What are Intravenous Immunoglobulin (IVIG) Adverse Drug Reactions (ADRs)?

IVIG Adverse Drug Reactions

IVIG carries a black box FDA warning for acute renal failure and thromboembolism, with most adverse reactions being mild and infusion-related (headache, fever, flushing), but serious complications including hemolytic anemia, aseptic meningitis, and anaphylaxis can occur, particularly in high-risk patients. 1, 2

Immediate/Infusion-Related Reactions (Most Common)

These occur during or within hours of infusion and are typically rate-dependent:

• Headache is the most frequently reported immediate adverse effect, occurring in up to 57% of patients in some series 3, 4
• Fever and chills develop in 10-35% of children under 2 years and less frequently in older patients 1, 4
• Flushing, malaise, chest tightness, myalgia, and fatigue are common mild reactions 3, 5
• Nausea, vomiting, and diarrhea occur frequently 1, 3
• Blood pressure changes and tachycardia can develop during infusion 3, 5
• Back and abdominal pain may begin within 10 minutes of injection 1

Most immediate reactions resolve with slowing or temporarily stopping the infusion, plus symptomatic treatment with analgesics, antihistamines, or corticosteroids 3, 4

Serious Delayed Adverse Reactions

Acute Renal Failure

• Occurs primarily with sucrose-containing IVIG products due to osmotic tubular injury 3, 5
• Usually presents as oliguric, transient renal dysfunction 3, 5
• High-risk patients include: age >65 years, pre-existing renal insufficiency (CrCl <60 mL/min), diabetes mellitus, dehydration, hypertension, or concurrent nephrotoxic medications 2, 3
• Prevention requires: adequate hydration, avoiding nephrotoxic agents (NSAIDs, contrast media, aminoglycosides), using non-sucrose products, slow infusion rates, and monitoring serum creatinine/BUN closely 2, 3

Thromboembolic Events

• Result from hyperviscosity, especially with high-dose or rapid infusion 3, 5
• Risk factors: advanced age, prior thromboembolism, immobilization, diabetes, hypertension, dyslipidemia, cardiovascular disease 1, 3
• Both venous and arterial thromboses can occur 6
• Prevention: slow infusion rate, adequate hydration, caution in high-risk patients 3, 5

Aseptic Meningitis Syndrome

• Begins within hours to 2 days after treatment 1
• Presents with: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, vomiting 1
• More frequent with high-dose therapy (2 g/kg) 1
• Resolves within days after discontinuation without sequelae 1

Hemolytic Anemia

• Documented but under-recognized complication, especially after high-dose IVIG 6, 7
• Can be clinically significant, occasionally requiring red blood cell transfusion 7
• More common with large individual or cumulative doses 7
• May present with decreased hemoglobin on CBC or elevated bilirubin on metabolic panel 7

Anaphylaxis and Anaphylactoid Reactions

• Classic anaphylaxis symptoms: flushing, facial swelling, dyspnea, cyanosis, anxiety, hypotension, loss of consciousness, potentially death 1
• Symptoms appear within seconds to hours after infusion 1
• Particular risk in IgA-deficient patients with anti-IgA antibodies, though this is extremely rare 1, 3
• Treatment: immediate discontinuation, epinephrine, oxygen, antihistamines, IV steroids, cardiorespiratory support 1

Other Documented Adverse Reactions

• Hematologic: leukopenia, neutropenia, monocytopenia, disseminated intravascular coagulation 6
• Skin reactions including rash and pruritus 3, 4
• Volume overload, particularly in cardiac transplant or heart failure patients 1, 2
• Rare: arthritis, autoimmune phenomena 3

Critical Management Principles

• Infusion rate matters: Most adverse reactions correlate with faster infusion rates; slower administration reduces risk 3, 5, 4
• Hydration is essential before and during infusion, especially in high-risk patients 3, 5
• Monitor for volume overload in cardiac patients 2
• Use low concentration products when possible 3
• IgA deficiency is NOT a contraindication to IVIG therapy despite theoretical anaphylaxis risk; reactions are exceedingly rare 1
• Some patients who react to IVIG may tolerate subcutaneous immunoglobulin 1

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 2
• Watch for clinical signs of hemolysis with moderate to high cumulative doses 7