What to do in case of an allergic reaction to iron supplements?

Management of Allergic Reactions to Iron Supplements

Stop the iron supplement immediately and recognize that most reactions to intravenous iron are not true allergies but complement activation-related pseudo-allergy (CARPA), while true allergic reactions to oral iron are extremely rare. 1

Immediate Management Based on Reaction Severity

For Mild to Moderate Reactions (Flushing, Myalgias, Back Pain, Nausea)

• Stop the infusion immediately and switch IV line to normal saline to keep vein open 1
• Monitor the patient for 15 minutes—most reactions are self-limiting and resolve spontaneously 1
• Avoid diphenhydramine as it can worsen hypotension, tachycardia, and sedation, potentially converting a minor reaction into a serious adverse event 1
• If symptoms persist after 15 minutes, administer:
  • Hydrocortisone 200 mg IV (or equivalent corticosteroid) 1
  • Ondansetron 4-8 mg IV for nausea 1
  • Second-generation antihistamine (loratadine 10 mg PO or cetirizine 10 mg IV/PO) for urticaria 1
  • Normal saline IV for mild hypotension to maintain systolic BP >100 mmHg 1

For Severe Reactions (Anaphylaxis with Hypotension, Wheezing, Airway Compromise)

• Administer epinephrine 0.3-0.5 mg intramuscularly in the anterolateral thigh immediately 1
• May repeat epinephrine once if needed 1
• Consider β2 agonist nebulizer (Albuterol 0.083%) for bronchospasm 1
• Provide supportive care with IV fluids and oxygen 1
• True IgE-mediated anaphylaxis to IV iron is extremely rare, occurring in approximately 1:200,000 administrations 1, 2

Rechallenge Protocol After Resolution

If symptoms completely resolve and iron is still needed, rechallenge can be considered 1:

• Discuss with patient and provide reassurance 1
• Restart infusion approximately 15 minutes after symptom resolution 1
• Reduce infusion rate to 50% of initial rate 1
• If well tolerated after 15 minutes, slowly increase to desired rate 1
• Stop immediately if symptoms recur 1

Switching Iron Formulations

For Oral Iron Reactions

• True allergic reactions to oral iron are extraordinarily rare (major reactions occur in approximately 1:200,000) 2
• If gastrointestinal side effects are the issue rather than true allergy, consider:
  • Switching to alternate-day dosing to reduce side effects 1
  • Taking with food to improve tolerance 1
  • Trying different oral formulation (ferrous sulfate, gluconate, fumarate, or bisglycinate) 1
• Switch to IV iron if oral iron is truly not tolerated despite these adjustments 1

For IV Iron Reactions

• Iron sucrose is the safest IV formulation with the lowest risk of allergic reactions 2
• Avoid iron dextran as it has the highest risk of allergic reactions among IV preparations 2
• Low molecular weight iron dextran has fewer adverse effects than high molecular weight dextran if dextran must be used 2
• Cross-reactivity between different IV iron preparations is not universal, so switching formulations is reasonable 3

Key Clinical Distinctions

Most IV iron reactions are CARPA, not true allergy 1:

• CARPA occurs without prior sensitization and is characterized by flushing, myalgias, arthralgias, back pain, and chest pressure 1
• CARPA lacks signs of true anaphylaxis (no systemic hypotension, wheezing, periorbital edema, respiratory stridor, or GI pain) 1
• True IgE-mediated anaphylaxis involves airway compromise, mucosal swelling, circulatory collapse, and GI symptoms 1

Risk Factors Requiring Extra Caution

Patients at higher risk for reactions include those with 4, 5:

• Previous reaction to iron infusion
• Multiple drug allergies
• Severe atopy or asthma
• Systemic inflammatory diseases
• Fast infusion rates

For high-risk patients, iron sucrose should be used and iron dextran avoided 2

Prevention Strategies

• All IV iron must be administered by personnel trained in emergency treatment with immediate access to epinephrine and corticosteroids 2
• Premedication is controversial and should be limited to patients with substantial risk factors (multiple drug allergies, prior reaction, asthma) 1
• No physiological basis exists for routine 30-minute post-infusion observation as IV iron does not cause severe delayed reactions 1
• Inform patients about possible delayed flu-like symptoms (arthralgias, myalgias, fever) that may occur hours to days later and respond to NSAIDs 1

Important Pitfall to Avoid

Do not assume a rash is from iron supplementation without considering that iron deficiency itself causes pruritus in 25% of patients with systemic pruritus 3. Iron replacement often resolves this pruritus completely 3.