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Epostim® (Solution) Instructions for Use

ATC Code

B03XA01 (Erythropoietin)

Active Substance

Epoetin beta (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Erythropoiesis stimulant

Pharmacotherapeutic Group

Antianemic drugs; other antianemic drugs

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.

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, Cmax in plasma is reached after 12-28 hours. The bioavailability of epoetin beta after subcutaneous administration is 23-42% compared to intravenous administration. Vd is equal to the blood volume or twice its value. T1/2 in the terminal phase is 13-28 hours. After intravenous administration, the T1/2 of the active substance is 4-12 hours. The T1/2 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.

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

ICD-10 code Indication
D63.0 Anemia in neoplastic disease (C00-D48*)
D63.8 Anemia in other chronic diseases classified elsewhere*
P61.2 Anemia of prematurity
Z51.4 Preparatory procedures for subsequent treatment or examination, not elsewhere classified
ICD-11 code Indication
3A71.Z Anemia of chronic disease, unspecified
KA8B Anemia of prematurity
QB9A Preparatory procedures for subsequent treatment

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Determine the dose, regimen, and duration of treatment individually based on anemia severity, patient condition, and underlying disease.

Administer subcutaneously or intravenously.

For adult patients with chronic kidney disease on dialysis, initiate treatment at 50 International Units per kilogram of body weight three times per week intravenously.

For adult patients with chronic kidney disease not on dialysis, initiate treatment at a lower dose to achieve a target hemoglobin not exceeding 10 g/dL.

Adjust the dose based on the individual hemoglobin response; do not exceed the hemoglobin level of 12 g/dL.

If the hemoglobin increase exceeds 2 g/dL in any four-week period, reduce the dose.

For anemia in adult cancer patients receiving chemotherapy, initiate treatment at 450 International Units per kilogram subcutaneously once per week or 150 International Units per kilogram subcutaneously three times per week.

Discontinue epoetin beta in oncology patients following the completion of a chemotherapy course.

For prevention of anemia in preterm newborns (750-1500 g, <34 weeks gestation), administer 250 International Units per kilogram subcutaneously three times per week.

For augmentation of autologous blood donation in adults with moderate anemia and no iron deficiency, administer 600 International Units per kilogram intravenously twice weekly for three weeks prior to surgery.

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

Monitor hemoglobin regularly, at least once per week during the dose adjustment phase and periodically during maintenance therapy.

Monitor blood pressure before and during treatment; control hypertension prior to initiation and manage any exacerbation during therapy.

Withhold therapy if hemoglobin levels exceed the target range or if severe adverse events occur.

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 potassium and phosphate levels.

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 hepatic insufficiency. 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 should be used only if the expected 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 hepatic insufficiency.

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

Can be used 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 hepatic insufficiency.

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 therapy period. 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 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, hepatic insufficiency, 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, along with an increase in hemoglobin, the serum ferritin concentration decreases. Ferritin levels 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.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 1000 IU/1 ml: syringes 1 or 3 pcs., ampoules 5 or 10 pcs., vials 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 syringe
Epoetin beta 1000 IU

1 ml – syringes (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (3) – cardboard packs.
1 ml – vials (1) – cardboard packs.
1 ml – vials (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 2000 IU/1 ml: syringes 1 or 3 pcs; amp. 5 or 10 pcs., vials 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 ml
Epoetin beta 2000 IU

1 ml – syringes (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (3) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
1 ml – vials (1) – cardboard packs.
1 ml – vials (5) – plastic contour packs (1) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 5000 IU/1 ml: syringes 1 or 3 pcs; amp. 5 or 10 pcs., vials 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 ml
Epoetin beta 5000 IU

1 ml – syringes (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (3) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
1 ml – vials (1) – cardboard packs.
1 ml – vials (5) – plastic contour packs (1) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Manufactured By

Pharmstandard-UfaVITA OJSC (Russia)

Or

Oncotarget, LLC (Russia)

Packaging and Quality Control Release

PHARMSTANDARD-UfaVITA, JSC (Russia)

Quality Control Release

PHARMAPARK, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 10000 IU/1 ml: amp. 5 or 10 pcs., fl. 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 ml
Epoetin beta 10000 IU

1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
1 ml – vials (5) – plastic contour packs (2) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Labeled By

NPO PETROVAKS PHARM, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 2000 IU/1 ml: syringes 1 or 3 pcs; amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 ml
Epoetin beta 2000 IU

1 ml – syringes (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (3) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
1 ml – vials (1) – cardboard packs.
1 ml – vials (5) – plastic contour packs (1) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Labeled By

NPO PETROVAKS PHARM, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 10000 IU/1 ml: syringes 1 or 3 pcs; amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 ml
Epoetin beta 10000 IU

1 ml – syringes (1) – plastic contour packs (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (6) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.

Marketing Authorization Holder

Pharmapark, LLC (Russia)

Dosage Form

Bottle Rx Icon Epostim® Solution for intravenous and subcutaneous administration 4000 IU/1 ml: syringes 1 or 3 pcs., ampules 5 or 10 pcs., vials 1 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration 1 syringe
Epoetin beta 4000 IU

1 ml – syringes (1) – cardboard packs.
1 ml – syringes (1) – plastic contour packs (3) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
1 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
1 ml – vials (1) – cardboard packs.
1 ml – vials (5) – plastic contour packs (1) – cardboard packs.

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