When to Use Intravenous Iron for Iron Deficiency Anemia
Intravenous iron should be used as first-line therapy when patients have intolerance to oral iron, fail to respond to oral iron supplementation, have hemoglobin below 10 g/dL, have active inflammatory conditions, or have malabsorption disorders. 1, 2
Primary Indications for IV Iron
Oral Iron Failure or Intolerance
Patients who do not tolerate oral iron due to gastrointestinal side effects (nausea, constipation, dyspepsia) should receive IV iron. 1, 2 These adverse effects occur frequently and lead to poor compliance with oral supplementation. 1
Treatment failure is defined as no improvement in ferritin levels or hemoglobin after an adequate trial of oral iron (typically 2-4 weeks). 1, 2 Only 21% of early non-responders to oral iron will respond to continued oral therapy, compared to 65% who respond to IV iron. 1
Severe Anemia
- Hemoglobin below 10 g/dL (100 g/L) is an indication for IV iron as first-line therapy. 1, 2 This threshold allows for more rapid correction of severe anemia. 1
Malabsorption Conditions
Active Inflammatory States
Patients with clinically active inflammatory bowel disease should receive IV iron as first-line therapy. 1, 2 Inflammation upregulates hepcidin, which blocks intestinal iron absorption, rendering oral iron ineffective. 1
Congestive heart failure patients with iron deficiency (ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20%) benefit from IV iron to improve exercise capacity. 1, 3
Ongoing Blood Loss
- Patients with chronic gastrointestinal blood loss exceeding intestinal absorption capacity (portal hypertensive gastropathy, gastric antral vascular ectasia, angiodysplasia) require IV iron. 2, 4
Diagnostic Criteria Before IV Iron
Iron deficiency is confirmed when: 1, 3
- Ferritin ≤100 ng/mL, OR
- Ferritin ≤300 ng/mL when transferrin saturation ≤30% (in inflammatory states)
Hemoglobin thresholds defining anemia: 1
- <12 g/dL in women
- <13 g/dL in men
Administration Considerations
Formulation Selection
Choose IV iron formulations that replace iron deficits in 1-2 infusions (ferric carboxymaltose, iron isomaltoside, low molecular weight iron dextran) over those requiring multiple doses. 1, 2 This improves convenience and compliance.
Ferric carboxymaltose is FDA-approved for patients with intolerance or unsatisfactory response to oral iron, allowing doses up to 750 mg per infusion (maximum 1,500 mg total). 3
Safety Profile
All IV iron formulations have similar safety profiles; true anaphylaxis is very rare (<0.1%). 1, 2 Most reactions are complement activation-related pseudo-allergies (infusion reactions), not true allergic reactions. 1, 2
Low molecular weight iron dextran requires a test dose due to boxed warning for anaphylaxis risk. 1 Newer formulations (iron sucrose, ferric gluconate, ferumoxytol, ferric carboxymaltose) do not require test doses. 1
Clinical Scenarios Where Oral Iron May Be Appropriate
Oral iron can be considered first-line only when ALL of the following are present: 1
- Mild anemia (hemoglobin >10 g/dL)
- Clinically inactive disease (no active inflammation)
- No previous intolerance to oral iron
- No malabsorption conditions
Even in these cases, alternate-day dosing (rather than daily) may improve tolerance and absorption by avoiding hepcidin upregulation. 1
Common Pitfalls to Avoid
Do not continue oral iron indefinitely without reassessing response. Check ferritin and hemoglobin after 2-4 weeks; lack of improvement mandates switching to IV iron. 1, 2
Do not assume oral iron will work in inflammatory conditions. Elevated hepcidin blocks absorption regardless of dose or formulation. 1
Do not withhold IV iron due to outdated safety concerns. Modern formulations have excellent safety profiles when administered appropriately. 1, 2, 5
Do not forget to investigate underlying causes of iron deficiency, particularly gastrointestinal malignancy in appropriate populations. 1