What is the preferred method of iron replacement, intravenous (IV) iron or oral iron supplements?

Iron Replacement: IV versus Oral

For most patients with iron deficiency anemia, oral iron should be the first-line treatment, but intravenous iron is preferred in specific clinical scenarios including active inflammatory bowel disease, severe anemia (hemoglobin <10 g/dL), intolerance to oral iron, or when rapid repletion is required. 1

Clinical Decision Algorithm

Start with Oral Iron If:

• Mild anemia with hemoglobin ≥10 g/dL 1
• Clinically inactive disease (particularly in IBD patients) 1
• No prior intolerance to oral iron 1
• No malabsorption conditions (e.g., post-bariatric surgery) 1
• Iron loss does not exceed oral absorption capacity 1

Switch to IV Iron If:

• Active inflammatory bowel disease 1
• Severe anemia with hemoglobin <10 g/dL (100 g/L) 1
• Previous intolerance to oral iron 1
• Inadequate response to oral iron (hemoglobin fails to increase by 1 g/dL within 2 weeks, or ferritin fails to increase within 1 month) 1
• Need for erythropoiesis-stimulating agents 1
• Acute anemia with hemodynamic instability 1
• Chronic kidney disease (especially dialysis-dependent) 1
• Heart failure patients requiring improved exercise capacity 2

Oral Iron Administration

Dosing Strategy

• Standard dose: 100-200 mg elemental iron daily 1
• Once daily dosing is sufficient because hepcidin elevation after iron intake blocks further absorption for up to 48 hours 1
• Consider alternate-day dosing to improve tolerance and potentially absorption, though this requires further validation 1

Optimization Tips

• Take on empty stomach with 80 mg vitamin C for optimal absorption, though evidence for vitamin C is mixed 1
• Avoid tea and coffee within 1 hour as they powerfully inhibit iron absorption 1
• Can take with food if gastrointestinal side effects occur, accepting reduced absorption 1
• Do not crush or chew tablets to avoid tooth staining and altered absorption 3

Expected Response

• Hemoglobin should increase by at least 1 g/dL within 2 weeks 1
• Continue for 2-3 months after hemoglobin normalization to replenish iron stores 3
• Monitor hemoglobin approximately every 4 weeks until normal range achieved 3

Common Side Effects

• Constipation (12%), diarrhea (8%), nausea (11%) 1
• Gastrointestinal adverse effects are dose-related 1

Intravenous Iron Administration

Efficacy Advantages

• More effective than oral iron with faster response rates in multiple randomized studies 1
• Better tolerated than oral iron in most patients 1
• In critically ill inflammatory patients, associated with reduced hospital length of stay and 90-day mortality 1

Dosing

• For patients ≥50 kg: 750 mg IV in two doses separated by ≥7 days (total 1,500 mg per course) 2
• For patients <50 kg: 15 mg/kg body weight in two doses separated by ≥7 days 2
• Alternative: Single dose of up to 1,000 mg in adults 2
• Formulations allowing 1-2 infusions are preferred (e.g., ferric carboxymaltose, ferric derisomaltose) 1

Safety Profile

• Serious reactions are very rare (approximately 1:200,000 with modern formulations) 1
• Most reactions are complement activation-related pseudo-allergy, not true allergic reactions 1
• Mild reactions (1:200): Stop infusion, restart after 15 minutes at slower rate 1
• Severe reactions: Corticosteroids may help; avoid diphenhydramine as side effects can mimic worsening reaction 1

Cost Consideration

• IV iron is substantially more expensive than oral formulations 1
• Medication costs range from $405 to $3,896 per course, not including infusion visit costs 1

Special Populations

Inflammatory Bowel Disease

• IV iron is first-line for active disease 1
• Oral iron may exacerbate IBD through reactive oxygen species generation (Fenton reaction), though clinical significance is debated 1
• Oral iron acceptable for mild anemia in clinically inactive disease 1

Chronic Kidney Disease

• IV iron preferred, especially in dialysis-dependent patients 1

Heart Failure

• IV iron improves exercise capacity in iron-deficient patients with NYHA class II/III 2
• Dosing based on weight and hemoglobin level, with maintenance doses if ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 2

Critical Pitfalls to Avoid

• Discontinuing oral iron prematurely before stores are replenished (continue 2-3 months after hemoglobin normalization) 3
• Prescribing excessive oral iron doses (>200 mg/day) that increase side effects without improving efficacy 1
• Checking ferritin too early after IV iron (wait 8-10 weeks as levels are falsely elevated initially) 1
• Failing to check serum phosphate in patients requiring repeat IV iron courses within 3 months 2
• Assuming oral iron failure without assessing adherence, ongoing blood loss, or malabsorption 1, 3