What is the role of ferrous sulfate in treating iron deficiency anemia?

Ferrous Sulfate for Iron Deficiency Anemia

Ferrous sulfate is the first-line oral treatment for iron deficiency anemia, administered once daily at 50-100 mg elemental iron (approximately 200 mg ferrous sulfate), which is equally effective as multiple daily doses and better tolerated. 1, 2

Optimal Dosing Strategy

Once-daily dosing is superior to multiple daily doses because iron absorption triggers hepcidin elevation that blocks subsequent iron absorption by 35-45% for the remainder of the day. 1 The British Society of Gastroenterology specifically recommends 50-100 mg elemental iron once daily for moderately severe anemia, which translates to a single 200 mg ferrous sulfate tablet (containing 65 mg elemental iron). 1, 3

• Alternate-day dosing may provide similar total iron absorption with better tolerability, though this requires further study. 1, 2
• Traditional three-times-daily dosing is outdated and offers no absorption advantage. 1

Treatment Duration and Monitoring

Continue treatment for 3 months after hemoglobin normalization to replenish iron stores. 2

• Expect hemoglobin to rise by at least 10 g/L within 2 weeks of starting therapy. 1
• If this response is absent, it predicts treatment failure with 90% sensitivity and 79% specificity. 1
• After normalization, monitor hemoglobin every 3 months for 1 year, then every 6 months for 2-3 years. 1, 2

Enhancing Absorption

Add vitamin C (250-500 mg) with iron administration to improve absorption. 2

• Avoid tea and coffee within 1 hour of taking iron, as they are powerful absorption inhibitors. 1
• Take on an empty stomach if tolerated, though food may reduce gastrointestinal side effects at the cost of some absorption. 1

When to Switch to Intravenous Iron

Switch to IV iron if:

• Hemoglobin fails to rise by 10 g/L after 2 weeks of adherent oral therapy 1
• Ferritin does not increase after 1 month of treatment 1, 2
• Patient has active inflammatory bowel disease, post-bariatric surgery anatomy, or ongoing blood loss exceeding oral absorption capacity 1, 2
• Intolerable gastrointestinal side effects occur (nausea, constipation, diarrhea affect 12-30% of patients) 1, 2

Common Pitfalls

Gastrointestinal side effects are 2-3 times more common with oral iron than placebo or IV iron, but discontinuation rates in trials are relatively low (0-24%). 1 However, real-world discontinuation rates reach 40% in observational studies. 1

Modified-release preparations are not recommended as they are less suitable for prescribing and offer no proven advantage. 1

Failure to respond has multiple causes beyond poor absorption: non-compliance, continued bleeding, concurrent B12/folate deficiency, systemic inflammation, bone marrow pathology, or hemolysis. 1

Cost and Availability

Ferrous sulfate is the least expensive iron formulation at approximately $0.30-$4.50 per month, compared to $405-$3,896 for IV iron preparations (excluding infusion costs). 1, 2 This makes it the most cost-effective first-line option when oral therapy is feasible. 2, 4