What are the recommended pre‑medications, doses, and timing for an adult receiving intravenous immunoglobulin (IVIG), and when should a short‑acting corticosteroid be added?

Premedications for IVIG in Adults

Standard premedication for IVIG consists of diphenhydramine 25-50 mg (oral or IV) and acetaminophen 650-1000 mg orally, administered 30 minutes before infusion, with corticosteroids (prednisone 20 mg or hydrocortisone 100 mg IV) reserved for patients with a documented history of prior infusion reactions. 1

Standard Premedication Protocol

Routine premedication for all patients:

• Diphenhydramine 25-50 mg (oral or IV) given 30 minutes before infusion 1
• Acetaminophen 650-1000 mg orally given 30 minutes before infusion 1

These medications significantly reduce the risk of common infusion reactions including headaches, fever, chills, flushing, and nausea, which occur in 24-36% of patients receiving high-dose IVIG 2, 3.

When to Add Corticosteroids

Add a short-acting corticosteroid in the following scenario:

• Patients with documented history of previous infusion reactions to IVIG 1

Corticosteroid options:

• Prednisone 20 mg orally before infusion 1
• Hydrocortisone 100 mg IV administered 20 minutes before infusion (alternative) 1

The evidence does not support routine corticosteroid premedication for all patients, as most adverse effects are mild and manageable with antihistamines and acetaminophen alone 2, 3. Corticosteroids should be reserved for higher-risk patients rather than used universally.

Critical Pre-Administration Screening

Before first IVIG administration, check:

• Serum IgA level to identify patients at risk for severe anaphylaxis; use IgA-depleted preparations if deficiency is detected 1
• Renal function (serum creatinine, urine output) 1
• Thrombotic risk factors (advanced age, previous thromboembolism, immobilization, diabetes, hypertension, dyslipidemia) 1, 3
• Cardiac function, especially in patients with cardiac dysfunction or fluid overload risk 1

Administration Strategy to Minimize Reactions

Key safety measures:

• Slow infusion rate over several hours reduces toxicity and cytokine-related reactions 1, 3
• Adequate hydration before and during infusion prevents renal failure, thromboembolic events, and aseptic meningitis 3
• Use ideal or adjusted body weight for dosing in obese patients to prevent excessive dosing 1
• Divide total dose over 2 days in patients with cardiac dysfunction to minimize fluid overload 1

Common Pitfalls to Avoid

Do not routinely premedicate with corticosteroids unless there is a documented history of infusion reactions, as this adds unnecessary medication exposure without proven benefit for most patients 1, 2.

Avoid rapid infusion rates in high-risk patients (elderly, dehydrated, renal impairment, thrombotic risk factors), as this increases the risk of serious adverse events including renal failure and thromboembolism 3.

Do not perform plasmapheresis immediately after IVIG as it will remove the administered immunoglobulin 1.

Recognize that switching IVIG products may trigger new adverse reactions even in patients who previously tolerated another formulation well; maintain vigilance when changing products 4.

Management of Breakthrough Reactions

If reactions occur despite premedication:

• Stop the infusion immediately and maintain IV access with normal saline 3
• Administer symptomatic treatment: analgesics, NSAIDs, additional antihistamines 3
• Consider IV corticosteroid (hydrocortisone 100-500 mg IV) for moderate reactions that do not resolve spontaneously within 15 minutes 5
• Monitor for at least 15 minutes after symptom resolution before considering rechallenge 5

For subsequent infusions in patients who experienced reactions, add corticosteroid premedication as outlined above 1.