Treatment of Low Ferritin (Iron Deficiency)
Oral iron supplementation with ferrous sulfate 100-200 mg elemental iron daily is the first-line treatment for most patients with low ferritin, but intravenous ferric carboxymaltose (1000 mg over 15 minutes) should be used when oral iron fails, in malabsorption conditions, or when rapid repletion is needed. 1, 2
Initial Oral Iron Therapy
Ferrous sulfate remains the standard first-line treatment for uncomplicated iron deficiency, administered at 100-200 mg elemental iron daily. 1 However, recent evidence demonstrates that alternate-day dosing (every other day) achieves superior iron absorption and causes fewer gastrointestinal side effects compared to daily dosing, as daily administration increases hepcidin levels which blocks subsequent iron absorption. 1, 3
Optimal Oral Iron Regimen:
- Ferrous sulfate 100-200 mg elemental iron on alternate days (not daily) 1, 2, 3
- Single morning dose is preferable to divided doses, as split dosing throughout the day elevates hepcidin and reduces absorption from the second dose 3
- Co-administer with vitamin C (250-500 mg or ascorbic acid) to enhance absorption 1, 2
- Continue for 3 months after hemoglobin normalization to replenish iron stores 1
Common Pitfall to Avoid:
The traditional recommendation of "three times daily" dosing is now outdated—this approach paradoxically reduces total iron absorption by triggering hepcidin elevation. 3
When to Use Intravenous Iron Instead
IV iron should be considered first-line (not just for oral iron failure) in specific clinical scenarios: 1, 2
- Active inflammatory bowel disease 2
- Hemoglobin <100 g/L 2
- Previous intolerance to oral iron 1, 2
- Malabsorption conditions (celiac disease, gastric bypass) 2
- Ongoing blood loss 2
- Need for rapid iron repletion (preoperative optimization) 1
- Chronic kidney disease 1
IV Iron Dosing Protocol:
Ferric carboxymaltose is the preferred IV formulation, administered as a single dose of 1000 mg over 15 minutes. 1, 2 This slow-release, high-dose formulation enables iron penetration into the central nervous system through H-ferritin binding and macrophage uptake, unlike fast-release formulations (iron sucrose) which lack this property. 1
Total dose calculation based on body weight and hemoglobin: 2
| Hemoglobin Level | Body Weight <70 kg | Body Weight ≥70 kg |
|---|---|---|
| 100-120 g/L (women) or 100-130 g/L (men) | 1000 mg | 1500 mg |
| 70-100 g/L | 1500 mg | 2000 mg |
Alternative IV formulations include low molecular weight iron dextran and ferumoxytol (similar pharmacology to ferric carboxymaltose), though these have less robust evidence. 1 Iron sucrose is conditionally recommended only in specific populations like end-stage renal disease with transferrin saturation <20%. 1
Critical Safety Warning:
Reactions during IV iron infusions are rare (<1:250,000) but potentially life-threatening—risk is highest with high molecular weight iron dextran, which should be avoided. 1 Ferric carboxymaltose and other modern carbohydrate-bound formulations have substantially lower risk. 1
Monitoring Treatment Response
Recheck hemoglobin, ferritin, and transferrin saturation at 8-10 weeks after starting treatment (not earlier). 1, 2, 4
Do not measure ferritin immediately after IV iron administration—levels will be falsely elevated for several weeks. 1, 2
Long-Term Monitoring Schedule:
- Every 3 months for the first year after correction 1, 2
- Then every 6-12 months thereafter 2, 4
- Re-treat when ferritin drops <100 ng/mL or hemoglobin falls below 12 g/dL (women) or 13 g/dL (men) 2
Critical Safety Limits
Never supplement iron when ferritin is normal or elevated—this is potentially harmful. 1, 2 Iron overload can cause end-organ damage affecting the pancreas, liver, and heart. 1
Upper safety thresholds to avoid toxicity: 1, 2
- Ferritin should not exceed 500-800 ng/mL during treatment 1, 2
- Transferrin saturation should remain <50% 2
- In patients receiving repeated prophylactic hemin (for porphyria), begin therapeutic phlebotomy when ferritin exceeds 1000 ng/mL 1
Special Considerations
Inflammatory Conditions:
In patients with inflammatory bowel disease, chronic kidney disease, or heart failure, iron deficiency may exist even with ferritin 30-100 ng/mL—use transferrin saturation or hepcidin for confirmation, and always check C-reactive protein to exclude acute inflammation causing falsely elevated ferritin. 2
Genetic Iron Disorders:
Patients with TMPRSS6 mutations (iron-refractory iron deficiency anemia) typically do not respond to oral iron and require IV iron, though complete hemoglobin normalization is rarely achieved. Monitor ferritin and avoid exceeding 500 mg/L to prevent iron overload, especially in children. 1