When is intravenous iron indicated for iron‑deficiency anemia and what is the recommended dosing and administration protocol?

Intravenous Iron for Iron Deficiency Anemia: Indications and Dosing

Intravenous iron should be used when patients cannot tolerate oral iron, fail to respond to oral iron therapy, have hemoglobin below 10 g/dL, or have conditions that impair iron absorption such as active inflammatory bowel disease, post-bariatric surgery, or celiac disease. 1

Specific Indications for IV Iron

When to choose IV over oral iron:

• Oral iron intolerance – gastrointestinal side effects preventing compliance 1
• Inadequate response to oral iron – ferritin levels fail to improve after adequate trial 1
• Hemoglobin <10 g/dL – requires more rapid correction 1
• Active inflammatory bowel disease – inflammation impairs oral iron absorption 1
• Post-bariatric surgery – disrupted duodenal absorption 1
• Celiac disease with persistent deficiency despite gluten-free diet 1
• Chronic kidney disease – particularly non-dialysis dependent patients 1, 2
• Heart failure with iron deficiency – to improve exercise capacity 2
• Need for erythropoiesis-stimulating agents – IV iron enhances ESA response 1

Recommended IV Iron Formulations and Dosing

Prefer formulations that allow complete iron repletion in 1-2 infusions rather than multiple smaller doses. 1 The newer high-dose formulations offer superior convenience and reduce healthcare resource utilization. 3, 4

High-Dose Single or Double Infusion Formulations (Preferred):

Ferric carboxymaltose (Ferinject/Injectafer):

• 1,000 mg over 15 minutes as single dose (for patients ≥50 kg) 1, 2
• Alternative: 750 mg × 2 doses separated by ≥7 days (total 1,500 mg) 2
• For patients <50 kg: 15 mg/kg × 2 doses separated by ≥7 days 2
• Most convenient option with excellent safety profile 1, 5

Ferric derisomaltose:

• 1,000 mg in single infusion 3
• Rapidly repletes iron with very low rates of serious hypersensitivity reactions 3, 6

Iron isomaltoside 1000:

• Can deliver up to 1,000 mg in single dose 1
• Available in Europe and multiple countries 1

Multiple-Dose Formulations (Less Preferred):

Iron sucrose (Venofer):

• 200 mg over 10 minutes per dose 1
• Requires multiple visits (typically 5 doses for 1,000 mg total) 1, 6
• Less convenient but well-established safety profile 1

Low molecular weight iron dextran (Cosmofer):

• Can give up to 20 mg/kg (total dose infusion) over 6 hours 1
• Requires test dose due to 0.6-0.7% risk of serious reactions 1
• Associated with historical fatalities; generally avoided in favor of newer agents 1

Dosing Calculations

For general iron deficiency anemia, use simplified weight-based dosing rather than complex formulas: 1

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

1

This simplified approach is superior to Ganzoni's formula, which is inconvenient, error-prone, and underestimates iron requirements. 1 For hemoglobin <7 g/dL, add an additional 500 mg to these totals. 1

Administration Protocol

All IV iron must be given in facilities with resuscitation equipment immediately available. 1 Despite low risk, anaphylaxis can occur with any formulation. 1

Key administration points:

• No test dose required for ferric carboxymaltose, iron sucrose, ferric derisomaltose, or ferumoxytol 1, 3
• Test dose mandatory for iron dextran preparations 1
• Monitor for extravasation – causes prolonged brown discoloration 2
• Infusion reactions (complement activation-related pseudo-allergy) are the most common adverse events, NOT true anaphylaxis 1
• True anaphylaxis is extremely rare with modern formulations 1, 3

Expected Response and Monitoring

Expect hemoglobin increase of ≥2 g/dL within 4 weeks of treatment. 1 While IV iron produces more rapid initial hemoglobin rise, the hemoglobin level at 12 weeks is similar to oral iron therapy. 1

Monitor hemoglobin and red cell indices:

• Every 3 months for 1 year after normalization 1
• Then annually 1
• Check again if anemia symptoms recur 1

For repeat courses within 3 months, check serum phosphate levels – particularly with ferric carboxymaltose, which carries increased hypophosphatemia risk. 2, 5 Treat hypophosphatemia as medically indicated. 2

Critical Safety Considerations

Upper limits for ongoing IV iron therapy:

• Transferrin saturation >50% 1
• Serum ferritin >800 ng/mL 1

These thresholds prevent potential iron overload, though true organ damage from hemochromatosis requires dramatically higher ferritin levels and >20 g excess iron accumulation. 1

Cardiovascular safety: Recent evidence shows single high-dose ferric derisomaltose associated with fewer cardiovascular adverse events and longer time to first cardiovascular event compared to multiple lower doses of iron sucrose. 6 This benefit was consistent in patients with and without heart failure. 6

Avoid intramuscular iron – painful, tissue-damaging, and associated with unacceptable side effects. 1