the highest possible degree of cleaning in accordance with modern technological capabilities. In particular, in the quantitative analysis of the Active ingredient of the drug Binocrit® even the trace amounts of cell lines used for drug production are not detected.

The biological activity of epoetin alfa was confirmed in an in vivo experiment (studies were conducted on healthy rats and rats with anemia, as well as on mice with polycythemia). After use of epoetin alfa, the number of red blood cells, reticulocytes, hemoglobin concentration, and 59Fe uptake rate increase.

In vitro studies on incubation with epoetin alfa revealed an increase in the incorporation of 3 N-thymidine into erythroid nucleated spleen cells (in mouse spleen cell culture). Studies on the culture of human bone marrow cells have shown that epoetin alfa specifically stimulates erythropoiesis and does not affect leukopoiesis. No cytotoxic effect of erythropoietin on human bone marrow cells was detected.

Erythropoietin is a growth factor that mainly stimulates the formation of red blood cells. Erythropoietin receptors can be present on the surface of various tumor cells.

The introduction of epoetin alfa is accompanied by an increase in hemoglobin, hematocrit, serum iron, improves blood supply to tissues and heart function. The most significant effect of epoetin alfa was observed in anemia caused by chronic renal failure, as well as in patients with a number of malignancies and systemic diseases.

Pharmacokinetics

Intravenous use of

T1 / 2 epoetin alfa after repeated intravenous use is about 4 hours in healthy volunteers and about 5 hours in patients with chronic renal failure. In children, the T1 / 2 of epoetin alfa is about 6 hours.

P / C introduction

With subcutaneous use, the concentration of epoetin alfa in blood plasma is significantly lower than with intravenous use, the time to reach Cmax of epoetin alfa in blood plasma is about 12-18 hours after use. Cmax of epoetin alfa with subcutaneous use is only 1/20 of the concentration with intravenous use.

The drug does not have the ability to accumulate – the concentration of epoetin alfa in blood plasma 24 hours after the first injection is determined to be the same as 24 hours after the last injection.

With subcutaneous use, T1/2 of epoetin alfa is difficult to determine, it is about 24 hours. The bioavailability of epoetin alfa with subcutaneous use is significantly lower than with its intravenous use, and is estimated at about 20%.

Indications

— anemia in adults and children due to chronic renal failure (CRF), including anemia due to chronic renal failure in children and adults on hemodialysis, as well as in adults on peritoneal dialysis; severe anaemia of renal origin accompanied by clinical symptoms in adults with renal failure who haven’t had a hemodialysis;

— treatment of anemia and decrease the need for blood transfusions in adults receiving treatment with chemotherapeutic drugs about solid tumours, malignant lymphoma or multiple myeloma, as well as in patients with a high risk of complications of blood transfusions, due to severe General condition (in connection with cardiovascular diseases, if the anemia was observed before the start of chemotherapy);

— for improving the effectiveness of the transfusion of autologous blood under predeposit collection programs of the blood before the surgery, in patients with a hematocrit level equal to 33-39%, to facilitate autologous blood collection and reduce the risk associated with the use of allogenic blood transfusions if the expected need for transfused blood exceeds the number which can be obtained by the method of autologous collection without the use of Epoetin alfa. Treatment is indicated for patients with moderately severe anemia (with hemoglobin concentration of 10-13 g/DL or 6.2-8.1 mmol/l), no iron deficiency, if you intend to significant blood loss, as well as with extensive surgical interventions, when you may need a large amount of transfused blood (5 or more volumes in men and 4 or more for women);

— to reduce the risk of allogenic blood transfusion in adults who do not have iron deficiency, before elective orthopedic surgery with a high risk of complications during blood transfusions. The use of the drug is limited only in patients with moderate-to-severe anemia (for example, hemoglobin concentration of 10-13 g/DL), in that case, if they are not included in the program of collecting autologous blood prior to surgery with an anticipated blood loss of 900 to 1800 ml;

— anemia in HIV-infected patients receiving therapy with zidovudine, when endogenous erythropoietin level less than 500 IU/ml.

How to take, course of use and dosage

Treatment with Binocrit® should be carried out under the supervision of a specialist doctor who has the appropriate qualifications and experience in treating patients who are indicated for therapy with erythropoiesis stimulants.

Treatment of symptomatic anemia in adults and children with chronic renal failure (CRF)

Binocrit® in patients with CRF is administered intravenously. Due to the fact that the clinical manifestations of anemia and residual phenomena may vary depending on age, gender and overall severity of the disease, an individual assessment of the condition of each patient is carried out.

The target level of hemoglobin concentration is 10-12 g / dl (6.2-7.5 mmol/l) in adults and 9.5-11 g / dl (5.9-6.8 mmol/l) in children.

Long-term increases in hemoglobin concentrations of more than 12 g/dl (7.5 mmol/l) are not recommended. If the hemoglobin concentration increases by more than 2 g/dl (1.25 mmol/l) per month or if it exceeds 12 g/dl (7.5 mmol/L) for a long period of time, the dose of Binocrit®should be reduced by 25%. If the hemoglobin concentration exceeds 13 g/dl (8.1 mmol/l), it is necessary to stop treatment until the hemoglobin decreases to 12 g/dl (7.5 mmol/L) and then resume therapy with Binocrit®, reducing the initial dose by 25%.

Due to interindividual variability, the hemoglobin concentration may be higher or lower than the optimal (target) value.

Treatment should be prescribed in such a way that the minimum effective dose of Binocrit® provides the necessary control of hemoglobin and clinical manifestations of the disease.

Before starting treatment and during the treatment period, the concentration of iron in the blood plasma should be monitored, if necessary, additional iron preparations should be prescribed.

Adult patients receiving hemodialysis

Treatment is carried out in two stages:

Correction stage

Intravenously, Binocrit® is administered at a dose of 50 IU/kg 3 times a week. If necessary, the dose is adjusted gradually over 4 weeks. Increase or decrease the dose-no more than 25 IU / kg 3 times a week.

Maintenance therapy stage

Dose adjustment to maintain the required hemoglobin level: Hb 10-12 g / dl (6.2-7.5 mmol / l).

The recommended total weekly dose of Binocrit® is from 75 to 300 IU / kg, administered intravenously at 25-100 IU / kg 3 times a week.

In patients with severe anemia (Hb < 6 g / dl, or < 3.75 mmol / L), it may be necessary to use higher maintenance doses than in patients with higher hemoglobin concentrations (< 8 g / dl, or

Use in children receiving hemodialysis

Correction stage

Binocrit® is administered intravenously at a dose of 50 IU/kg 3 times a week. If necessary, the dose is adjusted gradually over 4 weeks. Increase or decrease the dose-no more than 25 IU / kg 3 times a week.

Maintenance therapy stage

Dose adjustment to maintain the required hemoglobin level: Hb 9.5-11 g / dl (5.9-6.8 mmol / l).

In most cases, children with a body weight of less than 30 kg should be treated with higher maintenance doses than in children with a higher body weight and in adults.

In children with severe anemia (Hb < 6.8 g / dl, or < 4.25 mmol / L), higher maintenance doses are recommended than in children with higher hemoglobin concentrations (Hb > 6.8 g/dl, or < 4.25 mmol/L). Higher maintenance doses are recommended than in children with higher hemoglobin concentrations (Hb >> 4.25 mmol/L).

Adult patients receiving peritoneal dialysis

Treatment is carried out in two stages.

Correction stage

The initial dose is 50 IU / kg 2 times a week iv.

Maintenance therapy stage

Dose adjustment to maintain the required hemoglobin level: Hb 10-12 g / dl (6.2-7.5 mmol / l). The maintenance dose is from 25 to 50 IU / kg 2 times a week,2 equal injections.

Adults with renal insufficiency who have not received dialysis

Treatment is carried out in two stages.

Correction stage

The initial dose is 50 IU / kg 3 times a week IV, followed by an increase of 25 IU/kg (3 times a week) if necessary, until the target dose is reached (the dose should be increased gradually for at least 4 weeks).

Maintenance therapy stage

Dose adjustment to maintain the required hemoglobin level: Hb 10-12 g / dl (6.2-7.5 mmol / l). The maintenance dose is from 17 to 33 IU / kg 3 times a week iv. The maximum dose should not exceed 200 IU / kg 3 times a week.

Treatment of anemia in patients after chemotherapy

The drug Binocrit® is administered subcutaneously (at a concentration of Hb The dose of the drug is selected by the doctor taking into account the severity of anemia, age, gender and general severity of the patient’s condition on an individual basis. It is also necessary to take into account fluctuations in the concentration of hemoglobin, adjusting the dose of the drug to take into account the normal values of hemoglobin concentrations of 10 g / dl ( 6.2 mmol / l) – 12 g/dl (7.5 mmol/l). It is not recommended to exceed the hemoglobin concentration of more than 12 g / dl (7.5 mmol / L); recommendations for dose adjustment in such cases are given below.

Treatment should be administered in such a way that the minimum effective dose of epotin alfa provides the necessary control of symptoms of anemia. Therapy with Binocrit® should be continued for 1 month after the end of the course of chemotherapy.

The initial dose of the drug is 150 IU / kg, administered subcutaneously 3 times a week. Alternatively, the drug can be administered at a dose of 450 IU/kg subcutaneously once a week.

— in the case of increasing hemoglobin concentration by at least 1 g/DL (>0.62 mmol/l) or the increase in the number of reticulocytes ≥40,000 cells/µl on the initial parameters after 4 weeks of treatment, the dose is 150 IU/kg 3 times per week or 450 IU/kg 1 time per week, and remains unchanged.

— with an increase in the concentration of hemoglobin <1 g / dl (< 0.62 mmol / l) and an increase in the number of reticulocytes If after another 4 weeks of treatment at a dose of 300 IU/kg 3 times a week, the hemoglobin concentration increases ≥1 g / dl (≥0.62 mmol / L) or the number of reticulocytes increases ≥40,000 cells/µl, the dose of the drug should remain the same and be 300 IU / kg 3 times a week. However, if the increase in hemoglobin concentration < 1 g / dl (< 0.62 mmol / L) and the increase in the number of reticulocytes

Recommended dosage regimen of Binocrit®

Dose adjustment to maintain the hemoglobin concentration in the range of 10-12 g / dl

If the hemoglobin concentration increases by more than 2 g/dl (1.25 mmol/l) per month or if the hemoglobin level exceeds 12 g/dl (7.5 mmol/L), the dose of the drug should be reduced by 25-50%.

If the hemoglobin concentration exceeds 13 g / dl (8.1 mmol / l), it is necessary to stop treatment until its value decreases to 12 g/dl (7.5 mmol/L), and then resume therapy with epoetin alfa, reducing the initial dose by 25%.

Adult patients participating in an autologous blood collection program before surgery

Binocrit® is administered intravenously after completing the blood donation procedure. Patients with mild anemia (with a hematocrit level of 33-39%) who require ≥4 units of blood should be treated with Binocrit® at a dose of 600 IU/kg of body weight 2 times a week for 3 weeks before surgery.

All patients receiving Binocrit® should be additionally prescribed iron supplements (orally at a dose of 200 mg / day) during the entire course of therapy. The use of the iron preparation should be prescribed before starting therapy with Binocrit®, as early as possible, several weeks before the start of autologous blood collection.

Adult patients undergoing elective orthopedic surgery

Binocrit® is administered subcutaneously.

The recommended dose of Binocrit® is 600 IU / kg once a week for 3 weeks preceding surgery (21,14 and 7 days before surgery), as well as on the day of surgery. If the preoperative period is shorter than 3 weeks, Binocrit® should be administered daily at a dose of 300 IU / kg for 10 consecutive days, before surgery, on the day of surgery and for 4 days after it. If the preoperative hemoglobin concentration is 15 g / dl (9.38 mmol / L) or higher, the drug should be discontinued. Make sure that patients are not iron-deficient before starting treatment with Binocrit®.

All patients receiving Binocrit® therapy should receive the required amount of bivalent iron (200 mg / day orally) during the entire course of therapy.

Method of use

Binocrit® is a sterile, preservative-free product intended exclusively for single-use use. The required amount of the drug should be administered. The drug should not be administered as an intravenous infusion or mixed with other medications.

Intravenous injection

The duration of the injection is 1-5 minutes, depending on the total dose. For hemodialysis, a bolus injection can be used during the dialysis procedure through a convenient venous port in the dialysis line. An alternative is an injection made at the end of the dialysis procedure through a fistula needle, then 10 ml of an isotonic sodium chloride solution is injected to clear the needle and ensure a satisfactory introduction of the drug into the bloodstream.

Patients with possible temperature reactions to intravenous use of drugs, slow use of the drug is recommended.

Subcutaneous injection

Do not exceed the maximum injection volume of 1 ml per injection site. In the case of high volume injections, a larger number of injection sites should be selected. Injections are given in the thigh muscle or in the area of the anterior abdominal wall.

Storage conditions

At a temperature of 2-8 °C (do not freeze).

Shelf

life is 2 years.

Active ingredient

Epoetin alfa

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Anemia