What are the guidelines for iron supplements in treating iron deficiency anemia?

Iron Supplements for Iron Deficiency Anemia

Start with oral ferrous sulfate 200 mg once daily—this is the preferred first-line treatment due to its effectiveness, low cost, and superior tolerability compared to multiple daily dosing. 1, 2

First-Line Oral Iron Therapy

Ferrous sulfate is the gold standard formulation because it contains 65 mg of elemental iron per 200 mg tablet, is the least expensive option, and no other oral iron preparation has demonstrated superior efficacy. 1, 3

Optimal Dosing Strategy

• Prescribe ferrous sulfate 200 mg (65 mg elemental iron) once daily—never multiple times per day, as once-daily dosing improves tolerance while maintaining equal or better iron absorption due to hepcidin regulation. 1, 2
• Take on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur. 1
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when transferrin saturation is severely low. 1, 2
• If side effects occur, switch to every-other-day dosing, which increases fractional iron absorption and improves tolerance with similar efficacy. 1

Alternative Oral Formulations

• Ferrous fumarate (106 mg elemental iron per 325 mg tablet) and ferrous gluconate (38 mg elemental iron per 325 mg tablet) are equally effective alternatives if ferrous sulfate is not tolerated. 1, 2
• These alternatives offer no therapeutic advantage—the choice is purely based on tolerability and cost. 1

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. 1, 2
• Check hemoglobin at 4 weeks; failure to rise by 2 g/dL indicates poor compliance, continued blood loss, or malabsorption. 1, 2
• Continue oral iron therapy for 3 months after hemoglobin normalizes to fully replenish iron stores—total treatment typically lasts 6-7 months. 1, 2
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year. 1, 2

When to Switch to Intravenous Iron

Intravenous iron should replace oral therapy in specific clinical scenarios:

Absolute Indications for IV Iron

• Active inflammatory bowel disease with hemoglobin <10 g/dL—inflammation-induced hepcidin elevation severely impairs oral iron absorption, making IV iron first-line therapy. 4, 2
• Intolerance to at least two different oral iron preparations (e.g., ferrous sulfate, ferrous fumarate, and ferrous gluconate). 1, 2
• Post-bariatric surgery patients—disrupted duodenal absorption mechanisms make oral iron ineffective. 1, 2
• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence. 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity. 1

Relative Indications for IV Iron

• Hemoglobin <10 g/dL in patients requiring rapid correction. 4
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy. 1, 2
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%). 1
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%). 1

Preferred IV Iron Formulations

• Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk and improve convenience. 1, 2
• Ferric carboxymaltose (500-1000 mg single doses delivered within 15 minutes) is a preferred formulation. 1
• All IV iron formulations have similar overall safety profiles; true anaphylaxis is very rare (0.6-0.7%). 1
• Most reactions are complement activation-related pseudo-allergy (infusion reactions) that respond to slowing the infusion rate. 1

Special Population Considerations

Inflammatory Bowel Disease

• Oral iron should only be used in patients with mild anemia (hemoglobin >10 g/dL) and clinically inactive disease who have not been previously intolerant to oral iron. 4
• IV iron is first-line treatment when hemoglobin <10 g/dL with active inflammation—oral iron is poorly absorbed and may worsen inflammation. 4
• Treat active inflammation first to enhance iron absorption and reduce iron depletion. 1, 2
• In the presence of inflammation, ferritin up to 100 mg/L may still indicate iron deficiency; ferritin 30-100 mg/L with transferrin saturation <20% suggests combined iron deficiency and anemia of chronic disease. 4

Pregnant Women

• Start oral low-dose iron 30 mg/day at the first prenatal visit for prevention. 1, 2
• Treat anemia with 60-120 mg/day elemental iron. 1, 2
• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation. 1, 2
• IV iron is indicated during second and third trimesters if oral iron fails or is not tolerated. 1

Celiac Disease

• Ensure strict adherence to gluten-free diet to improve iron absorption. 1, 2
• Screen with antiendomysial antibody and IgA measurement (to exclude IgA deficiency which makes the test unreliable). 4, 1
• Progress to IV iron if iron stores do not improve despite dietary compliance. 1, 2

Post-Bariatric Surgery

• IV iron is preferred due to disrupted duodenal absorption mechanisms. 1, 2

Diagnostic Workup for Underlying Cause

Patients >45 Years

• Investigate with both upper GI endoscopy with small bowel biopsy and colonoscopy due to increasing incidence of significant pathology with age. 4, 2
• 90% of patients should have bidirectional endoscopy unless a firm cause is found with the first investigation. 4, 2

Patients <45 Years

• Perform endoscopy only if upper GI symptoms, alarm features, or family history of colon cancer are present. 4, 1, 2
• Otherwise, perform antiendomysial antibody testing (with IgA measurement) to exclude celiac disease. 4, 1, 2
• In menstruating women, assess menstrual blood loss first, as menorrhagia accounts for iron deficiency in 5-10% of this population. 1, 2

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, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2
• Do not fail to identify and treat the underlying cause of iron deficiency while supplementing. 1, 2
• Do not prescribe oral iron to patients with active inflammatory bowel disease and hemoglobin <10 g/dL—this is ineffective and potentially harmful. 1
• Do not defer iron replacement therapy while awaiting investigations unless colonoscopy is scheduled within days, as iron can interfere with visualization. 1

Failure to Respond to Treatment

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

• Reassess for ongoing blood loss. 4, 1, 2
• Evaluate for malabsorption syndromes. 1, 2
• Verify patient adherence to therapy. 1, 2
• Consider further gastrointestinal investigation with small bowel evaluation. 2
• Consider hematology consultation for complex cases. 1

If no hemoglobin rise occurs within 4 weeks:

• Assess for non-adherence, ongoing blood loss, or malabsorption. 1, 2
• Switch to IV iron if intolerance or malabsorption is confirmed. 1, 2

Quality Targets

• Resolution of anemia should be achieved by 6 months in 80% of patients. 4, 2
• 90% of non-responders should be considered for further investigation. 4, 2