What are the potential complications of iron infusion?

Complications of Iron Infusion

Iron infusions can cause both immediate infusion reactions and delayed adverse effects, with hypophosphatemia being a significant concern particularly with ferric carboxymaltose formulations. 1

Immediate Infusion Reactions

Types of Reactions

1. Non-IgE-mediated hypersensitivity reactions (CARPA)

   • Most common type of reaction
   • Caused by complement activation related pseudo-allergy triggered by iron nanoparticles
   • Can occur without prior sensitization
   • Symptoms include:
     • Flushing
     • Myalgias/arthralgias
     • Back pain
     • Chest pressure

2. True IgE-mediated hypersensitivity reactions (anaphylaxis)

   • Extremely rare but life-threatening
   • Requires prior sensitization
   • Symptoms include:
     • Airway compromise
     • Mucosal swelling
     • Circulatory manifestations
     • Gastrointestinal symptoms

Severity Classification

• Mild reactions: Pruritus, flushing, urticaria, chest tightness, back/joint pain
• Moderate reactions: Above plus transient cough, shortness of breath, tachycardia, mild hypotension
• Severe/life-threatening reactions: Sudden onset with rapid progression, loss of consciousness, significant hypotension, airway angioedema, involvement of multiple organ systems 1

Risk Factors

• Previous reaction to iron infusion
• Fast iron infusion rate
• Multiple drug allergies
• Severe atopy
• Systemic inflammatory diseases
• Early pregnancy (contraindication)
• Serious comorbidities (worsen impact if reaction occurs) 1, 2

Management of Infusion Reactions

Mild Reactions

1. Stop the infusion
2. Monitor for 15 minutes
3. If symptoms resolve, restart at 50% of initial infusion rate
4. For urticaria: Consider second-generation antihistamines (loratadine 10mg or cetirizine 10mg)
5. For nausea: Consider ondansetron 4-8mg IV

Moderate Reactions

1. Stop the infusion
2. Monitor closely
3. Consider IV corticosteroid (hydrocortisone 200mg)
4. If symptoms resolve completely, consider rechallenge at slower rate

Severe Reactions

1. Stop infusion immediately
2. Call emergency services/resuscitation team
3. Administer epinephrine 0.3mg IM (1mg/mL) into anterolateral thigh
4. Manage as anaphylaxis from any cause 1

Important Cautions

• Avoid diphenhydramine (first-generation antihistamines) as they can convert minor reactions into hemodynamically significant events through hypotension, tachycardia, diaphoresis, and sedation
• Avoid vasopressors except in true anaphylaxis for the same reason 1

Delayed Complications

Hypophosphatemia

• Most common with ferric carboxymaltose (FCM)
• Occurs within first 2 weeks after administration
• Incidence: 47-75% with FCM vs <10% with other formulations
• Can be severe and prolonged (up to 6 months)
• Severity classification:
  • Mild: <LLN-2.5 mg/dL
  • Moderate: <2.5-2 mg/dL
  • Severe: <2-1.0 mg/dL
  • Life-threatening: <1.0 mg/dL
• Symptoms: fatigue, proximal muscle weakness, bone pain (mimicking iron deficiency)
• Can lead to osteomalacia with prolonged deficiency 1, 3

Other Delayed Reactions

• Flu-like symptoms
• Arthralgias/myalgias
• Fever
• Usually last up to 24 hours
• Manageable with NSAIDs
• Symptoms lasting >few days require medical evaluation 1

Formulation-Specific Considerations

1. Ferric carboxymaltose (Injectafer)

   • High risk of hypophosphatemia (47-75%)
   • Can cause severe and prolonged hypophosphatemia requiring supplementation 4, 3

2. Ferumoxytol (Feraheme)

   • Also used as MRI contrast agent
   • Radiologist should be notified if MRI planned within 3 months 1

3. Iron dextran formulations

   • Higher risk of anaphylactoid reactions than non-dextran irons 1

4. Ferric gluconate (Ferrlecit)

   • Contains benzyl alcohol as preservative (caution in pregnancy)
   • Higher labile iron release requiring lower doses 5

Rechallenge After Reactions

• Patients with mild/moderate reactions with complete resolution can be rechallenged
• Rechallenge to alternative formulation is generally well-tolerated (successful in 68 of 69 patients in one study)
• Consider slower infusion rate and premedication for rechallenge 1, 6

Prevention Strategies

1. Slow infusion rate (reduces reaction risk)
2. Careful observation during first 10 minutes (when immediate reactions most likely occur)
3. Appropriate patient selection (avoid in early pregnancy, use caution with multiple allergies)
4. Staff education on recognition and management of reactions
5. Patient education about possible delayed reactions 1

Iron infusion reactions are rare but require prompt recognition and appropriate management to prevent serious outcomes. The choice of iron formulation should consider the patient's risk factors, particularly for hypophosphatemia with ferric carboxymaltose.