ZOSTAVAX®

[Zoster Vaccine Live (Oka/Merck)]

Approved by the Food and Drug

Administration on May 25, 2006

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 Description

• Lyophilized preparation of the Oka/Merck strain of live,

attenuated VZV.
• Each 0.65-mL dose contains a minimum of 19,400 plaque-
forming units (PFU).
• Each dose also contains sucrose, hydrolyzed porcine
gelatin, sodium chloride, monosodium L-glutamate, sodium
phosphate dibasic, potassium phosphate monobasic, and
potassium chloride; residual components of MRC-5 cells,
including DNA and protein, and trace quantities of neomycin
and bovine calf serum.
• Contains no preservatives.

Description

• ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is a lyophilized preparation

of the Oka/Merck strain of live, attenuated VZV.
• Each 0.65-mL dose of the vaccine contains a minimum of 19,400 plaque-forming
units (PFU) of attenuated virus.
• Each dose also contains sucrose, hydrolyzed porcine gelatin, sodium chloride,
monosodium L-glutamate, sodium phosphate dibasic, potassium phosphate
monobasic, and potassium chloride; residual components of MRC-5 cells, including
DNA and protein, and trace quantities of neomycin and bovine
calf serum.
• The product does not contain preservatives.

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 Indications and Usage

• ZOSTAVAX is indicated for the prevention of herpes zoster

(shingles) in individuals 60 years of age and older.
• ZOSTAVAX is not indicated for the treatment of
zoster or postherpetic neuralgia.

Indications and Usage

• ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is indicated for the prevention of

herpes zoster (or shingles) in individuals 60 years of age and older.
• ZOSTAVAX is not indicated for the treatment of zoster or postherpetic neuralgia.

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 Contraindications

• ZOSTAVAX should not be administered to individuals:

– With a history of anaphylactic/anaphylactoid reaction to gelatin,
neomycin, or any other component of the vaccine (see WARNINGS).
– With a history of primary or acquired immunodeficiency states
including leukemia; lymphomas of any type, or other malignant
neoplasms affecting the bone marrow or lymphatic system;
or AIDS or other clinical manifestations of infection with human
immunodeficiency viruses (see WARNINGS).
– On immunosuppressive therapy, including high-dose corticosteroids.
– With active untreated tuberculosis.
– Who are or may be pregnant (see PRECAUTIONS, Pregnancy).

Contraindications

ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is contraindicated in individuals who:

• Have a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any
other component of the vaccine (see WARNINGS).
• Have a history of primary or acquired immunodeficiency states including leukemia;
lymphomas of any type, or other malignant neoplasms affecting the bone marrow or
lymphatic system; or AIDS or other clinical manifestations of infection with human
immunodeficiency viruses (see WARNINGS).
• Are on immunosuppressive therapy, including high-dose corticosteroids.
• Have active untreated tuberculosis.
• Are or may be pregnant. (Please refer to PRECAUTIONS, Pregnancy in the
Prescribing Information.)

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 Clinical Pharmacology:
The Shingles Prevention Study Design

Subjects Enrolled
N=38,546 Adverse Event
(AE) Substudy
n=6,616

Immunogenicity
Substudy
n=1,395

Age 60 to 69 years Age ≥70 years

n=20,747 n=17,799

Zoster vaccine Placebo Zoster vaccine Placebo

n=10,378 n=10,369 n=8,892 n=8,907

Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284.

Clinical Pharmacology: The Shingles Prevention Study Design

• The Shingles Prevention Study was a placebo-controlled, randomized, double-blind
study.1
• The study enrolled a total of 38,546 subjects who were 60 years of age or older.1
• Randomization was stratified by age1:
– 60 to 69 years of age
– ≥70 years of age
• Subjects were randomized to receive either a single dose of zoster vaccine (n=19,270)
or placebo (n=19,276).1
• The median follow-up of the study was 3.1 years (range 31 days to 4.9 years).
• The study excluded people who were immunocompromised or using corticosteroids on
a regular basis, anyone with a previous history of HZ, and
those with conditions that might interfere with study evaluations, including people with
cognitive impairment, severe hearing loss, those who were non-ambulatory and those
whose survival was not considered to be at least 5 years.
• The clinical trial included 2 substudies1:
– The Adverse Event (AE) Monitoring Substudy, which comprised
6,616 subjects.
– An immunogenicity substudy, which comprised 1,395 subjects.
• Zoster cases were confirmed by polymerase chain reaction (93%), viral
culture (1%), or in the absence of viral detection, by the Clinical Evaluation Committee
(6%).
• Individuals in both vaccination groups who developed zoster were given famciclovir
and, as necessary, pain medications.1

Reference:
1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
N Engl J Med. 2005;352:2271–2284.
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 Patient Demographics in the
Shingles Prevention Study

Vaccine Group Placebo Group

Characteristic N=19,270 N=19,276
Age n (%)
60 to 69 years 10,378 (53.9) 10,369 (53.8)
≥70 years 8,892 (46.1) 8,907 (46.2)
Gender n (%)
Male 11,403 (59.2) 11,357 (58.9)
Female 7,867 (40.8) 7,919 (41.1)
Race n (%)
White 18,393 (95.4) 18,381 (95.4)
Black 395 (2.0) 420 (2.2)
Hispanic 265 (1.4) 248 (1.3)
Other or unknown 217 (1.1) 227 (1.2)
Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284.

Patient Demographics in the Shingles Prevention Study

• Baseline patient characteristics were similar in both vaccination groups

in the Shingles Prevention Study.1
– The age distribution of enrolled patients was 59 to 99 years in
both groups.
– The gender distribution was 59% male and 41% female.1
– The racial distribution of white (95%), black (2%), Hispanic (1%), and other
(1%) was also similar in both groups.1

Reference:
1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
N Engl J Med. 2005;352:2271–2284.
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 Prevention of Herpes Zoster

–51% Placebo
700 (95% CI: 44%, 58%) ZOSTAVAX

600 642
Number of zoster cases
500
–64%
400 (95% CI: 56%, 71%)
–41%
300 315 334 (95% CI: 28%, 52%)

261
200
156 –18%
100 122 (95% CI: –29%, 48%)
47 37
0
11.1 5.4 10.8 3.9 11.4 6.7 12.2 9.9
Incidence rate of zoster per 1,000 person-years

Overall 60–69 70–79 ≥80

Age (years)

Prevention of Herpes Zoster

• ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] significantly reduced the risk of

developing zoster compared with placebo*: 315/19,254 cases (5.4 cases per 1,000
person-years) vs 642/19,247 cases [11.1 cases per 1,000 person-years]). The
protective efficacy was 51% (95% CI: 44%, 58%).1
– Vaccine efficacy for the prevention of zoster was highest for those subjects
60 to 69 years of age and declined with increasing age.
– ZOSTAVAX reduced the incidence of zoster by 64% in individuals
60 to 69 years of age (ZOSTAVAX, n=10,370; placebo, n=10,356);
by 41% in individuals 70 to 79 years of age (ZOSTAVAX, n=7,621; placebo,
n=7,559); and by 18% in individuals 80 years of age or
older (ZOSTAVAX, n=1,263; placebo, n=1,332).
• As with any vaccine, vaccination with ZOSTAVAX may not result in protection
of all vaccine recipients.
• The duration of protection after vaccination with ZOSTAVAX is unknown. In the
Shingles Prevention Study, protection from zoster was demonstrated through 4
years of follow-up. The need for revaccination has not been defined.

*Primary analysis was performed on the modified intent-to-treat (MITT) population that
included all randomized patients who were followed for at least 30 days postvaccination and
did not develop an evaluable case of zoster within the first 30 days postvaccination.

Reference:
1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
N Engl J Med. 2005;352:2271–2284.
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 Postherpetic Neuralgia* in the
Shingles Prevention Study

50 Placebo ZOSTAVAX

With Postherpetic Neuralgia

40

% of HZ Cases 30
–26%
(95% CI: –69%, 68%)

–39%** –55% 25.5

20 (95% CI: 7%, 59%) (95% CI: 18%, 76%)
17.2 18.9
–5%
10 12.5 (95% CI: –107%, 56%)
8.6 6.9 6.6 7.7
0
Number of PHN Cases 80 27 23 8 45 12 12 7
Number of HZ Cases 642 315 334 122 261 156 47 37

Overall 60–69 70–79 ≥80

Age (years)
*Zoster-associated pain rated as ≥3 on a 10-pt scale and occurring or persisting at least 90 days after rash onset.
**Age-adjusted estimate based on the age strata (60–69 and ≥70 years of age) at randomization.

Postherpetic Neuralgia in the Shingles Prevention Study

• Postherpetic neuralgia was defined as zoster-associated pain (rated as ≥3 on a 10-

point scale by the patient) occurring or persisting at least 90 days following the
onset of rash in evaluable cases of zoster.
• Overall, the benefit of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] in the
prevention of postherpetic neuralgia can be primarily attributed to the effect of the
vaccine on the prevention of zoster. Vaccination with ZOSTAVAX reduced the
incidence of postherpetic neuralgia in individuals 70 years of age and older who
developed zoster postvaccination.
• Following completion of the Shingles Prevention Study, a separate analysis was
conducted to evaluate the reduction in PHN in the group of individuals who have
been vaccinated with ZOSTAVAX, but who had developed zoster. In the analysis,
the overall efficacy of ZOSTAVAX for reduction of postherpetic neuralgia in patients
who developed zoster following vaccination was 39% (95% CI: 7%, 59%). This is an
age-adjusted estimate calculated based on the age strata of 60 to 69 and 70 years
of age and older at randomization.
• The vaccine efficacy against postherpetic neuralgia in patients who developed
zoster following vaccination was 5% (95% CI: –107%, 56%) in patients 60 to 69
years of age; 55% (95% CI: 18%, 76%) in patients 70 to 79 years of age: and 26%
(95% CI: –69%, 68%) in patients 80 years of age and older.

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 Specific Complications* of Zoster Among
HZ Cases in the Shingles Prevention Study

ZOSTAVAX Placebo
Complication (N = 19,270) (N = 19,276)
% Among % Among
( n = 321) (n = 659)
Zoster Cases Zoster Cases
Allodynia 135 42.1 310 47.0

Bacterial Superinfection 3 0.9 7 1.1

Dissemination 5 1.6 11 1.7
Impaired Vision 2 0.6 9 1.4
Ophthalmic Zoster 35 10.9 69 10.5
Peripheral Nerve Palsies (motor) 5 1.6 12 1.8
Ptosis 2 0.6 9 1.4
Scarring 24 7.5 57 8.6
Sensory Loss 7 2.2 12 1.8
N=number of subjects randomized
n=number of zoster cases, including those cases occurring within 30 days postvaccination, with these data available
*Complications reported at a frequency of ≥1% in at least one vaccination group among patients with zoster.

Specific Complications of Zoster Among HZ Cases in the Shingles Prevention

Study

• The table shows the number of patients with specific complications of zoster among
zoster cases that were reported in the Shingles Prevention Study at a frequency of
≥1% in at least one vaccination group among subjects with zoster.
– The number of zoster cases included the cases that developed within 30
days after vaccination.
• Prespecified zoster-related complications were reported less frequently in subjects
who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] compared to subjects
who received placebo.
• Among HZ cases, zoster-related complications were reported at similar rates in both
vaccination groups.
• Visceral complications reported by fewer than 1% of subjects with zoster included 3
cases of pneumonitis and 1 case of hepatitis in the placebo group, and 1 case of
meningoencephalitis in the vaccine group.

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 Immunogenicity Substudy

In the Shingles Prevention Study, ZOSTAVAX elicited higher VZV-specific

antibody responses at 6 weeks after vaccination compared with placebo

2.00

in VZV antibody*
Fold increase
1.75 1.7 (95% CI: 1.6, 1.8)

1.50

1.25
1.0
1.00
ZOSTAVAX Placebo
n= 691 n= 704

*As measured by gpELISA=glycoprotein enzyme-linked immunosorbent assay.

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Immunogenicity Substudy

• Immune responses to vaccination were evaluated in a subset of 1,395 subjects

enrolled in the Shingles Prevention Study.
• The vaccine elicited higher VZV-specific antibody responses at 6 weeks after
vaccination compared with placebo.
– There was a 1.7-fold increase in VZV antibody geometric mean titers (GMT)
as measured by gpELISA* (95% CI: 1.6, 1.8).
– The specific antibody level that correlates with protection from zoster has not
been established.

*gpELISA = glycoprotein enzyme-linked immunosorbent assay.

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 Warnings

• Vaccination with a live attenuated vaccine, such as ZOSTAVAX, may

result in a more extensive vaccine-associated rash or disseminated
disease in individuals who
are immunosuppressed. Safety and efficacy of ZOSTAVAX have not
been evaluated in individuals on immunosuppressive therapy, nor in
individuals receiving daily topical or inhaled corticosteroids or low-dose
oral corticosteroids.
• Neomycin allergy commonly manifests as a contact dermatitis, which is
not a contraindication to receiving this vaccine. Persons with a history of
anaphylactic reaction to topically or systemically administered neomycin
should not receive ZOSTAVAX (see CONTRAINDICATIONS).
• ZOSTAVAX is not a substitute for VARIVAX* [Varicella Virus Vaccine
Live (Oka/Merck)] and should not be used in children.

*Registered trademark of Merck & Co., Inc.

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Warnings

• Vaccination with a live attenuated vaccine, such as ZOSTAVAX® [Zoster Vaccine

Live (Oka/Merck)], may result in a more extensive vaccine-associated rash or
disseminated disease in individuals who are immunosuppressed.
• Safety and efficacy of ZOSTAVAX have not been evaluated in individuals on
immunosuppressive therapy, nor in individuals receiving daily topical or inhaled
corticosteroids or low-dose oral corticosteroids.
• Neomycin allergy commonly manifests as a contact dermatitis, which is not a
contraindication to receiving this vaccine. Persons with a history of anaphylactic
reaction to topically or systemically administered neomycin should not receive
ZOSTAVAX (see CONTRAINDICATIONS).
• ZOSTAVAX is not a substitute for VARIVAX* [Varicella Virus Vaccine Live
(Oka/Merck)] and should not be used in children.

*Registered trademark of Merck & Co., Inc.

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 Selected Precautions

• General
– As with any vaccine, adequate treatment provisions, including
epinephrine injection (1:1000), should be available for immediate
use should an anaphylactic/anaphylactoid reaction occur.
– Deferral of vaccination should be considered in acute illness
(eg, fever >38.5°C [>101.3°F])
– The duration of protection is unknown. In the Shingles Prevention
Study, protection from zoster was demonstrated through 4 years
of follow-up. The need for revaccination has not been defined.
– As with any vaccine, vaccination with ZOSTAVAX may not result in
protection of all
vaccine recipients.
– The use of ZOSTAVAX in individuals with a previous history
of zoster has not been studied.

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Selected Precautions

• As with any vaccine, adequate treatment provisions, including epinephrine injection

(1:1000), should be available for immediate use should an
anaphylactic/anaphylactoid reaction occur.
• Deferral of vaccination should be considered in acute illness (eg, fever >38.5°C
[>101.3°F]).
• The duration of protection after vaccination with ZOSTAVAX® [Zoster Vaccine Live
(Oka/Merck)] is unknown. In the Shingles Prevention Study, protection from zoster
was demonstrated through 4 years of follow-up. The need for revaccination has not
been defined.
• As with any vaccine, vaccination with ZOSTAVAX may not result in protection of all
vaccine recipients.
• The use of ZOSTAVAX in individuals with a previous history of zoster has not been
studied.

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 Selected Precautions (cont)

• Transmission
– Transmission of the vaccine virus has not been reported
in clinical trials.
– Postmarketing experience with varicella vaccines suggests that
transmission of vaccine virus may occur rarely between vaccinees
who develop a varicella-like rash and susceptible contacts.
– Transmission of vaccine virus from varicella vaccine recipients
without a VZV-like rash has been reported but has not been
confirmed.
– The risk of transmitting the attenuated vaccine virus to a susceptible
individual should be weighed against the risk of developing natural
zoster that could be transmitted to a susceptible individual.
– Vaccinees should be informed of the theoretical risk of transmitting
the vaccine virus to varicella-susceptible individuals, including
pregnant women who have not had chickenpox.

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Selected Precautions (cont)

• Transmission of the vaccine virus has not been reported in clinical trials.
• Postmarketing experience with varicella vaccines suggests that transmission of
vaccine virus may occur rarely between vaccinees who develop a varicella-like rash
and susceptible contacts.
• Transmission of vaccine virus from varicella vaccine recipients without a VZV-like
rash has been reported but has not been confirmed.
• The risk of transmitting the attenuated vaccine virus to a susceptible individual
should be weighed against the risk of developing natural zoster that could be
transmitted to a susceptible individual.
• Vaccinees should be informed of the theoretical risk of transmitting the vaccine virus
to varicella-susceptible individuals, including pregnant women who have not had
chickenpox.

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 Selected Precautions (cont)

• Drug Interactions
– 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.
• Pregnancy (Category C)
– ZOSTAVAX should not be administered to pregnant females;
furthermore, pregnancy should be avoided for 3 months following
vaccination.
• Nursing Mothers
– Caution should be exercised if ZOSTAVAX is administered to a
nursing woman.
• Pediatric Use
– ZOSTAVAX should not be used in children.

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Selected Precautions (cont)

• Concurrent administration of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] and

antiviral medications known to be effective against VZV has not been evaluated.
Concurrent administration of ZOSTAVAX and other vaccines
has not been evaluated.
• ZOSTAVAX should not be administered to pregnant females; furthermore,
pregnancy should be avoided for 3 months following vaccination.
• Some viruses are excreted in human milk; however, it is not known whether VZV is
secreted in human milk. Therefore, caution should be exercised if ZOSTAVAX is
administered to a nursing woman.
• ZOSTAVAX should not be used in children.

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 Adverse Reactions

• ZOSTAVAX was evaluated for safety in approximately

21,000 adults.
• Shingles Prevention Study
– Routine safety monitoring
• ZOSTAVAX: n=15,925; placebo: n=16,005
• Patients were actively followed for safety outcomes through Day 42
postvaccination.
• Subjects were followed passively for safety after Day 42 postvaccination
to the end of the study.
– AE Monitoring Substudy
• ZOSTAVAX: n=3,345; placebo: n=3,271
• Vaccination report cards used to record AEs for
42 days postvaccination
• Monthly surveillance for hospitalization 2 to 5 years postvaccination

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Adverse Reactions

• Overall, ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] has been evaluated in

approximately 21,000 adults.
• In the Shingles Prevention Study, patients were given either a single dose of the
zoster vaccine (n=19,270) or placebo (n=19,276).
• 15,925 subjects who received ZOSTAVAX and 16,005 subjects who received
placebo, were actively followed for safety outcomes through Day 42
postvaccination. Patients were followed passively for safety after Day 42
postvaccination to the end of the study.
• Patients enrolled in the AE Monitoring substudy (3,345 who received ZOSTAVAX
and 3,271 who received placebo) used vaccination report cards to record AEs
during the 42-day postvaccination period. Monthly surveillance for hospitalization
was conducted through the end of the study, 2 to 5 years postvaccination.
– 97% of patients in both vaccination groups completed the vaccination report
cards.

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

Relative
ZOSTAVAX Placebo Risk
n/N n/N (RR)
Cohort % % (95% CI)
Overall Study Cohort 255/18,671 254/18,717 1.01
(all ages) 1.4% 1.4% (0.85, 1.20)
60-69 years old 113/10,100 101/10,095 1.12
1.1% 1.0% (0.86, 1.46)
70-79 years old 115/7,351 132/7,333 0.87
1.6% 1.8% (0.68, 1.11)
≥80 years old 27/1,220 21/1,289 1.36
2.2% 1.6% (0.78, 2.37)
AE Monitoring Substudy Cohort 64/3,326 41/3,249 1.53
(all ages) 1.9 1.3 (1.04, 2.25)
60-69 years old 22/1,726 18/1,709 1.21
1.3% 1.1% (0.66, 2.23)
70-79 years old 31/1,383 19/1,367 1.61
2.2% 1.4% (0.92, 2.82)
≥80 years old 11/217 4/173 2.19
5.1% 2.3% (0.75, 6.45)

N = number of subjects in cohort with safety follow-up

n = number of subjects reporting an SAE 0–42 days postvaccination

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Number of Subjects With ≥1 Serious Adverse Experience (0-42 Days

Postvaccination) in the Shingles Prevention Study

• In the overall study population, SAEs occurred at a similar rate of 1.4% in patients
who received either ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] or placebo
(relative risk [RR]: 1.01).
– Investigator-determined, vaccine-related SAEs were reported for
2 subjects vaccinated with ZOSTAVAX (asthma exacerbation and
polymyalgia rheumatica) and 3 patients who received placebo
(Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia
rheumatica).
• In the AE Monitoring Substudy, the rate of SAEs was increased in the group that
received ZOSTAVAX compared to the placebo group (1.9% vs 1.3%, respectively;
RR: 1.53).
• The overall incidence of death occurring from Day 0 to Day 42 postvaccination was
similar in both groups: 14 deaths occurred in subjects who received ZOSTAVAX
and 16 deaths occurred in the placebo group. The most common cause of death in
both groups was cardiovascular disease (10 in the group who received ZOSTAVAX
and 8 in the group who received placebo). The overall incidence of death occurring
at any time during the study was similar between vaccination groups (4.1%).

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

AE Monitoring Substudy Entire Study Cohort

ZOSTAVAX Placebo ZOSTAVAX Placebo

N = 3,326 N = 3,249 N = 18,671 N = 18,717

n (%) n (%) n (%) n (%)

Overall Cardiovascular events by body system 20 (0.6) 12 (0.4) 81 (0.4) 72 (0.4)

Coronary Artery Disease-related conditions1 10 (0.3) 5 (0.2) 45 (0.2) 35 (0.2)

N=number of subjects with safety follow-up

n=number of subjects reporting SAE within the category
1CAD-related conditions: angina pectoris, coronary artery disease, coronary occlusion, cardiovascular disorder, myocardial

ischemia, & myocardial infarction

17

Selected Serious Adverse Experiences (SAE) Reported More Frequently After

ZOSTAVAX than After Placebo Days 0-42 Postvaccination in the Shingles
Prevention Study

• This table displays selected cardiovascular SAEs occurring in the SPS

within 42 days postvaccination.
• For the entire Shingles Prevention Study population, the rates of overall
cardiovascular events (0.4%), including coronary artery disease-related conditions
(0.2%), were similar in subjects vaccinated with ZOSTAVAX® [Zoster Vaccine Live
(Oka/Merck)] or placebo.
• In the AE Monitoring Substudy of the Shingles Prevention Study, between Days 0 to
42 postvaccination, the rate of overall cardiovascular events was higher after
ZOSTAVAX (0.6%) than after placebo (0.4%), including the rate of coronary artery
disease-related conditions postvaccination (ZOSTAVAX 0.3%, placebo 0.2%).

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 Injection-Site and Systemic
Adverse Experiences

Reported by vaccine report card in ≥1% of adults who received ZOSTAVAX or

placebo (0 to 42 days postvaccination) in the AE monitoring substudy of the
Shingles Prevention Study

ZOSTAVAX Placebo

(n = 3,345) (n= 3,271)

Adverse Experience % %

Injection Site
Erythema* 33.7 6.4
Pain/tenderness* 33.4 8.3
Swelling* 24.9 4.3
Hematoma 1.4 1.4
Pruritus 6.6 1.0
Warmth 1.5 0.3
Systemic
Headache 1.4 0.8

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

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Injection-Site and Systemic Adverse Experiences

• Vaccine-related injection-site reactions and systemic AEs reported at

an incidence of 1% or greater in the AE Monitoring Substudy are shown
in the table.
• Most of these AEs were reported as mild in intensity.
• The overall incidence of vaccine-related injection-site reactions was significantly
greater in subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)]
(48%) compared with those who received placebo (17%).
• The numbers of patients with elevated temperature (≥38.3°C [≥101.0°F]) within 42
days postvaccination were similar in the ZOSTAVAX and the placebo groups (0.8%
vs 0.9%, respectively).

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 Adverse Events Occurring
After Day 42 Postvaccination
• 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.

19

Adverse Events Occurring after Day 42 Postvaccination

• This slide shows adverse events occurring after Day 42 postvaccination through the
end of the study, a total of 4.9 years.

19
 Noninjection-Site Rash

• Shingles Prevention Study (0–42 days postvaccination)

– 53 noninjection-site zoster-like rashes reported
• 17 for ZOSTAVAX vs 36 for placebo
• Oka/Merck strain of VZV not detected in any of the 41
evaluable specimens
– 59 varicella-like rashes reported
• VZV not detected in any of the 10 evaluable specimens

• Other clinical trials

– Low reported rates of noninjection-site zoster-like and
varicella-like rashes

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Noninjection-Site Rash

• Within the 42-day postvaccination reporting period in the Shingles Prevention Study,
noninjection-site zoster-like rashes were reported in 17 subjects who received
ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] and in 36 subjects who received
placebo.
– Of the 53 rashes reported, 41 had specimens that were adequate for
polymerase chain reaction (PCR) testing.
– Wild-type VZV was detected in 25 specimens (5 for the zoster vaccine and
20 for placebo).
– Oka/Merck strain of VZV was not detected in any of these specimens.
• Of reported varicella-like rashes (n=59), VZV was not detected in any of the
10 specimens that were adequate for PCR testing.
• In all other clinical trials with the zoster vaccine, the rates of reported noninjection-
site zoster-like and varicella-like rashes within 42 days after vaccination were also
low; of the 17 reported varicella-like and noninjection-site, zoster-like rashes in
subjects receiving either the zoster vaccine or placebo, 10 were adequate for PCR
testing. The Oka/Merck strain was identified by PCR from specimens of 2 subjects
who reported varicella-like rashes (onset on Day 8 and 17).

20
 Dosage and Administration

• For SUBCUTANEOUS ADMINISTRATION only; do not inject

intravascularly.
• ZOSTAVAX is administered as a single dose.
• Reconstitution procedure
– Reconstitute immediately upon removal from freezer.
– To reconstitute, first withdraw entire contents of diluent vial into a syringe; inject all the
diluent into a vial of lyophilized vaccine; gently agitate to mix thoroughly.
– Injection procedure:
• Withdraw entire contents of reconstituted vaccine into a syringe.
• Inject total volume subcutaneously, preferably into upper arm.

• ADMINISTER IMMEDIATELY AFTER RECONSTITUTION.

• DISCARD RECONSTITUTED VACCINE IF NOT USED WITHIN
30 MINUTES.
• DO NOT FREEZE RECONSTITUTED VACCINE.

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Dosage and Administration

• ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is for subcutaneous administration

only; do not inject intravascularly.
• Individuals should receive a single dose.
• Reconstitute immediately upon removal from freezer.
• To reconstitute, first withdraw the entire contents of the diluent vial
into a syringe.
– Inject all of the diluent in the syringe into the vial of lyophilized
vaccine and gently agitate to mix thoroughly.
• Withdraw entire contents of reconstituted vaccine into a syringe and inject
the total volume subcutaneously, preferably into upper arm.
• The vaccine should be administered immediately after reconstitution,
to minimize loss of potency.
• Discard reconstituted vaccine if not used within 30 minutes.
• Do not freeze the reconstituted vaccine.

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 Conditions for Storage

• ZOSTAVAX
– STORE FROZEN at an average temperature of –15°C (+5°F) or
colder until it is reconstituted for injection.
• Any freezer, including frost-free, that has a separate sealed
freezer door and reliably maintains an average temperature
of –15°C or colder is acceptable for storing ZOSTAVAX.
• Diluent
– Store diluent separately at room temperature (20°C to 25°C,
68°F to 77°F) or in refrigerator (2°C to 8°C, 36°F to 46°F).

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Conditions for Storage

• ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] should be stored frozen

at an average temperature of –15ºC (+5ºF) or colder until it is reconstituted
for injection.
– Any freezer, including frost-free, that has a separate sealed freezer door and
reliably maintains an average temperature of –15ºC or colder is acceptable
for storing ZOSTAVAX.
• The diluent should be stored separately at room temperature (20°C to 25°C, 68°F to
77°F) or in refrigerator (2°C to 8°C, 36°F to 46°F).

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 Before administering
ZOSTAVAX,
please read the Prescribing Information by clicking
the link below

Click here to access the Prescribing Information and

Patient Product Information

www.MerckVaccines.com
www.ZOSTAVAX.com

ZOSTAVAX is a registered trademark of Merck & Co., Inc. 20651999(1)-08/07-ZOS

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