pharmachologic effect
Hematopoiesis stimulator. Recombinant epoetin beta is a glycoprotein synthesized in mammalian cells into which the gene encoding human erythropoietin is embedded. Its composition, biological and immunological properties are identical to endogenous human erythropoietin.
Specifically stimulates erythropoiesis, activates mitosis and maturation of red blood cells from the precursor cells of the erythrocyte series. The administration of the drug leads to an increase in hemoglobin and hematocrit levels, improvement of blood supply to tissues and heart function.
The most pronounced effect from the use of Vero-epoetin is observed in anemia caused by chronic renal failure.
Indications
Prevention and treatment of anemia:
- in patients with chronic renal failure (including those on hemodialysis);
— in patients with solid tumors during antitumor therapy;
- for HIV infection (caused by the use of zidovudine);
- with multiple myeloma;
- for low-grade non-Hodgkin's lymphomas;
— for chronic lymphocytic leukemia;
- for rheumatoid arthritis;
- in premature newborns born weighing less than 1.5 kg.
To reduce the volume of blood transfused during major surgical interventions and acute blood loss.
Contraindications
- partial red cell aplasia after previous therapy with any erythropoietin;
- uncontrolled arterial hypertension;
— impossibility of carrying out adequate anticoagulant therapy;
- myocardial infarction within a month after the event;
- unstable angina;
- increased risk of deep vein thrombosis and thromboembolism as part of a pre-deposit blood collection program before surgery;
- porphyria;
- hypersensitivity to the drug or its components.
The drug should be prescribed with caution in case of thrombosis (history), malignant neoplasms, sickle cell anemia, moderate anemia without iron deficiency, refractory anemia, epilepsy and chronic liver failure.
Vero-Epoetin liof. d/r-ra for intravenous and subcutaneous injection. 2000 IU fl. glass No. 10
Indications
Symptomatic anemia in chronic kidney disease in patients on dialysis; symptomatic anemia of renal origin in patients not yet receiving dialysis; treatment of symptomatic anemia in adult patients with solid and hematologic non-myeloid tumors receiving chemotherapy; prevention of anemia in premature newborns born with a body weight of 750-1500 g before the 34th week of pregnancy. Increasing the volume of donor blood intended for subsequent autotransfusion. The reported risk of thromboembolic events should be taken into account. Use for this indication is indicated only in patients with moderate anemia (Hb 100-130 g/l (6.21-8.07 mmol/l), without iron deficiency), if it is impossible to obtain a sufficient amount of banked blood, and planned major elective surgery may require extensive blood volume (>4 units for women or >5 units for men).
pharmachologic effect
Recombinant human erythropoietin (purified glycoprotein), consisting of 165 amino acids, which, as a mitogenic factor and differentiation hormone, promotes the formation of red blood cells from partially determined erythropoiesis precursor cells. Recombinant epoetin beta, obtained by genetic engineering, is identical in its amino acid and carbohydrate composition to human erythropoietin.
Epoetin beta after intravenous and subcutaneous administration increases the number of red blood cells, reticulocytes and hemoglobin levels, as well as the rate of incorporation of iron (59Fe) into cells, specifically stimulates erythropoiesis without affecting leukopoiesis. No cytotoxic effect of epoetin beta on human bone marrow or skin cells has been detected.
Drug interactions
With the simultaneous use of drugs that affect hematopoiesis (for example, iron supplements), the stimulating effect of epoetin beta may be enhanced.
Epoetin beta should not be mixed with solutions of other drugs.
Dosage regimen
Doses, regimen and duration of treatment are determined individually and depend on the severity of anemia, the severity of the patient’s condition, the nature of the disease, and the patient’s age. Injected subcutaneously and intravenously.
Contraindications for use
History of hypersensitivity to epoetin beta; uncontrolled arterial hypertension; myocardial infarction or stroke within the previous month, unstable angina or increased risk of deep vein thrombosis (with a history of venous thromboembolism) - when prescribed to increase the volume of donor blood for autohemotransfusion.
Carefully
Refractory anemia in the presence of blast-transformed cells, thrombocytosis, epilepsy and chronic liver failure. Body weight less than 50 kg to increase the volume of donor blood for subsequent autotransfusion.
Use in children
It can be used in children according to indications, in doses and regimens recommended according to age.
When treating anemia associated with chronic kidney disease, epoetin beta should not be used in children under 2 years of age.
Restrictions for children
Use with caution
Restrictions for elderly patients
No data
Use for liver dysfunction
Use with caution in chronic liver failure.
Restrictions for liver dysfunction
Use with caution
Use during pregnancy and breastfeeding
During pregnancy and breastfeeding, epoetin beta is used only when the expected benefit to the mother outweighs the potential risk to the fetus or child.
In experimental studies
no teratogenic effect was detected.
Restrictions when breastfeeding
Use with caution
Restrictions during pregnancy
Use with caution
Use for renal impairment
Use with caution in patients with nephrosclerosis who are not receiving hemodialysis, as a more rapid deterioration of renal function is possible.
Restrictions for impaired renal function
Use with caution
special instructions
During therapy with epoetin beta, platelet counts, hematocrit and hemoglobin should be regularly monitored.
Epoetin beta should be used with caution in refractory anemia in the presence of blast-transformed cells, epilepsy, thrombocytosis and chronic liver failure.
The therapeutic effectiveness of epoetin beta may be reduced if there is a deficiency of iron, folic acid, or vitamin B12.
Iron deficiency should be excluded before starting treatment with epoetin beta, as well as throughout the entire period of therapy. If necessary, additional therapy with iron supplements may be prescribed in accordance with clinical recommendations.
The effectiveness of treatment decreases with iron deficiency in the body, with infectious and inflammatory diseases, and hemolysis.
The possibility of epoetin beta influencing the growth of certain types of tumors, especially bone marrow malignancies, cannot be completely excluded.
While using epoetin beta, it is necessary to monitor blood pressure levels, paying attention to the occurrence or worsening of unusual headaches. This may require adjustment of therapy or prescription of antihypertensive drugs.
Use with caution for epilepsy, thrombocytosis, liver failure, vascular insufficiency, and malignant neoplasms; in patients with nephrosclerosis not receiving hemodialysis, since a more rapid deterioration of renal function is possible.
The decision to use epoetin beta in patients with nephrosclerosis not receiving dialysis must be made individually, since the possibility of a more rapid deterioration of renal function cannot be completely excluded. In most cases, along with an increase in hemoglobin, the concentration of ferritin in the serum decreases. Ferritin levels must be determined throughout the course of treatment. If it is less than 100 ng/ml, iron replacement therapy is recommended.
Patients who donate autologous blood and are in the pre- or postoperative period should also receive additional adequate amounts of iron until ferritin levels normalize.
Side effect
From the cardiovascular system:
arterial hypertension, hypertensive crisis, shunt thrombosis.
From the nervous system:
encephalopathy (more often during hypertensive crises), headache, confusion.
From the blood coagulation system:
rarely - thrombocytosis, thrombotic complications.
From the hematopoietic system:
partial red cell aplasia (PRCA).
Allergic reactions:
rarely - skin rash, itching, urticaria, anaphylactoid reactions.
For the skin and subcutaneous tissues:
Stevens-Johnson syndrome.
From the laboratory parameters:
a decrease in plasma ferritin with a simultaneous increase in hemoglobin, an increase in the level of potassium and phosphates in plasma.
Other:
flu-like syndrome, local reactions.
Side effects
From the body as a whole: sometimes (at the beginning of treatment) - flu-like symptoms (dizziness, drowsiness, fever, headache, myalgia, arthralgia).
Allergic reactions: urticaria, itching, angioedema.
Immunopathological reactions: in some cases (with long-term use) - the formation of neutralizing antibodies to erythropoietin with or without the development of partial red cell aplasia.
Dermatological reactions: mild or moderate skin rash, eczema.
From the cardiovascular system: dose-dependent increase in blood pressure, worsening of arterial hypertension (most often in patients with uremia); in some cases - a hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic convulsions.
From the blood coagulation system: thrombocytosis; in some cases - shunt thrombosis (in patients on hemodialysis, with a tendency to hypotension or with an aneurysm, stenosis).
Metabolism: decreased serum ferritin; in patients with uremia - hyperkalemia and hyperphosphatemia.
Local reactions: hyperemia, burning, mild or moderate pain at the injection site (more often occur with subcutaneous administration).
Other: breathing disorders; in some cases - exacerbation of porphyria.
Vero-Epoetin 2000ME lyof for prepared solution for injection No. 10
Dosage
2000 IU
Active substance
Epoetin beta
Manufacturer
LENS-Pharm LLC (Russia)
Shelf life
2 years
Storage conditions
In a dry place, protected from light, at a temperature of 2–8 °C
Registration certificate number
LS-000258 dated 04/29/2005
Description of the dosage form
Porous amorphous mass of white or almost white color.
Pharmacokinetics
With intravenous administration of Vero-Epoetin in healthy individuals and patients with uremia, T1/2 is 5–6 hours. With subcutaneous administration of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 28 hours after administration, T1/2 - 13-28 hours. With intravenous administration, T1/2 - 4-12 hours. Bioavailability of Vero-Epoetin with subcutaneous administration - 25-40%.
Pharmacodynamics
Epoetin beta is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of red blood cells from erythrocyte precursor cells. Recombinant epoetin beta is synthesized in mammalian cells into which the gene encoding human erythropoietin is integrated. In its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The administration of epoetin beta leads to an increase in hemoglobin and hematocrit, improving blood supply to tissues and heart function. The most pronounced effect of the use of epoetin beta is observed in anemia caused by chronic renal failure. In very rare cases, with long-term use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin with or without the development of partial red cell aplasia may be observed.
Contraindications
Hypersensitivity to the drug or its components, partial red cell aplasia after previous therapy with any erythropoietin, uncontrolled hypertension, failure to receive adequate anticoagulant therapy, myocardial infarction within a month after the event, unstable angina or increased risk of deep vein thrombosis and thromboembolism as part of a pre-deposit blood collection program before surgery, porphyria.
Carefully
- thrombosis (history), malignant neoplasms, sickle cell anemia, moderate anemia without iron deficiency, refractory anemia, epilepsy and chronic liver failure, pregnancy, breastfeeding.
Use during pregnancy and breastfeeding
Since there is no sufficient experience with the use of erythropoietin during pregnancy and breastfeeding, Vero-Epoetin should be prescribed only if the expected benefits from its use outweigh the possible risk to the fetus, child and mother.
Directions for use and doses
PC
or
i.v.
_
Treatment of anemia in patients with chronic renal failure:
subcutaneously or intravenously, for patients on hemodialysis - through an arteriovenous shunt at the end of the dialysis session. When changing the route of administration, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Vero-Epoetin, to achieve the same therapeutic effect, a dose of 20–30% less is required than with intravenous administration). Treatment with Vero-Epoetin includes two stages:
I. Correction stage:
with subcutaneous administration of Vero-Epoetin, the initial single dose is 30 IU/kg 3 times a week. When administering Vero-Epoetin intravenously, the initial single dose is 50 IU/kg. The correction period lasts until the optimal level of hemoglobin (100–120 g/l in adults and 95–110 g/l in children) and hematocrit (30–35%) is achieved. These indicators must be monitored weekly. The following situations are possible:
1) Hematocrit increases from 0.5 to 1% per week. In this case, the dose is not changed until optimal values are achieved.
2) The rate of increase in hematocrit is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times.
3) Growth rate of more than 1% per week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times.
4) Hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.
The effectiveness of therapy depends on a correctly selected individual treatment regimen.
II. Maintenance therapy phase:
to maintain hematocrit at a level of 30–35%, the dose of Vero-Epoetin used at the correction stage should be reduced by 1.5 times. Then the maintenance dose of Vero-Epoetin is selected individually, taking into account the dynamics of hematocrit and hemoglobin.
After stabilization of hemodynamic parameters, it is possible to switch to the administration of Vero-Epoetin once every 1–2 weeks.
Prevention and treatment of anemia in patients with solid tumors:
Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of serum erythropoietin is less than 200 IU/ml, the initial dose of Vero-Epoetin for intravenous administration is 150 IU/kg. With the subcutaneous route of administration, the initial dose of Vero-Epoetin can be reduced to 100 IU/kg. If there is no response, the dose may be increased to 300 IU/kg. Further increase in dose seems inappropriate. It is not recommended to prescribe erythropoietin to patients with serum endogenous erythropoietin levels above 200 IU/ml.
Prevention and treatment of anemia in patients with HIV infection:
IV epoetin beta at a dose of 100–150 IU/kg 3 times a week is effective in HIV patients receiving Zidovudine therapy, provided that the patient's serum endogenous erythropoietin level is less than 500 IU/ml and the dose of Zidovudine is less than 4200 mg per week. With subcutaneous administration, the dose of Vero-Epoetin can be reduced by 1.5 times.
Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphomas and chronic lymphocytic leukemia:
in these patients, the advisability of treatment with epoetin beta is determined by the inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. If the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/ml, Vero-Epoetin is administered subcutaneously at a starting dose of 100 IU/kg 3 times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of epoetin beta is adjusted upward or downward every 3–4 weeks. If, upon reaching a weekly dose of 600 IU/kg, an increase in hemoglobin levels is not observed, further use of epoetin beta should be discontinued as ineffective.
Prevention and treatment of anemia in patients with rheumatoid arthritis:
in patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Treatment of anemia in these patients is carried out with Vero-Epoetin with subcutaneous administration at a dose of 50–75 IU/kg 3 times a week. If the hemoglobin content increases by less than 10 g/l, after 4 weeks of treatment, the dose of Vero-Epoetin is increased to 150–200 IU/kg 3 times a week. Further increase in dose seems inappropriate.
Treatment and prevention of anemia in premature infants born with low birth weight:
Vero-Epoetin is administered subcutaneously at a dose of 200 IU/kg 3 times a week, starting from the 6th day of life until the target hemoglobin and hematocrit values are achieved, but not more than 6 weeks.
Prevention of anemia during major surgical interventions and acute blood loss:
Vero-epoetin is administered intravenously or subcutaneously 3 times a week at a dose of 100–150 IU/kg until hematocrit and hemoglobin content normalize.
Side effects
In some cases, flu-like symptoms (dizziness, drowsiness, fever, headache, myalgia, arthralgia) are observed at the beginning of treatment.
Allergic reactions are possible, namely, mild or moderate skin rash, urticaria, itching, angioedema, eczema.
From the cardiovascular system:
a dose-dependent increase in blood pressure is possible, a worsening of arterial hypertension (most often in patients with uremia), in some cases - a hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic convulsions.
From the circulatory system:
thrombocytosis, in some cases - shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or with an aneurysm, stenosis, etc.).
Local reactions:
hyperemia, burning, mild or moderate pain at the injection site (more often occur with subcutaneous administration).
From the laboratory parameters:
decreased serum ferritin levels; in patients with uremia, hyperkalemia and hyperphosphatemia may occur.
Other:
complications associated with breathing problems or changes in blood pressure; very rarely - immune reactions are possible (induction of antibody formation with or without the development of partial red cell aplasia), exacerbation of porphyria.
Interaction
With simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding to erythrocytes. Experience in the clinical use of Vero-Epoetin to date has not revealed any evidence of its pharmacological incompatibility with other drugs. However, to avoid possible incompatibility or decreased activity, Vero-Epoetin should not be mixed with solutions of other drugs.
Overdose
Symptoms:
increased side effects.
Treatment:
symptomatic, with high levels of hemoglobin and hematocrit, bloodletting is indicated.
special instructions
During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin. In patients with uremia on hemodialysis, due to an 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 are necessary. In the pre- and postoperative period, Hb should be monitored more often if its initial level was less than 140 g/l. It must be remembered that Vero-Epoetin does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled arterial hypertension or with thrombotic complications, an increase in the dose of antihypertensive and/or anticoagulant drugs may be required. If a hypertensive crisis develops, urgent measures are taken to provide medical care to the patient; treatment with Vero-Epoetin should be interrupted. When Vero-Epoetin is prescribed to patients with liver failure, its metabolism may slow down and erythropoiesis may be markedly increased. The safety of Vero-Epoetin in this group of patients has not been established. We also cannot exclude the possibility of Vero-Epoetin influencing the growth of certain types of tumors, incl. bone marrow tumors. The possibility that a preoperative increase in Hb levels may predispose to the development of thrombotic complications should be considered. Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamin, severe Al3+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment . In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is less than 100 ng/ml, oral iron replacement therapy is recommended at a rate of 200–300 mg/day (for children 100–200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be prescribed as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements in a dose of up to 200 mg/day. In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the level of urea, creatinine and K + within normal limits. Serum electrolyte levels should also be monitored in these patients. When using epoetin beta in women of reproductive age, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy. During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy. Given the possible more pronounced effect of epoetin beta, 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 assessed. After this, the dose can be reduced or increased according to the scheme presented above.
Pharmgroups
Hematopoiesis stimulants
Pharmaceutical actions
hematopoietic
special instructions
During treatment with Vero-epoetin, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin.
In patients with uremia on hemodialysis, due to an 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 are necessary.
In the pre- and postoperative period, hemoglobin should be monitored more often if its initial level was less than 140 g/l. It must be remembered that Vero-epoetin does not replace blood transfusion, but reduces the volume and frequency of its use.
In patients with controlled hypertension or thrombotic complications, an increase in the dose of antihypertensive drugs and/or anticoagulants may be required. If a hypertensive crisis develops during emergency treatment, treatment with Vero-epoetin should be interrupted.
When Vero-epoetin is prescribed to patients with liver failure, its metabolism may slow down and erythropoiesis may be significantly increased. The safety of Vero-epoetin in this group of patients has not been established.
We also cannot exclude the possibility of interaction of Vero-epoetin on the growth of certain types of tumors, incl. bone marrow tumors.
The possibility that a preoperative increase in hemoglobin levels may predispose to the development of thrombotic complications should be considered.
Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamin, severe aluminum poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment.
In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is less than 100 ng/ml, replacement therapy with iron preparations for oral administration is recommended at the rate of 200-300 mg/day (for children 100-200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be prescribed as early as possible.
Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements in a dose of up to 200 mg/day.
In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the levels of urea, creatinine and potassium within normal limits. Serum electrolyte levels should also be monitored in these patients.
Considering the possible more pronounced effect of Vero-epoetin, 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 and the dose/response ratio is assessed. After this, the dose can be reduced or increased.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy.
Epoetin-vero 2000me 10 pcs. lyophilisate for preparing solution
pharmachologic effect
Hematopoiesis stimulator.
Composition and release form Epoetin-vero 2000me 10 pcs. lyophilisate for preparing solution
Recombinant Human Erythropoietin 1000 ME 2000 ME 4000 ME 10000 ME, low molecular weight medical polyvinylpyrrolidone (povidone), citrate-phosphate buffer to obtain a solution with a pH of 6.9.
Lyophilisate for the preparation of a solution for intravenous and subcutaneous administration 1000 IU, 2000 IU, 4000 IU or 10000 IU.
1, 5 or 10 bottles along with instructions for use in a cardboard pack.
Description of the dosage form
Porous amorphous mass of white or almost white color.
Directions for use and doses
Intravenously and subcutaneously.
A Vero-epoetin solution is prepared by adding 1 ml of physiological solution to the lyophilisate.
Treatment of anemia in patients with chronic kidney disease
Vero-epoetin is administered subcutaneously or intravenously (over 2 minutes). For patients on hemodialysis - through an arteriovenous shunt at the end of the dialysis session.
For patients not receiving hemodialysis, it is preferable to administer the drug subcutaneously to avoid puncture of peripheral veins. The goal of treatment is a hemoglobin (Hb) level of 100-120 g/l. Hb should not exceed 120 g/l. If Hb increases by more than 20 g/l (1.3 mmol/l) over 4 weeks, the dose of the drug should be reduced. In patients with arterial hypertension, cardiovascular and cerebrovascular diseases, the weekly increase in Hb and its target values should be determined individually, depending on the clinical picture. The patient should be carefully monitored in order to select the minimum dose sufficient to ensure the maximum effect of the drug.
Treatment with Vero-epoetin includes two stages:
1. Correction stage: When administering the drug Vero-epoetin subcutaneously, the initial single dose is 20 IU/kg 3 times a week. If the increase in Hb is insufficient (less than 2.5 g/l per week), the dose can be increased every 4 weeks by 20 IU/kg 3 times a week. The total weekly dose of the drug can also be divided into daily administrations. When administering Vero-epoetin intravenously, the initial dose is 40 IU/kg 3 times a week. If there is insufficient increase in Hb after a month, the dose can be increased to 80 IU/kg 3 times a week.
If necessary, the dose should be increased in the future by 20 IU/kg 3 times a week at monthly intervals.
Regardless of the route of administration, the maximum dose should not exceed 720 IU/kg per week.
2. Maintenance therapy stage: To maintain the target Hb level (100-120 g/l), the dose should first be reduced by 2 times from the previous one. Then the maintenance dose of Vero-epoetin is selected individually, with an interval of 2 or 4 weeks. When administered subcutaneously, the dose can be administered in one dose or divided into 3 or 7 administrations per week. After stabilization on the background of a single dose per week, you can switch to a single dose at a two-week interval, in which case an increase in dose may be necessary.
Treatment is usually long-term. If necessary, it can be interrupted at any time.
Prevention and treatment of anemia in patients with solid tumors
Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of serum erythropoietin is less than 200 IU/ml, the initial dose of Vero-epoetin is 150 IU/kg for intravenous administration. When administered subcutaneously, the initial dose of Vero-epoetin can be reduced to 100 IU/kg. If there is no response, the dose may be increased to 300 IU/kg. Further increase in dose seems inappropriate. It is not recommended to prescribe erythropoietin to patients with serum endogenous erythropoietin levels above 200 IU/ml.
Prevention and treatment of anemia in patients with HIV infection
Intravenous administration of epoetin beta at a dose of 100-150 IU/kg 3 times a week is effective in HIV patients receiving zidovudine therapy, provided that the patient's serum endogenous erythropoietin level is less than 500 IU/ml and the dose of zidovudine is less than 4200 mg/mL. week. When administered subcutaneously, the dose of Vero-epoetin can be reduced by 1.5 times.
Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphomas and chronic lymphocytic leukemia
In these patients, the advisability of treatment with epoetin beta is determined by the inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. When the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/ml, Vero-epoetin is administered subcutaneously at a starting dose of 100 IU/kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of epoetin beta is adjusted upward or downward every 3-4 weeks. If, upon reaching a weekly dose of 600 IU/kg, an increase in hemoglobin levels is not observed, further use of epoetin beta should be discontinued as ineffective.
Prevention and treatment of anemia in patients with rheumatoid arthritis
In patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Anemia in these patients is treated with Vero-epoetin when administered subcutaneously at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin level increases by less than 10 g/l after 4 weeks of treatment, the dose of Vero-epoetin is increased to 150-200 IU/kg 3 times a week. Further increase in dose seems inappropriate
Treatment and prevention of anemia in premature infants born with low birth weight
Vero-epoetin is administered subcutaneously at a dose of 250 IU/kg three times a week, starting from the 3rd day of life until the target hemoglobin and hematocrit values are achieved, but not more than 6 weeks.
Prevention of anemia during major surgical interventions and acute blood loss
Vero-epoetin is administered intravenously or subcutaneously three times a week at a dose of 100-150 IU/kg until hematocrit and hemoglobin content normalize.
Pharmacodynamics
Epoetin beta is a glycoprotein that specifically stimulates erythropoiesis, activates mitosis and maturation of red blood cells from erythrocyte precursor cells. Recombinant epoetin beta is synthesized in mammalian cells into which the gene encoding human erythropoietin is integrated. In its composition, biological and immunological properties, epoetin beta is identical to natural human erythropoietin. The administration of epoetin beta leads to an increase in hemoglobin and hematocrit, improving blood supply to tissues and heart function. The most pronounced effect of the use of epoetin beta is observed in anemia caused by chronic renal failure. In very rare cases, with long-term use of erythropoietin for the treatment of anemic conditions, the formation of neutralizing antibodies to erythropoietin may be observed with or without the development of partial red cell aplasia.
Pharmacokinetics
With intravenous administration of Vero-epoetin in healthy individuals and patients with uremia, the half-life is 5-6 hours. With subcutaneous administration of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 28 hours after administration, the half-life is 13- 28 hours. When administered intravenously, the half-life is 4-12 hours. The bioavailability of Veroepoetin when administered subcutaneously is 25-40%.
Indications for use Epoetin-vero 2000me 10 pcs. lyophilisate for preparing solution
Symptomatic anemia in chronic kidney disease in patients on dialysis.
Symptomatic anemia of renal origin in patients not yet receiving dialysis. Prevention and treatment of anemia in patients with solid tumors, whose anemia was a consequence of antitumor therapy.
Prevention and treatment of anemia in HIV-infected patients (AIDS) caused by the use of Zidovudine.
Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis.
Treatment and prevention of anemia in premature infants born with low body weight up to 1.5 kg.
To reduce the volume of blood transfused during major 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 hypertension, failure to receive adequate anticoagulant therapy, myocardial infarction within a month after the event, unstable angina or increased risk of deep vein thrombosis and thromboembolism within pre-deposit blood collection program before surgery, porphyria.
With caution: in patients with thrombosis (history), with malignant neoplasms, with sickle cell anemia, in patients with moderate anemia without iron deficiency, in patients with refractory anemia, epilepsy and chronic liver failure.
Application of Epoetin-vero 2000me 10 pcs. lyophilisate for preparing a solution during pregnancy and breastfeeding
Since humans do not have sufficient experience with the use of erythropoietin during pregnancy and lactation, Vero-epoetin should be prescribed only if the expected benefits from its use outweigh the possible risk to the fetus and mother.
special instructions
During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin. In patients with uremia on hemodialysis, due to an 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 are necessary. In the pre- and postoperative period, Hb should be monitored more often if its initial level was less than 140 g/l. It must be remembered that Vero-epoetin does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled hypertension or thrombotic complications, an increase in the dose of antihypertensive and/or anticoagulant drugs may be required. If a hypertensive crisis develops, urgent measures are taken to provide medical care to the patient; treatment with Vero-epoetin should be interrupted. When Veroepoetin is prescribed to patients with liver failure, its metabolism may slow down and erythropoiesis may be markedly increased. The safety of Vero-epoetin in this group of patients has not been established. We also cannot exclude the possibility of interaction between Vero-epoetin and the growth of certain types of tumors, including bone marrow tumors. The possibility that a preoperative increase in Hb levels may predispose to the development of thrombotic complications should be considered. Before starting treatment, possible causes of an inadequate reaction to the drug should be excluded (deficiency of iron, folic acid, cyanocobalamine, severe A13+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment. In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is less than 100 ng/ml, replacement therapy with iron preparations for oral administration is recommended at the rate of 200-300 mg/day (for children 100-200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be started as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements at a dose of up to 200 mg/day. In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the level of urea, creatinine and K + within normal limits. Serum electrolyte levels should also be monitored in these patients. When using epoetin beta in women of reproductive age, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy. During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy. Given the possible more pronounced effect of epoetin beta, 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 and the dose/response ratio is assessed. After this, the dose can be reduced or increased according to the scheme presented above.
Overdose
In case of an overdose of Vero-epoetin, increased side effects may occur.
Treatment: symptomatic, with high levels of hemoglobin and hematocrit, bloodletting is indicated.
Side effects Epoetin-vero 2000me 10 pcs. lyophilisate for preparing solution
Cardiovascular system: the emergence or intensification of existing arterial hypertension, especially in the case of a rapid increase in hematocrit; hypertensive crisis with symptoms of encephalopathy (headaches and confusion, sensory and motor disorders - speech disorders, gait, up to tonic-clonic convulsions); thromboembolic complications in cancer patients and in patients preparing for autotransfusion (a clear causal relationship with the drug has not been established). Nervous system: headache, incl. sudden onset migraine-like headache.
Hematopoietic system: dose-dependent increase in the number of platelets (not beyond normal limits and disappearing with continued therapy), especially after intravenous administration of the drug; thrombocytosis, thrombosis of shunts (possibly with inadequate heparinization), especially in patients with a tendency to decrease blood pressure (BP) or with complications of an arteriovenous fistula (for example, stenosis, aneurysm, etc.).
Laboratory indicators: a decrease in the concentration of ferritin in the serum simultaneously with an increase in Hb, a decrease in serum indicators of iron metabolism. In patients with uremia there is hyperphosphatemia.
In premature newborns: a decrease in the concentration of ferritin in the blood serum, a slight increase in the number of platelets, especially before the 12-14th day of life.
Other: allergic skin reactions: rash, itching, urticaria, reactions at the injection site; anaphylactoid reactions; flu-like syndrome (especially at the beginning of therapy): fever, chills, headache, pain in the limbs or bones, malaise.
Drug interactions
With simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding to erythrocytes.
Experience in the clinical use of Vero-epoetin to date has not revealed any evidence of its pharmacological incompatibility with other drugs. However, to avoid possible incompatibility or decreased activity, Vero-epoetin should not be mixed with solutions of other drugs.
Use during pregnancy and breastfeeding
There is no sufficient experience with the use of the drug during pregnancy and lactation (breastfeeding).
The use of Vero-epoetin during pregnancy and lactation is possible only if the expected benefits from its use for the mother exceed the possible risk for the fetus and child.
When using the drug in women of reproductive age, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy.
Drug interactions
With the simultaneous use of Vero-epoetin with cyclosporine, the binding of the latter to erythrocytes may increase and, therefore, it may be necessary to adjust the dose of cyclosporine.
Pharmaceutical interactions
To date, no evidence of pharmacological incompatibility of Vero-epoetin with other drugs has been identified. However, to avoid possible incompatibility or decreased activity, Vero-epoetin should not be mixed with solutions of other drugs.
Mode of application
For the treatment of anemia in chronic renal failure, Vero-epoetin is administered subcutaneously or intravenously (for patients on hemodialysis, through an arteriovenous shunt at the end of the dialysis session). When changing the route of administration, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Vero-epoetin, to achieve the same therapeutic effect, a dose of 20-30% less than with intravenous administration is required).
Correction stage
For subcutaneous administration of Vero-epoetin, the initial dose is 30 IU/kg 3 times a week. For intravenous administration of Vero-epoetin, the initial dose is 50 IU/kg 3 times a week. The correction period lasts until the optimal level of hemoglobin (100-120 g/l in adults and 95-110 g/l in children) and hematocrit (30-35%) is achieved. These indicators must be monitored weekly. The following situations are possible:
1. Hematocrit increases from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved.
2. The rate of increase in 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 rate of increase in hematocrit is more than 1.0% per week. It is necessary to reduce the single dose of the drug by 1.5 times.
4. Hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.
Maintenance therapy phase
To maintain the hematocrit at a level of 30-35%, the dose of Vero-epoetin used at the correction stage should be reduced by 1.5 times. Then the maintenance dose of Vero-epoetin is selected individually, taking into account the dynamics of hematocrit or hemoglobin. After stabilization of hemodynamic parameters, it is possible to switch to the administration of Vero-epoetin once every 1-2 weeks.
When preventing and treating anemia in patients with solid tumors, it is recommended to determine the level of endogenous erythropoietin before starting therapy. When the concentration of serum erythropoietin is less than 200 IU/ml, the initial dose of Vero-epoetin is 150 IU/kg for intravenous administration. With the subcutaneous route of administration, the initial dose of Vero-epoetin can be reduced to 100 IU/kg. If there is no response, the dose may be increased to 300 IU/kg. Further increase in dose seems inappropriate. It is not recommended to prescribe Vero-epoetin to patients with serum endogenous erythropoietin levels above 200 IU/ml.
In the prevention and treatment of anemia in patients with HIV infection, intravenous administration of Vero-epoetin at a dose of 100-150 IU/kg 3 times a week is effective in HIV patients receiving zidovudine therapy, provided that the level of the patient's serum endogenous erythropoietin is less than 500 IU/ml, and the dose of zidovudine is less than 4200 mg/week. With subcutaneous administration, the dose of Vero-epoetin can be reduced by 1.5 times.
In the prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia, the advisability of treatment with Vero-epoetin is determined by the inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. If the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/ml, Vero-epoetin is administered subcutaneously at a starting dose of 100 IU/kg 3 times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of the drug is adjusted upward or downward every 3-4 weeks. If, upon reaching a weekly dose of 600 IU/kg, an increase in hemoglobin levels is not observed, further use of Vero-epoetin should be discontinued as ineffective.
In rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. For the prevention and treatment of anemia in patients with rheumatoid arthritis, Vero-epoetin is administered subcutaneously at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin level increases by less than 10 g/l after 4 weeks of treatment, the dose of Vero-epoetin is increased to 150-200 IU/kg 3 times a week. Further increase in dose seems inappropriate.
For the treatment and prevention of anemia in premature infants born with low body weight, Vero-epoetin is administered subcutaneously at a dose of 200 IU/kg 3 times a week, starting from the 6th day of life until the target hemoglobin and hematocrit values are achieved, but no more 6 weeks.
When preventing anemia during extensive surgical interventions and acute blood loss, Vero-epoetin is administered intravenously or subcutaneously 3 times a week at a dose of 100-150 IU/kg until hematocrit and hemoglobin content normalize.
Vero-Epoetin
Treatment of anemia in patients with chronic renal failure: subcutaneously or intravenously for 2 minutes, for hemodialysis patients - through an arteriovenous shunt at the end of the dialysis session. For patients not receiving hemodialysis, it is preferable to administer the drug subcutaneously to avoid accidental entry into peripheral veins. The goal of treatment is to achieve a hematocrit of 30-35% or eliminate the need for blood transfusion. The weekly increase in hematocrit should not exceed 0.5%. In patients with arterial hypertension, cardiovascular and cerebrovascular diseases, the weekly increase in hematocrit and its weekly indicators should be determined individually depending on the clinical picture. For some patients, the optimal rate is below 30%.
Correction stage: subcutaneous injection, initial dose - 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 can be increased to 40 IU/kg 3 times a week. The total weekly dose can be divided into daily administrations in smaller doses or administered in one dose.
When administered intravenously (slowly over 2 minutes), the initial dose is 40 IU/kg 3 times a week. If there is insufficient increase in hematocrit after 4 weeks, the dose can 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 4-week intervals. Regardless of the route of administration, the maximum dose should not exceed 720 IU/kg/week.
Maintenance therapy: to maintain the hematocrit within 30-35%, the dose is initially reduced by 2 times from the dose of the previous injection. Subsequently, the maintenance dose is selected for each patient individually, at intervals of 1-2 weeks, so that the hematocrit is maintained within 30-35%. For subcutaneous administration, the weekly dose can be administered in one dose or divided into 3 or 7 administrations per week. When the condition stabilizes, you can switch to a single dose with an interval of 2 weeks; in this case, you may need to increase the dose. Treatment is lifelong and can be interrupted if necessary.
In children, the dose of the drug depends on age: the younger the child, the higher doses he requires. Since individual response to the drug cannot be predicted, it is advisable to start with the recommended dosage regimen.
Prevention of anemia in premature newborns: subcutaneously, at 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 the 3rd day of life.
Prevention and treatment of anemia in cancer patients: for patients with solid tumors receiving chemotherapy with Pt drugs, treatment is indicated if Hb before chemotherapy is not higher than 130 g/l. SC, initial dose - 450 IU/kg/week, divided into 3 or 7 injections. If the increase in Hb is not sufficient, the dose is doubled after 4 weeks. Treatment is continued 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. An increase in Hb of more than 20 g/l per month or above 140 g/l should be avoided. If Hb increases by more than 20 g/l per month, the dose is reduced by 50%. If Hb exceeds 140 g/L, the drug is discontinued until Hb decreases to 120 g/L or less, and then treatment is resumed at a dose of 50% of the previous weekly dose.
In patients with multiple myeloma and low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukemia, the initial dose is 450 IU/kg/week. The weekly dose can be divided into 3 or 7 injections. If the increase in Hb is insufficient after 4 weeks (by less than 10 g/l), the dose is doubled. If after 8 weeks of treatment Hb does not increase by at least 10 g/l, the drug should be discontinued. The maximum dose should not exceed 900 IU/kg per week.
For chronic lymphocytic leukemia, treatment should be continued until 4 weeks after the end of chemotherapy. The highest dose should not exceed 900 IU/kg. If within 4 weeks of treatment Hb increases by more than 20 g/l, the dose is reduced by 2 times. If Hb exceeds 140 g/l, treatment must be interrupted until Hb reaches 130 g/l or less, after which therapy is resumed at a dose equal to 50% of the previous initial dose. Treatment should only be restarted if the most likely cause of the anemia is erythropoietin deficiency.
Preparing patients for donated blood collection for subsequent autohemotransfusion: IV or SC 2 times a week for 4 weeks. In cases 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 the volume of blood required for autohemotransfusion. The highest dose should not exceed 1600 IU/kg per week for intravenous administration and 1200 IU/kg/week for subcutaneous administration. Throughout the course of treatment, the hematocrit should not exceed 48%.
