What iron formulation is least likely to cause an allergic reaction?

Iron Formulations with Lowest Risk of Allergic Reactions

Iron sucrose is the iron formulation least likely to cause allergic reactions, with very few serious adverse events reported even in pediatric populations. 1

Comparison of IV Iron Formulations and Allergic Reaction Risk

Iron Dextran

• Highest risk of allergic reactions among IV iron preparations 1
• Anaphylaxis-like reactions occur in fewer than 1% of administrations 1
• Fatalities have been reported, though rare 1
• History of multiple drug allergies increases risk of reactions 1
• Test dose required prior to administration 1
• Low molecular weight iron dextran has fewer adverse effects than high molecular weight dextran 1

Iron Gluconate

• Lower risk of allergic reactions than iron dextran 1
• No fatalities have been reported in association with its use 1
• Test dose recommended but reactions to test doses have limited predictive value 1
• Anaphylaxis-like reactions occur in fewer than 1% of administrations 1
• Association with multiple drug allergies has not been reported 1

Iron Sucrose

• Most studied iron preparation in children with the best safety profile 1
• Very few serious adverse reactions observed across multiple studies 1
• In 6 studies with 232 children receiving 1624 doses, very few serious adverse reactions were reported 1
• Approved in the USA for use in children from 2 years of age 1
• Recommended for intermittent infusions in pediatric patients 1

Newer Iron Formulations

• Third-generation iron preparations (ferric carboxymaltose, iron isomaltoside, ferumoxytol) have high complex stability and comparable safety profiles 2
• Allow rapid application of high doses of iron 2
• Ferric carboxymaltose has been associated with hypophosphatemia, particularly with repeated dosing 1
• Ferumoxytol is also used as an MRI contrast agent and requires radiologist notification if MRI is performed within 3 months of infusion 1

Oral Iron Formulations

• Generally have lower risk of serious allergic reactions compared to IV formulations 1
• Available options include:
  • Ferrous sulfate (65 mg elemental iron per 325 mg tablet) 1
  • Ferrous gluconate (35 mg elemental iron per 325 mg tablet) 1
  • Ferrous fumarate (108 mg elemental iron per 325 mg tablet) 1
  • Polysaccharide-iron complex (150 mg elemental iron) 1
  • Ferrous bisglycinate (25 mg elemental iron per tablet) 1
• Rates of mild reactions with oral iron are approximately 1:200 and rates of major reactions are approximately 1:200,000 1

Clinical Recommendations for Minimizing Allergic Reactions

• For patients with history of multiple drug allergies, avoid iron dextran and consider iron sucrose as the safest option 1
• All IV iron should be administered by personnel trained to provide emergency treatment with immediate access to medications needed for treating serious allergic reactions 1
• For oral iron supplementation in patients with risk of reactions, ferrous gluconate may be better tolerated than other formulations 1
• When using IV iron, monitor patients for at least 15-60 minutes after administration 1
• Have emergency medications (epinephrine, diphenhydramine, corticosteroids) readily available when administering IV iron 1
• For mild infusion reactions, stopping the infusion and restarting 15 minutes later at a slower rate may be sufficient 1
• For more severe reactions, corticosteroids may be beneficial 1
• Avoid diphenhydramine for managing reactions as its side effects can be mistaken for worsening of the reaction 1

Special Considerations

• Being truly allergic to IV iron is very rare—most reactions are complement activation-related pseudo-allergy 1
• Test doses have limited value in predicting severe reactions to subsequent doses 1
• An uneventful response to one iron preparation does not preclude an adverse reaction to another or to repeat administration of the same agent 1
• Caution is warranted with every dose of iron dextran that is administered 1