Epoetin beta - instructions for use, dose, side effects, contraindications

Active substanceEpoetin betaEpoetin beta

Similar drugsTo uncover

Vero-epoetin

lyophilizate in / in PC

VEROPHARM SA Russia

Recormon®

solution in / in PC

Hoffmann-La Roche Ltd. Switzerland

Recormon®

lyophilizate PC

Hoffmann-La Roche Ltd. Switzerland

Epostim®

solution in / in PC

FARMAPARK, LLC Russia

Epoetin beta

solution in / in PC

MICROGEN FGUP Scientific and Production Association Russia

Erythropoietin

solution in / in PC

BINNOFARM, CJSC Russia

Dosage form: & nbspsolution for intravenous and subcutaneous administration

Composition:

1 ml contains:

Active substance:

Epoetin beta (Human recombinant erythropoietin) 500 ME or 2000 ME, or 3000 ME, or 4000 ME.

Excipients:

Albumin solution of 10% in terms of dry albumin - 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

Description:

A clear, colorless liquid.

Pharmacotherapeutic group:Hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:

Epoetin beta is a glycoprotein consisting of 165 amino acids, which, being a mitogenic factor and a differentiation hormone, promotes the formation of erythrocytes from partially determined progenitor cells of erythropoiesis.

By its composition, biological and immunological properties epoetin beta is identical to natural human erythropoietin.

The administration of epoetin beta intravenously or subcutaneously leads to an increase in the number of erythrocytes, reticulocytes and hemoglobin levels, and also increases the rate of iron incorporation (⁵⁹Fe) into cells and specifically stimulates erythropoiesis without affecting leukopoiesis.

With chronic leukocytic leukemia, the reaction to epoetin beta therapy occurs two weeks later than in patients with myeloma, non-Hodgkin's lymphomas and solid tumors.

Pharmacokinetics:

With subcutaneous administration of TC_mOh - 12-28 h, with intravenous administration - 15 min.

T_1/2with subcutaneous injection - 13-28 h, with intravenous administration - 4-12 h.

Indications:

Prevention and treatment of anemia of various genesis:

- anemia in chronic renal failure (including in patients on hemodialysis);

- Anemia in patients with solid tumors receiving chemotherapy;

- anemia in adult patients with myeloma and low-grade non-Hodgkin's lymphomas and chronic lymphocytic leukemia receiving antitumor therapy;

- with relative deficiency of endogenous erythropoietin (defined as disproportionately low relative to the degree of anemia of erythropoietin concentration in the blood serum);

- prevention of anemia in premature newborns born with a body weight of 0.750-1.5 kg to 34 weeks of gestation;

- an increase in the volume of donor blood for subsequent autotransfusion.

Contraindications:

Hypersensitivity to serum albumins, severe arterial hypertension.

When used to increase the volume of donor blood for autohemotransfusion (in addition): a previous myocardial infarction or stroke with a duration of less than 1 month, unstable angina, the risk of deep vein thrombosis and thromboembolism.

Carefully:

Pregnancy, the period of breastfeeding, refractory anemia in the presence of blast-transformed cells, thrombocytosis, epilepsy, hepatic insufficiency, moderate severe anemia (Hb 100-130 g / l or hematocrit 30-39%, without deficiency Fe), body weight less than 50 kg (to increase the volume of donor blood for subsequent autotransfusion).

Pregnancy and lactation:

There is no sufficient experience in pregnancy and breastfeeding. During pregnancy and during breastfeeding Epoetin beta should be appointed only in the event that,When the possible benefits of its use exceed the potential risk.

Dosing and Administration:

Treatment of anemia in patients with chronic renal failure: injected subcutaneously or intravenously for 2 minutes (with subcutaneous administration requires the use of smaller doses of the drug).

Patients on hemodialysis - through the arteriovenous shunt at the end of the dialysis session.

Patients who do not receive hemodialysis, preferably the drug is administered subcutaneously to avoid accidental entry into the peripheral veins.

The aim of the treatment is to achieve a hematocrit of 30-35% or to eliminate the need for blood transfusion. The weekly increase in hematocrit should not exceed 0.5%.

In patients with hypertension, cardiovascular and cerebrovascular diseases, the weekly increase in hematocrit and its weekly values should be determined individually depending on the clinical picture. For some patients, the optimal indicator is lower 30%.

Treatment is carried out in 2 stages.

Correction stage: subcutaneously, the initial dose is 20 IU / kg 3 times a week. In case of insufficient increase in hematocrit (less than 0.5% per week) every 4 weeks, the dose may increase by 20IU / kg 3 times a week. The total weekly dose can be divided into daily injections in smaller doses or administered in 1 dose.

With intravenous administration, the initial dose is 40 IU / kg 3 times a week. If there is insufficient increase in hematocrit after 4 weeks, the dose may be increased to 80 IU / kg 3 times a week. If it is necessary to further increase the dose, it can be increased by 20 IU / kg 3 times a week at a 4-week interval. Regardless of the mode of administration, the maximum dose should not exceed 720 IU / kg / week.

At a growth rate of hematocrit more than 1% per week, a single dose should be reduced.

Supportive therapy: to maintain a hematocrit at a level of 30-35%, the dose is initially reduced by 2 times the dose of the previous injection. In the future, the maintenance dose is selected for each patient individually, with an interval of 1-2 weeks, so that the hematocrit is maintained at 30-35%. With subcutaneous administration, a weekly dose can be administered in 1 dose or divided into 3 or 7 administrations per week. When the condition is stabilized, you can switch to a single injection at an interval of 2 weeks, in which case an increase in dose may be required. Treatment for life, if necessary, you can interrupt.

Prevention and treatment of anemia in cancer patients:

Patients with solid tumors receiving chemotherapy, treatment is shown for Hb before the start of chemotherapy is not higher than 130 g / l. Subcutaneously, the initial dose is 450 IU / kg / week, divided into 3 or 7 injections. With insufficient increase in Hb After 4 weeks, the dose is doubled. Treatment continues until 3 weeks after the end of chemotherapy. If during the first cycle of chemotherapy Hb, despite treatment with the drug, decreases by more than 10 g / l, further use of the drug may be ineffective. It should be avoided to increase Hb more than 20 g / l per month or above 140 g / l. As H increasesb more than 20 g / l per month, the dose is reduced by 50%. If nb exceeds 140 g / l, the drug is canceled until Hb will not decrease to 120 g / l or less, and then resume treatment at a dose of 50% of the previous weekly dose.

In patients with myeloma and low-grade non-Hodgkin's lymphomas or chronic lymphocytic leukemia the initial dose is 450 IU / kg / week. The drug is administered subcutaneously. The weekly dose can be divided into 3 or 7 injections. With insufficient increase in Hb After 4 weeks (less than 10 g / l), the dose is doubled. If after 8 weeks of treatment, Hb Do not increase by at least 10 g / l, the drug should be discarded. The maximum dose should not exceed 900 IU / kg per week.

With chronic lymphocytic leukemia treatment should continue until 4 weeks after the end of chemotherapy. The highest dose should not exceed 900 IU / kg. If for 4 weeks of treatment Hb increases by more than 20 g / l, the dose is reduced by 2 times. If nb exceeds 140 g / l, treatment should be discontinued until Hb will not reach 130 g / L or less, after which the therapy is resumed at a dose equal to 50% of the previous initial dose. Treatment should be resumed only if the most likely cause of anemia is the failure of erythropoietin.

Prevention of anemia in premature newborns: subcutaneously, in a dose of 250 IU / kg 3 times a week. The course of treatment is 6 weeks. Treatment should begin as early as possible, preferably from 3 days of life.

Children and teenagers. In children and adolescents, the dose of the drug depends on age: the smaller the age of the child, the higher the dose of epoetin beta is required. Since an individual response to the drug can not be predicted, it is advisable to start with the recommended dosing regimen (see Fig."Treatment of anemia in patients with chronic renal failure" and "Prevention of anemia in preterm infants").

Preparation of patients for fetal donation for subsequent autohemotransfusion: intravenously or subcutaneously 2 times a week for 4 weeks. In the case where the hematocrit (33% or more) allows blood sampling, the drug is administered at the end of the procedure. The dose of the drug is determined individually, depending on the patient's erythrocyte reserve and on the volume of blood required for autohemotransfusion. The highest dose should not exceed 1600 IU / kg per week with intravenous administration and 1200 IU / kg / week with subcutaneous injection. Throughout the course of treatment, the hematocrit should not exceed 48%.

Side effects:

From the side of the cardiovascular system: often - increasing blood pressure or strengthening the already available arterial hypertension, especially in the case of a rapid increase in hematocrit; hypertensive crisis with the phenomena of encephalopathy (headache, confusion, sensory and motor disorders - speech disorders, gait, up to tonic-clonic seizures),thrombosis of shunts (possibly with inadequate heparinization), especially in patients with a tendency to hypotension or with complications of arteriovenous fistula (stenosis, aneurysm), thromboembolism (no clear causal relationship with the drug has been established).

On the part of the organs of hematopoiesis: rarely - dose-dependent thrombocytosis (not exceeding the norm and disappearing with the continuation of therapy), especially after intravenous administration; rarely - the formation of neutralizing antibodies to epoetin beta with the development of partial red cell aplasia or without it.

Laboratory indicators: in patients with uremia - giperkaliemia, hyperphosphataemia. Reduction of ferritin (simultaneously with the increase in hematocrit) - mainly in premature infants, especially from the 12th to the 14th day of life; decreased serum exchange rates Fe.

Allergic reactions: rash, itching, hives; rarely anaphylactoid reactions.

Other: headache (including suddenly occurring migraine-like), rarely - influenza-like symptoms (especially at the beginning of treatment): fever, chills, headache, pain in the extremities, ossalgia, malaise; reaction at the site of administration.

Overdose:

The therapeutic index of Epoetin beta is very wide, but individual response to therapy at the beginning of treatment should be taken into account. Available excessive pharmacodynamic response, i.e. excessive erythropoiesis with life-threatening cardiovascular complications. At a high Hb it is necessary to temporarily interrupt therapy with Epoetin beta (see "Method of administration and dose"). If necessary, phlebotomy can be performed.

Interaction:

The experience of the clinical use of Epoetin beta has so far not revealed any facts of pharmacological incompatibility with other drugs.

The results of experimental studies have shown that erythropoietin does not enhance the myelotoxic effect of such cytostatics as cyclophosphamide, fluorouracil, etoposide and cisplatin.

To avoid possible incompatibilities or decreases in activity Epoetin beta Do not mix with solutions of other medications.

Special instructions:

Inadequate use of the drug by healthy people (for example, as a dope) can cause a sharp increase in hematocrit, accompanied by life-threatening complications from the cardiovascular system.

Because of the possible development of anaphylactoid reactions, the first dose of the drug should be administered under the supervision of a doctor.

Periodically monitor the hematocrit until it reaches a value of 30-35% (Hb 100-120 g / l). In the future, these indicators should be determined weekly.

Because of the increase in hematocrit, it is often necessary to increase the dose of heparin during hemodialysis. With inadequate heparinization, a blockage of the dialysis system and thrombosis of the shunts are possible, especially in patients with a tendency to hypotension or with complications of arteriovenous fistula (stenosis, aneurysm, etc.). In such patients, an early revision of the shunt and the timely prevention of thrombosis (eg, ASA) are recommended. Prior to the initiation of epoetin beta treatment, cyanocobalamin and folic acid deficiency should be excluded. it reduces the effectiveness of the drug.

A sharp increase in the concentration of Al³⁺, due to the treatment of renal insufficiency, can weaken the effectiveness of epoetin beta. The decision to use the drug in patients with nephrosclerosis, not on dialysis, must be taken individually, because in such patients, a more rapid deterioration in kidney function is not excluded.During treatment it is recommended to periodically monitor the concentration of K⁺ and phosphates in serum. When hyperkalaemia occurs, it is necessary to temporarily discontinue the drug before the concentration of K⁺.

It is recommended to control blood pressure, incl. between dialysis sessions, with a rapid increase in hematocrit, and in cancer patients, especially at the beginning of treatment. The increase in blood pressure can be stopped by drugs, in the absence of effect, a temporary break in the treatment with epoetin beta is necessary. With the development of hypertensive crisis carry out urgent measures.

In cancer patients and in patients preparing for subsequent autotransfusion and receiving epoetin beta, a higher incidence of thromboembolic complications was noted, although there was no clear causal relationship with taking the drug.

In the first 8 weeks of therapy, a weekly count of blood cells (especially platelets) is necessary. With an increase in the number of platelets by more than 150 thousand / μl from the initial value, treatment should be discontinued.

If epoetin beta prescribe before fetching autologous donor blood, one should follow the recommendations on the procedure of donation: blood can be taken only in patients with hematocrit 33% or more (or Hb not less than 110 g / l).

Particular care should be taken in patients with a body weight of less than 50 kg. The volume of blood taken at one time should not exceed 12% of the estimated volume of the patient's blood. In most cases, concomitantly with the increase in hematocrit, the concentration of serum ferritin decreases. Therefore, all patients with anemia of renal genesis and with a serum ferritin concentration of less than 100 μg / l or a transferrin saturation of less than 20% are advised to take oral medication Fe in a dose of 200-300 mg / day.

Patients with oncological and hematological diseases therapy with drugs Fe conduct on the same principles; with patients with myeloma, non-Hodgkin's lymphomas or chronic lymphocytic leukemia with transferrin saturation of less than 25%, 100 mg Fe per week intravenously.

Preterm Children with Oral Therapy Fe in a dose of 2 mg / day should be given as soon as possible (at the latest - 14 days of life).The dose of Fe is corrected depending on the concentration of serum ferritin. If it persistently persists below 100 mcg / ml or there are other signs of a deficiency of Fe, the dose of preparations of Fe should be increased to 5-10 mg / day and therapy should be performed until the symptoms of Fe deficiency are eliminated.

In patients who are preparing to donate blood for subsequent autotransfusion, as well as having an indication of a temporary deficit Fe, oral therapy with drugs Fe in a dose of 300 mg / day should be started simultaneously with epoetin beta therapy and continue until the normalization of ferritin values. If, despite oral drug substitution therapy Fe, signs of insufficiency develop Fe (ferritin concentration 20 μg / L and less or transferrin saturation less than 20%), it is necessary to consider the question of additional intravenous administration of drugs Fe.

Form release / dosage:Solution for intravenous and subcutaneous injection, 500 ME, 2000 ME, 3000 ME and 4000 ME.

Packaging:1 ml with activity 500 ME or 2000 ME, or 3000 ME, or 4000 ME in ampoules or 1 ml with an activity of 2000 ME in syringes.

For 5 or 10 ampoules in a contour cell package. One contour pack with instructions for use in a pack of cardboard.

1 syringe in a planar cell package.For 1, 5 or 6 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, dark place 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N000525 / 01

Date of registration:20.01.2012 / 15.08.2013

Expiration Date:Unlimited

The owner of the registration certificate:MICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Manufacturer: & nbsp

MICROGEN FGUP NGO Russia

Representation: & nbspMICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Epoetin beta (Epoietin beta)