Binocrit, 2000 me/ml 1 ml syringes 6 pcs

Erythropoietin is a glycoprotein that stimulates erythropoiesis, activates mitosis and maturation of erythrocytes 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. Four hydrocarbon chains are linked to the protein by three N-glycoside bonds and one O-glycoside bond. Epoetin alpha, produced using genetically engineered technology, is a purified glycoprotein and is identical in amino acid and carbohydrate composition to human erythropoietin excreted from the urine of anemic patients.

Binocrit® has the highest possible degree of purification according to current technological capabilities. In particular, in quantitative analysis of the active ingredient of Binocrit® even trace amounts of cell lines are not detected.

The biological activity of epoetin alfa was confirmed in an in vivo experiment (studies were performed on healthy rats and rats with anemia as well as on mice with polycythemia). After epoetin alfa administration the number of erythrocytes, reticulocytes, hemoglobin concentration and 59Fe absorption rate increase.

In in vitro studies, incubation with epoetin alfa revealed increased incorporation of 3H-thymidine into erythroid nucleated cells of the spleen (in mouse spleen cell culture). Studies on human bone marrow cell culture showed that epoetin alfa specifically stimulates erythropoiesis and has no effect on leukopoiesis. Cytotoxic effects of erythropoietin on human bone marrow cells were not revealed.

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

The administration of epoetin alfa is accompanied by an increase in hemoglobin, hematocrit, serum iron, contributes to improved blood supply to tissues and heart function. The most significant effect of epoetin alfa is observed in anemia caused by chronic renal insufficiency and also developed in patients with a number of malignant tumors and systemic diseases.

Pharmacokinetics

Injection

The T1/2 of epoetin alfa after repeated IV administration is about 4 h in healthy volunteers and about 5 h in patients with chronic renal failure. In children the T1/2 of epoetin alfa is about 6 h.

P/K administration

The plasma concentration of epoetin alfa is significantly lower when administered p/k than when administered intravenously; the time to reach Cmax of epoetin alfa in plasma is about 12-18 h after administration. Cmax of epoetin alfa when administered by injection is only 1/20th of the concentration when administered intravenously.

The drug has no ability to cumulate – plasma concentration of epoetin alfa 24 hours after the first injection is the same as 24 hours after the last injection.

When administered by injection the T1/2 of epoetin alfa is difficult to determine, it is about 24 hours. The bioavailability of epoetin alfa when administered by mouth is significantly lower than when administered by IV and is estimated to be about 20%.

Indications

– Anemia in adults and children due to chronic renal failure (CRF), including. anemia due to CKD in children and adults on hemodialysis and in adults on peritoneal dialysis; severe anemia of renal genesis with clinical symptoms in adults with renal failure who have not yet had hemodialysis;

– Management of anemia and reduction of the need for blood transfusions in adults treated with chemotherapeutic agents for solid tumors, malignant lymphoma, or multiple myeloma, and in those at high risk for complications from hemotransfusions due to generalized severity (due to cardiovascular disease if anemia was also present before chemotherapy);

To improve the efficacy of autologous blood transfusion as part of a preoperative blood collection program before surgery in patients with hematocrit levels of 33-39%, to facilitate autologous blood collection and to reduce the risk associated with allogeneic hemotransfusions if the expected need for transfused blood exceeds the amount that can be obtained by autologous collection without epoetin alfa. Treatment is indicated in patients with moderately severe anemia (with hemoglobin concentrations of 10-13 g/dL or 6.2-8.1 mmol/l), without iron deficiency, if significant blood loss is expected, and also in 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);

– for risk reduction during allogeneic blood transfusion in adults without iron deficiency, before elective orthopedic surgery, in case of high risk of complications during hemotransfusions. The use of the drug is limited – only in patients with moderately severe anemia (e.g., with a hemoglobin concentration of 10-13 g/dL) if they are not included in the program of autologous blood collection before surgery with an expected blood loss of 900 to 1800 ml;

Anemia in HIV patients receiving zidovudine therapy with endogenous erythropoietin levels less than 500 IU/ml.

Active ingredient

How to take, the dosage

The treatment with Binocrit® must be supervised by a specialist physician with appropriate qualifications and experience in treating patients who are indicated for therapy with erythropoiesis stimulants.

The treatment of symptomatic anemia in adults and children with chronic renal failure (CKD)

Binocrit® in patients with CKD is administered by IV. Because clinical manifestations of anemia and residual effects may vary with age, gender and overall disease severity; individual assessment of each patient’s condition is performed.

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 increases in hemoglobin over 12 g/dL (7.5 mmol/L) are not recommended. If hemoglobin concentration increases more than 2 g/dl (1.25 mmol/l) in a month or if it exceeds 12 g/dl (7.5 mmol/l) for a long time, it is necessary to decrease Binocrit® medicine dose by 25%. If hemoglobin concentration exceeds 13 g/dL (8.1 mmol/L), it is necessary to stop the treatment until hemoglobin decreases to 12 g/dL (7.5 mmol/L) and then resume the treatment with Binocrit® with 25% decrease of the starting dose.

Hemoglobin concentrations may be higher or lower than optimal (target) values due to interindividual variability.

The treatment should be prescribed so that the lowest effective dose of Binocrit® provides adequate control of hemoglobin and clinical manifestations of the disease.

Physical iron concentrations in plasma should be monitored before and during treatment; if necessary, additional iron preparations should be prescribed.

Adult patients receiving hemodialysis

Treatment is carried out in two stages:

The correction phase

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

The maintenance therapy phase

The dose adjustment in order to maintain the required level of hemoglobin: Hb 10-12 g/dL (6.2-7.5 mmol/L).

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

In patients with severe anemia (Hb < 6 g/dL, or < 3.75 mmol/L), higher maintenance doses may be necessary than in patients with higher hemoglobin concentrations (< 8 g/dL, or < 5 mmol/L).

Use in children receiving hemodialysis

The correction phase

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

The maintenance therapy phase

Dose adjustment to maintain the desired hemoglobin level: Hb 9.5-11 g/dL (5.9-6.8 mmol/L).

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

Adult patients receiving peritoneal dialysis

Treatment is in two stages.

The correction phase

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

The maintenance phase

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

Adults with renal failure who have not had dialysis

The treatment is given in two stages.

The correction phase

The initial dose is 50 IU/kg 3 times per week by IV, with subsequent increases of 25 IU/kg (3 times per week) if necessary until the target dose is reached (increase the dose gradually over at least 4 weeks).

The maintenance therapy phase

Dose adjustment to maintain desired hemoglobin levels: Hb 10-12 g/dL (6.2-7.5 mmol/L). The maintenance dose is 17 to 33 IU/kg 3 times a week by IV. The maximum dose should not exceed 200 IU/kg 3 times a week.

The treatment of anemia in patients after chemotherapy

Binocrit® is given by injection (at a Hb+10 g/dL (6.2 mmol/L). The dose is individually adjusted by the physician taking into account the severity of anemia, age, sex and general severity of the patient’s condition. It is also necessary to take into account the hemoglobin concentration fluctuations by adjusting the applied dose of the drug taking into account the normal values of hemoglobin concentration from 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l). Dose adjustments beyond 12 g/dL (7.5 mmol/L) are not recommended.

The treatment should be prescribed so that the lowest effective dose of epoetin alfa provides the necessary control of anemia symptoms. Therapy with Binocrit® should be continued for 1 month after completion of chemotherapy.

The initial dose of the drug is 150 IU/kg administered by p/k 3 times a week. Alternate use of the drug in a dose of 450 IU/kg p/kg once a week is possible.

If there is an increase of at least 1 g/dL (>0.62 mmol/L) in hemoglobin or if the reticulocyte count increases ≥40,000 cells/μL from baseline after 4 weeks, the dose is 150 IU/kg 3 times weekly or 450 IU/kg once weekly and no change.

If hemoglobin concentration <1 g/dL (<0.62 mmol/L) and reticulocyte count <40,000 cells/μL increase from initial values, the drug dose should be increased to 300 IU/kg 3 times weekly. If after an additional 4 weeks of treatment with 300 IU/kg 3 times weekly, the hemoglobin concentration has increased ≥1 g/dL (≥0.62 mmol/L) or the reticulocyte count has increased ≥40,000 cells/μL, the dose should remain the same at 300 IU/kg 3 times weekly. However, if increase of hemoglobin concentration < 1 g/dl (< 0.62 mmol/l) and reticulocyte count increase < 40,000 cells/μl over initial values, treatment with Binocrit® is considered to be ineffective and should be stopped.

Recommended route of administration of Binocrit®

Dose adjustment to maintain hemoglobin concentration within 10-12 g/dL

If hemoglobin concentration increases more than 2 g/dL (125 mmol/L) per month or if hemoglobin levels exceed 12 g/dL (7.5 mmol/L), the dose of the drug should be reduced by 25-50%.

If hemoglobin exceeds 13 g/dL (8.1 mmol/L), we should stop treatment until it drops to 12 g/dL (7.5 mmol/L), and then we resume therapy with epoetin alfa, reducing the starting dose by 25%.

Adult patients participating in an autologous blood collection program prior to surgery

Binocrit® is administered by IV after completion of the blood donation procedure. Patients with a mild degree of anemia (hematocrit level 33-39%) who require ≥4 units of blood should be treated with Binocrit® at a dose of 600 IU/kg body weight 2 times weekly for 3 weeks prior to the surgical procedure.

All patients receiving Binocrit® should be additionally treated with iron (oral dose 200 mg/day) during the whole course of therapy. The use of iron preparations should be prescribed prior to initiation of 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 by injection.

The recommended dose of Binocrit® is 600 IU/kg once weekly during the 3 weeks preceding surgery (21, 14, and 7 days before surgery) and 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 surgery. If preoperative hemoglobin concentration is 15 g/dL (9.38 mmol/L) or higher, the drug should be discontinued. It should be made sure that patients do not have iron deficiency before treatment with Binocrit®.

All patients treated with Binocrit® should receive adequate divalent iron (200 mg/day orally) for the duration of therapy.

Means of administration

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

Intravenous injection

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

Patients with possible temperature reactions to IV administration are advised to administer the drug slowly.

Intravenous injection

The maximum injection volume of 1 ml per injection site should not be exceeded. If larger amounts are injected, more injection sites should be chosen. Injections are given in the thigh muscle or in the area of the anterior abdominal wall.

Similarities