Vioxx Saftey Info Deleted
The New England Journal of Medicine said it had determined that Merck deleted data about three heart attacks among Vioxx users, and other relevant data, prior to submitting its analysis from the so-called Vigor trial to the Journal in 2000.
The trial compared the safety of Vioxx with naproxen, a widely used rheumatoid arthritis drug.
"The evidence has raised questions about the integrity of the data on adverse cardiovascular events in the article and about some of the article's conclusions," the Journal said in a statement on its Web site.
In response, Merck said it promptly and appropriately disclosed the results of the study, correctly stated possible risks of Vioxx and extensively disclosed the Vigor data to the medical community.
Vioxx was withdrawn in September 2004 after being shown to double the risk of heart attack and stroke in patients taking it for over 18 months. More than 6,000 lawsuits have been filed against Merck in the United States, alleging Vioxx caused heart attacks and deaths.
Cox-2 & NSAIDs Lawsuits & Problems
Within weeks two major categories of painkillers linked to side effects
Vioxx was taken off the market after Merck & Co. discovered it doubled the risk of heart attack and stroke. When patients taking Vioxx made the switch to similar competitor Celebrex, within weeks Pfizer Inc. announced a study showed the drug also increased the risk of heart problems that appeared more significant than Vioxx. Days later, the National Institutes of Health said it found a similar, though smaller, risk with Aleve (generic name naproxen).
Concerned and confused patients are swamping doctors' offices with questions, but many doctors do not even know what to say. NSAIDs, or nonsteroidal anti-inflammatory drugs, are the most widely used class of drugs that includes aspirin, ibuprofen, naproxen and other drugs. For years, NSAIDs have been used for various ailments, but the drugs carry the risk of inducing serious stomach and intestine bleeding. About 20 percent of people that want pain relief cannot take NSAIDs because of the bleeding risks.
Cox-2 inhibitors include now recalled Vioxx, Celebrex and Bextra and were introduced in the late 1990s as an alternative to NSAIDs. The Cox-2 drugs were supposed to provide pain relief without the risk of bleeding problems, and the drugs quickly became popular even though some studies did show the drugs did not always prevent bleeding in the stomach or intestines.
Patients that are more at risk for heart trouble because of age or medical history are being advised against Cox-2 drugs and to take NSAIDs only when the pain gets really bad. A major study published in the Archives of Internal Medicine showed abruptly halting the use of naproxen and other NSAIDs increased the risk of having a heart attack within the next 30 days by 50 percent - especially in patients with rheumatoid arthritis or lupus.
NSAIDs are the most widely used drugs taken by tens of millions of people. Some experts believe that while the links to serious cardiovascular events is discouraging for some groups of people, there is a plus side. A great number of people take NSAIDs on a casual basis but may not even really need NSAID therapy.
Aleve Increases Heart Risk
New risks put old drugs in spotlight
By Scott Hensley / Wall Street Journal
A government finding that Aleve, the widely used pain reliever, appears to increase the risk for heart problems underscores how little is known about possible side effects of some common older medicines.
Although much attention has been paid recently to drug-safety problems that have emerged in newer prescription drugs, such as Vioxx, the same scrutiny hasn't been applied to older over-the-counter medicines and prescription drugs that long ago went generic. The reasons have to do with changing regulatory standards and economic incentives.
These older pills came to market decades ago as prescription drugs when standards for approval were more relaxed -- Aleve, generically called naproxen, was available by prescription only for nearly 20 years before the over-the-counter version was approved a decade ago. Prescription-strength naproxen still is sold.
In the past, studies were smaller and less comprehensive, sometimes lasting weeks or months. Today, studies can run for years.
One reason safety problems such as these are coming to light now is that larger, longer drug trials -- such as the government's Alzheimer's disease-prevention study that sounded alarm bells about Aleve -- are putting some of these older drugs to more rigorous tests. A clinical trial can tease out safety signals that may have been lurking undetected or underappreciated.
Aleve marks the fourth major painkiller in recent months to show signs of raising the odds of heart attack and stroke. The others were Pfizer's Bextra and Celebrex and Merck & Co.'s Vioxx. Those three are so-called Cox-2 inhibitors, a new category in the broader class of painkillers known as nonsteroidal anti-inflammatory drugs, or NSAIDs, including Aleve.
For years, Aleve was thought to be protective of the heart, like aspirin. Indeed, Merck has cited that to explain why patients taking Vioxx had more heart problems than patients taking naproxen in a clinical trial.
But the heart-protection assumption about Aleve hadn't been proven in rigorous clinical trials. When it was put to a careful test -- the Alzheimer's study sponsored by the National Institutes of Health -- a safety check turned up the indication that Aleve appeared to increase by about 50 percent the risk of cardiovascular problems, such as strokes and heart attack, in elderly patients taking the drug daily for several years.
Aleve's maker, Bayer AG, said the findings contradict nearly 30 years' experience of safe use of the drug. Bayer agrees with the FDA that consumers should carefully follow the instructions of the Aleve label, which limits treatment of pain to 10 days or less, unless otherwise directed by a doctor.
See http://www.detnews.com/2004/health/0412/26/A01-42089.htm for full article.
FDA: Don't overdo pain pills
By Rita Rubin, USA TODAY
Just because you can buy a pain reliever along with your morning coffee and doughnut at the local convenience store doesn't necessarily mean it's safe to pop the pills for weeks on end.
Time release: Pain relievers shouldn't be taken longer than 10 days, according to the FDA.
By Tim Sloan, AFP
That's the message the Food and Drug Administration is trying to get out to consumers. If you think you need to take naproxen, ibuprofen or aspirin — all nonsteroidal anti-inflammatory drugs, or NSAIDs — for longer than 10 days, do so under a doctor's supervision, the agency is now advising. And don't take any more pills a day than the label, or your doctor, recommends.
If your doctor has prescribed Celebrex or Bextra, two newer NSAIDs known as COX-2 inhibitors, you and your doctor should discuss whether you really need to take the drugs, according to a just-released health advisory from the FDA.
If you're at risk for a heart attack or stroke but not for digestive tract bleeding, you probably should stick with an older NSAID. Theoretically, the COX-2 inhibitors are less likely to cause digestive tract bleeding, but Pfizer, maker of Celebrex and Bextra, has not yet been able to convince the FDA that it should be able to make that claim on the drugs' labels.
In recent weeks, studies comparing Celebrex, Bextra, Vioxx and naproxen — an older NSAID sold over-the-counter as Aleve — with a placebo have shown that they could increase the risk of heart attack and stroke, especially if taken for long periods or by people who are at high risk for such problems. Merck pulled its COX-2 inhibitor, Vioxx, off the market Sept. 30, but Celebrex and Bextra remain.
In light of the new information about risks of heart attack and stroke, Jenkins said, the FDA is requiring that researchers re-evaluate all prevention studies — in which healthy people are given a drug to see whether it prevents a disease or condition — involving Celebrex or Bextra.
Pfizer, maker of Celebrex and Bextra, says a planned FDA advisory committee meeting on COX-2 inhibitors in February "is the appropriate forum for a thorough review of all available data."
Meanwhile, the company said Friday in a statement that "patients should continue to consult their doctor to ensure they get the pain treatment appropriate for their individual medical need."
see full article at USAToday.com
FDA Warns on Taking Naproxen for More Than 10 Days
The FDA warned that patients taking the nonprescription painkiller naproxen should consult a physician if they plan to take the drug for more than 10 days. Naproxen, which is also marketed under the brand name Aleve by Bayer AG, has also been linked to cardiac problems.
Alzheimer's Desease & Prevention Trial - Aleve (Naproxen) Risk
The Alzheimer's Disease and Prevention Trial (ADAPT), which included 2400 patients, did, however, report an increased cardiovascular risk among patients taking Aleve (naproxen), an over-the-counter pain reliever.
“This is important new information that should be considered by doctors and patients as they evaluate the various treatments for arthritis and pain,” said Hank McKinnell, chairman and chief executive officer of Pfizer. “Millions of people simply can't get through their day without pain relief. That's why all the emerging information about arthritis medicines-prescription and over-the-counter-must be fully evaluated by the U.S. Food and Drug Administration and other regulatory authorities.
Naproxen Woes Hurt Some, Help Others
A U.S. Food and Drug Administration warning on the generic painkiller naproxen -- used in such over-the-counter medicines as Aleve -- hit two German drugmakers but seemed to help the fortunes of troubled Pfizer and its Celebrex arthritis drug on Tuesday.Late Monday, the U.S. National Institutes of Health halted a clinical trial using naproxen involving patients at risk of developing Alzheimer's disease. The NIH suspended until further notice the use of both naproxen and the Cox-2 inhibitor Celebrex, in a large, three-arm, national Alzheimer's prevention trial.
The trial was designed to assess the potential long-term use of the two drugs in decreasing the risk of developing Alzheimer's disease in people 70 years of age or older who were considered to be at increased risk because of family history, but did not have symptoms of the disease.
While overseas makers of the naproxen suffered some ill effects, the news seemed to help Pfizer (PFE: news, chart, profile), which recovered some of the losses it felt when Celebrex was found to cause cardiac risk with high doses in tests on cancer patients. CIBC Equity Research said the NIH report was good news for Pfizer.
"This news is likely to increase confusion, but as the dust settles the opportunity for Pfizer is for rationality to return to the market," said analyst Mara Goldstein. "While we still believe that use of Cox-2s will decline and place pressure on EPS, we are less inclined to think that a broad-based withdrawal is likely."
Pfizer was up 3.2 percent, to $25.04. On Friday, Pfizer said a long-term study of Celebrex linked the drug when administered in high doses to an increased risk of heart attacks. The company has decided to halt all advertising for the drug. The company's shares plunged 16.2 percent from Friday through Monday.
Meanwhile, Germany's Bayer - which makes the popular over-the-counter pain drug Aleve - regained some of its losses and was off 15 cents to $33.66. And Stada Arzneimit, which sells the naproxen drug Prodolor, fell 1.4 to $19.48 euros on the German stock exchange.
However, shares of Swiss drug giant Roche, which markets the naproxen treatment Naprosyn, ended Monday's session up 1.9 percent to $112.25.
"It's not a big product for them. Probably most of the sales are as an over-the-counter product -- and that business has been sold to Bayer," said Max Herrmann, an analyst at ING Financial Markets.
"I doubt there are very significant sales as a generic -- as the branded version of Naprosyn -- so I don't think it's going to have a big impact on Roche," he added.
The trial was designed to assess the potential long-term use of the two drugs in decreasing the risk of developing Alzheimer's disease in people 70 years of age or older who were considered to be at increased risk because of family history but did not show symptoms of the disease.
Preliminary information from that study showed some evidence of increased risk of cardiovascular and cerebrovascular events in patients taking naproxen rather than a placebo, the NIH reported.
Patients taking over-the-counter naproxen should carefully follow the label instructions and should not take naproxen for periods longer than 10 days, the FDA warned.
No significant risk was found in the trial for patients taking celecoxib, according to the NIH, but the use of these drugs in the study was suspended in part because of last week's findings to test the effectiveness of celecoxib in preventing colon cancer.
Merck withdrew its arthritis drug Vioxx from the market in late September after a clinical trial linked long-term usage to an increased incidence of heart attack and stroke.
Naproxen first was sold as a prescription drug under the trade name Naprosyn in 1976. The FDA approved its use as an over-the-counter drug in 1994.
Other analysts saw the NIH report as good news for Pfizer and Celebrex.
In what UBS Investment Research called "the latest twist," the NIH study suggests Celebrex is safer than Naproxen.
UBS analyst Carl Seiden told clients in a note Tuesday "it is increasingly unlikely that Celebrex will be forcibly pulled from the market."
Friedman Billings Ramsey agreed that the "naproxen heartbreaker [is] good for Celebrex," and maintained its "outperform" recommendation on Pfizer shares.
Analyst David Moskowitz said the NIH study bolstered Celebrex's safety record and cast doubt on naproxen.
"Pfizer has 10 years of Celebrex data for 40,000 patients in a well-controlled clinical setting, in contrast to a lack of long-term safety data on NSAIDs like naproxen," Moskowitz told clients.