What is the next step for a patient with iron deficiency whose iron levels are not improving with oral iron supplements?

Management of Iron Deficiency Not Responding to Oral Iron Supplements

Switch to intravenous iron therapy when oral iron supplementation fails to improve ferritin levels, as this represents either intolerance, malabsorption, or a condition where oral iron cannot be adequately absorbed. 1

Initial Assessment and Optimization

Before abandoning oral iron, ensure the current regimen is optimized:

• Verify dosing frequency: Reduce to once daily dosing at most, as more frequent dosing increases hepcidin levels and actually decreases absorption while worsening side effects 1
• Add vitamin C supplementation: Co-administer at least 80 mg of vitamin C with oral iron to enhance absorption, as vitamin C is the most potent enhancer of non-heme iron absorption 1, 2
• Consider every-other-day dosing: This alternative schedule may achieve similar iron absorption with better tolerability for some patients 1
• Optimize timing: Take iron on an empty stomach in the morning when hepcidin levels are lowest, though if intolerable, taking with food is acceptable despite reduced absorption 2

Indications for Switching to Intravenous Iron

Proceed directly to IV iron if any of the following apply:

• Ferritin levels fail to improve after an adequate trial (typically 4 weeks) of optimized oral iron therapy 1
• Patient cannot tolerate oral iron despite dosing adjustments 1
• Conditions causing malabsorption are present, including:
  • Active inflammatory bowel disease with compromised absorption 1
  • Post-bariatric surgery, particularly procedures disrupting duodenal iron absorption 1
  • Celiac disease or other malabsorptive conditions 1
• Ongoing blood loss that exceeds oral iron replacement capacity 1

Intravenous Iron Administration

Select high-dose IV iron formulations that can replace iron deficits with 1-2 infusions rather than multiple infusions (such as ferric carboxymaltose or ferric derisomaltose at 500-1000 mg per infusion) 1, 3

Safety Considerations:

• All IV iron formulations have similar safety profiles, with true anaphylaxis being very rare 1
• Most reactions are complement activation-related pseudo-allergy (infusion reactions), not true allergic reactions, and should be managed accordingly 1
• Monitor phosphate levels during IV iron therapy, particularly with ferric carboxymaltose, which carries increased risk of hypophosphatemia 3
• IV iron must be administered in medical facilities by providers trained to manage potential hypersensitivity reactions 3

Ongoing Management

• Monitor hemoglobin response within the first 4 weeks of any iron therapy 1
• Continue treatment for approximately 3 months after hemoglobin normalization to adequately replenish marrow iron stores 1
• Consider long-term maintenance iron therapy if the underlying cause of iron deficiency is unknown or irreversible 1

Common Pitfalls to Avoid

• Do not continue ineffective oral iron indefinitely—reassess after 4 weeks if no improvement 1
• Do not defer iron replacement while awaiting diagnostic investigations unless colonoscopy is imminent 1
• Avoid excessive vitamin C supplementation (>500 mg daily) in patients with hemochromatosis or iron overload, as this can accelerate iron deposition and worsen cardiac function 2
• Do not assume all oral iron failures are due to non-compliance—malabsorption and inflammation are common causes 1