What is the best approach to treat a patient with iron deficiency anemia?

Treatment of Iron Deficiency Anemia

First-Line Oral Iron Therapy

Start with ferrous sulfate 200 mg once daily (containing 65 mg elemental iron), taken on an empty stomach, as this is the most cost-effective and evidence-based first-line treatment for iron deficiency anemia. 1

• Once-daily dosing is superior to multiple daily doses because it improves gastrointestinal tolerance while maintaining equal or better iron absorption due to hepcidin regulation that blocks absorption for 48 hours after iron intake 1, 2
• No single oral iron formulation has any therapeutic advantage over another—the choice is purely economic 1
• Alternative formulations (ferrous gluconate 38 mg elemental iron per 325 mg tablet, or ferrous fumarate 106 mg elemental iron per 325 mg tablet) are equally effective if ferrous sulfate is not tolerated 1

Optimizing Oral Iron Absorption

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when iron saturation is severely low 1, 2
• If gastrointestinal side effects occur with daily dosing, switch to alternate-day dosing, which increases fractional iron absorption and improves tolerance with similar efficacy 3, 1
• Taking iron with food is acceptable if gastrointestinal side effects occur, though absorption on an empty stomach is optimal 1

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 3, 1, 2
• Check hemoglobin at 4 weeks—failure to rise by 2 g/dL indicates poor compliance, continued blood loss, malabsorption, or concurrent vitamin B12/folate deficiency 3, 1
• Continue oral iron therapy for 3 months after hemoglobin normalizes to fully replenish iron stores 3, 1, 2
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year 1

When to Switch to Intravenous Iron

Switch to intravenous iron if the patient meets any of these specific criteria:

• Intolerance to at least two different oral iron preparations 3, 1
• Failure of hemoglobin to rise by 2 g/dL after 4 weeks of compliant oral therapy 3, 1
• Active inflammatory bowel disease with hemoglobin <10 g/dL 1
• Post-bariatric surgery patients (due to disrupted duodenal absorption) 1
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 1
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 1

Intravenous Iron Formulations

Prefer IV iron formulations that can replace iron deficits with 1-2 infusions rather than multiple infusions to minimize infusion reactions. 1

• Ferric carboxymaltose (500-1000 mg single doses, delivered within 15 minutes) is a preferred IV iron formulation 1
• Iron dextran can be given as a total dose infusion but carries a higher risk of anaphylaxis (0.6-0.7%) requiring test doses and resuscitation facilities available 3, 1
• Iron sucrose requires multiple visits with maximum 200 mg per infusion over 10 minutes 3
• Iron sucrose is FDA-approved for iron deficiency anemia in patients with chronic kidney disease 4
• Ferric gluconate is FDA-approved for iron deficiency anemia in adult and pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis 5

Identifying and Treating the Underlying Cause

Always investigate and treat the underlying cause of iron deficiency while supplementing iron:

• In premenopausal women, assess menstrual blood loss first, as menorrhagia accounts for iron deficiency in 5-10% of menstruating women 1
• Screen for celiac disease with antiendomysial antibody and IgA measurement, as this is a common cause of malabsorption 1
• In men and postmenopausal women, perform bidirectional endoscopy (gastroscopy and colonoscopy) to evaluate for gastrointestinal blood loss 1
• In patients with inflammatory bowel disease, treat active inflammation first to enhance iron absorption and reduce iron depletion 1

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 1, 2
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1, 2
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 1
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 2
• Do not fail to identify and treat the underlying cause while supplementing iron 1

Special Population Considerations

• Pregnant women: Start oral low-dose iron 30 mg/day at first prenatal visit for prevention; treat anemia with 60-120 mg/day elemental iron; refer if hemoglobin <9.0 g/dL 1
• Inflammatory bowel disease with active inflammation and hemoglobin <10 g/dL: Use IV iron as first-line treatment 1
• Post-bariatric surgery patients: IV iron is preferred due to anatomic considerations affecting duodenal absorption 1

Failure to Respond

If anemia does not resolve within 6 months despite appropriate iron therapy:

• Reassess for ongoing blood loss 1
• Evaluate for malabsorption syndromes 1
• Consider further gastrointestinal investigation 1
• Verify patient adherence to therapy 1
• Consider hematology consultation for complex cases 1