Rotavirus Vaccine, Live, Oral, Pentavalent

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 (serotype P7) from the bovine rotavirus parent strain. The fifth reassortant virus expresses the attachment protein, P1A (genotype P[8]), herein referred to as serotype P1A[8], from the human rotavirus parent strain and the outer capsid protein of serotype G6 from the bovine rotavirus parent strain (see Table 7).

Table 7

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. RotaTeq contains no preservatives.

In the manufacturing process for RotaTeq, a porcine-derived material is used. DNA from porcine circoviruses (PCV) 1 and 2 has been detected in RotaTeq. PCV-1 and PCV-2 are not known to cause disease in humans.

RotaTeq is a pale yellow clear liquid that may have a pink tint.

The plastic dosing tube and cap do not contain latex.

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Rotavirus oral vaccine contains up to five strains of rotavirus. It is made from both human and animal sources.

Infection with rotavirus can affect the digestive system of babies and young children, causing severe stomach or intestinal illness.

The rotavirus oral vaccine is used to help prevent this disease in children.

This vaccine works by exposing your child to a small dose of the virus, which causes the body to develop immunity to the disease. This vaccine will not treat an active infection that has already developed in the body.

Rotavirus oral vaccine is for use in children between the ages of 6 weeks and 32 weeks old.

Like any vaccine, the rotavirus oral vaccine may not provide protection from disease in every person.

Your child should not receive this vaccine if he or she has ever had a life-threatening allergic reaction to a rotavirus oral vaccine, or if the child has severe combined immunodeficiency disease (SCID). This vaccine should not be given if the child has a history of an intestinal problem called intussusception (in-tuh-suh-SEP-shun).

Your child can still receive a vaccine if he or she has a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until the child gets better before receiving this vaccine.

Before your child receives this vaccine, tell the doctor if your child has recently had a fever. Also tell the doctor if anyone living with or caring for the child has cancer or a weak immune system, or is receiving treatments that can weaken the immune system (such as radiation, chemotherapy, or steroids).

Always wash your hands after handling the diapers of a child who has been given the rotavirus oral vaccine. Small amounts of the virus may be passed in the child's stool and could possibly infect others who come into contact with the child's stool.

Keep track of any and all side effects your child has after receiving this vaccine. When the child receives a booster dose, you will need to tell the doctor if the previous dose caused any side effects.

Be sure your child receives all recommended doses of this vaccine. Your child may not be protected from rotavirus if the doses aren't given within 4 to 10 weeks of each other, or if the child does not receive the full series of vaccines.

Avoid receiving the doses of this vaccine in different clinics or from different doctors. Your child should receive the same brand of rotavirus oral vaccine for all doses given. Different brands of this vaccine may not have the same dosing or booster schedule.

Call your doctor as soon as possible if your child (after receiving a rotavirus oral vaccine) has stomach pain or bloating, vomiting (especially if it is golden-brown to green in color), bloody stools, grunting or excessive crying, and eventually weakness and shallow breathing.

Becoming infected with rotavirus is much more dangerous to your child's health than receiving this vaccine. However, like any medicine, this vaccine can cause side effects, but the risk of serious side effects is extremely low.

Your doctor or pharmacist can provide more information about this vaccine. Additional information is available from your local health department or the Centers for Disease Control and Prevention.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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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 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).

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.

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.

Table 1: Confirmed cases of intussusception in recipients of RotaTeq as compared with placebo recipients during 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).

Table 2: Intussusception cases by day range in relation to dose in REST

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 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.

All seizures reported in the phase 3 trials of RotaTeq (by vaccination group and interval after dose) are shown in Table 3.6

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

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.

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).

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.

Table 4: Solicited adverse experiences within the first week after doses 1, 2, and 3 (Detailed Safety Cohort)

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.

Table 5: 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 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.

Table 6: Solicited adverse experiences within the first week of doses 1, 2, and 3 among pre-term infants

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 following the use of RotaTeq:

Anaphylactic reaction

Intussusception (including death)

Hematochezia

Gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency Disease (SCID)

Urticaria

Angioedema

Kawasaki disease

Transmission of vaccine virus strains from vaccine recipient to non-vaccinated contacts.

The temporal association between vaccination with RotaTeq and intussusception was evaluated in the Post-licensure Rapid Immunization Safety Monitoring (PRISM) program², an electronic active surveillance program comprised of 3 US health insurance plans.

More than 1.2 million RotaTeq vaccinations (507,000 of which were first doses) administered to infants 5 through 36 weeks of age were evaluated. From 2004 through 2011, potential cases of intussusception in either the inpatient or emergency department setting and vaccine exposures were identified through electronic procedure and diagnosis codes. Medical records were reviewed to confirm intussusception and rotavirus vaccination status.

The risk of intussusception was assessed using self-controlled risk interval and cohort designs, with adjustment for age. Risk windows of 1-7 and 1-21 days were evaluated. Cases of intussusception were observed in temporal association within 21 days following the first dose of RotaTeq, with a clustering of cases in the first 7 days. Based on the results, approximately 1 to 1.5 excess cases of intussusception occur per 100,000 vaccinated US infants within 21 days following the first dose of RotaTeq. In the first year of life, the background rate of intussusception hospitalizations in the US has been estimated to be approximately 34 per 100,000 infants.3

In an earlier prospective post-marketing observational cohort study conducted using a large US medical claims database, the risks of intussusception or Kawasaki disease resulting in emergency department visits or hospitalizations during the 30 days following any dose of vaccine were analyzed among 85,150 infants receiving one or more doses of RotaTeq from February 2006 through March 2009. Medical charts were reviewed to confirm these diagnoses. Evaluation included concurrent (n = 62,617) and historical (n=100,000 from 2001-2005) control groups of infants who received diphtheria, tetanus and acellular pertussis vaccine (DTaP) but not RotaTeq.

Confirmed intussusception cases in the RotaTeq group were compared with those in the concurrent DTaP control group and in the historical control group. The data were analyzed postdose 1 and post any dose, in both 7 day and 30 day risk windows. A statistically significant increased risk of intussusception after RotaTeq vaccination was not observed.

One confirmed case of Kawasaki disease (23 days post-dose 3) was identified among infants vaccinated with RotaTeq and one confirmed case of Kawasaki disease (22 days post-dose 2) was identified among concurrent DTaP controls (relative risk = 0.7; 95% CI: 0.01-55.56).

In addition, general safety was monitored by electronic search of the automated records database for all emergency department visits and hospitalizations in the 30-day period after each dose of RotaTeq compared with: 1) days 31-60 after each dose of RotaTeq (self-matched controls) and 2) the 30-day period after each dose of DTaP vaccine (historical control subset from 2004-2005, n=40,000). In safety analyses which evaluated multiple follow-up windows after vaccination (days: 0-7, 1-7, 8-14 and 0-30), no safety concerns were identified for infants vaccinated with RotaTeq when compared with self-matched controls and the historical control subset.

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.4

Read the entire FDA prescribing information for RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent)