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  • CLASSES

    Disease-Specific Immunoglobulins - Antiviral

    DEA CLASS

    Rx

    DESCRIPTION

    Globulin fraction of human plasma; consists of high titers of varicella-zoster IgG
    Used for post-exposure prophylaxis of varicella in high risk individuals
    Severe hypersensitivity reactions may occur

    COMMON BRAND NAMES

    VARIZIG

    HOW SUPPLIED

    VARIZIG Intramuscular Inj Pwd F/Sol: 125IU
    VARIZIG Intramuscular Inj Sol: 125IU

    DOSAGE & INDICATIONS

    For post-exposure varicella (chickenpox) infection prophylaxis to reduce varicella severity in high-risk patients defined as premature neonates, neonates and infants < 1 year old, pregnant women, newborns of women with varicella shortly before or after delivery, immunocompromised children and adults without a past history of varicella unless the patient is undergoing a bone marrow transplantation, and adults without evidence of immunity.
    NOTE: Varicella-zoster immune globulin has an orphan drug status for the passive immunization of exposed, susceptible individuals who are at risk of complications from varicella.
    Intramuscular dosage
    Adults

    Administer as soon as possible after exposure and within 10 days (ideally within 96 hours). Consider a second dose if additional varicella exposures occur >= 3 weeks after initial administration. Dosage based on bodyweight :
    >= 40.1 kg: 625 International units (5 vials) IM.
    30.1—40 kg: 500 International units (4 vials) IM.
    20.1—30 kg: 375 International units (3 vials) IM.

    Premature Neonates, Neonates, Infants, Children, and Adolescents

    Administer as soon as possible after exposure and within 10 days (ideally within 96 hours). Consider a second dose if additional varicella exposures occur >= 3 weeks after initial administration. Dosage is based on bodyweight :
    >= 40.1 kg: 625 International Units/dose (5 vials) IM.
    30.1—40 kg: 500 International Units/dose (4 vials) IM.
    20.1—30 kg: 375 International Units/dose (3 vials) IM.
    10.1—20 kg: 250 International Units/dose (2 vials) IM.
    2.1—10 kg: 125 International Units/dose (1 vial) IM.
    <= 2 kg: 62.5 International Units/dose (one-half vial) IM.

    MAXIMUM DOSAGE

    Adults

    >= 40.1 kg: 625 International units/dose IM.
    30.1—40 kg: 500 International units/dose IM.
    20.1—30 kg: 375 International units/dose IM.

    Geriatric

    >= 40.1 kg: 625 International units/dose IM.
    30.1—40 kg: 500 International units/dose IM.
    20.1—30 kg: 375 International units/dose IM.

    Adolescents

    >= 40.1 kg: 625 International units/dose IM.
    30.1—40 kg: 500 International units/dose IM.
    20.1—30 kg: 375 International units/dose IM.
    10.1—20 kg: 250 International units/dose IM.

    Children

    >= 40.1 kg: 625 International units/dose IM.
    30.1—40 kg: 500 International units/dose IM.
    20.1—30 kg: 375 International units/dose IM.
    10.1—20 kg: 250 International units/dose IM.
    2.1—10 kg: 125 International units/dose IM.

    Infants

    10.1—20 kg: 250 International units/dose IM.
    2.1—10 kg: 125 International units/dose IM.
    < 2 kg: 62.5 International units/dose IM.

    Neonates

    2.1—10 kg: 125 International units/dose IM.
    <= 2 kg: 62.5 International units/dose IM.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that 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. Do not use if turbid and/or discoloration is observed.

    Intramuscular Administration

    Reconstitution:
    Reconstitute the vial(s) shortly before planned administration to the patient. Using aseptic technique, add 1.25 ml of the supplied sterile diluent to a vial; direct the diluent to the side of the vial. Do not use any other diluent for reconstitution. Gently tilt and invert the vial to wet the pellet; avoid frothing. Gently swirl the upright vial until dissolved (< 10 minutes). Do not shake.
    Storage: Store the reconstituted product at 2—8 degrees C (36—46 degrees F) for up to 12 hours before use. Do not freeze. Discard any unused reconstituted product or diluent.
     
    Intramuscular injection:
    Do not exceed 3 ml per injection site; if needed, divide the dose and administer in at least 2 injection sites such as the deltoid muscle or the anterolateral aspects of the upper thigh. Do not use the gluteal region as a routine injection site. If the gluteal region is used, only use the upper, outer quadrant because of the risk of sciatic nerve injury.

    STORAGE

    VARIZIG:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    IgA deficiency

    Varicella-zoster immune globulin is contraindicated for use by patients known to have anaphylactic or severe systemic reactions to human immune globulin preparations. Varicella-zoster immune globulin is also contraindicated for use by IgA-deficient patients with antibodies against IgA and a history of hypersensitivity, as they may have an anaphylactoid reaction. Patients with IgA deficiency often develop antibodies against IgA and are more likely to have anaphylactic or immune-mediated adverse reactions to pooled immunoglobulin products. Varicella-zoster immune globulin has < 40 mcg/ml of IgA.

    Infection

    As with other products derived from or purified with human blood components, the possibility of transmission of infectious agents such as the variant Creutzfeldt-Jakob disease agent and, theoretically, the Creutzfeldt-Jakob disease agent exists in patients receiving varicella-zoster immune globulin. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of infection transmission from varicella-zoster immune globulin. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. Discuss the risks and benefits of this product with the patient before administration.

    Coagulopathy, hemophilia, thrombocytopenia

    Only administer varicella-zoster immune globulin to patients who have severe thrombocytopenia or any coagulopathy like hemophilia that would contraindicate intramuscular injections if the expected benefits outweigh the potential risks.

    Pregnancy

    Varicella-zoster immune globulin is indicated for post-exposure prophylaxis in high-risk patients such as pregnant women. The manufacturer recommends use during pregnancy only when clearly needed; FDA pregnancy category C drug. According to the recommendations of the Advisory Committee on Immunization Practices, strongly consider varicella zoster immune globulin for pregnant women without evidence of immunity who have been exposed because pregnant women might be at higher risk for severe varicella and complications. Administration of varicella-zoster immune globulin to these women has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella. Thus, the primary indication for varicella-zoster immune globulin in pregnant women is to prevent complications of varicella in the mother rather than to protect the fetus.

    Breast-feeding

    No data are available from the manufacturer regarding use of varicella-zoster immune globulin during breast-feeding; excretion into breast milk is unknown. 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.

    Vaccination

    The immune globulins present in varicella-zoster immune globulin may impair the efficacy of live virus vaccination such as measles, mumps or rubella (MMR). Antibodies in immune globulin products may interfere with patient responses to live vaccines because the continued presence of high concentrations of passively acquired antibody may interfere with an active antibody response. Live virus vaccinations should be delayed until approximately 3 months after varicella-zoster immune globulin administration; it may be necessary to revaccinate persons who receive varicella-zoster immune globulin shortly after receiving live virus vaccinations. Tell the immunizing physician about recent therapy with immune globulin products.

    Cardiac disease, coronary artery disease, diabetes mellitus, geriatric, heart failure, hypertriglyceridemia, obesity, thromboembolic disease

    Thrombotic events may occur during or after treatment with immune globulin products. Cautious use of varicella-zoster immune globulin is warranted in patients with a history of cardiac disease or thromboembolic disease. Patients at risk for thrombotic events are geriatric patients, those with a history of atherosclerosis (coronary artery disease), multiple cardiovascular risk factors, impaired cardiac output (heart failure), coagulation disorders, prolonged periods of immobilization, obesity, diabetes mellitus, acquired or inherited thrombophilic disorder, a history of vascular disease, a history of a previous thrombotic or thromboembolic event, and/or known or suspected hyperviscosity. Assessment of baseline blood viscosity may be warranted for patients at risk for hyperviscosity such as those with cryoglobulins, fasting chylomicronemia, hypertriglyceridemia, or monoclonal gammopathies.

    ADVERSE REACTIONS

    Severe

    serum sickness / Delayed / 0-1.0
    anaphylactic shock / Rapid / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    erythema / Early / Incidence not known

    Mild

    injection site reaction / Rapid / 2.0-9.0
    headache / Early / 2.0-4.0
    fatigue / Early / 0-2.0
    chills / Rapid / 0-2.0
    rash (unspecified) / Early / Incidence not known
    nausea / Early / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Efficacy of live attenuated virus vaccines such as measles/mumps/rubella Vaccines, MMR; rotavirus vaccine; and varicella virus vaccine live may be impaired by varicella-zoster immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after varicella-zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken.
    Measles/Mumps/Rubella Vaccines, MMR: (Major) Efficacy of live attenuated virus vaccines such as measles/mumps/rubella Vaccines, MMR; rotavirus vaccine; and varicella virus vaccine live may be impaired by varicella-zoster immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after varicella-zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken.
    Rotavirus Vaccine: (Major) Defer vaccination with live virus vaccines until approximately 3 months after Varicella Zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken. The efficacy of live attenuated virus vaccines such as Rotavirus Vaccine may be impaired by Varicella Zoster 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) Efficacy of live attenuated virus vaccines such as measles/mumps/rubella Vaccines, MMR; rotavirus vaccine; and varicella virus vaccine live may be impaired by varicella-zoster immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after varicella-zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken.

    PREGNANCY AND LACTATION

    Pregnancy

    Varicella-zoster immune globulin is indicated for post-exposure prophylaxis in high-risk patients such as pregnant women. The manufacturer recommends use during pregnancy only when clearly needed; FDA pregnancy category C drug. According to the recommendations of the Advisory Committee on Immunization Practices, strongly consider varicella zoster immune globulin for pregnant women without evidence of immunity who have been exposed because pregnant women might be at higher risk for severe varicella and complications. Administration of varicella-zoster immune globulin to these women has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella. Thus, the primary indication for varicella-zoster immune globulin in pregnant women is to prevent complications of varicella in the mother rather than to protect the fetus.

    No data are available from the manufacturer regarding use of varicella-zoster immune globulin during breast-feeding; excretion into breast milk is unknown. 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

    Varicella-zoster immune globulin is a preparation of purified human immune globulin G (IgG) containing antibodies to varicella zoster virus and, thus, provides passive immunization for non-immune individuals exposed to the varicella zoster virus. The product may reduce the severity of varicella infections. No convincing evidence exists that the product reduces the incidence of chickenpox infection after exposure to the virus or that established varicella infections can be modified with the product. Of note, varicella-zoster immune globulin might extend the incubation period of the virus from 10—21 days to >= 28 days.

    PHARMACOKINETICS

    Varicella-zoster immune globulin is administered via intramuscular (IM) injection. Antibody protection against the varicella zoster virus generally lasts for 3 weeks after product administration in both children and adults. The exact fate of human immunoglobulin products is not well defined, but the mean serum half-life is 26.2 +/- 4.6 days after receipt of 12.5 International units/kg IM.

    Intramuscular Route

    The mean peak of varicella antibodies occurred 4.5 +/- 2.8 days after receipt of 12.5 International units/kg IM. Administer varicella-zoster immune globulin as soon as possible after varicella zoster virus exposure.