Painkiller Aleve faces questions on safety

WASHINGTON — The epidemic of bad news about the potential risks of popular anti-inflammatory medications expanded yesterday as federal officials said that naproxen, a painkiller sold by prescription and also over the counter as Aleve, might increase people's risk of heart attack or stroke.

The new findings bring to three the number of widely used anti-inflammatory drugs suddenly in the spotlight for their potential health risks.

Vioxx was pulled from the market this fall, and its sister drug Celebrex was linked to heart attacks and strokes last week, stopping a major clinical trial.

Researchers uncovered the potential problem with naproxen on Friday during a review of data from a large, ongoing study by the National Institutes of Health. As part of that study, which has aimed to see if anti-inflammatory drugs can help delay the onset of Alzheimer's disease, 2,500 elderly people have been receiving regular doses of naproxen or Celebrex.

The review of the Alzheimer's study, triggered by Celebrex's recent woes, surprised officials by revealing a 50 percent increase in heart attacks or strokes among study participants taking naproxen, compared with those who had been taking a placebo. But there was no apparent increase in heart attacks or strokes among those taking Celebrex — a reassuring, if somewhat confusing, finding.

With many volunteers already expressing unease about their participation in the Alzheimer's study because of the recent reports on Celebrex, and with new evidence suggesting naproxen may have problems of its own, NIH officials and study leaders decided to suspend the study as a "precautionary measure."

Officials emphasized that they are not sure what to make of the preliminary findings.

"This is a very confusing situation," said Dr. Sandra Kweder, deputy director of the Food and Drug Administration's Office of New Drugs.

Naproxen has been on the market since 1976, she noted, and "this is the first evidence we've seen that suggests there is a risk."

She and other officials acknowledged, however, that no one seems to have studied the long-term safety of naproxen or, for that matter, any of the other popular painkillers known as nonsteroidal anti-inflammatory drugs, or NSAIDs.

It is a large class that includes such commonly taken medicines as ibuprofen (such as Motrin and Advil), naproxen (such as Naprosyn and Aleve) and the COX-2 inhibitors Celebrex (chemical name celecoxib) and Vioxx (rofecoxib).

"It may be a problem for all nonsteroidal anti-inflammatory drugs, because we've never had an opportunity to examine this question," said Dr. John Breitner of the Seattle Veterans Affairs Medical Center, lead researcher of the Alzheimer's study.

Breitner and others noted that some of the warning signals emerging may be false alarms.

In the Alzheimer's study, for example, in which 70 people experienced a stroke or heart attack out of 2,500 participants, the 50 percent increase in risk seen with naproxen may or may not prove to be "statistically significant" — a scientific term that would suggest the association is not simply due to chance.

"We need more information [from research]. That's the bottom line," Breitner said.

Dr. Elias Zerhouni, director of NIH, also emphasized that the amount of risk deemed acceptable in the Alzheimer's study is smaller than what might be deemed acceptable in day-to-day medical practice.

Participants in the study are healthy, so it would be unethical to place them in harm's way on the unproven chance that one of the drugs may help prevent Alzheimer's. By contrast, Zerhouni noted, it is often appropriate to give people drugs that carry modest risks if those people can clearly be helped by those drugs.

Breitner said there are "certainly many clinical indications" for the use of naproxen.

Nonetheless, FDA officials took the opportunity to warn the public to use NSAIDs only as directed. In the case of over-the-counter NSAIDs, that means not exceeding the doses on the label or taking them for longer than recommended. Patients taking prescription NSAIDs should talk to their doctors to reconsider whether they remain the best drugs for them, officials said — while conceding that the agency had no definitive data to help doctors make those decisions.

Kweder said the FDA was not considering any immediate regulatory action regarding naproxen, pending further review.

Compiled from reports by The Washington Post and Seattle Times staff reporter Warren King.