What is the recommended dosage and administration of ferrous sulphate (Iron Supplement) for a patient with Iron Deficiency Anemia (IDA) to optimize iron absorption and bioavailability?

Optimal Dosing and Administration of Ferrous Sulphate for Iron Deficiency Anemia

For adults with iron deficiency anemia, prescribe ferrous sulphate 200 mg (65 mg elemental iron) once daily, taken in the fasting state, as this represents the best compromise between efficacy and tolerability. 1, 2

Recommended Dosing Regimen

• Start with ferrous sulphate 200 mg (65 mg elemental iron) once daily rather than multiple daily doses, as once-daily dosing improves gastrointestinal tolerance while maintaining equal or superior iron absorption. 1

• Administer in the fasting state (on an empty stomach) to maximize absorption, though taking with food is acceptable if gastrointestinal side effects occur. 1, 3

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when transferrin saturation is severely low. 1, 3

Alternative Dosing Strategy for Better Tolerance

• Consider alternate-day dosing (every 48 hours) if daily dosing causes intolerable side effects, as this approach increases fractional iron absorption and significantly reduces gastrointestinal adverse events (relative risk 0.56 for GI side effects). 1, 4

• Alternate-day dosing with 120 mg elemental iron produces similar hemoglobin increments after the same total dose, with significantly lower prevalence of nausea compared to 60 mg twice daily. 1

• The rationale is that oral iron doses ≥60 mg stimulate an acute hepcidin increase that persists 24 hours and blocks further iron absorption, but subsides by 48 hours. 4

Expected Response and Monitoring

• Expect hemoglobin to rise by at least 10 g/L (1 g/dL) after 2 weeks of daily oral iron therapy—absence of this rise is strongly predictive of subsequent treatment failure (sensitivity 90.1%, specificity 79.3%). 1

• Check hemoglobin at 4 weeks, expecting approximately 2 g/dL rise as confirmation of adequate response. 1, 3, 5

• Continue oral iron for 2-3 months after hemoglobin normalizes to replenish iron stores, though the optimal duration remains unclear. 1

• Monitor hemoglobin every 4 weeks until normal range is reached, then every 3 months for the first year, and again after another year. 1

Optimizing Bioavailability

• Morning administration is preferred over afternoon or evening dosing, as the circadian increase in plasma hepcidin is augmented by morning iron doses, reducing absorption from subsequent doses. 4

• Avoid taking with calcium, tea, coffee, or antacids, which significantly impair iron absorption through chelation or pH changes. 3

• The standard ferrous sulphate tablet (324 mg) contains 65 mg elemental iron, providing 362% of the U.S. recommended daily intake. 2

When Standard Oral Iron Fails

• Switch to alternate-day dosing first before abandoning oral therapy entirely, as this improves tolerance while maintaining efficacy. 1, 4

• Try alternative ferrous salts (ferrous fumarate or ferrous gluconate) if ferrous sulphate is not tolerated, though evidence does not support superior tolerability. 1, 3

• Consider intravenous iron if intolerance persists despite trying at least two different oral preparations, or if hemoglobin fails to rise by 10 g/L after 2 weeks of compliant therapy. 1, 5

Critical Pitfalls to Avoid

• Never prescribe multiple daily doses (e.g., three times daily)—this increases gastrointestinal side effects without improving efficacy due to hepcidin-mediated absorption blockade. 1, 4

• Do not use modified-release preparations, as they are considered less suitable for prescribing and may release iron beyond the duodenum where absorption is optimal. 1

• Do not switch between different traditional iron salts expecting better tolerance—this practice is not supported by evidence. 1

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

• Do not overlook vitamin C supplementation when response is suboptimal, as ascorbic acid significantly enhances iron bioavailability. 1, 3, 6

Causes of Treatment Failure

• Non-compliance is the most common cause—verify adherence before escalating therapy. 1

• Ongoing blood loss exceeding replacement capacity requires identification and treatment of the source. 1, 5

• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery) require intravenous iron as oral absorption is severely impaired. 1, 5

• Concurrent vitamin B12 or folate deficiency prevents adequate hemoglobin response despite iron repletion. 1

• Chronic inflammatory conditions elevate hepcidin and block iron absorption—intravenous iron is more effective in these patients. 1, 5

Special Considerations for Bioavailability

• Liquid iron formulations (naturally iron-rich mineral waters with added ascorbate) demonstrate equivalent or superior bioavailability compared to ferrous sulphate tablets in vitro. 6

• Lower therapeutic doses (80 mg elemental iron) are equally effective as higher doses (200 mg) for managing IDA, supporting the use of once-daily 65 mg dosing. 7

• Prolonged-release formulations show non-inferior efficacy to standard ferrous sulphate with significantly lower incidence of moderate-to-severe gastrointestinal adverse events (5.6% vs 13.9%, p=0.007). 8