CDC Advisory Panel Votes to Recommend Merck's Shingles Vaccine, ZOSTAVAX(R), for Vaccination of Adults Age 60 and Over.

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. announced today that the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) voted unanimously to recommend that adults 60 years of age and older be vaccinated with ZOSTAVAX[R] [Zoster Vaccine Live (Oka/Merck)] to help prevent shingles (herpes zoster), a frequently painful disease marked by a blistering rash.

ZOSTAVAX was approved by the U.S. Food and Drug Administration (FDA) on May 25 for the prevention of shingles in individuals 60 years of age and older. ZOSTAVAX is not a treatment for shingles or postherpetic neuralgia (long-term nerve pain that can be a complication of shingles). ZOSTAVAX is given by a single dose by injection.

"ZOSTAVAX is the only medical option approved for the prevention of shingles and represents a major public health advance for people age 60 and older," said Mark Feinberg, M.D., Ph.D., vice president of Policy, Public Health and Medical Affairs, Merck Vaccines. "While a number of health plans are already offering insurance coverage of ZOSTAVAX, the panel's recommendation is likely to further increase coverage of the vaccine and further expand access to it among older people in the United States." The ACIP recommendations do not result in requirements for vaccine coverage by insurers; however, private insurers typically follow the Committee's guidance.

The ACIP also considered additional recommendations pertaining to specific uses of the vaccine. Details of the ACIP recommendations for ZOSTAVAX will be available from the CDC. The recommendations are under review by the director of the CDC and the Department of Health and Human Services and will become official when published in the CDC's Morbidity and Mortality Weekly Report.

Anyone who has been infected with chickenpox - that's more than 90 percent of adults in the United States - is at risk for shingles. The risk for shingles increases as people get older. About 40 to 50 percent of the estimated one million cases of shingles that occur each year in the United States occur in people age 60 and older. In people who have had chickenpox, shingles can occur at any time, without warning.

The first signs of shingles are often felt and may not be seen and may include itching, tingling, or burning. A few days later a rash of fluid-filled blisters appears, usually on one side of the body or face. The blisters may take two to four weeks to heal. Shingles can be painful and can cause serious problems. For most people, the pain from the shingles rash lessens as it heals. But for some people, shingles can cause long-term nerve pain, called postherpetic neuralgia or PHN. Long-term nerve pain has been described as burning, stabbing, throbbing, and/or shooting pain. Other problems that may result from shingles include skin infection, muscle weakness, scarring and decrease or loss of vision or hearing.

ZOSTAVAX is contraindicated in persons with a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine; 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; with AIDS or other clinical manifestations of infection with human immunodeficiency viruses; and with active untreated tuberculosis. ZOSTAVAX is also contraindicated in persons on immunosuppressive therapy, including high-dose corticosteroids, and in women who are or may be pregnant.

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. The use of ZOSTAVAX in individuals with a previous history of shingles has not been studied.

Studies of ZOSTAVAX included more than 40,000 people

ZOSTAVAX was studied in more than 40,000 people, more than 21,000 of whom received the active vaccine. The efficacy and safety of a single dose of ZOSTAVAX was evaluated in the largest of these studies, the landmark Shingles Prevention Study (SPS) of 38,546 men and women 60 years of age and older who had no previous history of shingles. This randomized, double-blind, placebo-controlled study was a Department of Veterans Affairs study conducted in collaboration with the National Institute of Allergy and Infectious Diseases at the National Institutes of Health and Merck at 22 U.S. research sites.

In the study, participants were randomized to groups given either ZOSTAVAX (N=19,270) or a placebo (N=19,276) and followed for the development of shingles for a median duration of 3.1 years. All subjects with clinically diagnosed shingles were offered antiviral treatment, as well as standard-of-care treatment for pain, as necessary.

ZOSTAVAX significantly reduced the risk of developing shingles compared with placebo by 51 percent (315 cases [5.4 cases per 1,000 person-years] vs. 642 cases [11.1 cases per 1,000 person-years], respectively; p<0.001) in the SPS. Efficacy of ZOSTAVAX for the prevention of shingles was highest for those 60 to 69 years of age and declined with increasing age.

Overall, the benefit of ZOSTAVAX in the prevention of long-term nerve pain from shingles (postherpetic neuralgia) can be primarily attributed to the vaccine's effect on the prevention of shingles. Vaccination with ZOSTAVAX reduced the incidence of long-term nerve pain from shingles in individuals 70 years of age and older who were vaccinated with ZOSTAVAX but went on to develop shingles. Following completion of the SPS, a separate analysis was conducted to evaluate the reduction in postherpetic neuralgia in the group of individuals who had been vaccinated with ZOSTAVAX but who had developed shingles. In the analysis, ZOSTAVAX reduced the overall incidence of postherpetic neuralgia by a statistically significant 39 percent compared to the placebo group. A statistically significant reduction in postherpetic neuralgia was seen in individuals aged 70 to 79 (55 percent) and a nonstatistically significant reduction in postherpetic neuralgia was seen in those aged 60 to 69 (5 percent) and 80 and older (26 percent) in the analysis.

Safety Profile of ZOSTAVAX

In the Adverse Event Monitoring Study (AEMS), which included a subgroup of individuals from the SPS, vaccine-related injection site and systemic adverse events seen in the first 42 days after vaccination in one percent or greater of the individuals who received ZOSTAVAX (n=3,345) included headache (1.4 percent) and the following injection-site reactions: erythema (33.7 percent), pain/tenderness (33.4 percent), swelling (24.9 percent), hematoma (1.4 percent), pruritus (6.6 percent), and warmth (1.5 percent). Most of these adverse experiences were reported as mild in intensity.

In the overall study population in the SPS, serious adverse experiences (SAEs) occurred at a similar rate (1.4 percent) in subjects vaccinated with ZOSTAVAX or placebo. In the AEMS, the rate of SAEs was increased in the group who received ZOSTAVAX (1.9 percent) as compared to the placebo group (1.3 percent) in the first 42 days after vaccination. Investigator-determined, vaccine-related serious adverse experiences were reported for two subjects vaccinated with ZOSTAVAX (asthma exacerbation and polymyalgia rheumatica) and three subjects who received placebo (Goodpasture's syndrome, anaphylactic reaction, and polymyalgia rheumatica).

In the entire SPS study population, the rates of overall cardiovascular events (0.4 percent) including coronary artery disease related conditions (0.2 percent) were similar in subjects vaccinated with ZOSTAVAX or placebo. In the AEMS of the SPS, in the first 42 days after vaccination, the rate of overall cardiovascular events was higher after ZOSTAVAX (0.6 percent) than after placebo (0.4 percent), including the rate of coronary artery disease-related conditions (ZOSTAVAX, 0.3 percent; placebo, 0.2 percent).

Selected Important Information about ZOSTAVAX

ZOSTAVAX is a live attenuated vaccine. There is a theoretical risk of transmitting the vaccine virus to close contacts who are varicella-susceptible, including those who have problems with their immune system or are pregnant. ZOSTAVAX is not a substitute for VARIVAX([R]) [Varicella Virus Vaccine Live (Oka/Merck)] and should not be used in children. 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 SPS, protection with ZOSTAVAX was demonstrated through four years of follow-up. The need for revaccination has not been defined.

Concurrent administration of ZOSTAVAX and antiviral medications known to be effective against the varicella zoster virus has not been evaluated. Concurrent administration of ZOSTAVAX and other vaccines has not been evaluated.

About the Advisory Committee on Immunization Practices (ACIP)

The ACIP develops written recommendations for the routine administration of vaccines, along with schedules regarding the appropriate dosage and dosing frequency, and contraindications applicable to the vaccines.

The goals of the Committee, which consists of 15 experts in immunization and related fields, are to provide advice which will assist the CDC and the nation in reducing the incidence of vaccine-preventable diseases and to increase the safe usage of vaccines and related biological products.

Availability of ZOSTAVAX

Merck makes ZOSTAVAX, as well as its other adult vaccines, available free of charge through a U.S. patient assistance program for low-income individuals for whom the vaccines are medically appropriate. Through this program, Merck provides free vaccines to adults who are uninsured and who are unable to afford vaccines. Merck's adult vaccines became available through this program in September. For more information on the Merck Adult Vaccines Patient Assistance Program, go to www.merckhelps.com.

Outside the United States, ZOSTAVAX was approved for licensure in the European Union and in Australia in May of this year, and Merck has filed regulatory applications for ZOSTAVAX in other world markets. Merck plans to begin to commercialize ZOSTAVAX outside of the United States in 2007.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Merck Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this document should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

Prescribing information and patient product information for ZOSTAVAX[R] is attached and is also available at www.zostavax.com.

Product photos and photos of people being vaccinated with ZOSTAVAX[R], are available at www.pimsmultimedia.com/ZOSTAVAX.

ZOSTAVAX[R] is a registered trademark of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A.

                                                              9703300

    ZOSTAVAX(R)

    (Zoster Vaccine Live (Oka/Merck))

    DESCRIPTION

    ZOSTAVAX*

    is a lyophilized preparation of the Oka/Merck strain of live,
attenuated varicella-zoster virus (VZV). The virus was initially
obtained from a child with naturally-occurring varicella, then
introduced into human embryonic lung cell cultures, adapted to and
propagated in embryonic guinea pig cell cultures and finally
propagated in human diploid cell cultures (WI-38). Further passage of
the virus was performed at Merck Research Laboratories (MRL) in human
diploid cell cultures (MRC-5). The cells, virus seeds, virus bulks and
bovine serum used in the manufacturing are all tested to provide
assurance that the final product is free of adventitious agents.
ZOSTAVAX, when reconstituted as directed, is a sterile preparation for
subcutaneous administration. Each 0.65-mL dose contains a minimum of
19,400 PFU (plaque-forming units) of Oka/Merck strain of VZV when
reconstituted and stored at room temperature for up to 30 minutes.
Each dose also contains 31.16 mg of sucrose, 15.58 mg of hydrolyzed
porcine gelatin, 3.99 mg of sodium chloride, 0.62 mg of monosodium
L-glutamate, 0.57 mg of sodium phosphate dibasic, 0.10 mg of potassium
phosphate monobasic, 0.10 mg of potassium chloride; residual
components of MRC-5 cells including DNA and protein; and trace
quantities of neomycin and bovine calf serum. The product contains no
preservatives.

    CLINICAL PHARMACOLOGY

    Background

    Herpes zoster (HZ), commonly known as shingles or zoster, is a
manifestation of the reactivation of varicella zoster virus (VZV),
which, as a primary infection, produces chickenpox (varicella).
Following initial infection, the virus remains latent in the dorsal
root or cranial sensory ganglia until it reactivates, producing
zoster. Zoster is characterized by a unilateral, painful, vesicular
cutaneous eruption with a dermatomal distribution.
    Although the rash is the most distinctive feature of zoster, the
most frequently debilitating symptom is pain. Pain associated with
zoster may occur during the prodrome, the acute eruptive phase, and
the postherpetic phase of the infection. This later phase is most
commonly referred to as postherpetic neuralgia (PHN).
    Serious complications, such as scarring, bacterial superinfection,
allodynia, cranial and motor neuron palsies, pneumonia, encephalitis,
visual impairment, hearing loss, and death can occur as the result of
zoster.

    Mechanism of Action

    The risk of developing zoster appears to be related to a decline
in VZV-specific immunity. ZOSTAVAX was shown to boost VZV-specific
immunity, which is thought to be the mechanism by which it protects
against zoster and its complications. (See Immunogenicity.)

    Clinical Studies

    Efficacy of ZOSTAVAX was evaluated in the Shingles Prevention
Study (SPS),(1)a placebo-controlled, double-blind clinical trial in
which 38,546 subjects 60 years of age or older were randomized to
receive a single dose of either ZOSTAVAX (n=19,270) or placebo
(n=19,276). Subjects were followed for the development of zoster for a
median of 3.1 years (range 31 days to 4.90 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. Randomization was stratified by age, 60-69 and Greater
Than or Equal to70 years of age. Zoster cases were confirmed by
Polymerase Chain Reaction (PCR) (93%), viral culture (1%), or in the
absence of viral detection, as determined by the Clinical Evaluation
Committee (6%). Individuals in both vaccination groups who developed
zoster were given famciclovir, and, as necessary, pain medications.
The primary efficacy analysis included all subjects randomized in the
study who were followed for at least 30 days postvaccination and did
not develop an evaluable case of HZ within the first 30 days
postvaccination (Modified Intent-To-Treat (MITT) analysis).
    ZOSTAVAX significantly reduced the risk of developing zoster when
compared with placebo (Table 1). Vaccine efficacy for the prevention
of HZ was highest for those subjects 60-69 years of age and declined
with increasing age.

                                Table 1
   Efficacy of ZOSTAVAX on HZ Incidence Compared with Placebo in the
                      Shingles Prevention Study*

                ZOSTAVAX                Placebo
        ------------------------------------------------
Age        #     # HZ  Incidence   #     # HZ  Incidence   Vaccine
 group** subjects cases rate of  subjects cases rate of     Efficacy
 (yrs.)                 HZ per                  HZ per     (95% CI)
                         1000                    1000
                        person-                 person-
                          yrs.                    yrs.
----------------------------------------------------------------------
Overall   19254   315      5.4    19247   642     11.1  51% (44%, 58%)
----------------------------------------------------------------------
  60-69   10370   122      3.9    10356   334     10.8  64% (56%, 71%)
----------------------------------------------------------------------
  70-79    7621   156      6.7     7559   261     11.4  41% (28%, 52%)
----------------------------------------------------------------------
Greater
 Than or
 Equal
 to 80     1263    37      9.9     1332    47     12.2 18% (-29%, 48%)
----------------------------------------------------------------------

    * The analysis was performed on the Modified Intent-To-Treat
(MITT) population that included all subjects randomized in the study
who were followed for at least 30 days postvaccination and did not
develop an evaluable case of HZ within the first 30 days
postvaccination.
    ** Age strata at randomization were 60-69 and Greater Than or
Equal to70 years of age.
    Forty-five subjects were excluded from the MITT analysis (16 in
the group of subjects who received ZOSTAVAX and 29 in the group of
subjects who received placebo), including 24 subjects with evaluable
HZ cases that occurred in the first 30 days postvaccination (6
evaluable HZ cases in the group of subjects who received ZOSTAVAX and
18 evaluable HZ cases in the group of subjects who received placebo).
    Suspected HZ cases were followed prospectively for the development
of HZ-related complications. Table 2 compares the rates of PHN defined
as HZ-associated pain (rated as 3 or greater on a 10-point scale by
the study subject and occurring or persisting at least 90 days)
following the onset of rash in evaluable cases of HZ.

                                Table 2
   Postherpetic Neuralgia (PHN)* in the Shingles Prevention Study**

                                                ZOSTAVAX
                                  ------------------------------------
Age group (yrs.) +                   #     # HZ  # PHN Incidence% HZ
                                   subjects cases cases rate of  cases
                                                        PHN per  with
                                                         1,000    PHN
                                                        person-
                                                          yrs.
----------------------------------------------------------------------
Overall                              19254   315    27      0.5   8.6%
----------------------------------------------------------------------
60-69                                10370   122     8      0.3   6.6%
----------------------------------------------------------------------
70-79                                 7621   156    12      0.5   7.7%
----------------------------------------------------------------------
Greater Than or Equal to 80           1263    37     7      1.9  18.9%
----------------------------------------------------------------------


                                Placebo
                  ------------------------------------
Age group (yrs.) +   #     # HZ  # PHN Incidence% HZ  Vaccine efficacy
                   subjects cases cases rate of  cases against PHN in
                                        PHN per  with   subjects who
                                         1,000    PHN    develop HZ
                                        person-        postvaccination
                                          yrs.            (95% CI)
----------------------------------------------------------------------
Overall                                                         39%++
                     19247   642    80      1.4  12.5%       (7%, 59%)
----------------------------------------------------------------------
                                                                    5%
60-69                10356   334    23      0.7   6.9%    (-107%, 56%)
----------------------------------------------------------------------
                                                                   55%
70-79                 7559   261    45      2.0  17.2%      (18%, 76%)
----------------------------------------------------------------------
Greater Than or                                                    26%
 Equal to80           1332    47    12      3.1  25.5%     (-69%, 68%)
----------------------------------------------------------------------
*PHN was defined as HZ-associated pain rated as Greater Than or
Equal to3 (on a 0-10 scale), persisting or appearing more than 90 days
after onset of HZ rash using Zoster Brief Pain Inventory (ZBPI)(2).
** The table is based on the Modified Intent-To-Treat (MITT)
population that included all subjects randomized in the study who were
followed for at least 30 days postvaccination and did not develop an
evaluable case of HZ within the first 30 days postvaccination.
+ Age strata at randomization were 60-69 and Greater Than or Equal
to70 years of age.
++ Age-adjusted estimate based on the age strata (60-69 and
Greater Than or Equal to70 years of age) at randomization.

    The median duration of clinically significant pain (Greater Than
or Equal to3 on a 0-10 point scale) among HZ cases in the group of
subjects who received ZOSTAVAX as compared to the group of subjects
who received placebo was 20 days vs. 22 days based on the confirmed HZ
cases.
    Overall, the benefit of ZOSTAVAX in the prevention of PHN can be
primarily attributed to the effect of the vaccine on the prevention of
herpes zoster. Vaccination with ZOSTAVAX reduced the incidence of PHN
in individuals 70 years of age and older who developed zoster
postvaccination.
    Other prespecified zoster-related complications were reported less
frequently in subjects who received ZOSTAVAX compared to subjects who
received placebo. Among HZ cases, zoster-related complications were
reported at similar rates in both vaccination groups (Table 3).


                                Table 3
   Specific complications* of zoster among HZ cases in the Shingles
                           Prevention Study

  Complication                          ZOSTAVAX           Placebo
                                      (N = 19,270)      (N = 19,276)
----------------------------------------------------------------------
                                  (n = 321)   % Among  (n = 659)  %
                                              Zoster             Among
                                               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 Greater Than or Equal
to1% in at least one vaccination group among subjects with zoster.

    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.

    Immunogenicity

    Immune responses to vaccination were evaluated in a subset of
subjects enrolled in the Shingles Prevention Study (N=1395). VZV
antibody levels (Geometric Mean Titers, GMT), as measured by
glycoprotein enzyme-linked immunosorbent assay (gpELISA) 6 weeks
postvaccination, were increased 1.7-fold (95% CI: (1.6 to 1.8)) in the
group of subjects who received ZOSTAVAX compared to subjects who
received placebo; the specific antibody level that correlates with
protection from zoster has not been established.

    INDICATIONS AND USAGE

    ZOSTAVAX is indicated for prevention of herpes zoster (shingles)
in individuals 60 years of age and older.

    ZOSTAVAX is not indicated for the treatment of zoster or PHN.

    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).

    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.(3) 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.

    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, for
example, in the presence of fever Greater Than 38.5(degree)C (Greater
Than 101.3(degree)F).
    The duration of protection after vaccination with ZOSTAVAX is
unknown. In the Shingles Prevention Study (SPS), 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 (see CLINICAL PHARMACOLOGY, Clinical
Studies).

    Transmission

    In clinical trials with ZOSTAVAX, transmission of the vaccine
virus has not been reported. However, post-marketing 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.

    Information for Patients

    The health care provider should question the vaccine recipient
about reactions to previous vaccines (see CONTRAINDICATIONS). The
health care provider should also inform the vaccine recipient of the
benefits and risks of ZOSTAVAX. Patients should be provided with a
copy of the Patient Information Sheet at the end of this insert, and
be given an opportunity to discuss any questions or concerns.
    Vaccinees should also be informed of the theoretical risk of
transmitting the vaccine virus to varicella-susceptible individuals,
including pregnant women who have not had chickenpox. Patients should
also be told that pregnancy should be avoided for three months
following vaccination.
    Patients should be instructed to report any adverse reactions to
their health care provider.

    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.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    ZOSTAVAX has not been evaluated for its carcinogenic or mutagenic
potential, or its potential to impair fertility.

    Pregnancy

    Pregnancy Category C: Animal reproduction studies have not been
conducted with ZOSTAVAX. It is also not known whether ZOSTAVAX can
cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity. However, naturally occurring VZV infection is
known to sometimes cause fetal harm. Therefore, ZOSTAVAX should not be
administered to pregnant females; furthermore, pregnancy should be
avoided for three months following vaccination (see
CONTRAINDICATIONS).
    Vaccinees and health care providers are encouraged to report any
exposure to ZOSTAVAX during pregnancy by calling [phone].

    Nursing Mothers

    Some viruses are excreted in human milk; however, it is not known
whether VZV is secreted in human milk. Therefore, because some viruses
are secreted in human milk, caution should be exercised if ZOSTAVAX is
administered to a nursing woman.

    Pediatric Use

    ZOSTAVAX should not be used in children.

    Geriatric Use

    The median age of subjects enrolled in the largest (N=38,546)
clinical study of ZOSTAVAX was 69 years (range 59-99 years). Of the
19,270 subjects who received ZOSTAVAX, 10,378 were 60-69 years of age,
7,629 were 70-79 years of age, and 1,263 were 80 years of age or
older.

    ADVERSE REACTIONS

    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.

    Serious Adverse Reactions

    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 Greater Than or Equal to 1 Serious Adverse
                              Experience
     (0-42 Days Postvaccination) in the Shingles Prevention Study


Cohort                             ZOSTAVAX    Placebo  Relative Risk
                                      n/N        n/N       (95% CI)
                                       %          %
----------------------------------------------------------------------
Overall Study Cohort               255/18671  254/18717          1.01
(all ages)                               1.4%       1.4%  (0.85, 1.20)
----------------------------------------------------------------------
   60-69 years old                 113/10100  101/10095          1.12
                                         1.1%       1.0%  (0.86, 1.46)
   70-79 years old                  115/7351   132/7333          0.87
                                         1.6%       1.8%  (0.68, 1.11)
   Greater Than or Equal to 80       27/1220    21/1289          1.36
    years old                            2.2%       1.6%  (0.78, 2.37)
----------------------------------------------------------------------
AE Monitoring Substudy Cohort        64/3326    41/3249          1.53
(all ages)                               1.9%       1.3%  (1.04, 2.25)
----------------------------------------------------------------------
   60-69 years old                   22/1726    18/1709          1.21
                                         1.3%       1.1%  (0.66, 2.23)
   70-79 years old                   31/1383    19/1367          1.61
                                         2.2%       1.4%  (0.92, 2.82)
   Greater Than or Equal to 80        11/217      4/173          2.19
    years old                            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

    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


                                       AE Monitoring   Entire Study
                                          Substudy         Cohort
                                     ZOSTAVAX Placebo ZOSTAVAX Placebo
                                      N = 3326 N = 3249  N =     N =
                                                        18671   18717
                                       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
    conditions*                       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
*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 (Goodpasture's syndrome, anaphylactic reaction, and
polymyalgia rheumatica).

    Deaths

    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.

    Most Common Adverse Reactions

    Adverse Events Reported in the AE Monitoring Substudy of the SPS

    Injection-site and systemic adverse experiences reported at an
incidence Greater Than or Equal to 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 Greater Than or Equal to1% of Adults Who
  Received ZOSTAVAX or Placebo (0-42 Days Postvaccination) in the AE
         Monitoring Substudy of the Shingles Prevention Study

  Adverse Experience               ZOSTAVAX             Placebo

                                  (N = 3345)           (N = 3271)
                                       %                   %
----------------------------------------------------------------------
  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.

    The numbers of subjects with elevated temperature (Greater Than or
Equal to38.3(degree)C (Greater Than or Equal to101.0(degree)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
Greater Than or Equal to1% 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%)).

    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.

    Clinical Safety with High Potency ZOSTAVAX

    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).

    VZV rashes following vaccination

    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).

    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.(4)

    DOSAGE AND ADMINISTRATION

    FOR SUBCUTANEOUS ADMINISTRATION.

    Do not inject intravascularly.

    ZOSTAVAX is administered as a single dose.

    Caution: Use only sterile syringes free of preservatives,
antiseptics, and detergents for each injection and/or reconstitution
of ZOSTAVAX. Preservatives, antiseptics and detergents may inactivate
the vaccine virus.
    Reconstitute the vaccine using only the diluent supplied. The
supplied diluent is free of preservatives or other antiviral
substances which might inactivate the vaccine virus.
    Use a separate sterile needle and syringe for reconstituting and
administration of ZOSTAVAX to prevent transfer of infectious diseases.
    ZOSTAVAX is stored frozen and should be reconstituted immediately
upon removal from the freezer. The diluent should be stored separately
at room temperature or in the refrigerator.
    To reconstitute the vaccine: Withdraw the entire contents of the
diluent vial into a syringe. Parenteral drug products should be
inspected visually for particulate matter and discoloration prior to
administration, whenever solution and container permit. ZOSTAVAX when
reconstituted is a semi-hazy to translucent, off-white to pale yellow
liquid.
    Inject all of the diluent in the syringe into the vial of
lyophilized vaccine and gently agitate to mix thoroughly.
    Withdraw the entire contents into a syringe and inject the total
volume of reconstituted vaccine subcutaneously; preferably in the
upper arm.
    THE VACCINE SHOULD BE ADMINISTERED IMMEDIATELY AFTER
RECONSTITUTION, TO MINIMIZE LOSS OF POTENCY.

    DISCARD RECONSTITUTED VACCINE IF IT IS NOT USED WITHIN 30 MINUTES.

    DO NOT FREEZE reconstituted vaccine.

    Needles should be disposed of properly and should not be recapped.

    HOW SUPPLIED

    No. 4963-00 -- ZOSTAVAX is supplied as follows: (1) a package of 1
single-dose vial of lyophilized vaccine, NDC 0006-4963-00 (package A);
and (2) a separate package of 10 vials of diluent (package B).
    No. 4963-41 -- ZOSTAVAX is supplied as follows: (1) a package of
10 single-dose vials of lyophilized vaccine, NDC 0006-4963-41 (package
A); and (2) a separate package of 10 vials of diluent (package B).

    Handling and Storage

    During shipment, to ensure that there is no loss of potency, the
vaccine must be maintained at a temperature of -20(degree)C
(-4(degree)F) or colder.
    ZOSTAVAX SHOULD BE STORED FROZEN at an average temperature of
-15(degree)C (+5(degree)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(degree)C or colder is acceptable for storing ZOSTAVAX.
    For information regarding stability under conditions other than
those recommended, call 1-800-MERCK-90.

    Before reconstitution, protect from light.

    The diluent should be stored separately at room temperature (20 to
25(degree)C, 68 to 77(degree)F), or in the refrigerator (2 to
8(degree)C, 36 to 46(degree)F).

    REFERENCES

    1. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb
LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A,
Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison
VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts
RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK,
Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA,
Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM,
Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS,
Wang WW, Annunziato PW, Silber JL. A Vaccine to Prevent Herpes Zoster
and Postherpetic Neuralgia in Older Adults. NEJM 2005;352:2271-84.
    2. Coplan PM, Schmader K, Nikas A, Chan ISF, Choo P, Levin MJ, et
al. Development of a measure of the burden of pain due to herpes
zoster and postherpetic neuralgia for prevention trials: Adaptation of
the brief pain inventory. J Pain 2004;5(6):344-56.
    3. Reitschel RL, Bernier R. Neomycin sensitivity and the MMR
vaccine. JAMA 1981;245(6):571.
    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.

    Manuf. and Dist. by:

    Merck & Co., Inc.,
    Whitehouse Station, NJ, 08889, USA

    Issued May 2006

    Printed in USA

    *Registered trademark of Merck & Co., Inc.

    Copyright (C) 2006 Merck & Co., Inc.

    Whitehouse Station, NJ, USA

    All rights reserved

    **Registered trademark of Merck & Co., Inc.
9703300

    Patient Information about

    ZOSTAVAX(R) (pronounced "ZOS tah vax")

    Generic name: (Zoster Vaccine Live (Oka/Merck))

    You should read this summary of information about ZOSTAVAX* before
you are vaccinated. If you have any questions about ZOSTAVAX after
reading this leaflet, you should ask your health care provider. This
information does not take the place of talking about ZOSTAVAX with
your doctor, nurse, or other health care provider. Only your health
care provider can decide if ZOSTAVAX is right for you.

    What is ZOSTAVAX and how does it work?

    ZOSTAVAX is a vaccine that is used for adults 60 years of age or
older to prevent shingles (also known as zoster).
    ZOSTAVAX works by helping your immune system protect you from
getting shingles and the associated pain and other serious
complications. If you do get shingles even though you have been
vaccinated, ZOSTAVAX may help prevent the nerve pain that can follow
shingles in some people.
    As with any vaccine, ZOSTAVAX may not protect everyone who
receives the vaccine.
    ZOSTAVAX cannot be used to treat shingles once you have it. If you
do get shingles, see your health care provider within the first few
days of getting the rash.

    What do I need to know about shingles and the virus that causes
it?

    Shingles is a rash that is usually on one side of the body. The
rash begins as a cluster of small red spots that often blister. The
rash can be painful. Shingles rashes usually last up to 30 days, and
for most people the pain associated with the rash lessens as it heals.
    People who have problems with their immune system may have a
greater risk of getting more widespread rashes and longer-lasting
pain.
    Shingles is caused by the same virus that causes chickenpox. Once
a person has had chickenpox, the virus can live, but remain inactive,
in one or more nerve roots in your body for many years. For reasons
that are not fully understood, the virus may become active again. Age
and problems with the immune system may increase your risk of getting
shingles.

    Can I get ZOSTAVAX?

    You can receive ZOSTAVAX if you are 60 years of age or older, but
only your health care provider can decide if ZOSTAVAX is right for
you.

    Who should not receive ZOSTAVAX?

    You should not receive ZOSTAVAX if you:

    --  are allergic to any of its ingredients. This includes
        allergies to gelatin or neomycin.

    --  have a disease or condition that causes a weakened immune
        system such as an immune deficiency, including leukemia,
        lymphoma, HIV/AIDS or are taking high doses of steroids by
        injection or by mouth.

    --  have active TB (tuberculosis) that is not being treated.

    --  are pregnant or may be pregnant.

    *Registered trademark of Merck & Co., Inc.

    Copyright (C) 2006 Merck & Co., Inc.

    Whitehouse Station, NJ, USA

    All rights reserved

    What should I tell my health care provider before I receive
ZOSTAVAX?

    You should tell your health care provider if you:

    --  have or have had any medical problems.

    --  are taking any medications, including those that might weaken
        your immune system.

    --  have any allergies, including allergies to neomycin or have
        had an allergic reaction to another vaccine.

    --  become pregnant within 3 months of getting the vaccine.
        Vaccine recipients are encouraged to report any exposure to
        ZOSTAVAX during pregnancy by calling [phone].

    --  are breast-feeding.

    --  have had shingles in the past.

    --  may be in close contact (including household contact) with
        someone who may be pregnant and has not had chickenpox or been
        vaccinated against chickenpox, or someone who has problems
        with their immune system.

    How is ZOSTAVAX given?

    ZOSTAVAX is given as a single dose by injection under the skin.

    What are the possible side effects of ZOSTAVAX?

    Redness, pain, swelling, itching, warmth, and bruising at the site
where the injection was given, and headache were the most common side
effects that people in the clinical studies reported after receiving
the vaccine. Talk to your health care provider about other possible
side effects.
    Call your health care provider right away if any medical condition
you have gets worse or you develop any new or unusual symptoms after
you receive ZOSTAVAX.

    What are the ingredients in ZOSTAVAX?

    Active Ingredient: a weakened form of the varicella-zoster virus.

    Inactive Ingredients: sucrose, hydrolyzed porcine gelatin, sodium
chloride, monosodium L-glutamate, sodium phosphate dibasic, potassium
phosphate monobasic, potassium chloride.

    What else should I know about ZOSTAVAX?

    This leaflet summarizes information about ZOSTAVAX. If you would
like more information, talk to your health care provider or visit the
website: www.ZOSTAVAX.com.

    Rx Only

    Issued May 2006

    Manuf. and Dist. by:

    Merck & Co., Inc., Whitehouse Station, NJ 08889, USA