Zoster vaccine (Zostavax®): a guide to its use in preventing herpes zoster and postherpetic neuralgia

Zostavax is a one-dose, high-potency, live, attenuated varicella zoster virus (VZV) vaccine indicated to prevent herpes zoster and herpes zoster-related postherpetic neuralgia in immunocompetent adults aged 50 years. In clinical trials, zoster vaccine provided VZV-specific cell-mediated immunity, reduced herpes zoster-related burden of illness, and decreased the incidence of herpes zoster and postherpetic neuralgia. - The Shingles Prevention Study was a randomized, doubleblind, protective efficacy trial that included adults aged 60 years who had a history of varicella or had been resident in the continental US for 30 years, and no history of herpes zoster.[6,7] Participants received a single subcutaneous injection of zoster vaccine (n = 19 254) or placebo (n = 19 247), and were followed for up to 4.5 years.[6] Zoster vaccine was effective in reducing the burden of illness associated with herpes zoster in older adults.[6] This primary endpoint reflects the incidence, duration and severity of herpes zoster, and was based on herpes zoster severity-of-illness scores. Statistical analysis of this endpoint determined a vaccine efficacy score, which was the percentage reduction in the herpes zoster burden-of-illness score for zoster vaccine versus placebo.[6] For all participants, the herpes zoster burden-of-illness score in zoster vaccine recipients was less than half that of placebo recipients (p < 0.001) and the vaccine efficacy for burden-of-illness was 61% (95% CI 51, 69), which met the prespecified efficacy criterion (figure 1). This efficacy criterion was also met in analyses that stratified the sample according to age group and sex (figure 1), suggesting that these factors had little impact on vaccine efficacy.[6] Zoster vaccine led to an 2-fold reduction in the incidence of herpes zoster relative to placebo (5.4 vs 11.1 cases per 1000 person-years; p < 0.001). The vaccine efficacy for herpes zoster incidence was 51% (95% CI 44, 58).[6] Vaccine efficacy for herpes zoster incidence did not differ significantly Table I. Prescribing summary of zoster vaccine (Zostavax ) in the EU[4]a What is its approved indication? Prevention of herpes zoster and herpes zoster-related postherpetic neuralgia in adults aged 50 y What is the composition of the vaccine? Contains not less than 19 400 plaque-forming units per dose of the Oka/Merck strain of varicella zoster virus How should it be administered? Single 0.65 mL dose as a subcutaneous injection (preferably in the deltoid region) How is it available and how should it be stored? Powder (vial) plus solvent for suspension for injection (vial or prefilled syringe): mix prior to administration to prepare one dose Prior to reconstitution: refrigerate at 28 C in the original packaging After reconstitution: use immediately (stable for 30 min when stored at 2025 C) In which populations is the vaccine contraindicated? Individuals with primary or acquired immunodeficiency, or active untreated tuberculosis Individuals receiving immunosuppressive treatments (including high-dose corticosteroids, but excluding topical or inhaled corticosteroids, low-dose systemic corticosteroids or corticosteroid replacement therapy) What precautions should be taken with its use? Consider postponing vaccination in individuals with fever What is the theoretical risk of secondary transmission of the vaccine virus? Although secondary transmission of the vaccine virus was not reported in clinical trials of this vaccine, post-marketing experience with varicella vaccines suggests that transmission may occur rarely between vaccinees who develop a varicella-like rash and susceptible contacts (e.g. varicella zoster virus-susceptible infants) There have also been reports of transmission of vaccine virus from varicella vaccine recipients who did not develop a varicella-like rash The theoretical risk of transmission of the attenuated vaccine virus to a susceptible individual should be weighed against the risk of developing natural herpes zoster that could be transmitted to a susceptible individual Can it be administered concomitantly with other vaccines? May be administered concomitantly with inactivated influenza vaccine (as a separate injection at different body sites) Should not be administered concomitantly with 23-valent pneumococcal vaccine (immunogenicity of zoster vaccine may be reduced) a Consult local prescribing information for further details. according to sex, but was significantly lower in participants aged 70 years than in participants aged 6069 years (38% vs 64%, p < 0.001).[6] No vaccine virus DNA was detected in any participant with suspected herpes zoster, indicating that the vaccine did not cause the herpes zoster in those cases.[6] Compared with placebo, zoster vaccine led to an 3-fold reduction in the incidence of clinically significant postherpetic neuralgia (0.5 vs 1.4 cases per 1000 person-years; p < 0.001). The vaccine efficacy for postherpetic neuralgia incidence was 67% (95% CI 48, 79), which met the prespecified efficacy criterion of a 62% relative reduction in the incidence of the condition, with the lower bound of the 95% CI >25%. When subgroup analyses were performed according to age and sex, the vaccine efficacy for postherpetic neuralgia incidence was 63% for all subgroups, and met the criterion in all instances except for the subgroup aged 6069 years (vaccine efficacy for postherpetic neuralgia incidence 66% [95% CI 20, 87]).[6] Moreover, relative to placebo recipients, zoster vaccine recipients who developed herpes zoster had a shorter median duration of pain and discomfort associated with the condition, lower mean herpes zoster severity-of-illness scores, and a decrease in herpes zoster-related interference with activities of daily living.[6,8] In the overall population, zoster vaccine was associated with reductions relative to placebo in herpes zoster-related interference with activities of daily living and the effect of herpes zoster on measures of healthrelated quality of life.[8] y or aged 5059 years? Zoster vaccine was also effective in reducing the incidence of herpes zoster in a study in adults aged 5059 years with no history of herpes zoster.[9] Over a period of 2.2 years in a randomized, double-blind study, 30 cases of herpes zoster were reported in 11 211 recipients of zoster vaccine compared with 99 cases in 11 228 recipients of placebo, which equates to an incidence rate 1.99 vs 6.57 per 1000 person-years. The prespecified success criterion for zoster vaccine was met, as its estimated vaccine efficacy was 69.8% (95% CI 54.1, 80.6).[9] Zoster vaccine was effective in reducing the incidence of herpes zoster and its associated burden of illness through to the year 7 follow-up in a subsample of zoster vaccine recipients from the Shingles Prevention Study who were Age 6069y Age 70y Fig. 1. Efficacy of zoster vaccine in reducing the burden of illness associated with herpes zoster in adults aged 60 y. Weighted average h (...truncated)