"The U.S. Food and Drug Administration today approved Procysbi (cysteamine bitartrate) for the management of nephropathic cystinosis in children and adults. Procysbi was granted orphan product designation because it is intended to treat a rare dis"...
CMV-IGIV is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk of transmission of recognized blood-borne viruses is considered to be low because of the viral inactivation and removal properties in the Cohn-Oncley cold ethanol precipitation procedure used for purification of immune globulin products (13-15). Until 1993, cold ethanol manufactured immune globulins licensed in the United States had not been documented to transmit any viral agent. However, during a brief period in late 1993 to early 1994, intravenous immune globulin made by one U.S. manufacturer was associated with transmission of Hepatitis C virus (16). To further guard against possible transmission of blood-borne viruses, including Hepatitis C, CMV-IGIV is treated with a solvent detergent viral inactivation procedure (2) known to inactivate a wide spectrum of lipid enveloped viruses, including HIV-1, HIV-2, Hepatitis B, and Hepatitis C (17). However, because new blood-borne viruses may yet emerge, some of which may not be inactivated by the manufacturing process or by solvent detergent treatment, CMV-IGIV, like any other blood product, should be given only if a benefit is expected.
Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis and death (18-25). Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentrations available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many IGIV products, those containing sucrose as a stabilizer (and given at daily doses of 350 mg/kg or greater) account for a disproportionate share of the total number (18). Cytogam® contains sucrose as a stabilizer. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure.
During administration, the patient's vital signs should be monitored continuously and careful observation made for any symptoms throughout the infusion. Epinephrine should be available for the treatment of an acute anaphylactic reaction (see PRECAUTIONS section).
Cytogam® (cytomegalovirus immune globulin intravenous human) 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 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® (cytomegalovirus immune globulin intravenous human) and again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered. The recommended rate of Cytogam® (cytomegalovirus immune globulin intravenous human) 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 sequestration (33) [See ADVERSE REACTIONS]. IGIV recipients should be monitored for clinical signs and symptoms of hemolysis [See PRECAUTIONS:Laboratory Tests].
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 ventilatory support.
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 IGIV (35-37)(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].
Pregnancy Category C:
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. Transfusion 1985;25:516-522.
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 1996;35:231-233.
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;8:1788-1794.
19. Cantu TG, Hoehn-Saric EW, Burgess KM, Racusen L, Scheel PJ. Acute renal failure associated with immunoglobulin therapy. Am J Kidney Dis 1995;25:228-234.
20. Hansen-Schmidt S, Silomon J, Keller F. Osmotic nephrosis due to high-dose intravenous immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis. Am J Kidney Dis 1996;28: 451-453.
21. Tan E, Hajinazarian M, Bay W, Neff J, Mendell JR. Acute renal failure resulting from intravenous immunoglobulin therapy. Arch Neurol 1993;50:137-139.
22. Winward D, Brophy MT. Acute renal failure after administration of intravenous immunoglobulin: Review of the literature and case report. Pharmacotherapy 1995;15:765-772.
23 Phillips AO. Renal failure and intravenous immunoglobulin [letter; comment]. Clin Nephrol 1992;37:217.
24. Lindberg HA, Wald MH, Barker MH. Renal changes following administration of hypertonic solutions. Arch Intern Med 1939;63:907-918.
25. Rigdon RH, Cardwell ES. Renal lesions following the intravenous injection of a hypertonic solution of sucrose. Arch Intern Med 1942;69:670-690.
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 1999;13:129-135.
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 1986;2:217-218.
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.
Last reviewed on RxList: 10/30/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Cytogam Information
Cytogam - User Reviews
Cytogam User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
Find out what women really need.