Oral Iron Replacement Regimen
Start with ferrous sulfate 65 mg elemental iron (one 200 mg ferrous sulfate tablet) once daily, taken in the morning on an empty stomach with vitamin C, and consider switching to alternate-day dosing if gastrointestinal side effects occur. 1, 2
Formulation Selection
Ferrous sulfate is the preferred formulation because it is the least expensive option with no therapeutic advantage of other formulations 1. Alternative ferrous salts (fumarate, gluconate) are acceptable but offer no clinical benefit over ferrous sulfate 2.
Key equivalents for elemental iron content:
- Ferrous sulfate 200 mg = 65 mg elemental iron
- Ferrous fumarate 200 mg = 65 mg elemental iron
- Ferrous gluconate 300 mg = 37 mg elemental iron
Dosing Frequency: Daily vs. Alternate-Day
Initial approach: Once daily dosing with 50-100 mg elemental iron 2. The evidence strongly supports that:
- Oral iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours, reducing absorption of subsequent doses 3, 4
- Alternate-day dosing (every other day) achieves similar or superior total iron absorption compared to daily dosing 1, 4
- Fractional iron absorption is significantly higher with alternate-day administration (21.8% vs 16.3% with daily dosing) 4
- Gastrointestinal side effects are substantially lower with alternate-day dosing (9% vs 45% with daily dosing) 5
If gastrointestinal intolerance occurs with daily dosing, switch to alternate-day dosing with the same or double dose (e.g., 120 mg elemental iron every other day) 1, 2.
Timing and Administration
Morning dosing on an empty stomach is critical 6, 3:
- Take iron at 0800h (±1 hour) before breakfast
- Avoid afternoon or evening doses, as circadian hepcidin elevation reduces absorption 3
- Patient should remain upright for 30-60 minutes after dosing to prevent pill esophagitis 6
Avoid divided doses (e.g., twice daily). Split dosing increases serum hepcidin and reduces overall iron absorption without benefit 4.
Enhancing Absorption
Add vitamin C (ascorbic acid) ~100 mg with each iron dose 1, 6:
- Can use vitamin C tablet or a glass of orange/citrus juice
- If unavailable, take with plain water (not milk, tea, or coffee)
Avoid these absorption inhibitors:
- Food (especially cereals, grains)
- Calcium supplements
- Antacids, H2 blockers, proton pump inhibitors
- Tea, coffee, milk 6
Monitoring and Duration
Check hemoglobin at 2-4 weeks 2:
- Expect Hb rise of at least 10 g/L after 2 weeks of daily therapy 2
- Failure to achieve this predicts treatment failure (sensitivity 90.1%, specificity 79.3%) 2
Continue treatment for 3 months after hemoglobin normalization to replenish iron stores 2.
After iron repletion, monitor CBC every 6 months to detect recurrent iron deficiency 2.
When to Switch to Intravenous Iron
- Oral iron not tolerated despite alternate-day dosing
- Ferritin levels fail to improve after adequate oral trial
- Conditions impairing absorption (inflammatory bowel disease with active inflammation, post-bariatric surgery, celiac disease)
- Ongoing blood loss exceeding replacement capacity
Common Pitfalls
- Prescribing multiple daily doses: This increases hepcidin and paradoxically reduces total absorption 4
- Not adding vitamin C: Misses significant absorption enhancement 1
- Taking with food or coffee: Dramatically reduces bioavailability 6
- Switching between ferrous salts for intolerance: No evidence supports this practice; switch to alternate-day dosing or IV iron instead 2
- Stopping too early: Must continue 3 months post-normalization to replenish stores 2