What is the appropriate starting dose for supplemental iron in an adult patient with iron deficiency anemia?

Appropriate Starting Dose for Supplemental Iron in Adults with Iron Deficiency Anemia

Start with 50-100 mg of elemental iron once daily, taken in the morning on an empty stomach, using ferrous sulfate 200 mg tablets (which provide 65 mg elemental iron) as the first-line agent. 1, 2

First-Line Oral Iron Therapy

Recommended Formulation and Dose

• Ferrous sulfate 200 mg tablets (providing 65 mg elemental iron) are the gold standard and most cost-effective option, costing approximately £1.00 for a 28-day supply compared to £47.60 for newer formulations like ferric maltol 1, 2, 3

• A single daily dose of 50-100 mg elemental iron is optimal, as doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours and blocks subsequent iron absorption 1, 2, 4

• Taking a second dose the same day results in 35-45% reduction in absorption due to elevated hepcidin, making multiple daily doses ineffective and more likely to cause side effects 2, 4

Timing and Administration

• Take iron in the morning on an empty stomach (1-2 hours before or after meals) to maximize absorption, though this may increase gastrointestinal side effects 1, 2

• Avoid afternoon or evening dosing after a morning dose, as the circadian increase in plasma hepcidin is augmented by morning iron and persists throughout the day 4

Alternative Ferrous Salts (If Ferrous Sulfate Not Tolerated)

• Ferrous fumarate provides 69-106 mg elemental iron per tablet (depending on formulation) and costs £1.00-1.40 for 28 days 1, 5

• Ferrous gluconate provides 37-38 mg elemental iron per tablet and costs £2.18 for 28 days 1, 5

• However, switching between different ferrous salts is not supported by evidence for improving tolerability 1, 2

Monitoring Response and Adjusting Treatment

Expected Response Timeline

• Hemoglobin should rise by at least 10 g/L within 2 weeks of starting daily oral iron therapy; failure to achieve this strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) 1, 2

• Monitor hemoglobin within the first 4 weeks to confirm adequate response and detect non-responders early 1, 2

• Continue treatment for approximately 3 months after hemoglobin normalizes to ensure adequate repletion of iron stores 1, 2

If Standard Dosing Not Tolerated

• Consider alternate-day dosing with 100-200 mg elemental iron, which leads to significantly increased fractional iron absorption compared to daily dosing, though the rate of hemoglobin rise may be slower initially 1, 2, 4

• Reduce the dose to the lower end of the range (50 mg daily) or consider taking with food, though this reduces absorption 1

• Ferric maltol 30 mg twice daily may be considered for patients with previous intolerance to traditional iron salts, though it is considerably more expensive (£47.60 vs £1.00 for 28 days) and produces slower iron loading 1, 2

When to Escalate to Intravenous Iron

Consider intravenous iron replacement for patients in whom oral iron is not effective, not absorbed, or not tolerated, or presenting with severe anemia. 1

• Intravenous iron should be first-line in patients with chronic disease, continuing blood loss, impaired absorption (inflammatory bowel disease, post-bariatric surgery), or gastrointestinal inflammatory pathology 1, 2

• Parenteral iron produces a clinically meaningful hemoglobin response within one week and should be considered as an alternative to blood transfusion in most cases 1

• For IV iron, the dose can be guided by total iron deficit (Ganzoni formula) or a total empiric dose of 1 gram, with interval reassessment 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses (e.g., three times daily), as this increases side effects without improving absorption due to hepcidin-mediated blockade 2, 4

• Do not use modified-release preparations, as they are indicated as "less suitable for prescribing" by the British National Formulary 1, 2

• Do not rely on multivitamin preparations as the sole source of iron supplementation, as they typically contain insufficient elemental iron (up to 14 mg) for treating iron deficiency anemia 1, 2

• Avoid taking iron with tea, coffee, or calcium-containing foods/medications, which significantly inhibit absorption 2

Strategies to Enhance Absorption

• Consider taking iron with vitamin C (250-500 mg), which enhances absorption by forming a chelate with iron 2

• Avoid concurrent use of H2-blockers or proton pump inhibitors, which impair iron absorption 1

Failure to Respond: Investigate Further

If hemoglobin fails to rise by ≥10 g/L after 2 weeks, investigate for:

• Non-compliance with therapy 1, 2
• Malabsorption (celiac disease, atrophic gastritis, inflammatory bowel disease) 1
• Continued bleeding 1, 2
• Concurrent vitamin B12 or folate deficiency 1, 2
• Bone marrow pathology or hemolysis 1