What are the adverse effects of intravenous immunoglobulin (IVIg)?

Adverse Effects of Intravenous Immunoglobulin (IVIg)

Immediate and Infusion-Related Reactions

IVIg causes mild to moderate adverse effects in 10-36% of infusions, with headaches being the most common complaint, occurring in up to 70% of patients, though serious life-threatening complications remain rare at less than 1%. 1, 2

Common Mild Reactions (occur during or within hours of infusion):

• Headaches occur in 8.9% of infusions and affect 70.6% of patients at some point during treatment 2
• Fever and chills develop in 10-35% of children under 2 years, less frequently in older patients 1
• Gastrointestinal symptoms including nausea, vomiting, and diarrhea occur frequently 1, 3
• Back and abdominal pain may begin within the first 10 minutes of injection 4, 1
• Constitutional symptoms including malaise, fatigue, myalgia, flushing, and perspiration 3, 5
• Cardiovascular changes such as blood pressure fluctuations and tachycardia 3, 6
• Other reactions include joint pain, dizziness, drowsiness, pruritus, rash, and vasodilation 4

These mild reactions typically resolve within hours to 1-2 days and may require pretreatment with corticosteroids or acetaminophen if repeated doses are needed 4

Serious Life-Threatening Complications

Anaphylaxis and Anaphylactoid Reactions

Anaphylaxis presents with flushing, facial swelling, dyspnea, cyanosis, anxiety, hypotension, and loss of consciousness, appearing within seconds to hours after infusion, and requires immediate discontinuation of IVIg plus administration of epinephrine, oxygen, antihistamines, IV steroids, and cardiorespiratory support. 4, 1

• IgA-deficient patients with anti-IgA antibodies face particular risk, though this is extremely rare 1, 3
• Critical point: IgA deficiency is NOT an absolute contraindication to IVIg therapy despite theoretical anaphylaxis risk 1
• Some patients who react to IVIg may tolerate subcutaneous immunoglobulin as an alternative 1

Acute Renal Failure (FDA Black Box Warning)

Acute renal failure carries a black box FDA warning and typically occurs 1-10 days after IVIg administration, usually presenting as oliguric and transient renal dysfunction, particularly with sucrose-containing products due to osmotic injury. 1, 3, 7

High-risk patients requiring special precautions:

• Age >65 years 1
• Pre-existing renal insufficiency 1, 3
• Diabetes mellitus 1, 3
• Dehydration 1, 3
• Hypertension 1, 3
• Concurrent nephrotoxic medications 1, 3

Prevention strategy: Use non-sucrose-containing products, ensure adequate hydration before infusion, administer at slow infusion rates in low concentration, and monitor serum creatinine and BUN closely during and after treatment 1, 3

Thromboembolic Events (FDA Black Box Warning)

Thromboembolism including stroke and myocardial infarction occurs due to hyperviscosity, particularly in patients with advanced age, prior thromboembolism, immobilization, diabetes, hypertension, dyslipidemia, cardiovascular disease, or those receiving high-dose IVIg at rapid infusion rates. 1, 3, 6

• Volume overload can occur, particularly in cardiac transplant or heart failure patients 1

Aseptic Meningitis Syndrome

Aseptic meningitis begins within hours to 2 days after treatment, presenting with severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting, occurring more frequently with high-dose therapy (2 g/kg body weight). 4, 1

• Discontinuation of IVIg results in remission within days without sequelae 4

Other Serious but Rare Complications

• Neutropenia 3
• Autoimmune hemolytic anemia 3
• Skin reactions 3
• Arthritis (rare) 3
• Pseudohyponatremia (important to recognize) 3

Infectious Disease Transmission Risk

IVIg is derived from human plasma, carrying a possible risk of virus transmission and theoretical risk of Creutzfeldt-Jakob disease transmission, though stringent donor screening, plasma testing, and viral inactivation processes have substantially reduced these risks. 4

Critical Management Principles

To minimize adverse effects, administer IVIg at slow infusion rates using low concentration products in well-hydrated patients, particularly avoiding rapid infusion in those with known risk factors for renal or thromboembolic complications. 3, 6

Treatment of Immediate Reactions:

• Slow or temporarily discontinue the infusion 3
• Administer symptomatic therapy with analgesics, NSAIDs, antihistamines 3, 7
• Use glucocorticoids for more severe reactions 3

Monitoring Requirements:

• Regular monitoring of IgG trough levels, blood cell counts, and serum chemistry every 6-12 months minimum 1
• Close monitoring of serum creatinine and BUN during and after infusion in high-risk patients 1
• Monitor vital signs including oxygen saturation during infusion 8

Common Pitfalls to Avoid

• Do not withhold IVIg solely based on IgA deficiency without documented anti-IgA antibodies and prior severe reactions 1
• Do not use sucrose-containing products in patients with renal risk factors 1, 3
• Do not administer rapid infusions in elderly patients or those with cardiovascular risk factors 3, 6
• Do not forget to ensure adequate hydration before and during infusion 3, 6