What are the guidelines for intravenous (IV) iron correction in patients with iron deficiency anemia?

Intravenous Iron Correction Guidelines

First-Line Treatment: Oral Iron

Start with ferrous sulfate 200 mg once daily (containing 65 mg elemental iron) as the preferred first-line treatment for iron deficiency anemia, as it is the most cost-effective option with proven efficacy. 1, 2

• Once-daily dosing is superior to multiple daily doses because it improves tolerance while maintaining equal or better iron absorption due to hepcidin regulation that blocks absorption for 48 hours after each dose 2, 3
• Alternative oral formulations (ferrous fumarate 106 mg elemental iron or ferrous gluconate 38 mg elemental iron) are equally effective if ferrous sulfate is not tolerated 1, 2
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption 1, 2
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores 1, 2

Expected Response to Oral Iron

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1, 2
• Check hemoglobin at 4 weeks; failure to rise by 2 g/dL indicates poor compliance, continued blood loss, or malabsorption 2

Absolute Indications for Intravenous Iron

Switch to IV iron when oral iron fails or is contraindicated based on these specific criteria:

Oral Iron Failure

• Intolerance to at least two different oral iron preparations (ferrous sulfate, ferrous fumarate, or ferrous gluconate) 1, 2, 3
• Hemoglobin fails to increase by at least 1 g/dL within 2 weeks of starting oral iron in anemic patients 3
• Ferritin levels remain low after 1 month of adherent oral iron therapy 3

Malabsorption States (IV Iron Preferred First-Line)

• Active inflammatory bowel disease with hemoglobin <10 g/dL - hepcidin upregulation blocks oral absorption 1, 2, 3
• Post-bariatric surgery patients (especially Roux-en-Y gastric bypass or duodenal switch) - disrupted duodenal iron absorption 2, 3
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 2, 3
• Chronic kidney disease - inflammation-mediated hepcidin upregulation blocks oral absorption 2, 3

Severity-Based Indications

• Severe anemia (hemoglobin <10 g/dL) requiring faster correction 3
• Acute anemia with hemodynamic instability 3
• Ongoing gastrointestinal blood loss exceeding oral iron absorption capacity 2, 3

Special Clinical Scenarios

• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) - improves symptoms and quality of life 2
• Cancer patients - inflammation impairs oral absorption 3
• Patients requiring erythropoiesis-stimulating agents - functional iron deficiency develops with increased erythropoiesis 3

IV Iron Formulations and Dosing

Prefer IV iron formulations that can replace iron deficits with 1-2 infusions rather than multiple-dose regimens for patient convenience and reduced risk of reactions. 2, 3

Ferric Carboxymaltose (Ferinject/Injectafer) - Preferred Option

• For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course) 4
• Alternative single-dose regimen: 15 mg/kg body weight up to maximum 1,000 mg as single dose 4
• For patients <50 kg: 15 mg/kg IV in two doses separated by at least 7 days 4
• Infusion time: 15 minutes minimum when diluted in 250 mL normal saline (concentration ≥2 mg iron/mL) 4
• Can also be given as slow IV push at 100 mg per minute for doses ≤750 mg, or over 15 minutes for 1,000 mg 4

Iron Dextran (Cosmofer)

• Can be given as total dose infusion (20 mg/kg, maximum single dose) over 6 hours 1
• Risk of serious reactions is 0.6-0.7%, with rare true anaphylaxis 1, 3
• Requires resuscitation facilities available 1, 3
• Cost: £79.70 per gram of iron 1

Iron Sucrose (Venofer)

• Maximum 200 mg per infusion over 10 minutes 1
• Requires multiple visits for complete iron repletion 1
• Cost: £70.80 per gram of iron 1

Ferric Derisomaltose

• Can deliver 1,000 mg iron in single infusion 5
• Very low rates of serious or severe hypersensitivity reactions 5

Safety Considerations for IV Iron

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. 3

Managing Infusion Reactions

• For mild infusion reactions: stop the infusion and restart 15 minutes later at a slower rate 3
• For severe reactions: corticosteroids may be beneficial; avoid diphenhydramine as its side effects can mimic worsening reactions 3
• Most reactions respond to slowing the infusion rate rather than requiring epinephrine 2
• All IV iron formulations have similar overall safety profiles and efficacy 3

Mandatory Precautions

• Resuscitation facilities must be available when administering any IV iron formulation 1, 3
• Monitor for extravasation; brown discoloration at extravasation site may be long-lasting 4
• Check serum phosphate levels in patients requiring repeat courses within 3 months 4

Contraindications

• Active infection - iron supplementation may promote bacterial growth 3
• Iron overload or hemochromatosis 3

Monitoring After IV Iron

• Check hemoglobin and ferritin at 4-12 weeks post-infusion 6
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1, 2
• Administer maintenance doses if serum ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 4

Special Population Dosing

Heart Failure Patients (NYHA Class II/III)

Use weight and hemoglobin-based dosing algorithm: 4

• Weight <70 kg:

  • Hb <10 g/dL: 1,000 mg Day 1, then 500 mg Week 6
  • Hb 10-14 g/dL: 1,000 mg Day 1 only
  • Hb >14 to <15 g/dL: 500 mg Day 1 only

• Weight ≥70 kg:

  • Hb <10 g/dL: 1,000 mg Day 1, then 1,000 mg Week 6
  • Hb 10-14 g/dL: 1,000 mg Day 1, then 500 mg Week 6
  • Hb >14 to <15 g/dL: 500 mg Day 1 only

• Maintenance: 500 mg at 12,24, and 36 weeks if ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 4

Pregnant Women

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 2
• Treat anemia with 60-120 mg/day elemental iron orally 2
• Refer for further evaluation if hemoglobin <9.0 g/dL 2
• IV iron indicated during second and third trimesters if oral iron fails 2

Critical Pitfalls to Avoid

• Don't continue oral iron indefinitely without response - reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 2
• Don't use multiple daily doses of oral iron - this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 2
• Don't stop iron therapy when hemoglobin normalizes - continue for 3 months to replenish stores 1, 2
• 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 3
• Don't confuse infusion reactions with true anaphylaxis - treat complement activation reactions appropriately rather than permanently discontinuing IV iron 3
• Don't fail to identify and treat the underlying cause of iron deficiency while supplementing 1, 2
• Don't overlook vitamin C supplementation when oral iron response is suboptimal 1, 2
• Don't underdose IV iron - calculate total iron need and administer adequate replacement 6

When Treatment Fails

If anemia does not resolve within 6 months despite appropriate iron therapy: 2

• Reassess for ongoing blood loss
• Evaluate for malabsorption syndromes
• Consider further gastrointestinal investigation
• Verify patient adherence to therapy
• Consider hematology consultation for complex cases