Despite Risks, Pain Relievers Given OK by FDA
FDA Panel Says Vioxx Can Come Back, Celebrex, Bextra Should Stay
Feb. 18, 2005 - An FDA advisory panel says the arthritis drug Vioxx can return to the market and sister drugs
Celebrex and Bextra should stay.
But experts say these drugs -- members of a group called Cox-2 inhibitors -- should carry strict warnings that they
can raise the risk of heart attacks and stroke.
The panel also recommended that labels for many of the more than 20 older anti-inflammatory drugs be updated to warn
consumers and doctors that they may carry a heart risk. Three of these, ibuprofen, naproxen, and ketoprofen, are
available over the counter.
Experts at the hearings expressed a degree of frustration that companies have not performed enough studies clearly
addressing the safety of Cox-2 inhibitors and older pain relievers. Several urged regulators to require more safety
studies as a condition for allowing the drugs to stay on the market.
"If these products are going to be on the market it should be essential that we get additional evidence," said panel
member Thomas Fleming, PhD.
Victory for Vioxx?
The panel also recommended, by a single vote, to leave the door open for Merck & Co. to return Vioxx to the market
following a self-imposed recall. Merck said that it would consider returning the drug to the market if the FDA allowed
it, but today's 17-15 decision made it unclear how the company would proceed. The FDA does not have to follow its
committees' recommendations, though it usually does.
Fleming was among the majority of experts who called for the FDA to limit any future Vioxx use to its lowest 12.5 mg
dose. Evidence has shown higher doses raise blood pressure and the risk of heart attacks and stroke.
It remains unclear whether Merck will attempt to remarket Vioxx with a low-dose restriction or whether the FDA would
allow them to do so.
Merck released a brief statement saying that the company "looks forward" to discussions with the FDA.
Officials vowed at the beginning of this week's hearing to act within a few weeks of today's decisions.
Experts strongly resisted banning Celebrex, citing limited evidence that it is safe at lower doses. At the same time,
most urged regulators to bar the use of higher doses that were shown in one major study to increase the risk of heart
attack and strokeincrease the risk of heart attack and stroke by up to 3.5 times.
The panel more narrowly gave its approval to allow the continued sale of Bextra, strongly urging in a 17-to-13 vote,
with two abstentions, not to ban the drug provided its manufacturer, Pfizer, warns patients of its risks and quickly
perform studies establishing its safety.
"Taking them out of the hands of physicians as though they were a smoking gun is probably too extreme," said Robert
H. Dworkin, PhD, a professor and researcher at the University of Rochester School of Medicine and Dentistry in New
York.
But the FDA should also require strict "black box" warnings on all three Cox-2 drugs to alert patients and doctors to
their risks, panel members said. A black box warning is the most serious warning placed on the labeling of a
prescription medication.
Warnings for Older Pain Relievers
The committee unanimously recommended that more than 20 older anti-inflammatory drugs also carry precautions of
potential heart risks on their labels. It did not specify which drugs should carry the warnings or how strong they
should be.
Some of the older NSAIDs, including diclofenac and Mobic, are similar chemically to Cox-2 drugs and may have to carry
warnings because of limited evidence that they can influence heart attacks. Many others have never been studied to
determine their potential effects on the heart.
A study among California Medicaid patients showed an increased risk of heart attack with several older
anti-inflammatory drugs, including ibuprofen. That drug appeared to raise the users' risk of heart attack by 11%.
FDA scientist David Graham, MD, referred to this as "small but significant" since tens of millions of Americans use
the drug regularly.
Other anti-inflammatory drugs, including indomethacin and Mobic, also appeared to raise heart attack risk by 40% to
70%, according to the study.
Graham said the data suggest that researchers must take a closer look at older anti-inflammatory drugs to learn more
about their possible safety concerns.
"Clearly this is going to be a complex undertaking," panelist John Jenkins, MD, said. "Not all members of this class
have the same amount of data."
Panelists warned that attaching strict warnings to Cox-2 drugs while giving weaker warnings to older
anti-inflammatory drugs could be dangerous if it drove patients to take traditional drugs that may also have similar
risks.
"They would have the false reassurance that there's not a problem, and we don't know that there's not a problem," he
said.
Naproxen, sold under many brand names including Aleve, could end up being the only anti-inflammatory exempt from
warnings because of several studies that show it causes significantly fewer heart and stroke problems than do Cox-2
drugs.
FDA experts said that previous reports linking naproxen to an increase in heart attacks were unjustified and
unnecessarily scared the public.
Naproxen is better for you than the other anti-inflammatory drugs right now at least in terms of heart risk, Wood
said.
Weighing the Good and the Bad
Cox-2 drugs are favored by many doctors because they may be less likely to cause stomach ulcers and bleeding than
older anti-inflammatory drugs.
Experts ultimately struggled with a puzzle: Is the potential benefit of fewer stomach problems worth the small but
probable increased risk of heart attacks? And which patients are at the highest risk for the drugs' potentially
negative effects?
Steven Nissen, MD, medical director at The Cleveland Clinic, said that decisions on whether or not to take Bextra,
Celebrex, or other drugs remain "filled with shades of gray."
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that has been in business for over 5 years, delivering medications to thousands of customers every day! Now is the
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Feb. 18, 2005 - An FDA advisory panel says the arthritis drug Vioxx can return to the market and sister drugs
Celebrex and Bextra should stay.
But experts say these drugs -- members of a group called Cox-2 inhibitors -- should carry strict warnings that they
can raise the risk of heart attacks and stroke.
The panel also recommended that labels for many of the more than 20 older anti-inflammatory drugs be updated to warn
consumers and doctors that they may carry a heart risk. Three of these, ibuprofen, naproxen, and ketoprofen, are
available over the counter.
Experts at the hearings expressed a degree of frustration that companies have not performed enough studies clearly
addressing the safety of Cox-2 inhibitors and older pain relievers. Several urged regulators to require more safety
studies as a condition for allowing the drugs to stay on the market.
"If these products are going to be on the market it should be essential that we get additional evidence," said panel
member Thomas Fleming, PhD.
Victory for Vioxx?
The panel also recommended, by a single vote, to leave the door open for Merck & Co. to return Vioxx to the market
following a self-imposed recall. Merck said that it would consider returning the drug to the market if the FDA allowed
it, but today's 17-15 decision made it unclear how the company would proceed. The FDA does not have to follow its
committees' recommendations, though it usually does.
Fleming was among the majority of experts who called for the FDA to limit any future Vioxx use to its lowest 12.5 mg
dose. Evidence has shown higher doses raise blood pressure and the risk of heart attacks and stroke.
It remains unclear whether Merck will attempt to remarket Vioxx with a low-dose restriction or whether the FDA would
allow them to do so.
Merck released a brief statement saying that the company "looks forward" to discussions with the FDA.
Officials vowed at the beginning of this week's hearing to act within a few weeks of today's decisions.
Experts strongly resisted banning Celebrex, citing limited evidence that it is safe at lower doses. At the same time,
most urged regulators to bar the use of higher doses that were shown in one major study to increase the risk of heart
attack and strokeincrease the risk of heart attack and stroke by up to 3.5 times.
The panel more narrowly gave its approval to allow the continued sale of Bextra, strongly urging in a 17-to-13 vote,
with two abstentions, not to ban the drug provided its manufacturer, Pfizer, warns patients of its risks and quickly
perform studies establishing its safety.
"Taking them out of the hands of physicians as though they were a smoking gun is probably too extreme," said Robert
H. Dworkin, PhD, a professor and researcher at the University of Rochester School of Medicine and Dentistry in New
York.
But the FDA should also require strict "black box" warnings on all three Cox-2 drugs to alert patients and doctors to
their risks, panel members said. A black box warning is the most serious warning placed on the labeling of a
prescription medication.
Warnings for Older Pain Relievers
The committee unanimously recommended that more than 20 older anti-inflammatory drugs also carry precautions of
potential heart risks on their labels. It did not specify which drugs should carry the warnings or how strong they
should be.
Some of the older NSAIDs, including diclofenac and Mobic, are similar chemically to Cox-2 drugs and may have to carry
warnings because of limited evidence that they can influence heart attacks. Many others have never been studied to
determine their potential effects on the heart.
A study among California Medicaid patients showed an increased risk of heart attack with several older
anti-inflammatory drugs, including ibuprofen. That drug appeared to raise the users' risk of heart attack by 11%.
FDA scientist David Graham, MD, referred to this as "small but significant" since tens of millions of Americans use
the drug regularly.
Other anti-inflammatory drugs, including indomethacin and Mobic, also appeared to raise heart attack risk by 40% to
70%, according to the study.
Graham said the data suggest that researchers must take a closer look at older anti-inflammatory drugs to learn more
about their possible safety concerns.
"Clearly this is going to be a complex undertaking," panelist John Jenkins, MD, said. "Not all members of this class
have the same amount of data."
Panelists warned that attaching strict warnings to Cox-2 drugs while giving weaker warnings to older
anti-inflammatory drugs could be dangerous if it drove patients to take traditional drugs that may also have similar
risks.
"They would have the false reassurance that there's not a problem, and we don't know that there's not a problem," he
said.
Naproxen, sold under many brand names including Aleve, could end up being the only anti-inflammatory exempt from
warnings because of several studies that show it causes significantly fewer heart and stroke problems than do Cox-2
drugs.
FDA experts said that previous reports linking naproxen to an increase in heart attacks were unjustified and
unnecessarily scared the public.
Naproxen is better for you than the other anti-inflammatory drugs right now at least in terms of heart risk, Wood
said.
Weighing the Good and the Bad
Cox-2 drugs are favored by many doctors because they may be less likely to cause stomach ulcers and bleeding than
older anti-inflammatory drugs.
Experts ultimately struggled with a puzzle: Is the potential benefit of fewer stomach problems worth the small but
probable increased risk of heart attacks? And which patients are at the highest risk for the drugs' potentially
negative effects?
Steven Nissen, MD, medical director at The Cleveland Clinic, said that decisions on whether or not to take Bextra,
Celebrex, or other drugs remain "filled with shades of gray."
Don't put your risk at health, and order from other risky online pharmacies. We're the only true internet pharmacy
that has been in business for over 5 years, delivering medications to thousands of customers every day! Now is the
only time to buy and have your prescription medications delivered privately and discreetly to your door.
Order Now and Save over 20%
