FDA Approves Merck's ROTATEQ(R), The Only Vaccine in the U.S. to Prevent Rotavirus Gastroenteritis, a Leading Cause of Severe Infant Diarrhea; ROTATEQ Fits Into Routine Well-Baby Visit Schedule

"Virtually all children will experience rotavirus. While somechildren experience mild symptoms of rotavirus, infection can besevere and lead to dehydration that can be fatal," said Paul Offit,M.D., chief of infectious diseases, The Children's Hospital ofPhiladelphia and co-inventor of the vaccine. "The FDA approval of thisvaccine is exciting for pediatricians because they will now have a wayto help protect infants from rotavirus. For the many people who haveworked on the research and development of this vaccine for nearly 20years, to see that effort result in the availability of a vaccine toprevent this common and unpredictable disease is something to be proudof."

ROTATEQ can be given during the current routine well baby visitsat two, four, and six months of age. It is ready-to-use withoutre-formulation or mixing and is the only oral vaccine approved for usein infants in the U. S. The Advisory Committee on ImmunizationPractices (ACIP) is expected to decide whether ROTATEQ should be addedto the current pediatric immunization schedule of recommended vaccineslater this month. ROTATEQ should not be used in infants that areallergic to any component of the vaccine.

ROTATEQ is a pentavalent vaccine that targets the strains ofrotavirus responsible for more than 90 percent of rotavirus disease inthe U.S. Among children under five in the United States, it isestimated that 2.7 million episodes of rotavirus gastroenteritis occureach year, leading to approximately 250,000 emergency room (ER) visitsand up to 70,000 hospitalizations. In the U.S., children are at thegreatest risk for severe rotavirus disease from six to 24 months ofage. By the time they are five years old, approximately one out ofevery 17 children in the U.S. will visit the emergency room, and oneout of every 65 will be hospitalized for rotavirus gastroenteritis inthe U.S. Published surveys show that many pediatricians and familyphysicians believe rotavirus gastroenteritis is a significant diseasefor children and that 94 percent of physicians would use a rotavirusvaccine.

ROTATEQ Prevented Rotavirus Disease with A Safety Profile Similarto Placebo

The FDA approval of ROTATEQ is based on data from Merck's PhaseIII clinical trials of more than 70,000 infants, including theRotavirus Efficacy and Safety Trial (REST), one of the largestpre-licensure vaccine clinical trials ever conducted.

Among infants observed in Phase III clinical trials, ROTATEQprevented 98 percent of severe cases of rotavirus gastroenteritis andprevented 74 percent of rotavirus gastroenteritis cases of anyseverity caused by serotypes targeted by the vaccine (G1, G2, G3, G4)compared to placebo through the first full rotavirus season aftervaccination. In REST, ROTATEQ reduced hospitalizations by 96 percentand ER visits by 94 percent for rotavirus gastroenteritis caused byserotypes targeted by the vaccine through the first two years afterthe third dose. As with any vaccine, vaccination with RotaTeq may notresult in complete protection in all recipients.

Because intussusception was associated with a previously licensedrotavirus vaccine made by another manufacturer, one of the primarygoals of REST was to evaluate the safety of ROTATEQ with respect tointussusception. Intussusception takes place when the bowel folds inon itself, causing an intestinal blockage. It is a naturally occurringevent, which occurs in approximately one in two thousand infants underthe age of two each year. In REST, ROTATEQ did not increase the riskof intussusception compared to placebo. Within one year after thefirst dose, there were 13 cases of intussusception in the vaccinegroup and 15 in the placebo group.

The incidence of serious adverse events within six weeks of a doseof ROTATEQ was comparable among vaccine and placebo recipients. Themost frequently reported serious adverse events were bronchiolitis,gastroenteritis, pneumonia, pyrexia, and urinary tract infection.

Pricing and CPT Code for ROTATEQ

ROTATEQ is available for ordering. The catalog price for ROTATEQis $62.50 per dose when purchased as a pack of 10 single-dose tubes.The American Medical Association has established a Current ProceduralTerminology (CPT)(R) code of "90680"(1). CPT codes allow for theidentification and potential reimbursement of existing commonprocedures, services and products; new and emerging technologies, aswell as the collection of data to facilitate performance measures.

Selected Important Information about ROTATEQ

ROTATEQ is indicated for the prevention of rotavirusgastroenteritis in infants and children caused by the serotypes G1,G2, G3, and G4 when administered as a 3-dose series to infants betweenthe ages of 6 to 32 weeks. The first dose of ROTATEQ should beadministered between 6 and 12 weeks of age. The efficacy of ROTATEQbeyond the second season after vaccination was not evaluated. Thesafety and efficacy of ROTATEQ have not been established in infantsless than six weeks of age or greater than 32 weeks of age. No safetyor efficacy data are available for the administration of ROTATEQ toinfants who are potentially immunocompromised, including: those withcertain disorders of the bone marrow or lymphatic system, those onimmunosuppressive therapy or with an immunodeficient condition, orthose who have received blood products within six weeks ofvaccination. In more than 11,000 infants in clinical trials, aVaccination Report Card was used to report the presence of adverseevents for 42 days after each dose. Fever was observed at similarrates in vaccine and placebo recipients. Adverse events that occurredat a statistically higher incidence within six weeks of any dose amongrecipients of ROTATEQ as compared with placebo recipients werediarrhea, vomiting, otitis media (ear infection), nasopharyngitis(inflammation of the nasal passages and the pharynx), andbronchospasm.

Worldwide Availability of ROTATEQ Remains a Priority

In addition to filing for licensure in more than 50 countries in2005, Merck recently announced a collaborative effort with PATH toconduct clinical studies of ROTATEQ in Africa and Asia. The trials arean important step in the process of making a rotavirus vaccineavailable in these regions.

"With the approval of ROTATEQ, Merck continues its tradition ofdeveloping vaccines that address important unmet medical needs," saidMark Feinberg, M.D., Ph.D, vice president of policy, public health andmedical affairs, Merck Vaccines. "Because of the high rotavirusmortality rates seen in the developing world, we plan to initiateclinical trials of ROTATEQ in economically disadvantaged countries inAfrica and Asia. Merck is firmly committed to workingwith our partners in the global public health community to makeROTATEQ available to infants and children worldwide as quickly aspossible," Dr. Feinberg said.

Two Additional Merck Vaccines Under Review with FDA

Merck has two other vaccines currently under review by the FDA.The FDA and other regulatory agencies around the world are reviewingapplications for ZOSTAVAX(R), Merck's investigational vaccine toprevent shingles and shingles-associated pain in adults, andGARDASIL(R), Merck's investigational HPV and cervical cancer vaccine.

The ACIP currently recommends vaccines for use in children toprevent diphtheria, Haemophilus influenzae type b, hepatitis A,hepatitis B, influenza, measles, meningococcal disease, mumps,pertussis, pneumococcal disease, polio, rubella, tetanus andvaricella. Merck makes vaccines to help protect against seven of these14 diseases.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceuticalcompany dedicated to putting patients first. Established in 1891,Merck currently discovers, develops, manufactures and markets vaccinesand medicines to address unmet medical needs. The Company devotesextensive efforts to increase access to medicines through far-reachingprograms that not only donate Merck medicines but help deliver them tothe people who need them. Merck also publishes unbiased healthinformation as a not-for-profit service. For more information, visitwww.merck.com.

Forward-Looking Statement

This press release, including the financial information thatfollows, contains "forward-looking statements" as that term is definedin the Private Securities Litigation Reform Act of 1995. Thesestatements are based on management's current expectations and involverisks and uncertainties, which may cause results to differ materiallyfrom those set forth in the statements. The forward-looking statementsmay include statements regarding product development, productpotential or financial performance. No forward-looking statement canbe guaranteed, and actual results may differ materially from thoseprojected. Merck undertakes no obligation to publicly update anyforward-looking statement, whether as a result of new information,future events, or otherwise. Forward-looking statements in this pressrelease should be evaluated together with the many uncertainties thataffect Merck's business, particularly those mentioned in thecautionary statements in Item 1 of Merck's Form 10-K for the yearended Dec. 31, 2004, and in its periodic reports on Form 10-Q and Form8-K, which the Company incorporates by reference.

ROTATEQ(R) is a registered trademark of Merck & Co., Inc.

(1)Current Procedural Terminology (CPT) (C) American MedicalAssociation. All Right Reserved.

See attached prescribing information.

Patient Information

RotaTeq(R)** (pronounced "RO-tuh-tek")

rotavirus vaccine, live, oral, pentavalent

You should read this information before your child receives theRotaTeq vaccine and ask your child's doctor any questions you mayhave. Your child will need 3 doses of the vaccine over the course of afew months. So read the leaflet before your child receives each doseof the vaccine in case any of the information about the vaccinechanges. This leaflet is a summary of certain information about thevaccine. If you would like additional information, your health careprovider can give you more complete information about this vaccinethat is written for health care professionals. This leaflet does nottake the place of talking with your child's doctor.

What is RotaTeq and How Does it Work?

RotaTeq is a vaccine that can help protect your child from gettinga virus infection that can cause fever, vomiting, and diarrhea. Thevaccine is given by mouth at 3 different times, each about one to twomonths apart. Nearly all children become infected with the rotavirusby the time they are 5 years old.

RotaTeq helps protect against diarrhea and vomiting only if theyare caused by the rotavirus. It does not protect against diarrhea andvomiting that are caused by anything else.

RotaTeq may not fully protect all children that get the vaccine,and if your child already has the virus it will not help them.

What are the Symptoms of a Rotavirus Infection?

Infection with the Rotavirus is the most common cause of severediarrhea in infants. Sometimes the diarrhea and vomiting can be severeand lead to the loss of body fluids (dehydration) and even to death.

Signs that your infant is dehydrated include:

-- Sleepiness

-- Dry mouth and tongue

-- Fussiness

-- Dry diaper for several hours

If your infant shows signs that they are dehydrated, you shouldcall the doctor immediately.

What should I tell the doctor before my child gets RotaTeq?

There are some things your doctor should know before your childgets the vaccine. You should tell your doctor if your child:

-- Has any illness with fever. A mild fever or cold by itself is not a reason to delay taking the vaccination.

-- Has diarrhea or has been vomiting.

-- Has not been gaining weight.

-- Is not growing as expected.

-- Has a blood disorder.

-- Has any type of cancer.

-- Has a weak immune system because of a disease (this includes HIV/AIDS).

-- Gets treatment or takes medicines that may weaken the immune system (such as high doses of steroids) or has received a blood transfusion or blood products within the past 42 days.

-- Was born with gastrointestinal problems, or has had a blockage or abdominal surgery.

-- Has regular close contact with a member of the family or household who has a weakened immune system. For example, a person in the house with cancer or one who is taking medicines that may weaken their immune system.

Who should not receive RotaTeq?

Your child should not get the vaccine if:

-- He or she had an allergic reaction after getting a dose of this vaccine.

-- He or she is allergic to any of the ingredients of the vaccine. A list of ingredients can be found at the end of this leaflet.

What are the possible side effects of RotaTeq?

The most common side effects reported after taking RotaTeq werediarrhea, vomiting, fever, runny nose and sore throat, wheezing orcoughing, and ear infection.

These are NOT all the possible side effects of RotaTeq. You canask your doctor or health care provider for a more complete list.

If your child develops sudden abdominal pain; vomiting, blood intheir stools or other changes in their bowel movements, it may be asign of a serious problem. You should call the doctor immediately.

If your child seems to be having any side effects that are notmentioned in this leaflet, please call your doctor or other healthcareprovider. If the condition continues or worsens, you should seekmedical attention.

You, as a parent or guardian may also report any adverse reactionsto your child's health care provider or directly to the VaccineAdverse Event Reporting System (VAERS). The VAERS toll-free number is1-800-822-7967 or report on line to www.vaers.hhs.gov.

Can RotaTeq be given with other vaccines?

Your child may get RotaTeq at the same time as other childhoodvaccines.

How is RotaTeq given?

The vaccine is given by mouth. Your child will receive 3 doses ofthe vaccine. The first dose is given when your child is 6 to 12 weeksof age, the second dose is given 4 to 10 weeks later and the thirddose is given 4 to 10 weeks after the second dose. The last (third)dose should be given to your child by 32 weeks of age.

Your health care provider will gently squeeze the vaccine intoyour child's mouth (see Figure 1). Your infant may spit out some orall of it. If this happens, the dose does not need to be given againduring that visit.

Figure 1:

What do I do if my child misses a dose of RotaTeq?

All 3 doses of the vaccine should be given to your child by 32weeks of age. Your health care provider will tell you when your childshould come for the follow-up doses. It is important to keep thoseappointments. If you forget or are not able to go back at the plannedtime, ask your health care provider for advice.

What else should I know about RotaTeq?

This leaflet gives a summary of certain information about thevaccine. If you have any questions or concerns about RotaTeq, talk toyour health care provider. You can also visit www.rotateq.com.

What are the ingredients in RotaTeq?

Active Ingredient: 5 live rotavirus strains (G1, G2, G3, G4, andP1).

Inactive Ingredients: sucrose, sodium citrate, sodium phosphatemonobasic monohydrate, sodium hydroxide, polysorbate 80 and also fetalbovine serum.

Rx only

Issued February 2006

Registered trademark of MERCK & Co., Inc., Whitehouse Station, NJ,08889 USA

COPYRIGHT (C) 2006 MERCK & Co., Inc.

All rights reserved

RotaTeq (R)9714300
(Rotavirus Vaccine, Live, Oral, Pentavalent)

DESCRIPTION

RotaTeq* is a live, oral pentavalent vaccine that contains 5 live
reassortant rotaviruses. The rotavirus parent strains of the
reassortants were isolated from human and bovine hosts. Four
reassortant rotaviruses express one of the outer capsid proteins (G1,
G2, G3, or G4) from the human rotavirus parent strain and the
attachment protein (P7) from the bovine rotavirus parent strain. The
fifth reassortant virus expresses the attachment protein, P1A
(genotype P(8)), hereafter referred to as P1(8), from the human
rotavirus parent strain and the outer capsid protein G6 from the
bovine rotavirus parent strain (see Table 1).

Table 1

Bovine Reassortant
Rotavirus Outer Surface
Parent Protein
Human Rotavirus Strain and Composition Minimum Dose
Parent Strains Outer (Human Levels
and Outer Surface Surface Rotavirus (10(6)
Name of Protein Protein Component in infectious
Reassortant Compositions Composition Bold) units)
----------------------------------------------------------------------
G1 WI79 - G1, P1(8) G1, P7(5) 2.2
----------------------------- -----------------------------
G2 SC2 - G2, P2(6) WC3 - G6, G2, P7(5) 2.8
----------------------------- P7(5) -----------------------------
G3 WI78 - G3, P1(8) G3, P7(5) 2.2
----------------------------- -----------------------------
G4 BrB - G4, P2(6) G4, P7(5) 2.0
----------------------------- -----------------------------
P1(8) WI79 - G1, P1(8) G6, P1(8) 2.3
----------------------------------------------------------------------

The reassortants are propagated in Vero cells using standard cell
culture techniques in the absence of antifungal agents.
The reassortants are suspended in a buffered stabilizer solution.
Each vaccine dose contains sucrose, sodium citrate, sodium phosphate
monobasic monohydrate, sodium hydroxide, polysorbate 80, cell culture
media, and trace amounts of fetal bovine serum. There are no
preservatives or thimerosal present.
RotaTeq is a pale yellow clear liquid that may have a pink tint.

CLINICAL PHARMACOLOGY

Rotavirus is a leading cause of severe acute gastroenteritis in
infants and young children, with over 95% of these children infected
by the time they are 5 years old.(1) The most severe cases occur among
infants and young children between 6 months and 24 months of age.(2 )

Mechanism of Action

The exact immunologic mechanism by which RotaTeq protects against
rotavirus gastroenteritis is unknown (see CLINICAL STUDIES,
Immunogenicity). RotaTeq is a live viral vaccine that replicates in
the small intestine and induces immunity.

CLINICAL STUDIES

Overall, 72,324 infants were randomized in 3 placebo-controlled,
phase 3 studies conducted in 11 countries on 3 continents. The data
demonstrating the efficacy of RotaTeq in preventing rotavirus
gastroenteritis come from 6,983 of these infants from the US
(including Navajo and White Mountain Apache Nations) and Finland who
were enrolled in 2 of these studies: the Rotavirus Efficacy and Safety
Trial (REST) and Study 007. The third trial, Study 009, provided
clinical evidence supporting the consistency of manufacture and
contributed data to the overall safety evaluation.
The racial distribution of the efficacy subset was as follows:
White (RotaTeq 68%, placebo 69%); Hispanic-American (RotaTeq 10%,
placebo 9%); Black (2% in both groups); Multiracial (RotaTeq 4%,
placebo 5%); Asian (<1% in both groups); Native American (RotaTeq 15%,
placebo 14%), and Other (<1% in both groups). The gender distribution
was 52% male and 48% female in both vaccination groups.
The efficacy evaluations in these studies included: 1) Prevention
of any grade of severity of rotavirus gastroenteritis; 2) Prevention
of severe rotavirus gastroenteritis, as defined by a clinical scoring
system; and 3) Reduction in hospitalizations due to rotavirus
gastroenteritis.
The vaccine was given as a three-dose series to healthy infants
with the first dose administered between 6 and 12 weeks of age and
followed by two additional doses administered at 4- to 10-week
intervals. The age of infants receiving the third dose was 32 weeks of
age or less. Oral polio vaccine administration was not permitted;
however, other childhood vaccines could be concomitantly administered.
Breast-feeding was permitted in all studies.
The case definition for rotavirus gastroenteritis used to
determine vaccine efficacy required that a subject meet both of the
following clinical and laboratory criteria: (1) greater than or equal
to 3 watery or looser-than-normal stools within a 24-hour period
and/or forceful vomiting; and (2) rotavirus antigen detection by
enzyme immunoassay (EIA) in a stool specimen taken within 14 days of
onset of symptoms. The severity of rotavirus acute gastroenteritis was
determined by a clinical scoring system that took into account the
intensity and duration of symptoms of fever, vomiting, diarrhea, and
behavioral changes.
The primary efficacy analyses included cases of rotavirus
gastroenteritis caused by serotypes G1, G2, G3, and G4 that occurred
at least 14 days after the third dose through the first rotavirus
season post vaccination.
Analyses were also done to evaluate the efficacy of RotaTeq
against rotavirus gastroenteritis caused by serotypes G1, G2, G3, and
G4 at any time following the first dose through the first rotavirus
season postvaccination among infants who received at least one
vaccination (Intent-to-treat, ITT).

Rotavirus Efficacy and Safety Trial

Primary efficacy against any grade of severity of rotavirus
gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or
G4 through the first rotavirus season after vaccination was 74.0% (95%
CI: 66.8, 79.9) and the ITT efficacy was 60.0% (95% CI: 51.5, 67.1).
Primary efficacy against severe rotavirus gastroenteritis caused by
naturally occurring serotypes G1, G2, G3, or G4 through the first
rotavirus season after vaccination was 98.0% (95% CI: 88.3, 100.0),
and ITT efficacy was 96.4%, (95% CI: 86.4, 99.6). See Table 2.

Table 2
Efficacy of RotaTeq against any grade of severity of and severe*
G1-4 rotavirus gastroenteritis through the first rotavirus season
postvaccination in REST

Per Protocol Intent-to-Treat+
RotaTeq Placebo RotaTeq Placebo
---------------------------------------------------------------------
Subjects
vaccinated 2,834 2,839 2,834 2,839
Gastroenteritis cases
Any grade of
severity 82 315 150 371
Severe* 1 51 2 55
---------------------------------------------------------------------
Efficacy estimate % and (95% confidence interval)
---------------------------------------------------------------------
Any grade of 74.0 60.0
severity (66.8, 79.9) (51.5, 67.1)
Severe* 98.0 96.4
(88.3, 100.0) (86.4, 99.6)
---------------------------------------------------------------------
*Severe gastroenteritis defined by a clinical scoring system based on
the intensity and duration of symptoms of fever, vomiting, diarrhea,
and behavioral changes

+ITT analysis includes all subjects in the efficacy cohort who
received at least one dose of vaccine.

The efficacy of RotaTeq against severe disease was also
demonstrated by a reduction in hospitalizations for rotavirus
gastroenteritis among all subjects enrolled in REST. RotaTeq reduced
hospitalizations for rotavirus gastroenteritis caused by serotypes G1,
G2, G3, and G4 through the first two years after the third dose by
95.8% (95% CI: 90.5, 98.2). The ITT efficacy in reducing
hospitalizations was 94.7% (95% CI: 89.3, 97.3) as shown in Table 3.

Table 3
Efficacy of RotaTeq in reducing G1-4 rotavirus-related
hospitalizations in REST

Per Protocol Intent-to-Treat*
RotaTeq Placebo RotaTeq Placebo
--------------------------------------------------------------------
Subjects vaccinated 34,035 34,003 34,035 34,003
Number of
hospitalizations 6 144 10 187
--------------------------------------------------------------------
Efficacy estimate %
and
(95% confidence 95.8 94.7
interval) (90.5, 98.2) (89.3, 97.3)
--------------------------------------------------------------------
*ITT analysis includes all subjects who received at least one dose
of vaccine.

Study 007

Primary efficacy against any grade of severity of rotavirus
gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or
G4 through the first rotavirus season after vaccination was 72.5% (95%
CI: 50.6, 85.6) and the ITT efficacy was 58.4% (95% CI: 33.8, 74.5).
Primary efficacy against severe rotavirus gastroenteritis caused by
naturally occurring serotypes G1, G2, G3, or G4 through the first
rotavirus season after vaccination was 100% (95% CI: 13.0, 100.0) and
ITT efficacy against severe rotavirus disease was 100%, (95% CI: 30.9,
100.0) as shown in Table 4.

Table 4
Efficacy of RotaTeq against any grade of severity of and severe*
G1-4 rotavirus gastroenteritis through the first rotavirus season
postvaccination in Study 007

Per Protocol Intent-to-Treat+
RotaTeq Placebo RotaTeq Placebo
---------------------------------------------------------------------
Subjects
vaccinated 650 660 650 660
Gastroenteritis cases
Any grade of
severity 15 54 27 64
Severe* 0 6 0 7
---------------------------------------------------------------------
Efficacy estimate % and (95% confidence interval)
---------------------------------------------------------------------
Any grade of 72.5 58.4
severity (50.6, 85.6) (33.8, 74.5)
Severe* 100.0 100.0
(13.0, 100.0) (30.9, 100.0)
---------------------------------------------------------------------
*Severe gastroenteritis defined by a clinical scoring system based
on the intensity and duration of symptoms of fever, vomiting,
diarrhea, and behavioral change
+ITT analysis includes all subjects in the efficacy cohort who
received at least one dose of vaccine.

Multiple Rotavirus Seasons

The efficacy of RotaTeq through a second rotavirus season was
evaluated in a single study (REST). Efficacy against any grade of
severity of rotavirus gastroenteritis caused by rotavirus serotypes
G1, G2, G3, and G4 through the two rotavirus seasons after vaccination
was 71.3% (95% CI: 64.7, 76.9). The efficacy of RotaTeq in preventing
cases occurring only during the second rotavirus season
postvaccination was 62.6% (95% CI: 44.3, 75.4). The efficacy of
RotaTeq beyond the second season postvaccination was not evaluated.

Rotavirus Gastroenteritis Regardless of Serotype

The rotavirus serotypes identified in the efficacy subset of REST
and Study 007 were G1, P1(8); G2, P1(4); G3, P1(8); G4, P1(8); and G9,
P1(8).
In REST, the efficacy of RotaTeq against any grade of severity of
naturally occurring rotavirus gastroenteritis regardless of serotype
was 71.8% (95% CI: 64.5, 77.8) and efficacy against severe rotavirus
disease was 98.0% (95% CI: 88.3, 99.9). The ITT efficacy starting at
dose 1 was 51.0% (95% CI: 41.7, 58.9) for any grade of severity of
rotavirus disease and was 96.4% (95% CI: 86.4, 99.6) for severe
rotavirus disease.
In Study 007, the primary efficacy of RotaTeq against any grade of
severity of rotavirus gastroenteritis regardless of serotype was 72.7%
(95% CI: 51.9, 85.4) and efficacy against severe rotavirus disease was
100% (95% CI: 12.7, 100). The ITT efficacy starting at dose 1 was
48.0% (95% CI: 21.6, 66.1) for any grade of severity of rotavirus
disease and was 100% (95% CI: 31.0, 100.0) for severe rotavirus
disease.

Rotavirus Gastroenteritis By Serotype

The efficacy against any grade of severity of rotavirus
gastroenteritis by serotype in REST is shown in Table 5.

Table 5
Serotype-specific efficacy of RotaTeq against any grade of
severity of rotavirus gastroenteritis among infants in REST through
the first rotavirus season postvaccination (Per Protocol)

Serotype Number of cases % Efficacy
identified by RotaTeq Placebo (95% Confidence
PCR (N=2,834) (N=2,839) Interval)
----------------- -------------------
Serotypes present in RotaTeq
----------------------------------------------------------------------
G1, P1(8) 72 286 74.9 (67.3, 80.9)
----------------------------------------------------------------------
G2, P1(4) 6 17 63.4 (2.6, 88.2)
----------------------------------------------------------------------
G3, P1(8) 1 6 NS
----------------------------------------------------------------------
G4, P1(8) 3 6 NS
----------------------------------------------------------------------
Serotypes not present in RotaTeq
----------------------------------------------------------------------
G9, P1(8) 1 3 NS
----------------------------------------------------------------------
Unidentified* 11 15 NS
----------------------------------------------------------------------
N=number vaccinated
NS=not significant
----------------------------------------------------------------------
*Includes rotavirus antigen-positive samples in which the specific
serotype could not be identified by PCR

Immunogenicity

A relationship between antibody responses to RotaTeq and
protection against rotavirus gastroenteritis has not been established.
In phase 3 studies, 92.9% to 100% of 439 recipients of RotaTeq
achieved a 3-fold or more rise in serum anti-rotavirus IgA after a
three-dose regimen when compared to 12.3%-20.0% of 397 placebo
recipients.

INDICATIONS AND USAGE

RotaTeq is indicated for the prevention of rotavirus
gastroenteritis in infants and children caused by the serotypes G1,
G2, G3, and G4 when administered as a 3-dose series to infants between
the ages of 6 to 32 weeks. The first dose of RotaTeq should be
administered between 6 and 12 weeks of age (see DOSAGE AND
ADMINISTRATION).

CONTRAINDICATIONS

A demonstrated history of hypersensitivity to any component of the
vaccine.
Infants who develop symptoms suggestive of hypersensitivity after
receiving a dose of RotaTeq should not receive further doses of
RotaTeq.

PRECAUTIONS

General

Prior to administration of RotaTeq, the health care provider
should determine the current health status and previous vaccination
history of the infant, including whether there has been a reaction to
a previous dose of RotaTeq or other rotavirus vaccine.
Febrile illness may be reason for delaying use of RotaTeq except
when, in the opinion of the physician, withholding the vaccine entails
a greater risk. Low-grade fever (<100.5(degree)F (38.1(degree)C))
itself and mild upper respiratory infection do not preclude
vaccination with RotaTeq.
The level of protection provided by only one or two doses of
RotaTeq was not studied in clinical trials.
As with any vaccine, vaccination with RotaTeq may not result in
complete protection in all recipients.
Regarding post-exposure prophylaxis, no clinical data are
available for RotaTeq when administered after exposure to rotavirus.

Intussusception

Following administration of a previously licensed live rhesus
rotavirus-based vaccine, an increased risk of intussusception was
observed.(3) In REST (n=69,625), the data did not show an increased
risk of intussusception for RotaTeq when compared to placebo. See
ADVERSE REACTIONS, Intussusception.

Immunocompromised Populations

No safety or efficacy data are available for the administration of
RotaTeq to infants who are potentially immunocompromised including:

-- Infants with blood dyscrasias, leukemia, lymphomas of any
type, or other malignant neoplasms affecting the bone marrow
or lymphatic system.

-- Infants on immunosuppressive therapy (including high-dose
systemic corticosteroids). RotaTeq may be administered to
infants who are being treated with topical corticosteroids or
inhaled steroids.

-- Infants with primary and acquired immunodeficiency states,
including HIV/AIDS or other clinical manifestations of
infection with human immunodeficiency viruses; cellular immune
deficiencies; and hypogammaglobulinemic and
dysgammaglobulinemic states. There are insufficient data from
the clinical trials to support administration of RotaTeq to
infants with indeterminate HIV status who are born to mothers
with HIV/AIDS.

-- Infants who have received a blood transfusion or blood
products, including immunoglobulins within 42 days.

No safety or efficacy data are available for administration of
RotaTeq to infants with a history of gastrointestinal disorders
including infants with active acute gastrointestinal illness, infants
with chronic diarrhea and failure to thrive, and infants with a
history of congenital abdominal disorders, abdominal surgery, and
intussusception. Therefore, caution is advised when considering
administration of RotaTeq to these infants.

Shedding and Transmission

Shedding was evaluated among a subset of subjects in REST 4 to 6
days after each dose and among all subjects who submitted a stool
antigen rotavirus positive sample at any time. RotaTeq was shed in the
stools of 32 of 360 (8.9%, 95% CI (6.2%, 12.3%)) vaccine recipients
tested after dose 1; 0 of 249 (0.0%, 95% CI (0.0%, 1.5%)) vaccine
recipients tested after dose 2; and in 1 of 385 (0.3%, 95% CI (<0.1%,
1.4%)) vaccine recipients after dose 3. In phase 3 studies, shedding
was observed as early as 1 day and as late as 15 days after a dose.
Transmission was not evaluated.
Caution is advised when considering whether to administer RotaTeq
to individuals with immunodeficient close contacts such as:

-- individuals with malignancies or who are otherwise
immunocompromised; or

-- individuals receiving immunosuppressive therapy.

There is a theoretical risk that the live virus vaccine can be
transmitted to non-vaccinated contacts. The potential risk of
transmission of vaccine virus should be weighed against the risk of
acquiring and transmitting natural rotavirus.

Information for Parents/Guardians

Parents or guardians should be given a copy of the required
vaccine information and be given the "Patient Information" appended to
this insert. Parents and/or guardians should be encouraged to read the
patient information that describes the benefits and risks associated
with the vaccine and ask any questions they may have during the visit.

Drug Interactions

Immunosuppressive therapies including irradiation,
antimetabolites, alkylating agents, cytotoxic drugs and
corticosteroids (used in greater than physiologic doses), may reduce
the immune response to vaccines.
For administration of RotaTeq with other vaccines, see DOSAGE AND
ADMINISTRATION, Use with Other Vaccines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Pediatric Use

Safety and efficacy have not been established in infants less than
6 weeks of age or greater than 32 weeks of age.
Data are available from clinical studies to support the use of
RotaTeq in pre-term infants according to their age in weeks since
birth (see ADVERSE REACTIONS, Safety in Pre-Term Infants).
Data are available from clinical studies to support the use of
RotaTeq in infants with controlled gastroesophageal reflux disease.

ADVERSE REACTIONS

71,725 infants were evaluated in 3 placebo-controlled clinical
trials including 36,165 infants in the group that received RotaTeq and
35,560 infants in the group that received placebo. Parents/guardians
were contacted on days 7, 14, and 42 after each dose regarding
intussusception and any other serious adverse events. The racial
distribution was as follows: White (69% in both groups);
Hispanic-American (14% in both groups); Black (8% in both groups);
Multiracial (5% in both groups); Asian (2% in both groups); Native
American (RotaTeq 2%, placebo 1%), and Other (<1% in both groups). The
gender distribution was 51% male and 49% female in both vaccination
groups.
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 Events

Serious adverse events occurred in 2.4% of recipients of RotaTeq
when compared to 2.6% of placebo recipients within the 42-day period
of a dose in the phase 3 clinical studies of RotaTeq. The most
frequently reported serious adverse events for RotaTeq compared to
placebo were:

bronchiolitis (0.6% RotaTeq vs. 0.7% Placebo),
gastroenteritis (0.2% RotaTeq vs. 0.3% Placebo),
pneumonia (0.2% RotaTeq vs. 0.2% Placebo),
fever (0.1% RotaTeq vs. 0.1% Placebo), and
urinary tract infection (0.1% RotaTeq vs. 0.1% Placebo).

Deaths

Across the clinical studies, 52 deaths were reported. There were
25 deaths in the RotaTeq recipients compared to 27 deaths in the
placebo recipients. The most commonly reported cause of death was
sudden infant death syndrome, which was observed in 8 recipients of
RotaTeq and 9 placebo recipients.

Intussusception

In REST, 34,837 vaccine recipients and 34,788 placebo recipients
were monitored by active surveillance to identify potential cases of
intussusception at 7, 14, and 42 days after each dose, and every 6
weeks thereafter for 1 year after the first dose.
For the primary safety outcome, cases of intussuception occurring
within 42 days of any dose, there were 6 cases among RotaTeq
recipients and 5 cases among placebo recipients (see Table 6). The
data did not suggest an increased risk of intussusception relative to
placebo.

Table 6
Confirmed cases of intussusception in recipients of RotaTeq as
compared with placebo recipients during REST

RotaTeq (n=34,837) Placebo (n=34,788)
----------------------------------------------------------------------
Confirmed intussusception
cases within 42 days of any
dose 6 5
Relative risk (95% CI)+ 1.6 (0.4, 6.4)
----------------------------------------------------------------------
Confirmed intussusception
cases within 365 days of
dose 1 13 15
Relative risk (95% CI) 0.9 (0.4, 1.9)
----------------------------------------------------------------------
+Relative risk and 95% confidence interval based upon group
sequential design stopping criteria employed in REST.

Among vaccine recipients, there were no confirmed cases of
intussusception within the 42-day period after the first dose, which
was the period of highest risk for the rhesus rotavirus-based product
(see Table 7).

Table 7
Intussusception cases by day range in relation to dose in REST

Dose 1 Dose 2 Dose 3 Any Dose
----------------------------------------------------------------------
Day Range RotaTeq Placebo RotaTeq PlaceboRotaTeqPlaceboRotaTeq Placebo
----------------------------------------------------------------------
1-7 0 0 1 0 0 0 1 0
----------------------------------------------------------------------
1-14 0 0 1 0 0 1 1 1
----------------------------------------------------------------------
1-21 0 0 3 0 0 1 3 1
----------------------------------------------------------------------
1-42 0 1 4 1 2 3 6 5
----------------------------------------------------------------------

All of the children who developed intussusception recovered
without sequelae with the exception of a 9-month-old male who
developed intussusception 98 days after dose 3 and died of
post-operative sepsis. There was a single case of intussusception
among 2,470 recipients of RotaTeq in a 7-month-old male in the phase 1
and 2 studies (716 placebo recipients).

Seizures

All seizures reported in the phase 3 trials of RotaTeq (by
vaccination group and interval after dose) are shown in Table 8.

Table 8
Seizures reported by day range in relation to any dose in the phase 3
trials of RotaTeq

Day range 1-7 1-14 1-42
-----------------------------------------------------
RotaTeq 10 15 33
Placebo 5 8 24
-----------------------------------------------------


Seizures reported as serious adverse experiences occurred in <0.1%
(27/36,150) of vaccine and <0.1% (18/35,536) of placebo recipients
(not significant). Ten febrile seizures were reported as serious
adverse experiences, 5 were observed in vaccine recipients and 5 in
placebo recipients.

Most Common Adverse Events

Solicited Adverse Events

Detailed safety information was collected from 11,711 infants
(6,138 recipients of RotaTeq) which included a subset of subjects in
REST and all subjects from Studies 007 and 009 (Detailed Safety
Cohort). A Vaccination Report Card was used by parents/guardians to
record the child's temperature and any episodes of diarrhea and
vomiting on a daily basis during the first week following each
vaccination. Table 9 summarizes the frequencies of these adverse
events and irritability.

Table 9
Solicited adverse experiences within the first week after doses 1,
2, and 3 (Detailed Safety Cohort)

Adverse Dose 1 Dose 2 Dose 3
experience
RotaTeq Placebo RotaTeq Placebo RotaTeq Placebo
----------------------------------------------------------------------
Elevated n=5,616 n=5,077 n=5,215 n=4,725 n=4,865 n=4,382
temperature 17.1% 16.2% 20.0% 19.4% 18.2% 17.6%
----------------------------------------------------------------------
n=6,130 n=5,560 n=5,703 n=5,173 n=5,496 n=4,989
Vomiting 6.7% 5.4% 5.0% 4.4% 3.6% 3.2%

Diarrhea 10.4% 9.1% 8.6% 6.4% 6.1% 5.4%

Irritability 7.1% 7.1% 6.0% 6.5% 4.3% 4.5%
----------------------------------------------------------------------
* Temperature (>=)100.5(degree)F (38.1(degree)C) rectal equivalent
obtained by adding 1 degree F to otic and oral temperatures and 2
degrees F to axillary temperatures

Other Adverse Events

Parents/guardians of the 11,711 infants were also asked to report
the presence of other events on the Vaccination Report Card for 42
days after each dose.
Fever was observed at similar rates in vaccine (N=6,138) and
placebo (N=5,573) recipients (42.6% vs. 42.8%). Adverse events that
occurred at a statistically higher incidence (i.e., 2-sided p-value
<0.05) within the 42 days of any dose among recipients of RotaTeq as
compared with placebo recipients are shown in Table 10.

Table 10
Adverse events that occurred at a statistically higher incidence
within 42 days of any dose among recipients of RotaTeq as compared
with placebo recipients

RotaTeq Placebo
Adverse event N=6,138 N=5,573
---------------------------------------------------
n (%) n (%)
---------------------------------------------------
Diarrhea 1,479 (24.1%) 1,186 (21.3%)
Vomiting 929 (15.2%) 758 (13.6%)
Otitis media 887 (14.5%) 724 (13.0%)
Nasopharyngitis 422 (6.9%) 325 (5.8%)
Bronchospasm 66 (1.1%) 40 (0.7%)
---------------------------------------------------

Safety in Pre-Term Infants

RotaTeq or placebo was administered to 2,070 pre-term infants (25
to 36 weeks gestational age, median 34 weeks) according to their age
in weeks since birth in REST. All pre-term infants were followed for
serious adverse experiences; a subset of 308 infants was monitored for
all adverse experiences. There were 4 deaths throughout the study, 2
among vaccine recipients (1 SIDS and 1 motor vehicle accident) and 2
among placebo recipients (1 SIDS and 1 unknown cause). No cases of
intussusception were reported. Serious adverse experiences occurred in
5.5% of vaccine and 5.8% of placebo recipients. The most common
serious adverse experience was bronchiolitis, which occurred in 1.4%
of vaccine and 2.0% of placebo recipients. Parents/guardians were
asked to record the child's temperature and any episodes of vomiting
and diarrhea daily for the first week following vaccination. The
frequencies of these adverse experiences and irritability within the
week after dose 1 are summarized in Table 11.

Table 11

Solicited adverse experiences within the first week of doses 1, 2,
and 3 among pre-term infants

Dose 1 Dose 2 Dose 3
Adverse event RotaTeq Placebo RotaTeq Placebo RotaTeq Placebo
----------------------------------------------------------------------
N=127 N=133 N=124 N=121 N=115 N=108
Elevated
temperature 18.1% 17.3% 25.0% 28.1% 14.8% 20.4%
----------------------------------------------------------------------
N=154 N=154 N=137 N=137 N=135 N=129
Vomiting 5.8% 7.8% 2.9% 2.2% 4.4% 4.7%

Diarrhea 6.5% 5.8% 7.3% 7.3% 3.7% 3.9%

Irritability 3.9% 5.2% 2.9% 4.4% 8.1% 5.4%
----------------------------------------------------------------------
* Temperature greater than or equal to 100.5(degree)F
(38.1(degree)C) rectal equivalent obtained by adding 1 degree F to
otic and oral temperatures and 2 degrees F to axillary temperatures

Reporting Adverse Events

Parents or guardians should be instructed to report any adverse
reactions to their health care provider. The US 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, including but not limited to the
reporting of events required by the National Childhood Vaccine Injury
Act of 1986. For information or a copy of the vaccine reporting form,
call the VAERS toll-free number at 1-800-822-7967 or report on line to
www.vaers.hhs.gov.(4 )

DOSAGE AND ADMINISTRATION

FOR ORAL USE ONLY. NOT FOR INJECTION.

The vaccination series consists of three ready-to-use liquid doses
of RotaTeq administered orally starting at 6 to 12 weeks of age, with
the subsequent doses administered at 4- to 10-week intervals. The
third dose should not be given after 32 weeks of age (see CLINICAL
STUDIES).
There are no restrictions on the infant's consumption of food or
liquid, including breast milk, either before or after vaccination with
RotaTeq.
Do not mix the RotaTeq vaccine with any other vaccines or
solutions. Do not reconstitute or dilute (see INSTRUCTIONS FOR USE).
Each dose is supplied in a container consisting of a squeezable
plastic, latex-free dosing tube with a twist-off cap, allowing for
direct oral administration. The dosing tube is contained in a pouch
(see INSTRUCTIONS FOR USE).

Use with Other Vaccines

In clinical trials, RotaTeq was routinely administered
concomitantly with diphtheria and tetanus toxoids and acellular
pertussis (DTaP), inactivated poliovirus vaccine (IPV), H. influenzae
type b conjugate vaccine (Hib), hepatitis B vaccine, and pneumococcal
conjugate vaccine (see CLINICAL STUDIES). The safety data available
are in the ADVERSE REACTIONS section.
There was no evidence for reduced antibody responses to the
diphtheria or tetanus toxoid components of DTaP or to the other
vaccines that were concomitantly administered with RotaTeq. However,
insufficient immunogenicity data are available to confirm lack of
interference of immune responses when RotaTeq is concomitantly
administered with childhood vaccines to prevent pertussis.

INSTRUCTIONS FOR USE


To administer the vaccine:



Tear open the pouch and remove the dosing tube.


Clear the fluid from the dispensing tip by holding tube vertically and
tapping cap.


Open the dosing tube in 2 easy motions:



1) Puncture the dispensing tip by screwing cap clockwise until it
becomes tight.


2) Remove cap by turning it counterclockwise.


Administer dose by gently squeezing liquid into infant's mouth toward
the inner cheek until dosing tube is empty. (A residual drop may
remain in the tip of the tube.)


If for any reason an incomplete dose is administered (e.g., infant
spits or regurgitates the vaccine), a replacement dose is not
recommended, since such dosing was not studied in the clinical
trials. The infant should continue to receive any remaining doses in
the recommended series.



Discard the empty tube and cap in approved biological waste containers
according to local regulations.

HOW SUPPLIED

No. 4047 - RotaTeq, 2 mL, a suspension for oral use, is a pale
yellow clear liquid that may have a pink tint. It is supplied as
follows:
NDC 0006-4047-31 package of 1 individually pouched single-dose
tube
NDC 0006-4047-41 package of 10 individually pouched single-dose
tubes.

Storage

Store and transport refrigerated at 2-8(degree)C (36-46(degree)F).
RotaTeq should be administered as soon as possible after being removed
from refrigeration. For information regarding stability under
conditions other than those recommended, call 1-800-MERCK-90.

Protect from light.

RotaTeq should be discarded in approved biological waste
containers according to local regulations.

The product must be used before the expiration date.

REFERENCES

1. Parashar UD et al. Global illness and deaths caused by
rotavirus disease in children. Emerg Infect Dis 2003;9(5):565-572.
2. Parashar UD, Holman RC, Clarke MJ, Bresee JS, Glass RI.
Hospitalizations associated with rotavirus diarrhea in the United
States, 1993 through 1995: surveillance based on the new ICD-9-CM
rotavirus-specific diagnostic code. J Infect Dis 1998;177:13-7.
3. Murphy TV, Gargiullo PM, Massoudi MS et al. Intussusception
among infants given an oral rotavirus vaccine. N Engl J Med
2001;344:564-572.
4. Centers for Disease Control and Prevention. General
recommendations on immunization: recommendations of the Advisory
Committee on Immunization Practices (ACIP) and the American Academy of
Family Physicians (AAFP). MMWR 2002;51(RR-2):1-35.

Issued February 2006

Printed in USA

* Registered trademark of MERCK & CO., Inc., Whitehouse Station,
NJ, 08889 USA

COPYRIGHT (C) 2006 MERCK & CO., Inc.

All rights reserved