Recogen

Approved Indications:

• Anemia in Chronic Kidney Disease (CKD):
• Indicated for anemia in adult and pediatric patients with CKD on dialysis and not on dialysis.
• Anemia in Cancer Patients Receiving Chemotherapy:
• Indicated for anemia due to myelosuppressive chemotherapy in patients with non-myeloid malignancies.
• Reduction of Allogeneic Blood Transfusion:
• Used to reduce the need for allogeneic RBC transfusions in anemic patients scheduled for elective, noncardiac, nonvascular surgery.
• Anemia Associated with Zidovudine Treatment in HIV-infected Patients:
• Indicated for anemia due to zidovudine in HIV-infected patients with endogenous serum erythropoietin ≤500 mUnits/mL.

Important Off-Label/Clinically Accepted Uses:

• Myelodysplastic Syndromes (MDS):
• Used to manage anemia in low-risk MDS patients.
• Anemia in Premature Infants:
• Occasionally used to reduce the need for transfusions in neonatal intensive care.

General Principles:

• Administer via IV or Subcutaneous (SC) route.
• Use the lowest effective dose to reduce RBC transfusion needs.
• Monitor hemoglobin levels regularly.

Adults with CKD on Dialysis:

• Initial dose (SC/IV): 50 to 100 units/kg, 3 times weekly.
• Adjust: Increase or decrease by 25% no more frequently than every 4 weeks.

Adults with CKD not on Dialysis:

• Initial dose: 50 to 100 units/kg SC/IV, once to three times weekly.
• Alternative: 10,000 units SC once weekly.

Pediatrics with CKD:

• Initial dose: 50 units/kg SC/IV, 3 times weekly.
• Adjustments based on hemoglobin response.

Chemotherapy-Induced Anemia:

• Initial dose: 150 units/kg SC thrice weekly or 40,000 units SC once weekly.
• Duration: Discontinue if no response after 8 weeks.

Zidovudine-induced Anemia in HIV:

• Dose: 100 units/kg IV/SC three times weekly.

Surgical Patients:

• 300 units/kg/day SC for 10 days before surgery, day of surgery, and 4 days after
  OR
  600 units/kg SC weekly for 3 weeks before surgery and on day of surgery.

Special Populations:

• Renal Impairment: Adjust based on hemoglobin target.
• Hepatic Impairment: Use with caution; no clear dose adjustment guidelines.
• Elderly: No dosage adjustment required but monitor closely.

Erythropoietin alfa is a recombinant human erythropoietin that stimulates erythropoiesis. It binds to erythropoietin receptors on erythroid progenitor cells in the bone marrow, activating the JAK2/STAT5 signaling pathway. This leads to proliferation and differentiation of committed erythroid progenitors into mature red blood cells. As a result, it increases reticulocyte counts, hemoglobin levels, and hematocrit, effectively correcting anemia and reducing the need for blood transfusions.

• Absorption:
  SC administration has a bioavailability of approximately 20–30%. Peak levels occur 12–18 hours post-injection.
• Distribution:
  Distributed mainly in plasma; volume of distribution (Vd) is low, ~0.04 L/kg.
• Metabolism:
  Cleared primarily by the liver and kidneys. Catabolized into amino acids and peptides.
• Elimination:
• Half-life:
• IV: ~4–13 hours
• SC: ~18–25 hours (prolonged absorption phase)
• Excretion: Mostly via liver; minimal unchanged drug excreted in urine.

• Pregnancy:
  Classified as FDA Category C. Animal studies have shown adverse fetal effects, but there are no adequate, well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk.
• Lactation:
  It is not known whether erythropoietin alfa is excreted in human milk. Caution is advised if administered to breastfeeding women. Monitor infant for adverse effects if use is necessary during lactation.

• Primary Class: Erythropoiesis-Stimulating Agent (ESA)
• Subclass: Recombinant Human Erythropoietin (rhEPO), Glycoprotein Hormone

• Hypersensitivity to erythropoietin alfa or any of its components
• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) following treatment with any erythropoietin
• Serious allergic reactions to mammalian cell-derived products or albumin (human)
• Recent surgery patients not receiving prophylactic anticoagulation

• Increased Risk of Mortality & Tumor Progression: In cancer patients receiving ESA; use only when anemia is due to chemotherapy.
• Cardiovascular Events: Risk of stroke, myocardial infarction, and thromboembolic events, particularly if hemoglobin >11 g/dL.
• Hypertension: Monitor and control before initiating therapy.
• Seizures: Higher risk during initial treatment phase.
• PRCA: Rare but serious; discontinue permanently if suspected.
• Monitoring: Regular hemoglobin checks (every 1–2 weeks initially), BP, and iron status.

Common:

• Hematologic: Hypertension, thrombosis, headache
• Gastrointestinal: Nausea, vomiting, diarrhea
• Musculoskeletal: Arthralgia, muscle pain
• General: Fever, fatigue, injection site reactions

Serious/Rare:

• Pure red cell aplasia (PRCA)
• Seizures
• Myocardial infarction
• Stroke
• Tumor progression in cancer patients

Timing & Severity:

• Most adverse effects occur within weeks of therapy initiation and may be dose-dependent. Monitor patients closely during dose adjustments.

• Cyclosporine: Competes for binding to RBCs; may need dose adjustment.
• Iron Supplements: Necessary for optimal erythropoiesis; deficiency may reduce efficacy.
• ACE Inhibitors/ARBs: May blunt response in some patients.
• Aluminum-containing antacids: Long-term use may affect bone marrow response.

CYP450 Interactions:
Erythropoietin alfa is not significantly metabolized via CYP450 enzymes.

• FDA Guidance: Emphasis on individualized dosing using the lowest effective dose to reduce the need for RBC transfusions.
• Black Box Warning Updates: Strengthened for cancer-related anemia due to increased mortality and tumor progression risk.
• NICE & KDIGO: Recommend restricted ESA use to specific Hb thresholds (typically <10 g/dL) in CKD and careful monitoring of iron status.

• Storage Temperature:
  Store in a refrigerator at 2°C to 8°C. Do not freeze.
• Light Protection:
  Keep in the original package to protect from light.
• Handling:
  Do not shake. Discard if solution is discolored or contains particles.
• Reconstitution/Preparation:
  Not applicable for prefilled syringes or single-dose vials. Administer immediately once opened.