What is the treatment for an allergic reaction to intravenous (IV) iron in a patient with a history of previous allergic reactions or sensitivities?

Treatment of Allergic Reactions to IV Iron

Stop the infusion immediately, switch the IV line to normal saline at keep-vein-open (KVO) rate, and manage based on reaction severity—most reactions are complement activation-related pseudo-allergy (CARPA) rather than true IgE-mediated allergies and resolve spontaneously within 15 minutes. 1

Immediate Management Algorithm

Step 1: Stop Infusion and Assess Severity

Upon any signs or symptoms during infusion, immediately stop the iron infusion, notify the physician, switch IV line to normal saline at KVO, and perform a rapid physical assessment. 1

Monitor vital signs continuously (blood pressure, pulse, respiratory rate, oxygen saturation, temperature) until stable. 1

Step 2: Classify Reaction Severity

Mild Hypersensitivity Reaction

Symptoms include: 1

• Pruritus
• Flushing
• Urticaria
• Chest tightness
• Back pain
• Joint pain

Management: 1

• Monitor for ≥15 minutes
• Maintain IV normal saline at KVO
• Consider IV hydrocortisone 100-500 mg 1
• Consider IV famotidine 20 mg (H2 antagonist) 1
• Avoid diphenhydramine and first-generation antihistamines—these can worsen hypotension, tachycardia, diaphoresis, sedation, and potentially convert minor reactions into hemodynamically significant serious adverse events 1, 2

Moderate Hypersensitivity Reaction

Mild symptoms PLUS: 1

• Transient cough
• Shortness of breath
• Tachycardia
• Hypotension (drop in systolic BP ≥30 mmHg from baseline or SBP ≤90 mmHg)

Management: 1

• All interventions for mild reactions
• If hypotensive: recline patient onto back and administer normal saline bolus 1000-2000 mL 1
• If hypoxemic: give oxygen by mask or nasal cannula 1
• Monitor closely for progression to severe reaction

Severe/Life-Threatening Reaction (Anaphylaxis)

Characterized by: 1

• Sudden onset with rapid intensification
• Loss of consciousness
• Severe hypotension (SBP drop ≥30 mmHg or SBP ≤90 mmHg)
• Angioedema of tongue and/or airway
• Involvement of ≥2 organ systems (cardiovascular, skin, respiratory, gastrointestinal)
• Stridor or bronchospasm

Management: 1, 2

• Immediately call emergency services or resuscitation team
• Administer epinephrine (1 mg/mL) 0.3 mg intramuscularly into the anterolateral mid-third portion of the thigh 1, 2
• May repeat epinephrine once if needed 1
• Consider β2 agonist nebulizer (albuterol 0.083% via nebulizer) 1
• Treat as moderate HSR plus full resuscitation protocols
• Aggressive fluid resuscitation if hypotensive
• Supplemental oxygen

Understanding the Mechanism: CARPA vs True Allergy

The vast majority of IV iron reactions are complement activation-related pseudo-allergy (CARPA), not true IgE-mediated allergic reactions. 1, 2

CARPA Characteristics: 1

• Occurs without prior sensitization
• Caused by labile free iron released from iron carbohydrate nanoparticles
• Characterized by flushing, myalgias, arthralgias, back pain, chest pressure
• Usually self-limited and resolves without treatment
• Does NOT present with systemic hypotension, wheezing, peri-orbital edema, respiratory stridor, or gastrointestinal pain

True IgE-Mediated Anaphylaxis: 1

• Requires prior sensitization
• Systemic life-threatening reaction
• Characterized by airway compromise, mucosal swelling, circulatory collapse, gastrointestinal symptoms
• Extremely rare (<1:200,000 to 1:250,000 administrations) 1, 3

Rechallenge Protocol After Reaction Resolution

If symptoms completely resolve and IV iron is still clinically necessary, rechallenge can be considered for mild to moderate reactions. 1, 2

Rechallenge Steps: 1

1. Discuss with patient and provide reassurance
2. Wait approximately 15 minutes after complete symptom resolution
3. Restart infusion at 50% of the initial infusion rate
4. Monitor closely for 15 minutes
5. If well tolerated, slowly increase to desired rate
6. Stop immediately if symptoms recur and manage as previously described

Over 80% of IV iron rechallenges are tolerable, safe, and successful without major serious incidents. 4

Alternative Formulations and Future Management

If reactions occur, consider switching to a different IV iron formulation, as reactions to one formulation do not predict reactions to another. 1, 2

The American Gastroenterological Association notes that being truly allergic to IV iron is very rare—almost all reactions are CARPA, which are idiosyncratic infusion reactions. 1

Iron sucrose and low-molecular-weight iron dextran have lower rates of hypersensitivity reactions compared to other formulations. 1

Critical Prevention Strategies

Pre-Infusion Risk Assessment: 1

Identify high-risk patients:

• History of severe asthma or eczema
• Mastocytosis
• Multiple drug allergies
• Prior reaction to IV iron
• Severe atopy

Infusion Protocol: 1

• Initiate iron infusion at slow rate—slower infusion rates are associated with lower reaction rates 1
• Observe closely during first 10 minutes (immediate reactions occur during first minute) 1
• All IV iron must be administered by personnel trained in emergency treatment with immediate access to epinephrine, corticosteroids, and resuscitation equipment 1, 2

Post-Infusion Education: 1

Educate patients on delayed reactions (flu-like symptoms, arthralgias, myalgias, fevers) that can occur hours to days after infusion and are managed with NSAIDs. 1

Common Pitfalls to Avoid

Never use diphenhydramine or first-generation antihistamines for IV iron reactions—their side effects (hypotension, tachycardia, sedation) can be mistaken for worsening of the reaction and can convert minor reactions into serious adverse events. 1, 2

Avoid aggressive treatment of self-limited CARPA reactions with vasopressors, as these can worsen outcomes. 1, 3

Do not assume test doses prevent reactions—most patients who experience severe reactions have successfully received both test doses and multiple therapeutic doses in the past. 1

There is no physiological basis to observe patients for 30 minutes post-infusion for delayed severe reactions, though the package insert recommends this. 1 However, patients should be educated about delayed mild reactions (flu-like symptoms) that can occur.