ZOSTAVAX SIDE EFFECTS

SIDE EFFECTS

The most frequent adverse reactions, reported in ≥ 1% of subjects vaccinated with ZOSTAVAX, were headache and injection-site reactions.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, rates of adverse reactions observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

ZOSTAVAX Efficacy and Safety Trial (ZEST) in Subjects 50 to 59 Years of Age

In the ZEST study, subjects received a single dose of either ZOSTAVAX (N=11,184) or placebo (N=11,212). The racial distribution across both vaccination groups was similar: White (94.4%); Black (4.2%); Hispanic (3.3%) and Other (1.4%) in both vaccination groups. The gender distribution was 38% male and 62% female in both vaccination groups. The age distribution of subjects enrolled, 50 to 59 years, was similar in both vaccination groups. All subjects received a vaccination report card (VRC) to record adverse events occurring from Days 1 to 42 postvaccination.

In the ZEST study, serious adverse events occurred at a similar rate in subjects vaccinated with ZOSTAVAX (0.6%) or placebo (0.5%) from Days 1 to 42 postvaccination.

In the ZEST study, all subjects were monitored for adverse reactions. An anaphylactic reaction was reported for one subject vaccinated with ZOSTAVAX.

Most Common Adverse Reactions and Experiences in the ZEST Study

The overall incidence of vaccine-related injection-site adverse reactions within 5 days post-vaccination was greater for subjects vaccinated with ZOSTAVAX as compared to subjects who received placebo (63.6% for ZOSTAVAX and 14.0% for placebo). Injection-site adverse reactions occurring at an incidence ≥ 1% within 5 days post-vaccination are shown in Table 1.

Table 1: Injection-Site Adverse Reactions Reported in ≥ 1% of Adults Who Received ZOSTAVAX or Placebo Within 5 Days Post-Vaccination in the ZOSTAVAX Efficacy and Safety Trial

Systemic adverse reactions and experiences reported during Days 1-42 at an incidence of ≥ 1% in either vaccination group were headache (ZOSTAVAX 9.4%, placebo 8.2%) and pain in the extremity (ZOSTAVAX 1.3%, placebo 0.8%), respectively.

The overall incidence of systemic adverse experiences reported during Days 1-42 was higher for ZOSTAVAX (35.4%) than for placebo (33.5%).

Shingles Prevention Study (SPS) in Subjects 60 Years of Age and Older

In the SPS, the largest clinical trial of ZOSTAVAX, 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 of the SPS, designed to provide detailed data on the safety profile of the zoster vaccine (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.

Serious Adverse Events Occurring 0-42 Days Postvaccination

In the overall SPS study population, serious adverse events 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 (Table 2).

Table 2: Number of Subjects with ≥ 1 Serious Adverse Events the Shingles Prevention Study

Among reported serious adverse events in the SPS (Days 0 to 42 postvaccination), serious cardiovascular events occurred more frequently in subjects who received ZOSTAVAX (20 [0.6%]) than in subjects who received placebo (12 [0.4%]) in the AE Monitoring Substudy. The frequencies of serious cardiovascular events were similar in subjects who received ZOSTAVAX (81 [0.4%]) and in subjects who received placebo (72 [0.4%]) in the entire study cohort (Days 0 to 42 postvaccination).

Serious Adverse Events Occurring Over the Entire Course of the Study

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

Fifty-one 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 the SPS, all subjects were monitored for vaccine-related SAEs. 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 (Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia rheumatica).

Deaths

The incidence of death was similar in the groups receiving ZOSTAVAX or placebo 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.

Most Common Adverse Reactions and Experiences in the AE Monitoring Substudy of the SPS

Injection-site adverse reactions reported at an incidence ≥ 1% are shown in Table 3. Most of these adverse reactions were reported as mild in intensity. The overall incidence of vaccine-related injection-site adverse reactions was significantly greater for subjects vaccinated with ZOSTAVAX versus subjects who received placebo (48% for ZOSTAVAX and 17% for placebo).6

Table 3: Injection-Site Adverse Reactions* in ≥ 1% of Adults Who Received ZOSTAVAX or Placebo Within 5 Days Postvaccination from the AE Monitoring Substudy of the Shingles Prevention Study

Headache was the only systemic adverse reaction reported on the vaccine report card between Days 0-42 by ≥ 1% of subjects in the AE Monitoring Substudy in either vaccination group (ZOSTAVAX 1.4%, placebo 0.8%).

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%]).

VZV Rashes Following Vaccination

Within the 42-day postvaccination reporting period in the ZEST, noninjection-site zoster-like rashes were reported by 34 subjects (19 for ZOSTAVAX and 15 for placebo). Of 24 specimens that were adequate for Polymerase Chain Reaction (PCR) testing, wild-type VZV was detected in 10 (3 for ZOSTAVAX, 7 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=124, 69 for ZOSTAVAX and 55 for placebo), 23 had specimens that were available and adequate for PCR testing. VZV was detected in one of these specimens in the ZOSTAVAX group; however, the virus strain (wild-type or Oka/Merck strain) could not be determined.

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 Polymerase Chain Reaction (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 clinical trials in support of the initial licensure of the frozen formulation 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 and placebo recipients. Of 17 reported varicella-like rashes and non-injection site zoster-like rashes, 10 specimens were available and adequate for PCR testing, and 2 subjects had varicella (onset Day 8 and 17) confirmed to be Oka/Merck strain.

Postmarketing Experience

The following additional adverse reactions have been identified during postmarketing use of ZOSTAVAX. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Gastrointestinal disorders: nausea

Infections and infestations: herpes zoster (vaccine strain)

Skin and subcutaneous tissue disorders: rash

Musculoskeletal and connective tissue disorders: arthralgia; myalgia

General disorders and administration site conditions: injection-site rash; pyrexia; injection-site urticaria; transient injection-site lymphadenopathy

Immune system disorders: hypersensitivity reactions including anaphylactic reactions

Reporting Adverse Events

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.²

SRC: NLM .