• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

  • Print
  • Share
  • E-mail

FDA Releases Final Study Results of a Mini-Sentinel Postlicensure Observational Study of Rotavirus Vaccines and Intussusception

FDA Safety Communication — June 13, 2013

FDA Releases Final Study Results of a Mini-Sentinel Postlicensure Observational Study of Rotavirus Vaccines and Intussusception

FDA Approves Required Revised Labeling for RotaTeq Based on the Study Results

Purpose: To inform the public and healthcare providers that FDA is releasing final study results disclaimer icon  from a Mini-Sentinel postlicensure observational study of intussusception (a form of bowel obstruction) after vaccination with RotaTeq (Merck and Co., Inc.) and Rotarix (GlaxoSmithKline Biologicals). 

RotaTeq and Rotarix are vaccines for the prevention of rotavirus gastroenteritis in infants 6 weeks to 32 weeks of age (RotaTeq) and infants 6 weeks to 24 weeks of age (Rotarix).  The study was conducted in Mini-Sentinel’s Postlicensure Rapid Immunization Safety Monitoring (PRISM) program, the largest vaccine safety surveillance program in the United States.

FDA has approved required revisions to the Prescribing Information and Patient Information for RotaTeq as a result of the new safety data from this Mini-Sentinel PRISM study.  New information was added to the Highlights, the existing intussusception subsection of the Warnings and Precautions section, and the Post-Marketing Experience section of the Full Prescribing Information, as well as to the Patient Information.  The Mini-Sentinel PRISM study is the largest study of intussusception after rotavirus vaccines to date and 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.

The data from the Mini-Sentinel PRISM study regarding the risk of intussusception following the use of Rotarix were inconclusive. Based on this study, no changes were made to the Prescribing Information or to the Patient Information for Rotarix.  However, based on data from an observational study previously conducted in Mexico, it is estimated that 1 to 3 additional cases of intussusception would occur per 100,000 vaccinated infants in the United States within 7 days following the first dose of Rotarix.  In September 2012, FDA announced that it had approved revisions to the Prescribing Information and to the Patient Information for Rotarix to include these results from the study in Mexico.

Background: Before the introduction of rotavirus vaccines, most children in the United States became infected with rotavirus before two years of age, causing an estimated 55,000-70,000 hospitalizations and 20-40 infant deaths in the United States each year.  RotaShield (Wyeth Laboratories) was the first vaccine licensed for the prevention of rotavirus gastroenteritis in infants.  RotaShield was voluntarily withdrawn from the market by the manufacturer after studies suggested an elevated risk of intussusception, estimated at approximately 1 case per 10,000 vaccine recipients. Prior to licensing RotaTeq and Rotarix, the risk of intussusception was assessed in large clinical trials of more than 60,000 children for each vaccine. No increased risk for intussusception was observed for either vaccine. However, several postlicensure studies conducted in other countries subsequently suggested potential increased risk of intussusception after both Rotarix and RotaTeq.  In 2010, FDA launched the Mini-Sentinel PRISM study to better quantify the potential risk of intussusception among U.S. children.  Mini-Sentinel is FDA’s safety monitoring program for all FDA regulated medical products and was created in 2009 in response to the Food and Drug Administration Amendments Act 2007.  PRISM is the component of Mini-Sentinel dedicated to vaccine safety.

Summary of Safety Issue
The association between intussusception and RotaTeq and Rotarix vaccination was evaluated in Mini-Sentinel’s PRISM program disclaimer icon .  More than 1.2 million RotaTeq vaccinations (507,000 first doses) and 103,000 Rotarix vaccinations (53,000 first doses) were evaluated among infants 5 through 36 weeks of age.  From 2004 through 2011, potential cases of intussusception were identified from the inpatient or emergency department settings, and vaccine exposures were identified through electronic procedure and diagnosis codes. Medical records were reviewed to confirm intussusception and vaccination status. 

The risk of intussusception was assessed in the 7 and 21 days after vaccination.  The study 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.

Recommendations Regarding Vaccination With RotaTeq and Rotarix
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.

Questions and Answers

What is intussusception?
Intussusception is a serious and potentially life-threatening condition that occurs when the intestine gets blocked. One portion of the intestine telescopes into a nearby portion, causing the intestinal obstruction.  The most common site is where the small intestine joins the large intestine. Because the two walls of the intestines press against each other, this causes inflammation, swelling, and eventually decreased blood flow. If it is not detected early, internal bleeding, a hole in the intestines and infection in the abdomen may occur because the intestinal tissue has died from the decreased blood flow.  With prompt detection and treatment, almost all patients fully recover.

Intussusception can occur spontaneously in the absence of vaccination.  People of any age can get intussusception, although it is most common among infants in the first year of life, generally between the ages of 5 and 9 months.  In the United States, intussusception occurs in approximately 34 in 100,000 infants per year.

Was the risk for intussusception evaluated before FDA approved RotaTeq ?
Merck and Co., Inc. studied more than 71,000 infants in three placebo-controlled clinical trials.  FDA evaluated these studies which showed no increase in the risk of intussusception in those who received RotaTeq compared to those who received placebo.

Was the risk for intussusception evaluated before FDA approved Rotarix?
GlaxoSmithKline Biologicals conducted a study of more than 63,000 infants to assess whether there was an increased risk of intussusception. FDA evaluated the study which showed that no increased risk for intussusception was found in infants receiving Rotarix compared to those who received placebo.

Are the vaccines that prevent rotavirus safe?
Although no medical products, such as vaccines or drugs, are 100 percent safe or effective, both Rotarix and RotaTeq have strong safety records, including clinical trials involving tens of thousands of infants as well as post-marketing experience with millions of recipients.

How can I report a suspected adverse event after vaccination?
Suspected adverse events may be reported to the Vaccine Adverse Event Reporting System (VAERS), which is co-managed by the FDA and the Centers for Disease Control and Prevention.