Please Reply to: HFM-370
October 3, 1994
Dear IGIV Manufacturer:
An aseptic meningitis syndrome (AMS) associated with the use of Immune Globulin Intravenous (Human) (IGIV) products has been reported in several publications (1-4). Most recently Sekul, et al., reported six cases among 54 patients treated for various neuromuscular diseases with high dose IGIV (2 g/kg) (1).
In addition, the Food and Drug Administration's MEDWatch program has received reports of 22 such events since 1986 involving six different IGIV products. Doses of IGIV in these reported events ranged from 0.2 to 2 g/kg. When it occurred, onset of AMS began within several hours to two days of treatment. The most common indication for treatment was idiopathic thrombocytopenic purpura. Among these 22 reports, 20 described positive CSF findings including pleocytosis, usually with neutrophils, and elevated protein levels. No fatalities have been reported due to IGIV-associated aseptic meningitis; however, extremely painful headaches occur. Discontinuation of treatment results in improvement within a few days. For these reasons we recommend modification of the Precautions section of IGIV product package inserts to alert physicians to the occurrence and characteristics of IGIV-associated AMS.
The new Precautions should convey the following information:
Please insert the new Precautions paragraph into your package insert and provide draft labeling for our review before the next printing of your package insert.
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Kathryn C. Zoon, Ph.D.
Center for Biologics Evaluation And Research
- Sekul E, Cupler E, Dalakas M. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: Frequency and risk factors. Ann Int Med, 1994;123:259-262.
- Kato E, Shindo S, Eto Y, Hashimoto N, Yamamoto M, Sakata Y, Hiyoshi Y. Administration of immune globulin associated with aseptic meningitis. JAMA, 1988;3269-3270.
- Casteels Van Daele M, Wijndaele L, Hunnick K, Gillis P. Intravenous immunoglobulin and acute aseptic meningitis. N Engl J Med, 1990; 323(9):614-615.
- Scribner C, Kapit R, Phillips E, Rickels N. Aseptic meningitis and intravenous immunoglobulin therapy. Ann Intern Med, 1994;121:305-306