Scientist: Weed out 'bad actor' painkillers

GAITHERSBURG, Md. -- The government should yank ''bad actor" painkillers, a Food and Drug Administration scientist who repeatedly has sparred with the agency told a panel yesterday reviewing painkiller safety.

David Graham said that heart dangers with the painkiller Vioxx began when people started taking the drug, not after an 18-month ''grace period" suggested by Merck & Co., the drug's manufacturer. Doses of Vioxx higher than 25 milligrams caused up to 18,000 extra heart attacks annually for every million men aged 65 to 74 who used it, according to Graham, associate director for science and medicine in the FDA's Office of Drug Safety.

Graham's presentation came during the second day of a three-day session on the risks, benefits, and future of a class of painkillers that includes Arcoxia, Bextra, Celebrex, Prexige, and Vioxx. Some who testified yesterday were grateful for pain relief they got from the drugs and urged the agency not to take them off the market.

But an unpublished study coauthored by Graham also linked high doses of the painkiller Celebrex to heart problems, suggesting the problem that pushed Vioxx off the market last fall is shared by other drugs in the same class.

And, to protect the public, painkillers that his new analysis linked to heightened heart risk -- like indomethacin, used to treat gout, and meloxicam, a painkiller that recently picked up in sales -- should be removed from the market, he said.

By contrast, consumers should be pointed to safer drugs. Graham and his coauthor found ''not a whiff" of a heart problem caused by the arthritis painkiller nabumetone.

That Graham testified at all was due to 11th-hour jockeying between US Senator Chuck Grassley and the FDA, which earlier told Graham not to testify about a study that had neither been published nor subjected to peer review. At the Iowa Republican's urging, FDA Acting Commissioner Lester Crawford assured Graham that he would not face reprisal if he spoke about unpublished studies. Graham thanked Crawford at the beginning of his talk.

The session -- crowded by analysts, drug company representatives, legislative aides, scientists, and international drug regulators -- comes as the FDA faces a credibility crisis over its handling of drug safety. The spotlight focused on the agency when antidepressants used by children worsened their conditions. The FDA added its strongest warnings to those drugs.

The withdrawal of Vioxx last fall and heart problems with a series of popular painkillers leveled new criticism at the drug regulators. In response, this week the FDA said it would create an independent drug safety board as a catalyst for speedier action when problems arise with drugs on the market.

The modest increase in heart risk found by Graham with a number of painkillers increases the odds of heart problems as much as smoking, said Dr. Steven Nissen, a Cleveland Clinic cardiologist.

Unlike his reception before Congress last fall, when Graham testified the FDA's culture was so flawed it could not prevent another Vioxx catastrophe, however, Graham faced a number of skeptics on the FDA advisory panel.

An industry representative took Graham to task for leaving out a statistic on a chart beneficial to Vioxx. A statistician quibbled with Graham's methods, saying the researcher committed the same statistical sins of studies that Graham faulted. A number of doctors said the risks from untreated pain in patients outweighed the modest heart risks found in Graham's review of popular painkillers.

Merck took issue with Graham's contention that heart risks with Vioxx appeared quickly after use. ''Any estimate of harm or impact from Vioxx is speculation," the company said in a statement. In fact, a top Merck research official said that the firm would consider returning Vioxx to the market if the FDA concludes that the benefits of the drug outweigh its hazards.

Indeed, the new-generation painkillers won praise during a two-hour public hearing.

Army Medical Corps Captain Christopher Grubb testified that Celebrex is so crucial the drug is one of a three-item ''pill pack" 82nd Airborne paratroopers are required to carry. ''If they get shot, you're more likely to bleed with" an older painkiller, said Grubb, a pain management specialist based in Fort Bragg, N.C.

Dimitra Poulos told the FDA panel she only has a 40-day supply of Vioxx left. Before taking the drug, the pain from rheumatoid arthritis was so intense she could not sit through a movie, take a walk, or dress on her own. ''Vioxx gave me my life back," Poulos said.

Betsy Chaney's cracked vertebrae numbed feeling in her hands. She regained it through taking Celebrex. ''Please don't take this medication that works so well for me," she said.

Chaney told the panel she's willing to risk theoretical heart woes to keep her very real quality of life. Just in case they disagree, she said in an interview that she's hoarded 180 pills. ''I still have some Vioxx left, if I have to."

Eileen Lacijan, however, wondered whether sequentially taking Vioxx, Celebrex, and Bextra since March 2000 triggered the heart attack she suffered last Aug. 12.

The registered nurse told the panel she doesn't drink alcohol, smoke, have diabetes, or a family history of heart disease. She exercises regularly, eats a healthy diet, and is not overweight. ''I thank God every day that I'm alive," Lacijan told them. ''However, I still have many unanswered questions about the cause of my heart attack."

Diedtra Henderson can be reached at dhenderson@globe.com.