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FDA Strengthens Syncope Warning on Gardasil Label


 

Patients who receive the Gardasil vaccine should sit or lie down in the office for at least 15 minutes after vaccination to prevent possible injury from falling during syncope, while being observed for paleness, sweating, dizziness, or other signs of a possible vasovagal reaction, the Food and Drug Administration recommended.

Because of continued reports of syncope and related traumatic injury, the FDA requested in June that Merck and Co. Inc., manufacturer of the vaccine, add this information to the warnings and precautions section of the label.

"The addition of syncope to the [label] emphasizes that health care providers and consumers should be alert that fainting may occur following vaccination with Gardasil, sometimes resulting in falling and injuries," the FDA said in a public information statement.

Up to 40% of adolescent syncope associated with Gardasil is also accompanied by tonic-clonic seizure-like activity, the FDA said. "If an individual faints and especially if seizure-like activity occurs, the individual should be placed in a position, such as lying down, to help restore blood flow to the brain."

Syncope has been listed on the label as a possible adverse event since October 2007, the statement said. However, the FDA's Vaccine Adverse Event Reporting System (VAERS) continues to receive reports of traumatic injuries related to fainting and falling after vaccination. In light of this, the agency decided to strengthen the label warning. Fainting doesn't appear to be unique to Gardasil, the statement added. "Syncope has been reported after administration of other adolescent and adult vaccines. … It can also occur with certain medications, after blood donation, or in response to pain."

The fact sheet did not give details of the injuries associated with the events. However, 70 episodes of syncope in U.S. patients were reported (MMWR 2008;57;457-60). These events occurred from January 2005 to July 2007. The reports noted that about 5% of the spells were considered serious, 38 occurred on the same day as vaccination, and 37 required hospitalization.

As of May 1, 2009, there were 13,758 VAERS reports of adverse events following more than 24 million Gardasil vaccinations in the United States.

Of these reports, 93% were considered nonserious and 7% serious. Nonserious adverse events include fainting, pain and swelling at the injection site, headache, nausea, and fever.

Serious adverse events include Guillain-Barré Syndrome (GBS), transverse myelitis, and blood clots. Additionally, as of May 1, the FDA has received 39 reports of death among females who have received the vaccine. Twenty-six of these reports have been confirmed, six are still under investigation, and seven are unconfirmed. According to a fact sheet on the VAERS Web site, "In the 26 reports confirmed, there was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine."

The VAERSfact sheet did not give details of all these deaths. However, details of deaths that had occurred from June 30, 2006, to August 31, 2008, were reported during an October 2008 postlicensure safety update held by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The committee reviewed 27 deaths following Gardasil vaccination; 17 of those had been confirmed. Deaths occurred in females aged 12–26 years with no discernible pattern to age or time since vaccine administration. Six occurred within 1 week of vaccination, five within 2–3 weeks, two within 3–9 weeks, and two within 9–17 weeks. One death occurred 288 days after vaccination, and one case had an unknown onset interval.

Other serious adverse events detailed during the committee meeting were syncope (70), venous thromboembolism (41), GBS (52), and transverse myelitis (10).

The vaccine is considered safe and effective, the FDA said in the public information statement. "Based on all of the information we have today, the Centers for Disease Control and Prevention continues to recommend Gardasil vaccination for the prevention of four types of human papillomavirus. As with all approved vaccines, CDC and FDA will continue to closely monitor the safety of Gardasil. Any problems detected with this vaccine will be reported to health officials, healthcare providers, and the public, and needed action will be taken to ensure the public's health and safety."

Information regarding adverse events associated with Gardasil is available on the FDA's VAERS Web site (www.cdc.gov/vaccinesafety/vaers/gardasil.htm

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