What are the next steps for a patient taking Feramax (iron supplement) with persistently low ferritin levels?

Management of Persistently Low Ferritin Despite Oral Iron (Feramax)

Switch to intravenous iron therapy, as oral iron supplementation is inadequate for most patients who fail to respond to initial oral therapy, and IV iron provides superior and more rapid correction of iron deficiency. 1

Immediate Assessment Steps

Before transitioning to IV iron, verify the following:

• Confirm true iron deficiency by checking both ferritin and transferrin saturation (TSAT) simultaneously 1

  • Iron deficiency is defined as ferritin <100 ng/mL OR ferritin 100-300 ng/mL with TSAT <20% 1
  • In inflammatory conditions, use ferritin <100 ng/mL as the threshold rather than <30 ng/mL 1

• Rule out ongoing blood loss as the cause of persistent deficiency 1

  • Consider GI investigation if indicated (especially in patients ≥50 years or with GI symptoms) 1
  • Screen for coeliac disease with tissue transglutaminase antibodies 1
  • Evaluate for menorrhagia in premenopausal women 1

• Assess for malabsorption or medication interference 2

  • Proton pump inhibitors significantly impair oral iron absorption and may cause suboptimal response 2
  • Consider stopping or reducing PPI if clinically appropriate 2

Why Oral Iron May Be Failing

Several factors explain inadequate response to oral iron:

• Poor absorption is common, particularly in inflammatory states where hepcidin is elevated 1
• Gastrointestinal side effects lead to poor adherence (constipation, nausea, diarrhea occur frequently) 1
• Inadequate dosing or duration may not replenish depleted stores 1
• Functional iron deficiency exists where iron stores appear adequate but iron is not bioavailable for erythropoiesis 1

Transition to Intravenous Iron Therapy

Intravenous iron is the recommended next step for patients not responding to oral supplementation. 1

Preferred IV Iron Formulations

Ferric carboxymaltose (Ferinject/Injectafer) is the most extensively studied and preferred option due to its ability to deliver large doses rapidly with favorable safety profile 1, 3, 4:

• Dosing for iron deficiency anemia 3:

  • For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course)
  • Alternative: Single dose of 15 mg/kg (maximum 1,000 mg) per course
  • For patients <50 kg: 15 mg/kg IV in two doses separated by at least 7 days

• Administration 3, 4:

  • Can be given as undiluted slow IV push over 15 minutes (for 1,000 mg dose)
  • Or diluted in up to 250 mL normal saline (concentration ≥2 mg iron/mL) infused over ≥15 minutes
  • Maximum single dose: 1,000 mg iron 1, 3

Alternative IV Iron Options

If ferric carboxymaltose is unavailable 1:

• Iron sucrose (Venofer): 200 mg over 10 minutes, requires multiple doses 1, 5
• Iron isomaltoside: Up to 1,000 mg over 15 minutes 1
• Low molecular weight iron dextran: Requires longer infusion (6 hours) and has higher anaphylaxis risk (0.6-0.7%) 1

Avoid high molecular weight iron dextran due to highest risk of serious reactions and fatalities 1

Safety Considerations for IV Iron

• Resuscitation facilities must be available during administration due to rare but potential anaphylaxis risk 1
• Monitor for hypersensitivity reactions for at least 30 minutes post-infusion 1
• Avoid extravasation as it causes prolonged brown skin discoloration 3
• Common side effects (1-10% incidence): dizziness, headache, hypertension, hypophosphataemia, injection-site reactions, nausea 1

Monitoring Serum Phosphate

Check serum phosphate levels in patients requiring repeat courses, especially if within 3 months 3:

• Hypophosphatemia can occur with IV iron and requires treatment if clinically significant 1, 3

Post-Treatment Monitoring

Reassess iron status 3 months after IV iron administration 1:

• Do NOT check iron studies within 4 weeks of IV iron administration, as ferritin levels are falsely elevated during this period and cannot accurately reflect iron status 1
• Measure hemoglobin, ferritin, and TSAT at 3 months 1
• Repeat iron studies should be done 8-10 weeks after treatment for oral iron 1

Provide additional iron repletion if needed based on 3-month results 1:

• If ferritin remains <100 ng/mL or ferritin 100-300 ng/mL with TSAT <20%, repeat IV iron 1
• If no response or hemoglobin decreases, investigate for other underlying causes including occult blood loss 1

Long-Term Management

• Monitor iron parameters 1-2 times per year after correction 1
• Re-evaluate if symptoms persist despite optimal treatment or if hemoglobin decreases 1
• Consider maintenance dosing in specific populations (e.g., heart failure patients may need 500 mg at 12,24, and 36 weeks if ferritin <100 ng/mL or ferritin 100-300 ng/mL with TSAT <20%) 3

Common Pitfalls to Avoid

• Do not continue ineffective oral iron indefinitely - this delays appropriate treatment and prolongs anemia-related morbidity 1
• Do not add ascorbic acid to oral iron as there is no evidence for effectiveness in treating iron deficiency anemia 1
• Do not check ferritin too early after IV iron (within 4 weeks) as it will be falsely elevated 1
• Do not administer IV iron if hemoglobin >15 g/dL 1, 3
• Do not exceed maximum single doses (1,000 mg for ferric carboxymaltose) 1, 3