Instruction for use: Epostin

Dosage form: Solution for intravenous and subcutaneous administration

Active substance: Epoetinum beta

ATX

B03XA01 Erythropoietin

Pharmacological group:

Stimulators of hemopoiesis

The nosological classification (ICD-10)

D63.0 Anemia in neoplasm: Anemia in chronic diseases; Anemia due to radiation damage; Radiation anemia; Anemia in patients with solid tumors; Pernicious anemia

D63.8 Anemia in other chronic diseases classified elsewhere: Anemia in chronic diseases; Anemia in immunological disorders; Anemia in peptic ulcer; Anemia in kidney diseases; Anemia with HIV treatment; Anemia in the background of chronic renal failure; Anemia in patients with myeloma; Symptomatic anemia; Symptomatic anemia of renal genesis; Anemia in HIV-infected patients; Renal anemia

P61.2 Anemia of prematurity: Anemia in preterm infants; Anemia of physiological preterm infants

Z100 * CLASS XXII Surgical practice: Abdominal surgery; adenomectomy; Amputation; Coronary angioplasty; Angioplasty of the carotid arteries; Antiseptic skin treatment for wounds; Antiseptic Hand; Appendectomy; atherectomy; Balloon coronary angioplasty; Vaginal hysterectomy; The coronary bypass; Interventions in the vagina and cervix; Interventions on the bladder; Intervention in the mouth; Restoration and reconstructive surgery; Hand hygiene of medical personnel; Gynecologic surgery; Gynecological intervention; Gynecological surgery; Hypovolemic shock during operations; Disinfection of purulent wounds; Disinfection of wounds edges; Diagnostic intervention; Diagnostic procedures; Cervical Diathermocoagulation; Long-surgery; Replacing the fistula catheters; Infection in orthopedic surgery; Artificial heart valve; cystectomy; Short-term outpatient surgery; Short-term operation; Short surgical procedures; Krikotireotomiya; Blood loss during surgery; Bleeding during surgery and in the postoperative period; Kuldotsentez; laser photocoagulation; laser coagulation; retinal laser coagulation; Laparoscopy; Laparoscopy in Gynecology; CSF fistula; Small gynecological operations; Small surgical procedures; Mastectomy and subsequent plastic; mediastinotomy; Microsurgical operations on the ear; Mukogingivalnye operation; suturing; Minor surgery; neurosurgical operation; Immobilization of the eyeball in ophthalmic surgery; testectomy; pancreatectomy; Perikardektomiya; The period of rehabilitation after surgery; The period of convalescence after surgery; Percutaneous transluminal coronary angioplasty; Pleural thoracentesis; Pneumonia postoperative and posttraumatic; Preparation for surgical procedures; Preparation for surgery; Preparation of the surgeon's hands before surgery; Preparation of the colon for surgical procedures; Postoperative aspiration pneumonia in neurosurgical and thoracic surgery; Postoperative nausea; Postoperative bleeding; postoperative granuloma; postoperative shock; The early postoperative period; myocardial revascularization; Radiectomy; gastric Resection; bowel resection; uterine Resection; liver Resection; enterectomy; Resection of part of the stomach; Reocclusion of the operated vessel; Bonding tissues during surgical procedures; Removal of sutures; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity; Condition after gastrectomy; Status after resection of the small intestine; Condition after tonsillectomy; Condition after removal of the duodenum; Condition after phlebectomy; Vascular surgery; Splenectomy; Sterilization of surgical instruments; Sterilization of surgical instruments; sternotomy; Dental surgery; Dental intervention in periodontal tissues; strumectomy; Tonsillectomy; Thoracic surgery; Thoracic surgery; total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinektomiya; Removal of a tooth; cataract surgery; Removal of cysts; tonsillectomy; Removal of fibroids; Removing the mobile primary teeth; Removing polyps; Removing broken tooth; Removal of the uterus body; Removal of sutures; Fistula likvoroprovodyaschih ways; Frontoetmoidogaymorotomiya; Surgical infection; Surgical treatment of chronic limb ulcers; Surgery; The surgery in the anal area; The surgery on the colon; Surgical practice; The surgical procedure; Surgical interventions; Surgery on the gastrointestinal tract; Surgical procedures on the urinary tract; Surgical procedures on the urinary system; Surgical intervention of the genitourinary system; Surgical procedures on the heart; Surgical manipulation; surgery; Surgery on the veins; Surgical intervention; Vascular surgery; Surgical treatment of thrombosis; Surgery; cholecystectomy; Partial gastric resection; hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass; tooth Extirpation; Extirpation of milk teeth; pulpectomy; pulsative cardiopulmonary bypass; tooth Extraction; teeth Extraction; cataract extraction; Electrocoagulation; endourological intervention; episiotomy; Etmoidotomiya; Complications after tooth extraction

Composition and release form

Solution for intravenous and subcutaneous injection 1 amp., Fl. Or a syringe

Recombinant human erythropoietin 1000 IU / ml; 2000 IU / mL; 4000 IU / ml; 5000 IU / mL; 10,000 IU / mL

Auxiliary substances: plasbumin 20 * - 2,5 mg; Sodium citrate dihydrate 5.8 mg; Sodium chloride - 5.84 mg; Citric acid - 0.057 mg; Water for injection - up to 1 ml

* Human albumin, sodium caprylate, acetyltryptophan

In ampoules, vials or syringes of 1 ml (1000 IU, 2000 IU, 4000 IU, 5000 IU, 10,000 IU); In a pack of cardboard 5 or 10 ampoules; 1 or 5 bottles; 1 or 3 syringes.

Description of dosage form

Clear colorless liquid.

Pharmachologic effect

Mode of action - Erythropoietic.

Pharmacodynamics

Epoetin beta-glycoprotein, specifically stimulating erythropoiesis, activates the mitosis and maturation of erythrocytes from the progenitor cells of the erythrocyte series. Recombinant epoetin beta is synthesized in mammalian cells in which a gene encoding human erythropoietin is inserted. In its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The introduction of epoetin beta 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 epoetin beta is observed in anemia caused by chronic renal failure. 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 IV the introduction of epoetin beta in healthy individuals and patients with uremia T1 / 2 - 5-6 hours With SC the introduction of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 18 hours after administration, T1 / 2 - 16-24 hours Bioavailability of epoetin beta with n / k introduction - 25-40%.

Indication of the drug Epostin

Anemia in patients with chronic renal failure, incl. Who are on hemodialysis;

Prevention and treatment of anemia in patients with solid tumors, which is a consequence of the antitumor therapy;

Prevention and treatment of anemia in HIV-infected patients caused by zidovudine;

Prevention and treatment of anemia in patients with myeloma, low-grade non-Hodgkin's lymphomas, chronic lymphocytic leukemia, in patients with rheumatoid arthritis;

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

Preparation of patients for surgical interventions with a planned large blood loss.

Contraindications

Hypersensitivity to the drug or its components;

Partial red cell aplasia after previous therapy with an erythropoietin;

Uncontrolled arterial hypertension;

Impossibility of conducting adequate anticoagulant therapy;

Myocardial infarction and acute violation of cerebral circulation - within a month after the event;

Unstable angina or an increased risk of deep vein thrombosis and thromboembolism within the pre-op program of blood collection before surgery;

Porphyria.

Carefully:

Thrombocytosis;

Moderate anemia (Hb - 100-130 g / l or hematocrit - 30-39%, without deficiency of Fe);

Thrombosis (in the anamnesis);

Sickle-cell anemia;

Malignant neoplasms;

Refractory anemia;

epilepsy;

Chronic hepatic impairment;

Patients with a body weight <50 kg (to increase the volume of donor blood for subsequent autotransfusion).

Application in pregnancy and breastfeeding

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

Side effects

From the side of the cardiovascular system: there may be a dose-dependent increase in blood pressure, a worsening of the course of arterial hypertension (most often in patients with uremia), in some cases - hypertensive crisis, a sharp increase in BP with symptoms of encephalopathy (headache, confusion) and generalized tonic- Clonic convulsions. To correct the increase in blood pressure, antihypertensives are prescribed or the dose of Epostin® is reduced.

Patients with uremia may develop hyperkalemia, hyperphosphataemia. As a therapeutic measure appoint the appropriate diet.

On the part of the circulatory system: there may be thrombocytosis, in some cases - shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or an aneurysm, stenosis, etc.). The use of Epostin® can lead to the development of the syndrome of increased blood viscosity (acute encephalopathy, reduction of hemodialysis effectiveness), increase in the level of creatinine and urea of blood (dialysis time increase, dialysis index - KT / Y 1.4-1.6). Rarely, skin allergic reactions to the components of the drug are noted - rash, hives, itching, anaphylactoid reactions, reactions at the injection site. Local reactions may manifest as hyperemia, burning, mild or moderate soreness at the site of administration (often occur with SC the introduction).

In rare cases, mainly at the beginning of treatment, it is possible to develop an influenza-like syndrome (fever, chills, headaches, weakness, arthralgia, myalgia). Very rarely possible immune reactions (induction of the formation of antibodies with the development of partial red cell aplasia or without it), exacerbation of porphyria.

Interaction

With the simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter because of the increase in its binding by erythrocytes. The experience of the clinical use of Epostin® has so far not revealed the facts of its pharmacological incompatibility with other drugs. Nevertheless, to avoid possible incompatibility or decrease in activity, Epostin® should not be mixed with solutions of other medications.

Dosing and Administration

IV, SC.

Treatment of anemia in patients with chronic renal failure: IV or SC. 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 the dose is corrected if necessary (in the case of the epistima® administration method, a 20-30% dose is required to achieve the same therapeutic effect than with the IV introduction). Treatment with Epostin® involves two stages.

1. Correction phase: with n / to the introduction of Epostin® the initial single dose is 30 IU / kg 3 times a week. With iv introduction of Epostin® 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% per week. In this case, the dose is not changed until the optimal values are achieved.

2. The rate of growth of hematocrit <0.5% per week. In this case, it is necessary to increase the single dose by a factor of 1.5.

3. Rate of increase> 1% per 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. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on a properly selected individual treatment regimen.

2. The stage of maintenance therapy: to maintain hematocrit at 30-35% dose Epostin®, achieved at the stage of correction, should be reduced by 1.5 times. Then, the maintenance dose of Epostin® is selected individually, taking into account the dynamics of the hematocrit and hemoglobin. After stabilization of hemodynamic indicators, a transition to the administration of Epostin® 1 every 1-2 weeks is possible.

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. At the concentration of erythropoietin in the serum <200 IU / l, the initial dose of Epostin® makes up to 150 IU / kg 3 times a week for IV administration. With the n / a method of administration, the initial dose of Epostin® can be reduced to 100 IU / kg 3 times a week. If there is no response, an increase in the dose to 300 IU / kg is possible 3 times a week. Further increase in the dose seems inappropriate. It is not recommended to appoint erythropoietin to patients with an endogenous erythropoietin content in the serum> 200 IU / L.

During therapy with Epostin®, it is undesirable to increase the hemoglobin level by more than 20 g / l per month or above 140 g / l. If the hemoglobin level is increased by more than 20 g / L per month, Epostin® dose should be halved. If the hemoglobin level exceeds 140 g / l, Epostim® is canceled until the hemoglobin level decreases to ≤120 g / l, after which the treatment resumes at a dose equal to 50% of the dose at which the drug was withdrawn.

Prevention and treatment of anemia in patients with HIV infection: intravenous administration of Epostin® in a dose of 100-150 IU / kg 3 times a week is effective in HIV-infected patients receiving zidovudine therapy, provided that the level of endogenous erythropoietin in serum Of the patient <500 IU / L, and the dose of zidovudine is <4200 mg per week. With SC the introduction, the dose of Epostin® can be reduced by a factor of 1.5.

Prevention and treatment of anemia in patients with myeloma, low-grade non-Hodgkin's lymphoma, and chronic lymphocytic leukemia: in these patients, the Feasibility of epoetin is the treatment for endogenous erythropoietin against the background of anemia. If hemoglobin content <100 g / l and serum erythropoietin <100 IU / L Epostin® is administered sc, at a starting dose of 100 IU / kg 3 times a week. Laboratory monitoring of hemodynamic parameters. If necessary, the dose of Epostin® is adjusted upwards or downwards every 3-4 weeks. If after 4 weeks, the hemoglobin level rises by 10 g / l, the treatment is continued at the previous dose. If after 4 weeks the hemoglobin rises by less than 10 g / l, an increase in the dose to 300 IU / kg 3 times a week is possible. If the level of hemoglobin did not increase by at least 10 g / l after 8 weeks of therapy with Epostin®, it is unlikely that the effect will develop, the drug should be discontinued. If the hemoglobin level increases by more than 20 g / l for 4 weeks of therapy, the dose of Epostin® should be halved. If the hemoglobin level exceeds 140 g / L, Epostin® treatment is suspended until the hemoglobin level drops to ≤130 g / L, after which the therapy continues at a dose equal to 50% of that at which the therapy was suspended.

With chronic lymphocytic leukemia, Epostin® treatment lasts for up to 4 weeks after the end of chemotherapy. The maximum dose should not exceed 300 IU / kg 3 times a week.

Treatment should be resumed only if the most likely cause of anemia is insufficient production of endogenous erythropoietin.

Prevention and treatment of anemia in patients with rheumatoid arthritis: In patients with rheumatoid arthritis, the synthesis of endogenous erythropoietin is suppressed under the influence of an increased concentration of pro-inflammatory cytokines. The treatment of anemia in these patients is carried out by Epostin® with an administration 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, Epostin® dose is increased to 150-200 IU / kg 3 times a week. Further increase in the.

Treatment and prevention of anemia in preterm infants born with low body weight: for the prevention and treatment of anemia in premature infants, the administration of Epotin® should begin as soon as possible, preferably from the 3rd day of life at a dose of 200 IU / Kg body weight IV or SC 3 times a week and last no more than 6 weeks. The effect of the drug in preterm neonates who have already undergone blood transfusion is slightly less than those who did not undergo blood transfusion.

Preparation of patients for surgical interventions with a planned large blood loss: the recommended dose of Epostin® is 450-600 IU / kg once a week for three weeks before the operation (21, 14 and 7 days before surgery) and on the day of Surgery. If it is necessary to shorten the period of the preoperative preparation, it is possible to apply Epostin® in a dose of 300 IU / kg p / c daily 10 days before the operation, on the day of the operation and 4 days after the operation.

If the hemoglobin level is in the pre-operative period is ≥150 g / l, Epostin should be discontinued.

All patients should receive oral iron at a dose of 200 mg / day throughout the course of treatment. If possible, additional oral administration of iron preparations should be provided prior to the initiation of Epothym® therapy to create a depot of iron in the patient's body.

Overdose

Symptoms: There may be an increase in side effects.

Treatment: symptomatic, with a high level of hemoglobin and hematocrit bloodletting is indicated.

Special instructions

During treatment, it is necessary to monitor the 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, hemoglobin should be monitored more often if its baseline level is <140 g / l. It should be remembered that epoetin beta does not replace blood transfusion, but reduces the volume and frequency of its use. Patients with controlled arterial hypertension or with thrombotic complications may need to increase the dose of antihypertensive and / or anticoagulant drugs. With the development of the hypertensive crisis, urgent measures are taken to provide medical care to the patient, treatment with epoetin beta should be discontinued. When prescribing epoetin beta, patients with hepatic insufficiency may have a slower metabolism and a marked increase in erythropoiesis. The safety of the use of epoetin beta in this group of patients is not established. It is also possible to exclude the possibility of the influence of epoetin beta on the growth of some types of tumors, incl. Tumors of the bone marrow. One should take into account the possibility that preoperative hemoglobin elevation can serve as a predisposing factor to the development of thrombotic complications. Before starting treatment, the possible causes of inadequate response to the drug should be excluded (iron deficiency, folic acid, cyanocobalamin, severe Al3 + poisoning, concomitant infections, inflammatory processes and trauma, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust the treatment. In most patients with uremia, oncological and HIV-infected patients, the serum ferritin level decreases simultaneously with the increase in hematocrit. The level of ferritin should be determined throughout the course of treatment. If it is <100 ng / ml, substitution therapy with iron for oral administration is recommended at the rate of 200-300 mg / day (for children 100-200 mg / day). For preterm infants, oral iron therapy at a dose of 2 mg / day should be given as soon as possible. Patients who take 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 beta may 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 K + within normal limits. These patients also need to monitor the level of electrolytes in the blood serum. When using epoetin beta in women of reproductive age, it is possible to resume menstruation. 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 practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, because of the increased risk of increased blood pressure at the beginning of therapy. Given the possible more pronounced effect of Epostim®, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first 2 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.

Storage conditions of the drug Epostin

In a dry, the dark place at a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life of the drug Epostin

2 years.

Do not use after the expiry date printed on the package.