What are the indications for intravenous (IV) iron versus oral iron supplementation in patients with iron deficiency anemia?

Indications for Intravenous Iron versus Oral Iron Supplementation

Oral iron should be tried first in most patients with iron deficiency anemia, but intravenous iron is indicated when patients cannot tolerate oral iron, fail to respond to oral iron despite adequate trial, or have conditions that impair iron absorption or require rapid correction. 1

Start with Oral Iron in These Situations

• Mild iron deficiency anemia (hemoglobin >10 g/dL) with clinically inactive disease should receive oral iron as first-line therapy 1
• Patients without gastrointestinal inflammation or malabsorption can effectively absorb oral iron 1, 2
• Non-pregnant patients without ongoing blood loss exceeding oral replacement capacity should trial oral iron first 1
• Oral iron is considerably less expensive than IV iron and avoids infusion-related risks 1

Switch to Intravenous Iron in These Specific Situations

Oral Iron Intolerance or Failure

• Intolerance to at least two different oral iron preparations (ferrous sulfate, ferrous gluconate, or ferrous fumarate) 1, 2
• Failure of hemoglobin to rise by 2 g/dL after 4 weeks of compliant oral therapy 1, 2
• Failure of ferritin levels to improve after 4 weeks despite documented adherence 2

Malabsorption Conditions

• Active inflammatory bowel disease with ongoing inflammation, where hepcidin elevation blocks iron absorption 1, 2
• Post-bariatric surgery patients with disrupted duodenal absorption mechanisms 1, 2
• Celiac disease with ongoing gluten exposure or inadequate response to oral iron despite gluten-free diet 1, 2
• Atrophic gastritis impairing iron absorption 3

Severity-Based Indications

• Hemoglobin below 10 g/dL (100 g/L) in patients with inflammatory bowel disease requires IV iron as first-line treatment 1, 2
• Severe anemia requiring rapid correction where waiting 3-4 weeks for oral iron response is unacceptable 1, 4

Chronic Inflammatory Conditions

• Chronic kidney disease (non-dialysis dependent) with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 1, 2, 5
• Heart failure (NYHA class II/III) with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) to improve exercise capacity 5, 3
• Cancer patients with iron deficiency and ongoing inflammation 3

Ongoing Blood Loss

• Gastrointestinal bleeding exceeding oral iron replacement capacity, such as from gastric antral vascular ectasia (GAVE) or angioectasias 1, 2
• Heavy menstrual bleeding when oral iron cannot keep pace with losses 2, 3

Pregnancy

• Second and third trimesters of pregnancy when oral iron is inadequate or not tolerated 2, 3

Need for Erythropoiesis-Stimulating Agents

• Patients requiring ESA therapy should receive IV iron to optimize response 1

Critical Pitfalls to Avoid

• Do not continue oral iron indefinitely without response—reassess at 4 weeks and switch to IV iron if hemoglobin fails to rise by 2 g/dL 1, 2
• Do not use IV iron as first-line therapy unless specific contraindications to oral therapy exist (inflammation, malabsorption, severe anemia, pregnancy) 1
• Do not delay IV iron in patients with active inflammatory bowel disease and hemoglobin <10 g/dL, as oral iron will be ineffective due to hepcidin elevation 1
• Infusion-related adverse events occur in 4.3% of IV iron recipients, including anaphylactoid reactions, hypotension, and shortness of breath 1
• Ferric carboxymaltose causes hypophosphatemia in 50-74% of patients, which can lead to bone pain, osteomalacia, and fractures 4
• Iron dextran carries higher risk of anaphylaxis compared to non-dextran formulations (ferric gluconate, iron sucrose, ferric carboxymaltose) 1, 2

Practical Algorithm

1. Diagnose iron deficiency: ferritin <30 ng/mL (or <100 ng/mL with inflammation and transferrin saturation <20%) 2, 3
2. Assess for contraindications to oral iron: active IBD, post-bariatric surgery, celiac disease, hemoglobin <10 g/dL with inflammation 1, 2
3. If no contraindications exist: start oral ferrous sulfate 200 mg once daily 1, 2
4. Reassess at 4 weeks: expect hemoglobin rise of 2 g/dL 1, 2
5. If inadequate response or intolerance: switch to IV iron formulation that replaces deficit in 1-2 infusions 1, 2, 5