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  • CLASSES

    Disease-Specific Immunoglobulins - Antiviral

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    CytoGam

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For primary cytomegalovirus (CMV) disease prophylaxis after organ transplantation, including kidney, lung, liver, pancreas, and heart transplantation.
    NOTE: Cytomegalovirus immune globulin has been designated an orphan drug by the FDA for this indication.
    In CMV seronegative recipients of a renal allograft from a CMV seropositive donor.
    Intravenous dosage
    Adults

    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.

    In CMV seronegative recipients of a heart, liver, lung, or pancreas allograft from a CMV seropositive donor.
    Intravenous dosage
    Adults

    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 CMV seronegative recipients of a bone marrow allograft from a CMV seropositive donor†.
    Intravenous dosage
    Adults

    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.

    For the treatment of cytomegalovirus (CMV) pneumonitis† in combination with ganciclovir in recipients of a bone marrow allograft.
    NOTE: Cytomegalovirus immune globulin has been designated an orphan drug by the FDA for this indication.
    Intravenous dosage (in combination with ganciclovir)
    Adults

    In a small open study, CMV-IGIV 400 mg/kg IV was administered on days 1, 2, and 7, then 200 mg/kg IV was administered on day 14 in combination with 14 days of ganciclovir IV for treatment of CMV pneumonia. Patients who were still symptomatic were given an additional 200 mg/kg dose on day 21. Thirteen of 25 patients treated with this 2-drug combination survived and the authors concluded this success rate was higher than with other regimens.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

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

    Elderly

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

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

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

    ADMINISTRATION

    Injectable Administration

    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.

    Intravenous Administration

    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.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from freezing
    - Refrigerate (between 36 and 46 degrees F)
    CytoGam:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store product in refrigerator (36 to 46 degrees F) and use within 6 hours after opening

    CONTRAINDICATIONS / PRECAUTIONS

    IgA deficiency, sucrose hypersensitivity

    Cytomegalovirus immune globulin (CMV-IGIV) is contraindicated for use by patients with a history of a prior severe reaction associated with the administration of CMV-IGIV or other human immunoglobulin (Ig) preparations (human immunoglobulin hypersensitivity). Persons with selective IgA 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 such as CMV-IGIV. Use caution in patients with sucrose hypersensitivity because CMV-IVIG contains sucrose.

    Pregnancy

    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.

    Breast-feeding

    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.

    Agammaglobulinemia, hypogammaglobulinemia

    Patients with agammaglobulinemia or severe hypogammaglobulinemia are at an increased risk of developing immune-mediated adverse reactions if they have not received immunoglobulins in the preceding 8 weeks or if they have never received CMV-IGIV.

    ADVERSE REACTIONS

    Severe

    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

    Moderate

    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

    Mild

    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

    DRUG INTERACTIONS

    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.
    Rubella Virus Vaccine Live: (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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.

    Intravenous Route

    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.