Vioxx: 'Inflammation' Spreads - Other Similar Drugs To Be Investigated

Categories

Pharma

Merck & Co has decided to pull its blockbuster arthritis and acute pain drug Vioxx, after evidence of an increased risk of heart attacks built up to levels that could not be contained any more. Patients and doctors are being warned to discontinue use and return unsold stocks of the drug.

The recall was reported on September 30, but the plot now seems to thicken. According to an AP story on yahoo news, scientists in Britain and the United States are calling for a review of a whole class of similar drugs that may have the same devastating effect on heart health.

Apparently, there had been plenty of warning signs on the side effect for years, but the FDA allowed Merck to gloss over them and continue heavy direct-to-consumer advertising, allowing the drug to turn into a billion-dollar seller, damaging heart health in the process.

The European Medicines Agency in London announced Wednesday it would review all drugs of this type in the wake of Merck & Co.'s decision to voluntarily withdraw Vioxx. Pfizer's Bextra, another best selling pain drug, is next in line, according to recent reports (see links at end of article).

Reports: Other Drugs May Raise Heart Risks

Original at Yahoo! Health - AP

By MARILYNN MARCHIONE, AP Medical Writer

Scientists in the United States and Great Britain are calling for a fresh look at Celebrex and other medications similar to Vioxx, the heavily advertised arthritis drug pulled from the market last week after a study suggested it doubled the risk of heart attacks and strokes.

The European Medicines Agency in London announced Wednesday it would review all drugs of this type in the wake of Merck & Co.'s decision to voluntarily withdraw Vioxx.

In the United States, a cardiologist who had researched these drugs published an article in the New England Journal of Medicine (news - web sites) suggesting problems might extend to the entire class of medications, not just Vioxx. Another prominent doctor writing in the same journal charged that the Food and Drug Administration did not do everything needed to make sure the drug was safe. He also called for a congressional review of the matter.

An FDA spokeswoman said the agency had no comment. Last week, FDA officials said problems were limited to Vioxx.

Pfizer, which makes Celebrex and a newer, similar drug called Bextra, disputed the medical journal reports and said its drugs are safe.

"The proof is really in the real-world data, and it hasn't been borne out," Pfizer's medical director, Dr. Gail Cawkwell, said of the heart problem risk.

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 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've been concerned all along," he said. "I believe this is a class effect," not just a problem with Vioxx, he said.

Cawkwell of Pfizer called his 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.

An article in the medical journal by 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."

Merck and FDA officials said the mechanism underlying the problem with Vioxx 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.

Republican Congressman Tom Davis of Virginia, who chairs the House Government Reform Committee, has 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.

___

Associated Press writer Linda A. Johnson in Trenton contributed to this report.

See also related:

Merck now under criminal investigation by the Justice Department for Vioxx scandal

The Vioxx scandal: damning Senate testimony reveals drug company, government complicity
Several scientists testifying before the Senate Finance Committee on November 17 provided substantial evidence that the drug company Merck and the US Food and Drug Administration (FDA) knew of safety problems years before the drug Vioxx was withdrawn from the market.

More than 100,000 people may have been harmed by Vioxx, says FDA scientist David Graham

New Study Links Pfizer's Bextra, Similar to Vioxx, to Heart Attacks
The incidence of heart attacks and strokes among patients given Pfizer's painkiller Bextra was more than double that of those given placebos, according to preliminary results of a study presented yesterday at the American Heart Association meeting in New Orleans.

Arthritis drug warnings 'ignored'
Vioxx was linked to heart problems - the arthritis drug should have been taken off the market years before it was finally withdrawn, say researchers.

After Vioxx: Pfizer's Bextra Found To Increase Heart Attacks
New York Times - Pfizer Warns of Risks From Its Painkiller
Pfizer warned doctors yesterday that one of its best-selling painkillers, Bextra, might increase the risk of heart attack or stroke in coronary artery bypass surgery patients. The announcement comes just two weeks after Merck removed from the market its painkiller, Vioxx, which is in the same class of medicines as Bextra, because a study showed that the risk of heart attacks doubled for patients who had taken Vioxx 18 months or longer. Pfizer said a clinical study involving more than 1,500 patients showed that those who had undergone bypass surgery and had taken Bextra intravenously and orally were at higher risk for heart attacks.

FDA Official Alleges Pressure to Suppress Vioxx Findings
By Marc Kaufman, Washington Post Staff Writer - Friday, October 8, 2004
A Food and Drug Administration official who sought to estimate the harm done to patients by side effects of the painkiller Vioxx said yesterday that his supervisors tried to suppress his conclusions, according to Sen. Charles Grassley (R-Iowa).

FDA silenced expert who raised concerns about Vioxx: U.S. Senator
WASHINGTON (AP) - The U.S. Food and Drug Administration silenced one of its drug experts who raised safety concerns weeks before Merck & Co. yanked the blockbuster drug Vioxx due to increased risks for heart attack and strokes, the chairman of the U.S. Senate finance committee said Thursday.

Good Riddance to a Bad Drug
New York Times - By ERIC J. TOPOL

After Vioxx Recall, Other Drugs Under the Microscope

Before Recall, Vioxx Approved for Kids!

Now Experts Are Saying Celebrex Is Also a Problem

Will we be as quick to swallow the next wonder drug?

Bextra: Study finds risk with Pfizer drug
By Gardiner Harris The New York Times - Thursday, November