Recormon10000 IU/0.6 ml

Recormon is a recombinant human erythropoietin (an erythropoiesis-stimulating agent, ESA) indicated for the treatment of anemia associated with specific clinical conditions. Indications below are organized by strength of evidence.

Established / Approved Indications

• Anemia associated with chronic kidney disease (CKD), including patients on dialysis (hemodialysis or peritoneal dialysis) and patients not yet on dialysis.
• Chemotherapy-induced anemia in patients with non-myeloid malignancies, where anemia is due to the effect of concomitant chemotherapy, to reduce the need for red blood cell transfusion.
• Prevention of anemia of prematurity in low-birth-weight premature infants, in markets where this indication is approved.
• Increasing yield of autologous blood from patients enrolled in a pre-operative autologous blood donation programme, to reduce exposure to allogeneic blood transfusion.

Important Limitations

• Recormon is not indicated for anemia due to iron, folate, or vitamin B12 deficiency, hemolysis, or bleeding; these underlying causes should be corrected first.
• Recormon is not intended to be used for the elective enhancement of athletic performance; such misuse can cause life-threatening cardiovascular complications.
• Use in cancer patients is intended only during a course of chemotherapy and only when anemia is not immediately life-threatening (see Precautions and Warnings for tumor progression risk).

Each pre-filled syringe/vial contains recombinant human Erythropoietin Beta (epoetin beta), produced by recombinant DNA technology in mammalian (Chinese hamster ovary) cell culture, as the active ingredient, available in strengths commonly ranging from 500 IU to 30,000 IU per mL, formulated as a sterile solution or lyophilized powder for injection with standard stabilizing excipients (e.g., human albumin or polysorbate, phosphate buffer, sodium chloride, urea).

Recormon is a glycoprotein produced by recombinant DNA technology that is structurally and biologically similar to endogenous human erythropoietin, the hormone naturally produced mainly by the kidneys that regulates red blood cell production. Recormon is classified as an erythropoiesis-stimulating agent (ESA) and is used to correct anemia in specific clinical settings by stimulating the bone marrow to produce more red blood cells.

Recormon is administered by subcutaneous or intravenous injection and is not taken orally, as it is a protein that would be degraded in the gastrointestinal tract.

Erythropoiesis-Stimulating Agent (ESA); Anti-anemic preparation (Recormon)

Mechanism of Action

Erythropoietin Beta binds to and activates the erythropoietin receptor on the surface of erythroid progenitor cells in the bone marrow. Receptor activation triggers the JAK2/STAT5 intracellular signaling pathway, which stimulates the proliferation, differentiation, and survival (by inhibiting apoptosis) of red blood cell precursors, ultimately increasing the release of reticulocytes and mature red blood cells into the circulation.

Pharmacokinetics

After subcutaneous injection, Erythropoietin Beta is absorbed slowly, reaching peak serum concentrations after 12–28 hours, with an elimination half-life of approximately 13–28 hours (longer than after intravenous administration). Bioavailability after subcutaneous injection is lower than after intravenous injection. The hematological response (rise in reticulocyte count) typically becomes apparent within 7–10 days, with a measurable rise in hemoglobin over 2–6 weeks.

Recormon is given only by subcutaneous or intravenous injection, never orally. It should be administered by a trained healthcare professional or by the patient/caregiver only after proper training on self-injection technique.

• Allow the pre-filled syringe or vial to reach room temperature before injection; do not shake vigorously, as this may denature the protein and reduce activity.
• Inspect the solution visually; do not use if discoloured or containing particulate matter.
• Each syringe or vial is for single use only; discard any unused portion.
• Rotate subcutaneous injection sites (thigh, abdomen, upper arm) to reduce local irritation.
• Do not mix Recormon with other medicinal products in the same syringe.

No clinically significant pharmacokinetic drug-drug interactions have been well established for Recormon in humans. It has not been shown to increase the myelotoxicity of cytostatic chemotherapy agents in available data.

• Iron supplementation: Adequate iron stores are required for an effective response to Recormon; iron supplementation is often needed concurrently, as iron deficiency will blunt the erythropoietic response (this is a supportive-therapy consideration rather than a true drug interaction).
• Androgens/other erythropoiesis-stimulating agents: Concomitant use with other agents that raise hemoglobin may increase the risk of excessive erythropoietic response; such combinations should be used cautiously and only with close hemoglobin monitoring.

Common and serious adverse effects reported with Recormon include:

• Very common/common: Hypertension, headache, injection-site reactions, flu-like symptoms (fever, chills, myalgia), arthralgia, and in premature infants, iron deficiency.
• Thromboembolic events: Including vascular access thrombosis in dialysis patients and venous thromboembolism in cancer patients (reported at a higher rate than in untreated controls).
• Rare but serious: Pure red cell aplasia (see Contraindications), severe cutaneous adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, anaphylactoid/hypersensitivity reactions, and seizures.

For the class-level boxed-warning risks of increased mortality, cardiovascular events, and tumor progression associated with higher hemoglobin targets, see Precautions and Warnings.

Pregnancy: There are limited clinical data on the use of Recormon in pregnant women. Recormon should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; use only under close physician supervision.

Lactation: It is not known whether Recormon is excreted in human milk in clinically significant amounts. A decision on whether to continue breastfeeding or continue/discontinue Recormon therapy should be made by weighing the benefit of breastfeeding to the infant against the benefit of therapy to the mother, in consultation with a physician.

Class Boxed-Warning Level Risks

Erythropoiesis-stimulating agents such as Recormon increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence when hemoglobin targets are higher than necessary. To minimize these risks:

• Use the lowest dose of Recormon sufficient to reduce the need for red blood cell transfusion; do not use Recormon to normalize hemoglobin or to reach a hemoglobin level above 12 g/dL.
• In patients with cancer, use Recormon only for chemotherapy-induced anemia and only when anemia is not immediately life-threatening; discontinue following completion of the chemotherapy course.
• In patients with chronic kidney disease, individualize dosing to maintain a hemoglobin level that minimizes transfusion need without exceeding recommended targets.

Other Precautions

• Hypertension: Blood pressure must be adequately controlled before starting therapy and monitored closely during treatment; Recormon should be used with caution or temporarily withheld if blood pressure is not well controlled.
• Pure red cell aplasia: If a patient develops a sudden loss of response to Recormon with severe anemia and low reticulocyte count, evaluate for antibody-mediated PRCA and discontinue Recormon (see Contraindications).
• Iron status: Iron stores should be evaluated and supplemented as needed before and during treatment, since iron deficiency reduces or prevents response.
• Seizures: Caution is advised, particularly in patients with chronic kidney disease with a seizure history.
• Hypersensitivity/severe skin reactions: Discontinue Recormon immediately if signs of a severe hypersensitivity or severe cutaneous reaction occur.
• Regular monitoring of blood pressure, hemoglobin (to avoid overshoot), and iron status is required throughout treatment with Recormon.

Overdose of Recormon can cause an excessive rise in hemoglobin/hematocrit (polycythemia) above the desired therapeutic range, which increases the risk of serious cardiovascular and thromboembolic complications, including severe hypertension. There is no specific antidote.

If overdose is suspected or hemoglobin rises excessively, seek immediate medical attention. Management is supportive and may include temporary withholding of Recormon, close monitoring of blood pressure and hemoglobin, and therapeutic phlebotomy if clinically indicated, as directed by a physician. Do not attempt to manage a suspected overdose at home; contact a doctor, hospital emergency department, or poison control service immediately.

Store Recormon in a refrigerator (2°C to 8°C); do not freeze. Keep the container in the outer carton to protect from light. Do not shake. If required for ambulatory use, a single unopened syringe may be kept at room temperature (below 25°C) for a limited period as specified on the product label, but should then be discarded if not used. Keep out of reach of children.

• Renal impairment: Anemia of chronic kidney disease is itself a primary indication for Recormon; dosing is individualized based on hemoglobin response rather than a formal renal dose-adjustment table.
• Hepatic impairment: Data are limited; use with caution and monitor closely.
• Pediatric patients: Recormon is used for anemia of chronic kidney disease in children under specialist supervision, and for prevention of anemia of prematurity in eligible low-birth-weight infants where this indication is approved (see Pediatric Uses). Safety and efficacy in other pediatric settings are not well established.
• Elderly patients: No specific dose adjustment is required based on age alone, but elderly patients, particularly those with cardiovascular disease, should be monitored closely given the class risks described in Precautions and Warnings.

Duration of Recormon therapy depends on the indication. In chronic kidney disease, treatment is typically long-term/chronic, continuing as long as anemia management is needed, with periodic dose review based on hemoglobin trends. In chemotherapy-induced anemia, Recormon is used only for the duration of the chemotherapy course and is generally discontinued approximately 4 weeks after the chemotherapy course ends. In prevention of anemia of prematurity, treatment is typically limited to about 6 weeks. In autologous blood donation programmes, treatment is limited to the pre-operative donation period (typically 3–4 weeks). The treating physician determines the exact duration based on clinical response.

Erythropoiesis-Stimulating Agents (ESAs); Hematopoietic/Hematinic Growth Factors; Anti-anemic preparations

Erythropoietin Beta is a recombinant analogue of endogenous erythropoietin. It acts by binding to the erythropoietin receptor (EpoR) expressed on erythroid progenitor cells (burst-forming units-erythroid and colony-forming units-erythroid) in the bone marrow. Receptor dimerization activates the receptor-associated tyrosine kinase JAK2, which phosphorylates and activates STAT5 and other downstream signaling pathways (including PI3K/Akt and MAPK), promoting progenitor cell proliferation, differentiation into mature erythrocytes, and inhibition of apoptosis. The net effect is an increase in circulating reticulocytes and red blood cells, raising hemoglobin and hematocrit.

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Recormon is approved for the treatment of anemia associated with chronic kidney disease in pediatric patients, using individualized, weight-based dosing under the supervision of a pediatric nephrology specialist; younger children may require relatively higher doses per kilogram to achieve a comparable response to adults.

Recormon is also used, in markets where this indication is approved, for the prevention of anemia of prematurity in low-birth-weight preterm infants (typically born before 34 weeks' gestation and weighing 750 g to 1500 g at the start of treatment), administered subcutaneously under neonatal specialist supervision.

For other pediatric uses (e.g., chemotherapy-induced anemia in children), safety and efficacy have not been well established, and use should occur only under specialist guidance with close monitoring.