Parenteral Iron Therapy for Iron Deficiency Anemia
Parenteral (intravenous) iron therapy should be reserved for patients who are intolerant to oral iron, fail to respond to oral iron therapy, or have conditions where oral iron absorption is impaired. 1
Primary Indications for Parenteral Iron
The most recent American Gastroenterological Association (AGA) guidelines from 2024 provide the clearest framework for when to use intravenous iron 1:
- Oral iron intolerance: When patients cannot tolerate oral iron preparations despite trying different formulations 1
- Failure to improve ferritin levels: After an adequate trial of oral iron therapy 1
- Malabsorption conditions: When the patient has a condition where oral iron is unlikely to be absorbed 1
The older British Society of Gastroenterology guidelines (2011) were more restrictive, recommending parenteral iron only after intolerance to at least two oral preparations or documented non-compliance 1. However, the 2024 AGA guidance reflects modern practice by being more pragmatic about when to transition to IV therapy 1.
Specific Clinical Scenarios Requiring Parenteral Iron
Inflammatory Bowel Disease (IBD)
Intravenous iron should be given to IBD patients with iron deficiency anemia and active inflammation that compromises absorption. 1 Active inflammation impairs iron absorption and increases iron depletion, making oral therapy ineffective 1.
Post-Bariatric Surgery
IV iron therapy should be used in patients who have undergone bariatric procedures that disrupt normal duodenal iron absorption. 1 This is particularly important for procedures like Roux-en-Y gastric bypass 1.
Celiac Disease
For celiac disease patients, ensure adherence to a gluten-free diet first to improve iron absorption 1. Consider oral iron supplementation initially, but transition to intravenous iron if iron stores do not improve 1.
Portal Hypertensive Gastropathy
Start with oral iron supplements initially 1. Intravenous iron should be used in patients with ongoing bleeding who do not respond to oral iron therapy 1.
Choice of Parenteral Iron Formulation
Intravenous iron formulations that can replace iron deficits with 1 or 2 infusions are preferred over those requiring more than 2 infusions. 1
The 2011 British guidelines provide specific formulation details 1:
- Ferric carboxymaltose (Ferinject): 1000 mg maximum single dose over 15 minutes 1
- Iron sucrose (Venofer): 200 mg over 10 minutes 1
- Iron dextran (Cosmofer): 20 mg/kg over 6 hours, can replenish iron in a single infusion 1
FDA labeling confirms ferric carboxymaltose can be given as 750 mg twice (separated by 7 days) or up to 1000 mg as a single dose in patients ≥50 kg 2. Iron sucrose requires multiple smaller doses of 100-200 mg 3.
Safety Considerations
Anaphylaxis Risk
All intravenous iron formulations have similar risks; true anaphylaxis is very rare. 1 The vast majority of reactions are complement activation-related pseudo-allergy (infusion reactions) rather than true anaphylaxis 1.
However, the 2011 guidelines note that iron dextran has a higher risk profile, with serious reactions occurring in 0.6-0.7% of patients and 31 reported fatalities between 1976 and 1996 1. Ferric carboxymaltose had no reported anaphylaxis at the time of those guidelines 1.
Resuscitation facilities must be available when administering any intravenous iron preparation. 1
Hypophosphatemia
A critical emerging concern is that ferric carboxymaltose causes hypophosphatemia in 50-74% of patients in prospective trials 4. This can lead to severe complications including bone pain, osteomalacia, and fractures 4. Check serum phosphate levels in patients requiring repeat courses of treatment or any repeat course within three months. 2
Important Clinical Caveats
Hemoglobin Response
Although the initial rise in hemoglobin is more rapid with parenteral iron, the rise in hemoglobin at 12 weeks is similar to oral iron therapy. 1 This means the long-term efficacy is equivalent, making the decision to use IV iron based primarily on tolerance and absorption issues rather than speed of response 1.
Avoid Extravasation
When administering IV iron, avoid extravasation as brown discoloration of the site may be long-lasting 2. Monitor carefully and discontinue at that site if extravasation occurs 2.
Older Guidelines Were More Conservative
The 2000 British guidelines stated that parenteral iron is "painful (when given intramuscularly), expensive, and may cause anaphylactic reactions" with "no quicker" hemoglobin rise than oral preparations 1. Modern formulations and administration techniques have improved safety profiles, and the 2024 AGA guidelines reflect a more liberal approach to IV iron use 1.