Epoetin alfa is 165 amino acid glycoprotein manufactured by recombinant DNA technology, which has similar biological effects as endogenous erythropoietin. Erythropoietin stimulates red blood cell production in-situ. It is a hormone produced in the kidney and augments the differentiation of erythroid progenitors in the bone marrow. Indications of epoetin are as below. 

FDA Approved[1][2][3][4]:

1. Chronic kidney disease patients who are on dialysis and not on dialysis 
2. The patient receiving myelosuppressive therapy for cancer
3. Anemia due to zidovudine in HIV-infected patient 
4. Reduction of allogeneic blood transfusion requirement in the patient who undergoes elective, noncardiac, nonvascular surgery

NON-FDA Approved[5][6][6][7][8][9][10][9][7][6]:

1. Blood transfusion refusing patients like Jehovah’s Witnesses 
2. Anemia during therapy for chronic hepatitis C 
3. Myelodysplastic syndrome 
4. Symptomatic management for anemia
5. Preterm anemia  

Epoetin alfa is a recombinant human erythropoietin, which is nearly identical to the endogenous hormone erythropoietin (EPO). Erythropoietin occurs in the peritubular cells of the kidney. Anemia and hypoxia are sensed by these cells and lead to the rapid secretion of EPO, which acts on erythroid marrow. Hypoxia-inducible factor (HIF-1) is a (HIF-1 alpha and HIF-1 beta) transcription factor that boosts the expression of erythropoietin in the setting of hypoxia. During the state of hypoxia, the prolyl hydroxylase is inactive, allowing the accumulation of HIF-1 alpha and activating erythropoietin expression, which stimulates erythroid progenitors. 

Erythropoietin binds to specific receptors (JAK-STAT-binding receptor) on the surface of its target cells. It subsequently alters the phosphorylation of intracellular proteins and activates transcription factors to regulate gene expression. The magnitude of increase in red blood cell concentration after administration of epoetin alfa is primarily dependant on the length of time this medication is maintained, not by its concentration level.

It induces erythropoiesis in a dose-dependent manner but does not affect the RBC lifespan which results in:

1. Stimulates the proliferation of colony-forming cells of the erythroid series
2. Induces hemoglobin formation and erythroblast maturation
3. Releases reticulocytes in circulation, followed by a rise in hematocrit and hemoglobin levels.[11]

A clinically significant increase in hemoglobin is usually not observed in less than two weeks because of the length required for erythropoiesis process. The erythroid progenitors take several days to mature and undergo release into the circulation.  

Epoetin alfa is available in single-dose, preservative-free, or multi-dose, preserved vials.

This medication can be administered via the intravenous or subcutaneous route. Subcutaneous is the preferred route for administration except in patients with end-stage kidney disease who are on maintenance hemodialysis. In dialysis patients and neonates, the IV route is recommended.[12] 

When injected intravenously, epoetin alfa clears from plasma with a half-life of 4 to 8 hours. However, the effect on bone marrow progenitors lasts much longer, and once-weekly dosing can be sufficient sometimes. Single vial dose is preservative-free, so, should be diluted in a syringe as a 1 to 1 dilution using normal saline in adults but do not dilute in neonates or infants.[13] Multiple-dose vials contain benzyl alcohol. Shaking of injection can denature the glycoprotein making the drug biologically inactive. This product should not be used if it is shaken or frozen.

The patients who are on erythropoietin therapy may develop absolute (decreased ferritin levels with low transferrin saturation) or functional iron deficiency (normal ferritin levels with low transferrin saturation). This deficiency results from an inability to move enough amount of iron rapidly from storage to support the enhanced erythropoiesis.

It increases the risk of serious cardiovascular events, vascular access thrombosis, stroke, myocardial infarction, venous thromboembolism in clinical studies when target Hb levels reach more than 11 g/dL or a rapid rise in hemoglobin over 1 g/dL over two weeks (U.S. Boxed Warning). Although epoetin alfa does not affect blood pressure directly, it may raise blood pressure in the early phase after administration when the hematocrit is increasing acutely. So, it should be used very carefully in patients with uncontrolled hypertension. Additionally, patients may require dosage adjustments of antihypertensive therapy after initiation of this medication. 

Pure red cell aplasia may occur in patients treated with specific epoetin alfa formulations. In chronic renal failure patients, chances of hypertensive encephalopathy and seizures have increased, particularly those who have a previous history of seizures. Headache, nausea, shortness of breath, edema,  vomiting, tachycardia, diarrhea have also been noted. Injection site erythema and flu-like symptoms (like arthralgias and myalgias) can occur, which lasts for 2 to 4 hours.

Due to a sudden increase in hematocrit, blood viscosity, and peripheral vascular resistance, particularly dialysis patients, may require to adjust anticoagulation. Serious thromboembolic events like increased clot formation in atrioventricular (AV) shunts, migratory thrombophlebitis, microvascular thrombosis, thrombosis of major vessels like retinal, temporal, pulmonary, and renal vessels increases. The risk of thrombotic events is even higher in adults with ischemic heart disease or congestive heart failure. So, lower target hematocrit should be preferable in these patients. Some dosage forms may contain benzyl alcohol, which is associated with fatal toxicity “gasping syndrome” in neonates.[14]

Absolute contraindications:

• Multiple dosage vials contain benzyl alcohol, so this formulation is contraindicated in neonates, infants, pregnant women, and breastfeeding women. (Single dosage vial which is preservative-free should be used) 
• Uncontrolled hypertension
• Known hypersensitivity to mammalian cell-derived products
• Known hypersensitivity to albumin 
• Pure red cell aplasia that begins after treatment

Absolute contraindications:

• Due to the delayed onset of erythropoiesis, it is contraindicated for acute correction of severe anemia or emergency transfusion.
• It should be used cautiously in with patients who have a history of seizures
• In patients with cancer receiving hormonal agents, biologic products, or radiotherapy
• In patients undergoing cardiac or vascular surgery
• In patients who receive myelosuppressive therapy when the anticipated outcome is curative