Intravenous Immunoglobulin

Intravenous immunoglobulin is a pooled human IgG product given by infusion for replacement in primary and secondary antibody deficiency and as immunomodulation in immune thrombocytopenia, Kawasaki disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, myasthenia gravis, dermatomyositis and several other conditions. Products differ in stabiliser, osmolality and rate limits, and prescribing by product matters.

Class. Pooled human immunoglobulin G, immunomodulator and antibody replacement.

Mechanism. In replacement therapy it provides specific antibodies. In immunomodulation it blocks Fc receptors, neutralises autoantibodies and cytokines, inhibits complement activation, and expands regulatory T cells.

Pharmacokinetics. Immediate full IgG levels, half-life about 3 to 4 weeks (shorter with high catabolism or protein loss), volume of distribution mostly intravascular early. Dose is calculated on body weight.

Doses use ideal or adjusted body weight in obese patients. Rate limits are product specific.

Primary immunodeficiency (replacement). 0.4 to 0.8 g/kg every 3 to 4 weeks, aiming for a trough IgG over 6 g/L (higher in bronchiectasis or severe infection). Loading: first dose of 0.4 to 0.8 g/kg.

Secondary immunodeficiency with recurrent infection (specialist). 0.2 to 0.4 g/kg every 3 to 4 weeks.

Immune thrombocytopenia. 1 g/kg as a single dose, repeated on day 2 if platelets remain low, or 0.4 g/kg daily for 5 days.

Kawasaki disease. 2 g/kg as a single infusion over 10 to 12 hours, with aspirin, within 10 days of fever onset.

Guillain-Barre syndrome. 0.4 g/kg daily for 5 days (total 2 g/kg).

Chronic inflammatory demyelinating polyneuropathy. Loading 2 g/kg over 2 to 5 days; maintenance 1 g/kg every 3 weeks, adjusted by response.

Multifocal motor neuropathy. 0.5 to 2 g/kg monthly, in divided doses.

Myasthenia gravis (exacerbation or crisis). 2 g/kg over 2 to 5 days (0.4 g/kg daily for 5 days).

Dermatomyositis (active, refractory). 2 g/kg monthly in 2 to 5 divided doses for at least 3 months.

Infusion rate. Start at about 0.5 mL/kg/hour (product specific, often 0.01 to 0.02 mL/kg/minute) for 15 to 30 minutes, then double stepwise every 15 to 30 minutes as tolerated to the product maximum (about 4 to 8 mL/kg/hour). Use slower rates and higher dilution in patients at risk of renal or thrombotic complications.

Maximum dose. Usually 2 g/kg for each course; give high risk patients no more than 1 g/kg on any one day.

Contraindications. Prior anaphylaxis to immunoglobulin, IgA deficiency with anti-IgA antibodies, and hyperprolinaemia for proline-stabilised products. Avoid sucrose-stabilised products in renal impairment.

Boxed-warning-level risks. Thrombosis (arterial and venous), and renal dysfunction with acute renal failure, osmotic nephrosis and death, mainly with sucrose-containing products and in patients over 65 years, with diabetes, hypovolaemia, sepsis or nephrotoxic drug use.

Adverse effects. Common: headache, flushing, fever, chills, nausea, myalgia, hypertension or hypotension (mostly infusion-rate related). Serious: thrombosis (myocardial infarction, stroke, pulmonary embolism), acute kidney injury, haemolysis (non-O blood groups, doses over 1 g/kg), aseptic meningitis (more with 2 g/kg), anaphylaxis, transfusion-related acute lung injury, hyponatraemia (pseudohyponatraemia), volume overload, neutropenia.

Major interactions. Live attenuated vaccines (measles, mumps, rubella, varicella; give 3 to 11 months after the infusion depending on the dose), nephrotoxic drugs and loop diuretics (raise renal risk), and laboratory tests (passively transferred antibodies cause false positive serology; direct antiglobulin test may turn positive).

Common prescribing errors. Dosing on actual weight in obesity; infusing too fast; using a sucrose-containing product in renal impairment; not hydrating; giving to IgA-deficient patients with anti-IgA antibodies.

Special groups.

• Pregnancy: compatible when indicated.

• Breastfeeding: compatible.

• Children: weight-based; Kawasaki dose 2 g/kg and immune thrombocytopenia dose 0.8 to 1 g/kg.

• Older adults: slower infusion and good hydration; higher thrombosis and renal risk.

• Kidney impairment: sucrose-free, iso-osmolar product, slowest rate, adequate hydration, and daily creatinine.

• Liver impairment: no adjustment.

• Region: product availability is limited and cost is high; ensure the product has virus inactivation steps and that the cold chain is maintained.

Formulations. 5 percent and 10 percent solutions (and lyophilised forms), 0.5 to 20 g vials. Store at 2 to 8 degrees Celsius or at room temperature as the product label states. Premedication with paracetamol, an antihistamine and hydrocortisone is used for patients with prior reactions.

Baseline. Creatinine and eGFR, IgA level and anti-IgA antibodies where available, hepatitis B and C and HIV serology (baseline stored sample), full blood count and blood group, blood pressure, hydration status, and thrombotic risk review.

Monitoring. Blood pressure, pulse and temperature every 15 to 30 minutes during rate increases, then hourly. Creatinine at baseline and 2 to 3 days after the course in high-risk patients. Trough IgG before each replacement dose. Full blood count 7 to 10 days after high doses for haemolysis.

Management of reactions. Slow or stop the infusion; give paracetamol, antihistamine and hydrocortisone for mild reactions; for anaphylaxis give intramuscular adrenaline 0.5 mg (adult) and do not rechallenge.

Stop or hold thresholds. Anaphylaxis, acute kidney injury, thrombosis, severe haemolysis, or aseptic meningitis with severe headache.

Referral and escalation. Specialist initiated. Refer for repeated reactions, renal injury, or thrombosis.