What are the recommended dosing regimens and safety considerations for intravenous immune globulin (IVIG) in different immunologic and inflammatory conditions?

IVIG Dosing and Safety Guidelines

Dosing Regimens by Indication

For most autoimmune and inflammatory conditions, administer 1-2 g/kg of ideal body weight divided over 2 consecutive days, while replacement therapy for immunodeficiency requires 300-400 mg/kg monthly. 1

Primary Immunodeficiency (Replacement Therapy)

• Start with 300-400 mg/kg IV monthly to maintain IgG trough levels above 500 mg/dL 1
• Alternative dosing: 400-800 mg/kg every 3-4 weeks depending on clinical response 2
• Adjust frequency to every 2-3 weeks if breakthrough infections occur despite adequate dosing 3

Immune Thrombocytopenic Purpura (ITP)

• Administer 1 g/kg as a single dose, which may be repeated if platelet response is insufficient 1
• Alternative FDA-approved regimen: 0.4 g/kg daily for 2-5 consecutive days 3

Kawasaki Disease

• Give 2 g/kg as a single IV infusion over 10-12 hours within the first 10 days of fever onset 1, 2
• If cardiac dysfunction is present, split the dose to 1 g/kg daily over 2 consecutive days to minimize fluid overload risk 1

Guillain-Barré Syndrome

• Standard regimen: 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) 1

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Use 1-2 g/kg of ideal body weight over 2 consecutive days for initial treatment 1
• Maintenance therapy typically requires repeated dosing every 3-4 weeks 4

Multisystem Inflammatory Syndrome in Children (MIS-C)

• Administer 2 g/kg based on ideal body weight 1
• Divide into 1 g/kg daily over 2 days if cardiac dysfunction or shock is present 1

Obese Patients (BMI ≥30 kg/m²)

• Calculate dose using ideal body weight (IBW) or adjusted body weight (ABW), never actual body weight 1

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Critical Pre-Administration Safety Assessment

IgA Deficiency Screening (Most Important Safety Step)

Check serum IgA levels before the first IVIG infusion in all patients to identify those at risk for fatal anaphylaxis 1, 2

• IgA deficiency alone is NOT an absolute contraindication—the actual risk is very small 5
• Anaphylaxis occurs only in rare IgA-deficient patients who have high levels of anti-IgA antibodies 5
• If IgA deficiency is detected, use IgA-depleted IVIG preparations 1, 2
• Some patients who react to IVIG may tolerate subcutaneous immunoglobulin (SCIg) as an alternative 5

Renal Function Assessment

• Evaluate serum creatinine and hydration status before infusion 1
• Patients with pre-existing renal dysfunction are at highest risk for acute renal failure 1, 6
• Avoid sucrose-containing IVIG products in patients with renal insufficiency due to osmotic injury risk 1

Thrombotic Risk Evaluation

Screen for risk factors including: 1, 6

• Advanced age
• Previous thromboembolic events
• Immobilization
• Diabetes mellitus
• Hypertension
• Dyslipidemia

Cardiac Function Assessment

• Evaluate cardiac function before administering high-dose IVIG, especially in patients with ejection fraction <35% 1
• Consider divided dosing and concurrent diuretics for patients with depressed cardiac function 1

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Premedication Protocol

Standard Premedication

• Administer acetaminophen (paracetamol) before starting the infusion to reduce mild infusion-related symptoms 1
• Add diphenhydramine for patients with history of mild reactions 1

High-Risk Patients

• Give corticosteroids (e.g., 20 mg prednisone) for patients with history of infusion reactions or when high-dose regimens are planned 1
• The need for premedication may diminish with repeated infusions as tolerance improves 1

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Administration Guidelines

Infusion Rate and Duration

• Ensure adequate hydration before starting the infusion 1, 6
• Begin at a slow rate and titrate upward as tolerated 1
• High-dose regimens (2 g/kg) typically require 10-12 hours 2
• Replacement therapy in ambulatory settings can be shortened to 2-3 hours 2

Monitoring During Infusion

• Continuously monitor vital signs (blood pressure, heart rate, temperature) throughout the infusion 1
• Watch for signs of anaphylaxis, especially in IgA-deficient patients 1
• Monitor renal function including urine output and serum creatinine during administration 1, 2

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Adverse Event Management

Timing of Common Reactions

• Within first 10 minutes: Back/abdominal pain, nausea, vomiting 1
• End of infusion and several hours after: Chills, fever, headache, myalgia, fatigue 1

Severe Reactions Requiring Immediate Action

Anaphylaxis (in IgA-deficient patients with anti-IgA antibodies): 1

1. Stop the infusion immediately
2. Administer epinephrine
3. Provide oxygen, antihistamines, IV steroids
4. Initiate cardiorespiratory support as needed

Aseptic Meningitis Syndrome (AMS): 1

• Develops within hours to 2 days after IVIG
• More frequent with high-dose regimens (2 g/kg)
• Presents with severe headache, nuchal rigidity, fever, photophobia, nausea, vomiting
• Discontinue IVIG—remission occurs within days without sequelae

Hemolytic Anemia: 1

• Coombs-positive hemolysis reported, particularly in AB blood type patients
• Risk increases after repeated high-dose (2 g/kg) infusions
• Monitor for signs of hemolysis after administration

Acute Renal Failure: 1, 6

• Usually oliguric and transient
• Occurs in insufficiently hydrated patients, especially with sucrose-stabilized products
• Monitor urine output and serum creatinine for 24-48 hours post-infusion

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Contraindications

Absolute Contraindications

• Prior anaphylaxis to human immunoglobulin products 5, 7
• History of severe reaction to IVIG preparations 1

Relative Contraindications (Require Risk-Benefit Assessment)

• Severe thrombocytopenia or coagulation disorders 1
• Pre-existing renal dysfunction 1
• High thrombotic risk 1

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Critical Pitfalls to Avoid

1. Do NOT use intramuscular immunoglobulin preparations for IV administration—only IV-formulated products are safe 1

2. Do NOT give IVIG before therapeutic plasma exchange—it will be removed; schedule IVIG after plasma exchange is completed 1

3. Do NOT administer a second high-dose IVIG course for refractory disease without evaluating alternatives—repeated high doses markedly increase risk of volume overload and hemolytic anemia 1

4. Avoid permanent central venous access solely for IVIG—infection risks and catheter complications outweigh benefits 2

5. Do NOT infuse rapidly in patients with cardiac dysfunction, renal impairment, or thrombotic risk factors—slow infusion rate and good hydration prevent most serious complications 6

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Vaccine Interactions

• Defer live-virus vaccines (measles, mumps, varicella) for ≥6 weeks to 3 months after IVIG 1
• High-dose IVIG (2 g/kg) requires deferring these vaccines for 11 months 1
• Administer live vaccines ≥14 days before IVIG if possible 1

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Post-Infusion Monitoring

• Continue renal function monitoring for 24-48 hours to identify delayed nephrotoxic effects 1
• Assess clinical response according to indication-specific parameters 1
• Watch for delayed complications: thromboembolism, aseptic meningitis, hemolytic anemia 1