How should I treat an adult with iron‑deficiency anemia using oral iron (including appropriate dose, timing with vitamin C, monitoring parameters) and when is intravenous iron indicated?

Oral Iron Replacement for Iron-Deficiency Anemia

Ferrous sulfate 200 mg (65 mg elemental iron) taken once daily in the morning on an empty stomach with 100–500 mg vitamin C is the optimal first-line treatment for iron-deficiency anemia in adults. 1, 2

First-Line Oral Iron Formulation

• Ferrous sulfate is the gold-standard formulation because no oral iron preparation has demonstrated superior efficacy or tolerability, and ferrous sulfate costs approximately £1.00 per 28-day supply compared to £47.60 for alternatives like ferric maltol. 1, 2
• Each 200 mg ferrous sulfate tablet delivers 65 mg elemental iron, which is the target dose range. 2
• Alternative ferrous salts (ferrous fumarate 69–106 mg elemental iron per tablet, ferrous gluconate 37 mg elemental iron per tablet) may be substituted if ferrous sulfate is not tolerated, though evidence does not support improved tolerability with switching. 2
• Avoid modified-release preparations entirely—they are classified as "less suitable for prescribing" because iron is released beyond the duodenum where absorption occurs. 2
• Multivitamin products containing ≤14 mg elemental iron are insufficient for treating iron-deficiency anemia. 2

Optimal Dosing Strategy

• Once-daily dosing of 50–100 mg elemental iron is superior to multiple daily doses because doses ≥60 mg trigger hepcidin elevation lasting 24 hours, reducing absorption of subsequent doses by 35–45%. 1, 2
• Alternate-day (every-other-day) dosing with 100–200 mg elemental iron markedly increases fractional iron absorption compared to daily dosing and reduces gastrointestinal side effects while maintaining efficacy. 1, 2, 3
• Take iron in the morning on an empty stomach (1–2 hours before meals) to maximize absorption, though this increases gastrointestinal side effects. 2, 4
• If gastrointestinal intolerance is severe, taking iron with food improves adherence despite reducing absorption—this trade-off may be necessary. 4

Vitamin C Co-Administration

• Add 100–500 mg vitamin C (or a glass of orange juice containing ~100 mg) when taking oral iron to enhance non-heme iron absorption by forming a chelate that prevents insoluble iron compounds and reduces ferric to ferrous iron. 1, 2, 4
• Vitamin C is particularly important when iron must be taken with food, as it allows absorption even when calcium or fiber is present. 4
• Contraindication: Patients with hemochromatosis or iron overload must completely avoid vitamin C supplements with iron because vitamin C accelerates iron mobilization and can cause cardiac arrhythmias, cardiomyopathy, and sudden death. 4

Monitoring Parameters

• Check hemoglobin at 2 weeks after initiating therapy—an increase of ≥10 g/L predicts treatment success with 90% sensitivity and 79% specificity. 2, 3
• If hemoglobin has not risen ≥10 g/L at 2 weeks, investigate for non-compliance, continued blood loss, malabsorption, or concurrent vitamin B12/folate deficiency. 2
• Monitor hemoglobin every 4 weeks until normalized. 2
• Continue treatment for 3 months after hemoglobin normalizes to replenish marrow iron stores. 2, 3
• Re-evaluate the complete iron panel (ferritin, transferrin saturation) after 4 weeks of oral therapy to determine adequacy of absorption. 2

Indications for Intravenous Iron

Intravenous iron is indicated when: 1, 5

• Oral iron is not tolerated despite dosing modifications (alternate-day dosing, taking with food, switching formulations)
• Ferritin levels do not improve after 4–8 weeks of optimized oral iron therapy
• Transferrin saturation remains <20% after adequate oral iron trial
• Conditions impairing oral iron absorption are present:
  • Inflammatory bowel disease with active inflammation 1, 6
  • Post-bariatric surgery (especially procedures disrupting duodenal absorption) 1, 5
  • Celiac disease with persistent deficiency despite strict gluten-free diet 2
  • Chronic kidney disease with eGFR <45 mL/min 2
• Chronic heart failure with iron deficiency (ferritin <100 μg/L and/or transferrin saturation <20%)—intravenous iron has demonstrated prognostic benefit, whereas oral iron has not 1
• Ongoing blood loss that cannot be controlled
• Second or third trimester of pregnancy 5

Intravenous Iron Formulation Selection

• Prefer high-dose formulations that replete total iron deficit in 1–2 infusions (ferric carboxymaltose, ferric derisomaltose delivering 500–1000 mg per infusion) over formulations requiring multiple visits. 1, 2
• All intravenous iron products have comparable safety profiles; true anaphylaxis is exceedingly rare (<1%). 1, 3
• Most adverse reactions are complement-activation-related pseudo-allergic infusion reactions (not true anaphylaxis) and should be managed with antihistamines and corticosteroids, not epinephrine. 1, 2
• Monitor serum phosphate before retreatment in patients requiring repeat courses within 3 months, as hypophosphatemia is a recognized adverse effect. 2

Special Population Considerations

Inflammatory Bowel Disease

• Limit oral iron to ≤100 mg elemental iron daily in patients with inactive IBD; higher doses may aggravate intestinal inflammation. 1, 2, 6
• Avoid oral iron entirely during active IBD flares—intravenous iron is mandatory because inflammation markedly reduces absorption and oral iron may exacerbate disease activity. 1, 6
• Ferric maltol 30 mg twice daily (total 60 mg elemental iron) is an alternative for IBD patients with prior intolerance to ferrous sulfate, though it costs £47.60 versus £1.00 for ferrous sulfate per 28 days. 2
• Monitor iron status every 3 months for at least 1 year after correction, then every 6–12 months thereafter. 1, 2

Chronic Kidney Disease

• Oral iron may be tried in predialysis patients, but intravenous iron is required if oral iron is ineffective, not tolerated, or if dialysis has commenced. 1
• Once eGFR falls below 45 mL/min, intravenous iron becomes the preferred route. 2
• Management should be coordinated with the nephrology team, as erythropoietin may also be needed. 1

Chronic Heart Failure

• Intravenous iron is preferred over oral iron in heart failure patients with iron deficiency (ferritin <100 μg/L and/or transferrin saturation <20%) because oral iron may be poorly absorbed due to gut edema and has not demonstrated prognostic benefit. 1
• Intravenous iron has shown prognostic benefit in meta-analyses for functional capacity, quality of life, and mortality. 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of iron—this increases gastrointestinal side effects without improving absorption due to hepcidin-mediated blockade. 1, 2
• Do not continue oral iron indefinitely without monitoring—failure to achieve expected hemoglobin rise by 2 weeks strongly predicts treatment failure and warrants investigation or escalation to intravenous iron. 2
• Do not take iron with tea, coffee, or calcium-containing foods/medications—these significantly inhibit absorption. 2, 4
• Do not rely on switching between different ferrous salts expecting better tolerability—evidence does not support this practice. 2
• Do not assume all intravenous iron reactions are anaphylaxis—most are infusion-related pseudo-allergies that do not preclude future intravenous iron when appropriate premedication and slower infusion rates are used. 1, 2