Epocrin (Epoetin alfa) ampoules

Release form and composition:

Solution for intravenous and subcutaneous administration of 1 ml

epoetin Alfa 1000 IU, 2000 IU, 4000 IU, 10000 IU

Excipients: human serum albumin 2.5 mg citric acid 0.057 mg, sodium chloride 5.84 mg sodium citrate, 5.8 mg, purified water to 1 ml.

1 ml – ampoules (10) – packaging sells contoured (1) – packs of cardboard.

Pharmacological action:Stimulant of erythropoiesis, recombinant human erythropoietin, a glycoprotein.Activates the mitosis and maturation of red blood cells from precursor cells of erythrocytic series. Recombinant epoetin Alfa is synthesized in mammalian cells, which are embedded in the gene encoding human erythropoietin. In its composition, biological and immunological properties of epoetin Alfa is identical to natural human EPO. Introduction epoetin alpha leads to increased levels of hemoglobin and hematocrit levels, improve blood supply to tissues and heart.The most pronounced effect from the use of epoetin alpha observed in anemia due to chronic renal failure.In very rare cases, prolonged use epoetin alpha for the treatment of anemic conditions can be observed the formation of neutralizing antibodies to EPO with the development of partial red cell aplasia.

Pharmacokinetics:Absorption and raspredelennoi p/to the introduction, the concentration of active substance in blood increases slowly, Cmax was achieved within 12-18 h. Bioavailability when s/to the introduction is 25-40%.Vyvedenie p/to the introduction of T1/2 at 16-24 h After in/with the introduction of T1/2 in healthy subjects and patients with uremia is 5-6 hours.

Indications:- anemia in patients with chronic renal failure (including hemodialysis)- prevention and treatment of anemia in patients with solid tumors that have arisen as a result of antitumor therapy – prevention and treatment of anemia caused by zidovudine in HIV-infected patients (AIDS) prevention and treatment of anemia in patients with multiple myeloma, non-Hodgkin’s lymphoma low grade, with chronic lymphocytic leukemia in patients with rheumatoid arthritis – prevention and treatment of anemia in premature infants born with low birthweight (1500 g)- to reduce the volume of transfused blood during extensive surgical interventions and acute blood loss.

Dosing regimen:for the treatment of anemia in patients with chronic renal failure epokrin impose s/to or/in patients undergoing hemodialysis through arteriovenous shunt at the end of the dialysis session. When changing the route of administration the drug is administered at the same dose, then dose adjust if necessary (when s/to the introduction apocrine to achieve the same therapeutic effect required a dose of 20-30% less than at/in the introduction). Treatment Apocrine includes 2 stages.1. The correction stage. When s/to the introduction apocrine initial dose of 30 IU/kg 3 times a week. At/in the introduction apocrine starting dose is 50 IU/kg 3 times a week. Correction period lasts until the optimal hemoglobin level (100-120 g/l in adults and 95-110 g/l in children) and haematocrit (30-35%). These indicators should be monitored weekly.The following situations are possible:

The effectiveness of therapy depends on the correct choice of individual scheme of treatment.2. Phase of maintenance therapy. To maintain a hematocrit level of 30-35% of the dose apocrine used in the correction stage, should be reduced 1.5 times. Then apocrine maintenance dose is selected individually taking into account the dynamics of hematocrit and hemoglobin. After stabilization of hematologic parameters, a transition to the introduction apocrine 1 time in 1-2 weeks.In the prevention and treatment of anemia in patients with solid tumors before using the product it is recommended to determine the level of endogenous erythropoietin. When the concentration of serum erythropoietin less than 200 IU/ml initial dose apocrine at/in the introduction is 150 IU/kg In the p/to the introduction of the initial dose apocrine can be reduced to 100 IU/kg If no response, may increase dose to 300 IU/kg Further dose increase is not reasonable. It is not recommended to assign apocrine patients with endogenic erythropoietin in the serum of more than 200 IU/ml For prophylaxis and treatment of anemia caused by the use of zidovudine in patients with HIV infection in intravenous apocrine at a dose of 100-150 IU/kg 3 times a week is effective, provided that the serum endogenous erythropoietin level less than 500 IU/ml, and the dose of zidovudine is less than 4.2 g per week. When s/to the introduction of dose apocrine can be reduced 1.5 times.The feasibility of apocrine for the prevention and treatment of anemia in patients with multiple myeloma, non-Hodgkin’s lymphoma low grade, with chronic lymphocytic leukemia is caused by inadequate synthesis of endogenous erythropoietin on the background of anemia. When the content of hemoglobin less than 100 g/l and serum erythropoietin level below 100 IU/ml epokrin enter n/a in the initial dose of 100 IU/kg 3 times a week. If necessary, the dose apocrine correct in the direction of increase or decrease every 3-4 weeks. If when reaching a weekly dose of 600 IU/kg increase in hemoglobin is not observed, Epocrin should be abolished, because its further use ineffective.The feasibility of apocrine for the prevention and treatment of anemia in patients with rheumatoid arthritis due to the fact that this disease is suppression of the synthesis of endogenous erythropoietin under the influence of increased concentration of proinflammatory cytokines. Epokrin enter n/a in the dose of 50-75 IU/kg 3 times a week. When increasing the content of hemoglobin less than 10 g/l after 4 weeks of treatment dose apocrine increase to 150-200 IU/kg 3 times a week. Further increase of the dose is impractical.For the prevention and treatment of anemia in premature infants born with low birthweight, Epocrin enter n/a in a dose of 200 IU/kg 3 times a week, starting from the 6th day of life until the achievement of targets for hemoglobin and hematocrit, but not more than 6 weeks.For the prevention of anemia in extensive surgical interventions and acute blood loss apocrine injected in/in or n/a 3 times a week at a dose of 100-150 IU/kg to normalize hematocrit and hemoglobin.

Side effects:In some cases, at the beginning of therapy it is noted flu-like symptoms: dizziness, drowsiness, fever, headache, myalgia, arthralgia.Of the cardiovascular system: possible dose-dependent hypertension, worsening of arterial hypertension (more common in patients with uremia) in some cases hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic seizures.From the metabolic: may decrease the concentration of serum ferritin in patients with uremia can hyperkalemia and hyperphosphatemia.Local reactions: possible redness, burning, mild or moderate pain at the injection site (often arise when s/to the introduction).Allergic reactions: mild or moderately severe skin rash, hives, itching, angioedema, eczema.Other: thrombocytosis in some cases thrombosis of the shunt (in patients, on hemodialysis, with a tendency to hypotension or aneurysm, stenosis) symptoms associated with respiratory failure or unstable AD immune response (induction of formation of antibodies with the development of partial red cell aplasia or not), exacerbation of porphyria.

Contra – indications: partial red cell aplasia after earlier treatment with any erythropoietin – uncontrolled hypertension – inability to perform adequate anticoagulant therapy – the period within 1 month after myocardial infarction – unstable angina – increased risk of deep vein thrombosis and thromboembolism in the framework of the program predeposit blood collection before the surgery, porphyria- hypersensitivity to the drug.With caution should appoint drug patients with thrombosis (history), with malignant neoplasms, sickle-cell anemia, in patients with moderate anemia without iron deficiency, in patients with refractory anemia, epilepsy and chronic liver failure.

Pregnancy and lactation:Since the experience of using epoetin alpha during pregnancy and lactation in humans is insufficient, Epocrin should be granted only in cases where the expected benefit of therapy for mother exceeds potential risk for fetus or infant.

Special instructions:When using epoetin Alfa in women of postreproductive age may resume menstruation. The patient should be warned of the possibility of pregnancy and the need to use reliable methods of contraception before therapy.During treatment necessary to monitor weekly AD, conduct a General analysis of blood, including determination of the hematocrit, platelet and ferritin. In patients with uremyei, on hemodialysis, due to the increase in hematocrit often need to increase the dose of heparin, and it is necessary to timely prevention of thrombosis and early revision of the shunt.In the pre – and postoperative period, hemoglobin should be monitored more frequently if its original level was less than 140 g/L. it Must be borne in mind that epoetin Alfa does not replace a blood transfusion, but reduces the volume and frequency of its application. In patients with controlled arterial hypertension or thrombotic complications may require increasing doses of antihypertensive and/or anticoagulant drugs. With the development of hypertensive crisis emergency treatment is carried out, epoetinum alpha treatment in such cases should be suspended.When assigning apocrine patients with hepatic insufficiency may slow its metabolism and a significant increase in erythropoiesis. The safety of epoetin alpha in this category of patients is not established.We cannot exclude the possibility of influence epoetin alpha on the growth of certain types of tumors, including tumors of the bone marrow.You should consider the possibility that the preoperative increase of hemoglobin levels may serve as a predisposing factor to the development of thrombotic complications. Before treatment should be excluded possible causes of inadequate response to the drug (iron deficiency, folic acid, cyanocobalamin, severe poisoning by aluminium ions, concomitant infections, inflammatory processes and trauma, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adapt treatment.Most patients with uremia, cancer and HIV-infected, the level of ferritin in plasma is reduced simultaneously with an increase in hematocrit. The level of ferritin to determine during the course of treatment. If it is less than 100 ng/ml, it is recommended that replacement therapy with iron preparations for oral administration of the rate of 200-300 mg/day (for children is 100-200 mg/day). Premature infants are iron preparations for oral administration at a dose of 2 mg/day should be appointed as early as possible. Patients who donate autologous blood and are in a pre – or postoperative period, should also receive appropriate therapy with iron preparations in a dose of 200 mg/day.In patients with uremia correction of anemia epoetin alpha can cause improved appetite and increased intake of potassium and proteins. In this regard, may require a periodic change of parameters of hemodialysis to maintain the level of urea, creatinine and potassium in the normal range. These patients also need to monitor the level of electrolytes in the blood serum.It should be borne in mind the possibility of reducing the AD at the beginning of therapy. Given the potential for a more pronounced effect apocrine, its dose should not exceed the dose of recombinant erythropoietin, which was used in the previous course of treatment. During the first two weeks, the dose is not changed, estimating the ratio of dose/response. After that, a dose can be reduce or increase according to the above scheme.Effects on ability to drive vehicles and management mekhanizmami the period of treatment to determine the optimal maintenance dose for patients with uremia should avoid activities potentially hazardous activities, require high concentration and high speed of psychomotor reactions.

Overdose: Symptoms: may increase side effects.Treatment: symptomatic therapy. At a high hemoglobin level and hematocrit are shown bleeding.

Drug interactions:At simultaneous application apocrine with cyclosporine increases the binding of the latter with the cell (you may need to adjust the dose of cyclosporine).Based on currently available experience, clinical application apocrine found no evidence of its pharmacological incompatibility with other drugs. However, to avoid potential incompatibility or loss of activity of apocrine cannot be mixed with solutions of other drugs.

Terms and conditions of storage: the Drug should be stored at 2° to 8°C. shelf Life – 2 years.