EPO

Dosing from the Literature

Published for anemia: label doses, most by body weight, for kidney disease, chemotherapy, zidovudine and surgery, and the trial doses behind them (Epogen label; Eschbach et al., 1989). Not published: any dose for healthy people outside a trial, and any hemoglobin target, dose or schedule that the label says does not carry the risks in its boxed warning.

The rows below are the doses as the current US label and the published trials give them, each with the population it was given to. The label’s doses are adjusted against weekly hemoglobin measurements and iron status, by prescribers, and every one of them sits under the boxed warning quoted in Side Effects & Risks.

What It Is

EPO is erythropoietin, a glycoprotein hormone that sets how many red blood cells are in circulation and is made in the kidney or liver of adult mammals (Jacobs et al., 1985); low oxygen switches its gene on, through an enhancer that work on human cells traced to a nuclear factor hypoxia itself induces (Semenza & Wang, 1992). It is a glycoprotein, not a short peptide. The Epogen label describes epoetin alfa as “a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology,” of about 30,400 daltons, produced by mammalian cells into which the human erythropoietin gene has been introduced, and carrying “the identical amino acid sequence of isolated natural erythropoietin” (Epogen label). UniProt records the human protein as a 193-residue precursor with a 166-residue chain after the signal peptide is cut, with three N-linked and one O-linked glycosylation site (UniProt P01588); the Amgen group that cloned the gene calculated 18,399 daltons for the protein chain, so most of the difference from the label’s figure is sugar (Lin et al., 1985).

The hormone was chased for decades before anyone had enough of it to use. In 1977 a University of Chicago group purified human erythropoietin from the urine of patients with aplastic anemia, reaching 70,400 units per mg of protein in a seven-step procedure (Miyake et al., 1977). In 1985 two groups published the gene: Amgen’s, which isolated it from a genomic library and expressed active hormone in Chinese hamster ovary cells (Lin et al., 1985), and a Genetics Institute group, which reported genomic and cDNA clones and noted that highly purified erythropoietin “may be useful in the treatment of various forms of anaemia, particularly in chronic renal failure” (Jacobs et al., 1985). Within a year ten patients on haemodialysis in Oxford were given it, and all of them made more reticulocytes and raised their haemoglobin, from a mean 6.1 g/dL across the ten to a mean 10.3 g/dL in the nine treated for 12 weeks (Winearls et al., 1986). The US trials followed in 1987 and 1989 (Eschbach et al., 1987; Eschbach et al., 1989), and FDA licensed epoetin alfa on June 1, 1989 (Drugs@FDA).

One license, BLA 103234, covers Epogen and Procrit: Amgen holds it and manufactures both, and the Procrit label is issued for Janssen Products (Drugs@FDA; Procrit label). The biosimilar Retacrit (epoetin alfa-epbx) was licensed on May 15, 2018 under BLA 125545, held by Hospira, a Pfizer company; its label states that it is biosimilar to Epogen/Procrit and is produced in a Chinese hamster ovary cell line (Drugs@FDA; Retacrit label). Two longer-acting relatives are licensed separately: darbepoetin alfa (Aranesp, Amgen, BLA 103951, approved September 17, 2001), dosed weekly to monthly, and methoxy polyethylene glycol-epoetin beta (Mircera, BLA 125164, approved November 14, 2007, its current US label issued by Vifor International), dosed every two weeks or monthly (Drugs@FDA; Aranesp label; Mircera label). Mircera’s label says it is not indicated for anemia due to cancer chemotherapy, and that a dose-ranging study of it was terminated early because of more deaths than with another ESA (Mircera label). In the European Union the agency’s medicines table lists epoetin alfa biosimilars (Binocrit, Abseamed, Epoetin Alfa Hexal, all authorised in August 2007), epoetin zeta (Retacrit, Silapo), epoetin beta (NeoRecormon; authorised 1997), epoetin theta (Eporatio, Biopoin), darbepoetin alfa (Aranesp; authorised 2001) and Mircera (2007); epoetin delta (Dynepo) is listed as withdrawn (European Medicines Agency medicines table, read October 4, 2026).

PubMed returns 2,393 records for “epoetin alfa” and 25,451 under the MeSH term Erythropoietin, 331 of the epoetin alfa records tagged as randomized controlled trials (searched October 4, 2026). About two-thirds of the “epoetin alfa” records, 1,515 of them, mention anemia (PubMed, searched October 5, 2026); a smaller literature covers its effects in healthy people and its detection in sport (Heuberger et al., 2013; Equey et al., 2025).

Mechanism of Action

Every finding below names its model: cells, mice, rats or people. Most of this work ran alongside the drug itself, in the decade after the gene was cloned (D’Andrea et al., 1989; Witthuhn et al., 1993).

• Erythropoietin receptor (EPOR), a JAK2-coupled cytokine receptor — The murine receptor was cloned from erythroleukemia cells in 1989 and found to be a 507-amino-acid polypeptide with a single membrane-spanning domain and no similarity to known proteins at the time (D’Andrea et al., 1989). The receptor has no kinase domain of its own; in cell work, erythropoietin induced tyrosine phosphorylation of the kinase JAK2 and activated it, and JAK2 associated with the membrane-proximal part of the receptor’s cytoplasmic tail that the receptor needs to work (Witthuhn et al., 1993).
• Survival, not creation, of red-cell progenitors — In mouse erythroid progenitor cells, withdrawal of erythropoietin produced the DNA fragments characteristic of apoptosis within 2 to 4 hours and the cells began dying by 16 hours; with the hormone they survived and matured into reticulocytes, and DNA cleavage fell by a factor of 2.6 (Koury & Bondurant, 1990). In mouse embryos engineered to lack erythropoietin or its receptor — they died around embryonic day 13 — committed erythroid progenitors (BFU-E and CFU-E) were still present in the fetal liver, so the hormone is needed for the proliferation, survival and terminal maturation of CFU-E progenitors rather than for their formation (Wu et al., 1995).
• Where it is made: cells between the tubules of the kidney cortex — In situ hybridization in anemic mouse kidneys labelled an uncommon cell type in the cortex, clearly neither glomerular nor tubular, sitting outside the tubular basement membrane, consistent with a subset of interstitial or capillary endothelial cells (Koury et al., 1988).
• Oxygen sensing through HIF — A 50-nucleotide enhancer 3′ of the human erythropoietin gene drove a sevenfold transcriptional induction under low oxygen in Hep3B cells, and bound a nuclear factor that hypoxia itself induced — the work that opened up hypoxia-inducible factor (Semenza & Wang, 1992).
• A second, non-erythropoietic receptor (the basis of ARA-290) — Membrane proteins from rat brain, heart, liver and kidney enriched for the erythropoietin receptor bound in a complex with the beta-common receptor (CD131), and neither erythropoietin nor carbamylated erythropoietin protected cardiomyocytes or spinal cord in beta-common-receptor knockout mice; the authors proposed this heteroreceptor as the tissue-protective one (Brines et al., 2004). A peptide built to copy the outward, water-facing side of helix B — 11 amino acids, in an order that does not occur in erythropoietin itself — was tissue-protective in rodent models without being erythropoietic in vitro or in vivo (Brines et al., 2008). Its pyroglutamate form, pHBSP, which that paper also synthesized and tested, is ARA-290 (Collino et al., 2015). Both papers were led by Brines and Cerami: ten of the 2004 paper’s 16 authors were minority stockholders of Warren Pharmaceuticals, and six of the 2008 paper’s 16 were its employees when the work was done; the company was commercializing tissue-protective cytokines and developing erythropoietin analogues (Brines et al., 2004; Brines et al., 2008).
• In people: the blood changes, and so does the plasma — A review of erythropoietin in healthy humans concludes that it raises arterial oxygen content both by increasing red-cell volume and by an equally important fall in plasma volume, lowers renin and aldosterone promptly, and raises arterial blood pressure even in healthy subjects; the same review reports that the functional effects on skeletal muscle appear limited (Lundby & Olsen, 2011).
• Receptors on tumor cells (a proposed explanation, not a proven one) — In 154 of 157 randomly assigned head-and-neck cancer patients whose tumors were stained, in a randomized trial of epoetin beta with radiotherapy, locoregional progression-free survival was substantially poorer with epoetin beta among those whose tumors stained positive for erythropoietin receptors (adjusted relative risk 2.07, 95% CI 1.27–3.36) and not among receptor-negative patients; the difference between the two relative risks was of borderline significance (P = .08) (Henke et al., 2006). A later study using archival tissue from the same trial measured receptor, JAK2 and HSP70 messenger RNA and found no difference in locoregional progression-free survival by expression level except in the 28 patients with unresected tumors (Miller et al., 2009).

What the Research Shows

The human trials are in the next section. What follows is the animal and laboratory record, most of it from the label’s own nonclinical section, and the label’s own summary of what the drug does to the blood in people.

• Reproductive toxicity in rats — Given to male and female rats before and during mating and to females to gestational day 7, 100 and 500 Units/kg a day caused slight increases in pre- and post-implantation loss and fewer live fetuses; the label notes that 100 Units/kg a day approximates its own starting dose (Epogen label). Pregnant rats and rabbits given intravenous doses the label states as up to 500 mg/kg a day during organogenesis showed no teratogenic effects, and rat pups exposed at 500 Units/kg a day late in pregnancy had fewer caudal vertebrae, less weight gain and delayed development alongside maternal toxicity (Epogen label).
• Genotoxicity and carcinogenicity — Epoetin alfa was negative in the bacterial reverse mutation assay, a mammalian cell gene mutation assay, an in vitro chromosomal aberration assay and the in vivo mouse micronucleus assay; its carcinogenic potential has not been evaluated (Epogen label).
• No central nervous system activity in animals — The label’s abuse section reports that in animal studies epoetin alfa did not distribute to the central nervous system and produced no behavioral effects consistent with central activity (Epogen label).
• Tissue protection in rodents, separable from red cells — Erythropoietin was protective in rodent models of ischemic, traumatic, toxic and inflammatory injury, and carbamylated erythropoietin, which does not bind the erythropoietin receptor, was protective without stimulating erythropoiesis (Brines et al., 2004). Helix-B peptides were protective in models of ischemic stroke, diabetes-induced retinal edema, peripheral nerve trauma and renal ischemia-reperfusion, and accelerated wound healing in rodents (Brines et al., 2008). Both of those papers were led by Brines and Cerami: ten of the 2004 paper’s 16 authors were minority stockholders of Warren Pharmaceuticals, and six of the 2008 paper’s 16 were its employees when the work was done; the company was commercializing tissue-protective cytokines and developing erythropoietin analogues (Brines et al., 2004; Brines et al., 2008). None of that preclinical neuroprotection has been confirmed in the human trials below (Ehrenreich et al., 2009; Nichol et al., 2015; Juul et al., 2020; Wu et al., 2022).
• What it does to the blood, in people — The reticulocyte count rises within 10 days and the hemoglobin and hematocrit within 2 to 6 weeks in most patients, at a rate that depends on the dose: in adults on dialysis given starting doses into a vein, 0.5 g/dL in 2 weeks at 50 Units/kg three times weekly, 0.8 at 100 and 1.2 at 150 (Epogen label).

Human Data

Published: PubMed tags 331 of the 2,393 “epoetin alfa” records as randomized controlled trials — records, not separate trials; some are secondary analyses of one trial and some use epoetin alfa only as the comparator (searched October 4, 2026). What follows is the record the label rests on, the trials that produced its boxed warning, and the trials in people who were not anemic. Registered, with no results posted: 13 trials that test the drug itself, alone or combined with another drug, have an estimated primary completion still ahead, eight of them recruiting and five not yet recruiting (ClinicalTrials.gov, searched October 5, 2026); the largest is a Phase 3 in 2,500 critically ill trauma patients (ClinicalTrials.gov NCT04588311), and Legal Status lists all 13. Not counted: a Phase 4 that mixes an erythropoietin gel into bone graft around dental implants, a local use rather than an injection (ClinicalTrials.gov NCT07523412). A Phase 3 of early against late epoetin alfa in lower-risk myelodysplastic syndromes is listed as active, its primary data collection finished in September 2023 and no results posted (ClinicalTrials.gov NCT03223961).

• Kidney disease, the first trials — Ten haemodialysis patients in Oxford, given rising intravenous doses of 3–192 IU/kg after each dialysis, all raised reticulocytes and haemoglobin, and none of the four who had been transfusion-dependent needed further transfusions after the first week; one had hypertensive encephalopathy and two had clotting in their arteriovenous fistulas (Winearls et al., 1986). In 25 US patients, 15–500 Units/kg three times weekly produced dose-dependent erythropoiesis; of 18 on effective doses, 12 who had required transfusions no longer needed them, 4 had a rise in blood pressure, and no antibodies to the hormone formed (Eschbach et al., 1987).
• The Phase 3 in hemodialysis, 333 patients (Eschbach et al., 1989) — Hematocrit rose from 0.223 to 0.35, or by more than 0.06 over baseline, within 12 weeks in 97.4%, and the 1,030 transfusions given in the previous six months were eliminated in all patients within 2 months. Adverse effects: iron deficiency in 43%, higher blood pressure in 35%, seizures in 5.4%, myalgias in 5%.
• Quality of life in dialysis, 118 patients (Canadian Erythropoietin Study Group, 1990) — Double-blind and placebo-controlled, three groups. Haemoglobin at six months was 74 g/L on placebo, 102 and 117 g/L on the two erythropoietin targets. Fatigue, physical symptoms, relationships and depression scores improved against placebo and the stress-test distance increased, but the six-minute walk and psychosocial scores did not; diastolic blood pressure rose, and 11 of 78 treated patients had their access clotted against 1 of 40 on placebo.
• HIV and zidovudine, 63 patients (Fischl et al., 1990) — Randomized, double-blind, placebo-controlled: 100 Units/kg three times weekly by intravenous bolus. Transfusions fell in patients whose own erythropoietin was ≤ 500 IU/L and not in those above it; serious side effects were no more common than on placebo. The label’s indication still carries that ≤ 500 mUnits/mL cut-off (Epogen label).
• Chemotherapy anemia, 344 patients (Witzig et al., 2005) — Double-blind, placebo-controlled, 40,000 Units weekly under the skin for 16 weeks: hemoglobin rose 2.8 g/dL against 0.9 on placebo, 25.3% were transfused against 39.6% (P = .005), and quality-of-life scores did not differ between the groups. The label counts the same 344-patient study differently, from week 5 through week 16 or the end of the study: 14% transfused against 28% (Epogen label).
• Children on chemotherapy, 222 patients (Razzouk et al., 2006) — Double-blind, placebo-controlled, 600–900 Units/kg intravenously weekly for 16 weeks in patients aged 5 to 18. Hemoglobin rose more and 38.7% were transfusion-free after 4 weeks against 22.5% (P = .010), but the health-related quality-of-life scores did not differ.
• Surgery, 316 and 145 patients (de Andrade et al., 1996; Goldberg et al., 1996; Epogen label) — In the placebo-controlled trial, in 316 patients scheduled for major orthopedic surgery and expected to need at least 2 units of blood, 300 IU/kg for 15 days cut exposure to donor blood to 16% against 45% on placebo in those whose baseline hemoglobin was above 10 and up to 13 g/dL (P = 0.024) (de Andrade et al., 1996). A second trial, of 145 patients by the label’s count, found 600 IU/kg weekly at least as effective as the daily 300 IU/kg regimen, with a larger rise in hemoglobin before surgery (1.44 against 0.73 g/dL) (Goldberg et al., 1996; Epogen label). Where no anticoagulant was given, mechanical clot prophylaxis being allowed, in 680 spinal-surgery patients deep vein thrombosis was found in 4.7% on epoetin alfa against 2.1% on standard care (Stowell et al., 2009).
• Aiming higher, trial one: 1,233 hemodialysis patients with heart disease (Besarab et al., 1998) — 618 assigned to a hematocrit of 42% and 615 to 30%, median 14 months of treatment. After 29 months there were 183 deaths and 19 non-fatal heart attacks in the normal-hematocrit group against 150 and 14 (risk ratio 1.3, 95% CI 0.9–1.9). The trial was halted, although the difference in event-free survival had not reached its prespecified stopping boundary, and the authors concluded against raising the hematocrit to 42% in such patients. The label’s analysis of the same trial, which it counts as 1,265 patients, gives all-cause mortality of 35% against 29% with a hazard ratio of 1.27 (1.04–1.54), and the primary endpoint of death or non-fatal heart attack a hazard ratio of 1.28 (1.06–1.56) (Epogen label).
• Aiming higher, trial two: CHOIR, 1,432 patients not on dialysis (Singh et al., 2006) — Open-label, epoetin alfa to a hemoglobin of 13.5 against 11.3 g/dL, median 16 months. The composite of death, heart attack, heart-failure hospitalization and stroke occurred 125 times against 97 (hazard ratio 1.34, 95% CI 1.03–1.74; P = 0.03), quality-of-life improvements were similar, and the trial was terminated early.
• Aiming higher, trial three: TREAT, 4,038 patients (Pfeffer et al., 2009) — Randomized, double-blind, placebo-controlled, in patients with type 2 diabetes and chronic kidney disease not on dialysis; 2,012 assigned to darbepoetin alfa to about 13 g/dL and 2,026 to placebo with rescue below 9. Neither primary composite was reduced (death or cardiovascular event: hazard ratio 1.05, 0.94–1.17). Stroke occurred in 101 patients on darbepoetin against 53 on placebo (hazard ratio 1.92, 1.38–2.68; P < 0.001). Transfusions were given to 297 against 496, and the improvement in fatigue was modest.
• Normalizing hemoglobin in earlier kidney disease: CREATE, 603 patients (Drüeke et al., 2006) — Epoetin beta to 13.0–15.0 g/dL against 10.5–11.5. Complete correction did not change the likelihood of a first cardiovascular event (58 against 47; hazard ratio 0.78, 0.53–1.14); dialysis was required in more patients in the fully corrected group (127 against 111, P = 0.03), while general health and physical function scores improved.
• Cancer, where survival got worse — In 939 women with metastatic breast cancer on first-line chemotherapy, most of them not anemic, epoetin alfa 40,000 U weekly to hold hemoglobin at 12–14 g/dL was stopped early for higher mortality; 12-month survival was 70% against 76% on placebo (P = .01) (Leyland-Jones et al., 2005). In 351 anemic head-and-neck cancer patients having curative radiotherapy, epoetin beta 300 IU/kg three times weekly brought haemoglobin above 14 g/dL in women or 15 g/dL in men in 82% of patients against 15% on placebo, but locoregional progression-free survival was poorer (adjusted relative risk 1.62, 95% CI 1.22–2.14; P = 0.0008) and so was survival (1.39, 1.05–1.84; P = 0.02) (Henke et al., 2003). Pooling 53 trials and 13,933 patients, mortality during the active study period was higher with these drugs (combined hazard ratio 1.17, 95% CI 1.06–1.30) and overall survival slightly worse (1.06, 1.00–1.12) (Bohlius et al., 2009).
• Critical illness, 1,460 patients (Corwin et al., 2007) — 40,000 U weekly for up to three weeks in intensive-care patients did not reduce the proportion transfused (relative risk 0.95, 0.85–1.06) and raised thrombotic events (hazard ratio 1.41, 1.06–1.86); mortality at day 29 tended lower (adjusted hazard ratio 0.79, 0.56–1.10), and in the prespecified trauma subgroup the adjusted hazard ratio was 0.37 (0.19–0.72).
• Brain and heart protection: five negative trials — In 522 patients with acute ischemic stroke given 40,000 IU intravenously within 6 hours and at 24 and 48 hours, no outcome favoured erythropoietin and deaths were 16.4% against 9.0% on placebo (odds ratio 1.98, 1.16–3.38; P = 0.01); 63.4% of the patients also received the clot-dissolving drug rtPA, and the authors raised the safety concern particularly for those patients (Ehrenreich et al., 2009). In 606 patients with moderate-to-severe traumatic brain injury, 40,000 units weekly for up to three doses did not reduce severe neurological dysfunction (relative risk 0.99, 0.83–1.18); deaths at 6 months were 11% against 16% (relative risk 0.68, 0.44–1.03; P = 0.07), and deep venous thrombosis of the lower limbs did not rise (Nichol et al., 2015). Those survival signals, with the trauma subgroup above, are what a running Phase 3 in 2,500 trauma patients is testing; its registry record names the brain-injury trial as the research behind it (ClinicalTrials.gov NCT04588311). In 941 infants born at 24–27 weeks, high-dose erythropoietin did not lower death or severe neurodevelopmental impairment at 2 years (26% against 26%) (Juul et al., 2020). In 501 newborns with hypoxic-ischemic encephalopathy already receiving therapeutic hypothermia, it did not lower death or impairment (52.5% against 49.5%) and serious adverse events were more frequent (0.86 against 0.67 per child; relative risk 1.26, 1.01–1.57) (Wu et al., 2022). In 222 patients after a heart attack treated with angioplasty — a dose-escalation safety phase, then a single 60,000 U intravenous dose as the efficacy phase — infarct size did not differ in the efficacy cohort (measured in 136 patients, then 124), the composite of death, heart attack, stroke or stent thrombosis occurred in 5 of the 125 patients who received epoetin alfa against none of 97 on placebo (P = .04), and in the 21 patients aged 70 or older the infarct was larger (19.9% against 11.7% of left-ventricular mass; P = .03) (Najjar et al., 2011).
• Healthy and trained people — In 48 well-trained male cyclists randomly assigned to a mean 6,000 IU a week of epoetin beta (24 men) or saline (24) for 8 weeks, haemoglobin, maximal power output (351.55 W against 341.23 W) and VO2 max (60.121 against 57.415 mL/min/kg) were higher in the epoetin beta group, while the submaximal test and the Mont Ventoux race time (1 h 40 min 32 s against 1 h 40 min 15 s) did not differ; all adverse events were grade 1–2 (Heuberger et al., 2017). In 20 male athletes given 5,000 U three times weekly (10 men) or placebo (10) for 4 weeks, mean hematocrit rose from 42.7% to 50.8% and VO2 max by 7% (P = 0.001) in the EPO group, and neither changed on placebo (Birkeland et al., 2000). In a small placebo-controlled study in healthy non-athletes — its abstract reports that eight subjects received either epoetin or placebo — VO2 max rose about 12% with epoetin and time to exhaustion at a fixed workload by 54%, but fell by 26.8% when the workload was set to the same relative intensity (Thomsen et al., 2007). Before its own trial, the group that ran it published a systematic review of this literature in 2013: no scientific basis from which to conclude that it enhances performance in elite cyclists, and possible harms in that population that have not been adequately researched but “appear to be worrying, at least” (Heuberger et al., 2013). A later systematic review, of 10 studies in well-trained endurance athletes published from 2010 on, found that it raises total hemoglobin mass, hemoglobin and hematocrit and raises maximal oxygen uptake, that maximal performance measures such as power output tend to rise with it, and that its effect on submaximal performance is still unsettled (Alberdi-Garciandia & Santos-Concejero, 2025).
• Antibodies that stop red-cell production — In 13 patients who developed pure red-cell aplasia on recombinant erythropoietin, serum blocked erythroid colony formation by normal marrow and neutralizing anti-erythropoietin antibodies were identified (Casadevall et al., 2002). Reports to FDA and the manufacturers from January 1998 to April 2004 counted 175 cases with Eprex, a formulation of epoetin alfa marketed outside the US, 11 with Neorecormon (epoetin beta) and 5 with Epogen; after procedures for storing, handling and administering Eprex were adopted, the exposure-adjusted incidence fell by 83% worldwide (Bennett et al., 2004). In a later registry of 15,333 patients on subcutaneous treatment, 5 cases were confirmed among 23 patients with lost or absent response: an incidence of 35.8 per 100,000 patient-years for Eprex against 14.0 for NeoRecormon and Aranesp, a difference that was not statistically significant (rate ratio 2.56, 95% CI 0.43–15.31) (Macdougall et al., 2015).

The evidence meter on the EPO card reads “Approved drug”: epoetin alfa is an FDA-approved hormone replacement for anemia, the use its card’s group stands for (Drugs@FDA; Epogen label). Approved is not the same as safe at any dose, and it is not the same as useful for everything it has been tried for: the stroke, brain-injury, newborn, preterm and heart-attack trials above were all negative (Ehrenreich et al., 2009; Nichol et al., 2015; Juul et al., 2020; Wu et al., 2022; Najjar et al., 2011).

Pipeline

• Phase 4 EpoAid, epoetin alfa with or without intravenous iron in sepsis or septic shock (200 planned, investigator-sponsored) (NCT06670963), primary completion est. Dec 2026
• Phase 4, ferric derisomaltose with EPO and tranexamic acid before bone-tumor surgery in anemia or iron deficiency, against conventional treatment (160 planned; not yet recruiting, though its January 2026 start date has passed and the record was last updated in January 2026) (NCT07314424), primary completion est. Oct 2027
• Phase 3 EPO-TRAUMA, epoetin alfa against placebo in mechanically ventilated trauma patients (2,500 planned, ANZIC-RC) (NCT04588311), primary completion est. Dec 2026
• Phase 3 ENCASE, Megalabs’ epoetin alfa against Epogen in haemodialysis patients with anemia (280 planned; not yet recruiting, though its July 2025 start date has passed and the record was last updated in August 2024) (NCT06352138), primary completion est. Mar 2027
• Phase 1/2, luspatercept alone or with epoetin alfa in lower-risk myelodysplastic syndromes, in patients who had failed erythropoiesis-stimulating agents or were ineligible for them (150 planned, Groupe Francophone des Myelodysplasies) (NCT05181735), primary completion est. Dec 2028
• Phase 2 MyeloMATCH substudy, luspatercept alone, with epoetin alfa or with emavusertib in lower-risk myelodysplastic syndromes (270 planned, NCI; not yet recruiting) (NCT07463820), primary completion est. Dec 2027
• Phase 1 EVEREST, epoetin alfa with everolimus toward immunosuppression withdrawal after liver transplant (20 planned, NIAID) (NCT06832189), primary completion est. Jun 2030
• Phase 1 SCEMPI, epoetin alfa-epbx with melatonin in very preterm infants with intraventricular hemorrhage (60 planned, Johns Hopkins) (NCT05617833), primary completion est. Sep 2027
• Phase 1, Nanogen’s epoetin alfa (Nanokine) against Eprex, single subcutaneous doses in healthy volunteers (44 planned, not yet recruiting) (NCT06919861), primary completion est. Dec 2026
• Early Phase 1, erythropoietin for three days in newborns with hypoxic-ischemic encephalopathy (Assiut University, 3 planned; not yet recruiting, though its November 2024 start date has passed and the record was last updated in September 2024) (NCT06590155), primary completion est. Feb 2029
• Randomized trial (CIPAT) of iron sucrose, human erythropoietin and vitamin C before major cardiac surgery in iron-deficiency anemia, against standard care (400 planned, no phase registered, Second Affiliated Hospital of Zhejiang University) (NCT06012760), primary completion est. Jan 2028
• Randomized long-term sub-study of the same iron, erythropoietin and vitamin C regimen before cardiac surgery, quality of life at one year (400 planned, no phase registered, Second Affiliated Hospital of Zhejiang University) (NCT06968936), primary completion est. Jun 2029
• Randomized trial of EPO 40,000 IU into a vein against saline in acute respiratory distress syndrome (40 planned, no phase registered, Second Affiliated Hospital of Wenzhou Medical University; listed as recruiting in a record last updated in May 2023) (NCT05857891), primary completion est. Oct 2026

Reconstitution & Storage

There is nothing to reconstitute in the approved products: Epogen, Procrit and Retacrit are supplied as clear, colorless liquids, in single-dose vials of 2,000, 3,000, 4,000, 10,000 and (Procrit and Retacrit) 40,000 Units per mL, and in multiple-dose vials of 20,000 Units per mL or 20,000 Units per 2 mL that contain benzyl alcohol; vials are the only form the three labels list, while the longer-acting relative Aranesp also comes in prefilled syringes (Epogen label; Procrit label; Retacrit label; Aranesp label). What one research-chemical catalog entry read for this page lists is powder, and no label covers it.

• Storage, from the label — The vials are kept at 36 °F to 46 °F (2 °C to 8 °C), in their carton to protect them from light, not frozen and not shaken; the label states that Epogen that has been shaken or frozen is not to be used (Epogen label). Unused portions of a multiple-dose vial are discarded 21 days after the first entry, and single-dose vials are discarded after one use even if liquid remains (Epogen label).
• Dilution — The label does not dilute it and does not mix it with other drug solutions, with one exception it describes: preservative-free Epogen from a single-dose vial may be mixed in a syringe with bacteriostatic 0.9% sodium chloride with 0.9% benzyl alcohol in a 1:1 ratio at the time of administration, and not for pregnant or lactating women, neonates or infants, because of the benzyl alcohol (Epogen label).
• Benzyl alcohol — The multiple-dose vials contain 11 mg of benzyl alcohol per mL and are contraindicated in neonates, infants, pregnant and lactating women; the label records fatal “gasping syndrome” in premature neonates given benzyl alcohol-preserved drugs at 99 to 234 mg/kg a day, and says the minimum amount at which serious reactions may occur is not known (Epogen label).
• Units, not milligrams — Epoetin alfa is measured in Units, and the label’s doses are in Units per kg; darbepoetin alfa and Mircera are dosed in micrograms per kg instead (Epogen label; Aranesp label; Mircera label). A number in Units cannot be converted to milligrams of protein from anything on the label.
• Products outside the pharmacy — A research-chemical catalog entry read for this page lists EPO as powder vials of 3,000 IU, “for qualified laboratory research only. Not for human or veterinary use, diagnosis, treatment, or self-administration,” with no analytical file attached to the listing (catalog entry, October 4, 2026). No published study has tested such a product, and no label covers powder: the approved products are liquids, and their strength is stated in Units rather than milligrams of protein (Epogen label).

→ Peptide Calculator — vial-to-syringe math

Side Effects & Risks

• Hypertension — Reported in 27.7% of Epogen-treated dialysis patients against 12.5% on placebo in the label’s controlled studies; after starting and adjusting the dose, about 25% of patients on dialysis needed antihypertensive therapy started or increased, and hypertensive encephalopathy and seizures have been reported in chronic kidney disease. Uncontrolled hypertension is a contraindication (Epogen label).
• Seizures — The label states that Epogen increases the risk of seizures in chronic kidney disease (Epogen label); the Phase 3 trial recorded seizures in 5.4% of 333 hemodialysis patients (Eschbach et al., 1989).
• Clots — Vascular access thrombosis in 8.1% of treated dialysis patients against 2.1% on placebo, and thrombosis in 2.7% against 1% (Epogen label). In the Canadian trial, 11 of 78 treated patients had their access clotted against 1 of 40 (Canadian Erythropoietin Study Group, 1990). In spinal surgery without anticoagulant prophylaxis, deep vein thrombosis was found in 4.7% against 2.1% (Stowell et al., 2009), and in intensive care thrombotic events rose (hazard ratio 1.41, 1.06–1.86) (Corwin et al., 2007). Pulmonary embolism was reported in 1% of the 144 zidovudine-treated patients on Epogen and not reported on placebo (Epogen label).
• Death and cardiovascular events at higher hemoglobin — The three large target trials above (Besarab et al., 1998; Singh et al., 2006; Pfeffer et al., 2009), plus, in the label’s own account, increased mortality in a placebo-controlled study of coronary artery bypass surgery: 7 deaths among 126 patients on Epogen against none among 56 on placebo, four of them during dosing and all four associated with thrombotic events (Epogen label).
• Tumor progression and shorter survival in cancer — Nine randomized trials are tabulated on the label with decreased survival or decreased locoregional control (Epogen label); the independent meta-analysis found higher mortality during the study period across 53 trials (Bohlius et al., 2009).
• Pure red cell aplasia — Neutralizing antibodies to epoetin alfa that cross-react with the body’s own erythropoietin and with other erythropoiesis-stimulating agents can cause pure red cell aplasia or severe anemia; the label contraindicates the drug in anyone who develops it and says not to switch such patients to another agent (Epogen label; Casadevall et al., 2002). It has been reported mostly with subcutaneous dosing in chronic kidney disease (Epogen label), and incidence fell by 83% worldwide after storage and handling were changed for the product most affected (Bennett et al., 2004).
• Allergic and skin reactions — Anaphylaxis, angioedema, bronchospasm, rash and urticaria may occur; blistering and skin exfoliation including erythema multiforme and Stevens-Johnson syndrome / toxic epidermal necrolysis have been reported after approval (Epogen label).
• Common reactions — Each rate is the drug’s against placebo in the same placebo-controlled studies — three pooled for dialysis, four pooled for zidovudine, one study each for chemotherapy and surgery — and several are close. In dialysis patients: arthralgia 16.2% against 3.1%, pyrexia 10.1% against 8.3%, dizziness 9.5% against 8.3%, dialyzer clotting 8.1% against 4.2%, muscle spasm 7.4% against 6.3%, upper respiratory infection 6.8% against 5.2% (Epogen label). On zidovudine: pyrexia 42% against 34%, cough 26% against 14%, rash 19% against 7% (Epogen label). On chemotherapy: nausea 35% against 30%, vomiting 20% against 16%, myalgia 10% against 5%, arthralgia 10% against 6%, thrombosis 5% against 3% (Epogen label). In surgery patients at 300 U/kg: nausea 47% against 45%, vomiting 21% against 14%, pruritus 16% against 14%, injection-site pain 13% against 8% (Epogen label).
• What it does not do — The label states that Epogen has not been shown to improve quality of life, fatigue or patient well-being, and that it is not a substitute for transfusion in patients who need immediate correction of anemia (Epogen label). Two placebo-controlled trials measuring quality of life directly found no difference despite higher hemoglobin (Witzig et al., 2005; Razzouk et al., 2006). An earlier placebo-controlled dialysis trial did find less fatigue and fewer physical symptoms with it, alongside more hypertension and more clotted access (Canadian Erythropoietin Study Group, 1990), and the darbepoetin trial in diabetes reported a modest improvement in patient-reported fatigue (Pfeffer et al., 2009).
• In healthy people — The label’s abuse section states that abuse of drugs that increase erythropoiesis “by healthy persons may lead to life-threatening cardiovascular complications (e.g., stroke, myocardial infarction, or thromboembolism)” (Epogen label). A review of its physiology in healthy humans reports that it raises arterial blood pressure in healthy subjects and that its haemodynamic effects call for careful monitoring during administration; the same review concludes that its metabolic, hormonal and renal effects stay within physiologically acceptable limits and are reversible, and that “EPO seems safe to use for experimental purposes in healthy volunteers” (Lundby & Olsen, 2011). The systematic review of the cycling literature found the possible harms in that population inadequately researched (Heuberger et al., 2013).
• Drug interactions and pregnancy — The label lists no drug-interaction studies; in pregnancy the available data are insufficient to determine a drug-associated risk, the multiple-dose vials are contraindicated because of benzyl alcohol, and a lactating woman given them is advised by the label not to breastfeed for at least two weeks after the last dose (Epogen label).
• WADA — EPO is prohibited at all times, in and out of competition: WADA’s 2026 Prohibited List names “erythropoietins (EPO)” and “erythropoietin receptor agonists” in S2.1.1, with darbepoetins and methoxy polyethylene glycol-epoetin beta (CERA) in the same sub-class, and asialo and carbamylated EPO under innate repair receptor agonists in S2.1.5 (World Anti-Doping Agency, 2026). All substances in class S2 are non-Specified Substances (World Anti-Doping Agency, 2026).

Bloodwork & Monitoring

What the current label lists for the people it is prescribed to:

• Hemoglobin — Measured weekly after starting and after each dose change until it is stable and sufficient to minimize the need for transfusion, then at least monthly in chronic kidney disease; a rise of more than 1 g/dL in any two weeks brings a dose cut of 25% or more (Epogen label).
• Iron — Iron status is evaluated in all patients before and during treatment, with supplemental iron when ferritin is below 100 mcg/L or transferrin saturation below 20%; the label notes that most patients with chronic kidney disease will need supplemental iron during treatment (Epogen label). The Phase 3 trial found iron deficiency in 43% of 333 patients (Eschbach et al., 1989).
• Blood pressure — Controlled before and during treatment, and the drug reduced or withheld if blood pressure becomes difficult to control (Epogen label).
• Reticulocyte count, when response is lost — Severe anemia with a low reticulocyte count during treatment prompts the label to withhold the drug and test for neutralizing antibodies to erythropoietin (Epogen label).
• Other causes of anemia — The label corrects or excludes vitamin deficiency, metabolic or chronic inflammatory conditions and bleeding before treatment starts (Epogen label).
• Neurological symptoms — The label’s counselling section has patients contact their provider for new-onset neurologic symptoms or a change in seizure frequency (Epogen label).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

The combinations below are the ones a label specifies or a published study tested. No study was found pairing it with BPC-157, TB-500, thymosin beta-4, thymosin alpha-1, ARA-290, Semax, Selank, Cerebrolysin, SS-31, MOTS-c or humanin (PubMed and Europe PMC, searched October 4 and 5, 2026). Registered trials also give it with other drugs (Legal Status lists them); one pairs it with melatonin, a combination not yet tested in people: a Phase 1 at Johns Hopkins is giving melatonin with epoetin alfa-epbx to up to 60 very preterm infants with intraventricular hemorrhage, to define a safe combination dose; it is recruiting, its primary endpoint is serious adverse events, and no results are posted (ClinicalTrials.gov NCT05617833).

→ Peptide Calculator — vial-to-syringe math

Legal Status

Related Compounds

People researching EPO often also look at these:

Next Steps

References

1. Amgen Inc. EPOGEN (epoetin alfa) injection, for intravenous or subcutaneous use. Prescribing Information, Medication Guide and Instructions for Use (labeling revised 12/2024; initial U.S. approval 1989). DailyMed set ID 1f2d0b28-9cc5-4523-80b8-637fdaf3f7a5, SPL version 137, effective June 23, 2026. dailymed.nlm.nih.gov. Read October 4, 2026.
2. Janssen Products, LP. PROCRIT (epoetin alfa) injection, for intravenous or subcutaneous use. Prescribing Information (initial U.S. approval 1989; manufactured by Amgen Inc., U.S. License 1080). DailyMed set ID 0c721ba4-ae19-417f-aae1-221ed1a0866a, SPL version 31, effective April 9, 2025. dailymed.nlm.nih.gov. Read October 4, 2026.
3. Pfizer Laboratories (Hospira, Inc.). RETACRIT (epoetin alfa-epbx) injection, for intravenous or subcutaneous use. Prescribing Information (initial U.S. approval 2018; biosimilar to EPOGEN/PROCRIT). DailyMed set ID 3af26b0d-8ad0-44e1-a538-8bdb5ab39374, SPL version 19, effective June 22, 2025. dailymed.nlm.nih.gov. Read October 4, 2026.
4. Amgen Inc. ARANESP (darbepoetin alfa) injection. Prescribing Information. openFDA label set ID 0fd36cb9-c4f6-4167-93c9-8530865db3f9, effective July 7, 2026 (BLA 103951). api.fda.gov/drug/label.json. Read October 4, 2026.
5. Vifor (International) Inc. Mircera (methoxy polyethylene glycol-epoetin beta) injection. Prescribing Information. openFDA label set ID 22c56f2a-f73c-60e7-e054-00144ff88e88, effective August 14, 2026 (BLA 125164). api.fda.gov/drug/label.json. Read October 4, 2026.
6. U.S. Food and Drug Administration. Drugs@FDA records: EPOGEN/PROCRIT, BLA 103234 (Amgen; original approval June 1, 1989; all products prescription); RETACRIT, BLA 125545 (Hospira Inc.; original approval May 15, 2018); ARANESP, BLA 103951 (Amgen; September 17, 2001); MIRCERA, BLA 125164 (Hoffman-La Roche; November 14, 2007). api.fda.gov/drug/drugsfda.json. Read October 4, 2026.
7. U.S. Food and Drug Administration. Notice to Compounders: Changes that affect compounding as of March 23, 2020 (content current as of March 5, 2020), including that “biological products subject to licensure under section 351 of the PHS Act are not eligible for the exemptions for compounded drugs under sections 503A and 503B of the FD&C Act.” fda.gov/drugs/human-drug-compounding/notice-compounders-changes-affect-compounding-march-23-2020. Read October 4, 2026.
8. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download. Searched for erythropoietin and epoetin: no entry.
9. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download. Searched for erythropoietin and epoetin: no entry.
10. Code of Federal Regulations. 21 CFR 216.23 (bulk drug substances that can be used under section 503A) and 216.24 (drug products withdrawn or removed from the market). ecfr.gov. Read October 4, 2026: no entry for erythropoietin or epoetin.
11. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S2.1.1, erythropoietin receptor agonists — “darbepoetins (dEPO); erythropoietins (EPO); EPO-based constructs … EPO-mimetic agents”; S2.1.5, innate repair receptor agonists. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf.
12. European Medicines Agency. Medicines data table (medicines-output-medicines_json-report), entries for epoetin alfa (Binocrit, Abseamed, Epoetin Alfa Hexal), epoetin zeta (Retacrit, Silapo), epoetin beta (NeoRecormon), epoetin theta (Eporatio, Biopoin), darbepoetin alfa (Aranesp), methoxy polyethylene glycol-epoetin beta (Mircera) and epoetin delta (Dynepo, withdrawn). ema.europa.eu. Read October 4, 2026.
13. UniProt Consortium. UniProtKB P01588 (EPO_HUMAN), Erythropoietin: 193-residue precursor, chain 28–193, N-linked glycosylation at Asn-51, Asn-65 and Asn-110 and O-linked at Ser-153. rest.uniprot.org/uniprotkb/P01588. Read October 4, 2026.
14. Miyake T, Kung CK, Goldwasser E. Purification of human erythropoietin. J Biol Chem. 1977;252(15):5558-5564. PMID: 18467.
15. Lin FK, Suggs S, Lin CH, Browne JK, et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985;82(22):7580-7584. PMID: 3865178. DOI: 10.1073/pnas.82.22.7580.
16. Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature. 1985;313(6005):806-810. PMID: 3838366. DOI: 10.1038/313806a0.
17. Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet. 1986;2(8517):1175-1178. PMID: 2877323. DOI: 10.1016/s0140-6736(86)92192-6.
18. Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med. 1987;316(2):73-78. PMID: 3537801. DOI: 10.1056/NEJM198701083160203.
19. Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann Intern Med. 1989;111(12):992-1000. PMID: 2688507. DOI: 10.7326/0003-4819-111-12-992.
20. Canadian Erythropoietin Study Group. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. BMJ. 1990;300(6724):573-578. PMID: 2108751. DOI: 10.1136/bmj.300.6724.573.
21. Fischl M, Galpin JE, Levine JD, Groopman JE, et al. Recombinant human erythropoietin for patients with AIDS treated with zidovudine. N Engl J Med. 1990;322(21):1488-1493. PMID: 2186273. DOI: 10.1056/NEJM199005243222103.
22. Koury ST, Bondurant MC, Koury MJ. Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood. 1988;71(2):524-527. PMID: 3337914.
23. Koury MJ, Bondurant MC. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science. 1990;248(4953):378-381. PMID: 2326648. DOI: 10.1126/science.2326648.
24. D’Andrea AD, Lodish HF, Wong GG. Expression cloning of the murine erythropoietin receptor. Cell. 1989;57(2):277-285. PMID: 2539263. DOI: 10.1016/0092-8674(89)90965-3.
25. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993;74(2):227-236. PMID: 8343951. DOI: 10.1016/0092-8674(93)90414-l.
26. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12(12):5447-5454. PMID: 1448077. DOI: 10.1128/mcb.12.12.5447-5454.1992.
27. Wu H, Liu X, Jaenisch R, Lodish HF. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell. 1995;83(1):59-67. PMID: 7553874. DOI: 10.1016/0092-8674(95)90234-1.
28. Brines M, Grasso G, Fiordaliso F, Sfacteria A, et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A. 2004;101(41):14907-14912. PMID: 15456912. DOI: 10.1073/pnas.0406491101.
29. Brines M, Patel NS, Villa P, Brines C, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A. 2008;105(31):10925-10930. PMID: 18676614. DOI: 10.1073/pnas.0805594105.
30. Collino M, Thiemermann C, Cerami A, Brines M. Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacol Ther. 2015;151:32-40. PMID: 25728128. DOI: 10.1016/j.pharmthera.2015.02.005.
31. Besarab A, Bolton WK, Browne JK, Egrie JC, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339(9):584-590. PMID: 9718377. DOI: 10.1056/NEJM199808273390903.
32. Singh AK, Szczech L, Tang KL, Barnhart H, et al; CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085-2098. PMID: 17108343. DOI: 10.1056/NEJMoa065485.
33. Drüeke TB, Locatelli F, Clyne N, Eckardt KU, et al; CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071-2084. PMID: 17108342. DOI: 10.1056/NEJMoa062276.
34. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, et al; TREAT Investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361(21):2019-2032. PMID: 19880844. DOI: 10.1056/NEJMoa0907845.
35. Leyland-Jones B, Semiglazov V, Pawlicki M, Pienkowski T, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol. 2005;23(25):5960-5972. PMID: 16087945. DOI: 10.1200/JCO.2005.06.150.
36. Henke M, Laszig R, Rübe C, Schäfer U, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet. 2003;362(9392):1255-1260. PMID: 14575968. DOI: 10.1016/S0140-6736(03)14567-9.
37. Henke M, Mattern D, Pepe M, Bézay C, et al. Do erythropoietin receptors on cancer cells explain unexpected clinical findings? J Clin Oncol. 2006;24(29):4708-4713. PMID: 17028293. DOI: 10.1200/JCO.2006.06.2737.
38. Miller CP, Lowe KA, Valliant-Saunders K, Kaiser JF, et al. Evaluating erythropoietin-associated tumor progression using archival tissues from a phase III clinical trial. Stem Cells. 2009;27(9):2353-2361. PMID: 19544471. DOI: 10.1002/stem.156.
39. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009;373(9674):1532-1542. PMID: 19410717. DOI: 10.1016/S0140-6736(09)60502-X.
40. Witzig TE, Silberstein PT, Loprinzi CL, Sloan JA, et al. Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol. 2005;23(12):2606-2617. PMID: 15452187. DOI: 10.1200/JCO.2004.10.020.
41. Razzouk BI, Hord JD, Hockenberry M, Hinds PS, et al. Double-blind, placebo-controlled study of quality of life, hematologic end points, and safety of weekly epoetin alfa in children with cancer receiving myelosuppressive chemotherapy. J Clin Oncol. 2006;24(22):3583-3589. PMID: 16877725. DOI: 10.1200/JCO.2005.03.4371.
42. de Andrade JR, Jove M, Landon G, Frei D, Guilfoyle M, Young DC. Baseline hemoglobin as a predictor of risk of transfusion and response to Epoetin alfa in orthopedic surgery patients. Am J Orthop (Belle Mead NJ). 1996;25(8):533-542. PMID: 8871751.
43. Goldberg MA, McCutchen JW, Jove M, Di Cesare P, et al. A safety and efficacy comparison study of two dosing regimens of epoetin alfa in patients undergoing major orthopedic surgery. Am J Orthop (Belle Mead NJ). 1996;25(8):544-552. PMID: 8871752.
44. Stowell CP, Jones SC, Enny C, Langholff W, Leitz G. An open-label, randomized, parallel-group study of perioperative epoetin alfa versus standard of care for blood conservation in major elective spinal surgery: safety analysis. Spine (Phila Pa 1976). 2009;34(23):2479-2485. PMID: 19927096. DOI: 10.1097/BRS.0b013e3181bd163f.
45. Corwin HL, Gettinger A, Fabian TC, May A, et al; EPO Critical Care Trials Group. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007;357(10):965-976. PMID: 17804841. DOI: 10.1056/NEJMoa071533.
46. Ehrenreich H, Weissenborn K, Prange H, Schneider D, et al; EPO Stroke Trial Group. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009;40(12):e647-e656. PMID: 19834012. DOI: 10.1161/STROKEAHA.109.564872.
47. Nichol A, French C, Little L, Haddad S, et al; EPO-TBI Investigators. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015;386(10012):2499-2506. PMID: 26452709. DOI: 10.1016/S0140-6736(15)00386-4.
48. Juul SE, Comstock BA, Wadhawan R, Mayock DE, et al; PENUT Trial Consortium. A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants. N Engl J Med. 2020;382(3):233-243. PMID: 31940698. DOI: 10.1056/NEJMoa1907423.
49. Wu YW, Comstock BA, Gonzalez FF, Mayock DE, et al; HEAL Consortium. Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns. N Engl J Med. 2022;387(2):148-159. PMID: 35830641. DOI: 10.1056/NEJMoa2119660.
50. Najjar SS, Rao SV, Melloni C, Raman SV, et al; REVEAL Investigators. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial. JAMA. 2011;305(18):1863-1872. PMID: 21558517. DOI: 10.1001/jama.2011.592.
51. Heuberger JAAC, Rotmans JI, Gal P, Stuurman FE, et al. Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial. Lancet Haematol. 2017;4(8):e374-e386. PMID: 28669689. DOI: 10.1016/S2352-3026(17)30105-9.
52. Heuberger JA, Cohen Tervaert JM, Schepers FM, Vliegenthart AD, et al. Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk-benefit. Br J Clin Pharmacol. 2013;75(6):1406-1421. PMID: 23216370. DOI: 10.1111/bcp.12034.
53. Birkeland KI, Stray-Gundersen J, Hemmersbach P, Hallen J, Haug E, Bahr R. Effect of rhEPO administration on serum levels of sTfR and cycling performance. Med Sci Sports Exerc. 2000;32(7):1238-1243. PMID: 10912888. DOI: 10.1097/00005768-200007000-00009.
54. Alberdi-Garciandia A, Santos-Concejero J. Recombinant Human Erythropoietin Effects on Well-Trained Athletes’ Endurance Performance: A Systematic Review. Sports (Basel). 2025;13(3):78. PMID: 40137802. DOI: 10.3390/sports13030078.
55. Thomsen JJ, Rentsch RL, Robach P, Calbet JA, et al. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity. Eur J Appl Physiol. 2007;101(4):481-486. PMID: 17668232. DOI: 10.1007/s00421-007-0522-8.
56. Lundby C, Olsen NV. Effects of recombinant human erythropoietin in normal humans. J Physiol. 2011;589(Pt 6):1265-1271. PMID: 20807784. DOI: 10.1113/jphysiol.2010.195917.
57. Casadevall N, Nataf J, Viron B, Kolta A, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med. 2002;346(7):469-475. PMID: 11844847. DOI: 10.1056/NEJMoa011931.
58. Bennett CL, Luminari S, Nissenson AR, Tallman MS, et al. Pure red-cell aplasia and epoetin therapy. N Engl J Med. 2004;351(14):1403-1408. PMID: 15459301. DOI: 10.1056/NEJMoa040528.
59. Macdougall IC, Casadevall N, Locatelli F, Combe C, et al; PRIMS study group. Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS). Nephrol Dial Transplant. 2015;30(3):451-460. PMID: 25239637. DOI: 10.1093/ndt/gfu297.
60. Equey T, Broséus J, Baume N, Aikin R. Trends in the Detection of Erythropoietin Receptor Agonists (ERAs) in Anti-Doping: An Analysis of Recent Adverse Analytical Findings (AAFs). Drug Test Anal. 2025;17(8):1254-1259. PMID: 39586314. DOI: 10.1002/dta.3828.
61. Bachman E, Travison TG, Basaria S, Davda MN, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014;69(6):725-735. PMID: 24158761. DOI: 10.1093/gerona/glt154.
62. Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914-919. PMID: 18160461. DOI: 10.1210/jc.2007-1692.
63. Marchand A, Martin JA, Collot D, Hoang O, et al. Combined administration of microdoses of growth hormone and erythropoietin: Effects on performance and evaluation of GH detection capability using anti-doping methods. Drug Test Anal. 2019;11(11-12):1698-1713. PMID: 31301268. DOI: 10.1002/dta.2674.
64. Ballal SH, Domoto DT, Polack DC, Marciulonis P, Martin KJ. Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease. Am J Kidney Dis. 1991;17(1):29-33. PMID: 1986567. DOI: 10.1016/s0272-6386(12)80246-0.
65. Gaughan WJ, Liss KA, Dunn SR, Mangold AM, et al. A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients. Am J Kidney Dis. 1997;30(4):495-500. PMID: 9328363. DOI: 10.1016/s0272-6386(97)90307-3.
66. Mei C, Xu G, Zheng C, Xie Y, et al. Recombinant human erythropoietin plus all-trans retinoic acid and testosterone undecanoate for the treatment of anemia in patients with lower-risk myelodysplastic syndromes: a multicenter, single-arm, prospective trial. Haematologica. 2026;111(2):646-655. PMID: 40501398. DOI: 10.3324/haematol.2024.287055.
67. ClinicalTrials.gov. EPO-TRAUMA: A Randomised, Double-blind, Placebo-controlled Trial of Erythropoietin Alfa Versus Placebo in Mechanically Ventilated Critically Ill Patients Following Traumatic Injury (Australian and New Zealand Intensive Care Research Centre; recruiting; 2,500 planned; epoetin alfa 40,000 IU subcutaneously on days 1 and 8; estimated primary completion December 31, 2026). NCT04588311. Read October 4, 2026.
68. ClinicalTrials.gov. SCEMPI: Safety of Combined Therapy With Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage (Johns Hopkins University; Phase 1; recruiting; up to 60 infants; estimated primary completion September 2027). NCT05617833. Read October 4, 2026.
69. ClinicalTrials.gov. EpoAid: The Use of Epoetin Alfa and Iron Derisomaltose in the Treatment of Anemia in Patients With Sepsis or Septic Shock Hospitalized in the Intensive Care Unit (investigator-sponsored; Phase 4; recruiting; 200 planned; epoetin alfa 50 Units/kg intravenously 3 times weekly; estimated primary completion December 31, 2026). NCT06670963. Read October 5, 2026.
70. ClinicalTrials.gov. The Effect of Erythropoietin on Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome (Second Affiliated Hospital of Wenzhou Medical University; no phase registered; recruiting; 40 planned; 40,000 IU of recombinant human erythropoietin intravenously against saline; estimated primary completion October 31, 2026; record last updated May 15, 2023). NCT05857891. Read October 5, 2026.
71. ClinicalTrials.gov. EVEREST: Everolimus and Epoetin for Sustained Liver Transplant Tolerance (National Institute of Allergy and Infectious Diseases; Phase 1; recruiting; 20 planned; epoetin alfa 10,000 Units under the skin every 8 weeks for five doses; estimated primary completion June 1, 2030). NCT06832189. Read October 5, 2026.
72. ClinicalTrials.gov. ENCASE: Phase III, Multicentre, Double-blind, Randomised, Parallel, Equivalence Clinical Trial to Assess Efficacy, Safety of Megalabs Recombinant i/v Human Erythropoietin Compared to Epogen in Anaemia in Patients With Chronic Kidney Disease (Megalabs; Phase 3; not yet recruiting; 280 planned; intravenous epoetin alfa against Epogen in haemodialysis-dependent patients; estimated start July 2025; estimated primary completion March 2027; record last updated August 19, 2024). NCT06352138. Read October 5, 2026.
73. ClinicalTrials.gov. A Randomized, Two-treatment, Two-period, Crossover, Single-dose, Subcutaneous Injection Study Comparing the Pharmacokinetics, Pharmacodynamics, and Safety of Nanokine … With Eprex 4000 U … in Healthy Volunteers (Nanogen Pharmaceutical Biotechnology Joint Stock Company; Phase 1; not yet recruiting; 44 planned; single 4,000 IU subcutaneous doses; estimated primary completion December 2026). NCT06919861. Read October 5, 2026.
74. ClinicalTrials.gov. A Randomized Phase I/II Multicenter Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA (Groupe Francophone des Myelodysplasies; Phase 1/2; recruiting; 150 planned; luspatercept alone or with epoetin alfa (Eprex) 30,000 or 60,000 Units a week under the skin; estimated primary completion December 19, 2028). NCT05181735. Read October 5, 2026.
75. ClinicalTrials.gov. CIPAT: Effect of Iron Sucrose Combined With Human Erythropoietin and Vitamin C on Perioperative Allogeneic Red Blood Cell Infusion in Major Cardiac Surgery (Second Affiliated Hospital, Zhejiang University, School of Medicine; no phase registered; recruiting; 400 planned; intravenous iron sucrose 200 mg and vitamin C 2 g a day with human erythropoietin 150 IU/kg under the skin over three days in the week before surgery, against standard medical care; estimated primary completion January 31, 2028). NCT06012760. Read October 5, 2026.
76. ClinicalTrials.gov. Long-term Outcomes Sub-Study of Preoperative Combined Iron Therapy in Anemic Patients Undergoing Cardiac Surgery: A Randomized Controlled Trial (Second Affiliated Hospital, Zhejiang University, School of Medicine; no phase registered; recruiting; 400 planned; intravenous sucrose iron 200 mg, subcutaneous recombinant human erythropoietin 150 IU/kg and intravenous vitamin C 2 g once daily for three days in the week before surgery, against routine perioperative management; primary outcome quality of life (EQ-5D) one year after surgery; estimated primary completion June 30, 2029). NCT06968936. Read October 5, 2026.
77. ClinicalTrials.gov. The Effect of Preoperative Intravenous Ferric Derisomaltose and EPO and Tranexamic Acid Versus Usual Treatment in Patients With Preoperative Anemia or Iron Deficiency in Bone Tumor: a Single-center, Prospective, Open-label, RCT Study (investigator-sponsored; Phase 4; not yet recruiting; 160 planned; ferric derisomaltose, EPO 150 IU/kg under the skin and 0.5 g of tranexamic acid given locally before closure, against conventional treatment; estimated start January 1, 2026; estimated primary completion October 1, 2027; record last updated January 2, 2026). NCT07314424. Read October 5, 2026.
78. ClinicalTrials.gov. A Phase II Study of Combination Therapy With Luspatercept in Lower Risk Myelodysplasia: A Tier 1 MyeloMATCH Substudy (National Cancer Institute; Phase 2; not yet recruiting; 270 planned; luspatercept alone, with epoetin alfa under the skin weekly, or with emavusertib; estimated start December 18, 2026; estimated primary completion December 31, 2027). NCT07463820. Read October 5, 2026.
79. ClinicalTrials.gov. Role of Erythropoietin in Neonates With Hypoxic Ischemic Encephalopathy (Assiut University; Early Phase 1; not yet recruiting; 3 planned; erythropoietin for 3 days; estimated start November 24, 2024; estimated primary completion February 24, 2029; record last updated September 19, 2024). NCT06590155. Read October 5, 2026.
80. ClinicalTrials.gov. EPO-PRETAR: A Randomized Trial Testing Early vs Late Onset of EPO Alfa Treatment in Lower Risk MDS With Non RBC Transfusion Dependent Anemia and Without Del 5q (Groupe Francophone des Myelodysplasies; Phase 3; active, not recruiting; 124 planned; epoetin alfa 60,000 Units a week for at least 12 weeks; primary completion September 21, 2023, actual; no results posted). NCT03223961. Read October 5, 2026.
81. A research-chemical catalog entry for “EPO,” powder vials, specification 3,000 IU × 10 vials, “For qualified laboratory research only. Not for human or veterinary use, diagnosis, treatment, or self-administration,” with no reference file linked to the entry. Read October 4, 2026. The seller is not named: Kalios doesn’t name or link vendors.
82. Searches of October 4 and 5, 2026: PubMed, “epoetin alfa” (2,393 records; 331 tagged Randomized Controlled Trial; 1,515 of them mention anemia), Erythropoietin[Mesh] (25,451), Epoetin Alfa[Mesh] (1,931); PubMed and Europe PMC, erythropoietin or epoetin with BPC-157, TB-500 or thymosin beta-4 (2 records, both reviews naming the substances separately), with cibinetide or ARA-290 (61 records, all about the derived peptide, none a trial of the two together), with thymosin alpha-1 or thymalfasin (0), with Semax or Selank (0), with Cerebrolysin (4 reviews, no combination study), with elamipretide, SS-31, MOTS-c or humanin (2 animal records, no combination study), with melatonin in infants (54 records: animal combination studies and reviews, no published trial of the pair) and with growth hormone in athletes or volunteers (one published study of the combination, cited above); ClinicalTrials.gov, “epoetin alfa” (692 studies) and “erythropoietin” (1,332 studies, 149 with a recruiting, active, enrolling-by-invitation or not-yet-recruiting status; the 13 among them that test the drug itself, alone or combined with another drug, and have an estimated primary completion still ahead are cited above; one more, a topical erythropoietin gel in dental-implant surgery (NCT07523412), is not counted); FDA 503A and 503B categories lists and 21 CFR 216 (no entry); European Medicines Agency medicines table (the epoetins listed above).
83. ClinicalTrials.gov. Dimensional Changes of Peri-implant Tissues Following Jumping Gap Grafting Using Erythropoietin Gel Mixed With Xenograft. (A Randomized Controlled Clinical Study) (Ain Shams University; Phase 4; not yet recruiting; 26 planned; erythropoietin gel mixed with xenograft against xenograft alone; estimated primary completion October 12, 2026). NCT07523412. Read October 5, 2026.

Related Research

• ARA-290Innate Repair Receptor Agonist (EPO-derived)
• TestosteronePrimary Androgen
• InsulinPancreatic Hormone, Approved Replacement