Varicella Zoster Immune Globulin (Monograph)

Brand name: Varizig
Drug class: Antitoxins and Immune Globulins
ATC class: J06BB03
VA class: IM100

Medically reviewed by Drugs.com on May 20, 2024. Written by ASHP.

Introduction

Specific immune globulin (hyperimmune globulin). Varicella zoster immune globulin (VZIG) contains IgG prepared from plasma of donors selected for high titers of antibodies to varicella zoster virus (anti-VZV), and is used to provide temporary passive immunity to VZV.

Uses for Varicella Zoster Immune Globulin

Postexposure Prophylaxis of Varicella

Postexposure prophylaxis of varicella (chickenpox) in individuals without evidence of varicella immunity who are at high risk for severe varicella disease and complications. Designated an orphan drug by FDA for passive immunization in exposed, susceptible individuals at risk for varicella complications.

VZIG postexposure prophylaxis intended to reduce severity of varicella in susceptible, high-risk individuals; provides maximum benefit when administered as soon as possible (ideally within 96 hours) after VZV exposure. (See Dosage and Administration.) Manufacturer states there is no convincing evidence that VZIG reduces incidence of varicella after VZV exposure and no convincing evidence that VZIG would modify an established VZV infection.

US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that evidence of varicella immunity includes any of the following: documentation of age-appropriate varicella vaccination (1 dose of varicella vaccine in preschool children ≥12 months of age or 2 doses in school-aged children, adolescents, and adults), laboratory evidence of immunity or laboratory confirmation of prior varicella infection, birth in US before 1980 (US birth before 1980 not considered evidence of immunity for immunocompromised individuals, pregnant women, or health-care personnel), or history of varicella or herpes zoster (shingles, zoster) diagnosed or verified by a health-care provider. Consider individuals without such evidence susceptible to varicella.

Immunocompromised children, adolescents, and adults without evidence of varicella immunity exposed to VZV within the last 10 days should receive VZIG for postexposure prophylaxis. This includes those with primary or acquired immunodeficiency disorders (including HIV infection), neoplastic disease, or receiving immunosuppressive therapy. (See Individuals with Altered Immunocompetence under Cautions.) VZIG probably not necessary in those receiving immune globulin IV (IGIV) replacement therapy (≥400 mg/kg once monthly) if last IGIV dose was administered ≤3 weeks before exposure since such individuals are likely to be protected from VZV.

Neonates whose mothers had signs and symptoms of varicella at time of delivery (i.e., from 5 days before to 2 days after delivery) should receive VZIG for postexposure prophylaxis. Such neonates are at risk of severe, potentially fatal varicella and should receive VZIG regardless of whether the mother received VZIG. VZIG not necessary in neonates whose mothers had signs and symptoms of varicella >5 days before delivery since such infants should be protected from severe varicella by transplacentally acquired maternal antibody. VZIG not indicated in full-term neonates exposed postnatally to varicella (including those born to mothers who develop varicella >48 hours after delivery). Some clinicians recommend VZIG in exposed neonates who have severe skin disease and were born to mothers without evidence of immunity.

Certain premature neonates exposed to VZV during neonatal period should receive VZIG postexposure prophylaxis. Evaluate premature infants with substantial postnatal VZV exposure on an individual basis. VZIG recommended for premature neonates born at <28 weeks of gestation or with birthweight ≤1 kg who are exposed during neonatal period, regardless of mother's history of varicella or varicella vaccination. Also recommended for premature neonates born at ≥28 weeks of gestation who are exposed during neonatal period and have a mother without evidence of varicella immunity.

Pregnant women without evidence of varicella immunity exposed to VZV within the last 10 days should receive VZIG postexposure prophylaxis.

VZIG provides temporary passive immunity and may prevent or reduce severity of VZV infection if administered within 10 days after exposure.

Vaccination with varicella vaccine is preferred for postexposure prophylaxis in immunocompetent individuals exposed to VZV who have not previously received age-appropriate varicella vaccination and do not have evidence of varicella immunity.

When varicella vaccine is contraindicated or cannot be used and VZIG is unavailable, consider use of IGIV as an alternative since it contains anti-VZV.

Make decision to administer VZIG on an individual basis, depending on whether patient lacks evidence of varicella immunity, exposure is likely to result in infection, and patient is at greater risk for varicella complications than the general population.

ACIP states that exposures likely to result in varicella in susceptible individuals (i.e., those without evidence of varicella immunity) involve direct contact (i.e., face-to-face contact with an infectious person while indoors). Duration of face-to-face contact warranting postexposure prophylaxis with VZIG not certain. Some experts suggest VZIG if duration of close contact was >5 minutes; others define close contact as >1 hour. Susceptible individuals with continuous exposure to household members with varicella or disseminated herpes zoster are at greatest risk for infection. For hospital contacts, substantial exposure consists of sharing the same hospital room or direct face-to-face contact with an infectious person (e.g., health-care personnel).

Do not use for postexposure prophylaxis of varicella in immunocompromised children, adolescents, or adults with past history of varicella, unless individual is undergoing bone marrow transplantation.

VZIG not useful for treatment of clinical varicella or herpes zoster or for prevention of disseminated herpes zoster and not recommended for such use.

Varicella Zoster Immune Globulin Dosage and Administration

General

Provides maximum benefit when administered as soon as possible after VZV exposure. Ideally, administer within 4 days (96 hours) after VZV exposure. May be given within 10 days after exposure, preferably as soon as possible. (See Limitations of Effectiveness under Cautions.)

Previously available in US only under an investigational new drug application (IND) expanded access protocol; now approved by FDA and available commercially.

Administration

Labeled by FDA for IM injection only; has been administered by IV injection^{† [off-label]}.

Do not mix with any other drug or solution.

Do not administer concomitantly with varicella vaccine. (See Specific Drugs and Laboratory Tests under Interactions.)

IM Administration

Administer IM into deltoid muscle or anterolateral aspect of upper thigh.

Because of risk of injection-associated injury to sciatic nerve, use gluteal region only when necessary and use only the upper, outer quadrant.

Divide IM dose and administer into at least 2 IM injection sites, depending on patient size. Do not exceed 3 mL of reconstituted VZIG at each IM injection site.

Reconstitution

Reconstitute lyophilized powder by adding 1.25 mL of sterile diluent supplied by manufacturer to 125-unit vial using a suitable syringe and needle. Inject diluent slowly at an angle so that liquid is directed onto inside of vial wall. Wet pellet by gently tilting and inverting vial. Avoid frothing. Gently swirl upright vial until pellet dissolves (<10 minutes); do not shake.

Reconstituted solution for IM administration contains 100 units/mL.

Immediately prior to use, inspect visually for particulate matter and discoloration; do not use if turbid and/or discolored.

Vials are single-use only; after dose is given, discard partially used reconstituted vials and any remaining diluent.

Reconstituted solution may be stored for up to 12 hours at 2–8°C. (See Storage under Stability.)

Dosage

Pediatric Patients

Postexposure Prophylaxis of Varicella

Neonates (Including Premature Neonates)

IM

Single dose based on body weight. (See Table 1.)

Give dose as soon as possible after VZV exposure (ideally within 96 hours); may be given within 10 days of exposure.

Second dose can be considered in high-risk individuals if another VZV exposure occurs ≥3 weeks after first dose.

Susceptible Immunocompromised Children and Adolescents <18 Years of Age

IM

Single dose based on body weight. (See Table 1.)

Give dose as soon as possible after VZV exposure (ideally within 96 hours); may be given within 10 days of exposure.

Second dose can be considered in high-risk individuals if another VZV exposure occurs ≥3 weeks after first dose.

Adults

Postexposure Prophylaxis of Varicella

Susceptible Pregnant Women

IM

Single dose based on body weight. (See Table 2.)

Give dose as soon as possible after VZV exposure (ideally within 96 hours); may be given within 10 days of exposure.

Second dose can be considered in high-risk individuals if another VZV exposure occurs ≥3 weeks after first dose.

Susceptible Immunocompromised Adults

IM

Single dose based on body weight. (See Table 2.)

Give dose as soon as possible after VZV exposure (ideally within 96 hours); may be given within 10 days of exposure.

Second dose can be considered in high-risk individuals if another VZV exposure occurs ≥3 weeks after first dose.

Prescribing Limits

Pediatric Patients

Minimum dose is 62.5 units in small infants weighing <2 kg; maximum dose is 625 units in patients weighing >40 kg.

Adults

Maximum dose is 625 units in patients weighing >40 kg.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations. (See Geriatric Use under Cautions.)

Cautions for Varicella Zoster Immune Globulin

Contraindications

• History of anaphylactic or severe systemic (hypersensitivity) reactions to any human immune globulin preparation.

• IgA deficiency with antibodies against IgA and history of hypersensitivity reaction. (See IgA Deficiency under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Severe hypersensitivity reactions may occur.

Administer in a setting with appropriate equipment, medication, and personnel trained in management of hypersensitivity, anaphylaxis, and shock.

If hypersensitivity reaction occurs, discontinue immediately and initiate appropriate therapy as indicated.

IgA Deficiency

Individuals with IgA deficiency and antibodies to IgA are at greater risk of severe hypersensitivity and anaphylactic reactions.

Varizig contains trace amounts (<40 mcg/mL) of IgA. As little as 15 mcg of IgA per mL of blood product may elicit an anaphylactic reaction in individuals with IgA deficiency.

Thrombotic Events

Thrombotic events may occur during or following treatment with immune globulin preparations.

Patients at risk of thrombotic events include those with history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], monoclonal gammopathies).

Coagulation Disorders

Because VZIG is administered IM (see Administration under Dosage and Administration), do not use in individuals with severe thrombocytopenia or any coagulation disorder that contraindicates IM injection unless expected benefits outweigh potential risks.

Risk of Transmissible Infectious Agents in Plasma-derived Preparations

Because VZIG is prepared from pooled human plasma, it is a potential vehicle for transmission of infectious agents, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.

Manufacturing process for VZIG includes a solvent/detergent inactivation process and a filtering procedure to remove both enveloped and non-enveloped viruses.

Because no purification method has been shown to be totally effective in removing risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing process or chemical (solvent/detergent) treatment procedures currently used, administer VZIG only when a benefit is expected.

Report any infection believed to have been transmitted by VZIG to manufacturer at 800-768-2304.

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.

Immunocompromised individuals without evidence of varicella immunity are at high risk of severe or disseminated varicella and generally should receive VZIG for postexposure prophylaxis.

Recommended for postexposure prophylaxis in individuals without evidence of varicella immunity who are immunosuppressed because they are receiving corticosteroid therapy in a dosage ≥2 mg/kg daily or ≥20 mg daily (prednisone or equivalent).

Not indicated for individuals who previously received age-appropriate varicella vaccination and subsequently became immunocompromised as the result of disease or immunosuppressive therapy later in life.

Consider bone marrow transplant recipients susceptible to varicella regardless of previous history of varicella or varicella vaccination in themselves or in their donors. However, those who develop varicella or herpes zoster after transplantation should be considered immune to varicella.

Varicella developed in some immunocompromised individuals who received VZIG postexposure prophylaxis. Varicella pneumonitis not reported in these patients; some had received concomitant acyclovir.

Limitations of Effectiveness

May prevent or modify varicella if given within 10 days of exposure. Limited data suggest incidence of varicella is comparable when VZIG is given within 4 days or >4 days (up to 10 days) after VZV exposure; attenuation of varicella might be achieved when given up to 10 days after exposure.

Immune globulins not effective once disease is established.

Use of VZIG for postexposure prophylaxis in pregnant women exposed to VZV may prevent or reduce severity of varicella in the woman, but such prophylaxis in the mother does not prevent fetal infection.

VZIG may not prevent varicella and may prolong the incubation period from 10–21 days to ≥28 days. Closely observe patient for signs and symptoms of varicella for 28 days after exposure; immediately initiate antiviral therapy if signs or symptoms of varicella occur.

VZIG provides only short-term passive immunity against VZV (see Duration of Immunity under Cautions). Unless varicella vaccine is contraindicated, administer active immunization with the vaccine ≥5 months after VZIG. (See Specific Drugs and Laboratory Tests under Interactions.) Varicella vaccine not needed if patient developed varicella despite administration of VZIG.

Duration of Immunity

Duration of protection against VZV following administration of VZIG unknown. Single VZIG dose provides passive immunity to VZV that should last about 3 weeks.

In susceptible individuals at high risk who cannot receive varicella vaccine, consider a second VZIG dose if another exposure to VZV occurs ≥3 weeks after first VZIG dose.

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.

Do not administer VZIG that has been mishandled or has not been stored at the recommended temperature. (See Storage under Stability.)

Inspect all immune globulins upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether VZIG is usable.

Serologic Testing

After VZIG dose, passively acquired anti-VZV antibodies are present in serum and may interfere with some serologic tests, including tests used to determine immunity to VZV. (See Specific Drugs and Laboratory Tests under Interactions.)

Because some patients who receive VZIG for postexposure prophylaxis may have asymptomatic varicella infection, some experts recommend follow-up serologic testing ≥2 months after VZIG to determine immune status in case a subsequent exposure occurs. Other experts suggest that serologic tests are unreliable in immunocompromised individuals and asymptomatic infection in such individuals may not confer lasting protection; these experts recommend use of VZIG in immunocompromised individuals after subsequent VZV exposure, regardless of serologic test results.

When serologic testing is performed to determine immune status after natural varicella, positive antibody results are reliable but negative antibody results may not be reliable.

Specific Populations

Pregnancy

Category C.

Use during pregnancy only when clearly needed. (See Uses.)

ACIP states there are no known risks for the fetus from use of immune globulin preparations for passive immunization in pregnant women.

Lactation

Not known whether VZIG is distributed into milk; use with caution.

Pediatric Use

Safety and efficacy established for postexposure prophylaxis of varicella in pediatric patients, including preterm neonates and infants, term neonates and infants, children, and adolescents.

Geriatric Use

Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether geriatric individuals respond differently than younger adults.

Use with caution in individuals ≥65 years of age who are at increased risk of thrombotic events. (See Thrombotic Events under Cautions.)

Administer only by IM injection; do not exceed recommended dosage.

Common Adverse Effects

Pain at injection site, headache, chills, rash, nausea.

Drug Interactions

Live Vaccines

Antibodies present in immune globulin preparations, including VZIG, may interfere with immune responses to some live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live (VAR); no evidence that immune globulin preparations interfere with immune responses to influenza virus vaccine live intranasal, yellow fever virus vaccine live, or typhoid vaccine live oral. (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

Immune globulin preparations not expected to have clinically important effects on immune responses to inactivated vaccines or toxoids; therefore, inactivated vaccines, recombinant vaccines, polysaccharide vaccines, and toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after VZIG. Neonates who received VZIG at birth can receive age-appropriate inactivated vaccines according to the usually recommended childhood immunization schedule.

Specific Drugs and Laboratory Tests

Varicella Zoster Immune Globulin Pharmacokinetics

Absorption

Bioavailability

Following IM administration of VZIG, bioavailability expected to be almost 100%. Anti-VZV antibodies are detected within 2–3 days and concentrations peak within 3–7 days.

Following IV^{† [off-label]} administration of VZIG, peak concentrations attained in <3 hours.

Although concentrations of passively acquired antibody are higher and achieved more quickly following IV^{† [off-label]} administration than IM administration, levels of circulating antibodies over time are expected to be similar with both routes.

Distribution

Extent

Following administration of VZIG, anti-VZV is expected to be quickly distributed between plasma and extravascular spaces.

Not known whether VZIG is distributed into milk.

Elimination

Metabolism

Immune globulins are metabolized in the reticuloendothelial system.

Half-life

Based on other immune globulins, half-life is expected to show interindividual variation and to be about 23–30 days following IM administration.

Anti-VZV antibodies persist for ≥6 weeks after single VZIG dose. Protection against VZV may last approximately 3 weeks.

Stability

Storage

Parenteral

Powder for Injection

2–8°C. Do not freeze.

After reconstitution, may be stored for up to 12 hours at 2–8°C. Do not freeze; discard if frozen.

Does not contain thimerosal or any other preservatives.

Actions

• VZIG is a lyophilized preparation of purified IgG fraction containing anti-VZV prepared from plasma of healthy adults with high titers of anti-VZV.

• Potency of VZIG is expressed in international units by comparison to the WHO international anti-VZV immune globulin reference preparation. Each vial contains approximately 125 units of anti-VZV.

• Provides passive immunity in susceptible individuals exposed to VZV.

• Anti-VZV antibodies in VZIG bind to proteins on VZV, and may prevent or reduce severity of varicella infection if administered to susceptible individuals within 10 days after exposure. Exact concentration of anti-VZV antibodies necessary to prevent or attenuate varicella not known.

• Primary VZV infection results in varicella (chickenpox); reactivation of infection results in herpes zoster.

• Varicella usually is self-limited in otherwise healthy children. In neonates or immunocompromised children or adults, varicella is associated with a high risk of severe or disseminated disease (e.g., pneumonia, encephalitis, multiple organ system involvement) and death.

• Maternal-fetal transmission of VZV can cause congenital varicella syndrome resulting in low birthweight, cutaneous scarring, limb hypoplasia, microcephaly, cortical atrophy, chorioretinitis, cataracts, and other anomalies and may result in fetal death. Congenital varicella syndrome occurs most frequently in infants born to women who had varicella during the first 20 weeks of gestation. Severe neonatal infection, including fatalities, can occur when varicella develops in neonates born to women who had onset of varicella from 5 days before to 2 days after delivery.

• Varicella is highly contagious; the secondary infection rate is 85% in healthy, susceptible individuals exposed through household contact. Individuals usually contagious from 1–2 days before rash onset until all lesions have crusted (typically 4–7 days after rash onset). Immunocompromised individuals may be contagious for a longer period of time, presumably because their immune system is depressed allowing viral replication to persist.

• In susceptible immunocompromised children exposed to VZV, postexposure prophylaxis with VZIG decreases, but does not eliminate, the risk of infection (attack rate following such prophylaxis is decreased to ≤60%); however, VZIG substantially decreases the incidence of severe varicella in those who do become infected.

• When VZIG postexposure prophylaxis is used in neonates exposed to VZV in utero within 7 days of delivery, the rate of infection is not substantially decreased compared with neonates who do not receive postexposure prophylaxis; however the incidence of severe neonatal varicella and fatal outcomes is substantially decreased in those who do become infected.

• In susceptible pregnant women exposed to varicella, postexposure prophylaxis with VZIG decreases the rate of infection to about 30%. Use of VZIG in susceptible pregnant women may prevent or ameliorate varicella in the mother, but does not appear to prevent viremia, fetal infection, congenital varicella syndrome, or varicella in her neonate.

Advice to Patients

• Advise patient and/or patient's parent or guardian of the risks and benefits of VZIG.

• Advise patient and/or patient's parent or guardian that VZIG is intended to reduce the severity of varicella (chickenpox); importance of contacting clinician if signs and symptoms of varicella develop.

• Advise patient and/or patient's parent or guardian that VZIG is prepared from pooled human plasma. Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, VZIG is a potential vehicle for infectious agents. (See Risk of Transmissible Infectious Agents in Plasma-derived Preparations under Cautions.)

• If patient has had a severe, potentially life-threatening reaction to human immune globulin products or any other immune globulin product, importance of not receiving VZIG unless risk is justified.

• Advise patients with IgA deficiency that they may develop anti-IgA antibodies and could have a severe, potentially life-threatening allergic reaction to VZIG. VZIG is contraindicated in individuals with IgA deficiency and anti-IgA antibodies and history of hypersensitivity reactions. (See IgA Deficiency under Cautions.)

• Importance of discontinuing VZIG immediately if an allergic or anaphylactic reaction occurs; if shock occurs, treat appropriately using current medical standards.

• Because VZIG may impair the immune response to certain live virus vaccines (e.g., MMR, VAR), importance of informing clinicians administering vaccines about recent use of VZIG.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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