When should intravenous (IV) iron be given to patients with iron deficiency anemia?

When to Give IV Iron

Intravenous iron should be given when patients cannot tolerate oral iron, fail to show improvement in hemoglobin (≥1 g/dL within 2 weeks) or ferritin (within 1 month) despite adherent oral supplementation, or have conditions that impair iron absorption such as inflammatory bowel disease, post-bariatric surgery, or chronic kidney disease. 1

Primary Indications for IV Iron

Oral Iron Failure or Intolerance

• Administer IV iron when hemoglobin fails to increase by at least 1 g/dL within 2 weeks of starting oral iron in anemic patients 1
• Switch to IV iron when ferritin levels remain low after 1 month of adherent oral iron therapy 1, 2
• Use IV iron for patients experiencing gastrointestinal side effects (nausea, constipation, dyspepsia) that prevent adherence to oral therapy 2
• Oral iron increases hepcidin for up to 48 hours, blocking further absorption, which explains why some patients cannot respond adequately 1

Malabsorption States (IV Iron Preferred First-Line)

• Post-bariatric surgery patients require IV iron, particularly after procedures disrupting duodenal iron absorption (Roux-en-Y gastric bypass, duodenal switch) 2
• Active inflammatory bowel disease with pronounced disease activity necessitates IV iron due to hepcidin upregulation blocking oral absorption 1, 2
• Celiac disease patients should receive IV iron if stores don't improve after ensuring gluten-free diet adherence and attempting oral iron 2
• Chronic kidney disease patients require IV iron due to inflammation-mediated hepcidin upregulation 2

Severity-Based Indications

• Severe anemia (hemoglobin <10 g/dL or 100 g/L) is an indication for IV iron to achieve faster correction 1
• Acute anemia with hemodynamic instability requires IV iron 1
• Severe anemia-related fatigue warrants IV iron therapy 1
• Patients with ongoing iron loss exceeding oral iron absorption capacity need IV iron 1

Special Clinical Scenarios

• Cancer patients should receive IV iron due to inflammation impairing oral absorption 2
• Portal hypertensive gastropathy with ongoing bleeding unresponsive to oral therapy requires IV iron 2
• Patients requiring erythropoiesis-stimulating agents must receive IV iron concurrently, as functional iron deficiency develops with increased erythropoiesis 1

Practical Dosing Approach

Formulation Selection

• Prefer IV iron formulations requiring 1-2 infusions (ferric carboxymaltose 750-1000 mg, ferric derisomaltose 1000 mg, low-molecular-weight iron dextran 1000 mg) over multiple-dose regimens for patient convenience 1, 2
• Ferric carboxymaltose can be given as 750 mg twice one week apart or 1000 mg as a single dose 1
• For patients weighing ≥50 kg, the standard dose is 15 mg/kg up to 1000 mg per administration 3
• For patients <50 kg, give 15 mg/kg in two doses separated by at least 7 days 3

Administration Guidelines

• Administer as undiluted slow IV push at approximately 100 mg per minute, or dilute up to 1000 mg in no more than 250 mL sterile 0.9% sodium chloride and infuse over at least 15 minutes 3
• Do not dilute to concentrations less than 2 mg iron/mL to maintain stability 3
• Monitor for extravasation, as brown discoloration can be long-lasting 3

Safety Considerations

Reaction Management

• True anaphylaxis to IV iron is very rare (approximately 1:200,000); most reactions are complement activation-related pseudo-allergy (infusion reactions) occurring in approximately 1:200 patients 1, 2
• For mild infusion reactions, stop the infusion and restart 15 minutes later at a slower rate 1
• For severe reactions, corticosteroids may be beneficial; avoid diphenhydramine as its side effects can mimic worsening reactions 1
• All IV iron formulations have similar overall safety profiles and efficacy 1, 4

Monitoring Requirements

• Check serum phosphate levels in patients requiring repeat courses within 3 months or those at risk for hypophosphatemia 3, 5
• Ferric carboxymaltose carries the highest risk of hypophosphatemia (50-74% in prospective trials), potentially causing bone pain, osteomalacia, and fractures 5
• Resuscitation facilities must be available when administering IV iron 1

Contraindications

• Do not use IV iron during active infection, as iron supplementation may promote bacterial growth 2
• Avoid in patients with iron overload or hemochromatosis 1

Common Pitfalls to Avoid

• Don't delay IV iron in malabsorption states—patients with celiac disease, post-bariatric surgery, or active IBD inflammation will not respond to oral iron 2
• Don't confuse infusion reactions with true anaphylaxis; treat complement activation reactions appropriately rather than permanently discontinuing IV iron 2
• Don't forget to investigate and treat the underlying cause of iron deficiency concurrent with iron replacement 2
• Don't assume oral iron is adequate for patients with inflammatory conditions, as hepcidin blocks absorption 1, 2
• The cost of IV iron is substantially higher than oral formulations ($405-$3,896 per course vs. $0.30-$4.50 for 30 oral pills), but this must be weighed against treatment failure and ongoing symptoms 1