Doubts Escalate over Painkillers

DRUG SAFETY

Responding to troubling studies involving the COX-2 inhibitor class of drugs, FDA has released a public health advisory recommending limited use of COX-2 agents. Another class of painkillers, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), is also raising red flags.

FDA took action following the halt of a study involving Pfizer's COX-2 drug Celebrex (celecoxib). The 2,000-patient trial, conducted by the National Cancer Institute, was exploring how Celebrex might help prevent colon cancer. It was stopped because of an increased risk of both fatal and nonfatal cardiovascular events associated with the drug. In a statement, Pfizer CEO Hank McKinnell called the trial results "new" and "unexpected."

Patients taking 400 mg twice a day had 3.4 times the risk of cardiovascular problems, while 200-mg twice-daily doses increased the risk 2.5-fold. Recommended doses for the treatment of rheumatoid arthritis are 200 to 400 mg a day. A separate study on Celebrex sponsored by Pfizer, however, found no cardiovascular risk.

The FDA health advisory is an interim measure, as the agency has decided to evaluate all prevention studies involving Celebrex and Bextra (valdecoxib), Pfizer's other COX-2 painkiller and the only other COX-2 drug on the U.S. market. Bextra has been associated with cardiovascular risks in patients who have undergone heart surgery and now carries a warning label. These drugs are in the same class as Merck's Vioxx (rofecoxib), which was recently removed from the market due to increased cardiovascular risks.

In a press conference, Acting FDA Commissioner Lester M. Crawford said the agency is "leaving all options open" as FDA analyzes the data on the "science that has just come forward."

McKinnell said his company will stop direct-to-consumer advertising but will not cease marketing Celebrex, which had sales of $2.3 billion in the first nine months of 2004. In a statement, the firm points to a National Institutes of Health study on the use of Celebrex for the prevention of Alzheimer's disease that found no cardiovascular risks associated with the drug.

NIH recently halted that study because "preliminary results" suggest evidence of increased risk of cardiovascular events in participants taking the NSAID naproxen. Naproxen is sold by Bayer as the over-the-counter drug Aleve and by Roche as the prescription drug Naprosyn. Neither Bayer nor Roche has issued a statement reacting to the new findings.

NSAIDs as well as COX-2 inhibitors are now under scrutiny as FDA examines its procedures for evaluating the adverse effects of marketed drugs. The agency has scheduled an advisory committee meeting for February that will review drugs such as Vioxx, Celebrex, Bextra, and naproxen.