CytoGam

Cytomegalovirus (CMV) Antitoxins and Immunoglobulins

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Solution should be colorless, free of particulate matter, and not turbid.

Cytomegalovirus immune globulin (Cytogam) is administered intravenously.
Admixtures of CytoGam with other drugs have not been evaluated. It is recommended that CytoGam be administered separately from other parenteral drugs or medications that the patient may be receiving.
Reconstitution:
Reconstitute the lyophilized powder with 50 mL of sterile water for injection.
Do not shake the vials; avoid foaming.
Rotate vial gently to wet all undissolved powder; allow 30 minutes for dissolving powder.
IV infusion:
Begin infusion within 6 hours of reconstitution and complete within 12 hours.
Administer through a separate IV line using an administration set that contains an in-line filter (pore size 15 microns) and a constant infusion pump (i.e., IVAC pump or equivalent). A smaller in-line filter (0.2 microns) is also acceptable.
Solution may be piggybacked, if necessary, into preexisting line running 0.9% Sodium Chloride injection, 5% Dextrose injection, or 5% Dextrose and 0.9% Sodium Chloride injection combinations. Do not dilute CMV-IGIV more than 1:2 dilution.
The initial infusion rate should be 15 mg/kg/hour. If no adverse reactions occur after 30 minutes, increase dose to 30 mg/kg/hour. If no adverse reactions occur after 30 more minutes, increase dose to 60 mg/kg/hour. Total volume should not exceed 75 mL/hour.

anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
apnea / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
cyanosis / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
retinal thrombosis / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
cardiac arrest / Early / Incidence not known
hemolytic anemia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
oliguria / Early / Incidence not known
osmotic nephrosis / Early / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
anuria / Delayed / Incidence not known
coma / Early / Incidence not known
seizures / Delayed / Incidence not known
aseptic meningitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known

wheezing / Rapid / 0-6.0
hypotension / Rapid / Incidence not known
hypoxia / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
paresis / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
hemolysis / Early / Incidence not known
leukopenia / Delayed / Incidence not known
photophobia / Early / Incidence not known
bullous rash / Early / Incidence not known

arthralgia / Delayed / 0-6.0
fever / Early / 0-6.0
nausea / Early / 0-6.0
vomiting / Early / 0-6.0
muscle cramps / Delayed / 0-6.0
chills / Rapid / 0-6.0
back pain / Delayed / 0-6.0
flushing / Rapid / 0-6.0
pallor / Early / Incidence not known
drowsiness / Early / Incidence not known
tremor / Early / Incidence not known
headache / Early / Incidence not known
abdominal pain / Early / Incidence not known

CytoGam

Rx

Immunoglobulin product with a high titer of CMV-IVIG; used to attenuate primary CMV disease associated with organ or bone marrow transplantation.

150 mg/kg by IV infusion administered within 72 hours posttransplant. Subsequent single IV doses of 100 mg/kg are administered at 2, 4, 6, and 8 weeks posttransplant. Then, the dosage is decreased to 50 mg/kg IV as a single dose during weeks 12 and 16 posttransplant.

150 mg/kg IV given within 72 hours of transplant. Subsequent single doses of 150 mg/kg IV are given 2, 4, 6, and 8 weeks following transplantation. Then, the dosage is decreased to 100 mg/kg IV as a single dose during weeks 12 and 16 posttransplant. The manufacturer recommends consideration of adding ganciclovir in these patients. The efficacy of CMV-IVIG in preventing CMV and related infections was studied in a trial of patients receiving CMV-positive liver transplants. CMV-IVIG reduced the incidence of severe CMV-associated disease, including CMV pneumonia, multiorgan CMV disease, and invasive fungal disease in all serologic groups, regardless of recipient/donor CMV serologic status, except for the CMV-seropositive donor/CMV-seronegative recipient group.

In 1 study, bone marrow transplant patients were randomized to receive CMV-IVIG 200 mg/kg IV on days 8 and 6 pretransplant, on the day after marrow infusion, and on days 7, 14, 21, 28, 42, 56, and 70 for a total of 10 doses or no CMV-IVIG as primary prophylaxis of CMV infection. Although CMV viremia and excretion were less in the active drug group, there was no difference between groups with regard to clinical CMV disease.

150 mg/kg/dose IV twice weekly or 400 mg/kg/dose IV every other day for 3 to 5 doses as adjunctive therapy in combination with IV ganciclovir. Guidelines in hematopoietic stem cell transplant (HSCT) recipients and other oncology patients recommend consideration of adjunctive intravenous immunoglobulin (IVIG) for CMV pneumonia. For solid organ transplant recipients, adjunctive immunoglobulin therapy is not routinely recommended.

†Indicates off-label use

No dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations. (Major) Rubella Virus Vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of immunoglobulins because antibodies in these products can neutralize the vaccine.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Rubella Virus Vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of immunoglobulins because antibodies in these products can neutralize the vaccine.
Rotavirus Vaccine: (Major) Defer vaccination with live virus vaccines such as Rotavirus Vaccine until approximately 3 months after Cytomegalovirus immune globulin administration. Inform the immunizing physician of recent therapy with the immune globulin so that appropriate measures can be taken. The efficacy of live attenuated virus vaccines such as Rotavirus Vaccine may be impaired by Cytomegalovirus immune globulin administration; revaccination may be necessary. The passive transfer of antibodies from the immune globulin may impair the efficacy of live attenuated virus vaccines.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.

CytoGam/Cytomegalovirus Immune Globulin (Human) Intravenous Inj Sol: 1mL, 50mg

150 mg/kg/dose IV; higher doses of 400 mg/kg IV have been given off-label for the treatment of CMV pneumonitis.

150 mg/kg/dose IV; higher doses of 400 mg/kg IV have been given off-label for the treatment of CMV pneumonitis.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Cytomegalovirus immune globulin (CMV-IGIV) raises the relevant CMV antibodies to concentrations sufficient to attenuate or reduce the incidence of serious CMV disease. CMV—IGIV is primarily comprised of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. IgG1 and IgG3 are involved in viral neutralization, as well as, tissue protection and complement activation. Immunoglobulins, such as CMV-IGIV, inhibit the ability of extracellular viruses to infect their target cells. Viral neutralization limits the capacity of viruses to spread from an extracellular focus to an intracellular location. CMV-IGIV inhibits infection of cells with CMV because the virus cannot fix to key cell membrane targets, or because of interference with uncoating or entry.

Cytomegalovirus immune globulin (CMV-IGIV) is administered intravenously. CMV—IGIV is primarily comprised of immunoglobulin G (IgG), specifically subclasses IgG1 and IgG3. IgG is distributed from the plasma to other body compartments. Immunoglobulin catabolism occurs primarily in the plasma, but the liver may also have a role. IgG metabolism appears to be a multicompartmental, first-order process. Higher IgG concentrations increase the rate of metabolism and the shorten the half-life. The mean half-life of IgG is dependent on the subclass of the immunoglobulin. IgG1 has a half-life of 23—25 days, whereas, the half-life of IgG3 is only 9 days.

Protection derived from Cytomegalovirus immune globulin (CMV-IGIV) has a rapid onset, imparting relevant CMV antibody concentrations immediately after infusion. The duration of action of CMV-IGIV is 1—3 months.

No well-controlled studies have been conducted in pregnant women and it is not known if cytomegalovirus immune globulin (CMV-IGIV) can cause female harm or affect the reproductive system. According to the Advisory Committee on Immunization Practices, administration of immune globulin during pregnancy results in no known risk to the fetus. Administer CMV-IGIV to pregnant women only if clearly needed.

No data are available from the manufacturer regarding use of cytomegalovirus immune globulin (CMV-IGIV) during breast-feeding and it is not known if CMV-IGIV is excreted in breast milk. Case reports of two nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.