What is the recommended treatment for iron deficiency anemia?

Treatment of Iron Deficiency Anemia

Start with ferrous sulfate 200 mg once daily as a single morning dose on an empty stomach, which is the preferred first-line treatment due to superior tolerability and effectiveness compared to multiple daily dosing. 1

First-Line Oral Iron Therapy

Ferrous sulfate 200 mg once daily is the standard treatment for iron deficiency anemia in most patients, taken as a single morning dose rather than divided throughout the day. 1 This regimen maximizes absorption while minimizing gastrointestinal side effects that reduce compliance. 2

Dosing Strategy

• Take iron 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 when response is suboptimal. 1
• For doses ≥60 mg, consider alternate-day dosing rather than daily administration, as oral iron doses ≥60 mg stimulate an acute increase in hepcidin that persists 24 hours and reduces absorption of subsequent doses. 2
• Avoid afternoon or evening dosing after a morning dose, as the circadian increase in plasma hepcidin is augmented by morning iron administration. 2

Expected Response and Duration

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. 1
• Continue oral iron therapy for 3 months after anemia correction to fully replenish iron stores, not just until hemoglobin normalizes. 1
• If no hemoglobin rise occurs within 4 weeks, assess for non-adherence, ongoing blood loss, or malabsorption before continuing the same regimen. 1

Monitoring Schedule

• Check hemoglobin and red cell indices at 3-month intervals for the first year, then again after another year. 1
• Provide additional iron supplementation if hemoglobin or MCV falls below normal during follow-up. 1

Intravenous Iron Therapy

Switch to intravenous iron as first-line treatment in the following specific circumstances:

• Clinically active inflammatory bowel disease 3
• Hemoglobin below 100 g/L (10 g/dL) 3
• Previous intolerance to oral iron 3
• Patients requiring erythropoiesis-stimulating agents 3
• Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms 1
• Failure to respond to oral iron after 4 weeks despite compliance and absence of acute illness 3

The European Crohn's and Colitis Organization guidelines conclude that intravenous iron is more effective, shows a faster response, and is better tolerated than oral iron in these populations. 3

Special Population Considerations

Inflammatory Bowel Disease Patients

• Treat active inflammation first to enhance iron absorption and reduce iron depletion. 1
• Use oral iron only in patients with mild anemia whose disease is clinically inactive and who have not been previously intolerant to oral iron. 3
• Diagnostic criteria for iron deficiency depend on inflammation level: In remission, serum ferritin <30 mg/L indicates deficiency; with inflammation present, ferritin up to 100 mg/L may still indicate iron deficiency. 3

Pregnant Women

• Start oral, low-dose (30 mg/day) supplements at the first prenatal visit for primary prevention. 3
• For treatment of anemia, prescribe 60-120 mg/day of elemental iron. 3
• When hemoglobin normalizes for gestational stage, decrease the dose to 30 mg/day. 3
• If hemoglobin is less than 9.0 g/dL or hematocrit less than 27.0%, refer to a physician familiar with anemia during pregnancy for further evaluation. 3

Celiac Disease Patients

• Ensure strict adherence to gluten-free diet to improve iron absorption before expecting full response to supplementation. 1

Diagnostic Workup for Unexplained Iron Deficiency Anemia

The underlying cause must be identified while treating the anemia:

• Patients >45 years should undergo bidirectional endoscopy (gastroscopy and colonoscopy) due to increasing incidence of gastrointestinal malignancy with age. 1
• Patients <45 years should have endoscopy only if upper GI symptoms are present; otherwise, perform antiendomysial antibody testing to exclude celiac disease. 1
• Small bowel investigation is not routinely recommended after negative bidirectional endoscopy unless red flags are present (involuntary weight loss, abdominal pain, elevated CRP). 4

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses – once-daily or alternate-day dosing improves tolerability with similar or better efficacy. 1, 2
• Do not stop iron when hemoglobin normalizes – continue for 3 months to replenish stores. 1
• Do not continue ineffective oral iron beyond 4 weeks – reassess and switch to IV iron if hemoglobin fails to rise. 1
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1
• Do not fail to identify the underlying cause while supplementing iron. 1
• Do not use doses exceeding 200 mg daily – higher doses decrease fractional absorption and increase side effects without improving efficacy. 2

Management of Treatment Failure

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

• Reassess for ongoing blood loss, malabsorption syndromes, non-adherence, or misdiagnosis. 1
• Consider further gastrointestinal investigation with small bowel evaluation. 1
• Consider hematology consultation for complex cases. 1
• In patients where GI blood loss exceeds intestinal absorption capacity (e.g., intestinal angiodysplasia), intravenous iron supplementation is required. 5