The safety of Celebrex and other pain relievers was questioned Wednesday as scientists in the United States and regulatory agencies in Europe said they feared such drugs might raise the same risk of heart problems as those blamed on the arthritis medicine Vioxx.
One key researcher charged the U.S. Food and Drug Administration did not do everything needed to make sure the drug was safe and called for a congressional review of how Vioxx was approved.
Heavily advertised as an arthritis drug, Vioxx was pulled from the market last week after its maker said a study showed it doubled the risk of heart attack and stroke. But the FDA said similar prescription drugs were safe.
The European Medicines Agency in London announced it would review all drugs of this type. And researchers writing in the New England Journal of Medicine voiced their concerns as well with such drugs as Pfizer's popular Celebrex and its newer drug, Bextra.
The medical journal published two reports on the issue Wednesday on the Internet — more than two weeks ahead of their planned print publication — to help inform doctors and patients considering whether to stop using the drugs.
Studies done five years ago when Celebrex and Merck & Co.'s Vioxx were approved suggest that the same mechanism that inhibits inflammation and makes the drugs easier on the stomach than traditional painkillers also blocks a substance that prevents heart problems, according to Dr. Garret FitzGerald, a University of Pennsylvania cardiologist. FitzGerald led the studies, which were designed by him but funded by the drug companies.
"I believe this is a class effect," he said, meaning that the problem also applies to Celebrex and Bextra, which remain on the market.
Pfizer's medical director, Dr. Gail Cawkwell, insisted that its drugs are safe.
"The data for Celebrex is robust and exceeds, in the length of patients in studies and in the size of studies, the data Vioxx has," she said.
She called FitzGerald's contention "an interesting theory," but said, "there is no evidence" of increased risk of heart problems among the 75 million Americans who have taken Celebrex. Long-term studies are not yet available on Bextra, which was approved in 2001.
Celebrex is the 10th most popular drug in the United States, with annual sales of $2.7 billion, up 5 percent in a year, according to IMS Health, a company that tracks drug industry trends.
In a separate report also released by the medical journal, Dr. Eric Topol of the Cleveland Clinic chastised the FDA for not requiring Merck to do studies investigating heart problems with Vioxx when hints of them first appeared years ago, and for allowing the company to blitz consumers with TV ads touting the drug.
Vioxx was the largest prescription drug withdrawal in history, "but had the many warning signs along the way been heeded, such a debacle could have been prevented," Topol wrote. "Neither Merck nor the FDA fulfilled its responsibilities to the public...I believe there should be a full Congressional review of this case."
An FDA official said the agency would have no immediate comment.
When Merck voluntarily withdrew Vioxx, FDA officials said heart problems were unique to that drug and that the mechanism underlying them wasn't known.
But FitzGerald and colleagues published two studies in 1999 and another in 2001 suggesting that by selectively blocking one of the two substances called prostaglandins that lead to inflammation, these so-called cox-2 inhibitors were sparing the stomach at the expense of the heart.
"There's a good prostaglandin and a bad prostaglandin as far as the heart is concerned," he explained.
Suppressing both, as older painkillers like aspirin and other non-steroidal anti-inflammatory drugs, or NSAIDS do, helps the heart. But shutting down just the "good" one raises the risk of high blood pressure, hardening of the arteries and clotting, he reports.
FitzGerald also challenged Pfizer's contention that no science shows increased risk from Celebrex. The original report from one study involving Celebrex found no increased risk of heart problems, but it covered only six months of a year-long study, according to the cardiologist. A look at the full data "reveals signs of increased cardiovascular risk," he writes.
The medical journal will publish the new reports in its Oct. 21 print edition.
Meanwhile, Republican Congressman Tom Davis of Virginia, who chairs the House Government Reform Committee, sent a letter to FDA's acting commissioner, Dr. Lester Crawford, giving him two weeks to answer questions about how FDA tracks problems with drug safety, how it dealt with issues surrounding Vioxx, and whether the agency will study potential risks in similar drugs.
"In light of Merck's withdrawal of Vioxx from the market and other recent news stories examining FDA's review of the safety and efficacy of antidepressant drug use by children, I am concerned whether FDA has been sufficiently aggressive in monitoring drug safety," Davis wrote.