Immune Globulin IV

( IGIV )

Pronunciation: i-MUNE GLOB-ue-lin
Class: Immune globulin

Trade Names

Carimune NF
- Injection, lyophilized powder for solution immune globulin (human) 3, 6, 12 g

Flebogamma 5%
- Injection immune globulin (human) 5% (50 mg/mL)

Gammagard
- Injection immune globulin (human) 10% (100 mg/mL)

Gammagard S/D
- Injection immune globulin (human) 5% (50 mg/mL)

Gammaplex
- Injection, solution immune globulin (human) 5% (50 mg/mL)

Gamunex
- Injection immune globulin (human) 10% (100 mg/mL)

Privigen
- Injection immune globulin (human) 10% (100 mg/mL)

Gammagard S/D (Canada)
Sandoglobulin NF Liquid (Canada)

Pharmacology

Replaces normal human immunoglobulin G (IgG) antibodies. Promotes opsonization, fixes complement, and neutralizes bacteria, viruses, fungi, and parasites, and their toxins.

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Pharmacokinetics

Absorption

The onset is rapid; peak levels are reached immediately after infusion. Essentially 100% of the dose is immediately available in the recipient's circulation. Expect a rapid fall in serum IgG in the first wk after infusion, mainly because of equilibration of IgG between plasma and the extravascular space.

Distribution

After approximately 6 days, approximately 50% of the body pool partitions into the extravascular space, with the balance remaining in the serum.

Elimination

Half-life is approximately 21 to 42 days, but can vary from patient to patient.

Special Populations

Renal Function Impairment

No information available.

Hepatic Function Impairment

No information available.

Elderly

No information available.

Children

No information available.

Indications and Usage

Treatment of primary immunodeficiency states in patients unable to produce sufficient amounts of IgG antibodies.

Carimune NF

Maintenance treatment of patients with primary immunodeficiencies (eg, common variable immunodeficiency).

Carimune NF, Gamunex

Idiopathic thrombocytopenic purpura (ITP). Consider use in situations that require a rapid, temporary rise in platelet count (eg, prior to surgery).

Flebogamma, Gamunex

Primary (inherited) humoral immunodeficiency disorders (eg, variable immunodeficiency, X-linked agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome).

Gammagard

Primary immunodeficiency diseases (congenital X-linked gammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, severe combined immunodeficiencies).

Gammagard S/D

Primary immunodeficiency diseases; B-cell chronic lymphocytic leukemia (CLL); ITP; Kawasaki syndrome.

Gammaplex

For the replacement therapy of primary humoral immunodeficiency (humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiencies).

Gamunex

Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP).

Privigen

Primary immunodeficiency diseases; chronic immune thrombocytopenia purpura.

Unlabeled Uses

Posttransfusion purpura, Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy (as an alternative to plasma exchange). Prevention or treatment of autoimmune diseases (eg, rhesus hemolytic disease, rheumatoid arthritis), IgG4 subclass deficiencies, intractable epilepsy, cystic fibrosis, trauma, thermal injury (eg, severe burns), cytomegalovirus infection, neuromuscular disorders; prophylaxis of infections associated with bone marrow transplantation; GI protection; multiple sclerosis; myasthenia gravis.

Contraindications

Immediate hypersensitivity to human antibody product; selective IgA deficiency and circulating anti-IgA antibodies; possible aseptic meningitis syndrome; hypersensitivity or intolerance to any component of the product; history of severe or anaphylactic reaction to blood or blood-derived products.

Dosage and Administration

B-Cell CLL
Adults and Children Gammagard S/D

IV 400 mg/kg every 3 to 4 wk.

CIDP
Adults Gamunex

IV

Loading dose

2 g/kg (20 mL/kg) in divided doses over 2 to 4 consecutive days.

Maintenance dose

1 g/kg (10 mL/kg) over 1 day, or divided into 2 doses of 0.5 g/kg (5 mL/kg) given on 2 consecutive days, every 3 wk.

Immunodeficiency Syndrome
Adults and Children Carimune NF

IV 0.2 g/kg once a mo. (If clinical response is inadequate, increase dose to 0.3 g/kg or repeat infusion more frequently than once a mo.)

ITP
Adults and Children Carimune NF

IV For induction therapy, 0.4 g/kg on 2 to 5 consecutive days.

Maintenance - Chronic ITP

If after induction therapy the platelet count falls below 30,000/mcL and/or the patient manifests bleeding, 0.4 g/kg may be given as a single infusion. If an adequate response does not result, the dose can be increased to 0.8 to 1 g/kg given as a single infusion.

Gammagard S/D

IV 1 g/kg. Additional doses of up to 3 separate doses may be given on alternate days if needed, based on clinical response and platelet count.

Gamunex

IV 2 doses of 1 g/kg given on 2 consecutive days or 5 doses of 0.4 mg/kg given on 5 consecutive days. If, after the first of 2 daily 1 g/kg doses, an adequate increase in platelet count is observed at 24 h, withhold the second 1 g/kg dose.

Adults and Children older than 15 y of age Privigen

IV Two 1 g/kg doses on 2 consecutive days.

Children Carimune NF

IV

Acute ITP - Childhood

If an initial platelet count response to the first 2 doses is adequate (30,000 to 50,000/mcL), therapy may be discontinued after the second day of the 5-day course.

Kawasaki Syndrome
Adults and Children Gammagard S/D

IV 1 g/kg as a single dose or 400 mg/kg for 4 consecutive days beginning within 7 days of the onset of fever, administered with aspirin 80 to 100 mg/kg/day in 4 divided doses.

Primary Humoral Immunodeficiency
Adults and Children Gammaplex

IV 300 to 800 mg/kg (6 to 16 mL/kg) every 3 to 4 wk. Adjust the dosage over time to achieve the desired serum trough levels and clinical responses. If a patient misses a dose, administer the missed dose as soon as possible, then resume scheduled treatments every 3 or 4 wk, as applicable.

Primary Immunodeficiency Diseases
Adults and Children Flebogamma , Gammagard , Gammagard S/D , Gamunex

IV 300 to 600 mg/kg administered every 3 to 4 wk. Adjust dose over time to achieve desired trough levels and clinical response.

Adults and Children 3 y of age and older Privigen

IV 200 to 800 mg/kg at a dosing interval of 3 or 4 wk for 12 mo.

General Advice

• For administration by IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Reconstitute powder for injection immediately before use following manufacturer's guidelines for reconstitution. Do not shake during reconstitution process to avoid foaming.
• Contents of individual vials may be pooled under aseptic conditions into sterile infusion containers.
• Carefully follow recommended infusion rates to reduce risk of infusion-related adverse reactions (eg, changes in BP and pulse, flushing). Generally, infusions are started at low rates and then increased as tolerated. If adverse reactions occur, the infusion rate may be reduced or interrupted until symptoms subside, and then resumed at the rate that is comfortable for the patient.
• Ensure that immune globulin IV solutions that have been refrigerated are allowed to come to room temperature before infusing. Do not shake.
• Infuse immune globulin IV through separate IV line. Do not add any other medications or IV fluids to immune globulin IV infusion container. If other medications or IV fluids will be sequentially administered, flush IV line with dextrose 5% in water before and after infusion of immune globulin IV. Gamunex may be diluted with dextrose 5% in water if dilution is required.
• In-line filtration is acceptable but not required. Pore sizes of 15 microns or more will be less likely to slow infusion.
• Do not mix immune globulin IV with other medications or with products of different formulations or from different manufacturers.
• Do not administer if solution is discolored, cloudy, or turbid, or if particulate matter is noted.
• Gamunex is incompatible with saline.
• Hydrate the patient adequately prior to the initiation of Gammaplex infusion.

Storage/Stability

• Protect immune globulin IV solutions from freezing. Do not use any immune globulin IV solution that has been frozen.
• Store Carimune NF vials at controlled room temperature (less than 86°F). Administer Carimune immediately after reconstitution if reconstitution occurs outside of sterile laminar air flow conditions, or within 24 h if reconstitution is performed in sterile laminar flow hood using aseptic technique and solution is stored in refrigerator (36° to 46°F) during that time.
• Store Gamunex for up to 36 mo at 34° to 46°F. Gamunex also may be stored at temperatures not exceeding 77°F for up to 6 mo any time during the 36-mo shelf life, after which the product must be immediately discarded. Do not freeze.
• Store Flebogamma at 36° to 77°F. Protect from freezing. Promptly use the contents of any vial that has been entered. Discard partially used vials. Do not keep partially used vials for future use.
• Store Gammagard S/D at or below 76°F. Avoid freezing. When reconstitution is performed aseptically outside a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 h after reconstitution. When reconstitution is performed aseptically in a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into Viaflex bags and stored at 36° to 46°F for up to 24 h.
• Store Gammagard at 36° to 46°F for up to 36 mo. Do not freeze. Product may be stored at 77°F for 9 mo within the first 24 mo of the date of manufacture.
• Store Privigen at 77°F for up to 24 mo. Do not freeze. Protect from light.
• Store Gammaplex between 36° and 77°F. Do not freeze and do not use any solution that has been frozen; protect from light.

Drug Interactions

Hydantoins (eg, phenytoin)

The risk of hydantoin-induced hypersensitivity myocarditis may be increased. Use with caution. Monitor hematologic findings and cardiac function if these agents are coadministered.

Live virus vaccines

Passive transfer of antibodies may transiently interfere with the immune response to live virus vaccines such as measles, mumps, rubella, and varicella. Health care providers should be informed of recent therapy with immune globulin if patient is to receive vaccinations so appropriate measures can be taken.

Laboratory Test Interactions

After immunoglobulin infusion, the transitory rise of various passively transferred antibodies in the blood may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (eg, A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs) test.

Adverse Reactions

Cardiovascular

Hypertension; cardiac arrest, hypotension, thromboembolism, vascular collapse (postmarketing).

CNS

Asthenia, dizziness, fatigue, headache, insomnia; aseptic meningitis, coma, loss of consciousness, seizures, tremor (postmarketing).

Dermatologic

Bullous dermatitis, diaphoresis, ecchymosis, epidermolysis, erythema multiforme, flushing, petechiae, pruritus, purpura, rash, Stevens-Johnson syndrome, urticaria (postmarketing).

EENT

Ear pain, epistaxis, nasal congestion, nasopharyngitis, rhinorrhea, sore throat.

GI

Abdominal pain, diarrhea, increased conjugated bilirubin, nausea, stomach discomfort, vomiting.

Genitourinary

Acute renal failure, acute tubular necrosis, osmotic nephrosis, proximal tubular nephropathy.

Hematologic-Lymphatic

Decreased hematocrit, hemolysis, hemolytic anemia, hemorrhage, leukopenia, pancytopenia, positive direct antiglobulin (Coombs) test, thrombocytopenia (postmarketing).

Hepatic

Hepatic dysfunction (postmarketing).

Lab Tests

Increased BUN and creatinine.

Local

Injection-site reaction.

Musculoskeletal

Myalgia; arthralgia, back pain, leg cramps, limb pain, neck pain, rigors (postmarketing).

Respiratory

Acute respiratory distress syndrome, apnea, asthma, bronchitis, bronchospasm, cyanosis, dyspnea, hypoxemia, increased cough, pharyngitis, pulmonary edema, rhinitis, sinusitis, transfusion-related acute lung injury, upper respiratory tract infection, wheezing (postmarketing).

Miscellaneous

Accidental injury, chills, fever, pain, pain in extremities, tightness in chest.

Precautions

Warnings Immune globulin products have been associated with renal impairment, acute renal failure, osmotic nephrosis, and death. Products containing sucrose as a stabilizer account for a disproportionate share of the total number of cases of renal impairment and acute renal failure. For patients judged to be at increased risk of developing renal impairment, it may be prudent to reduce amount of product infused per unit of time. Do not exceed recommended doses, and ensure that the concentration and infusion rate are at the minimum level practicable.

Monitor Monitor vital signs throughout therapy. Monitor for signs and symptoms of hemolysis and pulmonary adverse reactions. Consider a baseline assessment of blood viscosity in patients at risk for hyperviscosity. Periodically monitor renal function and urinary output. Conduct a neurological examination on patients exhibiting signs/symptoms of aseptic meningitis syndrome, including CSF studies, to rule out other causes of meningitis.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Flebogamma

Safety and efficacy not established.

Gammagard

Safety and efficacy not established in neonates or infants.

Gamunex treatment of CIDP

Safety and efficacy not established.

Privigen Primary immunodeficiency

Safety and efficacy not established in children younger than 3 y of age.

Chronic ITP

Safety and efficacy not established in children younger than 15 y of age.

Elderly

Use with caution in patients older than 65 y of age and judged to be at increased risk of developing renal impairment.

Hypersensitivity

Hypersensitivity, including anaphylaxis, may occur.

Renal Function

Use with caution in patients with preexisting renal insufficiency and in patients judged to be at risk of developing renal impairment. Has been associated with renal impairment, acute renal failure, osmotic nephrosis, and death. Ensure that immune globulin IV is administered at the minimum concentration available and at the minimum rate of infusion practical in patients predisposed to acute renal failure.

Aseptic meningitis

Aseptic meningitis syndrome (including drowsiness, fever, nausea, painful eye movements, photophobia, rigidity at nape of neck, severe headache, and vomiting) may occur.

Hemolysis

Positive direct antiglobulin reaction and hemolysis may occur.

Hyperproteinemia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur.

Hypogammaglobulinemia

Patients with agammaglobulinemia or extreme hypogammaglobulinemia who have never received immunoglobulin substitution treatment or whose time from last treatment is more than 1 mL/min may be at risk of developing inflammatory reactions with an infusion rate of more than 1 mL/min.

Infection transmission

Immune globulin IV is made from human plasma and may contain infectious agents, such as viruses, that can cause disease.

Thrombotic events

May occur.

Transfusion-related acute lung injury (TRALI)

Noncardiogenic pulmonary edema (TRALI) may occur. Ensure that tests for antineutrophil antibodies in both the immune globulin IV and patient are performed and evaluated.

Patient Information

• Explain names, actions, and potential adverse reactions of the treatment regimen. Review the treatment regimen, including duration of treatment and monitoring, that will be required.
• Review benefits of therapy and risks, including potential to transmit disease and unknown infectious agents.
• Advise patient or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Instruct patient to immediately report any of the following to health care provider: decreased urine output, fever, fluid retention or swelling, painful eye movements, persistent or worsening nausea and vomiting, sensitivity to bright light, severe headache, stiff neck, sudden weight gain, unexplained drowsiness or fatigue, unexplained shortness of breath.

Copyright © 2009 Wolters Kluwer Health.