Immune Globulin (Intravenous)

Pronunciation

U.S. Brand Names

Carimune™ [DSC]; Carimune™ NF; Flebogamma®; Gamimune® N; Gammagard® S/D; Gammar®-P I.V.; Gamunex®; Iveegam EN; Octagam®; Panglobulin®; Panglobulin® NF; Polygam® S/D; Venoglobulin®-S [DSC]

Synonyms

IVIG

Generic Available

Canadian Brand Names

Gamimune® N; Gammagard® S/D; Gamunex®; Iveegam Immuno®

Use

Treatment of primary immunodeficiency syndromes (congenital agammaglobulinemia, severe combined immunodeficiency syndromes [SCIDS], common variable immunodeficiency, X-linked immunodeficiency, Wiskott-Aldrich syndrome); idiopathic thrombocytopenic purpura (ITP); Kawasaki disease (in combination with aspirin)

Prevention of bacterial infection in B-cell chronic lymphocytic leukemia (CLL); pediatric HIV infection; bone marrow transplant (BMT)

Use - Unlabeled/Investigational

Autoimmune diseases (myasthenia gravis, SLE, bullous pemphigoid, severe rheumatoid arthritis), Guillain-Barré syndrome; used in conjunction with appropriate anti-infective therapy to prevent or modify acute bacterial or viral infections in patients with iatrogenically-induced or disease-associated immunodepression; autoimmune hemolytic anemia or neutropenia, refractory dermatomyositis/polymyositis

Pregnancy Risk Factor

Pregnancy Implications

Immune globulins cross the placenta in increased amounts after 30 weeks gestation.

Lactation

Excretion in breast milk unknown

Contraindications

Hypersensitivity to immune globulin or any component of the formulation; selective IgA deficiency

Warnings/Precautions

Anaphylactic hypersensitivity reactions can occur, especially in IgA-deficient patients; studies indicate that the currently available products have no discernible risk of transmitting HIV or hepatitis B; aseptic meningitis may occur with high doses (

2 g/kg). Use with caution in the elderly, patients with renal disease, diabetes mellitus, volume depletion, sepsis, paraproteinemia, and nephrotoxic medications due to risk of renal dysfunction. Patients should be adequately hydrated prior to therapy. Acute renal dysfunction (increased serum creatinine, oliguria, acute renal failure) can rarely occur; usually within 7 days of use (more likely with products stabilized with sucrose). Use caution in patients with a history of thrombotic events or cardiovascular disease; there is clinical evidence of a possible association between thrombotic events and administration of intravenous immune globulin. For intravenous administration only.

Adverse Reactions

Frequency not defined.

Cardiovascular: Flushing of the face, tachycardia, hyper-/hypotension, chest tightness, angioedema, lightheadedness, chest pain, MI, CHF, pulmonary embolism

Central nervous system: Anxiety, chills, dizziness, drowsiness, fatigue, fever, headache, irritability, lethargy, malaise, aseptic meningitis syndrome

Dermatologic: Pruritus, rash, urticaria

Gastrointestinal: Abdominal cramps, diarrhea, nausea, sore throat, vomiting

Hematologic: Autoimmune hemolytic anemia, mild hemolysis

Hepatic: Liver function test increased

Local: Pain or irritation at the infusion site

Neuromuscular & skeletal: Arthralgia, back or hip pain, myalgia, nuchal rigidity

Ocular: Photophobia, painful eye movements

Renal: Acute renal failure, acute tubular necrosis, anuria, BUN increased, creatinine increased, nephrotic syndrome, oliguria, proximal tubular nephropathy, osmotic nephrosis

Respiratory: Cough, dyspnea, wheezing, nasal congestion, rhinorrhea, sinusitis

Miscellaneous: Diaphoresis, hypersensitivity reactions, anaphylaxis

Postmarketing and/or case reports: Abdominal pain, apnea, ARDS, bronchospasm, bullous dermatitis, cardiac arrest, Coombs' test positive, cyanosis, epidermolysis, erythema multiforme, hepatic dysfunction, hypoxemia, leukopenia, loss of consciousness, pancytopenia, pulmonary edema, rigors, seizure, Stevens-Johnson syndrome, thromboembolism, transfusion-related acute lung injury (TRALI), tremor, vascular collapse

Drug Interactions

Live virus, vaccines (eg, measles, mumps, rubella): May have impaired response to vaccines; separate administration by at least 3 months.

Stability

Stability and dilution is dependent upon the manufacturer and brand; do not mix with other drugs; do not freeze; do not shake, avoid foaming; discard unused portion:

Carimune™ NF, Panglobulin® NF: Prior to reconstitution, store at or below 30°C (86°F). Reconstitute with NS, D5W, or SWFI. Following reconstitution, store under refrigeration; use within 24 hours. Do not freeze.

Flebogamma®: Store at 2°C to 25°C (36°F to 77°F).

Gamimune® N: Store at 2°C to 8°C (36°F to 46°F).

Gammagard® S/D, Polygam® S/D: Store below 25°C (77°F). Reconstitute with SWFI; when diluted aseptically in a sterile laminar air flow hood, may store diluted solution under refrigeration for up to 24 hours. If reconstituted outside of laminar flow hood, use within 2 hours.

Gammar®-P I.V.: Store below 25°C (77°F). Reconstitute with SWFI.

Gamunex®: May be stored for up to 5 months at room temperature up to 25°C (up to 77°F) within 18 months of manufacture date.

Iveegam EN: Store at 2°C to 8°C (36°F to 46°F). Reconstitute with SWFI; use immediately after reconstitution.

Octagam®: Store at 2°C to 8°C (36°F to 46°F) for 24 months or 25°C (77°F) for 18 months.

Panglobulin®: Store at room temperature at below 30°C (86°F). Reconstitute with NS, D5W, or SWFI; when diluted aseptically in a sterile laminar flow hood, may store diluted solution under refrigeration for up to 24 hours.

Polygam® S/D: Store at room temperature at or below 25°C (77°F). Do not freeze.

Venoglobulin®-S: Store below 25°C (77°F).

Compatibility

Stable in D5W, D15W, D5¹/4NS; variable stability (consult detailed reference) in TPN. Gamunex® should be diluted in D5W only.

Y-site administration: Compatible: Fluconazole, sargramostim

Mechanism of Action

Replacement therapy for primary and secondary immunodeficiencies; interference with Fc receptors on the cells of the reticuloendothelial system for autoimmune cytopenias and ITP; possible role of contained antiviral-type antibodies

Pharmacodynamics/Kinetics

Onset of action: I.V.: Provides immediate antibody levels

Duration: Immune effect: 3-4 weeks (variable)

Distribution: Vd: 0.09-0.13 L/kg

Intravascular portion: Healthy subjects: 41% to 57%; Patients with congenital humoral immunodeficiencies: ~70%

Half-life elimination: IgG (variable among patients): Healthy subjects: 14-24 days; Patients with congenital humoral immunodeficiencies: 26-40 days; hypermetabolism associated with fever and infection have coincided with a shortened half-life

Dosage

Approved doses and regimens may vary between brands; check manufacturer guidelines. Note: Some clinicians dose IVIG on ideal body weight or an adjusted ideal body weight in morbidly obese patients. The volume of distribution of IVIG preparations in healthy subjects is similar to that observed with endogenous IgG. IVIG remains primarily in the intravascular space. Patients with congenital humoral immunodeficiencies appear to have about 70% of the IVIG available in the intravascular space.

Infants and Children: Prevention of gastroenteritis (unlabeled use): Oral: 50 mg/kg/day divided every 6 hours

Children: I.V.:

Pediatric HIV: 400 mg/kg every 28 days

Severe systemic viral and bacterial infections (unlabeled use): 500-1000 mg/kg/week

Children and Adults: I.V.:

Primary immunodeficiency disorders: 200-400 mg/kg every 4 weeks or as per monitored serum IgG concentrations

Flebogamma®, Gamunex®, Octagam®: 300-600 mg/kg every 3-4 weeks; adjusted based on dosage and interval in conjunction with monitored serum IgG concentrations.

B-cell chronic lymphocytic leukemia (CLL): 400 mg/kg/dose every 3 weeks

Idiopathic thrombocytopenic purpura (ITP):

Acute: 400 mg/kg/day for 5 days or 1000 mg/kg/day for 1-2 days

Chronic: 400 mg/kg as needed to maintain platelet count >30,000/mm³; may increase dose to 800 mg/kg (1000 mg/kg if needed)

Kawasaki disease: Initiate therapy within 10 days of disease onset: 2 g/kg as a single dose administered over 10 hours, or 400 mg/kg/day for 4 days. Note: Must be used in combination with aspirin: 80-100 mg/kg/day in 4 divided doses for 14 days; when fever subsides, dose aspirin at 3-5 mg/kg once daily for 6-8 weeks

Acquired immunodeficiency syndrome (patients must be symptomatic) (unlabeled use): Various regimens have been used, including:

200-250 mg/kg/dose every 2 weeks

400-500 mg/kg/dose every month or every 4 weeks

Autoimmune hemolytic anemia and neutropenia (unlabeled use): 1000 mg/kg/dose for 2-3 days

Autoimmune diseases (unlabeled use): 400 mg/kg/day for 4 days

Bone marrow transplant: 500 mg/kg beginning on days 7 and 2 pretransplant, then 500 mg/kg/week for 90 days post-transplant

Adjuvant to severe cytomegalovirus infections (unlabeled use): 500 mg/kg/dose every other day for 7 doses

Guillain-Barré syndrome (unlabeled use): Various regimens have been used, including:

400 mg/kg/day for 4 days

1000 mg/kg/day for 2 days

2000 mg/kg/day for one day

Refractory dermatomyositis (unlabeled use): 2 g/kg/dose every month x 3-4 doses

Refractory polymyositis (unlabeled use): 1 g/kg/day x 2 days every month x 4 doses

Chronic inflammatory demyelinating polyneuropathy (unlabeled use): Various regimens have been used, including:

400 mg/kg/day for 5 doses once each month

800 mg/kg/day for 3 doses once each month

1000 mg/kg/day for 2 days once each month

Dosing adjustment/comments in renal impairment: Clcr<10 mL/minute: Avoid use; in patients at risk of renal dysfunction, consider infusion at a rate less than maximum.

Administration

I.V. use only; for initial treatment, a lower concentration and/or a slower rate of infusion should be used. Administer in separate infusion line from other medications; if using primary line, flush with saline prior administration (Note: Venoglobulin®-S: Flush with D5W). Decrease dose, rate and/or concentration of infusion in patients who may be at risk of renal failure. Decreasing the rate or stopping the infusion may help relieve some adverse effects (flushing, changes in pulse rate, changes in blood pressure). Epinephrine should be available during administration. The lot numbers of vials used should be recorded.

Monitoring Parameters

Renal function, urine output, hemoglobin and hematocrit, infusion-related adverse reactions, anaphylaxis

Test Interactions

Octagam® contains maltose which may interfere with blood and urine glucose tests.

Dietary Considerations

Octagam® contains sodium 30 mmol/L

Patient Education

This medication can only be administered by infusion. You will be monitored closely during the infusion. If you experience nausea ask for assistance, do not get up alone. Do not have any vaccinations for the next 3 months without consulting prescriber. Immediately report chills; chest pain, tightness, or rapid heartbeat; acute back pain; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Additional Information

Intravenous Immune Globulin Product Comparison:

Carimune™ NF, Panglobulin® NF:

FDA indication: Primary immunodeficiency, ITP

Contraindication: IgA deficiency

IgA content: 720 mcg/mL

Plasma source: Pooled donors

Half-life: 23 days

IgG subclass (%):

IgG1 (60-70): 60.5

IgG2 (19-31): 30.2

IgG3 (5-8.4): 6.6

IgG4 (0.7-4): 2.8

Storage: Room temperature at or below 30°C (86°F); refrigerate after reconstitution

Recommendations for initial infusion rate: 0.5-1 mL/minute

Maximum infusion rate: 2 mg/kg/minute

Flebogamma®:

FDA indication: Primary immunodeficiency

Contraindication: IgA deficiency, intolerance to fructose/sorbitol, history of anaphylaxis with blood products

IgA content: <50 mcg/mL

Plasma source: Pooled donors

Half-life: 30-45 days

IgG subclass (%):

IgG1 (60-70): 70

IgG2 (19-31): 25

IgG3 (5-8.4): 3

IgG4 (0.7-4): 2

Storage: 2°C to 25°C

Recommendations for initial infusion rate: 0.01 mL/kg/minute

Maximum infusion rate: 0.1 mL/kg/minute (0.06 mL/kg/minute in renal impairment)

Gamimune® N:

FDA indication: Primary immunodeficiency, ITP

Contraindication: IgA deficiency

IgA content: 270 mcg/mL

Adverse reactions (%): 5.2

Plasma source: >2000 paid donors

Half-life: 21 days

IgG subclass (%):

IgG1 (60-70): 60

IgG2 (19-31): 29.4

IgG3 (5-8.4): 6.5

IgG4 (0.7-4): 4.1

Monomers (%): >95

Gamma globulin (%): >98

Storage: Refrigerate

Recommendations for initial infusion rate: 0.01-0.02 mL/kg/minute

Maximum infusion rate: 0.08 mL/kg/minute

Maximum concentration for infusion (%): 10

Gammagard® SD:

FDA indication: Primary immunodeficiency, ITP, CLL prophylaxis

Contraindication: None (caution with IgA deficiency)

IgA content: 0.92-1.6 mcg/mL

Adverse reactions (%): 6

Plasma source: 4000-5000 paid donors

Half-life: 24 days

IgG subclass (%):

IgG1 (60-70): 67 (66.8)*

IgG2 (19-31): 25 (25.4)

IgG3 (5-8.4): 5 (7.4)

IgG4 (0.7-4): 3 (0.3)

Monomers (%): >95

Gamma globulin (%): >90

Storage: Room temperature

Recommendations for initial infusion rate: 0.5 mL/kg/hour

Maximum infusion rate: 4 mL/kg/hour

Maximum concentration for infusion (%): 5

Gammar®-P I.V.:

FDA indication: Primary immunodeficiency

Contraindication: IgA deficiency

IgA content: <20 mcg/mL

Adverse reactions (%): 15

Plasma source: >8000 paid donors

Half-life: 21-24 days

IgG subclass (%):

IgG1 (60-70): 69

IgG2 (19-31): 23

IgG3 (5-8.4): 6

IgG4 (0.7-4): 2

Monomers (%): >98

Gamma globulin (%): >98

Storage: Room temperature

Recommendations for initial infusion rate: 0.01-0.02 mL/kg/minute

Maximum infusion rate: 0.06 mL/kg/minute

Maximum concentration for infusion (%): 5

Gamunex®:

FDA indication: Primary immunodeficiency, ITP

Contraindication: Caution in severe, selective IgA deficiency

IgA content: 40 mcg/mL

IgM content: <2 mcg/mL

Plasma source: Pooled donors

Half-life: 36 days

IgG subclass (%):

IgG1 (60-70): 65

IgG2 (19-31): 26

IgG3 (5-8.4): 5.6

IgG4 (0.7-4): 2.6

Monomer + dimer (%): 100

Gamma globulin (%): >98

Storage: 2°C to 8°C; may be stored at room temperature for 5 months (only during first 18 months after manufacture )

Recommendations for initial infusion rate: 0.01 mL/kg/minute

Maximum infusion rate: 0.08 mL/kg/minute

Maximum concentration for infusion (%): 10

Octagam®:

FDA indication: Primary immunodeficiency

Contraindications: IgA deficiency

IgA content: 100 mcg/mL

Half-life: Immunodeficiency: 40 days

IgG subclass (%):

IgG1 (60-70): 65

IgG2 (19-31): 30

IgG3 (5-8.4): 3

IgG4 (0.7-4): 2

Monomers (%): 90

Gamma globulin (%): 96

Storage: Refrigerated or room temperature

Recommendations for initial infusion rate: 0.6 mL/kg/hour

Maximum infusion rate: 4 mL/kg/hour

Maximum concentration for infusion: 5%

Polygram®:

FDA indication: Primary immunodeficiency, ITP, CLL

Contraindication: None (caution with IgA deficiency)

IgA content: 0.74 ± 0.33 mcg/mL

Adverse reactions (%): 6

Plasma source: 50,000 voluntary donors

Half-life: 21-25 days

IgG subclass (%):

IgG1 (60-70): 67

IgG2 (19-31): 25

IgG3 (5-8.4): 5

IgG4 (0.7-4): 3

Monomers (%): >95

Gamma globulin (%): >90

Storage: Room temperature

Recommendations for initial infusion rate: 0.5 mL/kg/hour

Maximum infusion rate: 4 mL/kg/hour

Maximum concentration for infusion (%): 10

Venoglobulin®-S:

FDA indication: Primary immunodeficiency, ITP

Contraindication: IgA deficiency

IgA content: 20-24 mcg/mL

Adverse reactions (%): 6

Plasma source: 6000-9000 paid donors

Half-life: 29 days

IgG subclass (%):

IgG1 (60-70): 62.3**

IgG2 (19-31): 32.8

IgG3 (5-8.4): 2.9

IgG4 (0.7-4): 2

Monomers (%): >98

Gamma globulin (%): >98

Storage: Room temperature

Recommendations for initial infusion rate: 0.01-0.02 mL/kg/minute

Maximum infusion rate: 0.04 mL/kg/minute

Maximum concentration for infusion (%):10

*Skvaril F and Gardi A, "Differences Among Available Immunoglobulin Preparations for Intravenous Use,"Pediatr Infect Dis J, 1988, 7:543-48.

**Roomer J, Morgenthaler JJ, Scherz R, et al, "Characterization of Various Immunoglobulin Preparations for Intravenous Application,"Vox Sang, 1982, 42:62-73.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

None reported

Mental Health: Effects on Psychiatric Treatment

None reported

Oncology: Emetic Potential

Low

Oncology: Vesicant

Dosage Forms

[DSC] = Discontinued product

Injection, powder for reconstitution [preservative free]:

Carimune™: 1 g, 3 g, 6 g, 12 g [contains sucrose] [DSC]

Gammar®-P I.V.: 1 g [DSC], 2.5 g [DSC], 5 g, 10 g [stabilized with human albumin and sucrose]

Iveegam EN: 0.5 g [DSC], 1 g [DSC], 2.5 g [DSC], 5 g [stabilized with glucose]

Panglobulin®: 6 g, 12 g [contains sucrose]

Injection, powder for reconstitution [preservative free, nanofiltered]:

Carimune™ NF: 3 g, 6 g, 12 g [contains sucrose]

Panglobulin® NF: 6 g, 12 g [contains sucrose]

Injection, powder for reconstitution [preservative free, solvent detergent treated]

Gammagard® S/D: 2.5 g, 5 g, 10 g [stabilized with human albumin, glycine, glucose, and polyethylene glycol]

Polygam® S/D: 5 g, 10 g [stabilized with human albumin, glycine, glucose, and polyethylene glycol]

Injection, solution [preservative free; solvent detergent-treated]:

Gamimune® N: 10% [100 mg/mL] (10 mL, 25 mL, 50 mL, 100 mL, 200 mL)

Octagam®: 5% [50 mg/mL] (20 mL, 50 mL, 100 mL, 200 mL) [sucrose free; contains sodium 30 mmol/L and maltose]

Venoglobulin®-S: 5% [50 mg/mL] (50 mL, 100 mL, 200 mL); 10% [100 mg/mL] (50 mL, 100 mL, 200 mL) [stabilized with human albumin] [DSC]

Injection, solution [preservative free]:

Flebogamma®: 5% (10 mL, 50 mL, 100 mL, 200 mL) [PEG precipitated/chromatography purified]

Gamunex®: 10% (10 mL, 25 mL, 50 mL, 100 mL, 200 mL) [caprylate/chromatography purified]

References

ASHP Commission on Therapeutics, "ASHP Therapeutic Guidelines for Intravenous Immune Globulin,"Am J Hosp Pharm, 1992, 49(3):652-4.

Blanchette VS, Luke B, Andrew M, et al, "A Prospective Randomized Trial of High-Dose Intravenous Immune Globulin G Therapy, Oral Prednisone Therapy, and No Therapy in Childhood Acute Immune Thrombocytopenic Purpura,"J Pediatr, 1993, 123(6):989-95.

Grillo JA, Gorson, KC, Ropper AH, et al, "Rapid Infusion of Intravenous Immune Globulin in Patients With Neuromuscular Disorders,"Neurology, 2001; 57:1699-1701.

Morrell A, "Pharmacokinetics of Intravenous Immunoglobulin Preparations,"Intravenous Immunoglobulins in Clinical Practice, Lee ML and Strand V eds, New York, NY: Marcel Dekker, Inc, 1997, 1-18.

NIH Consensus Conference, "Intravenous Immunoglobulin, Prevention and Treatment of Disease,"JAMA, 1990, 264(24):3189-93.

"University Hospital Consortium Expert Panel for Off-Label Use of Polyvalent Intravenously Administered Immunoglobulin Preparations Consensus Statement,"JAMA, 1995, 273(23):1865-70.

International Brand Names

Gamimune® N (CA); Gammagard® S/D (CA); Gamunex® (CA); Iveegam Immuno® (CA)