Significant Step in Merck’s Efforts to Expand Global Access to Rotavirus Vaccine

ROTATEQ^® (rotavirus vaccine, live, oral, pentavalent), the pentavalent rotavirus vaccine from Merck & Co., Inc., that helps prevent rotavirus gastroenteritis in infants and children, has been awarded pre-qualification status by the World Health Organization (WHO). WHO pre-qualification allows for expanded access to ROTATEQ and provides a greater opportunity to help protect millions of babies from rotavirus gastroenteritis.

Because ROTATEQ is pre-qualified by the WHO, the vaccine is eligible for procurement by the Pan American Health Organization (PAHO), UNICEF and other United Nations agencies for use in national vaccination programs. Expanded access to ROTATEQ is especially important in the world's least developed countries, where the consequences of rotavirus gastroenteritis can be very serious due in part to poorer access to healthcare and greater malnutrition. Rotavirus infects nearly all children worldwide by age 5 and causes approximately 1.9 million hospitalizations each year in developing countries. ROTATEQ is the only ready-to-use oral liquid rotavirus vaccine to receive WHO pre-qualification.

In the United States, ROTATEQ is indicated for use in infants and children for the prevention of rotavirus gastroenteritis caused by serotypes G1, G2, G3, and G4 and is administered orally as a three-dose series between the ages of 6 and 32 weeks.

“WHO pre-qualification of ROTATEQ is an important milestone in expanding the global availability of ROTATEQ, and importantly, for facilitating efforts to accelerate the introduction of the vaccine in the world's poorest countries,” said Mark Feinberg, M.D., Ph.D., vice president, Medical Affairs and Policy, Merck Vaccines and Infectious Diseases. “Merck's pledge to provide ROTATEQ to GAVI-eligible countries at prices at which we do not profit is another step to make this vaccine accessible to all who need it in every part of the world.”

WHO pre-qualification of ROTATEQ is based on quality, safety and efficacy data generated in the U.S., Latin America and Europe. Merck has committed to provide additional safety and efficacy data from Africa and Asia and is currently conducting clinical trials in these regions in partnership with the Rotavirus Vaccine Program (RVP) of PATH, an international, non-profit organization.

“Vaccines are the best hope for preventing severe rotavirus gastroenteritis,” said John Wecker, Ph.D., director, PATH Rotavirus Vaccine Program. “WHO’s pre-qualification of ROTATEQ is a major step in ensuring that rotavirus vaccines are accessible to children worldwide.”

In late 2006, the GAVI Alliance, recognizing the public health need for rotavirus vaccines, committed to provide funding for the introduction of rotavirus vaccines in eligible countries. Public sector programs in European and Latin American countries that require WHO pre-qualification status may now select ROTATEQ for use in national rotavirus vaccination programs.

WHO pre-qualification is part of Merck's systematic approach to the global introduction of ROTATEQ. In 2006, ROTATEQ was recommended for use in all children in the U.S. and in the same year, Merck created and implemented a first-of-its-kind donation and partnership program with the Nicaraguan Ministry of Health (MINSA), through which Merck introduced ROTATEQ in a GAVI-eligible country, Nicaragua. In the first two years of this ongoing three-year partnership, approximately 700,000 doses of ROTATEQ have been provided at no cost by Merck and the country has achieved rotavirus vaccination rates that are among the highest in the world.

About Rotavirus

Rotavirus is a leading cause of severe acute gastroenteritis in infants and young children. Rotavirus is highly prevalent and highly contagious, infecting nearly all children by age 5, many more than once, in both developed and developing countries. The virus causes more than two million hospitalizations and nearly 600,000 deaths worldwide among children under age 5 each year. Eighty percent of rotavirus-related deaths occur in developing countries. In the U.S., historically rotavirus has been responsible for an estimated 55,000 to 70,000 hospitalizations more than 200,000 emergency room visits, approximately 400,000 doctor visits and approximately 20-60 deaths per year among children under age 5.

About ROTATEQ

ROTATEQ is an oral liquid vaccine requiring no reconstitution or mixing.

The safety and efficacy of ROTATEQ were established in Phase 3 studies of more than 71,000 infants from 11 countries and included the landmark Rotavirus Efficacy and Safety Trial (REST), one of the largest pre-licensure vaccine clinical trials ever conducted. Approximately 18 million doses of ROTATEQ have been distributed worldwide through September 2008. ROTATEQ has been approved in 87 countries around the world and is available in more than 50 countries.

Select Safety Information about ROTATEQ

ROTATEQ should not be administered to infants with a demonstrated history of hypersensitivity to any component of the vaccine. No safety or efficacy data are available for the administration of ROTATEQ to infants who are potentially immunocompromised or to infants with a history of gastrointestinal disorders.

Caution is advised when considering whether to administer ROTATEQ to individuals with immunodeficient contacts.

More than 71,000 infants were evaluated in three Phase 3, placebo-controlled clinical trials. Serious adverse events occurred in 2.4 percent of recipients of ROTATEQ when compared to 2.6 percent of placebo recipients within the 42-day period of a dose of ROTATEQ. Hematochezia, reported as a serious adverse event for ROTATEQ compared to placebo, was less than 0.1 percent vs. less than 0.1 percent. The most frequently reported serious adverse events for ROTATEQ, compared to placebo, were bronchiolitis, gastroenteritis, pneumonia, fever, and urinary tract infection.

In a subset of more than 11,000 infants in these trials, the presence of adverse events was reported for 42 days after each dose. Fever was observed at similar rates in vaccine and placebo recipients (42.6 percent vs. 42.8 percent). Adverse events that occurred at a statistically higher incidence within 42 days of any dose among recipients of ROTATEQ, as compared with placebo recipients, were diarrhea (24.1 percent vs. 21.3 percent), vomiting (15.2 percent vs. 13.6 percent), otitis media (14.5 percent vs. 13.0 percent), nasopharyngitis (6.9 percent vs. 5.8 percent), and bronchospasm (1.1 percent vs. 0.7 percent).

In post-marketing experience, intussusception (including death) and Kawasaki Disease have been reported in temporal association with ROTATEQ.

ROTATEQ may not protect all vaccine recipients against rotavirus.

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 http://www.merck.com.

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 press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

Prescribing Information and Patient Product Information for ROTATEQ^® are attached and are also available at www.rotateq.com.

ROTATEQ^® is a registered trademark of Merck & Co. Inc., Whitehouse Station, N.J., USA

9714307

Patient Information

RotaTeq^®* (pronounced "RŌ-tuh-tek")

rotavirus vaccine, live, oral, pentavalent

Read this information carefully before your child receives each dose of RotaTeq in case any information about the vaccine changes. Your child will need 3 doses of the vaccine over the course of a few months. This leaflet is a summary of certain information about RotaTeq and does not take the place of talking with your child’s doctor, who can give you more complete information written for health care professionals.

What is RotaTeq and How Does it Work?

RotaTeq helps protect against an infection that nearly all children get called rotavirus. Rotavirus can cause fever, vomiting, and diarrhea which may be severe and can lead to loss of body fluids (dehydration), hospitalization and even death in some children. 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 should I tell the doctor before my child gets RotaTeq?

Tell your doctor if your child:

• Has illness with fever. A mild fever or cold by itself is not reason to delay taking the vaccine.
• Has diarrhea or has been vomiting.
• Has not been gaining weight or 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 family or household who has a weak immune system such as someone with cancer or someone taking medicines that weaken their immune system.

What other important information should I know?

Call your child's doctor right away if, following any dose of RotaTeq, your child has vomiting, diarrhea, severe stomach pain, blood in their stool or change in their bowel movements as these may be signs of intussusception. Intussusception is a serious and life-threatening event that occurs when a part of the intestine gets blocked or twisted and it requires immediate medical attention. Intussusception can occur when no vaccine has been given and the cause is usually unknown.

Since FDA approval, reports of infants with intussusception have been received by Vaccine Adverse Event Reporting System (VAERS). Intussusception occurred days and sometimes weeks after vaccination. Some of these infants required hospitalization and surgery on their intestine or a special enema to treat this problem. Death due to intussusception has also occurred.

Before FDA approval, RotaTeq was studied in 35,000 infants and no increased risk of intussusception was found compared to 35,000 infants who did not receive RotaTeq.

Contact your doctor if your child has any symptoms of intussusception, even if it has been several weeks since the last vaccine dose.

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 were diarrhea, vomiting, fever, runny nose and sore throat, wheezing or coughing, and ear infection.

Other reported side effects include: hives; Kawasaki disease (a serious condition of high fever, rash, red eyes, red mouth, swollen glands, swollen hands and feet).

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

If your child seems to be having any side effects that are not mentioned in this leaflet, please call your doctor or other health care provider. If the condition continues or worsens, you should seek medical attention.

You, as a parent or guardian, may also report any adverse reactions to your child’s health care provider or directly to the Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to www.vaers.hhs.gov.

Can RotaTeq be given with other vaccines?

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

How is RotaTeq given?

The vaccine is given by mouth. Your child will receive 3 doses of the vaccine. The first dose is given when your child is 6 to 12 weeks of age, the second dose is given 4 to 10 weeks later and the third dose 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 into your child’s mouth (see Figure 1). Your infant may spit out some or all of it. If this happens, the dose does not need to be given again during that visit.

Figure 1:

(Object omitted)

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 32 weeks of age. Your health care provider will tell you when your child should come for the follow-up doses. It is important to keep those appointments. If you forget or are not able to go back at the planned time, ask your health care provider for advice.

What else should I know about RotaTeq?

This leaflet gives a summary of certain information about the vaccine. If you have any questions or concerns about RotaTeq, talk to your 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, and P1).

Inactive Ingredients: sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80 and also fetal bovine serum.

Rx only

Issued July 2008

* Registered trademark of MERCK & Co., Inc., Whitehouse Station, NJ, 08889 USA COPYRIGHT © 2008 MERCK & Co., Inc. All rights reserved

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use RotaTeq safely and effectively. See full prescribing information for RotaTeq.

RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent)

Oral Solution

Initial U.S. Approval: 2006

-----------------------INDICATIONS AND USAGE---------------------

RotaTeq® is indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the G1, G2, G3 and G4 serotypes contained in the vaccine. (1)

-------------------DOSAGE AND ADMINISTRATION--------------------

• FOR ORAL USE ONLY. NOT FOR INJECTION. (2)
• 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. (2)

--------------------DOSAGE FORMS AND STRENGTHS-------------------

2 mL, oral solution of 5 live human-bovine reassortant rotaviruses which contains a minimum of 2.0 – 2.8 x 10⁶ infectious units (IU) per reassortant dose, depending on the serotype, and not greater than 116 x 10⁶ IU per aggregate dose. (3)

-------------------------CONTRAINDICATIONS-----------------------

• A demonstrated history of hypersensitivity to the vaccine or any component of the vaccine. (4)

---------------------WARNINGS AND PRECAUTIONS---------------------

• No safety or efficacy data are available for the administration of RotaTeq to infants who are potentially immunocompromised (e.g., HIV/AIDS). (5.1)
• No safety or efficacy data are available for the administration of RotaTeq to infants with a history of gastrointestinal disorders (e.g., active acute gastrointestinal illness, chronic diarrhea, failure to thrive, history of congenital abdominal disorders, abdominal surgery and intussusception). (5.2)
• Caution is advised when considering whether to administer RotaTeq to individuals with immunodeficient contacts. (5.4)

------------------------ADVERSE REACTIONS------------------------

Most common adverse events included diarrhea, vomiting, irritability, otitis media, nasopharyngitis, and bronchospasm. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Merck & Co., Inc. at 1-877-888-4231 or FDA at 1-800-822-7967 or www.vaers.hhs.gov².

--------------------USE IN SPECIFIC POPULATIONS-------------------

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.
• Infants with controlled gastroesophageal reflux disease. (8.4)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 07/2008

________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*

*Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

RotaTeq¹ 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 (2)).

2 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 (14)).

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 Dosage and Administration (2.2)).

For storage instructions (see How Supplied/Storage and Handling (16.1)).

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 Dosage and Administration (2.2)).

2.1 Use with Other Vaccines

In clinical trials, RotaTeq was administered concomitantly with other licensed pediatric vaccines (see Adverse Reactions (6.1), Drug Interactions (7.1), and Clinical Studies (14)).

2.2 Instructions for Use

3 DOSAGE FORMS AND STRENGTHS

RotaTeq, 2 mL for oral use, is a ready-to-use solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A(8) which contains a minimum of 2.0 – 2.8 x 10⁶ infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 10⁶ IU per aggregate dose.

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.

4 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.

5 WARNINGS AND PRECAUTIONS

5.1 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 data are available regarding potential vaccine virus transmission from vaccine recipient to non-vaccinated household or other contacts (see Warnings and Precautions (5.4)).

5.2 Gastrointestinal Illness

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. Caution is advised when considering administration of RotaTeq to these infants.

5.3 Intussusception

Following administration of a previously licensed live rhesus rotavirus-based vaccine, an increased risk of intussusception was observed.¹ In the Rotavirus Efficacy and Safety Trial (REST) (n=69,625), the data did not show an increased risk of intussusception for RotaTeq when compared to placebo. In post-marketing experience, cases of intussusception have been reported in temporal association with RotaTeq. (See Adverse Reactions (6.1 and 6.2).)

5.4 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.

RotaTeq is a solution of live reassortant rotaviruses and can potentially be transmitted to persons who have contact with the vaccine. The potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and transmitting natural rotavirus.

5.5 Febrile Illness

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°F (38.1°C)) itself and mild upper respiratory infection do not preclude vaccination with RotaTeq.

5.6 Incomplete Regimen

The clinical studies were not designed to assess the level of protection provided by only one or two doses of RotaTeq.

5.7 Limitations of Vaccine Effectiveness

RotaTeq may not protect all vaccine recipients against rotavirus.

5.8 Post-Exposure Prophylaxis

No clinical data are available for RotaTeq when administered after exposure to rotavirus.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

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:

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 intussusception occurring within 42 days of any dose, there were 6 cases among RotaTeq recipients and 5 cases among placebo recipients (see Table 1). The data did not suggest an increased risk of intussusception relative to placebo.

^*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 2).

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).

Hematochezia

Hematochezia reported as an adverse experience occurred in 0.6% (39/6,130) of vaccine and 0.6% (34/5,560) of placebo recipients within 42 days of any dose. Hematochezia reported as a serious adverse experience occurred in <0.1% (4/36,150) of vaccine and <0.1% (7/35,536) of placebo recipients within 42 days of any dose.

Seizures

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

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.

Kawasaki Disease

In the phase 3 clinical trials, infants were followed for up to 42 days of vaccine dose. Kawasaki disease was reported in 5 of 36,150 vaccine recipients and in 1 of 35,536 placebo recipients with unadjusted relative risk 4.9 (95% CI 0.6, 239.1).

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 4 summarizes the frequencies of these adverse events and irritability.

*Temperature (≥)100.5°F (38.1°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 5.

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 6.

*Temperature ≥100.5°F (38.1°C) rectal equivalent obtained by adding 1 degree F to otic and oral temperatures and 2 degrees F to axillary temperatures

6.2 Post-Marketing Experience

The following adverse events have been identified during post-approval use of RotaTeq from reports to the Vaccine Adverse Event Reporting System (VAERS).

Reporting of adverse events following immunization to VAERS is voluntary, and the number of doses of vaccine administered is not known; therefore, it is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to vaccine exposure using VAERS data.

In post-marketing experience, the following adverse events have been reported in infants who have received RotaTeq:

Reporting Adverse Events

Parents or guardians should be instructed to report any adverse reactions to their health care provider.

Health care providers should report all adverse events to the U.S. Department of Health and Human Services' Vaccine Adverse Events Reporting System (VAERS).

VAERS accepts 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.²

7 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.

7.1 Concomitant Vaccine Administration

In clinical trials, RotaTeq was administered concomitantly with diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus vaccine (IPV), H. influenzae type b conjugate (Hib), hepatitis B vaccine, and pneumococcal conjugate vaccine (see Clinical Studies (14)). The safety data available are in the ADVERSE REACTIONS section (see Adverse Reactions (6.1)).

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 adm