Binocrit

By its immunological and biological properties, binocritis is related to natural human erythropoietin (a hormone that stimulates the development of erythropoiesis processes - the production of red blood cells). In normal health, the synthesis of erythropoietin is carried out by the kidneys (90%), as well as the liver (10%). The drug helps to stabilize hematocrit and hemoglobin, and also reduces or eliminates the symptoms that occur as a result of anemia.

The active element of the drug is α-epoetin.

[1], [2]

Indications Binocrit

It is used in such situations:

• anemia associated with CKD (also anemia caused by CKD in individuals undergoing hemodialysis (children and adults) or peritoneal dialysis (adults));
• severe anemia with a renal etiology that develops clinical signs (adults with kidney failure who do not perform hemodialysis);
• anemia, when it is necessary to reduce the need for blood transfusion in adults who undergo chemotherapy in connection with a malignant lymphoma, multiple myeloma, or solid tumors. In addition, in people with an increased likelihood of developing complications during blood transfusion, associated with a severe general condition;
• to increase the therapeutic efficacy of blood transfusion during presumptive blood collection before performing surgery in people with hematocrit of 33-39% (to simplify blood collection and reduce the risk caused by the use of allogeneic transfusions when the need for blood is higher than the volume that dial with autologous intake without additional administration of α-epoetin);
• anemia of moderate intensity (with Hb values equal to 100-130 g / l), also without iron deficiency, when blood loss is expected, and in addition, during operations that require significant amounts of transfused blood;
• to reduce the likelihood of violations in 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 take zidovudine (with values of natural erythropoietin below 500 ME / ml).

[3]

Release form

The release of drugs is in the form of injection fluid, inside the syringe (volumes of 2,000, 4,000, or 20,000 IU).

[4], [5]

Pharmacodynamics

Erythropoietin is a glycoprotein necessary for stimulating the processes of erythropoiesis, and at the same time it activates the processes of mitosis and the formation of red blood cells from erythrocyte progenitor cells. The molecular mass index of EPO reaches approximately 32-40 thousand daltons. The volume of the protein fraction 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-glycosidic compound. The α-epoetin produced in genetic engineering processes is a purified glycoprotein. The carbohydrate and amino acid composition of a substance is similar to natural erythropoietin secreted from urine in people with anemia.

Binocrite has the highest cleaning performance consistent with current technological capabilities. For example, during the quantitative testing of the active drug element, it is impossible to determine even the trace number of cell lines through which the drug is manufactured.

The bioactivity of α-epoetin is confirmed by testing in vivo (performed with rats (healthy and suffering from anemia), and in addition in mice that have polycythemia). After the application of α-epoetin, the volumes of reticulocytes with erythrocytes, as well as hemoglobin indices, increase with the rate of absorption of Fe 59.

When testing in vitro during incubation with the component α-epoetin, potentiation of the incorporation of the 3H-thymidine element inside the splenic cells in mice (erythroid nucleus-containing) was found. Tests on human bone marrow cell culture revealed that α-epoetin promotes specific stimulation of erythropoiesis, while not affecting the processes of leukopoiesis. The cytotoxic activity of erythropoietin in relation to human bone marrow cells is not registered.

Erythropoietin is a growth factor that, for the most part, stimulates the formation of red blood cells. Erythropoietin endings can be found on the surface of a variety of tumor cells.

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

[6]

Pharmacokinetics

Intravenous injections.

The term half-life of α-epoetin when used repeatedly is approximately 4 hours in volunteers, as well as approximately 5 hours in people with chronic renal failure. The term half-life of α-epoetin in a child is approximately 6 hours.

Subcutaneous injections.

After subcutaneous administration, the plasma indices of α-epoetin are much lower than as a result of intravenous injection.

It takes 12–18 hours to obtain TCmax α-epoetin inside the blood plasma. The Cmax values of the component after the s / c injection are equal to only 1/20 of the indicators observed after intravenous injection.

The drug is not able to accumulate - the plasma level of α-epoetin after 24 hours from the moment of the 1st injection is similar to the values observed after 24 hours from the moment of the last injection.

After s / c injection, the term α-epoetin half-life is not easy to determine, but it is approximately 24 hours. The level of bioavailability of α-epoetin after s / c injection is much lower than marks after intravenous injection and is approximately 20%.

[7], [8], [9], [10],

Dosing and administration

Apply the drug must be subcutaneously or intravenously.

Therapy is performed under the supervision of a medical professional who has the necessary experience and qualifications to treat people who are prescribed substances that stimulate erythropoiesis.

Portion sizes.

Symptomatic type of anemia in the case of ESRD: the drug must be administered intravenously. Due to the fact that the clinical signs of anemia with its residual manifestations can be very different taking into account the sex and age of the person being treated, and with it the overall severity of the pathology, the condition of each person is assessed individually.

Hemoglobin targets are 10–12 g / dl for an adult and 9.5–11 g / dl for a child.

It is forbidden to prolong the hemoglobin level for a long time to levels above 12 g / dl. With an increase in hemoglobin values above 2 g / dL per month or a prolonged excess of 12 g / dL, a portion of Binocrite is required to be reduced by 25%. With hemoglobin values of more than 13 g / dl, therapy should be canceled until hemoglobin drops to 12 g / dl. After this, treatment is resumed, reducing the initial portion by 25%.

Due to personal variability, hemoglobin values may be lower or higher than the desired target level.

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

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

Adults who need hemodialysis.

Therapy must be implemented in 2 phases.

Correction phase. Intravenous administration of 50 IU / kg of the drug 3 times in a 7-day period. If required, a gradual dosage adjustment may be performed over a 1-month term.

It is allowed to increase or decrease the portion by a maximum of 25 IU / kg, 3 times in a 7-day period.

Supporting phase. The dosage is adjusted to maintain the hemoglobin markers required - in the range of 10-12 g / dL.

The size of the recommended total daily dose of drugs is about 75-300 IU / kg; the dose is administered intravenously - 25-100 IU / kg, 3 times in 7 days.

Persons with severely expressed anemia (hemoglobin - <6 g / dl) will probably require the introduction of elevated support portions (compared to situations when this indicator is higher - <8 g / dl).

Use for children in need of hemodialysis.

Therapy is performed in 2 stages.

Correctional stage. Intravenous drug use is 50 IU / kg 3 times in a 7-day term. If you need to adjust the portion, it should be a gradual process over 4 weeks. To reduce or increase the dosage should be a maximum of 25 IU / kg 3 times a week.

Supporting stage. It is necessary to adjust the dosage to maintain the required hemoglobin values - in the range of 9.5-11 g / dL.

Children with a weight less than 30 kg usually require the introduction of increased support portions (comparing with adults and children with higher weight).

Available clinical evidence suggests that during the six months of therapy, 3 portions of the drug should be administered 3 times per 7-day period (taking into account the patient's weight):

• <10 kg: average dosages - 100 IU / kg, supporting - 75-150 IU / kg;
• in the range of 10-30 kg: 75 or 60-150 IU / kg;
• > 30 th kg: 33 or 30-100 ME / kg.

Children with severe anemia (hemoglobin - <6.8 g / dl) should use increased maintenance portions (compared with children who have higher hemoglobin values -> 6.8 g / dl).

Adults who perform peritoneal dialysis.

The therapeutic cycle consists of 2 separate phases.

Correction phase. Intravenous injection of binocrit in the initial portion of 50 IU / kg, 2 times in 7 days.

Supporting 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 in 7 days, 2 equal in volume to the injection.

Adults with kidney failure who did not perform dialysis.

The treatment cycle includes 2 stages.

Correctional stage. First, an intravenous injection of 50 IU / kg 3 times in a 7-day term is prescribed; then, if needed, the portion may increase by 25 IU / kg (3 times in 7 days) until it reaches the target mark (increase occurs gradually, over a period of at least 1 month).

Supporting stage. It is necessary to change the dosage to maintain stable Hb values in the range of 10-12 g / dl. It is necessary to administer the IV method of 17-33 IU / kg of drug 3-fold over a 7-day period.

The total size of the weekly dosage max (3 times the use of drugs) is 200 IU / kg.

With anemia in people who have undergone chemotherapy.

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

It is required to take into account the fluctuations of hemoglobin indices, changing the input portion depending on the normal level of Hb: 10 g / dL - 12 g / dL. It is forbidden to exceed the level of Hb> 12 g / dl.

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

Continuing treatment with the indicated drug is indicated for one more month after the end of chemotherapeutic procedures.

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

With an increase in Hb values of at least 1 g / dL or an increase in the number of reticulocytes within ≥40000 cells / μl regarding the initial level after 4 weeks of therapy, the dose of the drug is 150 IU / kg (3 times in a 7-day period ) or 450 IU / kg (1 time for a 7-day period), and does not change in the future.

If Hb increases by <1 g / dl, and the number of reticulocytes by <40,000 cells / µl regarding baseline values, you need to increase the portion of Binocrite to 300 IU / kg with 3-fold use per week. In the case of an increase in hemoglobin values up to ≥1 g / dl, and the number of reticulocytes to ≥40000 cells / µl after the 1st month of the introduction of the above portion, it should be introduced further. In the absence of such an improvement and after the introduction of 300 IU / kg, the treatment should be considered ineffective and therefore cancel it.

Changing portions to maintain Hb elevations in the range of 10-12 g / dL.

With an increase in the level of Hb by 2+ g / dl per month, or if the Hb indicator is over 12 g / dl, it is required to reduce the dose of drugs by 25-50%. If the level of Hb is more than 13 g / dl, the therapy should be canceled before reducing these parameters to 12 g / dl. After this, the treatment is resumed, having previously reduced the initial portion by 25%.

Adults who are included in the blood sampling program before surgery.

The drug is administered intravenously after the end of the blood collection procedure. Persons with a light stage of anemia (hematocrit values within 33-39%) who need> 4 U of blood are required to enter 600 IU / kg of the element 2 times a day for the 7-day period during the 21st day before operations.

Patients who inject the drug, you must additionally take oral iron (a portion of 0.2 g per day) throughout the treatment cycle.

Start taking the funds Fe is required prior to the use of binocrit; This should be done a few weeks before the start of blood collection.

Adults who require elective orthopedic surgery.

Apply drugs need subcutaneously.

It is recommended to administer 600 IU / kg of the substance 1-fold for the 7-day period during the 21st day prior to surgery (on the 21st, 14th and 7th days), and with it on the day of the procedure itself. If the interval before the operation is less than 3 weeks, the medication is administered daily in a volume of 300 IU / kg (10-day term), and in addition, on the day of the surgery, and 4 more days after. If the Hb indices during the preoperative period are 15 g / dl or more, the use of the medication should be discontinued. Before starting the treatment course, you need to make sure that the patient does not have iron deficiency.

Every patient who is injected with binocrit needs to receive 2-valent Fe (orally, 0.2 g per day) throughout the entire treatment cycle.

[13]

Use Binocrit during pregnancy

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

Contraindications

Among the contraindications:

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

Use caution is recommended for such violations:

• thrombocytosis;
• malignant tumors;
• epilepsy syndrome (also available in history);
• failure of the liver or kidneys in the chronic phase;
• history of thrombosis;
• acute blood loss;
• anemia, which has a hemolytic or sickle cell character;
• lack of vitamins B9 or B12, as well as the element Fe.

[11], [12]

Side effects Binocrit

The main side signs are:

• disturbances of blood-clotting processes: thrombosis affecting shunts in people on hemodialysis;
• problems with the work of the cardiovascular system: worsening of the course of AH or the development of its malignant form, as well as hypertensive crisis;
• disorders of hematopoietic processes: thrombocytosis;
• lesions of the urethra: an increase in plasma values of uric acid, and in addition, urea and creatinine; the development of hyperphosphatemia or -kalemia;
• allergy symptoms: anaphylactic manifestations, epidermal rashes, angioedema, urticaria, immune signs and eczema;
• local disorders: burning, redness or pain in the area of the injection.

Overdose

The drug has a large therapeutic spectrum. In the case of intoxication, signs may appear that reflect the most pronounced manifestation of the drug effect of the hormone (an increase in hematocrit or hemoglobin values).

If hematocrit or hemoglobin reaches excessively high rates, phlebotomy can be performed. Symptomatic treatment measures are carried out when required.

[14], [15]

Interactions with other drugs

The use of drugs that inhibit erythropoiesis, can lead to a weakening of the therapeutic effect of α-epoetin.

The combination with cyclosporin can cause a drug interaction, because cyclosporin can be synthesized with red blood cells. With the combination of medication and cyclosporine, it is required to monitor the plasma values of the latter and change its dosage, taking into account the degree of hematocrit increase.

Women with carcinoma of the breast, occurring with the development of metastases, s / c injection of α-epoetin in a portion of 40,000 IU together with trastuzumab at a dosage of 6 mg / kg does not change the pharmacokinetics of the latter.

In order to prevent incompatibility or weakening of effectiveness, it is forbidden to mix the drug with solutions and other drugs.

[16], [17], [18]

Storage conditions

Binocrite must be maintained at temperature marks of 2-8 ° C.

[19]

Shelf life

Binocrite can be used for a 2-year period from the date of release of the medication.

[20]

Application for children

It is possible to prescribe α-epoetin in case of anemia caused by chronic kidney disease, children from 1 month old who are on dialysis. For infants less than 1 month, the efficacy and safety of drugs have not been studied.

Analogs

Analogues of drugs are means Epobiokrin and Gemax.

[21], [22]