Management of Iron Deficiency Despite Oral Ferrous Sulfate
When a patient has persistent iron deficiency (serum iron 44) despite taking ferrous sulfate, you should first assess for poor response by checking if hemoglobin has increased by at least 2 g/dL after 3-4 weeks of treatment, and if not, switch to intravenous iron after ruling out non-compliance, continued blood loss, or malabsorption. 1
Immediate Assessment Steps
Verify Treatment Failure
- Hemoglobin should rise by 2 g/dL within 3-4 weeks of oral iron therapy 1
- Ferritin should increase within one month in adherent patients 1
- If these parameters are not met, oral iron has failed and alternative management is required 1
Identify Causes of Oral Iron Failure
The most common reasons for persistent iron deficiency on oral ferrous sulfate include: 1
- Non-compliance (most common - often due to gastrointestinal side effects) 1
- Continued blood loss exceeding absorption capacity 1, 2
- Malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1
- Misdiagnosis (not true iron deficiency) 1
Treatment Algorithm
Step 1: Optimize Oral Iron Therapy First
Before abandoning oral iron entirely: 1
- Reduce dosing frequency to once daily or every other day - hepcidin remains elevated for 48 hours after iron intake, blocking further absorption with more frequent dosing 1
- Lower the dose - ferrous sulfate 200 mg twice daily (rather than three times daily) may be equally effective with better tolerance 1
- Add ascorbic acid 250-500 mg with each iron dose to enhance absorption, particularly when response is poor 1
- Take on empty stomach with vitamin C for optimal absorption 1
- Avoid tea and coffee within one hour of iron intake 1
Step 2: Switch to Intravenous Iron
Intravenous iron is indicated when: 1
- Patient cannot tolerate oral iron despite optimization attempts 1
- Blood counts or iron stores fail to improve with adherent oral therapy 1
- Conditions causing impaired absorption exist (active IBD, post-bariatric surgery) 1
- Iron loss exceeds oral absorption capacity (ongoing bleeding, angiodysplasia) 1, 2
Preferred IV formulations allow complete iron repletion in 1-2 infusions: 1
- Ferric carboxymaltose (1000 mg single dose, 15 minutes) 1
- Iron sucrose (200 mg bolus, 10 minutes) 1
- Iron dextran (20 mg/kg, 6 hours) - higher anaphylaxis risk (0.6-0.7%) 1
Step 3: Rule Out Underlying Pathology
If iron deficiency cannot be corrected or maintained, further investigation is mandatory: 1
- Upper GI endoscopy with duodenal biopsies to exclude celiac disease, H. pylori gastritis, or autoimmune gastritis 1
- Colonoscopy or barium enema to identify colonic sources of blood loss 1
- Consider capsule endoscopy or enteroscopy only if transfusion-dependent or visible blood loss despite negative upper and lower endoscopy 1
Special Considerations
Monitoring After Treatment
- Recheck hemoglobin and ferritin 8-10 weeks after initiating therapy 3
- Continue oral iron for 3 months after correction to replenish stores 1
- Monitor every 3 months for one year, then at 6-12 month intervals 1
Avoid Common Pitfalls
- Do not exceed ferritin >500 μg/L during IV iron treatment to avoid iron overload risk, especially in children 1
- Parenteral iron should only be used after failure of at least two oral preparations or documented intolerance 1
- Resuscitation facilities must be available when administering IV iron due to anaphylaxis risk 1
- Ferritin <100 μg/L warrants re-treatment with IV iron after successful initial correction 1
Context-Specific Guidance
For inflammatory bowel disease patients: 1
- Oral iron may exacerbate disease activity and alter microbiota 1
- IV iron is preferred in active disease 1
- Limit oral iron to ≤100 mg elemental iron daily if used 1
For rare genetic causes (IRIDA): 1