What is the recommended dosing regimen of oral ferrous sulfate for iron‑deficiency anemia in adults, pregnant patients, and children older than 6 months, and when should intravenous iron be employed?

Oral Iron Dosing for Iron‑Deficiency Anemia

For adults and children older than 6 months with iron‑deficiency anemia, prescribe ferrous sulfate 200 mg (≈65 mg elemental iron) once daily on an empty stomach, add vitamin C 500 mg with each dose, and continue for 3 months after hemoglobin normalizes; switch to intravenous iron when oral therapy fails after 4 weeks, when at least two oral formulations are not tolerated, or when specific malabsorption conditions are present. 1, 2, 3

First‑Line Oral Iron Regimen

• Ferrous sulfate 200 mg once daily is the gold‑standard oral formulation because it delivers ≈65 mg elemental iron per tablet at approximately £1.00 per 28‑day supply, making it the most cost‑effective option with efficacy equal to all other oral iron salts. 1, 2

• Once‑daily dosing is superior to multiple daily doses because iron doses ≥60 mg trigger hepcidin elevation that persists for 24–48 hours, blocking absorption of subsequent doses by 35–45% and increasing gastrointestinal side effects without improving hemoglobin response. 1, 2, 3

• Take on an empty stomach 1–2 hours before or after meals to maximize absorption, though taking with food is acceptable if gastrointestinal side effects occur. 2, 3

• Add vitamin C 500 mg with each iron dose to enhance absorption by forming a soluble chelate and reducing ferric to ferrous iron, especially critical when transferrin saturation is markedly low. 1, 2, 3

• Avoid tea and coffee within 1 hour of the iron dose because they strongly inhibit absorption. 2

Alternative Oral Formulations

• Ferrous fumarate (69–106 mg elemental iron per tablet) or ferrous gluconate (35–38 mg elemental iron per tablet) are equally effective if ferrous sulfate is not tolerated, although they are typically more expensive. 1, 2, 3

• Alternate‑day dosing with 100–200 mg elemental iron markedly increases fractional iron absorption compared with daily dosing, reduces gastrointestinal side effects, and maintains overall efficacy, though the rate of hemoglobin rise may be slower initially. 1, 2

• Ferric maltol 30 mg twice daily may be considered for patients with previous intolerance to traditional ferrous salts, especially those with inactive inflammatory bowel disease, but it costs £47.60 versus £1.00 for ferrous sulfate per 28 days and produces slower iron loading. 2, 3

• Do not prescribe modified‑release preparations because they release iron beyond the duodenum (the primary absorption site) and are classified as "less suitable for prescribing" by the British National Formulary. 1, 2

• Do not rely on multivitamin preparations as the sole iron source because they typically contain ≤14 mg elemental iron, which is insufficient for treating iron‑deficiency anemia. 2

Expected Response and Monitoring

• Check hemoglobin at 2–4 weeks; an increase of ≥10 g/L (≈1–2 g/dL) predicts treatment success with 90% sensitivity and 79% specificity. 1, 2, 3

• Failure to achieve a ≥10 g/L rise by 2 weeks strongly predicts overall treatment failure and warrants investigation for non‑compliance, continued blood loss, malabsorption, or concurrent vitamin B12/folate deficiency. 1, 2

• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores; total treatment duration is typically 6–7 months. 1, 2, 3

• Monitor hemoglobin and red‑cell indices every 3 months during the first year, then again after another year. 1, 3

Indications for Intravenous Iron

Absolute Indications

• Active inflammatory bowel disease with hemoglobin <10 g/dL because inflammation‑induced hepcidin elevation severely impairs oral iron absorption and oral iron may exacerbate intestinal inflammation. 1, 2, 3

• Intolerance to at least two different oral iron preparations (e.g., ferrous sulfate and ferrous fumarate or gluconate). 1, 2, 3

• Ferritin fails to improve after 4 weeks of compliant oral therapy despite adequate dosing and vitamin C supplementation. 1, 2, 3

• Post‑bariatric surgery patients because duodenal iron absorption is anatomically disrupted. 1, 2, 3

Relative Indications

• Celiac disease with inadequate response to oral iron despite strict adherence to a gluten‑free diet. 1, 2, 3

• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or ferritin 100–300 ng/mL with transferrin saturation <20%) because intravenous iron improves symptoms, quality of life, and mortality, whereas oral iron shows no prognostic benefit. 1, 2, 3

• Chronic kidney disease with functional iron deficiency (ferritin 100–300 ng/mL with transferrin saturation <20%); intravenous iron is preferred for dialysis patients and when eGFR <45 mL/min. 2, 3

• Ongoing gastrointestinal blood loss that exceeds the replacement capacity of oral iron. 2, 3

• Second and third trimesters of pregnancy when oral iron fails to correct anemia. 3, 4

Preferred Intravenous Iron Formulations

• Choose formulations that replenish the iron deficit in 1–2 infusions to minimize infusion‑related risk and improve convenience. 1, 2, 3

• Ferric carboxymaltose: 750–1000 mg per 15‑minute infusion; two doses given ≥7 days apart provide a total of 1500 mg. 1, 2, 3

• Ferric derisomaltose: 1000 mg can be delivered as a single infusion. 1, 2, 3

• Iron dextran is not recommended as first‑line because it carries a higher risk of anaphylaxis (≈0.6–0.7%); a test dose is required. 1, 3

• All intravenous iron products share a comparable safety profile; true anaphylaxis is exceedingly rare (<1%), and most adverse reactions are complement‑activation‑related pseudo‑allergic infusion reactions that respond to antihistamines, corticosteroids, and slower infusion rates rather than epinephrine. 1, 2, 3

• Intravenous iron produces a clinically meaningful hemoglobin rise within one week and should be considered an alternative to blood transfusion in most cases. 2, 3

• Monitor serum phosphate before retreatment in patients at risk or when repeat dosing is planned within 3 months, because hypophosphatemia is a recognized adverse effect, especially with ferric carboxymaltose. 2, 5

Special Population Dosing

Pregnant Women

• Start oral low‑dose iron 30 mg/day at the first prenatal visit for prevention in all pregnant women. 2, 3

• Prescribe 60–120 mg/day elemental iron for treatment of iron‑deficiency anemia during pregnancy. 2, 3

• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation. 3

• Intravenous iron is safe and effective during the second and third trimesters when oral iron fails to correct anemia. 3, 4

Children Older Than 6 Months

• A single daily dose of 40 mg elemental iron (e.g., ferrous sulfate drops) is as effective as three‑times‑daily dosing for treating iron‑deficiency anemia in infants and children aged 6–24 months, with similar rates of successful treatment (61% vs 56%) and minimal side effects. 6

Inflammatory Bowel Disease

• Limit oral elemental iron to ≤100 mg per day in patients with inactive inflammatory bowel disease because higher doses may trigger intestinal inflammation. 2, 3

• Avoid oral iron entirely during active inflammatory bowel disease flares; intravenous iron is mandatory. 1, 2, 3

• Monitor iron status every 3 months for at least 1 year after correction, then every 6–12 months thereafter. 2, 3

• Re‑initiate therapy when ferritin falls below 100 µg/L or hemoglobin drops below 12 g/dL (women) or 13 g/dL (men). 2, 3

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron because this increases gastrointestinal side effects without improving efficacy due to hepcidin‑mediated absorption blockade. 1, 2, 3

• Do not discontinue iron therapy when hemoglobin normalizes; continue for an additional 3 months to restore iron stores. 1, 2, 3

• Do not persist with oral iron beyond 4 weeks without a hemoglobin rise; reassess for adherence, malabsorption, ongoing blood loss, or need for intravenous iron. 1, 2, 3

• Do not use oral iron in active inflammatory bowel disease patients with hemoglobin <10 g/dL; intravenous iron is the appropriate first‑line option. 1, 2, 3

• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2, 3

• Do not fail to identify and treat the underlying cause of iron deficiency while providing supplementation. 1, 2, 3

• Do not assume that all intravenous iron reactions are true anaphylaxis; most are pseudo‑allergic and can be managed without abandoning future intravenous therapy. 2, 3

• Do not switch between different ferrous salts (ferrous sulfate, ferrous fumarate, ferrous gluconate) expecting better tolerability, as this is not supported by evidence. 1, 2