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

Indications for Intravenous Iron Infusion

Intravenous iron should be used when patients do not tolerate oral iron, when ferritin levels fail to improve despite adequate oral iron therapy, or when patients have conditions that impair oral iron absorption. 1

Primary Indications

Oral Iron Intolerance or Failure

• Patients experiencing intolerable gastrointestinal side effects from oral iron (nausea, constipation, dyspepsia) that prevent adherence should receive IV iron rather than continuing ineffective oral therapy 1, 2
• Treatment failure, defined as lack of improvement in ferritin or hemoglobin after an adequate trial of oral iron (typically 4-6 weeks), warrants switching to IV iron 1, 3
• Only 21% of patients who fail to respond to initial oral iron therapy will respond to continued oral treatment, compared to 65% who respond to IV iron 1

Malabsorption Conditions

• Post-bariatric surgery patients with iron deficiency anemia should receive IV iron, particularly after procedures disrupting duodenal iron absorption (Roux-en-Y gastric bypass, duodenal switch) 1
• Active inflammatory bowel disease with iron deficiency anemia requires IV iron due to elevated hepcidin levels blocking intestinal iron absorption 1, 3
• Celiac disease patients who fail to improve with gluten-free diet and oral iron supplementation should receive IV iron 1

Chronic Kidney Disease

• Non-dialysis dependent chronic kidney disease with iron deficiency anemia is an FDA-approved indication for IV iron 2
• IV iron is preferred in this population due to impaired erythropoietin response and functional iron deficiency 1

Ongoing Blood Loss

• Portal hypertensive gastropathy with iron deficiency anemia unresponsive to oral iron requires IV therapy 1
• Gastric antral vascular ectasia (GAVE) causing iron deficiency anemia should be treated with IV iron alongside endoscopic therapy 1
• Heavy uterine bleeding or other sources of ongoing blood loss where oral iron cannot keep pace with losses 4

Heart Failure

• Iron deficiency in heart failure patients (NYHA class II/III) is indicated for IV iron to improve exercise capacity, even without anemia 2
• This indication is based on ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 2

Rapid Correction Required

• Severe anemia (hemoglobin <10 g/dL) may benefit from IV iron for faster hemoglobin restoration compared to oral therapy 3
• Situations requiring rapid iron repletion before surgery or other time-sensitive interventions 5

Practical Administration Considerations

Formulation Selection

• Prefer IV iron formulations that can replace total iron deficit in 1-2 infusions (ferric carboxymaltose, ferric derisomaltose, low-molecular-weight iron dextran) rather than those requiring multiple visits 1
• Modern IV iron formulations have similar safety profiles with serious adverse events occurring in <1% of patients 1, 6

Safety Profile

• True anaphylaxis is very rare with modern IV iron preparations 1
• Most reactions are complement activation-related pseudo-allergy (CARPA), which resolve by temporarily stopping and restarting the infusion at a slower rate 1, 3
• Resuscitation facilities should be available, but the risk is substantially lower than with older iron dextran formulations 1

Common Pitfalls to Avoid

• Do not continue oral iron indefinitely in patients with malabsorption conditions or active inflammation—hepcidin upregulation prevents effective absorption 1, 3
• Do not assume ferritin >100 ng/mL excludes iron deficiency in inflammatory states; check transferrin saturation and consider functional iron deficiency 1
• Do not treat infusion reactions with vasopressors or H1 blockers as first-line—these are usually CARPA reactions that resolve with temporary cessation and slower infusion rates 6
• Monitor serum phosphate levels in patients receiving repeat courses within 3 months, particularly with ferric carboxymaltose, which can cause hypophosphatemia 2, 5