CDC Advisory Committee on Immunization Practices Votes to Recommend Inclusion of ROTATEQ(R) in the Vaccines for Children (VFC) Program.WHITEHOUSE Whitehouse may refer to:
Rotavirus /Ro·ta·vi·rus/ (ro´tah-vi?rus vaccine vaccine Preparation containing either killed or weakened live microorganisms or their toxins, introduced by mouth, by injection, or by nasal spray to stimulate production of antibodies against an infectious agent. , live, oral, pentavalent pentavalent having a valence of five. pentavalent antimony compounds see antimony. pentavalent organic arsenicals includes the pharmaceuticals arsanilic acid, roxarsone, nitarsone. See also organic arsenical. ) be included in the CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation Vaccines for Children (VFC VFC Vaccines for Children (program) VFC VESA (Video Electronics Standards Association) Feature Connector VFC Voltage to Frequency Converter VFC Vice Flotilla Commander VFC Flotilla Vice Commander VFC V. ) program. Since 1994, the VFC program has provided vaccines to children who are Medicaid-eligible, uninsured, underinsured un·der·in·sure tr.v. un·der·in·sured, un·der·in·sur·ing, un·der·in·sures To insure under a policy that provides inadequate benefits: Be certain that you are not underinsured against catastrophic illness. or Native American American, river, 30 mi (48 km) long, rising in N central Calif. in the Sierra Nevada and flowing SW into the Sacramento River at Sacramento. The discovery of gold at Sutter's Mill (see Sutter, John Augustus) along the river in 1848 led to the California gold rush of . Eligible children may receive recommended vaccines through VFC once the CDC contracts for the purchase of the vaccine. Yesterday, the ACIP unanimously voted to recommend that all infants Persons who are under the age of legal majority—at Common Law, 21 years, now generally 18 years. According to the sense in which this term is used, it may denote the age of the person, the contractual disabilities that non-age entails, or his or her status with regard to , starting at six to 12 weeks of age, be vaccinated with ROTATEQ to prevent rotavirus gastroenteritis gastroenteritis: see enteritis. gastroenteritis Acute infectious syndrome of the stomach lining and intestines. Symptoms include diarrhea, vomiting, and abdominal cramps. , a leading cause of severe dehydrating diarrhea diarrhea (dīərē`ə), frequent discharge of watery feces from the intestines, sometimes containing blood and mucus. It can be caused by excessive indulgence in alcohol or other liquids or foods that prove irritating to the stomach or in infants and young children. The ACIP recommended that the oral, ready-to-use, three-dose vaccine be given during the current routine well baby visits at two, four, and six months of age. On February February: see month. 3, the U.S. Food and Drug Administration (FDA FDA abbr. Food and Drug Administration FDA, n.pr See Food and Drug Administration. FDA, n.pr the abbreviation for the Food and Drug Administration. ) approved ROTATEQ, now the only vaccine available in the U.S. to prevent this serious and unpredictable disease, for use in infants between the ages of six to 32 weeks. ROTATEQ should not be used in infants that are allergic al·ler·gic adj. 1. Of, caused, or characterized by an allergy. 2. Having an allergy or exhibiting an allergic reaction to a substance. allergic pertaining to or caused by allergy. to any component of the vaccine. The ACIP now recommends vaccines for routine use in children to prevent diphtheria diphtheria (dĭfthēr`ēə), acute contagious disease caused by Corynebacterium diphtheriae (Klebs-Loffler bacillus) bacteria that have been infected by a bacteriophage. It begins as a soreness of the throat with fever. , Haemophilus Haemophilus Genus of tiny rod-shaped bacteria. All are strict parasites occurring in the respiratory tracts of warm-blooded animals, including humans, and in certain cold-blooded animals. Some require oxygen, others do not. H. influenza influenza or flu, acute, highly contagious disease caused by a virus; formerly known as the grippe. There are three types of the virus, designated A, B, and C, but only types A and B cause more serious contagious infections. type b, hepatitis A Hepatitis A Definition Hepatitis A is an inflammation of the liver caused by a virus, the hepatitis A virus (HAV). It varies in severity, running an acute course, generally starting within two to six weeks after contact with the virus, and lasting no , hepatitis B Hepatitis B Definition Hepatitis B is a potentially serious form of liver inflammation due to infection by the hepatitis B virus (HBV). It occurs in both rapidly developing (acute) and long-lasting (chronic) forms, and is one of the most common chronic , influenza, measles measles or rubeola (r  bē`ələ), highly contagious disease of young children, caused by a filterable virus and spread by droplet spray from the nose, mouth, , meningococcal disease, mumps, pertussis pertussis: see whooping cough. ,
pneumococcal pneumococcal /pneu·mo·coc·cal/ (-kok´al) pertaining to or caused by pneumococci. disease, polio polio: see poliomyelitis. , rotavirus, rubella rubella or German measles, acute infectious disease of children and young adults. It is caused by a filterable virus that is spread by droplet spray from the respiratory tract of an infected individual. , tetanus tetanus (tĕt`nəs, –ənəs) or lockjaw, acute infectious disease of the central nervous system caused by the toxins of Clostridium tetani. and varicella varicella: see chicken pox. .
Merck makes vaccines to help protect against eight of these 15 diseases.Selected Important Information about ROTATEQ 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 three-dose series to infants between the ages of six to 32 weeks. The vaccination vaccination, means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms. series consists of three ready-to-use liquid doses of ROTATEQ administered orally starting at six to 12 weeks of age, with the subsequent doses administered at four to 10 week intervals. The third dose should not be given after 32 weeks of age. As with any vaccine, vaccination with ROTATEQ may not result in complete protection in all recipients. The vaccine will also not help protect those children who already have the virus. The efficacy efficacy /ef·fi·ca·cy/ (ef´i-kah-se) 1. the ability of an intervention to produce the desired beneficial effect in expert hands and under ideal circumstances. 2. of ROTATEQ beyond the second season after vaccination was not evaluated. The safety and efficacy of ROTATEQ have not been established in infants less than six weeks of age or greater than 32 weeks of age. No safety or efficacy data are available for the administration of ROTATEQ to infants who are potentially immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). , including: those with certain disorders A
Medical treatment in which the immune system is purposefully thwarted. Such treatment is necessary, for example, to prevent organ rejection in transplant cases. or with an immunodeficient Immunodeficient A condition in which the body's immune response is damaged, weakened, or is not functioning properly. Mentioned in: AIDS condition, or those who received blood products within six weeks of vaccination. The most common adverse events reported after taking ROTATEQ in clinical trials were diarrhea, vomiting vomiting, ejection of food and other matter from the stomach through the mouth, often preceded by nausea. The process is initiated by stimulation of the vomiting center of the brain by nerve impulses from the gastrointestinal tract or other part of the body. , fever, runny nose runny nose Vox populi → medtalk Rhinorrhea and sore throat Sore Throat Definition Sore throat, also called pharyngitis, is a painful inflammation of the mucous membranes lining the pharynx. It is a symptom of many conditions, but most often is associated with colds or influenza. , wheezing Wheezing Definition Wheezing is a high-pitched whistling sound associated with labored breathing. Description Wheezing occurs when a child or adult tries to breathe deeply through air passages that are narrowed or filled with mucus as a or coughing Coughing Coughing helps break up secretions in the lungs so that the mucus can be suctioned out or expectorated. Patients sit upright and inhale deeply through the nose. They then exhale in short puffs or coughs. Coughing is repeated several times per day. , and ear infection. 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 regulatory agency Independent government commission charged by the legislature with setting and enforcing standards for specific industries in the private sector. The concept was invented by the U.S. around the world are reviewing applications for ZOSTAVAX Zostavax is a live vaccine developed by Merck & Co. which has been shown to reduce the incidence of herpes zoster (known as Shingles) by 51.3% in a pivotal phase III study of 38,000 adults aged 60 and older who received the vaccine. The vaccine also reduced by 66. (R), Merck's investigational vaccine to prevent shingles shingles: see herpes zoster. shingles or herpes zoster Acute viral skin and nerve infection. Groups of small blisters appear along certain nerve segments, most often on the back, sometimes after a dull ache at the site; pain becomes and shingles-associated pain in adults, and GARDASIL
Gardasil is a vaccine against certain types of the human papillomavirus (HPV), manufactured by Merck & Co.. The research that lead to the development of the vaccine began in the 1980s by groups at the University of Rochester, (R), Merck's investigational HPV HPV human papillomavirus. HPV abbr. human papilloma virus Human papilloma virus (HPV) and cervical cancer Cervical Cancer Definition Cervical cancer is a disease in which the cells of the cervix become abnormal and start to grow uncontrollably, forming tumors. vaccine. About Merck Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufacturers and markets vaccines and medicines to address unmet un·met adj. Not satisfied or fulfilled: unmet demands. medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching far-reach·ing adj. Having a wide range, influence, or effect: the far-reaching implications of a major new epidemic. 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 Not-for-profit An organization established for charitable, humanitarian, or educational purposes that is exempt from some taxes and in which no one in profits or losses. service. For more information, visit www.merck.com. Forward-Looking Statement forward-looking statement A projected financial statement based on management expectations. A forward-looking statement involves risks with regard to the accuracy of assumptions underlying the projections. This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and 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 cautionary statements in Item 1 of Merck's Form 10-K Form 10-K A report required by the SEC from exchange-listed companies that provides for annual disclosure of certain financial information. Form 10-K See 10-K. for the year ended Dec. 31, 2004, and in its periodic reports on Form 10-Q Form 10-Q See 10-Q. and Form 8-K Form 8-K The form required by the SEC when a publicly held company incurs any event that might affect its financial situation or the share value of its stock. Form 8-K See 8-K. , which the Company incorporates by reference. ROTATEQ(R) is a registered trademark of Merck & Co., Inc. See attached prescribing information.
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
|
|
||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion