Name: Intravenous Immune Globulin
Immune Globulin Intravenous

Carimune - ZLB Bioplasma Inc., Glendale, CA
Gamimune N - Bayer Corp., Elkhart, IN
Gammagard S/D - Baxter Healthcare Corp., Glendale, CA
Gammar-P I.V. - Aventis Behring LLC, Kankakee, IL
Iveegam EN - Baxter Healthcare Corp., Glendale, CA
Sandoglobulin I.V. - Novartis, East Hanover, NJ
Venoglobulin-S - Alpha Therapeutic Corp., Los Angeles, CA

Description/Contents: Commercial preparations of intravenous immune globulin (IVIG) are prepared by cold ethanol fractionation (the Cohn process) of human plasma derived from pools of 3000 to 10 000 donors. The products are purified by a variety of steps which may include enzymatic treatment at a low pH, fractionation, filtration and chromatography. The purified immunoglobulin is stabilized with glucose, maltose, glycine, sucrose, mannitol, or albumin. The final products contain more than 95% IgG (not less that 90% in monomeric), less than 2.5% IgA, and a negligible amount of IgM. Among the IgG subclasses, IgG1 varies from 55% to 70%, IgG2 from 30% to 38%, IgG3 from 0% to 6%, and IgG4 from 0.7% to 2.6%, according to the size and composition of the donor pools used in the various proprietary intravenous immune globulin preparations. Immune globulin preparations also contain certain immunomodulating peptides including soluble CD4, CD8, cytokines and HLA molecules, as well as antibodies against exogenous antigens, viruses, and bacteria.

Intravenous immune globulin preparations contain IgG antibodies against a wide spectrum of normal human proteins and anti-idiotypic antibodies directed against Fab, the antigen-binding region of these autoantibodies, because they are derived from large pools of human donors. In addition, they contain a broad range of immune antibodies directed against foreign antigens and pathogens, reflecting the size and diversity of the donor population.

Various viral inactivation processes, including solvent/detergent treatment, are typically applied. All intravenous immune globulin preparations distributed in the United States are considered safe from known pathogens.

• Primary immune deficiency:
  Congenital agammaglobulinemia
  Common variable immunodeficiency
  X-linked agammaglobulinemia
  Wiskott-Aldrich syndrome
  

• Secondary immune deficiency:
  Bone marrow transplant
  Septicemia prophylaxis
  Acute Graft-vs-Host Disease prophylaxis
  Chronic lymphocytic leukemia
  Pediatric HIV

• Kawasaki syndrome
• Idiopathic thrombocytopenic purpura
  Acute
  Chronic
  (Post-transfusion purpura)

• Neurological disorders
  Acute Guillain-Barré syndrome
  Chronic inflammatory demyelinating polyradiculoneuropathy
  Dermatomyositis (steroid-resistant)
  Multifocal motor neuropathy
  Myasthenia gravis

Dosage and Administration: Preparations of intravenous immune globulin are provided as sterile 5-10% solutions for storage at 2-8°C (36-46°F) or as lyophilized powder for storage at room temperature not exceeding 30°C (86°F). Lyophilized preparations can be reconstituted to a 3-12% solution with 0.9% Sodium Chloride Injection USP, 5% Dextrose, or Sterile Water.

The dose of IVIG depends upon the condition being treated and upon clinical response. The usual dose of IVIG for the treatment of primary immunodeficiency is 100 to 400 mg/kg every 3 to 4 weeks. In idiopathic thrombocytopenic purpura, the recommended dose is 400 mg/kg daily for 2 to 5 days or, 1 gm/kg daily for 2 days. For prophylaxis of bacterial infection in chronic lymphocytic leukemia, the recommended dose is 400 mg/kg every 3 to 4 weeks. During the first 15 to 30 minutes of administration, the rate of infusion should be slow and then slowly increased if it is tolerated. In neurological disorders, the typical course of treatment consists of 1-2 gm/kg in divided doses over 2-5 days.

Adverse Effects:Intravenous immune globulin is not associated with transfusion-transmitted infections. Recognized adverse effects include headache, aseptic meningitis, hypertension, fever, coronary vasospasm, hyperviscosity, thromboembolic events including stroke, skin reactions including urticaria, pruritis and petechiae, leukocytoclastic vasculitis (rarely in patients with cryoglobulinemia), anaphylactic reactions (particularly in IgA-deficient individuals sensitized to IgA), transiently positive direct antiglobulin reaction, rouleaux formation and transfusion related acute lung injury. Hemolysis has been documented rarely, presumably on the basis of the transfer of isoagglutinins (e.g., anti D or anti A,B)

Intravenous immune globulin preparations have been associated with renal dysfunction, acute renal failure, osmotic nephrosis and death, particularly in patients older than age 65 or with any degree of pre-existing renal insufficiency, diabetes mellitus, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, the product should be administered at the minimum concentration available at the slowest practical rate of infusion. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IVIG products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number.

Alternative Therapy:Management of the conditions for which intravenous immune globulin is given will vary with the condition in question. Neurological disorders that do not respond to intravenous immune globulin may be treated with plasma exchange or immunosuppressive medications. Immunodeficiency states may be treated with antibiotics. Idiopathic thrombocytopenic purpura may be treated with corticosteroids, immunosuppressive agents and intravenous anti-D (e.g., WinRho® S/D). Intravenous immune globulin should not be administered for volume expansion. Crystalloid electrolyte solutions, human serum albumin or colloid starch solutions (e.g. hetastarch, pentastarch) are preferable for this purpose.

Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001;345:747-755.

Dalakas MD. Intravenous Immune Globulin Therapy for Neurologic Diseases. Ann Int Med 1997;126:721-730.

Stiehm ER. Immune globulin therapy. In: Mintz PD, ed. Transfusion Therapy: Clinical Principles and Practice. Bethesda, MD: AABB Press, 1999.

Transfusion Guidelines

Plasma Guidelines	Antithrombin III Guidelines
Platelet Guidelines	Activated Protein Guidelines
Red Cell Guidelines	Factor IX Guidelines
Cryoprecipitate Guidelines	Factor VIII Guidelines
AICC/Porcine Factor VIII Guidelines	IVIG Guidelines Coagulation Factor VII Guidelines

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