Can patients with iron deficiency anemia take ferrous sulfate (iron supplement) 325 mg once daily as an alternative dosing regimen?

Ferrous Sulfate 325 mg Once Daily for Iron Deficiency Anemia

Yes, ferrous sulfate 325 mg once daily (providing 65 mg elemental iron) is an acceptable and evidence-based alternative dosing regimen for iron deficiency anemia, and may actually optimize absorption compared to multiple daily doses. 1, 2

Rationale for Once-Daily Dosing

Alternate-day or once-daily dosing may be superior to traditional multiple daily dosing because:

• Daily divided doses increase serum hepcidin levels, which paradoxically reduces iron absorption from subsequent doses taken the same day 3
• In iron-depleted women, alternate-day dosing resulted in 21.8% fractional iron absorption versus 16.3% with consecutive daily dosing (p=0.0013), with significantly higher total iron absorption (175.3 mg vs 131.0 mg over equivalent treatment periods) 3
• Once-daily dosing produced similar absorption to twice-daily divided dosing (11.8% vs 13.1%, p=0.33), but twice-daily dosing elevated hepcidin more (p=0.013) 3

Standard Dosing Recommendations

The British Society of Gastroenterology guidelines indicate that ferrous sulfate 200 mg tablets (65 mg elemental iron) taken once daily is a standard preparation listed in their treatment table 1

• The optimal dosage is 50-100 mg elemental iron daily, which 325 mg ferrous sulfate (65 mg elemental iron) satisfies 1
• Traditional recommendations of 200 mg elemental iron daily in divided doses may not be necessary and can worsen tolerability 1

Efficacy Evidence

Once-daily dosing demonstrates equivalent clinical efficacy:

• A randomized trial in 557 anemic children showed 61% successful treatment with single daily dosing versus 56% with three-times-daily dosing at the same total iron dose (40 mg elemental iron), with similar side effect profiles 4
• The recent JAMA review supports ferrous sulfate 325 mg daily or on alternate days as first-line therapy 2

Tolerability Advantages

Once-daily dosing improves adherence and persistence:

• Gastrointestinal side effects are dose-dependent; lower single doses are better tolerated than higher divided doses 1
• Simple dosing regimens promote medication adherence, which is critical since treatment requires 2 months to normalize hemoglobin plus 2-3 months to replenish iron stores 5
• Patient education, perceived efficacy, and tolerability are key factors in persistence with iron therapy 5

Optimal Administration

To maximize absorption from once-daily dosing:

• Take on an empty stomach (without food for 2 hours before or 1 hour after) 1
• Separate from calcium supplements by 1-2 hours 1
• Avoid taking with aluminum-based phosphate binders 1
• Taking alongside citrus fruits/drinks or vitamin C may aid absorption 1

Monitoring Response

Check hemoglobin at 2 weeks to assess response:

• An adequate response is defined as hemoglobin rise of at least 10 g/L after 2 weeks of daily oral iron 1
• Absence of this response has 90.1% sensitivity and 79.3% specificity for predicting subsequent treatment failure 1
• If no response occurs, consider non-compliance, malabsorption, ongoing blood loss, or need for parenteral iron 1

When Once-Daily Oral Iron Is Insufficient

Parenteral iron is indicated when:

• Oral iron is not tolerated despite once-daily dosing 6, 2
• Malabsorption is present (celiac disease, post-bariatric surgery, inflammatory bowel disease) 6, 2
• Ongoing blood loss exceeds oral replacement capacity 6
• Chronic inflammatory conditions exist (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 2

Common Pitfalls to Avoid

• Do not assume higher doses are better: Multiple daily doses increase hepcidin and may reduce overall absorption 3
• Do not take with food: This reduces absorption by up to 50% 1
• Do not stop treatment prematurely: Continue for 2-3 months after hemoglobin normalizes to replenish iron stores 5
• Do not use modified-release preparations: These are less suitable for prescribing per British guidelines 1