Epokrin - instructions for use, doses, side effects, contraindications

Active ingredient: Epoetin alfa (recombinant human erythropoietin), REPOETIN-SP: 1000 ME, 2000 ME, 4000 ME or 10,000 ME; auxiliary components: albumin, solution for infusions 10% in terms of dry albumin 2,500 mg, sodium citrate pentasecylhydrate 5,800 mg or sodium citrate dihydrate 4,776 mg, sodium chloride 5,840 mg, citric acid monohydrate 0.057 mg, water for injection up to 1 ml.

Description:

Transparent colorless liquid.

Pharmacotherapeutic group:hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:Epoetin alfa-glycoprotein, specifically stimulating erythropoiesis, activates the mitosis and maturation of erythrocytes from the progenitor cells of the erythrocyte series. Recombinant epoetin alfa is synthesized in mammalian cells in which a gene encoding human erythropoietin is inserted. By its composition, biological and immunological properties epoetin alfa is identical to natural human erythropoietin. The introduction of epoetin alfa leads to an increase in hemoglobin and hematocrit, an improvement in the blood supply of tissues and the work of the heart. The most pronounced effect of the use of epoetin alfa is observed in anemia caused by chronic renal insufficiency. In very rare cases, with the long-term use of Erythropoietin for the therapy of anemic conditions, the formation of neutralizing antibodies to erythropoietin may be observed with the development of partial red cell aplasia or without it

Pharmacokinetics:

With intravenous administration of epoetin alfa in healthy individuals and patients with uremia, the half-life period is 5-6 hours. With subcutaneous administration of epoetin alfa, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 18 hours after administration, the half-life is 16-24 h. The bioavailability of epoetin alfa with subcutaneous injection is 25-40%.

Indications:

Anemia in patients with chronic renal failure, including those on hemodialysis.

Prevention and treatment of anemia in patients with solid tumors, anemia in which was the result of anti-tumor therapy. Prevention and treatment of anemia in HIV-infected patients (AIDS) caused by zidovudine.

Prevention and treatment of anemia in patients with multiple myeloma, non-Hodgkin's lymphoma, low-grade, chronic lymphocytic leukemia.

Treatment and prevention of anemia in premature infants born with a low body weight of up to 1.5 kg.

To reduce the volume of blood transfused with extensive surgical interventions and acute blood loss.

Contraindications:

Hypersensitivity to the drug or its components, partial red cell aplasia after previous therapy with any erythropoietin, uncontrolled arterial hypertension, inability to conduct adequate anticoagulant therapy, myocardial infarction within a month after the event, unstable angina or increased risk of deep vein thrombosis and thromboembolism within predreezopotnoy program for collecting blood before surgery, porphyria.

Carefully:

In patients with thrombosis (in the anamnesis), with malignant neoplasms, with sickle cell disease, in patients with moderate anemia without iron deficiency, in patients with refractory anemia, epilepsy and chronic hepatic insufficiency.

Since there is no sufficient experience of using erythropoietin in pregnancy and lactation, epoetin alfa should be prescribed only if the expected benefits from its use exceed the possible risk to the fetus and the mother.

Dosing and Administration:

Treatment of anemia in patients with chronic renal failure: Epokrin® is administered subcutaneously or intravenously.

Patients who are on hemodialysis, the drug is injected through the arteriovenous shunt at the end of the dialysis session. When the method of administration is changed, the drug is administered in the previous dose, then, if necessary, the dose is corrected (with a subcutaneous route of administration of the drug Epokrin®, in order to achieve the same therapeutic effect, a dose of 20-30 % less than with intravenous administration). Treatment with Epokrin® consists of two steps:

1. Correction phase: When subcutaneously injected with Epokrin®,the initial single dose is 30 IU / kg 3 times a week. With the intravenous administration of the drug Epokrin®, the initial single dose is 50 IU / kg. The correction period lasts until the optimal hemoglobin level is reached (100-120 g / l in adults and 95-110 g / l in children) and hematocrit (30-35%). These indicators need to be monitored weekly. The following situations are possible:

1) The hematocrit rises from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved.

2) The growth rate of hematocrit is less than 0.5% per week. In this case it is necessary to increase the single dose by 1.5 times.

3) The growth rate is more than 1.0 % in Week. In this case, it is necessary to reduce the single dose of the drug by a factor of 1.5.

4) The hematocrit remains low or decreases. Required

analyze the causes of resistance.

The effectiveness of therapy depends on a properly selected

individual treatment regimen.

2. Stage of maintenance therapy: To maintain hematocrit at 30-35% dose Epokrin ®, used in the correction phase should be reduced by 1.5 times. Then, the maintenance dose of the drug is selected individually, taking into account the dynamics of hematocrit and hemoglobin.After stabilization of hemodynamic indicators, it is possible to switch to the administration of the drug Epokrin® once every 1-2 weeks.

Prevention and treatment of anemia in patients with solid tumors: Before the start of treatment it is recommended to carry out a determination of the level of endogenous erythropoietin. When the serum erythropoietin concentration is less than 200 IU / ml, the initial dose of Epokrin® is 150 IU / kg for the intravenous route. With the subcutaneous route of administration, the initial dose of Epokrin® can be reduced to UOME / kg. If there is no response, an increase in the dose to 300 IU / kg is possible. Further increase in the dose seems inappropriate. It is not recommended to appoint erythropoietin to patients with an endogenous erythropoietin content in the serum above 200 IU / ml.

Prevention and treatment of anemia in patients with HIV infection: Intravenous administration of the drug Epokrin® at a dose of 100-150 IU / kg 3 times a week is effective in HIV patients receiving zidovudine, provided that the serum endogenous erythropoietin level of the patient is less than 500 IU / ml and the dose of zidovudine is less than 4200 mg / week.When administered subcutaneously, the dose of Epokrin® can be reduced by a factor of 1.5.

Prevention and treatment of anemia in patients with myeloma, non-Hodgkin's lymphomas of low grade and with chronic lymphocytic leukemia: In these patients, the expediency of epoetin alfa treatment is due to an inadequate synthesis of endogenous erythropoietin against the background of anemia. If the hemoglobin content is below 100 g / l and the serum erythropoietin is below 100 IU / ml, Epokrin® is administered subcutaneously at the starting dose of IOME / kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of Epoque is adjusted upwards or downwards every 3-4 weeks. If no increase in hemoglobin is observed when a weekly dose of 600 IU / kg is reached, further use of Epokrin® should be discontinued as ineffective.

Prevention and treatment of anemia in patients with rheumatoid arthritis: patients with rheumatoid arthritis observed suppression synthesis of endogenous erythropoietin under the influence of an increased concentration of pro-inflammatory cytokines.Treatment of anemia in these patients is carried out by subcutaneous administration of the drug Epokrin® at a dose of 50-75 IU / kg 3 times a week. With an increase in hemoglobin content of less than 10 g / L after 4 weeks of treatment, the dose of the drug is increased to 150-200 IU / kg 3 times a week. Further increase in the dose seems inappropriate.

Treatment and prevention of anemia in premature infants, born with low body weight: Epokrin® is administered subcutaneously at a dose of 200 IU / kg three times a week starting from day 6 of life until the hemoglobin and hematocrit targets are reached, but no more than 6 weeks.

Prevention of anemia with extensive surgical interventions and acute blood loss: Epokrin® is administered intravenously or subcutaneously three times a week at a dose of 100-150 IU / kg until the hematocrit normalizes and the hemoglobin content.

Side effects:

In some cases, flu-like symptoms (dizziness, drowsiness, fever, headache, myalgia, arthralgia) are noted at the beginning of treatment. Allergic reactions are possible, viz., A mild to moderate skin rash, hives, itching, angioedema, eczema.

From the side of the cardiovascular system, a dose-dependent increase in blood pressure can be observed,worsening of the course of arterial hypertension (most often 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.

On the part of the hematopoiesis organs thrombocytosis can be observed, in some cases - thrombosis of shunts (in patients who are on hemodialysis, especially with a tendency to arterial hypotension or having complications from arteriovenous fistula, for example, stenosis, aneurysm, etc.).

Local reactions may manifest as hyperemia, burning, mild or moderate soreness at the site of administration (most often with subcutaneous injection).

On the part of laboratory indicators, there may be a decrease in serum ferritin content, a decrease in serum levels

exchange of iron. Patients with uremia may experience hyperkalemia and hyperphosphataemia.

Other side effects may include complications associated with respiratory failure or changes in blood pressure, very rarely possible immune reactions (induction of antibody formation with the development of partial red cell aplasia or without it), exacerbation of porphyria

Overdose:

When an overdose of Epokrin ® appears effects that reflect the extreme degree of its pharmacological effect. In the case of increased blood pressure, antihypertensives are prescribed, if it is not possible to reduce pressure with antihypertensive drugs, Epokrin® therapy should be discontinued. With high hemoglobin and hematocrit bloodletting is indicated.

Interaction:

With the simultaneous use of epoetin alfa with cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding by red blood cells.

The experience of the clinical use of the drug Epokrin® to date has not revealed the facts of its pharmacological incompatibility with other medications. Nevertheless, to avoid possible incompatibility or decrease in activity, Epokrin® should not be mixed with solutions of other medications.

Special instructions:

During treatment, it is necessary to monitor blood pressure weekly and conduct a general blood test, including determination of hematocrit, platelets and ferritin.In patients with uremia who are on hemodialysis because of the increase in hematocrit, it is often necessary to increase the dose of heparin, in addition, timely prevention of thrombosis and early revision of the shunt is necessary. In the pre- and postoperative period, Hb should be monitored more often if its baseline is less than 140 g / l. It must be remembered that epoetin alfa It does not replace blood transfusion, but reduces the volume and frequency of its use. Patients with controlled arterial hypertension or with thrombotic complications may require an increase in the dose of antihypertensive and / or anticoagulant drugs. With the development of hypertensive crisis, urgent measures are taken to provide medical care to the patient, treatment with epoetin alfa should be discontinued. When epoetin alfa is prescribed, patients with hepatic insufficiency may have a slower metabolism and a marked increase in erythropoiesis. The safety of epoetin alfa in this group of patients has not been established. You can not exclude the possibility of epoetin alfa influence on the growth of some types of tumors, including bone marrow tumors.It should be taken into account the possibility that the preoperative increase in Hb can serve as a predisposing factor to the development of thrombotic complications.

Before starting treatment, the possible causes of inadequate reaction to the drug should be excluded (iron deficiency, folic acid, cyanocobalomin, severe aluminum salt poisoning, concomitant infections, inflammatory processes and trauma, latent hemorrhage, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment. In most patients with uremia, oncological and HIV-infected patients, serum ferritin content decreases simultaneously with an increase in hematocrit. The content of serum ferritin should be monitored throughout the course of treatment. If it is less than 100 ng / ml, iron therapy is recommended at the rate of 200-300 mg / day (for children 100-200 mg / day). Premature children should receive iron therapy at a dose of 2 mg / day as soon as possible. Patients who donate autologous blood and are in pre- or postoperative period should also receive adequate therapy with iron preparations in a dose up to 200 mg / day.In patients with uremia, correction of anemia with epoetin alfa can cause an improvement in appetite and an increase in absorption of potassium and proteins. In this regard, periodic correction of hemodialysis parameters may be required to maintain the levels of urea, creatinine and potassium within normal limits. These patients also need to monitor the level of electrolytes in the blood serum.

When using epoetin alfa in women of reproductive age with anemia in the background of chronic renal failure, it is possible to resume menstruation as hemoglobin normalizes. The patient should be warned about the possibility of pregnancy and the need for reliable methods of contraception before the start of therapy. During the treatment period, before the optimal maintenance dose is established, patients with uremia should avoid Occupations with potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions, because of the increased risk of high blood pressure at the beginning of therapy. Given the possible more pronounced effect of the drug Epobrin®, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment.During the first two weeks, the dose is not changed, the dose / response ratio is evaluated. After this, the dose can be reduced or increased according to the above scheme.

Form release / dosage:Solution for intravenous and subcutaneous administration of 1000 ME, 2000 ME, 4000 ME or 10,000 ME

Packaging:

By 1000 ME, 2000 ME, 4000 ME or 10,000 ME in glass ampoules, 10 ampoules in a cassette contour pack. One cassette contour pack with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of 2 to 8 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N003686 / 01

Date of registration:29.05.2009

The owner of the registration certificate:GosNII OCHB FMBA, FSUE GosNII OCHB FMBA, FSUE Russia

Manufacturer: & nbsp

GosNII OCHB FMBA FSUE Russia

Information update date: & nbsp17.11.2015

Illustrated instructions

Instructions

Epokrin® (Epocrin®)