VA Class:IM100

ATC Class:J06BB03

AHFS Class:

• Antitoxins and Immune Globulins 80:04

Generic Name(s):

• Varicella Zoster Immune Globulin (Human)

Varicella zoster immune globulin (VZIG) is a specific immune globulin (hyperimmune globulin).36 VZIG contains immune globulin G (IgG) prepared from plasma of donors selected for high titers of antibodies to varicella zoster virus (anti-VZV)1 and is used to provide temporary passive immunity to VZV.1,27,36

Postexposure Prophylaxis of Varicella

Varicella zoster immune globulin (VZIG) is used for postexposure prophylaxis of varicella (chickenpox) in individuals who do not have evidence of varicella immunity and are at high risk for severe varicella and complications from the disease.1,27,46,100 VZIG is designated an orphan drug by the US Food and Drug Administration (FDA) for passive immunization in exposed, susceptible individuals who are at risk for varicella complications.2

Postexposure prophylaxis with VZIG is intended to reduce the severity of varicella in susceptible, high-risk individuals,1 and provides maximum benefit when administered as soon as possible (ideally within 96 hours) after exposure to varicella zoster virus (VZV).1,27,46 (See Dosage and Administration: Administration.) The manufacturer states that there is no convincing evidence that VZIG reduces the incidence of varicella after exposure to VZV and no convincing evidence that VZIG would modify an established VZV infection.1

A decision to administer VZIG for postexposure prophylaxis should be made on an individual basis, taking into consideration evidence of the patient's immunity to varicella, likelihood that the VZV exposure will result in infection, and whether the patient is at greater risk for varicella complications than the general population.27,100 High-risk individuals include immunocompromised children, adolescents, and adults,1,27,46,100,143,144 neonates of mothers who had varicella shortly before or after delivery,1,27,46,100 premature neonates,27,46,100 neonates and infants younger than 1 year of age,1 adults without evidence of varicella immunity,1 and pregnant women.1,27,46

The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that individuals are considered to have evidence of immunity to varicella if any of the following are true: documentation of age-appropriate varicella vaccination (1 dose of varicella virus vaccine live in preschool children 12 months of age or older or 2 doses in school-aged children, adolescents, and adults), laboratory evidence of immunity or laboratory confirmation of prior varicella infection, birth in the US before 1980 (US birth before 1980 is not considered evidence of immunity for immunocompromised individuals, pregnant women, or health-care personnel), or history of varicella (chickenpox) or herpes zoster (shingles, zoster) diagnosed or verified by a health-care provider.27 Individuals without such evidence should be considered susceptible to varicella.27

Vaccination with varicella virus vaccine live 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.27,100 VZIG is recommended for postexposure prophylaxis in susceptible individuals who cannot receive varicella virus vaccine live, including immunocompromised individuals, certain neonates, and pregnant women.27,100 If varicella virus vaccine is contraindicated or cannot be used and VZIG is unavailable, use of immune globulin IV (IGIV) can be considered as an alternative for postexposure prophylaxis since it contains anti-VZV.27,100

The ACIP states that exposures likely to result in varicella in susceptible individuals (i.e., those without evidence of varicella immunity) are those that involve direct contact (i.e., face-to-face contact with an infectious person while indoors).27 The duration of face-to-face contact that warrants postexposure prophylaxis with VZIG is not certain.27 Some experts suggest use of VZIG in susceptible individuals if the duration of close contact was more than 5 minutes; others define close contact as more than 1 hour.27,100 Susceptible individuals with continuous exposure to household members with varicella or disseminated herpes zoster are at greatest risk for infection.27 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 provider).27 (For additional information on the risks of VZV exposure and infection, see Varicella Virus Vaccine Live 80:12.)

VZIG should not be used for postexposure prophylaxis of varicella in immunocompromised children, adolescents, or adults with a past history of varicella, unless the individual is undergoing bone marrow transplantation.1

VZIG has not been shown to be useful for the treatment of clinical varicella or herpes zoster or for prevention of disseminated herpes zoster and is not recommended for such use.27,100

Immunocompromised Children, Adolescents, and Adults

Immunocompromised individuals are at high risk of severe or disseminated varicella (e.g., pneumonia, encephalitis, multiple organ system involvement) and fatalities have been reported.6,9,27,100,138 VZIG is recommended for postexposure prophylaxis in immunocompromised children, adolescents, and adults without evidence of varicella immunity who have had direct exposure to varicella or disseminated herpes zoster.27,46,100,143,144 This includes individuals with primary or acquired immunodeficiency disorders, human immunodeficiency virus (HIV) infection, or neoplastic disease and individuals receiving immunosuppressive therapy.27,100,143,144 (See Individuals with Altered Immunocompetence under Cautions: Warnings/Precautions.)

Postexposure prophylaxis with VZIG probably is not necessary in individuals who are receiving IGIV replacement therapy (400 mg/kg or more once monthly) and received a dose of IGIV 3 weeks or less before exposure to VZV since such individuals are likely to be protected from VZV.27,100,143

Neonates

Neonates whose mothers have signs and symptoms of varicella at the time of delivery (i.e., from 5 days before to 2 days after delivery) are at risk of severe, potentially fatal varicella and should receive VZIG for postexposure prophylaxis,27,46,100 regardless of whether the mother received VZIG.27 VZIG is not necessary in neonates whose mothers had signs and symptoms of varicella more than 5 days before delivery; such infants should be protected from severe varicella by transplacentally acquired maternal antibody.27 VZIG postexposure prophylaxis is not indicated in full-term neonates exposed postnatally to varicella (including those born to mothers who develop varicella more than 48 hours after delivery).27,100 However, some clinicians recommend use of VZIG in exposed neonates who have severe skin disease and were born to mothers who had no evidence of varicella immunity.100

Certain premature neonates who were exposed to VZV during the neonatal period should receive VZIG postexposure prophylaxis.27,46,100 Premature infants with substantial postnatal VZV exposure should be evaluated on an individual basis.27 VZIG is recommended for neonates born at less than 28 weeks of gestation or with birthweight 1 kg or less if they are exposed during the neonatal period; such neonates should receive VZIG regardless of the mother's history of varicella or varicella vaccination.27,46,100 VZIG also is recommended for premature neonates born at 28 weeks or more of gestation who are exposed during the neonatal period if the mother does not have evidence of varicella immunity.27,46,100 The majority of premature infants born at 28 weeks or more of gestation to mothers with varicella immunity should have enough maternal antibody to protect them from severe varicella and complications.27

Pregnant Women

Susceptible pregnant women may be at higher risk for severe varicella and complications (e.g., varicella pneumonia) than other susceptible adults.27,138 The ACIP states that VZIG should be strongly considered for postexposure prophylaxis in pregnant women who have been exposed to varicella and have no evidence of varicella immunity.27

There is evidence that susceptible pregnant women exposed to varicella who receive VZIG for postexposure prophylaxis have an infection rate of 30%, which is substantially lower than the expected rate of more than 70% in unimmunized women exposed to varicella.27 In a randomized, open-label, multicenter, active-controlled clinical trial in 60 pregnant women who did not have immunity to VZV, postexposure prophylaxis with VZIG (Varizig^® by IM injection, Varizig^® by IV injection†, comparator VZIG by IM injection) given in a dosage of 125 units/10 kg (maximum 625 units) following exposure to VZV resulted in an overall incidence of varicella of 33%.1 However, the incidence of clinical varicella was 64% in the subset of 28 women who received VZIG more than 24 hours after varicella exposure.1 The mean weighted constitutional illness scores were similar across all treatment groups and no serious complications of varicella were reported.1

Use of VZIG in susceptible pregnant women has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella; therefore, the primary indication for VZIG in such women is to prevent or ameliorate varicella in the mother rather than to protect the fetus.27

General

Varicella zoster immune globulin (VZIG) provides maximum benefit when administered in susceptible individuals as soon as possible after exposure to varicella zoster virus (VZV).27 Ideally, VZIG should be administered within 4 days (96 hours) after VZV exposure;1,27,46,100,143,144 however, the US Food and Drug administration (FDA) states that VZIG may be given within 10 days after exposure, preferably as soon as possible.46 (See Limitations of Effectiveness under Cautions: Warnings/Precautions.)

Although VZIG was previously available in the US only under an investigational new drug application (IND) expanded access protocol,3,4 VZIG has been approved by the US Food and Drug Administration (FDA) and is now commercially available.1

Administration

VZIG is labeled by the FDA for administration by IM injection only.1 VZIG also has been administered by IV injection†.5

VZIG should not be mixed with any other drug or solution.5

VZIG should not be administered concomitantly with varicella virus vaccine live.1,27,100 (See Live Vaccines under Drug Interactions: Vaccines.)

IM Injection

IM injections of VZIG should be given into the deltoid muscle or anterolateral aspect of the upper thigh.1

Because of the risk of injection-associated injury to the sciatic nerve, the gluteal region should be used only when necessary; if the gluteal region must be used, injections should be made only into the upper, outer quadrant.1

The IM dose should be divided and administered into at least 2 IM injection sites, depending on patient size.1 No more than 3 mL of reconstituted VZIG should be administered at each IM injection site.1

Reconstitution

For IM injection, vials of lyophilized VZIG labeled as containing 125 units should be reconstituted by adding 1.25 mL of sterile diluent supplied by the manufacturer using a suitable syringe and needle.1 The diluent should be injected slowly at an angle so that the liquid is directed onto the inside of the vial wall.1 The pellet should be wetted by gently tilting and inverting the vial.1 Frothing should be avoided.1 The upright vial should be gently swirled until the pellet dissolves (less than 10 minutes); the vial should not be shaken.1

The reconstituted solution for IM administration contains 100 units/mL.1

Immediately prior to use, reconstituted VZIG solution should be inspected visually for particulate matter and discoloration and should not be used if it is turbid and/or discolored.1

Reconstituted VZIG solution for IM administration may be stored for up to 12 hours at 2-8°C.1 Lyophilized VZIG and reconstituted VZIG solution should not be frozen; any solution that has been frozen should be discarded.1

VZIG vials are for single use only; partially used vials of reconstituted VZIG and any remaining diluent should be discarded after the dose is given.1

Dosage

Postexposure Prophylaxis of Varicella

For postexposure prophylaxis of varicella in susceptible, high-risk adults, adolescents, and children, VZIG is administered as a single dose based on body weight.1 (See Table 1.) VZIG should be given as soon as possible after VZV exposure (ideally within 96 hours),1,27,46,100,143 but may be given within 10 days of exposure.46

A second VZIG dose can be considered in high-risk individuals if another exposure to VZV occurs 3 weeks or longer after the first VZIG dose.1,27

The minimum dose of VZIG recommended by the manufacturer is 62.5 units in small infants weighing less than 2 kg; the maximum dose is 625 units in patients weighing more than 40 kg.1

Special Populations

There are no special population dosage recommendations.1 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Contraindications

History of anaphylactic or severe systemic (hypersensitivity) reactions to any human immune globulin preparation.1

IgA deficiency with antibodies against IgA and history of hypersensitivity reaction.1 (See IgA Deficiency under Warnings/Precautions: Sensitivity Reactions, in Cautions.)

Warnings/Precautions

Sensitivity Reactions

Severe hypersensitivity reactions may occur following administration of varicella zoster immune globulin (VZIG).1

VZIG should be administered in a setting with appropriate equipment, medication, and personnel trained in the management of hypersensitivity, anaphylaxis, and shock.1

If a hypersensitivity reaction occurs, VZIG should be discontinued immediately and appropriate therapy instituted as indicated.1

IgA Deficiency

Individuals with IgA deficiency and antibodies to IgA are at greater risk of severe hypersensitivity and anaphylactic reactions.1

Varizig^® contains trace amounts (less than 40 mcg/mL) of IgA.1 As little as 15 mcg of IgA per mL of blood product may elicit an anaphylactic reaction in individuals with IgA deficiency.5

Thrombotic Events

Thrombotic events may occur during or following treatment with immune globulin preparations.1

Patients at risk of thrombotic events include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.1

Clinicians should 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).1

Coagulation Disorders

Because VZIG is administered IM (see Dosage and Administration: Administration), the immune globulin should not be used in individuals with severe thrombocytopenia or any coagulation disorder that contraindicates IM injection unless the expected benefits outweigh the potential risks.1

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).1,20

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, the risk of pathogen transmission with plasma-derived preparations.1

The manufacturing process for VZIG includes a solvent/detergent inactivation process and a filtering procedure to remove both enveloped and non-enveloped viruses.1

Because no purification method has been shown to be totally effective in removing the 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 the chemical (solvent/detergent) treatment procedures currently used, VZIG should be administered only when a benefit is expected.1

Any infection believed to have been transmitted by VZIG should be reported to the manufacturer at 800-768-2304.1

Individuals with Altered Immunocompetence

VZIG may be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.27,143,144

Immunocompromised individuals without evidence of varicella immunity are at high risk of severe or disseminated varicella and generally should receive VZIG for postexposure prophylaxis.27,100 (See Immunocompromised Children, Adolescents, and Adults under Uses: Postexposure Prophylaxis of Varicella.)

VZIG is 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.27

Bone marrow transplant recipients should be considered susceptible to varicella regardless of the previous history of varicella or varicella vaccination in themselves or in their donors.27 However, those who develop varicella or herpes zoster after transplantation should be considered immune to varicella.27

Varicella has developed in some immunocompromised individuals who received postexposure prophylaxis with VZIG.1 Although varicella pneumonitis was not reported in these patients, some had received concomitant acyclovir.1

Limitations of Effectiveness

VZIG may prevent or modify varicella if given within 10 days of exposure to VZV.46 Limited data suggest that the incidence of varicella is comparable when VZIG is given within 4 days or more than 4 days (up to 10 days) after VZV exposure; attenuation of varicella might be achieved when the immune globulin is given up to 10 days after exposure.46

Immune globulins are not effective once disease is established.100

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.27,100

VZIG may not prevent varicella and may prolong the incubation period from 10-21 days to 28 days or longer.27,100 Patients who receive VZIG should be closely observed for signs and symptoms of varicella for 28 days after exposure; antiviral therapy should be initiated immediately if signs or symptoms of varicella occur.27

VZIG only provides short-term passive immunity against VZV (see Duration of Immunity under Cautions: Warnings/Precautions).27,100 Unless varicella virus vaccine live is contraindicated, patients who receive VZIG for postexposure prophylaxis should receive active immunization with the vaccine at least 5 months after VZIG.27,100 (See Live Vaccines under Drug Interactions: Vaccines.) Varicella virus vaccine live is not needed if the patient developed varicella despite administration of VZIG.27,100

Duration of Immunity

The duration of protection against VZV following administration of VZIG is unknown.27 A single VZIG dose provides passive immunity to VZV that should last about 3 weeks.27

In susceptible individuals at high risk who cannot receive varicella virus vaccine live, a second VZIG dose can be considered if another exposure to VZV occurs 3 weeks or longer after the first VZIG dose.1,27

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.36

All immune globulins should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.36

VZIG that has been mishandled or has not been stored at the recommended temperature (see Dosage and Administration: Administration) should not be administered.36

If there are concerns about mishandling, the manufacturer or state or local health departments should be contacted for guidance on whether VZIG is usable.36

Serologic Testing

After administration of VZIG, passively-acquired anti-VZV antibodies are present in serum and may interfere with serologic tests, including the Coombs' test and tests used to determine immunity to VZV.5

Anti-VZV antibodies from VZIG may cause false-positive tests for immunity to VZV for 3 months; such testing should not be performed until at least 3 months after the dose.5

Because some patients who receive VZIG for postexposure prophylaxis may have asymptomatic varicella infection, some experts recommend that follow-up serologic testing be done at least 2 months after VZIG to determine the patient's immune status in case a subsequent exposure occurs.100 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.100

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.100

Specific Populations

Pregnancy

Category C.1 (See Users Guide)

VZIG should be used during pregnancy only when clearly needed.1 (See Pregnant Women under Uses: Postexposure Prophylaxis of Varicella.)

The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that there are no known risks for the fetus from use of immune globulin preparations for passive immunization in pregnant women.36

Lactation

It is not known whether VZIG is distributed into milk.1 The immune globulin should be used with caution in nursing women.1

Pediatric Use

Safety and efficacy of VZIG have been evaluated for postexposure prophylaxis of varicella in pediatric patients, including preterm neonates and infants, term neonates and infants, children, and adolescents.1 (See Uses.)

Geriatric Use

Clinical studies of VZIG for postexposure prophylaxis of varicella did not include sufficient numbers of individuals 65 years of age or older to determine whether geriatric individuals respond differently than younger adults.1

VZIG should be used with caution in individuals 65 years of age and older who are at increased risk of thrombotic events.1 (See Thrombotic Events under Cautions: Warnings/Precautions.)

When used in geriatric individuals, VZIG should only be administered IM and the recommended dosage should not be exceeded.1

Common Adverse Effects

The most common adverse effects reported with VZIG in clinical trials in pregnant women, infants, and immunocompromised adults and children were injection site pain (2%), headache (2%), chills, fatigue, rash, and nausea.1 The highest incidence of adverse effect occurred in pregnant women and included injection site pain (9%), headache (4%), chills (2%), and fatigue (2%).1

Vaccines

Live Vaccines

Antibodies present in immune globulin preparations, including varicella zoster immune globulin (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).1,27,36 The duration of possible interference between immune globulin preparations and live virus vaccines appears to depend on antibody concentrations in the immune globulin; there is evidence that certain immune globulin preparations can inhibit the immune response to measles virus vaccine live and rubella virus vaccine live for more than 3 months.36 Although specific information regarding the effect of immune globulin preparations on immune responses to mumps virus vaccine live and VAR is not available, there is potential for similar interference since immune globulin preparations contain antibodies to these viruses.36

MMR and VAR should not be administered simultaneously with VZIG, and should be deferred until at least 5 months after VZIG.36 Revaccination with MMR and VAR may be necessary if these live virus vaccines are administered less than 5 months after VZIG.36 In addition, revaccination is necessary if VZIG was administered less than 14 days after MMR or VAR, unless serologic testing is feasible and indicates that there was an adequate response to the vaccines.36

There is 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.36 When indicated, these live vaccines can be administered simultaneously with or at any time before or after VZIG.36

Inactivated Vaccines and Toxoids

Immune globulin preparations are not expected to have a clinically important effect 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.36 Neonates who received VZIG at birth can receive age-appropriate inactivated vaccines according to the usually recommended childhood immunization schedule.100

Description

Varicella zoster immune globulin (VZIG) is a lyophilized preparation of purified immune globulin G (IgG) fraction containing antibodies to varicella zoster virus (anti-VZV) prepared from plasma of healthy adults with high titers of anti-VZV.1 Potency of VZIG is expressed in international units by comparison to the World Health Organization (WHO) international anti-VZV immune globulin reference preparation.1 Each vial contains 125 units of anti-VZV.1 Each 125-unit vial of VZIG contains less than 250 mg of total protein, mostly human IgG and also contains sodium chloride, glycine, and polysorbate 80;1 the diluent provided by the manufacturer contains 0.8% sodium chloride and sodium phosphate.1 The pH of reconstituted VZIG is 7.1 VZIG does not contain thimerosal or any other preservatives.1

VZIG provides passive immunity in susceptible individuals exposed to VZV.1 Anti-VZV antibodies in VZIG bind to proteins on varicella virus, and may prevent or reduce severity of varicella infection if administered to susceptible individuals within 10 days after exposure.5,27,46,100 After a single VZIG dose, anti-VZV antibodies persist for at least 6 weeks,5 and protection against VZV may last for approximately 3 weeks.27 The exact concentration of anti-VZV antibodies necessary to prevent or attenuate varicella is not known.5

Following IM administration, bioavailability of VZIG is expected to be almost 100%.5 Anti-VZV antibodies are detected within 2-3 days5 and concentrations peak within 3-7 days.1,5 Following IV† administration, peak concentrations are attained in less than 3 hours.5 Although concentrations of passively-acquired antibody are higher and achieved more quickly following IV† administration than IM administration,5,50 levels of circulating antibodies over time are expected to be similar with both routes.5 Anti-VZV is expected to be quickly distributed between plasma and extravascular spaces.5 Immune globulins are metabolized in the reticuloendothelial system.5 Based on studies with other immune globulins,5 the elimination half-life of VZIG is expected to show interindividual variation.1,5 Half-life has been reported to be about 23-30 days following IM administration .1,5

Advice to Patients

Advise patient and/or patient's parent or guardian of the risks and benefits of varicella zoster immune globulin (VZIG).1

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.1

Advise patient and/or patient's parent or guardian that VZIG is prepared from pooled human plasma.1 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 transmission of infectious agents.1,20 (See Risk of Transmissible Infectious Agents in Plasma-derived Preparations under Cautions: Warnings/Precautions.)

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.1

Advise patients with IgA deficiency that they may develop anti-IgA antibodies and could have a severe, potentially life-threatening allergic reaction to VZIG.1 VZIG is contraindicated in individuals with IgA deficiency and anti-IgA antibodies and history of hypersensitivity reactions.1 (See IgA Deficiency under Warnings/Precautions: Sensitivity Reactions, in Cautions.)

Importance of discontinuing VZIG immediately if an allergic or anaphylactic reaction occurs; if shock occurs, appropriate treatment should be administered using current medical standards.1

Because VZIG may impair the immune response to certain live virus vaccines (e.g., measles, mumps, and rubella virus vaccine live [MMR], varicella virus vaccine live [VAR]),1,27,36,100 importance of informing clinicians administering vaccines about recent use of VZIG.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Cangene Corporation. Varizig^® varicella zoster immune globulin (human) lyophilized powder for solution for injection for intramuscular administration only prescribing information. Winnipeg, Canada; 2012 Dec.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2012 Mar 12. [Web]

3. Centers for Disease Control and Prevention. A new product (variZIG™) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep . 2006; 55:209-10. [PubMed 16511443]

4. FFF Enterprises. VariZIG IND protocol. From FFF Enterprises website. [Web]

5. Cangene. VariZIG^® varicella zoster immune globulin (human) product monograph. Winnipeg, Canada; 2008 Jan 9.

6. Feldman S, Hughes WT, Daniel CB. Varicella in children with cancer: seventy-seven cases. Pediatrics . 1975; 56:388-97. [PubMed 1088828]

7. Whitley RJ. Varicella-zoster virus. In: Mandell GL, Bennett JE, Dolin R eds. Principles and practices of infectious diseases. 7th ed. Churchill Livingstone; 2009:1963-9.

9. Dolin R, Reichman RC, Mazur MH et al. Herpes zoster-varicella infections in immunosuppressed patients. Ann Intern Med . 1978; 89:375-88. [PubMed 210697]

20. US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jacob disease (CJD) and variant Creutzfeldt-Jacob disease (vCJD) by blood and blood products. May 2010. From FDA website. [Web]

27. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2007; 56(RR-4):1-40. [Fulltext MMWR]

36. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2011; 60:1-64.

46. Centers for Disease Control and Prevention (CDC). FDA Approval of an Extended Period for Administering VariZIG for Postexposure Prophylaxis of Varicella. MMWR Morb Mortal Wkly Rep . 2012; 61:212. [PubMed 22456121]

50. Koren G, Money D, Boucher M et al. Serum concentrations, efficacy, and safety of a new, intravenously administered varicella zoster immune globulin in pregnant women. J Clin Pharmacol . 2002; 42:267-4. [PubMed 11865962]

100. American Academy of Pediatrics. 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

101. Tschudy MM, Arcara KM, eds. Johns Hopkins: The Harriet Lane handbook. 19th ed. Philadelphia, PA: Elsevier; 2012.

126. Centers for Disease Control and Prevention. Provisional ACIP recommendations for postexposure prophylaxis of severe varicella during a varicella zoster immune globulin shortage. From CDC website. Accessed 2005 Dec 14. [Web]

138. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 12th ed. Washington DC: Public Health Foundation; 2011.

143. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep . 2009; 58:1-207; quiz CE1-4. [PubMedCentral]

144. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep . 2009; 58:1-166. [PubMedCentral][PubMed 19730409]