What are the side effects of Intravenous Immunoglobulin (IVIG)?

Side Effects of Intravenous Immunoglobulin (IVIG)

IVIG therapy is associated with a range of adverse effects from mild to severe, including headaches, fever, renal dysfunction, thrombosis, and anaphylaxis, with most reactions being mild and transient when proper administration protocols are followed. 1, 2

Common Adverse Effects

Mild to Moderate Reactions

• Immediate reactions (during or shortly after infusion):
  • Headaches (most common)
  • Flushing
  • Fever and chills
  • Fatigue
  • Nausea and vomiting
  • Diarrhea
  • Blood pressure changes and tachycardia
  • Back and abdominal pain
  • Myalgia
  • Rash and pruritus
  • Perspiration and vasodilation 1

Severe Adverse Effects

• Serious reactions (may be immediate or delayed):
  • Hypotension
  • Anaphylaxis and anaphylactoid reactions (particularly in IgA-deficient patients)
  • Renal dysfunction/acute renal failure (especially with sucrose-containing products)
  • Aseptic meningitis syndrome (AMS) - characterized by severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting
  • Thrombotic events - including stroke and myocardial infarction
  • Transient neutropenia
  • Hemolytic anemia 1, 2

Risk Factors for Serious Complications

Renal Dysfunction

• Dehydration
• Pre-existing renal disease
• Diabetes mellitus
• Advanced age
• Hypertension
• Use of nephrotoxic medications
• Sucrose-containing IVIG products 2, 3

Thrombotic Events

• Advanced age
• Previous thromboembolic events
• Immobilization
• Diabetes mellitus
• Hypertension
• Dyslipidemia
• High-dose IVIG
• Rapid infusion rate 2, 4, 3

Anaphylactic Reactions

• IgA deficiency with anti-IgA antibodies
• History of severe reaction to human immunoglobulin preparations 1, 2

Timing of Adverse Effects

• Immediate reactions: Occur during infusion or within minutes to hours

  • Anaphylactic symptoms can appear within seconds to hours after infusion 1
  • Back and abdominal pain, nausea, and vomiting can occur within the first 10 minutes of injection 1

• Delayed reactions: Occur hours to days after infusion

  • Aseptic meningitis typically begins within hours to 2 days after treatment 1
  • Thrombotic events and renal dysfunction may occur days after infusion 3
  • Chills, fever, headache, myalgia, and fatigue can begin at the end of infusion and continue for hours 1

Prevention of Adverse Effects

1. Pre-administration assessment:

   • Check serum IgA levels before administration (to identify IgA-deficient patients) 2
   • Assess cardiac function and fluid status before administration 2
   • Identify patients with risk factors for complications

2. Administration protocols:

   • Ensure proper hydration before and during infusion 4, 3
   • Use slow infusion rates, especially for initial doses and high-risk patients 2, 4
   • Consider pretreatment with corticosteroids or acetaminophen for patients with history of reactions 1
   • Use IgA-depleted IVIG for IgA-deficient patients 1, 2
   • Monitor vital signs during infusion 2

3. Product selection:

   • Consider non-sucrose-containing products for patients with renal risk factors 3
   • Use lower concentration products for high-risk patients 3

Management of Adverse Reactions

• For mild reactions: Slow or temporarily discontinue the infusion and provide symptomatic therapy 3
• For moderate reactions: Consider pretreatment with corticosteroids or acetaminophen for subsequent doses 1
• For severe reactions:
  • Immediate discontinuation of immune globulin
  • Administration of epinephrine, oxygen, antihistamines, IV steroids, and cardiorespiratory support as needed 1
  • For aseptic meningitis: Discontinuation of IVIG typically results in remission within days 1

Infectious Disease Risk

Although IVIG is made from human plasma, the risk of infectious disease transmission is extremely low due to:

• Stringent donor selection
• Testing of plasma
• Viral inactivation and removal processes during manufacturing 1

There is no recent evidence for transmission of HIV, HCV, HBV, or HTLV-1 through IVIG products 1.

Special Considerations

• Cardiac dysfunction: Patients require careful monitoring to prevent fluid overload; consider prophylactic diuretics 2
• Pregnancy: IVIG is considered safe for pregnant patients requiring treatment 2
• High-dose therapy: Higher risk of adverse effects, particularly aseptic meningitis 1, 5

By following proper administration protocols and identifying high-risk patients, most adverse effects can be prevented or minimized, making IVIG a relatively safe therapy for most patients.