Approved Products > Information on Rotarix - Labeling Revision Pertaining to Intussusception

Information on Rotarix - Labeling Revision Pertaining to Intussusception
September 22, 2010


Questions and Answers
What vaccines are licensed by FDA to protect infants from rotavirus disease?

After evaluating data from extensive clinical and non-clinical studies, FDA licensed RotaTeq, manufactured by Merck and Co., Inc., in February 2006 and Rotarix, manufactured by GlaxoSmithKline Biologicals (GSK), in April 2008.

Both are live virus vaccines given to infants by mouth to prevent rotavirus disease.

What changes have been made to the Prescribing Information and patient labeling for Rotarix?

Additional information has been added to the existing intussusception subsection of the Warnings and Precautions section to inform healthcare providers about preliminary results from a postmarketing study conducted in Mexico. An interim analysis of this study suggests an increased risk of intussusception in the 31 day time period after the first dose of Rotarix (relative risk of 1.8 with a 99% confidence interval of 1.0 to 3.1).

For the United States, these findings translate to potentially 0-4 additional cases of intussusception hospitalizations per 100,000 infants within 31 days of receiving the first dose of Rotarix. This takes into consideration the background rate of intussusception hospitalizations in the United States, which is approximately 34 in 100,000 infants per year1.

Further analysis showed that the increased number of intussusception cases occurred primarily within seven days after the first dose.

This information has also been included in the Postmarketing Experience subsection of the Adverse Reactions section of the prescribing information and in the information for the patient.

No changes have been made to the Contraindications or Indications for Use of Rotarix.

Why were these changes made to the labeling?

The preliminary study results that suggest an increased risk of intussusception following administration of Rotarix are from a postmarketing study conducted in Mexico. Although the results are preliminary and will require further evaluation, FDA approved revised labeling to inform healthcare providers of this finding.

The Mexican study is assessing the risk of intussusception with Rotarix occurring within 31 days after vaccination in infants less than one year of age. Additional investigation regarding these interim study results is ongoing and final study data are not yet available at this time, but will be reviewed by FDA when the final study report is available in 2011.

GSK is also conducting a postmarketing study in the United States to assess the potential risk of intussusception after vaccination and to identify unexpected serious risks that, based on available data, have the potential to occur with Rotarix. The study is ongoing.

Do the data from the postmarketing studies reviewed by FDA suggest an association between intussusception and Rotarix?

Preliminary data from the GSK postmarketing study in Mexico suggest that there may be a small increase in risk of intussusception in the 31-day time frame after the first dose of Rotarix (relative risk of 1.8 with a 99% confidence interval of 1.0 to 3.1).

For the United States, these findings translate to potentially 0-4 additional cases of intussusception hospitalizations per 100,000 infants within 31 days of receiving the first dose of Rotarix. This takes into consideration the background rate of intussusception hospitalizations in the United States, which is approximately 34 in 100,000 infants per year1.

Further analysis showed that the increased number of intussusception cases occurred primarily within seven days after the first dose.

Note that this study was conducted in Mexican children and the background rate of intussusception in Mexico, between 60 and 90 per 100,000 children per year, is higher than the United States.

The Vaccine Safety Datalink (VSD), a large database used by the CDC and FDA for vaccine safety monitoring, to date cannot determine the potential risk of intussusception after vaccination with Rotarix because Rotarix is not yet widely used in the healthcare settings which are part of the VSD.

The FDA will continue to evaluate the association between Rotarix and intussusception as final results become available from ongoing postmarketing studies being conducted in both the US and foreign countries.

Was the RotaTeq labeling changed with regard to intussusception?

No. The study conducted in Mexico did not evaluate RotaTeq. The information currently available to and evaluated by FDA does not suggest an increased risk of intussusception with RotaTeq. However, other studies are ongoing and additional information is being obtained and evaluated. One such study, conducted in the VSD, has shown no significant increased risk of intussusception to date. Two separate analyses have included 300,000 first doses and over 800,000 total doses of RotaTeq. While this information is helpful, the study is ongoing and additional doses will provide more safety information and help to better understand the potential risk of intussusception with RotaTeq. To date, this study is not large enough to rule out the level of risk suggested by the preliminary analysis of the postmarketing study of Rotarix in Mexico.

What is rotavirus disease and how commonly does it occur?

Rotavirus disease is the leading cause of severe diarrhea and dehydration in young infants worldwide. In the United States, the disease occurs more often during the winter. Before rotavirus vaccines were available, most children in the United States were infected with rotavirus before the age of two. In addition, rotavirus resulted in about 55,000-70,000 hospitalizations and 20-60 infant deaths in the United States each year.

Currently, rotavirus disease is estimated to be responsible for the deaths of more than 500,000 infants around the world each year, primarily in poorer countries.

What is intussusception?

Intussusception is a serious and potentially life-threatening condition that occurs when the intestine gets blocked or twisted. 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 and 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, and occurs spontaneously in the United States in approximately 34 in 100,000 healthy young infants and children per year.

Why are FDA and CDC monitoring the rotavirus vaccines so closely for intussusception?

Intussusception has been a concern for new rotavirus vaccines developed since the voluntary withdrawal of RotaShield by the manufacturer in 1999. RotaShield was voluntarily withdrawn from the market after studies suggested an elevated risk of intussusception. These studies suggested that there were 9 additional cases of intussusception per 100,000 infants who received RotaShield. The risk of intussusception for subsequent rotavirus vaccines (Rotarix and RotaTeq) has been assessed in large clinical trials prior to licensure. Although no increased risk for intussusception was observed in these trials, postmarketing studies to further evaluate the potential for intussusception and other rare adverse events are being conducted. Only after extensive post marketing experience with a vaccine can its safety and effectiveness be more fully understood, and a more complete picture obtained of a vaccine’s benefits and risks.

Are the rotavirus vaccines safe?

Although no medical products, such as drugs or vaccines, are 100 percent safe or effective, both vaccines have strong safety records, including clinical trials involving tens of thousands of infants as well as clinical experience with millions of recipients.

What is the most important information that FDA and CDC want health care providers to know?

It is important to be aware that preliminary data from a postmarketing study suggest a small increased risk of intussusception following administration with Rotarix, and to explain to parents and caregivers of infants that the benefits of vaccination with both Rotarix and RotaTeq outweigh any potential risks.

It is also important to explain the signs and symptoms of intussusception and the steps that should be taken if they do occur. In addition, FDA and CDC encourage healthcare providers to report intussusception or any adverse event following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at http://vaers.hhs.gov/index.

What is the most important information that FDA and CDC want parents and caregivers of children to know?

The benefits of rotavirus vaccination are substantial, and include prevention of hospitalization for severe rotavirus disease in the U.S. and of death in other parts of the world. Currently, the benefits of the vaccines, which are known, outweigh the suggested increased risk for intussusception or any other potential risks. FDA and CDC will continue to closely monitor the safety of both rotavirus vaccines.

Parents should contact their child's doctor immediately if the child has stomach pain, vomiting, diarrhea, blood in the stool or change in bowel movements, especially in the first seven days after the first dose of vaccine, as these may be signs of intussusception, or if the child has any of these symptoms at any time after vaccination, even if it has been several weeks since the last dose of vaccine.


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Footnote

1Reference: Tate JE et al, Trends in Intussusception Hospitalizations Among US Infants, 1193-2004: Implications for Monitoring the Safety of the New Rotavirus Vaccination Program. Pediatrics 2008;121; e1125-e1132.
Approved Products > Information on Rotarix - Labeling Revision Pertaining to Intussusception