What is the recommended approach for intravenous (IV) iron supplementation in patients with iron deficiency anemia?

Intravenous Iron Supplementation in Iron Deficiency Anemia

Use IV iron formulations that deliver 1,000-1,500 mg in 1-2 infusions as first-line therapy when oral iron fails, is not tolerated, or when malabsorption is present; all IV iron formulations have similar efficacy and safety profiles, with true anaphylaxis being exceedingly rare. 1

When to Use IV Iron

IV iron is indicated in the following specific situations:

• Oral iron intolerance – gastrointestinal side effects preventing adherence 1
• Inadequate response to oral iron – ferritin fails to increase within 1 month or hemoglobin fails to increase by 1 g/dL within 2 weeks 1
• Hemoglobin <10 g/dL – severe anemia requiring faster correction 1
• Active inflammatory bowel disease – inflammation impairs oral iron absorption 1
• Post-bariatric surgery – disrupted duodenal absorption 1
• Ongoing blood loss exceeding oral replacement capacity 1
• Patients requiring erythropoiesis-stimulating agents 1

Preferred IV Iron Formulations

Choose high-dose formulations that minimize infusion visits:

First-Line Options (1-2 infusions):

• Ferric carboxymaltose: 750-1,000 mg per dose, maximum 1,500 mg total (two doses separated by ≥7 days) 1, 2
• Ferric derisomaltose (iron isomaltoside): 1,000 mg single dose 1
• Ferumoxytol: 510-1,020 mg (one or two doses) 1
• Low-molecular-weight iron dextran: 1,000 mg single dose 1

Less Preferred (Multiple infusions required):

• Iron sucrose: 200-300 mg per dose, requiring 5 infusions over several weeks 1
• Ferric gluconate: 125 mg per dose, requiring 8 doses 1

The rationale for preferring high-dose formulations is practical—fewer infusions improve compliance and reduce healthcare costs without compromising safety or efficacy. 1

Dosing Strategy

Base total iron dose on hemoglobin level and body weight:

Simplified Dosing Scheme (preferred over Ganzoni formula):

Hemoglobin (g/dL)	Body Weight <70 kg	Body Weight ≥70 kg
10-12 (women) / 10-13 (men)	1,000 mg	1,500 mg
7-10	1,500 mg	2,000 mg

1

This simplified approach is more effective and has better compliance than Ganzoni formula-calculated dosing. 1 For patients with hemoglobin <7 g/dL, add an additional 500 mg to the calculated dose. 1

Evidence suggests 1,500 mg total cumulative dose is closer to actual iron deficit than the commonly used 1,000 mg, with significantly lower retreatment rates (5.6% vs 11.1%). 3

Administration Methods

For ferric carboxymaltose:

• 750 mg dose: Undiluted IV push over approximately 7.5 minutes (100 mg/minute) 2
• 1,000 mg dose: IV push over 15 minutes OR diluted in ≤250 mL normal saline infused over ≥15 minutes 2

For iron sucrose:

• 200 mg: Can be administered as 2-minute IV push (safe and practical based on 2,297 injections studied) 4
• Alternative: Dilute in 50-100 mL saline, infuse over 30-60 minutes 1

For iron dextran:

• Maximum 100 mg per dose to minimize arthralgias/myalgias 1
• Requires test dose due to anaphylaxis risk 1

Safety Profile

True anaphylaxis to IV iron is extremely rare (approximately 1:200,000). 1 The vast majority of reactions are complement activation-related pseudo-allergy (CARPA), not true allergic reactions. 1

Managing Infusion Reactions:

For mild reactions:

• Stop infusion immediately
• Wait 15 minutes
• Restart at slower rate 1

For more severe reactions:

• Corticosteroids may be beneficial 1
• Avoid diphenhydramine – its side effects can mimic worsening reactions 1

Common mild adverse events include transient metallic taste (17.9% of injections), which causes no significant distress. 4

Monitoring and Retreatment

Expected response to IV iron:

• Hemoglobin should increase by ≥2 g/dL within 4 weeks 1
• Ferritin and transferrin saturation should rise significantly 1

Retreatment criteria:

• Serum ferritin drops below 100 ng/mL 1
• Hemoglobin falls below 12 g/dL (women) or 13 g/dL (men) 1

Important caveat: Check serum phosphate levels in patients requiring repeat courses within 3 months, as ferric carboxymaltose carries risk of hypophosphatemia. 1, 2 Treat hypophosphatemia as medically indicated before repeating therapy.

Special Populations

Inflammatory Bowel Disease:

IV iron is first-line therapy for active disease regardless of hemoglobin level, as inflammation blocks oral iron absorption. 1 Oral iron may be used only in clinically inactive disease with mild anemia (Hb 11-12 g/dL). 1

Chronic Kidney Disease:

Target transferrin saturation ≥20% and ferritin ≥100 ng/mL. 1 IV iron is superior to oral iron in this population, producing greater increases in both hemoglobin and iron stores. 5

Heart Failure:

Specific weight and hemoglobin-based dosing protocols exist for iron deficiency in NYHA class II/III heart failure to improve exercise capacity. 2

Cost Considerations

While IV iron is substantially more expensive than oral formulations (medication costs range from $405-$3,896 per course vs $0.30-$4.50 for 30 oral tablets), the improved efficacy, faster response, and better tolerability justify its use in appropriate clinical scenarios. 1 Choose low-molecular-weight iron dextran ($405) or iron sucrose ($441.50) when cost is a primary concern, though these require more frequent dosing. 1