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Erythropoietin

EPO, Epoetin alfa

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Meta Information

ID:erythropoietin
Name:
Schema Version:2.4_uniform_evidence_2026_06_18

Created

2026-05-21T22:30:00Z

Model

phase-a-upgrade-claude-sonnet-4.6

Interactions

Target id:
/condition/uncontrolled-hypertension
Target name:
Uncontrolled Hypertension
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Erythropoietin can cause or worsen high blood pressure by increasing blood viscosity and through direct effects on blood vessels.
Actionable advice:
This should not be used when blood pressure is not well-controlled; blood pressure should be monitored closely during treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Do not take PROCRIT if you: • Have high blood pressure that is not controlled (uncontrolled hypertension).
Label source:
Action type:
avoid
Target id:
/condition/history-of-thrombosis
Target name:
History of Stroke, Heart Attack, or Blood Clots
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Erythropoietin increases red blood cell count, which thickens the blood and significantly raises the risk of serious cardiovascular and thromboembolic events.
Actionable advice:
Use should be avoided with a history of blood clots, stroke, or heart attack, unless under strict medical supervision for a critical indication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Label source:
FDA label: Epoetin alfa (Procrit)
Action type:
avoid
Target id:
/condition/active-malignancy
Target name:
Active Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some tumors have erythropoietin receptors, and stimulating them may promote tumor growth and worsen outcomes, particularly in certain cancers.
Actionable advice:
Use should be avoided in the presence of active cancer unless for palliative care of chemotherapy-induced anemia under an oncologist's direction.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers
Label source:
FDA label: Epoetin alfa (Procrit)
Action type:
avoid
Target id:
/condition/pure-red-cell-aplasia
Target name:
History of Pure Red Cell Aplasia (PRCA)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A history of antibody-mediated PRCA due to any erythropoietin product is a contraindication, as re-exposure will likely trigger a severe anemic response.
Actionable advice:
This should never be used in anyone with a history of PRCA caused by an erythropoiesis-stimulating agent.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT.
Label source:
Action type:
avoid
Target id:
/biomarker/iron-panel
Target name:
Adequate Iron Stores
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Erythropoietin stimulates red blood cell production, a process that requires significant amounts of iron; without adequate iron, the response will be blunted or absent.
Actionable advice:
Iron levels (ferritin and transferrin saturation) should be adequate before starting and throughout therapy, with iron supplementation as needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Virtually all patients will eventually require supplemental iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis stimulated by PROCRIT.
Label source:
Action type:
monitor
Target id:
/biomarker/hemoglobin-target-level
Target name:
Target Hemoglobin Level (e.g., >11-12 g/dL)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raising hemoglobin too high or too quickly increases blood viscosity and the risk of hypertension, stroke, and heart attack.
Actionable advice:
Hemoglobin levels should be monitored regularly, and the dose should be adjusted to avoid exceeding the target range (typically 10-12 g/dL).
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
Label source:
Action type:
avoid
Target id:
/condition/healthy-individual
Target name:
Healthy Individuals (Off-Label Use)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In healthy individuals without anemia, using erythropoietin (blood doping) dangerously thickens the blood, severely increasing the risk of stroke, heart attack, and pulmonary embolism.
Actionable advice:
Erythropoietin should not be used for performance enhancement or unproven longevity benefits due to life-threatening risks.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
use the lowest dose needed to avoid red blood cell transfusion.
Label source:
FDA label: Epoetin alfa (Procrit) — boxed warning establishes that ESA use carries serious cardiovascular/thrombotic risk in any setting and is approved only for anemia in specific conditions, supporting the safety prohibition against off-label use in healthy individuals
Action type:
avoid
Target id:
/procedure/major-surgery
Target name:
Major Surgery
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The increased risk of blood clots from erythropoietin is compounded by the immobility and inflammatory state associated with major surgery.
Actionable advice:
Use should be discontinued well before major elective surgery, and appropriate DVT prophylaxis should be in place if use is unavoidable.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Label source:
FDA label: Epoetin alfa (Procrit)
Action type:
avoid
Target id:
/intervention/lenalidomide
Target name:
Lenalidomide
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both lenalidomide and erythropoietin independently increase the risk of blood clots; using them together significantly elevates this risk.
Actionable advice:
Concurrent use should be avoided unless absolutely necessary and with appropriate thromboprophylaxis under medical supervision.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
the risk factors for VTE include the use of certain medications (eg, erythropoiesis-stimulating agents
Label source:
Primary literature: NCCN-aligned thromboprophylaxis review (Bajetta et al. Cancer 2008 + JHOP 2019 review of NCCN VTE risk factors)
Action type:
avoid
Target id:
/biomarker/vitamin-b12
Target name:
Adequate Vitamin B12 Levels
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B12 is a crucial cofactor for DNA synthesis in new red blood cells; deficiency can limit the effectiveness of erythropoietin therapy.
Actionable advice:
It is a good idea to check Vitamin B12 levels and correct any deficiency before or during treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Vitamin deficiencies: Folic acid or vitamin B12.
Label source:
Action type:
monitor
Target id:
/intervention/folate
Target name:
Adequate Folate (Vitamin B9) Levels
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Folate (Vitamin B9) is essential for the production of new red blood cells, and a deficiency will impair the body's response to erythropoietin.
Actionable advice:
It is a good idea to maintain adequate folate status through diet or supplementation during therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
• PROCRIT is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding (see PRECAUTIONS: Lack or Loss of Response).
Label source:
Action type:
informational_none
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ACE inhibitors can suppress the production of red blood cells (erythropoiesis), potentially blunting the therapeutic effect of exogenous erythropoietin.
Actionable advice:
It is worth being aware that a higher dose of erythropoietin may be needed when also taking an ACE inhibitor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
8.6 Race ACE inhibitors, including Zestril, have an effect on blood pressure that is less in black patients than in non blacks.
Label source:
Action type:
informational_none
Target id:
/class/arbs
Target name:
Angiotensin II Receptor Blockers (ARBs)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs can suppress erythropoiesis, similar to ACE inhibitors, potentially reducing the effectiveness of erythropoietin treatment.
Actionable advice:
Hemoglobin response should be monitored closely, as a higher erythropoietin dose may be required when taking an ARB.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
The median survival was shorter in the darbepoetin alfa treatment group (8 months) compared with the placebo group (10.8 months); HR 1.30, 95% CI: 1.07, 1.57.
Label source:
Action type:
monitor
Target id:
/condition/seizure-disorder
Target name:
Seizure Disorder / Epilepsy
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Seizures have been reported in patients receiving erythropoietin, possibly related to a rapid rise in blood pressure or hematocrit.
Actionable advice:
This is best used with caution in patients with a history of seizures, and it is a good idea to monitor closely for any neurological changes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Seizures in 1.6% (n = 1/63) of patients treated with PROCRIT TIW occurred in the context of a significant increase in blood pressure and hematocrit from baseline values.
Label source:
Action type:
monitor
Target id:
/condition/inflammation-infection
Target name:
Active Inflammation or Infection
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inflammatory states increase hepcidin levels, which blocks iron release and absorption, leading to a poor response to erythropoietin (functional iron deficiency).
Actionable advice:
Address the underlying cause of inflammation or infection to improve the effectiveness of erythropoietin therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
In these states, hepcidin levels increase and iron is blocked from entering the circulation.
Label source:
Primary literature: Fishbane S, Kidney Medicine 2020 — Inflammation and ESA Hyporesponsiveness
Action type:
informational_none
Target id:
/class/androgens
Target name:
Androgens (e.g., Testosterone)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Androgens can stimulate the bone marrow to produce more red blood cells, potentially enhancing the effect of erythropoietin.
Actionable advice:
Hemoglobin levels should be monitored carefully, as the dose of erythropoietin may need to be reduced when co-administered with androgens.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57%
Label source:
Primary literature: Bachman E et al., Am J Physiol Endocrinol Metab 2014 — Testosterone alters iron metabolism and stimulates red blood cell production
Action type:
adjust_with_prescriber
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is limited data on the safety of erythropoietin in human pregnancy; it should only be used if the potential benefit justifies the potential risk to the fetus.
Actionable advice:
Use during pregnancy is best only under strict medical guidance when clearly needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
PROCRIT should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.
Label source:
Action type:
informational_none
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown whether erythropoietin is excreted in human milk, and caution should be exercised when administering to a nursing woman.
Actionable advice:
It is important to talk to a healthcare provider about the risks and benefits before using while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Because many drugs are excreted in human milk, caution should be exercised when PROCRIT is administered to a nursing woman.
Label source:
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Erythropoietin is a primary treatment for anemia caused by chronic kidney disease, as the kidneys are the main site of natural EPO production.
Actionable advice:
Use is indicated for anemia of CKD, but requires careful dose titration and monitoring of hemoglobin, iron, and blood pressure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis.2 In normal subjects, plasma erythropoietin levels range from 0.01 to 0.03 Units/mL and increase up to 100- to 1000-fold during hypoxia or anemia.2 In contrast, in patients with chronic renal failure (CRF), production of erythropoietin is impaired, and this erythropoietin deficiency is the primary cause of their anemia.3,4 Chronic renal failure is the clinical situation in which there is a progressive and usually irreversible decline in kidney function.
Label source:
Action type:
adjust_with_prescriber
Target id:
/class/antacids
Target name:
Aluminum-Containing Antacids
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of aluminum-containing products, sometimes used as phosphate binders in renal disease, can potentially interfere with iron utilization and blunt the response to erythropoietin.
Actionable advice:
If taking aluminum-based binders, ensure iron status is closely monitored and consider alternative phosphate binders if EPO response is poor.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Aluminum can blunt the effect of erythropoietin, in part by interfering with iron bioavailability.
Label source:
Primary literature: Rosenlof K et al., Br J Haematol 1990 — The role of aluminum in the functional iron deficiency of EPO-treated patients
Action type:
monitor
Target id:
/biomarker/serum-potassium
Target name:
Serum Potassium
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Erythropoietin can occasionally cause an increase in serum potassium levels, particularly in patients with kidney disease.
Actionable advice:
Potassium levels should be monitored periodically during therapy, especially in patients with renal impairment.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic/monitoring inference: erythropoiesis-stimulating agents can occasionally raise serum potassium, particularly in CKD patients, so potassium monitoring is reasonable. Recognized effect.
Label source:
Class inference
Action type:
monitor