What are the different intravenous (IV) iron preparations, their risks, and benefits?

IV Iron Preparations: Comparison of Risks and Benefits

Intravenous iron preparations should be considered first-line therapy for patients with clinically active inflammatory disease, previous intolerance to oral iron, hemoglobin below 10 g/dL, or those requiring erythropoiesis-stimulating agents. 1, 2

Available IV Iron Preparations

Newer Stable Complexes (Higher Single Doses, Faster Administration)

1. Ferric Carboxymaltose (Injectafer)

   • Dosing: 750 mg per dose in US (up to 1500 mg total)
   • Administration time: 15 minutes
   • Benefits:
     • Rapid administration of large doses
     • No test dose required
     • Fewer infusions needed to reach target levels 3
     • Superior efficacy in replenishing iron stores 4, 5
   • Risks:
     • Hypophosphatemia (transient)
     • Infusion site reactions
     • Hypersensitivity reactions (rare)

2. Ferric Derisomaltose/Iron Isomaltoside 1000 (Monoferric)

   • Dosing: Up to 20 mg/kg (maximum 1500 mg)
   • Administration time: 15-30+ minutes
   • Benefits:
     • High single dose capability
     • No test dose required
   • Risks: Similar to other non-dextran formulations

3. Low Molecular Weight Iron Dextran (INFeD)

   • Indication: Treatment of patients with documented iron deficiency when oral administration is unsatisfactory or impossible 6
   • Administration: IV or IM
   • Benefits: Low cost, ability to give doses >1000 mg
   • Risks:
     • Carries boxed warning for anaphylaxis risk
     • Test dose recommended
     • Higher risk of hypersensitivity reactions due to larger carbohydrate shell 1

4. Ferumoxytol (Feraheme)

   • Dosing: 510 mg followed by second 510 mg dose 3-8 days later
   • Administration: IV infusion over at least 15 minutes
   • Benefits: Fewer doses needed compared to iron sucrose
   • Risks:
     • Boxed warning for serious hypersensitivity/anaphylaxis reactions
     • Requires 30-minute observation period
     • Contraindicated in patients with history of allergic reaction to any IV iron 7
     • Can interfere with MRI studies

Older Preparations (Lower Single Doses, Multiple Administrations)

1. Iron Sucrose (Venofer)

   • Maximum single dose: 200 mg
   • Administration time: Longer, multiple doses needed
   • Benefits:
     • Well-established safety profile
     • No test dose required
     • Safe in pregnancy 8
   • Risks:
     • Requires multiple administrations
     • Hypotension, taste disturbances

2. Ferric Gluconate (Ferrlecit)

   • Maximum single dose: 125 mg
   • Administration time: Longer, multiple doses needed
   • Benefits: No test dose required
   • Risks: Similar to iron sucrose

Selection Algorithm Based on Clinical Scenarios

1. Severe Iron Deficiency Anemia (Hb <10 g/dL):

   • First choice: Ferric carboxymaltose or ferric derisomaltose
   • Rationale: Allows rapid correction with fewer infusions 2

2. Inflammatory Bowel Disease:

   • First choice: Ferric carboxymaltose
   • Rationale: Recommended by European Crohn's and Colitis Organisation, effective in active inflammation 1

3. Chronic Kidney Disease:

   • Options: All formulations are suitable
   • For hemodialysis patients: Iron sucrose can be administered during dialysis sessions 1

4. Pregnancy:

   • First choice: Iron sucrose
   • Rationale: Most data supporting safety in pregnancy 8

5. History of Hypersensitivity Reactions:

   • Avoid: Iron dextran formulations
   • Consider: Ferric carboxymaltose (lower immunogenic potential) 9

6. Cost Considerations:

   • Most economical: Iron sucrose or iron dextran
   • Most cost-effective: Ferric carboxymaltose (fewer visits despite higher unit cost) 1

Common Pitfalls and Precautions

• Hypersensitivity reactions: Monitor all patients for at least 30 minutes after infusion 2
• Avoid IV iron in: Active infection, iron overload, anemia not due to iron deficiency 2
• Drug interactions: Do not administer on same day as anthracycline chemotherapy 2
• Monitoring: Check hemoglobin every 4 weeks until normalization, re-evaluate iron status 8-12 weeks after completion 2
• Dosing calculations: Use weight-based dosing for optimal repletion; consider Ganzoni formula or simplified dosing table for ferric carboxymaltose 1, 2

Comparative Efficacy

The newer IV iron formulations (ferric carboxymaltose, ferric derisomaltose, ferumoxytol) generally show similar efficacy in raising hemoglobin levels but require fewer infusions than older preparations. Ferric carboxymaltose has demonstrated rapid and sustained increases in hemoglobin and iron stores across multiple studies 4, 5, 10. A meta-analysis showed IV iron preparations provide significantly larger increases in ferritin (mean difference: 243 μg/L) and transferrin saturation (mean difference: 10.2%) compared to oral iron, with moderate increases in hemoglobin (mean difference: 0.9 g/dL) 1.