CytoGam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV), is an immunoglobulin G (IgG) containing a standardized amount of antibody to Cytomegalovirus (CMV). CMV-IGIV is formulated in final vial as a sterile liquid. The globulin is stabilized with 5% sucrose and 1% Albumin (Human). CytoGam® contains no preservative. The purified immunoglobulin is derived from pooled adult human plasma selected for high titers of antibody for Cytomegalovirus (CMV) (1). Source material for fractionation may be obtained from another U.S. licensed manufacturer. Pooled plasma was fractionated by ethanol precipitation of the proteins according to Cohn Methods 6 and 9, modified to yield a product suitable for intravenous administration. A widely utilized solvent-detergent viral inactivation process is also used (2). Certain manufacturing operations may be performed by other firms. Each milliliter contains: 50 ± 10 mg of immunoglobulin, primarily IgG, and trace amount of IgA and IgM; 50 mg of sucrose; 10 mg of Albumin (Human). The sodium content is 20-30 mEq per liter, i.e., 0.4-0.6 mEq per 20 ml or 1.0-1.5 mEq per 50 ml. The solution should appear colorless and translucent.

CytoGam® contains IgG antibodies representative of the large number of normal persons who contributed to the plasma pools from which the product was derived. The globulin contains a relatively high concentration of antibodies directed against Cytomegalovirus (CMV). In the case of persons who may be exposed to CMV, CytoGam® can raise the relevant antibodies to levels sufficient to attenuate or reduce the incidence of serious CMV disease.

Cytomegalovirus Immune Globulin Intravenous (Human) is indicated for the prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas and heart. In transplants of these organs other than kidney from CMV seropositive donors into seronegative recipients, prophylactic CMV-IGIV should be considered in combination with ganciclovir.


Clinical studies have shown a 50% reduction in primary CMV disease in renal transplant patients given CMV-IGIV (3) and a 56% reduction in serious CMV disease (4) in liver transplant patients given CMV-IGIV. CMV-IGIV prophylaxis was associated with increased survival in liver transplant recipients (5).

In two separate clinical trials, CytoGam® was shown to provide effective prophylaxis in renal-transplant recipients at risk for primary CMV disease. In the first randomized trial, (3) the incidence of virologically confirmed CMV-associated syndromes was reduced from 60% in controls (n=35) to 21% in recipients of CMV immune globulin (n=24) (p<0.01); marked leukopenia was reduced from 37% in controls to 4% in globulin recipients (p<0.01); and fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20% of controls (p=0.05). Serious CMV disease was reduced from 46% to 13%. There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17% of controls as compared with 4% of globulin recipients). There was no effect on rates of viral isolation or seroconversion although the rate of viremia was less in CytoGam® recipients. In a subsequent non-randomized trial in renal transplant recipients (n=36), (6) the incidence of virologically confirmed CMV-associated syndrome was reduced to 36% in the globulin recipients in comparison to a 60% incidence in control patients (n=35) in the randomized trial. The rates of serious CMV disease, and concomitant fungal and parasitic superinfection were similar to patients receiving CMV-IGIV in the first trial.

In a randomized, double-blind, placebo-controlled trial, in liver transplant recipients (4), the incidence of serious CMV-associated disease was reduced from 26% in the 72 control patients to 12% in the 69 CMV-IGIV recipients (p=0.02); serious CMV-associated disease included CMV disease in 2 or more organs, CMV pneumonia, or CMV-associated invasive fungal infection, the incidence of which was 18% in controls and 7% in CMV-IGIV recipients (p=0.04). In follow-up (5) of the liver transplant patients studied in this randomized controlled trial and a subsequent open-label trial (7), the one year survival of the 72 control patients was 72% versus 86% in the 90 recipients of CMV-IGIV (p=0.03). In the randomized control trial, the reduction in serious CMV-associated disease in CMV seronegative recipients of livers from a CMV seropositive donor (7/19 in the CMV-IGIV group vs. 9/19 in control) was less than in transplants with other donor and recipient serologic status (1/50 in the CMV-IGIV group vs. 10/53 in the control group). This finding was similar to that of Merigan et al. (8) in a study of ganciclovir prophylaxis after heart transplantation. In this study, patients received ganciclovir IV at 5mg/kg bid for the initial 14 days post-transplant, then at 6 mg/kg each day for 5 days per week through day 28.

Recent studies of combined prophylaxis with CMV-IGIV and ganciclovir have shown reductions in the incidence of serious CMV associated disease in CMV seronegative recipients of CMV seropositive organs below that expected from one drug alone (9-12).

Ham et al. (9) used CMV-IGIV with a dosage schedule of 150 mg/kg CMV-IGIV within 72 hours of transplant; 100 mg/kg at two, four, six and eight weeks following liver transplant and then 50 mg/kg at 12 and 16 weeks post-transplant in combination with ganciclovir (10 mg/kg/day for 14 days). The incidence of CMV disease was reduced from an expected 60-80% rate to 7% in 15 seronegative recipients of a seropositive organ.

Snydman (10) using the CMV-IGIV dosage schedule listed under DOSAGE AND ADMINISTRATION Section in combination with ganciclovir (10 mg/kg/day for 14 days) reduced the incidence of serious CMV disease in D+R- liver transplant recipients receiving placebo or one drug from 16/47 (34%) to 3/41 (7%) in patients receiving both drugs for prophylaxis.

Martin (11) using CMV-IGIV 100 mg/kg every two weeks for six weeks followed by 50 mg/kg every two weeks with a final dose at week 16, in combination with ganciclovir 10 mg/kg/day for 14 days after transplantation, observed severe CMV disease in 1/74 (1%) of CMV seronegative recipients of a kidney from a CMV seropositive donor, in 0/14 (0%) of CMV seronegative recipients of a kidney-pancreas transplant from a CMV seropositive donor and in 1/12 (8%) of CMV seronegative recipients of a liver from a CMV seropositive donor. The incidence of serious CMV disease with combined CMV-IGIV and ganciclovir prophylaxis was lower than previous experience with single drug prophylaxis.

Valantine and Luikart (12) compared prophylaxis with CMV-IGIV (biweekly for three months) in combination with ganciclovir prophylaxis (IV at 5mg/kg bid for the initial 14 days post-transplant, then at 6 mg/kg through day 28) in 16 CMV seronegative recipients of hearts from CMV seropositive donors with 16 matched controls receiving ganciclovir alone. The actuarial incidence of CMV disease was reduced from 55% in the ganciclovir group to 46% in the combined group (p</=0.06) and survival was increased from 61% to 94% (p</=0.001). In heart-lung or lung transplant patients in whom either the donor or recipient was CMV seropositive, the actuarial incidence of CMV disease in patients receiving ganciclovir alone (n=25) was 85% as compared to 36% of the 33 patients receiving both CMV-IGIV and ganciclovir (p</=0.05). Survival was 60% in the ganciclovir group and 80% in patients receiving CMV-IGIV and ganciclovir (p</=0.01).


CytoGam® should not be used in individuals with a history of a prior severe reaction associated with the administration of this or other human immunoglobulin preparations. Persons with selective immunoglobulin A deficiency have the potential for developing antibodies to immunoglobulin A and could have anaphylactic reactions to subsequent administration of blood products that contain immunoglobulin A, including CytoGam®.

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. All infections should be reported directly to your physician and to the Massachusetts Public Health Biologic Laboratories (617-983-6400). Please discuss the risk and benefits of this product with your physician.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis and death (18-20). 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 practical. 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 400 mg/kg or greater) account for a disproportionate share of the total number. 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).


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) or 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. For patients judged to be at risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing CytoGam® at rate of 180mg Ig/kg/hour or less. 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 )

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.

An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with Immune Globulin Intravenous (Human) (IGIV) treatment (21-24). 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, 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.

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 INFUSION section). Do not use if the solution is turbid.

Drug Interactions:    Antibodies present in immune globulin preparation may interfere with the immune response to live virus vaccines such as measles, mumps, and rubella; therefore, vaccination with live virus vaccines should be deferred until approximately three months after administration of CytoGam®. If such vaccinations were given shortly after CytoGam®, a revaccination may be necessary. Admixtures of CytoGam® with other drugs have not been evaluated. It is recommended that CytoGam® be administered separately from other drugs or medications which the patient may be receiving (see DOSING AND ADMINISTRATION section).

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.


Minor reactions such as flushing, chills, muscle cramps, back pain, fever, nausea, vomiting, arthralgia, and wheezing were the most frequent adverse reactions observed during the clinical trials of CytoGam®. The incidence of these reactions during the clinical trials was less than 6.0% of all infusions and such reactions were most often related to infusion rates. A decrease in blood pressure was observed in 1 of 1039 infusions in clinical trials of CytoGam®. If a patient develops a minor side effect, slow the rate immediately or temporarily interrupt the infusion.

Increases in serum creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following IGIV infusion. Progression to oliguria or anuria requiring dialysis has been observed. Types of severe renal adverse events that have been seen following IGIV therapy include acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis (18-20).

Severe reactions such as angioneurotic edema and anaphylactic shock, although not observed during clinical trials, are a possibility. Clinical anaphylaxis may occur even when the patient is not known to be sensitized to immune globulin products. A reaction may be related to the rate of infusion; therefore, carefully adhere to the infusion rates as outlined under "DOSAGE AND ADMINISTRATION." If anaphylaxis or drop in blood pressure occurs, discontinue infusion and use antidote such as diphenhydramine and adrenalin.


Although few data are available, clinical experience with other immunoglobulin preparations suggests that the major manifestations would be those related to volume overload.


The maximum recommended total dosage per infusion is 150 mg Ig/kg, administered according to the following schedule.

Type of Transplant
Kidney Liver, Pancreas
Lung, Heart
72 hours of transplant:
150 mg/kg 150 mg/kg
 2 weeks post transplant:
100 mg/kg 150 mg/kg
 4 weeks post transplant
100 mg/kg 150 mg/kg
 6 weeks post transplant:
100 mg/kg 150 mg/kg
 8 weeks post transplant:
100 mg/kg 150 mg/kg
12 weeks post transplant:
 50 mg/kg 100 mg/kg
16 weeks post transplant:
 50 mg/kg 100 mg/kg

Preparation for Administration.    Remove the tab portion of the vial cap and clean the rubber stopper with 70% alcohol or equivalent. DO NOT SHAKE VIAL; AVOID FOAMING.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Infuse the solution only if it is colorless, free of particulate matter and not turbid.

Infusion.    Infusion should begin within 6 hours after entering the vial and should be complete within 12 hours of entering the vial. Vital signs should be taken preinfusion, mid-way and post-infusion as well as before any rate increase. CytoGam® should be administered through an intravenous line using an administration set that contains an in-line filter (pore size 15µ) and a constant infusion pump (i.e., IVAC pump or equivalent). A smaller in-line filter (0.2µ) is also acceptable. Pre-dilution of CytoGam® before infusion is not recommended.

CytoGam® should be administered through a separate intravenous line. If this is not possible, CytoGam® may be "piggybacked" into a pre-existing line if that line contains either Sodium Chloride, Injection, USP, or one of the following dextrose solutions (with or without NaCl added): 2.5% dextrose in water, 5% dextrose in water, 10% dextrose in water, 20% dextrose in water. If a pre-existing line must be used, the CytoGam® should not be diluted more than 1:2 with any of the above-named solutions. Admixtures of CytoGam® with any other solutions have not been evaluated.

Initial Dose.   Administer intravenously at 15 mg Ig per kg body weight per hour. If no adverse reactions occur after 30 minutes, the rate may be increased to 30 mg Ig/kg/hr; if no adverse reactions occur after a subsequent 30 minutes, then the infusion may be increased to 60 mg Ig/kg/hr (volume not to exceed 75 ml/hour). DO NOT EXCEED THIS RATE OF ADMINISTRATION. The patient should be monitored closely during and after each rate change.

Subsequent Doses.    Administer at 15 mg Ig/kg/hr for 15 minutes. If no adverse reactions occur, increase to 30 mg Ig/kg/hr for 15 minutes and then increase to a maximum rate of 60 mg Ig/kg/hr (volume not to exceed 75 ml/hour). DO NOT EXCEED THIS RATE OF ADMINISTRATION. The patient should be monitored closely during each rate change.

CytoGam® should be used with caution in patients with pre-existing renal insufficiency and in patients judged to be at increased risk of developing renal insufficiency (including, but not limited to those with diabetes mellitus, age greater than 65, volume depletion, paraproteinemia, sepsis and patients receiving known nephrotoxic drugs). In these cases especially, it is important to assure that patients are not volume depleted prior to CytoGam® infusion. While most cases of renal insufficiency have occurred in patients receiving total doses of 400 mg Ig/kg or greater, no prospective data are presently available to identify a maximum safe dose, concentration or rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum practicable. The product should be infused at a rate of 180 mg Ig/kg/hr or less.

Potential adverse reactions are: flushing, chills, muscle cramps, back pain, fever, nausea, vomiting, wheezing, drop in blood pressure. Minor adverse reactions have been infusion rate related--if the patient develops a minor side effects (i.e., nausea, back pain, flushing), slow the rate or temporarily interrupt the infusion. If anaphylaxis or drop in blood pressure occurs, discontinue infusion and use antidote such as diphenhydramine and adrenalin.

To prevent the transmission of hepatitis viruses or other infectious agents from one person to another, sterile disposable syringes and needles should be used. The syringes and needles should not be reused.


CytoGam®, Cytomegalovirus Immune Globulin Intravenous (Human), is supplied in two single-dose vial forms:

NDC No. Total Quantity of
Volume Concentration
60574-3102-1 1000 mg ± 200 mg 20 ml 50 ± 10 mg/ml
60574-3101-1 2500 mg ± 500 mg 50 ml 50 ± 10 mg/ml


CytoGam® should be stored between 2° C and 8° C (35.6° F and 46.4° F), and used within 6 hours after entering the vial.


  1. Snydman DR, Melver J, Leszczynski J, et al. A pilot trial of a novel cytomegalovirus immune globulin in renal transplant recipients. Transplantation 38:553-557, 1984.
  2. Horowitz B, Wiebe ME, Lippin A, et al. Inactivation of viruses in labile blood derivatives. Transfusion; 25:516-522, 1985.
  3. Snydman DR, Werner BG, and Heinze-Lacey BH, et al. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal transplant recipients. NEJM 317:1049-1054, 1987.
  4. Snydman DR, Werner BG, Dougherty NN et al. Cytomegalovirus Immune Globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial. Ann Int Med 119:984-991, 1993.
  5. Falagas ME, Snydman DR, Ruthazer R. et al. Cytomegalovirus Immune Globulin (CMVIG) prophylaxis is associated with increased survival after orthotopic liver transplantation. Clin Transplantation, 11:432-437, 1997.
  6. Snydman DR, Werner BG, Tilney NL, et al. A final analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus immune globulin: Comparison of randomized and open-label trials. Transplant Proceed 23:1357-1360, 1991.
  7. Snydman DR, Werner BG, Dougherty NN, et al. A further analysis of the use of Cytomegalovirus Immune Globulin in orthotopic liver transplant patients at risk for primary infection. Transplant Proceed 26, suppl 1:23-27, 1994.
  8. Merigan TC, Renlund DG, Keay S et al. A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation. NEJM 326:1182-1186, 1992.
  9. Ham JM, Shelden SR, Godkin RR, et al. Cytomegalovirus prophylaxis with ganciclovir, acyclovir and CMV hyperimmune globulin in liver transplant patients receiving OKT3 induction. Transplant Proc 1995; 27 (5 suppl 1):31-33.
  10. Snydman DR. Combined CMV-IGIV and ganciclovir prophylaxis in CMV seronegative transplant recipients from CMV seropositive donors. Report on file, MedImmune, Inc.
  11. Martin M. CMV prophylaxis with combination ganciclovir and CMV hyperimmune globulin followed by high-dose acyclovir in solid organ transplant recipients. Report on file, MedImmune, Inc.
  12. Valantine H and Luikart H. Impact of CMV hyperimmune globulin on outcome after cardiothoracic transplantation: A comparative study of combined prophylaxis with CMVIG plus ganciclovir vs. ganciclovir alone. Report on file, MedImmune, Inc.
  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 vol. 35:231-233, April 11, 1996.
  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 26:210-213, 1986.
  15. McIver J, Grady G. Immunoglobulin preparations. In: Churchill WH and Kurtz SR, (ed): Transfusion Medicine. Boston: Blackwell; 1988.
  16. Schneider L, Geha R. Outbreak of Hepatitis C associated with intravenous immunoglobulin administration--United States, October 1993-June 1994. MMWR vol. 43:505-509, July 22, 1994.
  17. Edwards CA, Piet MPJ, Chin S, et al. Tri(nButyl) phosphate detergent treatment of licensed therapeutic and experimental blood derivatives. Vox Sang 52:53-59, 1987.
  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 Nephrology; 8: 1788-1793, 1997.
  19. Cantu TG, Hoehn-Saric EW, Burgess KM et al. Acute renal failure associated with immunoglobulin therapy. Am J. Kidney Dis; 25: 228-234, 1995.
  20. Hansen-Schmidt S., Silomon J, Keller F. Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin a nephritis. Am. J. Kidney Dis.; 28: 451-453, 1996.
  21. Sekul E, Culper E, Dalaks M. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy; Frequency and risk factors. Ann Int Med; 123:259-262, 1994.
  22. Kato E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA; 259:3269-3270, 1988.
  23. Casteels Van Daele M, Wijndaele L, Hunnick K, et al. Intravenous immunoglobulin and acute aseptic meningitis. NEJM; 323:614-615, 1990.
  24. Scribner C, Kapit R, Philips E, et al. Aseptic meningitis and intravenous immunoglobulin therapy. Ann Intern Med; 121:305-306, 1994.

For additional information concerning Cytomegalovirus Immune Globulin Intravenous (Human) contact:

Professional Services

MedImmune, Inc.

35 West Watkins Mill Road

Gaithersburg, MD 20878, USA


Manufactured by:



Boston, Massachusetts 02130, USA

U.S. Govt. License No. 64

Marketed by:

MedImmune Inc.

35 W. Watkins Mill Road

Gaithersburg, MD 20878

Revised April 2000


NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.