Epoetin beta (Solution) Instructions for Use

Marketing Authorization Holder

Microgen NPO, JSC (Russia)

ATC Code

B03XA01 (Erythropoietin)

Active Substance

Epoetin beta (Rec.INN registered by WHO)

Dosage Forms

	Epoetin beta	Solution for intravenous and subcutaneous administration 500 IU: 1 ml amp. 5 or 10 pcs.
		Solution for intravenous and subcutaneous administration 2000 IU: 1 ml amp. 5 or 10 pcs., 1 ml syringe 1, 5 or 6 pcs.
		Solution for intravenous and subcutaneous administration 3000 IU: 1 ml amp. 5 or 10 pcs.
		Solution for intravenous and subcutaneous administration 4000 IU: 1 ml amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

1 ml (500 IU) – ampoules (5) – carton packs.
1 ml (500 IU) – ampoules (10) – carton packs.

1 ml (2000 IU) – ampoules (5) – carton packs.
1 ml (2000 IU) – ampoules (10) – carton packs.
1 ml (2000 IU) – syringes (1) – carton packs.
1 ml (2000 IU) – syringes (5) – carton packs.
1 ml (2000 IU) – syringes (6) – carton packs.

1 ml (3000 IU) – ampoules (5) – carton packs.
1 ml (3000 IU) – ampoules (10) – carton packs.

1 ml (4000 IU) – ampoules (5) – carton packs.
1 ml (4000 IU) – ampoules (10) – carton packs.

Clinical-Pharmacological Group

Erythropoiesis stimulant

Pharmacotherapeutic Group

Hematopoiesis stimulant

Pharmacological Action

Recombinant human erythropoietin (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.

Epoetin beta after intravenous and subcutaneous administration increases the number of erythrocytes, reticulocytes and 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 was detected.

Pharmacokinetics

After subcutaneous administration, C_max in plasma is reached after 12-28 hours.

The bioavailability of epoetin beta with subcutaneous administration is 23-42% compared with intravenous administration.

V_d is equal to the volume of circulating blood or exceeds it by 2 times.

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 with 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 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 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 preserved 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 dosage, regimen, and duration of treatment individually based on anemia severity, patient condition, and underlying disease.

Administer subcutaneously or intravenously.

For anemia in chronic kidney disease in adult patients on dialysis, initiate treatment at 50 IU/kg three times per week intravenously.

For adult patients not yet on dialysis, use a subcutaneous route of administration with an initial dose of 30 IU/kg three times per week.

If the hematocrit increase is inadequate after 4 weeks, increase the dose incrementally.

Do not exceed a hematocrit of 35 vol%.

For anemia in adult cancer patients receiving chemotherapy, administer 30,000 IU once weekly subcutaneously or 150 IU/kg three times per week subcutaneously.

Discontinue if no response is observed after 8 weeks.

For premature newborns (750-1500 g, <34 weeks gestation), administer 250 IU/kg three times per week subcutaneously for anemia prevention.

For autologous blood donation, administer 600 IU/kg subcutaneously twice weekly for 3 weeks prior to surgery.

Ensure adequate iron stores before and during therapy; administer supplemental iron if serum ferritin falls below 100 ng/mL.

Monitor hemoglobin, hematocrit, blood pressure, and ferritin levels regularly and adjust the dose to maintain the target hemoglobin range.

Reduce the dose when the target hemoglobin is approached or the rate of rise exceeds 1 g/dL per two weeks.

Adverse Reactions

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

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 to increase 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 detected.

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, since 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 according to age.

When treating 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, as well as throughout the entire period 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, hemolysis.

The possibility of the effect 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, it is necessary to control the level of blood pressure, paying attention to the occurrence or intensification of unusual headaches.

In this case, correction of the ongoing therapy or the appointment of antihypertensive drugs may be required.

Use with caution in epilepsy, thrombocytosis, liver failure, vascular insufficiency, in malignant neoplasms; in patients with nephrosclerosis not receiving hemodialysis, since 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, since the possibility of a more rapid deterioration in renal function cannot be completely excluded.

In most cases, along with an increase in hemoglobin, the concentration of ferritin in the serum decreases.

The level of ferritin must be determined throughout the entire 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 the simultaneous use of drugs that affect 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.