What is the recommended dosing frequency for ferrous sulfate (iron supplement) 325mg in a patient with a new diagnosis of iron deficiency anemia?

Recommended Dosing Frequency for Ferrous Sulfate 325mg in Iron Deficiency Anemia

Take ferrous sulfate 325mg once daily, not multiple times per day, as once-daily dosing improves tolerability while maintaining equal or better iron absorption compared to multiple daily doses. 1, 2

Optimal Dosing Regimen

• Ferrous sulfate 325mg contains approximately 65mg of elemental iron, and the recommended dose is one tablet once daily. 1, 2

• Once-daily dosing is superior to multiple daily doses because oral iron stimulates hepcidin levels, which remain elevated for 48 hours after iron intake and block further iron absorption by 35-45%. 1

• Taking the tablet on an empty stomach optimizes absorption, though taking with food is acceptable if gastrointestinal side effects occur. 2

• Add vitamin C (ascorbic acid) 500mg with each iron dose to enhance absorption, especially critical in patients with severely low iron saturation. 1, 2

Alternative Dosing Strategy

• If once-daily dosing causes intolerable gastrointestinal side effects, switch to every-other-day dosing (ferrous sulfate 325mg every other day), which increases fractional iron absorption and improves tolerance with similar overall efficacy. 1

• Alternate-day dosing leads to significantly increased fractional iron and total iron absorption compared to daily dosing in iron-depleted individuals. 1

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. 1, 2

• If hemoglobin fails to rise by at least 10 g/L after 2 weeks of daily oral iron therapy, this strongly predicts subsequent failure to achieve sustained haematological response (sensitivity 90.1%, specificity 79.3%). 1

• Continue oral iron therapy for 3 months after hemoglobin normalizes to fully replenish iron stores, resulting in a total treatment duration of typically 6-7 months. 1, 2

• Monitor hemoglobin and red cell indices every 3 months for the first year after completing therapy, then again after another year. 1, 2

Critical Pitfalls to Avoid

• Never prescribe ferrous sulfate 325mg two or three times daily—this increases gastrointestinal side effects without improving efficacy due to hepcidin-mediated absorption blockade. 1, 2

• Gastrointestinal adverse effects (nausea, diarrhea, constipation) are significantly more common with oral ferrous sulfate than placebo (OR 2.32,95% CI 1.74-3.08), and there is no dose-effect relationship over the range 50-400mg of elemental iron per day. 1

• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores. 1, 2

• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2

When to Switch to Intravenous Iron

• Consider intravenous iron if the patient cannot tolerate at least two different oral iron preparations, if ferritin levels fail to improve after 4 weeks of compliant oral therapy, or if specific malabsorption conditions exist. 1, 2

• Active inflammatory bowel disease with hemoglobin <10 g/dL is an absolute indication for IV iron as first-line therapy, not oral iron. 1, 2

• Post-bariatric surgery patients with disrupted duodenal iron absorption should receive IV iron preferentially. 1, 2