What is the management for intravenous (IV) iron reactions?

Management of Intravenous (IV) Iron Reactions

The management of IV iron reactions should be based on reaction severity, with immediate cessation of infusion as the first step for all reactions, followed by severity-specific interventions including supportive care for mild reactions and epinephrine for severe anaphylaxis. 1, 2

Classification and Management of IV Iron Reactions

Mild Reactions

• Presentation: Flushing, myalgias, arthralgias, back pain, chest pressure
• Management:
  • Stop infusion immediately
  • Monitor for at least 15 minutes until resolution of symptoms
  • Most reactions will resolve spontaneously without treatment
  • Avoid first-generation antihistamines (diphenhydramine) and vasopressors as these can worsen reactions 1
  • For specific symptoms:
    • Nausea: Consider 5-HT3 antagonist (ondansetron 4-8 mg IV)
    • Urticaria: Consider second-generation antihistamine (loratadine 10 mg orally or cetirizine 10 mg IV/oral)
    • Mild hypotension: IV hydration
  • Consider rechallenge after symptom resolution at 50% of initial infusion rate 1

Moderate Reactions

• Presentation: More pronounced symptoms, hypoxemia
• Management:
  • Stop infusion immediately
  • Consider IV corticosteroids (hydrocortisone 200 mg or equivalent)
  • Provide oxygen by mask or nasal cannula for hypoxemia
  • Monitor until resolution of symptoms
  • Rechallenge may be considered after complete symptom resolution 1, 2

Severe/Anaphylactic Reactions (extremely rare)

• Presentation: Systemic hypotension, wheezing, peri-orbital edema, respiratory stridor, gastrointestinal pain
• Management:
  • Immediately stop infusion
  • Call emergency services
  • Administer epinephrine 0.3-0.5 mg IM in anterolateral thigh (first-line treatment)
  • Aggressive fluid resuscitation (1-2 L normal saline at 5-10 mL/kg in first 5 minutes)
  • Consider albuterol nebulizer for bronchospasm
  • IV corticosteroids (methylprednisolone 1-2 mg/kg IV)
  • For persistent hypotension: Consider vasopressors (dopamine 400 mg in 500 mL at 2-20 μg/kg/min)
  • For patients on beta-blockers: Consider glucagon 1-5 mg IV over 5 minutes
  • Monitor vital signs every 15 minutes until resolution 2

Post-Reaction Monitoring and Follow-up

• Mild-moderate reactions: Observe for 1-2 hours after symptom resolution
• Severe reactions: Observe for 24 hours with continued monitoring of vital signs
• Consider tryptase level measurement (optimal timing: 15 minutes to 3 hours after symptom onset) 2
• Inform patients about possible delayed reactions (flu-like symptoms, arthralgias, myalgias, fever) which typically last up to 24 hours and can be managed with NSAIDs 1
• Symptoms lasting more than a few days require evaluation, as they may indicate other issues like hypophosphatemia 1

Prevention of Future Reactions

• Risk factors for reactions include:

  • Previous reaction to IV iron
  • Fast iron infusion rate
  • Multiple drug allergies
  • Severe atopy
  • Systemic inflammatory diseases
  • Asthma
  • Mastocytosis 2, 3

• For patients with previous reactions:

  • Consider alternative iron formulations
  • Use slower infusion rates
  • Avoid rechallenge in patients with severe reactions 2

Important Caveats

• Most reactions to modern IV iron formulations are complement activation-related pseudo-allergy (CARPA), not true IgE-mediated hypersensitivity 1, 4
• Avoid aggressive treatment of minor infusion reactions with first-generation antihistamines or vasopressors, as this can convert self-limited reactions into significant adverse events 1, 5
• Hypophosphatemia is a potential side effect of certain IV iron formulations (particularly ferric carboxymaltose) and should be monitored, especially with symptoms like fatigue, muscle weakness, and bone pain persisting beyond a few days 1
• Ensure resuscitation equipment and medications are readily available, and staff is trained in recognition and management of infusion reactions 2