CYTOGAM (cytomegalovirus immune globulin (human))

Drug overview for CYTOGAM (cytomegalovirus immune globulin (human)):

Generic name: cytomegalovirus immune globulin (human) (CMV ih-MYOON GLOB-you-lin)
Drug class: Cytomegalovirus (CMV) Immune Globulin
Therapeutic class: Biologicals

Cytomegalovirus immune globulin IV (CMV-IGIV) is a specific immune globulin (hyperimmune globulin). CMV-IGIV contains immunoglobulin G (IgG) prepared from plasma of adults selected for high titers of CMV antibody.

Cytomegalovirus immune globulin IV (CMV-IGIV) is used to provide passive immunity to cytomegalovirus (CMV) in certain individuals at risk for primary CMV infection or disease or secondary) CMV disease (reactivation of CMV). CMV-IGIV has been designated an orphan drug by the US Food and Drug Administration (FDA) for the prevention or attenuation of primary CMV disease in immunosuppressed organ transplant recipients. CMV-IGIV is labeled by the FDA for prophylaxis of CMV disease in CMV-seronegative or CMV-seropositive recipients of kidney, liver, lung, pancreas, or heart transplant.

With the exception of CMV-seronegative recipients of kidneys from CMV-seropositive donors, CMV-IGIV prophylaxis should be considered in conjunction with ganciclovir. CMV-IGIV has been used in an attempt to prevent primary or secondary CMV disease in allogeneic bone marrow transplant (BMT) patients+; however, the role of the immune globulin in this patient population is less clearly established than its role in solid organ transplant recipients. CMV-IGIV also has been used in conjunction with ganciclovir for the treatment of CMV pneumonitis+ in transplant recipients, and has been designated an orphan drug by the FDA for use in conjunction with ganciclovir for the treatment of CMV pneumonia in bone marrow transplant recipients.

Ensuring that CMV-seronegative transplant recipients receive only blood products that have been screened for CMV and organs or bone marrow from CMV-seronegative donors substantially decreases the risk for posttransplant CMV infection and disease in these individuals; however, CMV-seronegative donors may not be available since 40-100% of adults in the US have serologic evidence of CMV infection. (See Pharmacology: Cytomegalovirus and Infection.) Therefore, various strategies have been used for CMV prophylaxis in solid organ transplant or BMT patients at risk for primary CMV infection or disease or for reactivation of CMV, including short- or long-term antiviral agent prophylaxis and/or passive immunization with CMV-IGIV or immune globulin IV (IGIV). In addition, as an alternative to routine CMV prophylaxis, selective use of preemptive antiviral agent therapy (initiated after transplant based on detection of CMV) with or without CMV-IGIV has been used for the prevention of CMV disease in transplant patients.

Each of these strategies has certain advantages and disadvantages and all have limited efficacy since no regimen has been found to effectively and consistently prevent active CMV disease in all individuals at risk. A meta-analysis of 11 prospective, randomized trials evaluating use of CMV-IGIV for CMV prevention in solid organ transplant recipients indicated that such prophylaxis was associated with reduced CMV disease, reduced all-cause mortality, and reduced CMV-associated deaths (except in those undergoing kidney transplantation), but did not reduce CMV infection and had no effect on the incidence of rejection episodes. However, another data analysis of randomized (or quasi-randomized), controlled trials indicated that use of CMV-IGIV or IGIV in solid organ transplant recipients did not reduce the risk of CMV disease, CMV infection, or all-cause mortality compared with placebo or no treatment and that use of CMV-IGIV or IGIV in conjunction with antivirals (acyclovir, ganciclovir) was no more effective than use of the antiviral alone in reducing the risk of CMV disease or all-cause mortality.

Further study is needed to identify optimum regimens for CMV prophylaxis based on the degree of risk associated with the CMV status of the patient prior to transplant (i.e., CMV-seronegative or -seropositive), the particular transplant procedure (i.e., kidney, liver, lung, heart, bone marrow), and immunosuppressive regimen administered. In addition, further study is needed to compare the relative efficacy and safety of routine CMV prophylaxis with that of preemptive CMV therapy and to identify which patients would derive the most benefit from these differing strategies. The relative efficacy and safety of CMV-IGIV and IGIV for the prevention of CMV disease in solid organ transplant recipients or allogeneic BMT patients have not been clearly established in prospective, randomized, controlled studies. While it is unclear whether CMV-IGIV offers any therapeutic advantage over IGIV, some clinicians suggest that CMV-IGIV may be preferred if an immune globulin is used for CMV prophylaxis in solid organ transplant recipients since it contains a standardized CMV antibody content that is 4-8 times higher than that contained in IGIV.