CYTOGAM does not contain a preservative. The vial should be entered only once for administration
purposes and the infusion should begin within 6 hours. The infusion schedule should be adhered to
closely (see DOSAGE AND ADMINISTRATION: Infusion section). Do not use if the solution is turbid.
Although systemic allergic reactions are rare (see ADVERSE REACTIONS section), epinephrine and
diphenhydramine should be available for treatment of acute allergic symptoms. If hypotension or
anaphylaxis occur, the administration of the immunoglobulin should be discontinued immediately and an
antidote should be given as noted above.
Assure that patients are not volume depleted prior to the initiation of IGIV. Periodic monitoring of renal
function tests and urine output is particularly important in patients judged to have a potential increased
risk for developing acute renal failure. Renal function, including the measurement of blood urea
nitrogen (BUN) and serum creatinine should be assessed prior to the initial infusion of CYTOGAM and
again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product
should be considered. The recommended rate of CYTOGAM infusion for prophylaxis of CMV disease
in solid organ transplant patients is 60 mg Ig/kg/hr (see DOSAGE AND ADMINISTRATION).
Aseptic Meningitis Syndrome
An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with
Immune Globulin Intravenous (Human) (IGIV) treatment.26-29 The syndrome usually begins within
several hours to two days following IGIV treatment. It is characterized by symptoms and signs including
severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea
and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several
thousand cells per cu.mm., predominantly from the granulocytic series, and elevated protein levels up to
several hundred mg/dL. Patients exhibiting such symptoms and signs should receive a thorough
neurological examination, including CSF studies, to rule out other causes of meningitis. AMS may
occur more frequently in association with high dose (2 g/kg) IGIV treatment. Discontinuation of IGIV
treatment has resulted in remission of AMS within several days without sequelae.
Immune Globulin Intravenous (Human) (IGIV) products can contain blood group antibodies which may
act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive
direct antiglobulin reaction and, rarely, hemolysis.30-32 Hemolytic anemia can develop subsequent to
IGIV therapy due to enhanced RBC sequestration33 (see ADVERSE REACTIONS). IGIV recipients
should be monitored for clinical signs and symptoms of hemolysis (see PRECAUTIONS: Laboratory
Transfusion-Related Acute Lung Injury (TRALI)
There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury
(TRALI)] in patients administered IGIV.34 TRALI is characterized by severe respiratory distress,
pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within 1-6
hours after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate
IGIV recipients should be monitored for pulmonary adverse reactions. If TRALI is suspected,
appropriate tests should be performed for the presence of anti-neutrophil antibodies in both the product
and patient serum (see PRECAUTIONS: Laboratory Tests).
Thrombotic events have been reported in association with IGIV35-37 (see ADVERSE REACTIONS).
Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors,
advanced age, impaired cardiac output, and/or known or suspected hyperviscosity. The potential risks
and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom
IGIV administration is being considered. Baseline assessment of blood viscosity should be considered
in patients at risk for hyperviscosity, including those with cryoglobulins, fasting
chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies (see PRECAUTIONS: Laboratory Tests).
If signs and/or symptoms of hemolysis are present after IGIV infusion, appropriate confirmatory
laboratory testing should be done (see PRECAUTIONS).
If TRALI is suspected, appropriate tests should be performed for the presence of anti-neutrophil
antibodies in both the product and the patient serum (see PRECAUTIONS).
Because of the potentially increased risk of thrombosis, baseline assessment of blood viscosity should
be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting
chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies (see PRECAUTIONS).
Animal reproduction studies have not been conducted with Cytomegalovirus Immune Globulin
Intravenous (Human). It is also not known whether Cytomegalovirus Immune Globulin Intravenous
(Human) can cause fetal harm when administered to a pregnant woman or can affect reproduction
capacity. Cytomegalovirus Immune Globulin Intravenous (Human) should be given to a pregnant woman
only if clearly needed.
2. Horowitz B, Wiebe ME, Lippin A, et al. Inactivation of viruses in labile blood derivatives.
13. Bossell, et al. Safety of therapeutic immune globulin preparations with respect to transmission of
human T-lymphotropic virus type III / lymphadenopathy-associated virus infection. MMWR
14. Wells MA, Wittek AE, Epstein JS, et al. Inactivation and partition of human T-cell lymphotropic
virus type III, during ethanol fractionation of plasma. Transfusion 1986;26:210-213.
15. McIver J, Grady G. Immunoglobulin preparations. In: Churchill WH, and Kurtz SR, editors.
Transfusion Medicine. Boston: Blackwell Scientific Publications; 1988.
16. Schneider L, Geha R. Outbreak of Hepatitis C associated with intravenous immunoglobulin
administration - United States, October 1993 - June 1994. MMWR 1994;43:505-509.
17. Edwards CA, Piet MPJ, Chin S, et al. Tri(nButyl) phosphate detergent treatment of licensed
therapeutic and experimental blood derivatives. Vox Sang 1987;52:53-59.
18. Cayco AV, Perazella MA, Hayslett JP. Renal insufficiency after intravenous immune globulin
therapy: A report of two cases and an analysis of the literature. J Am Soc Nephrol 1997;8:1788-
26. Sekul E, Culper E, Dalakas M. Aseptic meningitis associated with high-dose intravenous
immunoglobulin therapy; Frequency and risk factors. Ann Intern Med 1994;121:259-262.
27. Kato E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis.
JAMA 1988; 259:3269-3270.
28. Casteels Van Daele M, Wijindaele L, Hunnick K, et al. Intravenous immunoglobulin and acute aseptic
meningitis. N Engl J Med 1990;323:614-615.
29. Scribner C, Kapit R, Philips E, et al. Aseptic meningitis and intravenous immunoglobulin therapy.
Ann Intern Med 1994;121:305-306.
30. Copelan EA, Strohm PL, Kennedy MS, Tutschka PJ. Hemolysis following intravenous immune
globulin therapy. Transfusion 1986;26:410-412.
31. Thomas MJ, Misbah SA, Chapel HM, Jones M, Elrington G, Newsom-Davis J. Hemolysis after
high-dose intravenous Ig. Blood 1993;15:3789.
32. Reinhart WH, Berchtold PE. Effect of high dose intravenous immunoglobulin therapy on blood
rheology. Lancet 1992;339:662-664.
33. Kessary-Shoham H, Levy Y, Shoenfeld Y, Lorber M, Gershon H. In vivo administration of
intravenous immunoglobulin (IVIg) can lead to enhanced erythrocyte sequestration. J Autoimmun
34. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusion-related acute lung injury after the infusion
of IVIG. Transfusion 2001;41:264-268.
35. Dalakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of precipitant
thromboembolic events. Neurology 1994;44:223-226.
36. Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of
autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet
37. Wolberg AS, Kon RH, Monroe DM, Hoffman M. Coagulation factor XI is a contaminant in
intravenous immunoglobulin preparations. Am J Hematol 2000;65:30-34.