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

Guidelines for Intravenous Iron Supplementation

Intravenous iron should be considered first-line treatment for patients with clinically active inflammatory bowel disease, hemoglobin below 100 g/L (10 g/dL), previous intolerance to oral iron, or those requiring erythropoiesis-stimulating agents, while oral iron may be reserved for patients with mild anemia and clinically inactive disease. 1

Clinical Indications for IV Iron

When to Choose IV Over Oral Iron:

• Active inflammatory disease - IV iron is more effective, shows faster response, and is better tolerated than oral iron in patients with active inflammation 1
• Hemoglobin <100 g/L (10 g/dL) - IV iron should be first-line at this threshold 1
• Previous oral iron intolerance - Common gastrointestinal adverse events (20.8% discontinuation rate with oral iron vs 4.5% with IV iron) make IV iron preferable 2
• Need for erythropoiesis-stimulating agents - IV iron enhances response to these medications 1
• Chronic kidney disease on hemodialysis - Oral iron cannot maintain adequate stores in this population; regular IV iron prevents functional iron deficiency 1
• Intestinal malabsorption (celiac disease, atrophic gastritis, bariatric surgery) - IV iron bypasses absorption issues 3

Oral iron may be used only in patients with mild anemia, clinically inactive disease, and no previous intolerance 1

Available IV Iron Formulations

Modern carbohydrate-based preparations allow safe administration of large single doses 1, 4:

• Ferric carboxymaltose (Ferinject/Injectafer) - 1000 mg over 15 minutes; most convenient for single-dose replacement 1, 5
• Iron sucrose (Venofer) - 200 mg over 10 minutes; no test dose required 1, 6, 7
• Iron dextran (Cosmofer) - 20 mg/kg over 6 hours; highest risk of serious reactions (0.6-0.7%) 1
• Sodium ferric gluconate - 125 mg doses 1

Key safety distinction: High molecular weight iron dextran carries the highest anaphylaxis risk, while modern preparations (ferric carboxymaltose, iron sucrose) have serious adverse event rates <1% 1, 4

Dosing Protocols

Ferric Carboxymaltose (Preferred for Rapid Repletion)

For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1500 mg per course), OR 15 mg/kg up to maximum 1000 mg as single dose 5

For patients <50 kg: 15 mg/kg IV in two doses separated by at least 7 days 5

Iron Sucrose

Standard dosing: 200 mg IV push over 10 minutes, administered twice weekly until total iron requirement met 1, 6, 8

For IBD patients: Single doses up to 7 mg/kg (maximum 500 mg) over 3.5 hours have been studied 2

For hemodialysis patients: 100-200 mg directly into dialysis line 2-3 times weekly 1, 6

No test dose required - unlike iron dextran, iron sucrose does not require test dosing 1, 6

Calculating Total Iron Requirement

Base calculation on: Baseline hemoglobin and body weight 1

Target iron parameters:

• Transferrin saturation ≥20% 1
• Serum ferritin ≥100 ng/mL 1
• Hemoglobin 11-12 g/dL (women) or 12-13 g/dL (men) 1

Diagnostic Criteria for Iron Deficiency

Without inflammation (CRP normal): Serum ferritin <30 ng/mL indicates iron deficiency 1

With inflammation (elevated CRP): Serum ferritin up to 100 ng/mL may still represent iron deficiency 1

Anemia of chronic disease: Ferritin >100 ng/mL with transferrin saturation <20% 1

Mixed picture: Ferritin 30-100 ng/mL suggests combination of true iron deficiency and anemia of chronic disease 1

Monitoring and Follow-Up

Initial assessment: Complete blood count, serum ferritin, transferrin saturation, and CRP 1

During treatment:

• Hemoglobin response typically evident after 3 doses of iron sucrose 7
• Wait at least 7 days after 200 mg dose before rechecking iron parameters 6
• Therapeutic response defined as hemoglobin increase ≥2 g/dL within 4 weeks 6

After normalization:

• Monitor every 3 months for first year 1, 6
• Then annually if stable 1
• Re-treat when ferritin drops <100 ng/mL or hemoglobin falls below 12-13 g/dL (gender-dependent) 1

For patients at risk: Check serum phosphate levels before repeat courses within 3 months due to risk of hypophosphatemia with ferric carboxymaltose 5, 4

Safety Considerations and Administration

Resuscitation facilities must be available during all IV iron administrations despite low risk profile 1, 6

Anaphylaxis risk: Extremely rare with iron sucrose (<1:200,000) and ferric carboxymaltose 6, 4

Common side effects: Arthralgia, hypotension, injection site reactions (22-29% incidence) 1, 6

Avoid extravasation - brown discoloration may be long-lasting; discontinue infusion immediately if extravasation occurs 5

Contraindications:

• Active infection - defer IV iron therapy 6
• Known hypersensitivity to IV iron preparations 1

Emerging concern with ferric carboxymaltose: Hypophosphatemia affects 50-74% of patients, potentially causing bone pain, osteomalacia, and fractures through FGF23-mediated hyperphosphaturic mechanism 4

Special Populations

Chronic kidney disease on hemodialysis: Regular prophylactic IV iron (100 mg per dialysis session, 3 times weekly) prevents functional iron deficiency and improves erythropoiesis better than oral iron 1

Inflammatory bowel disease: IV iron demonstrates superior gastrointestinal tolerability compared to oral iron (4.5% vs 20.8% discontinuation rates) and should be first-line in active disease 1, 2

Critically ill patients: In anemic critically ill patients with iron deficiency confirmed by low hepcidin levels, 1 g of IV iron as carbohydrate product is associated with reduced hospital length of stay and 90-day mortality 1

Premenopausal women <50 years: GI investigation not routinely required unless symptoms present, family history of colorectal cancer, or persistent anemia after iron supplementation 1

Common Pitfalls to Avoid

Do not rely solely on ferritin in inflammatory states - ferritin is an acute phase reactant and may be falsely elevated; use transferrin saturation and clinical context 1

Do not delay IV iron in appropriate candidates - waiting for oral iron failure in patients with active inflammation, severe anemia, or malabsorption wastes time and worsens quality of life 1

Do not exceed ferritin target of 500 μg/L - risk of iron overload toxicity increases above this threshold 6

Do not administer repeat courses of ferric carboxymaltose within 3 months without checking phosphate - risk of severe hypophosphatemia and bone complications 5, 4

Do not use high molecular weight iron dextran as first choice - highest serious reaction rate (0.6-0.7%) and 31 reported fatalities between 1976-1996 1