What is the typical treatment regimen for a patient with iron deficiency anemia (IDA) using ferrous sulfate (iron supplement)?

Ferrous Sulfate 325 mg for Iron Deficiency Anemia

First-Line Treatment Recommendation

Start with ferrous sulfate 325 mg (65 mg elemental iron) once daily, not three times daily, as this provides equal efficacy with better tolerability and improved absorption. 1, 2, 3

The British Society of Gastroenterology and American Gastroenterological Association both strongly recommend once-daily dosing over traditional multiple-daily-dose regimens because hepcidin levels remain elevated for 48 hours after iron intake, blocking subsequent iron absorption when doses are given more frequently. 1, 2

Optimal Dosing Strategy

• Take ferrous sulfate 325 mg once daily on an empty stomach for maximum absorption, though taking with food is acceptable if gastrointestinal side effects occur 1, 2, 3
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when transferrin saturation is severely low 1, 2
• Alternate-day dosing (every other day) is an acceptable alternative if daily dosing causes intolerable side effects, as fractional iron absorption actually increases with this schedule while maintaining similar overall efficacy 1, 2

Research confirms that once-daily dosing produces similar hemoglobin responses to three-times-daily dosing without increased side effects. 4

Expected Response and Monitoring

• Check hemoglobin at 4 weeks, expecting a rise of approximately 2 g/dL 1, 2, 3
• Failure to achieve at least a 10 g/L (1 g/dL) rise after 2 weeks strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) and warrants reassessment for non-compliance, malabsorption, ongoing blood loss, or need for intravenous iron 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish bone marrow iron stores 1, 2, 3
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year to detect recurrent iron deficiency 1, 2

When to Switch to Intravenous Iron

Consider intravenous iron if any of the following criteria are met:

• Intolerance to at least two different oral iron preparations (ferrous sulfate, ferrous fumarate, or ferrous gluconate) 1, 2, 3
• No improvement in ferritin levels after 4 weeks of compliant oral therapy 1, 2
• Active inflammatory bowel disease with hemoglobin <10 g/dL 1, 2, 3
• Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms 2, 3
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 2, 3
• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) 1, 2
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%), as intravenous iron improves symptoms and quality of life 1, 2, 3
• Second and third trimesters of pregnancy if oral iron fails 2, 3
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2

For intravenous iron, prefer formulations that can replace iron deficits in 1-2 infusions (such as ferric carboxymaltose 750-1000 mg or low molecular weight iron dextran) rather than multiple infusions. 1, 2

Alternative Oral Formulations

If ferrous sulfate 325 mg is not tolerated, switch to:

• Ferrous fumarate 322 mg (106 mg elemental iron) once daily 1, 2
• Ferrous gluconate 300 mg (37 mg elemental iron) once daily 1, 2
• Ferric maltol 30 mg twice daily for patients with inflammatory bowel disease who cannot tolerate traditional iron salts, though this is considerably more expensive 1

All oral iron formulations have equivalent efficacy—the choice is purely based on tolerability and cost. 2 Ferrous sulfate remains the least expensive and most cost-effective option. 1, 2

Critical Pitfalls to Avoid

• Never prescribe ferrous sulfate 325 mg three times daily—this increases gastrointestinal side effects without improving efficacy due to hepcidin-mediated absorption blockade after the first dose 1, 2
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish iron stores 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal, as ascorbic acid significantly enhances iron absorption 1, 2
• Do not delay iron replacement therapy while awaiting diagnostic workup unless colonoscopy is imminent within days 1, 2
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to intravenous iron if hemoglobin fails to rise by at least 1-2 g/dL 1, 2
• Do not use modified-release iron preparations, as they are less suitable for prescribing due to unpredictable iron release beyond the duodenum where absorption is optimal 1

Special Considerations

For patients with achlorhydria (autoimmune gastritis, Helicobacter pylori gastritis, proton pump inhibitor use): Standard ferrous sulfate may have reduced efficacy due to impaired iron solubilization. Consider duodenal-release formulations or earlier transition to intravenous iron if response is inadequate. 5

For pregnant women: Start with oral low-dose iron 30 mg/day at first prenatal visit for prevention, and treat anemia with 60-120 mg/day elemental iron (approximately ferrous sulfate 325 mg once or twice daily). 2, 3

For inflammatory bowel disease patients: Treat active inflammation first to enhance iron absorption and reduce iron depletion. Use intravenous iron as first-line when hemoglobin <10 g/dL with active inflammation. 1, 2