Rotavirus Vaccines and
Intussusception - a Mini-Sentinel Postlicensure
Observational Study. The association between intussusception and RotaTeq and Rotarix
vaccination was evaluated in Mini-Sentinel’s PRISM
program and identified an increased risk of intussusception 21 days following the first dose of RotaTeq,
with the majority of cases occurring in the first 7 days. No increased risk was identified after the
second or third doses. Based on these results, approximately 1 to 1.5 additional cases of intussusception
would occur per 100,000 vaccinated U.S. infants within 21 days following the first dose of RotaTeq.
FDA believes that the benefits of RotaTeq and Rotarix vaccination continue to outweigh the risks associated with vaccination, including the risk of intussusception. FDA recommends that parents closely watch their infants for signs of intussusception, especially within the first 7 days after vaccination with RotaTeq or Rotarix. These symptoms include stomach pain, vomiting, diarrhea, blood in the stool or change in bowel movements. It is important to contact the child's healthcare provider if the child has any of these signs at any time after vaccination, even if it has been several weeks since the last dose of vaccine.
FDA Safety Communication 6-13-13
RotaTeq package insert updated to include
updated information on intussusception.
A Mini-Sentinel PRISM study, the largest study of intussusception after rotavirus vaccines to date, identified an increased risk of intussusception in the 21 day time period after the first dose of RotaTeq, with most cases occurring in the first 7 days after vaccination. No increased risk was found after the second or third doses. These findings translate into 1 to 1.5 additional cases of intussusception per 100,000 first doses of RotaTeq.
RotaTeq Package Insert |
FDA Safety Communication 6-13-13
Rotarix package insert
updated to include 2 items under Warnings and
Precautions: (1) Rotavirus shedding
in stool occurs after vaccination with peak
excretion around day 7 after Dose 1. (2) In a
postmarketing, observational study conducted in
Mexico, cases of intussusception were observed in
temporal association within 31 days following the
first dose of ROTARIX, with a clustering of cases in
the first 7 days.
Rotarix Package Insert |
FDA update 9-7-12
Rare potential risk of
the benefits of vaccination outweigh any small risk
have identified rare cases of gasteroenteritis that
may have been caused by rotavirus vaccine in the US,
Australia and elsewhere. Rarely, cases have
occurred in vaccine recipient’s close household
contacts. Virus strains in the vaccine may reassort
to make a virus that can cause diarrhea.
Donato CM et al. JID 2012;206(3):377-83
Payne DC et al. Pediatrics 2010;125(2):e438-41
Study finds Rotavirus
Vaccine not linked to intussusception in infants
Among US infants 4-34 weeks old who
received RV5, there was no increase in the risk of
intussusception compared with infants who did not
receive the rotavirus vaccine.
Shui IM et al. JAMA 2012;307(6):598-604.
Vaccine: Rare Side Effect Possible
Questions and answers for parents and caregivers on
CDC website. [Sep 22 2010]
insert updated [Sep 2010]
Recommendations for Rotavirus Vaccines
The US FDA has
further evaluated the scientific information and
determined that vaccination should continue using
both approved products - RotaTeq and Rotarix.
Both vaccines have proven safety records and the
earlier recommendation to suspend use of Rotarix was
made so the FDA could more closely examine the
evidence. Currently available information
indicates that neither PCV-1 nor PCV-2 poses a
health risk to humans. [May 14, 2010]
FDA Updates on Rotavirus Vaccine
FDA Advisory Committee holds meeting on
PCV-1 and Rotavirus
Following a recent finding that porcine circovirus
type 1 has been detected in Rotarix vaccine, a GSK
rotavirus vaccine, the Vaccines and Related
Biological Products Advisory Committee convened a
public meeting on May 7 to discuss current knowledge
and emerging data. No decisions regarding
rotavirus vaccine use or recommendations were
expected or occurred at this meeting; the FDA will
take the discussion into account when making future
recommendations regarding rotavirus vaccine use.
The majority of committee members believe that the
benefits of rotavirus vaccines far outweigh the
risks; most members called for further studies and
believe that physicians will need to explain the
risks and benefits to their patient’s parents.
[May 7, 2010]
Advisory Committee website (transcript and
meeting slides should be posted shortly) |
Journal of Virology
paper on PCV 1 in Rotarix
Victoria, et al have published results of analysis
of 8 vaccines: one vaccine, a GSK rotavirus vaccine
called Rotarix, contained a porcine circovirus-1
authors conclude the paper with this statement, "In
view of the demonstrated benefit and safety of
Rotarix the implications (if any) on current
immunization policies of the detection of PCV1 DNA
of unknown infectivity for humans needs to be
link [April 13 2010]
More information on the study on FDA website.
FDA Advisory Panel
A plan from GlaxoSmithKline and
further recommendations will be announced at the FDA
Advisory Panel meeting on May 7, 2010.
FDA recommends temporary suspension of use
of Rotarix; no restrictions on more widely used
rotavirus vaccine, RotaTeq
PCV1 (porcine circorvirus 1) DNA has been detected
in Rotarix; PCV1 is not known to cause harm in
humans or other animals.
(Mar 22 2010)
Link to FDA Press Release |
link to other FDA documents |
Two Rotavirus Vaccines now available in the U.S.
The FDA has approved
Rotarix, making is the second Rotavirus vaccine
available on the US market (in addition to Merck's
RotaTeq). GlaxoSmithKline's vaccine is a
two dose series to be given between 6 and 24 weeks
of age. Rotarix protects against G1, G3, G4
and G9 strains of rotavirus.
vaccine has been associated with any increased risk
The US FDA
has approved a revised
for Merck and Co's rotavirus vaccine, RotaTeq.
The label now includes this information regarding
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).
The reported cases of Kawasaki disease following RotaTeq
are not more than would be expected in the general
Rotavirus infection is a common cause of severe diarrhea
and hospitalization. The cause of Kawasaki disease,
characterized by high fever, is unknown and has not been
linked to any vaccine including rotavirus vaccine.
CDC and FDA continue to monitor the safety of RotaTeq
(and all vaccines) and encourage reporting of any cases
of Kawasaki disease (and any severe adverse event)
following vaccination to VAERS. For a copy of the
vaccine reporting form, call 1-800-822-7967 or report
More information is
available from the CDC at
information update on rotavirus vaccine 02-14-2007
Food and Drug Administration (FDA) posted a
notification on February 13, 2007, to encourage
health care workers to recognize and report possible
vaccine adverse events following the introduction of
Merck & Co., Inc.’s RotaTeq® vaccine. The notification
is intended to provide health care workers with an
update on information collected as part of the US
Vaccine Adverse Event Reporting System (VAERS), which is
routinely used for tracking vaccine safety.
February 2006, the Advisory Committee on Immunization
Practices (ACIP) to the CDC unanimously recommended
routine use of RotaTeq® in US infants to prevent
rotavirus, the leading cause of severe diarrhea,
vomiting, fever, and dehydration in infants and young
Because of a suspected association between
intussusception (a rare, life-threatening blockage of
the intestine) and an earlier rotavirus vaccine (RotaShield®),
the US CDC and FDA are monitoring the new RotaTeq®
vaccine with particular care. Prior to last year’s FDA
approval of Merck’s vaccine, investigators conducted a
rigorous clinical trial with more than 70,000 subjects
and found that RotaTeq® was not associated with an
increased risk of intussusception, or other serious
adverse events, when compared to placebo.
In the US,
intussusception is estimated to spontaneously occur in
approximately one in 2,000 healthy young infants and
children per year. While 28 reported cases of
intussusception were identified through post-marketing
surveillance following administration of RotaTeq®, it is
important to note, as the FDA states,
number of intussusception cases reported to date after
RotaTeq administration does not exceed expected
background rates among unvaccinated children of the same
age. In fact, the number of reported
cases is lower than expected based on estimates of
naturally-occurring episodes of intussusception in
children in this age range (CDC, unpublished data).
reports of the FDA notice implied a link between the
vaccine and intussusception that is not supported by the
data. The ACIP will conduct their regularly-scheduled
review of the safety tracking data during their upcoming
meeting on February 21, 2007.
The US FDA approved a new
RotaTeq, for use at 2, 4 and 6 months
of age (to be completed by 32 weeks of age). RotaTeq,
approved on February 3, 2006, is a 3-dose, oral vaccine
marketed by Merck and Company. This vaccine
contains no thimerosal (or any other preservative).
The CDC's advisory committee
(ACIP) recommended rotavirus vaccine be given to infants
at well-baby visits at 2, 4 and 6 months of age.
RotaTeq is a different
vaccine from the rotavirus vaccine withdrawn from the
market in 1999 because of an association with an
increased risk of intussusception (a rare blockage or
twisting of the intestine). RotaTeq was
specifically evaluated in a large-scale study of 70,000
children for signs of a similar association and no
association was found. Because of the experience
with the previous vaccine, RotaTeq will continue to be
monitored closely: a post-licensure study will be
conducted in 44,000 children and the manufacturer will
follow stringent reporting criteria for 3 years.