Vero-Epoetin (Lyophilisate) Instructions for Use

ATC Code

B03XA01 (Erythropoietin)

Active Substance

Epoetin beta (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Erythropoiesis stimulant

Pharmacotherapeutic Group

Hematopoiesis stimulant

Pharmacological Action

Recombinant human erythropoietin (a purified glycoprotein) consisting of 165 amino acids, which, being a mitogenic factor and a differentiation hormone, promotes the formation of erythrocytes from partially determined erythroid progenitor cells. Recombinant Epoetin beta, obtained by genetic engineering, is identical to human erythropoietin in its amino acid and carbohydrate composition.

After intravenous and subcutaneous administration, Epoetin beta increases the number of erythrocytes, reticulocytes, and the hemoglobin level, as well as the rate of iron (⁵⁹Fe) incorporation into cells, specifically stimulates erythropoiesis without affecting leukopoiesis. No cytotoxic effect of epoetin beta on the bone marrow or on human skin cells has been identified.

Pharmacokinetics

After subcutaneous administration, C_max in plasma is reached after 12-28 hours. The bioavailability of epoetin beta after subcutaneous administration is 23-42% compared to intravenous administration. V_d is equal to the blood volume or twice its value. T_1/2 in the terminal phase is 13-28 hours. After intravenous administration, the T_1/2 of the active substance is 4-12 hours. The T_1/2 of the terminal phase after subcutaneous administration is longer than after intravenous administration and averages 13-28 hours.

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 hematological non-myeloid tumors receiving chemotherapy; prevention of anemia in preterm newborns born with a body weight of 750-1500 g before the 34th week of pregnancy. Increase in the volume of donor blood intended for subsequent autotransfusion. The registered 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 stored blood, and a planned major elective surgical intervention may require a large volume of blood (>4 units for women or >5 units for men).

ICD codes

Dosage Regimen

Determine the dose, route, and duration of treatment individually based on anemia severity, clinical condition, and patient age.

Administer subcutaneously or intravenously. For chronic kidney disease patients on dialysis, initiate at 50 International Units per kilogram body weight three times weekly intravenously.

For chronic kidney disease patients not on dialysis, initiate at a lower subcutaneous dose to minimize hypertension risk. Adjust the dose to maintain a hemoglobin level not exceeding 120 g/L.

For chemotherapy-induced anemia in adult cancer patients, initiate at 450 International Units per kilogram subcutaneously once weekly or 150 International Units per kilogram three times weekly.

For anemia of prematurity in preterm newborns (750-1500 g), administer 250 International Units per kilogram subcutaneously three times weekly for up to 6 weeks.

For preoperative autologous blood donation, administer 600 International Units per kilogram subcutaneously twice weekly for 3 weeks prior to surgery in patients with moderate anemia and no iron deficiency.

Monitor hemoglobin levels regularly. Adjust the dose in small increments no more frequently than every four weeks. Reduce the dose if the hemoglobin rise exceeds 20 g/L in a four-week period.

Discontinue therapy if hemoglobin does not respond after 8 weeks of escalation or if a rapid rise in hemoglobin occurs despite dose reduction.

Ensure adequate iron stores before and during therapy. Administer supplemental iron if serum ferritin falls below 100 µg/L or transferrin saturation is below 20%.

Adverse Reactions

From the cardiovascular system arterial hypertension, hypertensive crisis, shunt thromboses.

From the nervous system encephalopathy (more often with hypertensive crises), headache, confusion.

From the blood coagulation system rarely – thrombocytosis, thrombotic complications.

From the hematopoietic system: pure red cell aplasia (PRCA).

Allergic reactions rarely – skin rash, itching, urticaria, anaphylactoid reactions.

From the skin and subcutaneous tissues Stevens-Johnson syndrome.

From laboratory parameters decrease in plasma ferritin content with a simultaneous increase in hemoglobin, increase in plasma levels of potassium and phosphates.

Other flu-like syndrome, local reactions.

Contraindications

Hypersensitivity to epoetin beta in history; 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 autologous blood transfusion.

With caution

Refractory anemia in the presence of blast-transformed cells, thrombocytosis, epilepsy, and chronic liver failure. Body weight less than 50 kg for increasing the volume of donor blood for subsequent autotransfusion.

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, Epoetin beta is used only if the intended benefit to the mother outweighs the potential risk to the fetus or child.

In experimental studies, no teratogenic effect was identified.

Use in Hepatic Impairment

Use with caution in chronic liver failure.

Use in Renal Impairment

Use with caution in patients with nephrosclerosis not receiving hemodialysis, as a more rapid deterioration in renal function is possible.

Pediatric Use

It is possible to use in children according to indications, in doses and regimens recommended for the respective age.

For the treatment of anemia associated with chronic kidney disease, Epoetin beta should not be prescribed to children under 2 years of age.

Special Precautions

During therapy with epoetin beta, platelet, hematocrit, and hemoglobin levels 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 efficacy of epoetin beta may decrease with iron, folic acid, and vitamin B₁₂ deficiency.

Iron deficiency should be ruled out before starting treatment with epoetin beta and throughout the entire course of therapy. If necessary, additional therapy with iron preparations may be prescribed in accordance with clinical guidelines.

The effectiveness of treatment decreases with iron deficiency in the body, with infectious and inflammatory diseases, and hemolysis.

The possibility of the influence of epoetin beta on the growth of some types of tumors, especially on malignant neoplasms of the bone marrow, cannot be completely excluded.

During the use of epoetin beta, blood pressure levels should be monitored, paying attention to the occurrence or intensification of unusual headaches. In this case, correction of the ongoing therapy or prescription of antihypertensive agents may be required.

Use with caution in epilepsy, thrombocytosis, liver failure, vascular insufficiency, in malignant neoplasms; in patients with nephrosclerosis not receiving hemodialysis, as a more rapid deterioration in renal function is possible.

The decision to use epoetin beta in patients with nephrosclerosis not receiving dialysis should be made individually, as the possibility of a more rapid deterioration in renal function cannot be completely excluded. In most cases, simultaneously with an increase in hemoglobin, the concentration of ferritin in the serum decreases. The ferritin level should be determined throughout the course of treatment. If it is less than 100 ng/ml, replacement therapy with iron preparations is recommended.

Patients donating autologous blood and in the pre- or postoperative period should also receive an adequate amount of iron additionally until ferritin levels normalize.

Drug Interactions

With simultaneous use of drugs affecting hematopoiesis (for example, iron preparations), the stimulating effect of epoetin beta may be enhanced.

Epoetin beta should not be mixed with solutions of other medicinal products.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.