What is the recommended treatment for iron deficiency?

Treatment of Iron Deficiency

First-Line Oral Iron Therapy

Start ferrous sulfate 200 mg (65 mg elemental iron) once daily immediately upon diagnosis—this is the most cost-effective and equally efficacious oral formulation. 1

• Once-daily dosing is superior to multiple daily doses because hepcidin remains elevated for approximately 48 hours after iron intake, blocking subsequent absorption and increasing gastrointestinal side effects without improving efficacy. 2, 1
• Take on an empty stomach for optimal absorption; if gastrointestinal intolerance occurs, taking with food is acceptable. 1
• Add vitamin C 500 mg with each iron dose to markedly enhance absorption, especially critical when transferrin saturation is severely low. 2, 1
• Avoid tea and coffee within 1 hour of the iron dose, as these strongly inhibit absorption. 1
• Alternative formulations—ferrous fumarate (106 mg elemental iron) or ferrous gluconate (38 mg elemental iron)—are equally effective if ferrous sulfate is not tolerated, though typically more expensive. 2, 1

Expected Response and Treatment Duration

• Hemoglobin should rise by approximately 2 g/dL after 3–4 weeks of adequate oral therapy. 2, 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores; total treatment duration is typically 6–7 months. 2, 1
• Monitor hemoglobin and red cell indices every 3 months during the first year, then again after another year. 2, 1

Absolute Indications for Intravenous Iron (First-Line IV Therapy)

Switch to intravenous iron when oral therapy fails or is contraindicated:

• Active inflammatory bowel disease with hemoglobin <10 g/dL—inflammation-driven hepcidin markedly impairs oral absorption, making IV iron first-line therapy. 2, 1
• Intolerance to at least two different oral iron preparations (e.g., ferrous sulfate and ferrous fumarate or gluconate). 2, 1
• Post-bariatric surgery patients—duodenal absorption is anatomically disrupted. 1, 3
• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence. 1
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%)—IV iron improves symptoms and quality of life. 1, 3
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity. 1
• Ferritin levels fail to improve after 4 weeks of compliant oral therapy. 1

Preferred Intravenous Iron Formulations

Choose IV iron preparations that can replace iron deficits in 1–2 infusions to minimize infusion-related risk and improve convenience. 2, 1, 3

• Ferric carboxymaltose (Injectafer): 750–1000 mg per 15-minute infusion; two doses given ≥7 days apart provide a total of 1500 mg. 2, 3, 4
• Ferric derisomaltose: 1000 mg as a single infusion. 1, 4
• Avoid iron dextran as first-line due to higher anaphylaxis risk (0.6–0.7%). 2, 1
• All IV iron formulations have similar overall safety profiles; true anaphylaxis is very rare. 1
• Most infusion reactions are complement-activation pseudo-allergies that respond to slowing the infusion rate. 1
• Administer in a setting equipped with resuscitation facilities. 2, 3

Special Population Considerations

Inflammatory Bowel Disease

• IV iron is first-line when hemoglobin <10 g/dL with active inflammation—oral iron is poorly absorbed and may worsen inflammation. 2, 1
• For mild anemia (hemoglobin >10 g/dL) with quiescent disease, oral iron may be used if absorption is adequate. 1
• Treat active inflammation first to enhance iron absorption and reduce iron depletion. 1

Pregnant Women

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention. 1
• Treat anemia with 60–120 mg/day elemental iron. 1
• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation. 1
• IV iron is safe and effective during second and third trimesters when oral iron fails. 1

Chronic Kidney Disease

• IV iron is preferred for dialysis patients. 1
• Either IV or oral iron for non-dialysis CKD stages 3–5. 1

Investigation of Underlying Cause

Do not delay iron therapy while awaiting diagnostic workup, unless colonoscopy is scheduled within days (iron can impair endoscopic visualization). 2, 1

• All adult men and post-menopausal women require bidirectional endoscopy (upper endoscopy + colonoscopy) to exclude gastrointestinal malignancy. 2, 1
• Pre-menopausal women: Assess menstrual blood loss first—menorrhagia, pregnancy, and breastfeeding account for iron deficiency in 5–10% of menstruating women. 1
• Screen for celiac disease with antiendomysial antibody and IgA measurement—present in 3–5% of iron-deficiency cases. 2, 1
• Test for Helicobacter pylori and eradicate if present. 2, 1

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade. 2, 1
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores. 2, 1
• Do not persist with oral iron beyond 4 weeks without hemoglobin rise—reassess for malabsorption, ongoing loss, or need for IV iron. 1
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 2, 1
• Do not fail to identify and treat the underlying cause of iron deficiency while supplementing. 2, 1
• Do not use oral iron in active IBD patients with hemoglobin <10 g/dL—IV iron is the appropriate first-line option. 2, 1

Failure to Respond Algorithm

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

1. Verify patient adherence to therapy. 1
2. Reassess for ongoing blood loss (occult GI bleeding, menorrhagia). 1
3. Evaluate for malabsorption syndromes (celiac disease, IBD, post-bariatric surgery). 1
4. Check for concurrent vitamin B12 or folate deficiency. 1
5. Consider further gastrointestinal investigation. 2, 1
6. Switch to intravenous iron if oral therapy failure is confirmed. 1