ARCHIVED - Varizig™ as the Varicella Zoster Immune Globulin for the Prevention of Varicella In At-Risk Patients


Canada Communicable Disease Report

Canada Communicable Disease Report
Volume 32 • ACS-8 15 October 2006

An Advisory Committee Statement (ACS)

National Advisory Committee on Immunization (NACI)*†

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The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to immunization. The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of the Public Health Agency of Canada's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

NACI has recommended varicella zoster immune globulin (VarIg) for the post-exposure prevention of varicella in high-risk patients who cannot receive varicella vaccine1,2. The previous sole supplier of VarIg for North America (the Massachusetts Public Health Biologic Laboratories, Boston, MA) discontinued production in October 2004 because of declining disease incidence after varicella vaccine was licensed in the United States3. The product produced by the Massachusetts Public Health Biologic Laboratories will be referred to as VZIG in this statement. The available supply of VZIG in Canada is expected to be depleted by the end of 2006.

In November 2005, a varicella zoster immune globulin preparation named VariZIG™ (Cangene Corporation, Winnipeg, Man.) was approved for use in Canada. This statement provides information about VariZIG™, discusses post-exposure prevention strategies for varicella and outlines NACI's recommendations for VariZIG™ use.


VariZIG™ is a sterile, freeze-dried gamma globulin (IgG) preparation containing high titres of antibodies to varicella zoster virus (anti-VZV). It has been available through the Canadian Blood Services and Hema Quebec since February 2006.

VariZIG™ is manufactured from the plasma of healthy North American donors with high titres of anti-VZV. Donors and donated units are screened for hepatitis B, hepatitis C and HIV. The manufacturing process includes passage through a Planova 35 nm virus filter which effectively removes lipid-enveloped and non-enveloped viruses on the basis of size, and a solvent/ detergent treatment step (using tri-n-butyl phosphate and Triton X-100), which effectively inactivates lipid-enveloped viruses. These two processes are designed to increase product safety by reducing the risk of viral transmission of several viruses, including HIV, hepatitis B and hepatitis C. There is no latex in the product.

The lyophilized powder is available in single-use, 125 IU vials and must be reconstituted with the provided sterile diluent before use. Unlike VZIG, VariZIG™ is not available in the 625 IU vial size. The lyophilized product should be stored at +2° C to +8° C until the expiry date and must not be frozen. The diluent can be stored at room temperature.

The manufacturer's instructions for reconstitution of the product should be followed4. Although VariZIG™ is approved for intramuscular (IM) and intravenous (IV) use, NACI recommends using the IM route for post-exposure prophylaxis (see below). When properly reconstituted for IM injection, a vial provides approximately 1.2 mL of VariZIG™ at a concentration of 100 IU/mL. It should be given into the deltoid muscle or the anterolateral aspect of the upper thigh. The reconstituted product does not contain any preservative and so should be given as soon as possible after reconstitution, although it can be stored for up to 12 hours at +2°C to +8°C prior to use.

The most common adverse effects noted in studies of VariZIG™ include pain at the injection site (17%), headache (7%) and rash (5%)4,5. Less frequently reported adverse reactions were myalgia, chills, fatigue, nausea and flushing.

A contraindication to the use of VariZIG™ is an anaphylactic reaction to a previous dose of VariZIG™, VZIG or other immune globulin products. In addition, health care providers must weigh the potential benefit of treatment with VariZIG™ against the potential of anaphylactoid reactions occurring in persons with IgA deficiency, since the product contains trace quantities of IgA. As with any vaccine administration, providers should be prepared for the management of anaphylaxis after VariZIG™ administration.

VariZIG™ is only approved in Canada for the post-exposure prevention of varicella in susceptible pregnant women4,5. In a comparative study involving 57 susceptible pregnant women, 17 received IM VariZIG™, 21 received IV VariZIG™, and 19 received IM VZIG after exposure to varicella. After 6 weeks follow-up, clinical varicella developed in 29% of the women who had received either IM or IV VariZIG™ as compared with 42% of women who had received the IM VZIG5. The study was too small to detect any difference in the severity of varicella experienced by the participants. Although higher serum titres of anti-VZV were more rapidly attained after IV VariZIG™ than IM VariZIG™, the importance of this finding is unclear, as the clinical efficacy was the same in both treatment arms5.

VariZIG™ has not received federal regulatory approval for VZIG's other clinical indications (see recommendations below). However, the clinical effectiveness of VariZIG™ is expected to be similar to that obtained with VZIG, since the levels of anti-VZV are similar to those of VZIG. Pediatric clinical data are not currently available for VariZIG™, and it is not known whether the product is excreted in human milk.

Post-exposure prevention of varicella

The decision to administer VarIg should be based on all four of the following considerations1,6.

  1. the exposed person is susceptible to varicella (non-immune);
  2. there has been significant exposure to varicella zoster virus;
  3. the person is at increased risk of severe varicella; and
  4. post-exposure immunization with varicella vaccine is contraindicated.

Determining immunity/susceptibility: With the exception of allogenic stem cell transplant patients, persons who are considered immune to varicella include those with previous:

  • history of varicella illness obtained from an adolescent or adult or from a child's parent(s);
  • physician-diagnosed varicella
  • laboratory-confirmed varicella (by culture, polymerase chain reaction or antibody seroconversion);
  • laboratory evidence of immunity;
  • documented immunization with age-appropriate doses of varicella vaccine.

Healthy persons and most immunocompromised persons who are considered varicella immune by the above criteria do not require prophylaxis with VarIg. An exception is recipients of allogenic stem cell transplants who should be considered susceptible in the post-transplantation period. These persons should be offered VarIg after known exposure to varicella.

Adolescents and adults who have a negative or uncertain past history of varicella and no documentation of vaccination should have serologic tests to establish susceptibility, since as many as 70% to 95% of such individuals have immunity to varicella. However, delays in obtaining test results should not delay appropriate post-exposure varicella management.

Persons with a past history of varicella may be assumed to be immune. However, patients should be advised that it is still possible that varicella will develop as a result of re-infection (estimated by one community-based study to occur in 4.5% to 13.3% of cases7) or because the past diagnosis of varicella was incorrect. A positive history of varicella may become a less reliable indicator of protection in the future as circulation of varicella virus decreases and the incidence of infection declines. Infrequently, infection can result in those whose serologic tests are positive, as some tests lack optimal specificity8.

Persons who have received age-appropriate doses of varicella vaccine in the past may be assumed to be varicella immune, with the exception of recipients of allogenic stem cell transplants. However, patients should be advised that they may still get varicella, as vaccine-modified disease can be expected to occur in 3% to 4% of vaccinees per year according to prelicensure efficacy studies. Vaccine-modified disease are likely to be milder than natural infection2. A recent review summarizing 14 studies found vaccine efficacy/effectiveness for any severity of infection to be in the range of 43% to 98%, most studies showing efficacy well over 70%8. Serologic testing of vaccinees is not recommended, especially since commercially available antibody tests may not be sensitive enough to detect protective antibody levels after vaccination2.

Exposure assessment: Persons with varicella (chickenpox) are most contagious from 1 to 2 days before and up to 5 days after onset of the rash. Immunocompromised patients may be infectious until the crusting of all lesions. The skin lesions of zoster (shingles) are considered infectious from their onset until they have crusted and dried. The following situations are considered significant exposures to varicella zoster virus:

  • Continuous household contact (living in the same dwelling) with a person with varicella.
  • Being indoors for > 1 hour with a case of varicella.
  • Being in the same hospital room for > 1 hour, or > 15 minutes of face-to-face contact, with a patient with varicella.
  • Touching the lesions of a person with active varicella or zoster (shingles).

Risk of complications and/or contraindication to vaccine:

Susceptible children and adults with no known contraindications to varicella vaccination should be immunized before any exposure to varicella zoster virus. Post-exposure vaccination is effective in preventing or attenuating disease in previously unimmunized healthy persons if the vaccination can be carried out within 3 to 5 days of exposure9,10. However, post-exposure vaccination of immunocompromised persons is often contraindicated and may be less effective. Therefore, in susceptible immunocompromised patients, VarIg rather than vaccine should be used for the prevention of varicella.

Varicella vaccine is contraindicated in pregnant women. Because the risk of complications of chickenpox in pregnant women may be greater than in other adults, VarIg should be given to exposed, susceptible pregnant women. Maternal infection results in congenital varicella syndrome in ≤ 2% of pregnancies if the infection occurs at < 20 weeks' gestation. Although a study has shown that congenital varicella syndrome did not occur in the fetuses of 97 pregnant women given VarIg, this study is too small to conclude that VarIg will prevent or alter disease in the fetus11. Susceptible pregnant women should be given varicella vaccine after delivery, as long as 5 months have passed since VarIg administration.

Infants < 1 year of age are not eligible for varicella vaccination. They are generally protected by maternal antibody if their mothers had previous varicella infection or immunization. Therefore, VarIg is not indicated unless the mother has varicella that developed during the 5 days before to 48 hours after delivery or if significant exposure occurred in a neonatal or pediatric intensive care unit, under which circumstances there should be consultation with the infectious disease/infection control practitioner (see below).

Recommendations for use of VariZIG™

In jurisdictions where VZIG is still available, VZIG should be used for prophylaxis. VariZIG™ may be substituted once VZIG is no longer available.

As the clinical significance of more rapidly achieving higher anti-VZV titres using IV VariZIG™ is as yet unclear, NACI recommends that VariZIG™ be given by the IM route. Health care providers in Canada are more familiar with the IM route from previous experience with VZIG.

NACI recommends VariZIG™ for the following susceptible high-risk groups after exposure to varicella zoster virus1,4,12:

  1. Pregnant women.
  2. Immunocompromised patients, such as those with congenital or acquired immunodeficiency due to disease or treatment, including patients receiving high-dose systemic corticosteroid therapy (e.g. a dose of ≥ 2 mg/kg per day of prednisone or equivalent, or ≥ 20 mg per day, particularly when given for > 2 weeks). However, patients receiving regular monthly infusions of ≥ 400 mg/kg of IVIG and whose most recent dose was within 3 weeks before exposure do not require VariZIG™. This monthly infusion of IVIG has been found to maintain protective serum levels of varicella antibody comparable with that achieved with VarIg13.
  3. Newborn infants of mothers who have varicella that began during the 5 days before to 48 hours after delivery.
  4. For the management of significant varicella exposure in a neonatal or pediatric intensive care setting, consultation with the infectious diseases/infection control specialist regarding the potential use of VariZIG™ is advised.

VariZIG™ is not indicated in healthy adults. Varicella can be more severe in healthy adults than children, but the risk of varicella pneumonia appears to be lower than was formerly believed. Varicella vaccine within 3 to 5 days after exposure is the post-exposure management of choice for healthy adults. Acyclovir therapy initiated within 24 hours after onset of the rash is effective in accelerating skin lesion healing and can be used for this population as soon as possible after rash onset.

Dosing of VariZIG™ is based on body weight. The recommended dose is 125 IU for each 10 kg body weight up to a maximum of 625 IU. The minimum dose is 125 IU. As with other blood products, informed consent from patients or their parents/guardians must be obtained before administration of VariZIG™.

VariZIG™ is of maximal benefit if administered within 96 hours after first exposure. However, since the exact timing of transmission is unknown it can be used within 96 hours of the most recent exposure. Protection is believed to last for approximately 3 weeks. Subsequent exposures > 3 weeks after a dose of VariZIG™ would require additional doses if the criteria for VariZIG™ use outlined in the Post-exposure prevention of varicella section still exist.

Vaccination with any live virus vaccines should be deferred for 5 months after administration of VariZIG™. If VariZIG™ is inadvertently given < 14 days after vaccination with live virus vaccines, the person should be reimmunized with the live vaccine 5 months after administration of the VariZIG™2. Note that VariZIG™ may give detectable levels of antibody, causing false-positive tests of varicella immunity for up to 3 months after administration1.

As with VZIG, VariZIG™ may prolong the incubation period of varicella. For hospitalized patients and health care workers given VariZIG™, the infectious periods would range from 8 days after exposure to 28 days after last exposure, as compared with 8 days after first exposure to 21 days after last exposure without VariZIG™. Effective antiviral agents such as acyclovir can be used should varicella develop after VariZIG™administration 6,14-18.


  1. Health Canada. Varicella zoster immune globulin. In: Canadian immunization guide. 6th ed. Ottawa, 2002;248-50. Catalogue no. H49-8/2002E.

  2. National Advisory Committee on Immunization (NACI). Update on varicella. CCDR 2004;30(ACS-1):1-26.

  3. Advisory Committee on Immunization Practices. A new product (VariZIG™) for post-exposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR 2006;55:209-10.

  4. Cangene Corporation. VariZIG product monograph. Cangene Corporation, Winnipeg, Manitoba, 2005.

  5. 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;42:267-74.

  6. Committee on Infectious Diseases, American Academy of Pediatrics. Varicella zoster infections. 2003:672-86.

  7. Hall S, Maupin T, Seward J et al. Second varicella infections: Are they more common than previously thought? Pediatrics 2002;109:1068-73.

  8. Hambleton S, Gershon AA. Preventing varicella disease. Clin Microbiol Rev 2005;18:70-80.

  9. Watson B, Seward J, Yang A et al. Postexposure effectiveness of varicella vaccine. Pediatrics 2000;105:84-8.

  10. Salzman MB, Garcia C. Postexposure varicella vaccination in siblings of children with active varicella. Pediatr Infect Dis J 1998;17:256-57.

  11. Enders G, Miller E, Cradock-Watson J et al. Consequences of varicella and herpes zoster in pregnancy: Prospective study of 1739 cases. Lancet 1994;343:1548-51.

  12. Paryani SG, Arvin AM, Koropchak CM et al. Comparison of varicella zoster antibody titers in patients given intravenous immune serum globulin or varicella zoster immune globulin. J Pediatr 1984;105:200-5.

  13. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Varicella zoster immune globulin use in neonates and infants. Paediatr Child Health 1996;1:21-2.

  14. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Prevention of varicella in children and adolescents. Paediatr Child Health 2005;10:409-12.

  15. King SM, Gorensek M, Ford-Jones EL et al. Fatal varicella-zoster infection in a newborn treated with varicella-zoster immunoglobulin. Pediatr Infect Dis 1986;5:588-9.

  16. Miller E, Cradock-Watson JE, Ridehalgh MK. Outcome in newborn babies given anti-varicella-zoster immunoglobulin after perinatal maternal infection with varicella-zoster virus. Lancet 1989;2:371-3.

  17. Bakshi SS, Miller TC, Kaplan M et al. Failure of varicella-zoster immunoglobulin in modification of severe congenital varicella. Pediatr Infect Dis 1986;5:699-702.

  18. Zaia JA, Levin MJ, Preblud SR et al. Evaluation of varicella-zoster immune globulin: Protection of immunosuppressed children after household exposure to varicella. J Infect Dis 1983;147:737-43.

*Members: Dr. M. Naus (Chairperson), Dr. S. Deeks (Executive Secretary), Dr. S. Dobson, Dr. B. Duval, Dr. J. Embree, Ms. A. Hanrahan, Dr. J. Langley, Dr. K. Laupland, Dr. A. McGeer, Dr. S. McNeil, Dr. M.N. Primeau, Dr. B. Tan, Dr. B.Warshawsky.

Liaison Representatives: S. Callery (CHICA), Dr. J. Carsley (CPHA), Dr. J. Smith (CDC), Dr. D. Money (SOGC), A. Honish (CNCI), Dr. B. Larke (CCMOH), Dr. B. Law (ACCA), Dr. M. Salvadori (CPS), Dr. S. Rechner (CFPC), Dr. J. Salzman (CATMAT), Dr. D. Scheifele (CAIRE), Dr. P. Orr (AMMI Canada).

Ex-Officio Representatives: Dr. H. Rode (BGTD), Dr. M. Lem (FNIHB), Dr. J.W. Anderson (DND).

This statement was prepared by Dr. Bryna Warshawsky, Dr. Ben Tan and Dr. Shelley Deeks. It was approved by NACI and by the Public Health Agency of Canada (PHAC).

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