Varicella-Zoster Virus Vaccine (Zostavax)
Special Report
By Jessica C. Song, MA., PharmD, Pharmacy Residency Coordinator, Assistant Professor, Pharmacy Practice, University of the Pacific, Stockton, CA, Pharmacy Clerkship and Coordinator, Santa Clara Valley Medical Center, Section Editor, Managed Care, is Associate Editor for Infectious Disease Alert.
By Paul Hsiao, PharmD, Pharmacist Specialist at Santa Clara Valley Medical Center.
Jessica C. Song and Paul Hsiao report no financial relationships relevant to this field of study.
Herpes zoster results from reactivation of latent varicella-zoster virus (VZV) residing in the sensory ganglia of the cranial and spinal dorsal root ganglia. It is estimated that up to one million adults in the United States experience this debilitating illness yearly, and the number of cases will likely increase in the future, because of the aging population. Furthermore, affected individuals may experience serious adverse consequences, including postherpetic neuralgia, paresis, myelopathy, and vasculopathy. Postherpetic neuralgia has been shown to persist for longer than one year in 36% and in 47%, respectively, in those older than 60 years and 70 years.1
Concerns about the burden of illness associated with herpes zoster (HZ) episodes have stimulated the development of a novel method of prophylaxis against HZ in the elderly patient population. In December 2005, the Food and Drug Administration (FDA) approved the live attenuated VZV vaccine (Zostavax) for use in the prevention of HZ in adults, 60 years and older. Moreover, the Advisory Committee on Immunization Practices (ACIP) has recommended that this vaccine should be administered to all individuals age 60 and older.2 This article will: (1) review the pharmacology and FDA indications of VZV vaccine, (2) review the safety and efficacy of VZV vaccine, and (3) review the dosage and cost of this new vaccine.
VZV vaccine is marketed as a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV derived from children with varicella. The next step in the production of this vaccine involved the introduction of virus into human embryonic lung cell cultures and propagation in human embryonic lung cell cultures. Finally, propagation occurred in human diploid cell cultures.3
The commercially available VZV vaccine is marketed as a single-dose vial of lyophilized vaccine, that should be stored frozen at -200C° or colder. Reconstitution of the vaccine involves the use of the manufacturer-supplied, preservative-free diluent. In order to minimize potency decay of VZV vaccine, the reconstituted vaccine must be administered immediately. If the reconstituted product is not used within 30 minutes, it should be discarded.3
The FDA-approved dose of VZV is a single dose of 0.65 ml of the vaccine (minimum potency, 19,400 plaque-forming units) administered subcutaneously to adults age 60 and older. Individuals who have a history of anaphylactic/anaphylactoid reaction to gelatin or neomycin, who are immunocompromised (AIDS; leukemia; any type of lymphoma; receiving immunosuppressive therapy), who have active/untreated tuberculosis, or are pregnant, should not receive VZV.
Table 1 summarizes the key pharmacologic properties of VZV vaccine.1-5 See pages 102-103.
Clinical Efficacy of VZV Vaccine
VZV vaccine is marketed as a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV derived from children with varicella. The next step in the production of this vaccine involved the introduction of virus into human embryonic lung cell cultures and propagation in human embryonic lung cell cultures. Finally, propagation occurred in human diploid cell cultures.3
The commercially available VZV vaccine is marketed as a single-dose vial of lyophilized vaccine, which should be stored frozen at -200C or colder. Reconstitution of the vaccine involves the use of the manufacturer-supplied, preservative-free diluent. In order to minimize potency decay of VZV vaccine, the reconstituted vaccine must be administered immediately. If the reconstituted product is not used within 30 minutes, it should be discarded.3
The FDA-approved dose of VZV is a single dose of 0.65 ml of the vaccine (minimum potency, 19,400 plaque-forming units) administered subcutaneously to adults age 60 and older. Individuals who have a history of anaphylactic/anaphylactoid reaction to gelatin or neomycin, who are immunocompromised (AIDS; leukemia; any type of lymphoma; receiving immunosuppressive therapy), who have active/untreated tuberculosis, or are pregnant, should not receive VZV.
VZV vaccine has been studied for its efficacy in preventing HZ and postherpetic neuralgia in a total of 7 trials.5 Data from the "Shingles Prevention Study" provided sufficient evidence in support of the vaccine's efficacy against development of HZ and postherpetic neuralgia in adults older than 60 years.1,5
In brief, this study included 38,546 subjects from multiple Veterans Affairs Medical Centers throughout the United States (not including Hawaii), of whom 95% were Caucasians residing in the U.S. for a minimum of 30 years.1,5 The primary efficacy measures used in this pivotal study were incidence of postherpetic neuralgia and the HZ burden of illness score (BOI), a composite of the incidence, severity, and duration of pain/discomfort caused by HZ. Secondary efficacy measures included the incidence of HZ, duration of clinically significant HZ pain, and severity of HZ.
Because the focus of this study involved the use of a live vaccine, numerous exclusion criteria were set in place by the investigators. Immunodeficiency, inability to adhere to the study protocol, history of anaphylactic reaction to gelatin, allergic sensitivity to neomycin, prior HZ, prior receipt of varicella vaccine, premenopausal status, receipt of inactivated vaccine within the past 2 weeks, and receipt of antiviral therapy at the time of study enrollment precluded subjects from participating in the Shingles Prevention Study.5
Administration of a single dose of VZV (0.5 mL) resulted in a lower incidence (cases per 1000 patient years) of postherpetic neuralgia compared with placebo (0.46 vs. 1.38; relative risk, 0.665; 95% CI, 0.475 to 0.792, p < 0.001). In addition to superiority in prevention of postherpetic neuralgia, receipt of VZV resulted in significantly lower BOI scores compared with those observed in placebo-treated patients (2.21 vs. 5.68; relative risk, 0.611; 95% CI, 0.511 to 0.691, p < 0.001). The secondary endpoint of HZ incidence (cases per 1000 patient years) was noted to be significantly lower in VZV-treated subjects compared with placebo-treated patients (5.42 vs. 11.12; relative risk, 0.513; 95% CI, 0.442 to 0.576, p < 0.001). Of note, a post-hoc analysis revealed a much lower efficacy of VZV in preventing HZ in older patients (≥ 75 years), as vaccine efficacies were only 37% in participants 75 to 79 years of age, and 18% in participants over age 80 years. However, the proportion of subjects over age 80 years (~ 7%) and the number of HZ events were low in this study.1,5
Table 2 summarizes the key points of the Shingles Prevention Study. See page 103.
Conclusions
To date, VZV represents the only commercially available agent shown to prevent HZ and postherpetic neuralgia in older (especially 60-69 years), adult patients. Questions that remain to be answered include the efficacy of VZV in the oldest adult population (≥70 years), the duration of immune response (data available up to 4 years post-administration), and the safety/efficacy of VZV in non-Caucasian individuals.
References:
- Oxman MN, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271-2284.
- CDC Press Release. CDC's Advisory Committee Recommends "Shingles" Vaccination. Accessed on May 1, 2007. www.cdc.gov
- Live Zoster Vaccine (Zostavax ) prescribing information. Whitehouse Station, NJ: Merck & Co., Inc.: February 2007.
- Hornberger J, Robertus K. Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Ann Intern Med 2006;145:317-325.
- VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. National PBM Drug Monograph: Varicella Virus Vaccine Live (Zostavax ). November 2006. Accessed on May 11, 2007. www.pbm.va.gov
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