Binocrit

Binocrit in its immunological and biological properties is comparable to natural human erythropoietin (a hormone that stimulates the development of erythropoiesis processes - the production of red blood cells). In normal health, erythropoietin is synthesized by the kidneys (90%) and the liver (10%). The drug helps stabilize hematocrit and hemoglobin levels, and reduces or eliminates symptoms that occur as a result of anemia.

The active element of the drug is α-epoetin.

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Indications Binocrit

It is used in the following situations:

• anemia associated with CRF (also anemia caused by CRF in individuals undergoing hemodialysis (children and adults) or peritoneal dialysis (adults));
• severe anemia of renal etiology, in which clinical signs develop (in adults with renal failure who do not undergo hemodialysis);
• anemia, when it is necessary to reduce the need for blood transfusion in adults undergoing chemotherapy for malignant lymphoma, multiple myeloma or solid tumors. In addition, in people with an increased risk of complications during blood transfusion associated with a severe general condition;
• to increase the therapeutic efficacy of blood transfusion during pre-deposit blood collection prior to surgery in individuals with hematocrit values of 33-39% (to simplify blood collection and reduce the risk associated with the use of allogeneic transfusions when the need for blood is greater than the volume that can be collected with autologous collection without additional administration of α-epoetin);
• moderate anemia (with Hb values equal to 100-130 g/l), also without iron deficiency, when blood loss is expected, and in addition to this, during operations requiring significant volumes of transfused blood;
• to reduce the likelihood of complications during allogeneic blood transfusion in adults without iron deficiency, before performing an elective orthopedic procedure (with a high probability of complications during transfusion);
• anemia in people with HIV who are taking zidovudine (with natural erythropoietin levels below 500 IU/ml).

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Release form

The drug is released in the form of an injection liquid, inside a syringe (volumes of 2000, 4000 or 20000 IU).

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Pharmacodynamics

Erythropoietin is a glycoprotein necessary for stimulating erythropoiesis processes, and at the same time activates mitosis processes and the formation of erythrocytes from erythrocyte precursor cells. The molecular weight of EPO is approximately 32-40 thousand daltons. The volume of the fraction consisting of proteins is approximately 58% of the molecular weight; it consists of 165 amino acids. Protein synthesis of 4 hydrocarbon chains is carried out through 3 N-glycosidic and 1 O-glycoside compound. α-epoetin obtained through genetic engineering processes is a purified glycoprotein. The carbohydrate and amino acid composition of the substance is similar to natural erythropoietin secreted from the urine of people with anemia.

Binocrit has the highest purification rates, corresponding to current technological capabilities. For example, during quantitative testing of the active element of the drug, it is impossible to determine even a trace number of cell lines through which the drug is manufactured.

The bioactivity of α-epoetin is confirmed by in vivo testing (performed with rats (healthy and anemic), and also with mice with polycythemia). After the use of α-epoetin, the volumes of reticulocytes with erythrocytes, as well as hemoglobin levels, together with the rate of Fe 59 absorption, increase.

In vitro testing during incubation with the α-epoetin component revealed potentiation of the incorporation of the 3H-thymidine element inside spleen cells in mice (erythroid nucleated). Tests on human bone marrow cell culture revealed that α-epoetin promotes specific stimulation of erythropoiesis without affecting leukopoiesis processes. No cytotoxic activity of erythropoietin in relation to human bone marrow cells was registered.

Erythropoietin acts as a growth factor, mainly stimulating the formation of red blood cells. Endings related to erythropoietin can be found on the surface of various tumor cells.

The use of α-epoetin leads to an increase in the levels of hematocrit with hemoglobin and serum Fe, and in addition helps to improve tissue blood supply and cardiac function. α-epoetin is most effective in the case of anemia associated with chronic renal failure, and at the same time in anemia that occurs in individuals with a number of systemic pathologies and malignant tumors.

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Pharmacokinetics

Intravenous injections.

The half-life of α-epoetin after repeated administration is approximately 4 hours in volunteers and approximately 5 hours in individuals with CRF. The half-life of α-epoetin in a child is approximately 6 hours.

Subcutaneous injections.

Following subcutaneous administration, plasma levels of α-epoetin are much lower than those following intravenous injection.

It takes 12-18 hours to obtain the TСmax values of α-epoetin in blood plasma. The Cmax values of the component after a subcutaneous injection are only 1/20 of the values observed after an intravenous injection.

The drug is not capable of accumulating – the plasma level of α-epoetin after 24 hours from the moment of the first injection is similar to the values observed after 24 hours from the moment of the last injection.

After subcutaneous injection, the half-life of α-epoetin is not easy to determine, but is approximately 24 hours. The bioavailability of α-epoetin after subcutaneous injection is much lower than after intravenous injection and is approximately 20%.

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Dosing and administration

The drug must be administered subcutaneously or intravenously.

The therapy is performed under the supervision of a medical specialist with the necessary experience and qualifications to treat individuals who are prescribed substances that stimulate erythropoiesis processes.

Serving sizes.

Symptomatic type of anemia in case of CRF: the medication must be administered intravenously. Due to the fact that the clinical signs of anemia with its residual manifestations can differ greatly depending on the gender and age of the patient, and along with this, the general severity of the pathology, the condition of each person is assessed individually.

Target hemoglobin levels are 10-12 g/dL for an adult and 9.5-11 g/dL for a child.

It is prohibited to increase the hemoglobin level to marks above 12 g/dl for a long time. If the hemoglobin level increases above 2 g/dl in a month or if the mark of 12 g/dl is exceeded for a long time, the Binocrit dose should be reduced by 25%. If the hemoglobin level is above 13 g/dl, the therapy should be stopped until the hemoglobin drops to 12 g/dl. After that, the treatment is resumed, reducing the initial dose by 25%.

Due to individual variability, hemoglobin levels may be lower or higher than the required target level.

Therapy is carried out in such a way that the use of minimally effective doses of drugs allows for the required control of hemoglobin levels, as well as clinical signs of pathology.

Before starting therapy or already during it, it is necessary to monitor plasma Fe values and prescribe additional (if necessary) iron medications.

Adults who require hemodialysis.

The therapy must be implemented in 2 phases.

Correction phase. Intravenous administration of 50 IU/kg of the drug 3 times over a 7-day period. If necessary, gradual dosage adjustments can be made over a 1-month period.

The dose may be increased or decreased by a maximum of 25 IU/kg, 3 times over a 7-day period.

Maintenance phase. Dosage adjustments are made to maintain the required hemoglobin levels – in the range of 10-12 g/dl.

The recommended total weekly dose of the drug is approximately 75-300 IU/kg; the dose is administered intravenously – 25-100 IU/kg, 3 times over 7 days.

Individuals with severe anemia (hemoglobin <6 g/dL) will likely require higher maintenance doses (compared to those with higher hemoglobin <8 g/dL).

Use in children requiring hemodialysis.

The therapy is carried out in 2 stages.

Correction stage. Intravenous use of the drug - 50 IU/kg 3 times a day for a 7-day period. If it is necessary to adjust the dose, this should be a gradual process over 4 weeks. The dosage should be reduced or increased by a maximum of 25 IU/kg 3 times a week.

Maintenance stage. It is necessary to adjust the dosage to maintain the required hemoglobin values - within 9.5-11 g/dl.

Children weighing less than 30 kg usually require larger maintenance doses (compared to adults and heavier children).

Available clinical data indicate that during the six-month therapy period, the following doses of the drug should be administered 3 times over a 7-day period (taking into account the patient's weight):

• <10 kg: average dosage – 100 IU/kg, maintenance – 75-150 IU/kg;
• in the range of 10-30 kg: 75 or 60-150 IU/kg;
• >30 kg: 33 or 30-100 IU/kg.

Children with severe anemia (hemoglobin <6.8 g/dL) should receive higher maintenance doses (compared to children with higher hemoglobin values >6.8 g/dL).

Adults undergoing peritoneal dialysis.

The therapeutic cycle consists of 2 separate phases.

Correction phase. Intravenous injections of Binocrit in an initial dose of 50 IU/kg, 2 times over a 7-day period.

Maintenance phase. Changing the dosage to maintain the required hemoglobin values (10-12 g/dl). The size of such a portion is 25-50 IU/kg, 2 times over 7 days, 2 injections of equal volume.

Adults with renal failure who have not undergone dialysis.

The treatment cycle includes 2 stages.

Corrective stage. First, an intravenous injection of 50 IU/kg is prescribed 3 times over a 7-day period; then, if necessary, the dose can be increased by 25 IU/kg (3 times over 7 days) until it reaches the target level (the increase occurs gradually, over a period of at least 1 month).

Maintenance stage. The dosage should be changed to maintain stable Hb values in the range of 10-12 g/dl. It is necessary to administer 17-33 IU/kg of the drug intravenously 3 times over a 7-day period.

The total weekly dosage max (3 times a day use of the drug) is 200 IU/kg.

For anemia in people who have undergone chemotherapy.

Binocrit must be administered subcutaneously (with Hb values <10 g/dl). The portion size is individually selected by the doctor, taking into account the gender and age, as well as the severity of anemia and the general condition of the patient.

It is also necessary to take into account fluctuations in hemoglobin levels, changing the administered portion depending on the normal Hb level: 10 g/dl - 12 g/dl. It is prohibited to exceed the Hb level >12 g/dl.

Therapy is selected so that the introduction of the minimum effective dose of α-epoetin provides the required control of signs of anemia.

It is recommended to continue treatment with the indicated drug for another 1 month from the end of chemotherapy procedures.

The initial dosage of the drug is 150 IU/kg; it must be administered subcutaneously, 3 times over a 7-day period. An alternative regimen can be used - subcutaneously, 450 IU/kg, 1 time over a 7-day period.

If Hb values increase by at least 1 g/dL or the reticulocyte count increases by ≥40,000 cells/μL relative to the baseline level after 4 weeks of therapy, the dose of the drug is equal to 150 IU/kg (3 times over a 7-day period) or 450 IU/kg (1 time over a 7-day period), and does not change thereafter.

If the Hb values increase by <1 g/dL and the reticulocyte count by <40,000 cells/µL compared to the baseline values, the Binocrit dose should be increased to 300 IU/kg with 3-fold administration per week. If the Hb values increase to ≥1 g/dL and the reticulocyte count to ≥40,000 cells/µL after 1 month of administration of the above dose, it should be continued. If such improvement is not observed even after administration of 300 IU/kg, the treatment should be considered ineffective and therefore discontinued.

Adjusting portions to maintain Hb levels in the range of 10-12 g/dL.

If the Hb level increases by 2+ g/dl per month, or if the Hb indicator is over 12 g/dl, the dose of the drug should be reduced by 25-50%. If the Hb level is over 13 g/dl, therapy should be discontinued until these indicators decrease to 12 g/dl. After this, treatment is resumed, having previously reduced the initial dose by 25%.

Adults included in the pre-surgery blood collection program.

The drug is administered intravenously after the blood collection procedure is completed. People with mild anemia (hematocrit values within 33-39%) who require >4 U of blood are required to administer 600 IU/kg of the element, 2 times over a 7-day period during the 21st day before the operation.

Patients who are administered the drug must additionally take oral iron supplements (0.2 g per day) throughout the treatment cycle.

Fe supplementation should be started before Binocrit is used, and should be done several weeks before blood collection.

Adults requiring elective orthopaedic surgery.

The drug should be administered subcutaneously.

It is recommended to administer 600 IU/kg of the substance once a 7-day period for 21 days before surgery (on the 21st, 14th and 7th days), and also on the day of the procedure itself. If the interval before surgery is less than 3 weeks, the drug is administered daily in a volume of 300 IU/kg (10-day period), and also on the day of surgery and another 4 days after. If Hb values during the preoperative period are equal to 15 g/dl or more, the use of the drug should be discontinued. Before starting the treatment course, it is necessary to make sure that the patient does not have iron deficiency.

Each patient receiving Binocrit should receive divalent Fe (orally, 0.2 g per day) throughout the treatment cycle.

Use Binocrit during pregnancy

The medication can be administered during pregnancy or lactation, but only under medical supervision.

Contraindications

Among the contraindications:

• severe intolerance associated with α-epoetin;
• partial red cell aplasia that developed as a result of the use of erythropoietin;
• inability to use therapy aimed at preventing thrombosis;
• stroke or myocardial infarction that occurred during the last month before the start of therapy;
• unstable angina;
• increased blood pressure, with the inability to control it;
• increased risk of developing DVT or thromboembolic pathology in the medical history;
• a severe disorder affecting the peripheral, carotid and coronary arteries, as well as the cerebral vessels (for example, in the case of a recent stroke or myocardial infarction).

Caution in use is recommended in the following cases:

• thrombocytosis;
• tumors of a malignant nature;
• epilepsy syndrome (also present in the anamnesis);
• liver or kidney failure in the chronic phase;
• history of thrombosis;
• loss of blood of an acute nature;
• anemia of a hemolytic or sickle cell nature;
• deficiency of vitamins B9 or B12, as well as the element Fe.

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Side effects Binocrit

Main side effects:

• disorders of blood coagulation processes: thrombosis affecting shunts in people undergoing hemodialysis;
• problems with the functioning of the cardiovascular system: worsening of hypertension or development of its malignant form, as well as hypertensive crisis;
• disorders of hematopoiesis: thrombocytosis;
• urinary tract lesions: increased plasma uric acid levels, as well as urea and creatinine; development of hyperphosphatemia or -kalemia;
• allergy symptoms: anaphylactic reactions, epidermal rashes, Quincke's edema, urticaria, immune signs and eczema;
• local disturbances: burning, redness or pain at the injection site.

Overdose

The drug has a wide therapeutic spectrum. In case of intoxication, signs may appear that reflect the greatest expression of the drug effect of the hormone (increase in hematocrit or hemoglobin values).

If the hematocrit or hemoglobin reaches excessively high values, phlebotomy may be performed. Symptomatic treatment measures are carried out if necessary.

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Interactions with other drugs

The use of drugs that suppress erythropoiesis may lead to a weakening of the therapeutic effect of α-epoetin.

Combination with cyclosporine may cause drug interactions, because cyclosporine is capable of synthesizing with red blood cells. When combining the drug and cyclosporine, it is necessary to monitor the plasma values of the latter and change its dosage taking into account the degree of increase in hematocrit.

In women with breast carcinoma that develops metastases, subcutaneous injection of α-epoetin in a dose of 40,000 IU together with trastuzumab at a dosage of 6 mg/kg does not lead to changes in the pharmacokinetics of the latter.

To avoid incompatibility or reduced effectiveness, it is prohibited to mix the medication with solutions and other drugs.

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Storage conditions

Binocrit must be stored at temperatures between 2-8°C.

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Shelf life

Binocrit can be used for a period of 2 years from the date of release of the drug.

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Application for children

α-epoetin can be prescribed for anemia caused by CRF in children from 1 month of age who are on dialysis. The efficacy and safety of the drug have not been studied for infants under 1 month of age.

Analogues

Analogues of the drug are Epobiocrin and Gemax.

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