Bextra Label Updated with Boxed Warning Concerning Severe Skin Reactions and Warning Regarding Cardiovascular Risk

FDA Talk Paper

The Food and Drug Administration (FDA) announced today important new information on side effects associated with the use of Bextra, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) which is indicated for the treatment of osteoarthritis, rheumatoid arthritis and dysmenorrhea (menstrual pain). A "boxed" warning, strengthening previous warnings about the risk of life-threatening skin reactions and a new bolded warning contraindicating the use of Bextra in patients undergoing coronary artery bypass graft (CABG) surgery will be added to the label.

In addition, the FDA will also seek input from the public and from outside experts on the appropriate uses for Bextra and other NSAIDs at a previously-announced Advisory Committee meeting, to be held early in 2005.

Boxed and bolded warnings provide healthcare professionals and patients with important information on drugs that may be associated with serious side effects in a way that maximizes the drug?s benefits and minimizes its risks. Serious

Skin Reactions
The new boxed warning in the label states that patients taking Bextra have reported serious, potentially fatal skin reactions, including Steven-Johnson Syndrome and toxic epidermal necrolysis. These skin reactions are most likely to occur in the first 2 weeks of treatment, but can occur any time during therapy. In a few cases, these reactions have resulted in death. The labeling advises doctors that Bextra should be discontinued at the first appearance of a skin rash, mucosal lesions (such as sores on the inside of the mouth), or any other sign of allergic reactions. The new boxed warning also states that Bextra contains sulfa, and patients with a history of allergic reactions to sulfa may be at a greater risk of skin reactions.

As of November 2004, FDA had received reports of a total of 87 cases in the United States of severe skin reactions in association with Bextra, including Stevens-Johnson Syndrome and toxic epidermal necrolysis. Twenty of the 87 cases involved patients with a known allergy to sulfa. Of these 87 cases, 36 hospitalizations were reported, including 4 deaths. Other Cox-2 selective inhibitors and traditional NSAIDs such as naproxen and ibuprofen also have a risk for these rare, serious skin reactions, but the reported rate of these serious side effects appears to be greater for Bextra than for other COX-2 agents.

Cardiovascular Risks
In addition to highlighting serious skin reactions, the strengthened label warnings also highlight new data about cardiovascular risks. A recently-completed study conducted by Pfizer, which included over 1,500 patients treated after CABG, showed an increased cardiovascular risk in patients treated with Bextra compared to placebo. Observed cardiovascular events included thromboembolic events such as myocardial infarction (heart attack), cerebrovascular accident (stroke), deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clot in the lung).

Pfizer submitted the final report of the new CABG study to FDA on November 5, 2004. The report confirms the risk of the intravenous form (about 2 percent of patients had such an adverse event) and also shows that oral Bextra is associated with a lower, but some, risk (about 1 percent of patients) immediately following CABG surgery--a very specific medical setting. In the placebo group, about 0.5 percent of patients had an adverse cardiovascular event. Bextra is not approved for use in the treatment of postoperative pain of any type; however, FDA believes that these new findings should be made available to healthcare professionals and patients, and the bolded warning specifically contraindicates Bextra for treatment of pain immediately following CABG.

FDA urges health care providers and patients to report adverse event information to FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet . Reports can also be made directly to Pfizer, Inc., Peapack, N.J. at 1-800-323-4204.

U.S. Food and Drug Administration
FDA Talk Paper T04-56
December 9, 2004

Updated on: 09/07/12