Binocrit solution 10000IU/1ml syringes, 6pcs

Composition

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1 ml of solution for intravenous and subcutaneous use contains:

Active ingredient:

epoetin alfa 84 mcg;

excipients:

sodium dihydrogen phosphate dihydrate,

sodium hydrophosphate dihydrate,

sodium chloride,

glycine,

polysorbate 80,

hydrochloric acid,

sodium hydroxide,

water for injection

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 32000-40000 Da. 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.

The binocrit has the highest possible degree of cleaning in accordance with modern technological capabilities. In particular, the quantitative analysis of the Active ingredient of the drug Binocrit does not determine even the trace amounts of cell lines on which the drug is produced.

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 in erythroid nucleus-containing cells of the spleen (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 (CRF), as well as in patients with a number of malignancies and systemic diseases.

Pharmacokinetics

Intravenous use

of T_1/2 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 T_1/2 of epoetin alfa is about 6 hours.

Subcutaneous use

With subcutaneous use, the concentration of epoetin alfa in blood plasma is significantly lower than with intravenous use, the T_max of epoetin alfa in blood plasma is about 12-18 hours after use. The_cmax of epoetin alfa for subcutaneous use is only 1/20 of the concentration for 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 of T_1/2 epoetin alfa, it is difficult to determine, it is about 24 hours. Bioavailability of epoetin alfa with subcutaneous use is significantly lower than with intravenous use, 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 in adults on peritoneal dialysis;
• severe anaemia of renal origin accompanied by clinical symptoms in adults with renal failure who haven’t had dialysis;
• 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);
• with the aim of increasing 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, when the concentration of hemoglobin 1013 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.

Use during pregnancy and lactation

Appropriate controlled studies of the use of epoetin alfa by women during pregnancy have not been conducted. Based on the results of animal studies, reproductive toxicity was detected.

Therefore, patients with CRF should use Binocrit during pregnancy only if the intended 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 an autologous blood collection program before surgery.

Contraindications

• hypersensitivity to the Active ingredient and auxiliary substances included in the composition of the drug;
• partial red cell aplasia (PKKA) arising after erythropoietin treatment;
• uncontrolled hypertension;
• patients who for any reason are unable to get effective treatment for the prevention of thrombosis;
• myocardial infarction or stroke, which occurred within 1 month before the planned treatment; unstable angina; patients with a high risk of deep vein thrombosis and thromboembolic disease in history (in the context of improving the effectiveness of autologous blood transfusion);
• severe coronary, peripheral arterial, carotid arteries and blood vessels of the brain, including in patients who have had a recent myocardial infarction or stroke (within predeposit program blood collection before extensive surgery and not participating in the program transfusion of autologous blood).

With caution: malignant neoplasms, epileptic syndrome (including in the anamnesis), chronic renal and hepatic insufficiency, thrombocytosis, thrombosis (in the anamnesis), acute blood loss, sickle cell anemia, hemolytic anemia, iron -, _B12-or folate – deficient conditions.

Side effects

The following side effects are distributed according to the classification of organs and systems and frequency of occurrence: very common (≥1/10); common (≥1/100–

From the blood and lymphatic system: infrequently-thrombocythemia (in patients with malignant neoplasms); frequency unknown — antibody-mediated PCA 1, thrombocythemia (in patients with CRF).

Immune system disorders: frequency unknown — anaphylactic reaction, hypersensitivity.

From the nervous system: very often — headache (in patients with malignant neoplasms); often-convulsions (in patients with CRF), headache (in patients with CRF); infrequently — hemorrhagic stroke 2, convulsions (in patients with malignant neoplasms); frequency unknown — stroke 2, hypertensive encephalopathy, transient ischemic attacks.

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

From the cardiovascular system: often-deep vein thrombosis of the lower extremities (in patients with malignant neoplasms); increased blood pressure; frequency unknown — deep vein thrombosis of the lower extremities (in patients with CRF), arterial thrombosis, hypertensive crisis.

Respiratory disorders: common – pulmonary embolism 2 (in patients with malignant neoplasms); frequency unknown — pulmonary embolism 2 (in patients with CRF).

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

From the skin and its appendages: often-skin rash; frequency unknown-angioedema, urticaria.

From the musculoskeletal system: very often — arthralgia (in CRF); often-arthralgia (in patients with malignant neoplasms); infrequently-myalgia (in patients with malignant neoplasms); frequency unknown — myalgia (in CRF).

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

From the body as a whole: very often — hyperthermia (in patients with malignant neoplasms); flu — like condition (in CRF); often — flu-like condition (in patients with malignant neoplasms); frequency unknown-drug inefficiency, peripheral edema, hyperthermia (in CRF), injection site reactions.

Laboratory parameters: frequency unknown-antibodies to erythropoietin 1.

Others: often-thrombosis of the shunt of dialysis equipment (in patients with CRF).

1 The frequency of symptoms cannot be estimated based on clinical studies. 2 Including fatalities.

Interaction

There are no data on the interaction of epoetin alfa with other drugs. However, when used concomitantly with cyclosporine, interaction is possible, since the drug binds to red blood cells.

If treatment with Binocrit is carried out simultaneously with cyclosporine, it is necessary to monitor the concentration of cyclosporine depending on the degree of increase in hematocrit.

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

To avoid incompatibility or decrease in activity, it is not recommended to mix with solutions and other medications.

How to take, course of use and dosage

Intravenously, subcutaneously. 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. Dose management of symptomatic anemia in adults and children with CRF: Binocrit in patients with CRF is administered intravenously. Due to the fact that the clinical manifestations of anemia and residual effects may vary depending on the 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.

It is not recommended to increase the hemoglobin concentration more than 12 g/dl (7.5 mmol/l) for a long time. If the hemoglobin concentration increases 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 Binocrit 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 inter-individual 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 are treated in two stages.

Correction stage. Intravenous 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.

Stage of maintenance therapy. Dose adjustment to maintain the required hemoglobin level of 10-12 g / dl (6.2-7.5 mmol / l).

The recommended total weekly dose of the drug 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 is performed in two stages.

Correction stage. Intravenous 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.

Stage of maintenance therapy. Dose adjustment to maintain the required hemoglobin level of 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 given higher maintenance doses than in children with a higher body weight and adults.

Binocrit is administered subcutaneously.

The recommended dose of Binocrit is 600 IU / kg once a week for 3 weeks preceding the operation (21,14 and 7 days before the operation), as well as on the day of the operation. 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 Hb 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.

Overdose

The therapeutic range of the drug is wide.

In case of overdose, symptoms may occur that reflect the extreme degree of manifestation of the pharmacological action of the hormone (increased hemoglobin concentration or hematocrit).

If the hemoglobin or hematocrit levels are exceptionally high, phlebotomy may be used.

If necessary, symptomatic therapy is prescribed.

Special instructions

When prescribing the drug Binocrit in all patients, it is necessary to check and strictly control blood pressure. Caution should be exercised when using epoetin alfa in hypertensive patients if they do not receive the necessary treatment, the prescribed treatment is inadequate, or hypertension is poorly controlled. In this case, it may be necessary to start or strengthen the antihypertensive therapy that has already been used. If blood pressure cannot be normalized, treatment with epoetin alfa should be discontinued. Binocrit should be used with caution in the presence of epilepsy and chronic liver failure.

Patients with CRF and cancer should regularly monitor their hemoglobin levels until stable values are achieved and periodically thereafter.

Careful monitoring of hemoglobin levels is mandatory for all patients due to the increased potential risk of thromboembolic complications and an increase in the number of fatal cases when patients received treatment with hemoglobin levels exceeding the established norm for the use of the drug according to indications.

During treatment with Binocrit, there may be a moderate dose-dependent increase in the number of platelets within the normal range. With the continuation of the course of therapy, this indicator decreases again. During the first 8 weeks after starting therapy, it is recommended to regularly monitor the platelet count.

Before starting therapy, it is necessary to exclude all other causes of anemia (iron deficiency, hemolysis, blood loss, vitamin B12 or folic acid deficiency). In most cases, the level of ferritin in the blood serum decreases with a simultaneous increase in hematocrit.

All these additional factors of anemia should also be taken into account when increasing the dose of Binocrit in patients with neoplasms.

During the perioperative period, it is necessary to carefully monitor all blood parameters.

PCA After several months or years of treatment with erythropoietin by subcutaneous injection, cases of antibody-mediated PCA have been very rare. If patients have a dramatic decrease in the effectiveness of therapy due to a decrease in hemoglobin concentration (1-2 g/dl per month) against the background of an increased need for blood transfusions, it is necessary to check the number of reticulocytes and study the typical causes of non-response to the drug (for example, iron, folic acid or vitamin B12 deficiency, aluminum intoxication, infections or inflammation, bleeding or hemolysis).

If the reticulocyte count is low, taking into account anemia (for example, the reticulocyte index) (If the appearance of PCA mediated by antibodies to erythropoietin is suspected, Binocrit therapy should be stopped immediately. It is forbidden to prescribe any other therapy with erythropoietin because of the risk of cross-reaction. If indicated, patients may be prescribed the necessary therapy, such as blood transfusions.

In the event of a paradoxical decrease in the hemoglobin concentration and the development of severe anemia due to a low reticulocyte count, it is necessary to immediately stop treatment with epoetin and conduct a test for the presence of antibodies to erythropoietin. There are data on such manifestations in patients with hepatitis C treated with interferon and ribavirin simultaneously with epoetin. Epoetin is not intended for the treatment of anemia caused by hepatitis C.

Data on immunogenicity after subcutaneous use of Binocrit to patients at risk of developing antibody-mediated PCA, such as those with renal anemia, are limited. As a result, the drug should be administered intravenously to patients with renal anemia.

In order to minimize the risk of increased hypertension for patients with CRF, the rate of increase in hemoglobin should be approximately 1 g / dl (0.62 mmol / l) per month and should not exceed 2 g / dl (1.25 mmol/l) per month.

In patients with CRF, the hemoglobin concentration at the maintenance stage of treatment should not exceed the ULN recommended in the section “Dosage and use”. The results of clinical studies showed an increased risk of fatal outcomes and severe cardiovascular disorders with the introduction of erythropoiesis-stimulating drugs in order to increase the hemoglobin concentration more than 12 g/dl (7.5 mmol/l).

Clinical studies conducted under controlled conditions did not reveal significant benefits associated with the use of epoetins against the background of an increase in the concentration of hemoglobin above the level necessary to control the symptoms of anemia and prevent blood transfusions. Cases of shunt thrombosis have been reported in patients undergoing hemodialysis, in particular with a tendency to hypotension or due to the formation of arteriovenous fistulas (for example, stenosis, aneurysms, etc. ). Such patients are recommended for early shunt correction and prevention of thrombosis, for example with acetylsalicylic acid.

In some cases, hyperkalemia was observed. Treatment of anemia can lead to increased appetite and increased potassium and protein requirements. Periodically, the dialysis regimen should be adjusted to maintain the necessary urea, creatinine, and potassium levels. In patients with CRF, it is necessary to check the content of electrolytes in the blood serum. If elevated (or rising) serum potassium levels are detected, the feasibility of discontinuing epoetin alfa treatment should be evaluated until potassium levels normalize.

During treatment with epoetin alfa, it is often necessary to increase the dose of heparin during hemodialysis due to an increase in the hematocrit number. If heparinization is not as effective as possible, it may be necessary to cancel the dialysis regimen. According to available data, treatment of anemia with epoetin alfa in adult patients with renal insufficiency who have not yet received dialysis does not cause progression of renal failure.

Adult cancer patients with symptomatic anemia undergoing chemotherapy In some clinical situations, blood transfusions should be used to treat anemia in patients with cancer. The decision to prescribe recombinant erythropoietins should be made taking into account the ratio of benefits and possible risks for each patient individually and the specifics of the clinical situation. The following factors should be considered: the type and stage of development of the neoplasm; the degree of anemia; life expectancy; the environment in which the patient will be treated; and the patient’s own wishes.

When evaluating the feasibility of epoetin alfa therapy (the patient’s risk of blood transfusion) in cancer patients receiving chemotherapy, it is necessary to take into account the delay of 2-3 weeks after the introduction of epoetin alfa before the formation of red blood cells against the background of erythropoietin stimulation.

In order to minimize the risk of developing thrombotic events, it is necessary to monitor that the level of hemoglobin and the rate of its increase do not exceed acceptable indicators.

Due to the increasing number of cases of venous thrombotic complications in cancer patients receiving erythropoiesis-stimulating drugs, this risk and benefit of treatment with epoetin alfa should be carefully evaluated, especially in cancer patients with an increased risk of venous thrombotic complications, for example, against the background of obesity or the presence of venous thrombotic diseases in the family history (including deep venous thrombosis or pulmonary embolism).

Adult patients participating in an autologous blood collection program before surgery, all special precautions related to autologous blood collection programs should be observed, especially with regular blood transfusions.

Patients undergoing elective orthopedic surgery

For patients undergoing elective orthopedic surgery, it is necessary to determine the cause of anemia and, if possible, cure the anemia before starting therapy with epoetin alfa. Such patients may have a risk of developing thrombotic events, which should be carefully evaluated when prescribing treatment for patients in this group.

Patients undergoing elective orthopedic surgery should receive adequate antithrombotic prophylaxis due to the risk of venous thrombotic complications in surgical patients, especially those suffering from cardiovascular diseases. In addition, special precautions should be taken in patients with a predisposition to the development of deep vein thrombosis of the extremities. Patients with initial hemoglobin levels >13 g / dl (>8.1 mmol / L) have an increased risk of postoperative thrombotic/venous complications. Therefore, the drug should not be prescribed to patients with an initial hemoglobin level >13 g / dl (>>8.1 mmol / L).

Auxiliary substances

This medicine contains less than 1 mmol of sodium (23 mg) in one pre-filled syringe, i. e. it is virtually sodium-free.

Form of production

Solution for intravenous and subcutaneous use

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