epoetin alfa | Binocrit solution for iv and s / c injection. 10000 IU / 1ml syringes 6 pcs.

Release form

Solution for intravenous and subcutaneous injection

Packaging

6 syringes, 1 ml.

Pharmacological action of

Erythropoietin is a glycoprotein that stimulates erythropoiesis, activates mitosis and the maturation of red blood cells from red blood cell progenitors. The molecular weight of erythropoietin is about 32000-40000 Yes. The protein fraction is about 58% of the molecular weight and includes 165 amino acids. Four hydrocarbon chains are linked to a protein by three N-glycosidic bonds and one O-glycosidic bond. Epoetin alpha, obtained using genetic engineering technology, is a purified glycoprotein, in amino acid and carbohydrate composition it is identical to human erythropoietin, excreted from the urine of patients with anemia.

Binocrit has the highest possible degree of purification in accordance with modern technological capabilities. In particular, in the quantitative analysis of the active substance of the drug Binokrit, even trace amounts of cell lines on which the drug is produced are not determined.

The biological activity of epoetin alpha was confirmed in an in vivo experiment (studies were performed in healthy rats and rats with anemia, as well as in mice with polycythemia). After administration of epoetin alpha, the number of red blood cells, reticulocytes, hemoglobin concentration, and 59Fe absorption rate increase. In vitro studies, when incubated with epoetin alpha, an increase in the incorporation of 3H-thymidine in erythroid nucleated spleen cells (in mouse spleen cell culture) was detected. Studies on a culture of human bone marrow cells have shown that epoetin alpha specifically stimulates erythropoiesis and does not affect leukopoiesis. The cytotoxic effect of erythropoietin on human bone marrow cells was not detected.

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

The administration of epoetin alpha is accompanied by an increase in hemoglobin, hematocrit, serum iron, and improves blood supply to tissues and heart function. The most significant effect of epoetin alfa was noted in anemia caused by chronic renal failure (CRF), as well as in patients with a number of malignant neoplasms and systemic diseases.

Pharmacokinetics

Intravenous administration of

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

Subcutaneous administration of

With subcutaneous administration, the concentration of epoetin alpha in the blood plasma is determined to be significantly lower than with intravenous administration, Tmax of epoetin alpha in the blood plasma is about 12-18 hours after administration. Cmax of epoetin alfa for subcutaneous administration is only 1/20 of the concentration for intravenous administration. The drug does not have the ability to cumulate - the concentration of epoetin alpha in the blood plasma 24 hours after the first injection is determined to be the same as 24 hours after the last injection. With subcutaneous administration of T1 / 2 epoetin alpha is difficult to determine, it is about 24 hours. The bioavailability of epoetin alpha with subcutaneous administration is significantly lower than with intravenous administration, and is about 20%.

Indications

anemia in adults and children due to chronic renal failure, including: anemia due to chronic renal failure in children and adults on hemodialysis, as well as adults on peritoneal dialysis

severe renal anemia, accompanied by clinical symptoms in adults with kidney failure who have not had hemodialysis

treatment of anemia and reduction the need for a blood transfusion in adults receiving treatment with chemotherapeutic drugs for solid tumors, malignant lymphoma or multiple myeloma, as well as in individuals with a high risk of hemotransfusion complications due to a general severe condition (due to cardiovascular diseases, if anemia was noted even before chemotherapy was started)

in order to increase the efficiency of autologous blood transfusion as part of a pre-collection program for blood collection before surgery in patients with a hematocrit level of 33–39%, to facilitate the collection of autologous blood and reduce the risk associated with the use of allogeneic blood transfusions, if the expected need for transfused blood exceeds the amount that can be obtained by autologous collection without the use of epoetin alpha. Treatment is indicated for patients with moderate anemia (with a hemoglobin concentration of 10–13 g / dl or 6.2–8.1 mmol / l), without iron deficiency, if significant blood loss is expected, as well as with extensive surgical interventions, when a large volume of transfused blood may be required (5 or more volumes in men and 4 or more in women)

in order to reduce the risk of allogeneic blood transfusion in adults without iron deficiency before elective orthopedic surgery, if there is a high risk of complications during blood transfusions. The use of the drug is limited - only in patients with moderate anemia (for example, with a hemoglobin concentration of 1013 g / dl), if they are not included in the autologous blood collection program before surgery with an expected blood loss of 900 to 1800 ml of

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

Pregnancy and lactation

Appropriate controlled trials of the use of epoetin alfa in women during pregnancy have not been conducted. Based on animal studies, reproductive toxicity has been identified. As a result, patients with chronic renal failure should use Binocrit during pregnancy only if the expected benefit to the mother significantly exceeds the risk to the fetus.

The use of epoetin alfa is not recommended during pregnancy or lactation in patients participating in the autologous blood collection program before surgery.

Composition

1 ml solution for intravenous and subcutaneous administration contains:

Active ingredient: epoetin alpha 84 mcg

Excipients: sodium dihydrogen phosphate dihydrate, sodium hydrogen phosphate dihydrate, sodium chloride, glycine, polysorbate 80, hydrochloric acid, sodium hydroxide, water for injection.

Dosage and Administration

Intravenously, subcutaneously.

Treatment with Binocrit should be carried out under the supervision of a specialist who has the appropriate qualifications and experience in treating patients who are shown to be treated with drugs that stimulate erythropoiesis.

Doses

Treatment of symptomatic anemia in adults and children with chronic renal failure: Binocrit in patients with chronic renal failure is administered iv. Due to the fact that the clinical manifestations of anemia and residual effects may vary depending on the age, gender and general severity of the disease, conduct an individual assessment of the condition of each patient.

The target 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.

A prolonged increase in hemoglobin concentration of more than 12 g / dl (7.5 mmol / l) is not recommended. If the hemoglobin concentration rises by more than 2 g / dl (1.25 mmol / l) per month or for a long time exceeds 12 g / dl (7.5 mmol / l), it is necessary to reduce the dose of Binokrit by 25%. If the hemoglobin concentration exceeds 13 g / dl (8.1 mmol / l), it is necessary to discontinue treatment until hemoglobin is reduced to 12 g / dl (7.5 mmol / l) and then resume treatment with Binocrit, reducing the initial dose by 25%.

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

Treatment should be prescribed so that the minimum effective dose of Binocrit provides the necessary control of hemoglobin and the clinical manifestations of the disease.

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

Adult patients receiving hemodialysis

Treatment is carried out in two stages.

Stage of correction. Binocrit is administered intravenously at a dose of 50 IU / kg 3 times a week. If necessary, adjust the dose gradually, over 4 weeks.

Increase or decrease in dose - not more than 25 IU / kg 3 times a week.

Supportive care phase. Dose adjustment in order to maintain the necessary hemoglobin level of 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 (hemoglobin Use in children receiving hemodialysis

The treatment is carried out in two stages.

Correction step. 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. Increasing or decreasing the dose - not more than 25 IU / kg 3 times a week

Maintenance therapy stage: dose adjustment in order to maintain the necessary hemoglobin level of 9.5–11 g / dl (5.9–6.8 mmol / l).

In most cases, children with body weight less than 30 kg need to use more than high maintenance doses than in children with higher body weight and adults.

Binocrit is administered subcutaneously.

The recommended dose of Binocrit is 600 IU / kg once a week for 3 weeks prior to 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 prescribed daily at a dose of 300 IU / kg for 10 consecutive days, before surgery, on the day of surgery and within 4 days after it. If in the preoperative period the concentration of Hb is 15 g / dl (9.38 mmol / L) or higher, the use of the drug must be discontinued. Make sure that before starting treatment with Binocrit, patients do not have iron deficiency.

All patients receiving Binocrit therapy should receive the necessary amount of ferrous iron (by mouth 200 mg / day) throughout the course of therapy.

Side effects of

From the blood and lymphatic system: infrequently - thrombocythemia (in patients with malignant neoplasms) the frequency is unknown - PKKA mediated through antibodies1, thrombocythemia (in patients with chronic renal failure).

From the side of the immune system: frequency is unknown - anaphylactic reaction, hypersensitivity.

From the nervous system: very often - headache (in patients with malignant neoplasms) often - convulsions (in patients with chronic renal failure), headache (in patients with chronic renal failure), hemorrhagic stroke2, convulsions (in patients with malignant neoplasms) frequency unknown - stroke2, hypertensive encephalopathy, transient ischemic attacks.

From the side of the organ of vision: frequency unknown - retinal thrombosis.

From the CCC side: often - deep vein thrombosis of the lower extremities (in patients with malignant neoplasms) increased blood pressure frequency is unknown - deep vein thrombosis of the lower extremities (in patients with chronic renal failure), arterial thrombosis, hypertensive crisis.

On the part of the respiratory system: often - pulmonary embolism 2 (in patients with malignant neoplasms) the frequency is unknown - pulmonary embolism 2 (in patients with chronic renal failure).

From the gastrointestinal tract: very often - nausea often - diarrhea (in patients with neoplasms), vomiting infrequently - diarrhea (in patients with chronic renal failure).

On the part of the skin and its appendages: often - skin rash, frequency is unknown - angioedema, urticaria.

From the musculoskeletal system: very often - arthralgia (with chronic renal failure) often - arthralgia (in patients with malignant neoplasms) infrequently - myalgia (in patients with malignant neoplasms) the frequency is unknown - myalgia (with chronic renal failure).

Congenital, familial / genetic disorders: frequency unknown - porphyria.

On the part of the body as a whole: very often - hyperthermia (in patients with malignant neoplasms) flu-like state (with chronic renal failure) often - flu-like condition (in patients with malignant neoplasms) frequency is unknown - drug inefficiency, peripheral edema, hyperthermia (in chronic renal failure), reactions at the injection site.

Laboratory parameters: frequency unknown - antibodies to erythropoietin1.

Others: often - thrombosis of dialysis equipment shunt (in patients with chronic renal failure).

1 Frequency of manifestations cannot be estimated based on clinical studies.

2 Includes fatalities.

Drug Interaction

There are no data on the interaction of epoetin alfa with other drugs. However, when used with cyclosporine, interaction is possible because the drug binds to red blood cells. If Binocrit is given concomitantly with cyclosporine, it is necessary to control the concentration of cyclosporine depending on the degree of hematocrit increase.

There are no data on the interaction between epoetin alfa and granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocytic colony-stimulating factor (GM-CSF).

To avoid incompatibilities or reduce activity, it is not recommended to mix with solutions and other drugs.

Overdose

The therapeutic range of the drug is wide. With overdose, symptoms may occur that reflect the extreme degree of manifestation of the pharmacological action of the hormone (increased concentration of hemoglobin or hematocrit). At extremely high levels of hemoglobin or hematocrit, phlebotomy may be used. If necessary, symptomatic therapy is prescribed.

Storage conditions

At 2–8 РC (do not freeze).

Expiration

2 years.

Dosage form

Dosage form

solution for injection and infusion