What is the recommended dosage and treatment duration for ferrous sulfate in patients with iron deficiency anemia?

Ferrous Sulfate Dosing and Treatment Duration for Iron Deficiency Anemia

For most patients with iron deficiency anemia, the optimal regimen is 50-100 mg elemental iron taken once daily in the morning on an empty stomach, or alternatively 100-200 mg every other day, continued for 3 months after hemoglobin normalizes. 1

Optimal Dosing Strategy

Standard Daily Dosing

• Single daily dose of 50-100 mg elemental iron taken in the fasting state represents the best compromise for initial treatment 1
• Once daily dosing achieves similar hemoglobin response as twice or three times daily dosing, with significantly better tolerability 1
• Ferrous sulfate 325 mg contains approximately 65 mg elemental iron, making it a practical choice for daily dosing 2

Alternate-Day Dosing (Preferred for Absorption)

• Alternate-day administration of 100-200 mg elemental iron significantly increases fractional iron absorption compared to daily dosing 1
• This approach reduces gastrointestinal side effects by 44% (relative risk 0.56) 1
• Oral iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours but subsides by 48 hours, making alternate-day dosing physiologically superior 3

Timing Considerations

• Iron should be taken in the morning, not afternoon or evening, as the circadian increase in hepcidin is augmented by morning doses 3
• Ascorbic acid 250-500 mg may enhance absorption, though clinical evidence is limited 1
• Taking iron with food improves tolerability but decreases absorption 4

Treatment Duration and Monitoring

Duration

• Treatment must continue for 3 months after hemoglobin normalizes to adequately replenish iron stores 1, 5
• This typically requires 3-6 months of total therapy 5

Monitoring Schedule

• Check hemoglobin at 4 weeks: failure to achieve at least 10 g/L (1 g/dL) rise after 2-4 weeks predicts treatment failure 1
• Monitor blood counts every 4 weeks until hemoglobin normalizes 1
• After treatment completion, check blood counts every 3 months for the first year, then at 1 year, and subsequently only if symptoms recur 1

When to Switch to Intravenous Iron

Parenteral iron should be considered when: 1, 2

• No hemoglobin response after 4 weeks of adequate oral therapy
• Oral iron is not tolerated (gastrointestinal side effects)
• Impaired absorption exists (celiac disease, atrophic gastritis, post-bariatric surgery, inflammatory bowel disease)
• Chronic inflammatory conditions are present (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
• Ongoing blood loss exceeds oral replacement capacity
• Patient is in second or third trimester of pregnancy

IV Iron Dosing

• Total iron deficit should be calculated based on hemoglobin and body weight: typically 1000 mg for patients with Hb 10-12 g/dL and <70 kg, or 1500 mg for ≥70 kg 6
• Ferric carboxymaltose can be given as 1000 mg over 15 minutes as a single dose 4, 7
• Iron sucrose requires 200 mg doses given weekly until total requirement is met 4, 6
• Low molecular weight iron dextran (INFed) 200-400 mg can be given over 1 hour until 1 g total is administered, but requires test dosing 4

Critical Pitfalls to Avoid

Dosing Errors

• Do not prescribe divided daily doses (e.g., three times daily): this reduces absorption due to hepcidin elevation and increases side effects 1
• Do not switch between different ferrous salts for intolerance—instead consider ferric maltol, alternate-day dosing, or parenteral iron 1

Duration Errors

• Do not stop treatment when hemoglobin normalizes—continue for 3 additional months to replenish stores 1
• Stopping too early leads to rapid recurrence 1

Special Population Considerations

• In inflammatory bowel disease with active inflammation, limit elemental iron to 100 mg per day and use only in mild anemia with clinically inactive disease 1
• For active IBD or hemoglobin <10 g/dL, intravenous iron should be first-line treatment 1
• In critically ill anemic patients with iron deficiency confirmed by low hepcidin, give 1 g IV iron as a single dose 4

Response Assessment

A hemoglobin response is typically evident within 1 month of oral iron treatment 4. If no response occurs, assess for:

• Nonadherence due to side effects 4
• Malabsorption 4
• Ongoing blood loss exceeding iron intake 4
• Incorrect diagnosis 4

Recurrent anemia after successful treatment warrants further investigation for underlying causes 1.