In clinical trials, ZOSTAVAX has been evaluated for safety in approximately 21,000 adults. In the largest of these trials, the Shingles Prevention Study (SPS), subjects received a single dose of either ZOSTAVAX (n=19,270) or placebo (n=19,276). The racial distribution across both vaccination groups was similar: White (95%); Black (2.0%); Hispanic (1.0%) and Other (1.0%) in both vaccination groups. The gender distribution was 59% male and 41% female in both vaccination groups. The age distribution of subjects enrolled, 59-99 years, was similar in both vaccination groups.

The Adverse Event Monitoring Substudy (n=3,345 received ZOSTAVAX and n=3,271 received placebo) used vaccination report cards (VRC) to record adverse events occurring from Days 0 to 42 postvaccination (97% of subjects completed VRC in both vaccination groups). In addition, monthly surveillance for hospitalization was conducted through the end of the study, 2 to 5 years postvaccination.

The remainder of subjects in the SPS (n=15,925 received ZOSTAVAX and n=16,005 received placebo) were actively followed for safety outcomes through Day 42 postvaccination and passively followed for safety after Day 42.

Because clinical trials are conducted under conditions that may not be typical of those observed in clinical practice, the adverse reaction rates presented below may not be reflective of those observed in clinical practice.

In the overall study population, serious adverse experiences (SAEs) occurred at a similar rate (1.4%) in subjects vaccinated with ZOSTAVAX or placebo.

In the AE Monitoring Substudy, the rate of SAEs was increased in the group of subjects who received ZOSTAVAX as compared to the group of subjects who received placebo, from Day 0-42 postvaccination (Table 4).

Table 4
Number of Subjects with ≥1 Serious Adverse Experience (0-42 Days Postvaccination) in the Shingles Prevention Study

N=number of subjects in cohort with safety follow-up
n=number of subjects reporting an SAE 0-42 Days postvaccination

Table 5 displays selected cardiovascular SAEs occurring in the SPS within 42 days postvaccination.

Table 5
Selected Serious Adverse Experiences (SAEs) Reported More Frequently After ZOSTAVAX than After Placebo Days 0-42 Postvaccination in the Shingles Prevention Study

N=number of subjects with safety follow-up
n=number of subjects reporting SAE within the category
* CAD-related conditions: angina pectoris, coronary artery disease, coronary occlusion, cardiovascular disorder, myocardial ischemia, & myocardial infarction

Rates of hospitalizations were similar among subjects who received ZOSTAVAX and subjects who received placebo in the AE Monitoring Substudy, throughout the entire study.

Investigator-determined, vaccine-related serious adverse experiences were reported for 2 subjects vaccinated with ZOSTAVAX (asthma exacerbation and polymyalgia rheumatica) and 3 subjects who received placebo (Goodpastures syndrome, anaphylactic reaction, and polymyalgia rheumatica).

The overall incidence of death occurring Days 0 to 42 postvaccination was similar between vaccination groups during the Days 0-42 postvaccination period; 14 deaths occurred in the group of subjects who received ZOSTAVAX and 16 deaths occurred in the group of subjects who received placebo. The most common reported cause of death was cardiovascular disease (10 in the group of subjects who received ZOSTAVAX, 8 in the group of subjects who received placebo). The overall incidence of death occurring at any time during the study was similar between vaccination groups: 793 deaths (4.1%) occurred in subjects who received ZOSTAVAX and 795 deaths (4.1%) in subjects who received placebo.

Injection-site and systemic adverse experiences reported at an incidence ≥1% are shown in Table 6. Most of these adverse experiences were reported as mild in intensity. The overall incidence of vaccine-related injection-site adverse experiences was significantly greater for subjects vaccinated with ZOSTAVAX versus subjects who received placebo (48% for ZOSTAVAX and 17% for placebo).

Table 6
Injection-Site and Systemic Adverse Experiences Reported by Vaccine Report Card in ≥1% of Adults Who Received ZOSTAVAX or Placebo (0-42 Days Postvaccination) in the AE Monitoring Substudy of the Shingles Prevention Study

^† Designates a solicited adverse experience. Injection-site adverse experiences were solicited only from Days 0-4 postvaccination.

The numbers of subjects with elevated temperature (≥38.3°C [≥101.0°F]) within 42 days postvaccination were similar in the ZOSTAVAX and the placebo vaccination groups [27 (0.8%) vs. 27 (0.9%), respectively].

The following adverse experiences in the AE Monitoring Substudy of the SPS (Days 0 to 42 postvaccination) were reported at an incidence ≥1% and greater in subjects who received ZOSTAVAX than in subjects who received placebo, respectively: respiratory infection (65 [1.9%] vs. 55 [1.7%]), fever (59 [1.8%] vs. 53 [1.6%]), flu syndrome (57 [1.7%] vs. 52 [1.6%]), diarrhea (51 [1.5%] vs. 41 [1.3%]), rhinitis (46 [1.4%] vs. 36 [1.1%]), skin disorder (35 [1.1%] vs. 31 [1.0%]), respiratory disorder (35 [1.1%] vs. 27 [0.8%]), asthenia (32 [1.0%] vs. 14 [0.4%]).

AE Monitoring Substudy subjects in the Shingles Prevention Study were monitored for hospitalizations through monthly automated phone queries and the remainder of subjects were passively monitored for safety in this study from Day 43 postvaccination through study end.

Over the course of the study (4.9 years), 51 individuals (1.5%) receiving ZOSTAVAX were reported to have congestive heart failure (CHF) or pulmonary edema compared to 39 individuals (1.2%) receiving placebo in the AE Monitoring Substudy; 58 individuals (0.3%) receiving ZOSTAVAX were reported to have congestive heart failure (CHF) or pulmonary edema compared to 45 (0.2%) individuals receiving placebo in the overall study.

In an additional clinical study, high potency ZOSTAVAX (203,000 plaque-forming units (pfu)) administered to 461 subjects was compared to a lower potency ZOSTAVAX (57,000 pfu; similar to potencies studied in the Shingles Prevention Study) administered to 234 subjects. Moderate or severe injection-site reactions were more common in the recipients of the higher potency ZOSTAVAX (17%) as compared to the lower potency recipients (9%). Among recipients of the higher potency ZOSTAVAX, 4 subjects (0.9%) reported SAEs (1 case each of angina pectoris, coronary artery disease, depression and enteritis); 1 subject (0.4%) receiving the lower potency ZOSTAVAX reported an SAE (lung cancer).

Within the 42-day postvaccination reporting period in the SPS, noninjection-site zoster-like rashes were reported by 53 subjects (17 for ZOSTAVAX and 36 for placebo). Of 41 specimens that were adequate for PCR testing, wild-type VZV was detected in 25 (5 for ZOSTAVAX, 20 for placebo) of these specimens. The Oka/Merck strain of VZV was not detected from any of these specimens.

Of reported varicella-like rashes (n=59), 10 had specimens that were available and adequate for PCR testing. VZV was not detected in any of these specimens.

In all other clinical trials in support of ZOSTAVAX, the reported rates of noninjection-site zoster-like and varicella-like rashes within 42 days postvaccination were also low in both zoster vaccine recipients and placebo recipients. Of the 17 reported varicella-like rashes and noninjection-site, zoster-like rashes, 10 specimens were available and adequate for PCR testing. The Oka/Merck strain was identified by PCR analysis from the lesion specimens of two subjects who reported varicella-like rashes (onset on Day 8 and 17).

The U.S. Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. For information or a copy of the vaccine reporting form, call the VAERS toll-free number at 1-800-822-7967 or report online to www.vaers.hhs.gov.⁴

Concurrent administration of ZOSTAVAX and antiviral medications known to be effective against VZV has not been evaluated. Concurrent administration of ZOSTAVAX and other vaccines has not been evaluated.

REFERENCES

4. Atkinson WL, Pickering LK, Schwartz B, Weniger BG, Iskander JK, Watson JC. General recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR 2002;51(RR02):1-36.

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