What dose of Intravenous Immunoglobulin (IVIg) should be used when restarting after a 48-hour interruption?

IVIg Interruption Management

If IVIg infusion is interrupted for 48 hours, restart the full dose from the beginning rather than continuing where you left off. The evidence base does not provide specific guidance on brief interruptions, but the pharmacokinetics and clinical practice patterns support restarting the complete dose to ensure adequate therapeutic levels.

Rationale for Restarting Full Dose

The decision to restart rather than continue is based on several key considerations:

• IVIg has a defined half-life of approximately 3-4 weeks, but therapeutic effect requires achieving adequate peak serum immunoglobulin G levels 1
• Peak serum IgG levels correlate with clinical outcomes - lower peak levels are associated with treatment failure and worse outcomes in conditions like Kawasaki disease 1
• Standard dosing regimens are designed as complete infusions to achieve specific therapeutic thresholds, typically 2 g/kg given over 10-12 hours for most indications 1

Clinical Context Matters

The approach depends on the indication:

For Kawasaki Disease

• Restart the full 2 g/kg dose if interrupted, as incomplete dosing may result in subtherapeutic levels 1
• The standard dose is 2 g/kg as a single infusion over 10-12 hours 1
• If fever persists or recurs ≥36 hours after completing the first full infusion, a second complete 2 g/kg dose is recommended 1

For Immune Thrombocytopenic Purpura (ITP)

• Restart the intended dose (typically 1 g/kg as a one-time dose for acute management) 1
• The original dosing was 0.4 g/kg/day for 5 consecutive days, later modified to 0.4 g/kg/day for 2 consecutive days 1

For Autoimmune Conditions (Pemphigus, Bullous Pemphigoid)

• Restart the full cycle of 2 g/kg divided over 3-5 days 1
• These conditions typically use monthly cycles, and incomplete dosing may compromise efficacy 1

Practical Considerations

Avoid attempting to "make up" partial doses for these reasons:

• No evidence supports dose adjustment calculations for interrupted infusions
• Risk of under-dosing with subtherapeutic effect outweighs the cost of repeating the full dose
• Most adverse effects are related to infusion rate rather than total dose 2, 3

Safety measures when restarting:

• Ensure adequate hydration before and during infusion to prevent renal complications 2, 3
• Use slow infusion rates, especially in patients with risk factors (advanced age, diabetes, hypertension, previous thromboembolism) 2, 3
• Monitor for immediate adverse effects (headache, flushing, fever, chills) which occur in 24-36% of infusions but are typically mild 2

Common Pitfalls to Avoid

• Do not attempt to calculate remaining dose based on time elapsed - this lacks evidence and risks inadequate treatment
• Do not assume the partially administered dose provides partial benefit - therapeutic thresholds matter more than cumulative exposure
• Do not rush the restart infusion - maintain appropriate infusion rates (typically starting at 0.5 mL/kg/hr and advancing as tolerated) to minimize adverse effects 3