Recormon^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

F. Hoffmann-La Roche, Ltd (Switzerland)

Manufactured By

Vetter Pharma-Fertigung, GmbH & Co. KG (Germany)

ATC Code

B03XA01 (Erythropoietin)

Active Substance

Epoetin beta

Dosage Forms

	Recormon®	Lyophilized powder for preparation of solution for injection 1000 IU: vial 10 pcs. in a set with solvent
		Lyophilized powder for preparation of solution for injection 2000 IU: vial 10 pcs. in a set with solvent
		Lyophilized powder for preparation of solution for injection 5000 IU: vial 10 pcs. in a set with solvent
		Lyophilisate for preparation of solution for subcutaneous administration 10,000 IU: two-chamber cartridge with solvent 1 pc.
		Lyophilisate for preparation of solution for subcutaneous administration 20,000 IU: two-chamber cartridge with solvent 1 pc.
		Solution for intravenous and subcutaneous administration 10,000 IU/0.6 ml: syringe-tubes 6 pcs. in a set with injection needles
		Solution for intravenous and subcutaneous administration 20,000 IU/0.6 ml: syringe-tubes 6 pcs. in a set with injection needles
		Solution for intravenous and subcutaneous administration 30,000 IU/0.6 ml: syringe-tubes 1 or 4 pcs. in a set with injection needles
		Solution for injection 500 IU/0.3 ml: syringe-tubes 1, 2, 3 or 6 pcs.
		Solution for intravenous and subcutaneous administration 1000 IU/0.3 ml: syringe-tubes 6 pcs. in a set with injection needles
		Solution for intravenous and subcutaneous administration 2000 IU/0.3 ml: syringe-tubes 6 pcs. in a set with injection needles
		Solution for injection 3000 IU/0.3 ml: syringe-tubes 1, 2, 3 or 6 pcs.
		Solution for injection 4000 IU/0.3 ml: syringe-tubes 1, 2, 3 or 6 pcs.
		Solution for injection 5000 IU/0.3 ml: syringe-tubes 1, 2, 3 or 6 pcs.
		Solution for injection 6000 IU/0.3 ml: syringe-tubes 1, 2, 3 or 6 pcs.

Dosage Form, Packaging, and Composition

Solution for IV and SC administration colorless, clear or slightly opalescent.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water for injections.

0.3 ml – syringe-tubes (3) in a set with injection needles (3 pcs.) – blister packs (2) – cardboard boxes.

Solution for IV and SC administration colorless, clear or slightly opalescent.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water for injections.

0.3 ml – syringe-tubes (3) in a set with injection needles (3 pcs.) – blister packs (2) – cardboard boxes.

Solution for IV and SC administration colorless, clear or slightly opalescent.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water for injections.

0.6 ml – syringe-tubes (3) in a set with injection needles (3 pcs.) – blister packs (2) – cardboard boxes.

Solution for IV and SC administration colorless, clear or slightly opalescent.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water for injections.

0.6 ml – syringe-tubes (3) in a set with injection needles (3 pcs.) – blister packs (2) – cardboard boxes.

Solution for IV and SC administration colorless, clear or slightly opalescent.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water for injections.

0.6 ml – syringe-tubes (1) in a set with injection needles (1 pc.) – blister packs (1) – cardboard boxes.
0.6 ml – syringe-tubes (1) in a set with injection needles (1 pc.) – blister packs (4) – cardboard boxes.

Lyophilisate for preparation of solution for SC administration as a homogeneous powder or porous mass, white or almost white; solvent – colorless, clear liquid; prepared solution – colorless, clear or slightly opalescent liquid.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.

Solvent: benzyl alcohol, benzalkonium chloride, water for injections.

Two-chamber cartridges with lyophilisate in the first chamber and 1 ml of solvent in the second chamber (1) – cardboard boxes.

Lyophilisate for preparation of solution for SC administration as a homogeneous powder or porous mass, white or almost white; solvent – colorless, clear liquid; prepared solution – colorless, clear or slightly opalescent liquid.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.

Solvent: benzyl alcohol, benzalkonium chloride, water for injections.

Two-chamber cartridges with lyophilisate in the first chamber and 1 ml of solvent in the second chamber (1) – cardboard boxes.

Lyophilized powder for preparation of solution for injection homogeneous, white; solvent – colorless clear liquid; prepared solution – colorless, clear or slightly opalescent liquid.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.

Solvent: water for injections – 1 ml.

1000 IU – vials (5) in a set with solvent (amp. 5 pcs.) – plastic trays (2) – cardboard boxes.

Lyophilized powder for preparation of solution for injection homogeneous, white; solvent – colorless clear liquid; prepared solution – colorless, clear or slightly opalescent liquid.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.

Solvent: water for injections – 1 ml.

2000 IU – vials (5) in a set with solvent (amp. 5 pcs.) – plastic trays (2) – cardboard boxes.

Lyophilized powder for preparation of solution for injection homogeneous, white; solvent – colorless clear liquid; prepared solution – colorless, clear or slightly opalescent liquid.

Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.

Solvent: water for injections – 1 ml.

5000 IU – vials (5) in a set with solvent (amp. 5 pcs.) – plastic trays (2) – cardboard boxes.

Clinical-Pharmacological Group

Erythropoiesis stimulant

Pharmacotherapeutic Group

Hematopoiesis stimulant

Pharmacological Action

Hematopoiesis stimulant. 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 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 IV and SC 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 bone marrow or human skin cells has been identified.

Pharmacokinetics

Absorption

The bioavailability of epoetin beta after SC administration is 23-42%. In patients with uremia, prolonged absorption after SC administration provides a plateau of drug concentrations in serum. T_max– 12-28 h.

Distribution

V_d is equal to the blood volume or twice its value.

Elimination

In patients with uremia and in healthy volunteers, T_1/2 after IV administration is 4-12 h. T_1/2 of the terminal phase after SC administration is longer than after IV administration and averages 13-28 h.

Pharmacokinetics in special clinical cases

The pharmacokinetics of epoetin beta in patients with hepatic impairment has not been studied.

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;
• To increase the volume of donor blood intended for subsequent autotransfusion (taking into account the registered risk of thromboembolic events and only for patients with moderate anemia (Hb 100-130 g/l or 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);
• Prevention of anemia in preterm newborns born with a body weight of 750-1500 g up to the 34th week of pregnancy.

ICD codes

Dosage Regimen

Treatment of anemia in patients with chronic kidney disease

Administer SC or IV over 2 min. For patients on hemodialysis – via the arteriovenous shunt at the end of the dialysis session. For patients not receiving hemodialysis, it is preferable to administer the drug SC 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) in 4 weeks, the drug dose should be reduced. In patients with arterial hypertension, cardiovascular and cerebrovascular diseases, the weekly increase in hemoglobin and its target levels should be determined individually, depending on the clinical picture. Careful monitoring of the patient should be carried out to select the minimum dose sufficient to ensure the maximum effect of the drug. Treatment with Recormon^® is carried out in 2 stages.

Correction stage. SC, initial dose – 20 IU/kg 3 times a week. With insufficient increase in Hb (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.

IV, initial dose – 40 IU/kg 3 times a week. With insufficient increase in Hb after one month, the dose can be increased to 80 IU/kg 3 times a week. If necessary, the dose should be further increased 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.

Maintenance therapy. To maintain the target Hb level (100-120 g/l), the dose should initially be reduced by half from the previous dose. Subsequently, the maintenance dose is selected individually, at intervals of 2 or 4 weeks. With SC administration, the weekly dose can be administered in one dose or divided into 3 or 7 administrations per week. With stabilization of the condition against the background of administration once a week, it is possible to switch to administration once every 2 weeks, in which case an increase in dose may be required.

Treatment with Recormon^® is usually long-term. If necessary, it can be interrupted at any time.

Treatment of symptomatic anemia in patients with solid and hematological non-myeloid tumors receiving chemotherapy

The drug is administered SC, at an initial dose of 30,000 IU per week (450 IU/kg per week), once or dividing the weekly dose into 3 or 7 administrations.

Therapy with Recormon^® is indicated for Hb≤110 g/l (6.83 mmol/l). The Hb level should not exceed 130 g/l (8.07 mmol/l).

If Hb increases by 10 g/l (0.62 mmol/l) after 4 weeks – therapy should be continued at the same dose.

If Hb increases by less than 10 g/l (0.62 mmol/l) after 4 weeks – the dose should be doubled.

If there is no increase in Hb by 10 g/l (0.62 mmol/l) after 8 weeks – treatment should be interrupted, as a response to Recormon^® therapy is unlikely.

Treatment should be continued for 4 weeks after the end of chemotherapy.

The maximum dose should not exceed 60,000 IU per week.

When the target Hb level for a particular patient is reached, the drug dose should be reduced by 25-50%.

To prevent Hb from rising above 130 g/l, further dose reduction may be required.

If Hb increases by more than 20 g/l (1.3 mmol/l) per month, the dose of Recormon^® should be reduced by 25-50%.

Preparation of patients for donor blood collection for subsequent autologous blood transfusion

IV (over 2 min) or SC, 2 times a week for 4 weeks. In cases where the patient’s hematocrit (≥ 33%) allows blood collection, Recormon^® should be administered at the end of the procedure.

Throughout the course of treatment, the hematocrit should not exceed 48%.

The dose of the drug is determined by the transfusiologist and surgeon individually, depending on the volume of blood that will be taken from the patient and his erythrocyte reserve

1. The volume of blood that will be taken from the patient depends on the expected blood loss, available blood preservation methods and the general condition of the patient; it must be sufficient to avoid transfusion of blood from another donor.
2. The volume of blood that will be taken from the patient is expressed in units (1 unit is equivalent to 180 ml of erythrocytes).
3. The possibility of donation depends mainly on the patient’s blood volume and initial hematocrit. Both indicators determine the endogenous erythrocyte reserve, which is calculated by the following formula

Endogenous erythrocyte reserve = blood volume [ml] x (hematocrit – 33) :100

Women blood volume [ml] = 41 [ml/kg] x body weight [kg] + 1200 [ml]

Men blood volume [ml] = 44 [ml/kg] x body weight [kg] + 1600 [ml] (for body weight ≥ 45 kg).

The indication for the use of Recormon^® and its single dose are determined by nomograms, based on the required volume of donor blood and the endogenous erythrocyte reserve. The maximum dose should not exceed 1600 IU/kg per week with IV administration and 1200 IU/kg per week with SC administration.

Prevention of anemia in preterm newborns

The drug is used only in syringe-tubes. Administer SC at a dose of 250 IU/kg 3 times a week, as early as possible, preferably from the 3rd day of life, for 6 weeks.

In children and adolescents, the dose of the drug depends on age: as a rule, the younger the age, the higher the doses of Recormon^® are required. But since the individual response to the drug cannot be predicted, it is advisable to start with the standard dosing regimen. For treatment of anemia associated with chronic kidney disease, Recormon^® should not be prescribed to children under 2 years of age.

In clinical studies in elderly patients, no need for dose adjustment was identified.

Rules for using the drug

The syringe-tube with Recormon^® is ready for use. The solution contained in it is sterile and does not contain preservatives. Only a clear, colorless or slightly opalescent solution without visible inclusions should be used. If some amount of the drug remains in the syringe-tube after injection, its re-administration is not allowed.

Instructions for using the syringe-tube

Before injection, it is necessary to wash your hands.

1. Remove one syringe-tube from the package and make sure that the solution is clear, colorless and does not contain visible inclusions. Remove the cap from the syringe.
2. Remove one needle from the packaging, attach it to the syringe, and remove the protective cap from the needle.
3. Remove air from the syringe and needle by holding the syringe vertically and gently pushing the plunger upward. Press the plunger until the required dose of Recormon^® remains in the syringe.
4. Wipe the skin at the injection site with an alcohol swab. Pinch the skin between the thumb and forefinger. Holding the syringe barrel close to the needle, insert the needle under the skin. Inject the Recormon^® solution. Quickly withdraw the needle and press the injection site with a sterile dry cotton ball.

The cartridge with Recormon^® for the Reco-Pen pen injector is a dual-chamber cartridge containing a lyophilisate for preparing a solution for subcutaneous administration and a solvent with preservatives. The finished solution is obtained by inserting the cartridge into the Reco-Pen pen injector according to the instructions for the Reco-Pen.

Cartridges with Recormon^® should only be used in the Reco-Pen pen injector. It is recommended to use needles for the Reco-Pen pen injector (e.g., “Penfine” needles). The prepared solution in the cartridge is stored for 1 month at a temperature from 2°C (35.6°F) to 8°C (46.4°F). After inserting the cartridge, the Reco-Pen pen injector should be taken out of the refrigerator only for the duration of the injection.

Adverse Reactions

Cardiovascular system frequently – onset or worsening of pre-existing arterial hypertension (>1%, <10%), especially in case of a rapid increase in hematocrit; hypertensive crisis with manifestations of encephalopathy (headaches and confusion, sensory and motor disturbances - speech and gait disturbances, up to tonic-clonic seizures), thromboembolic complications in cancer patients (>0.1%, <1%) and in patients preparing for autotransfusion (a clear causal relationship with the drug has not been established).

Central nervous system >1%, <10% - headaches, including suddenly occurring migraine-like headaches.

Hematopoietic system dose-dependent increase in platelet count (not exceeding the normal range and disappearing with continued therapy), especially after intravenous administration of the drug; <0.01% - thrombocytosis; >0.01%, <0.1% - shunt thrombosis (possible with inadequate heparinization), especially in patients with a tendency to decreased blood pressure or with complications of an arteriovenous fistula (including stenosis, aneurysm).

Allergic reactions rarely (from ≥ 1/10,000 to ≤ 1/1,000) – skin rash, itching, urticaria; very rarely (≤ 1/10,000) – anaphylactoid reactions.

Laboratory parameters decrease in serum ferritin concentration simultaneously with an increase in Hb, decrease in serum iron metabolism parameters; in patients with uremia – transient hyperkalemia (a clear causal relationship with the drug has not been established), hyperphosphatemia. In premature newborns – decrease in serum ferritin concentration (>10%), slight increase in platelet count, especially up to the 12th-14th day of life.

Other reactions at the injection site; flu-like symptoms (especially at the beginning of therapy; usually mild or moderate and disappear within a few hours or days), including fever, chills, headaches, limb or bone pain, general malaise.

Post-marketing surveillance: during therapy with Recormon^®, isolated cases (0.107 cases per 10,000 patient-years with intravenous and subcutaneous use of Recormon^® for the treatment of renal anemia and 0.158 cases per 10,000 patient-years with subcutaneous administration of Recormon^® for the treatment of renal anemia) of pure red cell aplasia (PRCA) caused by the formation of neutralizing anti-erythropoietin antibodies have been registered.

Contraindications

• 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;
• Children under 3 years of age (for cartridges with lyophilisate for preparing a solution for subcutaneous administration);
• Hypersensitivity to epoetin beta or any component of the drug;
• Hypersensitivity to benzoic acid – a metabolite of benzyl alcohol (when using Recormon^® for the Reco-Pen pen injector).

Use with caution in refractory anemia in the presence of blast-transformed cells, thrombocytosis, epilepsy, and chronic hepatic insufficiency; in patients with body weight less than 50 kg to increase the volume of donor blood for subsequent autotransfusion.

Use in Pregnancy and Lactation

Information on the safety of Recormon^® use during pregnancy, childbirth, and lactation (breastfeeding) was obtained from post-marketing experience.

During pregnancy or childbirth, Recormon^® should be prescribed with caution, as there is insufficient experience with its use during pregnancy and childbirth.

Endogenous erythropoietin is excreted in breast milk and is completely absorbed in the gastrointestinal tract of the newborn. The choice between continuing breastfeeding or continuing therapy with Recormon^® should be made taking into account the necessity of therapy for the mother and the benefits of breastfeeding for the child.

In experimental studies, it has been shown that Epoetin beta does not have a teratogenic effect on animals.

Use in Hepatic Impairment

Use with caution in chronic hepatic insufficiency.

Use in Renal Impairment

A sharp increase in aluminum content due to the treatment of renal failure may reduce the effectiveness of epoetin beta.

The decision to use Recormon^® in patients with nephrosclerosis not receiving dialysis should be made individually, as the possibility of a more rapid deterioration of renal function cannot be completely excluded.

Pediatric Use

For prevention of anemia in premature newborns, the drug is used only in pre-filled syringes. It is administered subcutaneously at a dose of 250 IU/kg 3 times a week, as early as possible, preferably from the 3rd day of life, for 6 weeks.

In children and adolescents, the dose of the drug depends on age: as a rule, the younger the age, the higher the doses of Recormon^® required. However, since the individual response to the drug is unpredictable, it is advisable to start with the standard dosing regimen. For treatment of anemia associated with chronic kidney disease, Recormon^® should not be prescribed to children under 2 years of age.

Contraindication: children under 3 years of age (for cartridges with lyophilisate for preparing a solution for subcutaneous administration).

Geriatric Use

In clinical studies in elderly patients, no need for dose adjustment was identified.

Special Precautions

Inappropriate use of the drug by healthy individuals (e.g., as a doping agent) may cause a sharp increase in Hb levels, accompanied by life-threatening cardiovascular complications.

Since anaphylactoid reactions have been noted in isolated cases, the first dose of the drug should be administered under medical supervision.

Platelet count, hematocrit, and Hb should be regularly monitored during therapy with Recormon^®.

Recormon^® should be used with caution in refractory anemia in the presence of blast-transformed cells, epilepsy, thrombocytosis, and chronic hepatic insufficiency. Before starting treatment with Recormon^®, vitamin B₁₂ and folic acid deficiency should be ruled out, as they reduce the effectiveness of therapy.

Iron deficiency should be ruled out before starting treatment with Recormon^® and throughout the entire therapy period. If necessary, additional therapy with iron preparations may be prescribed according to clinical guidelines.

When treating patients with severe forms of phenylketonuria, the presence of phenylalanine as an excipient should be taken into account: in each pre-filled syringe — up to 0.3 mg (in 1000 IU, 2000 IU dosages) or up to 0.6 mg (10,000 IU, 20,000 IU, 30,000 IU), in each cartridge – up to 0.5 mg.

Lack of effect. The most common causes of an incomplete response to treatment with erythropoiesis-stimulating agents are iron deficiency and inflammation (as a result of uremia or progressive metastatic cancer). The following conditions reduce the effectiveness of treatment with erythropoiesis-stimulating agents: chronic blood loss, bone marrow fibrosis, a sharp increase in aluminum concentration due to hemodialysis, folic acid or vitamin B₁₂ deficiency, hemolysis. If all the listed conditions are excluded and the patient experiences a sudden decrease in Hb, reticulocytopenia, and antibodies to erythropoietin are detected, a bone marrow examination should be performed to rule out PRCA. If PRCA develops, therapy with Recormon^® must be discontinued, and patients should not be switched to therapy with other erythropoiesis-stimulating agents.

PRCA caused by neutralizing anti-erythropoietin antibodies may be associated with therapy with erythropoiesis-stimulating agents, including therapy with Recormon^® (0.107 cases per 10,000 patient-years with intravenous and subcutaneous use of Recormon^® for the treatment of renal anemia; 0.158 cases per 10,000 patient-years with subcutaneous administration of Recormon^® for the treatment of renal anemia). It is not recommended to switch patients to therapy with Recormon^® if there is a suspicion or confirmed presence of neutralizing erythropoietin antibodies.

Effect on tumor growth. Epoetins are growth factors that primarily stimulate the formation of red blood cells. Erythropoietin receptors may be present on the surface of various tumor cells. It cannot be excluded that erythropoiesis-stimulating agents may stimulate the growth of any type of malignant tumor.

In clinical studies on the treatment of anemia in cancer patients with epoetin beta, no statistically significant worsening of survival and tumor progression was registered.

In patients with chronic kidney disease or malignant tumors receiving chemotherapy, episodes of increased blood pressure and worsening of pre-existing arterial hypertension may occur, especially with a sharp increase in Hb levels. Increased blood pressure can be controlled with medication; if there is no effect, a temporary break in treatment with Recormon^® is necessary. It is recommended to regularly monitor blood pressure (especially at the beginning of therapy), including between dialysis sessions in patients with renal anemia. In some patients with chronic kidney disease, a hypertensive crisis with manifestations of encephalopathy may occur even with normal or low blood pressure. Immediate consultation with a physician is necessary, especially if sudden acute migraine-like headaches occur.

During treatment with Recormon^®, it is recommended to periodically monitor the serum potassium level. If hyperkalemia occurs, it is necessary to temporarily discontinue Recormon^® until the potassium concentration normalizes.

Patients with chronic kidney disease require an increased dose of heparin during hemodialysis sessions due to the increase in Hb. Occlusion of the dialysis system may occur with inadequate heparinization. Early revision of the shunt and timely prevention of thrombosis (e.g., taking acetylsalicylic acid) are recommended.

A moderate dose-dependent increase in platelet count within the normal range is possible, especially after intravenous administration of Recormon^®, with a subsequent spontaneous return to normal values with continued therapy. During the first 8 weeks of therapy, a weekly blood count, and especially platelet count, is necessary.

If Recormon^® is prescribed prior to autologous blood donation, the recommendations for the donation procedure should be followed

• Blood can only be taken from patients with a hematocrit value ≥ 33% (or hemoglobin not less than 110 g/l (6.83 mmol/l));
• Particular caution should be exercised in patients with body weight less than 50 kg;
• The volume of blood taken at one time should not exceed 12% of the patient’s estimated blood volume.

An increase in platelet count within the normal range is possible in patients receiving Recormon^® prior to autologous blood donation, so the platelet count should be monitored weekly. Treatment with Recormon^® is interrupted if platelets increase by more than 150×10⁹/l or in case of thrombocytosis.

Treatment with Recormon^® is indicated only for those patients for whom it is most important to avoid homologous blood transfusion, taking into account the risk-benefit ratio of homologous transfusion.

A slight increase in platelet count is possible in the prevention of anemia in premature newborns (up to the 12th-14th day), so regular monitoring of platelets is recommended.

The decision to use Recormon^® in patients with nephrosclerosis not receiving dialysis should be made individually, as the possibility of a more rapid deterioration of renal function cannot be completely excluded.

In most cases, the serum ferritin concentration decreases simultaneously with the increase in hemoglobin. Therefore, all patients with renal anemia and a serum ferritin concentration of less than 100 µg/l or transferrin saturation of less than 20% are recommended to take oral iron preparations (Fe²⁺) at a dose of 200-300 mg/day.

Patients with oncological and hematological diseases are treated with iron preparations according to the same principles, while patients with multiple myeloma, non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia with transferrin saturation of less than 25% can be administered 100 mg of Fe³⁺ per week intravenously. Premature infants should be prescribed oral iron therapy at a dose of 2 mg Fe²⁺ per day as early as possible (at the latest – on the 14th day of life). The iron dose is adjusted depending on the serum ferritin level. If it persistently remains below 100 µg/ml or there are other signs of iron deficiency, the dose of iron preparations should be increased to 5-10 mg/day and therapy should be continued until the signs of iron deficiency are resolved.

For patients with moderate anemia before planned major surgery, the drug is prescribed taking into account the benefits of using epoetin beta and the increased risk of thromboembolic complications.

In patients preparing to donate blood for subsequent autotransfusion, since they have indications of temporary iron deficiency, oral therapy with iron preparations (Fe²⁺) at a dose of 300 mg/day should be started simultaneously with Recormon^® therapy and continued until ferritin levels normalize. If, despite oral iron replacement therapy, signs of iron deficiency develop (ferritin level ≤ 20 µg/l or transferrin saturation less than 20%), the issue of additional intravenous administration of iron preparations should be considered. The Recormon^® solution in the cartridge contains benzyl alcohol as a preservative, which can cause neurological and other complications in newborns, which can sometimes be fatal.

Effect on ability to drive vehicles and operate machinery

Studies on the effect of the drug on the ability to drive vehicles and operate machinery have not been conducted. Based on the mechanism of action and safety profile, Recormon^® does not have such an effect.

Overdose

The therapeutic index of Recormon^® is very wide; however, the individual response to therapy at the beginning of treatment should be taken into account. An excessive pharmacodynamic response is possible, i.e., excessive erythropoiesis with life-threatening cardiovascular complications.

If the Hb level is high, therapy with Recormon^® should be temporarily interrupted. If necessary, phlebotomy may be performed.

Drug Interactions

Data obtained to date have not revealed any interaction of Recormon^® with other drugs.

To avoid incompatibility or reduced activity of the drug, another solvent should not be used and the drug should not be mixed with other medicinal products or injection solutions.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 2°C (35.6°F) to 8°C (46.4°F); do not freeze.

Shelf Life

The shelf life is 2 years.

The Reco-Pen pen injector with the inserted cartridge can be stored for 1 month at a temperature of 2-8°C (35.6°F – 46.4°F).

Dispensing Status

The drug is dispensed by prescription.

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.