What is the appropriate treatment and management plan for a patient with iron deficiency anemia prescribed ferrous sulfate (tid, three times a day)?

Ferrous Sulfate TID Dosing for Iron Deficiency Anemia

Once-daily dosing of ferrous sulfate (50-100 mg elemental iron, equivalent to one 200 mg tablet) taken in the fasting state is superior to three-times-daily dosing and should be the preferred initial treatment regimen for iron deficiency anemia. 1

Why Once-Daily Dosing is Preferred Over TID

The 2021 British Society of Gastroenterology guidelines explicitly recommend against traditional three-times-daily dosing based on emerging evidence about iron absorption physiology and gastrointestinal tolerability 1:

• Once-daily dosing (50-100 mg elemental iron) provides optimal absorption while minimizing gastrointestinal side effects that reduce compliance 1
• A randomized trial demonstrated that 60 mg elemental iron twice daily produced faster hemoglobin rise than 120 mg on alternate days, but similar ultimate outcomes were achieved with lower total doses and significantly less nausea 1
• Intermittent dosing (less than daily) is associated with 44% lower risk of GI adverse events (relative risk 0.56; 95% CI 0.37-0.84) compared to daily dosing 1

Optimal Dosing Regimen

Start with ferrous sulfate 200 mg (65 mg elemental iron) once daily on an empty stomach 1:

• This provides the best compromise between efficacy and tolerability 1
• Traditional TID dosing (600 mg daily = 195 mg elemental iron) is no longer supported by evidence 1
• If once-daily dosing is not tolerated, alternate-day dosing is a reasonable alternative that maintains efficacy while further reducing side effects 1

Treatment Duration and Monitoring

Continue iron supplementation for 3 months after hemoglobin normalization to replenish iron stores 1, 2:

• Monitor hemoglobin and mean corpuscular volume (MCV) at 2 weeks to assess initial response 1
• Absence of ≥10 g/L hemoglobin rise after 2 weeks predicts treatment failure (sensitivity 90.1%, specificity 79.3%) 1
• After normalization, monitor every 4 weeks until hemoglobin is normal, then at 3-month intervals for one year, then annually 1, 2
• Check complete blood count and iron parameters (ferritin, transferrin saturation) at 4-8 weeks after completing treatment 1

When to Modify the Regimen

Switch from oral iron if:

• No hemoglobin response after 2 weeks of appropriate dosing 1
• Intolerance to at least two different oral iron preparations 2
• Ongoing blood loss, malabsorption, or inflammatory bowel disease where parenteral iron is more effective 1

Alternative oral options for intolerance include:

• Ferric maltol 30 mg twice daily (better tolerated but more expensive) 1
• Alternate-day ferrous sulfate dosing 1
• Different ferrous salt (though evidence for switching between salts is weak) 1

Common Pitfalls to Avoid

• Do not prescribe TID dosing - this outdated regimen increases side effects without improving outcomes 1
• Do not switch to modified-release preparations - these are considered less suitable for prescribing 1
• Do not check iron parameters within 4 weeks of starting treatment - circulating iron interferes with assays leading to spurious results 1
• Do not stop iron when hemoglobin normalizes - continue for 3 months to replenish stores 1, 2
• Do not use parenteral iron as first-line unless there is documented intolerance to oral preparations 2

Causes of Treatment Failure

If hemoglobin fails to rise appropriately, investigate 1:

• Non-compliance (most common)
• Ongoing blood loss
• Malabsorption
• Concurrent vitamin B12 or folate deficiency
• Chronic disease/inflammation
• Bone marrow pathology
• Hemolysis