For the F.D.A. and manufacturers, total certainty of a drug's safety can be elusive.
Posted on 11/20/2004 10:23:39 PM PST by neverdem
WASHINGTON — At a hearing Thursday on Capitol Hill, senators excoriated top federal drug regulators for failing to realize three years ago that Vioxx, a pain pill that Merck withdrew in September, was dangerous.
But the Food and Drug Administration today faces almost exactly the same situation with another arthritis drug, Bextra, that it did with Vioxx three years ago. And just as with Vioxx, it is far from clear what the agency should do. In a sign that they believe they acted appropriately in the Vioxx case, top agency officials are handling the Bextra situation exactly the same way.
Another disaster in the making? No one knows.
The parallels between Vioxx and Bextra are eerie. There are mounting worries about Bextra's safety, just as there were with Vioxx. Drug-safety advocates are calling Bextra a danger, just as they did with Vioxx. Pfizer, Bextra's maker, defends its drug just as Merck did. And studies of Bextra provide ammunition to both sides, just as studies of Vioxx did.
What should the F.D.A. do? The answer is as clear as mud, just as it was with Vioxx. The twin controversies demonstrate the problems that the F.D.A. routinely faces in trying to strike the right balance between the risks and benefits of prescription drugs.
There is almost never a perfect answer. In 2000, GlaxoSmithKline withdrew the drug Lotronex, which treats irritable bowel syndrome, after 70 patients taking the drug suffered ischemic colitis, an intestinal inflammation that can be fatal. But the F.D.A. was flooded with protests from patients who felt the drug was a lifesaver. So GlaxoSmithKline and the agency devised a plan to sell it under strict controls to a limited patient population.
Similarly, agency officials note that Vioxx was the only painkiller ever to prove that it cut the risk of ulcers in half, compared with older pain pills. One course of action Merck might have taken would have been to continue selling the medicine to users not at elevated risk of a heart attack.
Instead, Merck decided by itself that the drug should be withdrawn. Whether the F.D.A. would have insisted on such a move is unclear. Dr. Sandra Kweder, deputy director of the agency's office of new drugs, said it would have had to examine studies of the drug closely.
But she strongly defends the way the agency handled the Vioxx controversy. "The case of Vioxx is one where the agency left no stone unturned," she said. Indeed, she said, the system worked.
It's the same system the agency is using to examine worries about Bextra's safety. As with Vioxx, the agency has gathered a panel of independent experts to examine studies of the drug and tell the agency what to do. As with Vioxx, Dr. David Graham of the agency's office of drug safety hopes to launch a study with Kaiser Permanente, the giant California health maintenance organization, to examine the drug's effects in a large patient population.
"With Bextra, we are in the same situation as we were with Vioxx in terms of needing data," Dr. Graham told the Senate panel Thursday.
Dr. Eric Topol, a cardiologist at the Cleveland Clinic and an early critic of Vioxx, said that Bextra should immediately have a strong "black-box" warning placed on its label saying that the drug should not be used in patients with cardiovascular disease.
He said the best way to determine the potential side effects of Bextra would be to test it in patients with heart problems, but that at this point it would be unethical to do so. Two studies of Bextra sponsored by Pfizer showed that it increased the risks of heart attack and stroke among patients undergoing cardiac surgery. Studies of the drug in arthritis patients have shown no such increased risk.
Dr. Gail Cawkwell, Pfizer's worldwide medical director for Bextra and its cousin, Celebrex, agreed that the company cannot ethically test Bextra in patients at high risk for heart disease. Dr. Cawkwell also said that the company is negotiating with the F.D.A. over what new information should be put in the drug's label. Pfizer has already agreed to a "black-box" advisory to alert physicians to the risks of a rare but potentially fatal skin rash.
The company will launch a long-term test of Bextra in arthritis patients to examine its effect on the heart. But Dr. Cawkwell said that trial probably won't start until the end of next year and results most likely will not be available for several more years.
What should the F.D.A. do, since millions more patients may take Bextra in the meantime? Dr. Sidney Wolfe, director of Public Citizen's health research group, said he had advised patients to stop taking the drug. But even though he said he believed that worries about Bextra were even greater than those about Vioxx three years ago, he has not asked the F.D.A. to demand its withdrawal.
So the agency soldiers on with its same old process.
For the F.D.A. and manufacturers, total certainty of a drug's safety can be elusive.
Following the arguments on Bextra with great interest, since I've been taking the drug for 2 years (but am currently switching to Celebrex as per my dr's advice.)
It's a "sulfa" drug. I hope you have no history of allergies to them.
FReepmail me if you want on or off my health and science ping list.
No, I have no history of allergies to sulfa drugs. But I'm nervous at how the media is dumping on Bextra. And my dr. thinks a change to another painkilling drug is in order, says it's good to switch drugs after a time.
I took Bextra for two weeks, and by the end of that time, I was horribly depressed.
I'm a can-do kind of guy, not prone to depression.
I have been through some really hard times in the past, but things were going great--absolutely no reason to be bummed.
I figured the medication was the only thing different and I quit taking the drug.
I felt great (normal) in just a couple of days. I can handle a little joint pain, but forget being that bummed out.
ping
If you think you've had an adverse drug reaction(ADR) that hasn't been recognized, ask your doc to report it to the FDA. That's the main way anecdotal reports of ADRs get much attention from the FDA after a drug is approved, unless someone happens to be doing a large study for another reason.
The study that finally convinced Merck to pull it from the market because they monitored all cause morbidity and mortality was intended to show a decrease in colon polyps in patients who took Vioxx, IIRC.
When you get free samples from a doc, read the product information slips. That's what's in the Physician's Desk Reference(PDR) about that drug.
Weren't both Vioxx and Bextra both approved under Toon's watch? If so, wonder if Toon put any pressure on the FDA to issue and/or speed up the approvals?
I have been prescribed Vioxx, Celebrex, and other COX-2 inhibitors. NONE of them worked for me.
I have gone back to plain old ibuprofen.
Interestingly, in addition to current concerns about these drugs, post marketing data is showing that they are not much better than standard NSAIDS at preventing stomach bleeding... the main reason for their development.
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