Binocrit, 40000 me/ml 1 ml syringes 6 pcs

Erythropoietin is a glycoprotein that stimulates erythropoiesis and activates mitosis and maturation of erythrocytes 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 alpha, produced using genetically engineered technology, is a purified glycoprotein and is identical in amino acid and carbohydrate composition to human erythropoietin extracted from the urine of anemic patients.

Binocrit has the highest possible degree of purification according to modern technological capabilities. In particular during quantitative analysis of the active substance of Binocrit even trace amounts of cell lines are not defined.

Biological activity of epoetin alfa was confirmed in vivo experiment (studies were carried out on healthy rats and rats with anemia as well as on mice with polycythemia). After epoetin alfa injection 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 in 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 detected.

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 has been noted in anemia caused by chronic renal insufficiency (CKF) and also developed in patients with a number of malignant neoplasms and systemic diseases.

Pharmacokinetics

Intravenous administration

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

Subcutaneous administration

The plasma concentration of epoetin alfa is determined significantly lower by subcutaneous administration than by intravenous administration, the T_max of epoetin alfa in plasma is about 12-18 hours after administration. C_max epoetin alfa when administered subcutaneously 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 subcutaneously, the T_1/2 of epoetin alfa is difficult to determine; it is about 24 hours. The bioavailability of epoetin alfa when administered subcutaneously is significantly lower than when administered intravenously and is about 20%.

Indications

Active ingredient

Composition

1 ml of solution for intravenous and subcutaneous administration contains:

the active ingredient:

epoetin alfa 336 µg;

auxiliary substances:

Sodium dihydrophosphate dihydrate,

Sodium hydrophosphate dihydrate,

Sodium chloride,

glycine,

Polysorbate 80,

hydrochloric acid,

sodium hydroxide,

water for injection

How to take, the dosage

Intravenously, subcutaneously.

The treatment with Binocrit should be carried out under the supervision of a specialist with appropriate qualification and experience in the treatment of patients who are indicated for therapy with erythropoiesis stimulating drugs.

Doses

Treatment of symptomatic anemia in adults and children with CPN: Binocrit in patients with CPN is administered by IV. Due to the fact that clinical manifestations of anemia and residual phenomena may differ depending on age, sex and general severity of the disease, individual assessment of each patient’s condition is carried out.

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.

Hemoglobin concentrations above 12 g/dL (7.5 mmol/L) over a prolonged period are not recommended. If the hemoglobin concentration increases more than 2 g/dL (1.25 mmol/L) per month or exceeds 12 g/dL (7.5 mmol/L) for a long time, the dose of Binocrit should be reduced by 25%. If the hemoglobin concentration is more than 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 therapy with Binocrit, reducing the initial dose by 25%.

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

The treatment should be prescribed in such a way that the lowest effective dose of Binocrit provides the necessary control of hemoglobin and clinical manifestations of the disease.

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

Adult patients receiving hemodialysis

The 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. Dose adjustment in order to maintain the necessary level of hemoglobin 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 25-100 IU/kg 3 times a week.

In patients with severe anemia (hemoglobin Application in children receiving hemodialysis

The treatment is carried out in two stages.

The correction stage. Binocrit is administered intravenously at a dose of 50 IU/kg 3 times a 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 stage. Dose adjustment in order to maintain the necessary level of hemoglobin 9.5-11 g/dl (5.9-6.8 mmol/l).
In most cases in children with body weight less than 30 kg, higher maintenance doses should be used 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 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 Hb concentration is 15 g/dL (9.38 mmol/L) or higher, the drug should be discontinued. It should be ensured that patients have no iron deficiency before starting treatment with Binocrit.

All patients treated with Binocrit should receive adequate divalent iron (200 mg/day orally) during the whole course of therapy.

Interaction

There are no data on interaction of epoetin alfa with other drugs. However, when concomitant use with cyclosporine interaction is possible because the drug binds with red blood cells.

If the treatment by the drug Binocrit is carried out concomitantly with cyclosporine it is necessary to monitor the concentration of cyclosporine according to the degree of hematocrit increase.

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

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

Special Instructions

BP should be checked and closely monitored in all patients when Binocrit is prescribed. Caution should be exercised when using epoetin alfa in patients with hypertension if they are not receiving the necessary treatment, the prescribed treatment is inadequate, or the hypertension is poorly controlled. In this case, it may be necessary to initiate or intensify antihypertensive therapy that has already been used. If BP cannot be normalized, treatment with epoetin alfa should be discontinued. Binocrit is used with caution in the presence of epilepsy and chronic hepatic insufficiency.

CPN patients and cancer patients should have their hemoglobin levels monitored regularly until stable values are achieved and periodically thereafter.
Close monitoring of hemoglobin levels is mandatory for all patients due to increased potential risk of thromboembolic complications and an increase in fatal cases where patients were treated at hemoglobin levels greater than the established norm for the indication.

Moderate dose-dependent increases in platelet counts within the normal range may be observed during treatment with Binocrit. This amount decreases again with continuation of therapy. During the first 8 weeks after the start of therapy, it is recommended to monitor platelet count regularly.

Contraindications

With caution: malignant tumors, epilepsy syndrome (including history), chronic renal and hepatic insufficiency, thrombocytosis, thrombosis (history), acute blood loss, sickle cell anemia, hemolytic anemia, iron-, B12- or folate-deficient states.

Side effects

The following side effects are categorized according to organ and system classification and frequency of occurrence: very common (≥1/10); common (≥1/100-

Blood and lymphatic system disorders: infrequent – thrombocythemia (in patients with malignancies); frequency unknown – antibody-mediated PKKA1, thrombocythemia (in patients with CPN).

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

Nervous system disorders: very common – headache (in patients with malignancies); common – seizures (in patients with CKD), headache (in patients with CKD); infrequent – hemorrhagic stroke2, seizures (in patients with malignancies); frequency unknown – stroke2, hypertensive encephalopathy, transient ischemic attacks.

An organ of vision: frequency unknown – retinal thrombosis.

Particular system disorders: common – lower extremity deep vein thrombosis (in patients with malignant tumors); increased BP; common unknown – lower extremity deep vein thrombosis (in patients with CKD), arterial thrombosis, hypertensive crisis.

Respiratory system disorders: frequent – pulmonary embolism2 (in patients with malignancies); frequency unknown – pulmonary embolism2 (in patients with CKD).

Gastrointestinal disorders: very common – nausea; common – diarrhea (in patients with cancer), vomiting; infrequent – diarrhea (in patients with CKD).

Skin and its appendages: often – skin rash; frequency unknown – angioedema, urticaria.

Muscular system: very common – arthralgia (in CPN); common – arthralgia (in patients with malignancies); infrequent – myalgia (in patients with malignancies); common unknown – myalgia (in CPN).

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

Body in general: very common – hyperthermia (in patients with malignancies); flu-like condition (in COPD); common – flu-like condition (in patients with malignancies); frequency unknown – drug inefficacy, peripheral edema, hyperthermia (in COPD), injection site reactions.

Laboratory findings: frequency unknown – antibodies to erythropoietin1.

Others: common – dialysis equipment shunt thrombosis (in patients with CKD).

1 Frequency of manifestations cannot be estimated from clinical studies.
2 Including fatal cases.

Overdose

The therapeutic range of the drug is wide.

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

In extremely high hemoglobin or hematocrit levels, phlebotomy may be used.

Symptomatic therapy is indicated if necessary.

Pregnancy use

No properly controlled studies have been conducted on the use of epoetin alfa in women during pregnancy. Animal studies have shown reproductive toxicity.

As a consequence, patients with CKD should use Binocrit during pregnancy only if the anticipated 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 prior to surgery.

Similarities