FDA Adds New Warnings to Label of COX-2 Inhibitor Bextra Over Potential Heart, Skin Risks

FDA officials on Thursday announced that the label for Pfizer's COX-2 inhibitor Bextra will carry a warning about potential heart and blood-clotting risks, USA Today reports (Rubin, USA Today, 12/10). The drug's label also will include a strengthened warning about Bextra's potential to cause severe skin reactions (Hartford Courant, 12/10).

The warnings come after the recent voluntary withdrawal of Vioxx, a COX-2 inhibitor manufactured by Merck. Following the withdrawal, David Graham, associate director of drug safety in the FDA Office of Drug Safety, testified that Merck should have withdrawn the medication from the market years earlier and criticized FDA actions related to the medication.

He also named five prescription drugs currently on the market that present significant safety risks to consumers, including Bextra, which he said presents cardiovascular risks similar to those of Vioxx. In response, FDA officials defended the agency's actions and said that they did not plan to conduct a new review of the medications Graham cited. After the hearing, FDA officials said that they would consider an examination of agency prescription drug approval and safety review procedures (California Healthline, 11/22).

Pfizer on Oct. 15 warned physicians that Bextra, which is typically used to treat arthritis, might increase the risk of heart attack or stroke in patients who have had coronary artery bypass surgery. Preliminary results of a University of Pennsylvania study presented at the American Heart Association's annual conference indicated that Bextra doubles patients' risk for heart attack and stroke.

The study examined data from 5,930 participants in 12 clinical trials that involved Bextra. According to the study, participants who took Bextra experienced heart attacks or strokes 2.19 times as often as those who took a placebo (California Healthline, 11/18).

The new label will contain a "bold-faced warning" against prescribing and using Bextra for patients who have had heart bypass surgery, which the drug has not been approved for, according to USA Today. The label also "notes that studies in arthritis patients have not been large enough or long enough to detect an increased risk of cardiovascular problems," USA Today reports (USA Today, 12/10). The label also now includes a "black box" warning about the risk of developing the skin reaction Stevens Johnson syndrome (Los Angeles Times, 12/10).

Pfizer officials in November announced that the company likely will add the warning to Bextra's label because some patients taking the drug experienced the skin reaction. In the company's quarterly report, filed with the Securities and Exchange Commission, Pfizer said that a few patients taking Bextra developed Stevens Johnson syndrome, which results when the immune system rejects a drug and often involves severe blistering of the mucous membranes and skin. The risk of developing the syndrome is highest during the first two weeks a patient takes Bextra.

The drug's label has included information about the risk of Stevens Johnson Syndrome since 2002, according to Pfizer officials. Pfizer in October sent a letter to doctors warning them about the risks of the syndrome and saying that skin reactions have led to hospitalizations and deaths in a small number of patients. Stevens Johnson syndrome has about a 30% mortality rate (California Healthline, 11/9).

FDA officials said the agency continues to consider Bextra beneficial when taken for approved uses. A posting on the agency Web site states, "FDA believes that, based on what we know now, the overall benefit of Bextra outweighs the risk when used in properly selected patients as directed in the approved labeling" (Los Angeles Times, 12/10). Acting Deputy Director of FDA's drug division Douglas Throckmorton said that the updated label does not indicate a change in the FDA's "overall attitude" toward drug safety (USA Today, 12/10).

Pfizer spokesperson Mariann Caprino said, "There's no new information in the label. It's all been previously shared with the medical community."

Senate Finance Committee Chair Chuck Grassley (R-Iowa) said that he plans to ask FDA for information about how it evaluated Bextra's risks and how it decided how the drug would be regulated. According to the Times, Grassley "stopped short of calling for a recall of Bextra." In a statement, Grassley said, "When the FDA approves a drug, you should be able to bank on it. If a drug isn't safe, you should know the FDA will take it off the market" (Los Angeles Times, 12/10).

FDA will hold a panel discussion in February to review all COX-2 inhibitors (AP/New York Times, 12/10).

In related news, an editorial published this week in the Annals of Internal Medicine urged doctors not to prescribe COX-2 inhibitors to patients who are at risk of developing heart disease until more information is known (USA Today, 12/10).