Failed fat foe

The sad saga of "fen-phen"
A miracle. A diet drug that finally worked. A quick fix to end all quick fixes. That was the word on fen-phen -- a combination of fenfluramine or dexfenfluramine, plus phentermine. Each drug acted on a different part of the brain to reduce hunger pangs.
By themselves, the drugs were unspectacular, but combined they were almost miraculous. In the one (as in single, only, lone, isolated, solo, unique) test of their efficacy, 121 obese patients lost an average of 30 pounds apiece.
Caution: If you've taken either of the "fen" drugs (fenfluramine or dexfenfluramine) -- alone or in the fen-phen cocktail -- read this warning from the federal government.
The publication of that study in 1992 loosed a floodgate of desire to be young, beautiful, or at least thinner. In 1996, an estimated 6 million American patients, mainly women, and not all of them obese, took the combination -- dubbed fen-phen -- on the basis of that one study. After years of disrepute, diet drugs were as popular as ice-cream cake at a birthday party.
Doctors noted a few side effects, including a rare but deadly lung complication, and a woozy feeling attributable to phentermine, an amphetamine. But it was a price worth paying, apparently, and "fen-phen mills," as pundits branded the clinics that specialized in the drugs, flourished. At one of these mills, there was a frightening lack of medical supervision; doctors gave "very cursory exams" to six new patients every hour (see "How Fen-Phen..." in the bibliography).
Losing more than just bulk
Fen-phen lost its allure on Sept. 15, when manufacturers withdrew fenfluramine and dexfenfluramine from the market, in response to a July Food and Drug Administration advisory. The problem, noted in 100 patients and counting, was damage to heart valves. This little snafu can lead to endocarditis, a sometimes-fatal infection of the lining of the heart. (The Why Files covered heart bypass surgery and the health effects of obesity.)

Update
15 JULY 1998. On June 22, the Food and Drug Administration (FDA) removed a pain killer from the market after four patients who took it died from liver failure. The drug, Duract, made by Wyeth-Ayerst Laboratories, had been known to cause liver problems in patients who took it for longer than 10 days. Despite warnings on the package, some doctors did prescribe it for longer than that.
The move was seen as a humiliation for the FDA, which is widely regarded as the most effective drug regulator in the world. Four withdrawn drugs (fenfluramine, dexfenfluramine, Duract, and Posicor, a high blood pressure medicine) in nine months is "the worst record we have ever had; it's unprecedented," Thomas Moore told The New York Times (see "New Painkiller Is Withdrawn... " in the bibliography). Moore, a senior fellow in health policy at George Washington University Medical Center, studies drug safety, said, "We are paying the wages of the one-sided debate that we have had in this country that the speed of FDA approval is the only issue." Although those who favor rapid drug acceptances say lives will be lost because the agency is too sluggish, critics have pointed out that Duract, like fen-phen, was a "me-too" drug rather than a life-saving breakthrough.

.
Michael Weintraub, a University of Rochester professor of clinical pharmacology who'd done the only study of fen-phen, professed dismay at the way his work had been interpreted. "I never thought of it as a magic pill," he told the New York Times (see "How Fen-Phen..." in the bibliography). "Every time I hear that word I sort of cringe."
As with so many current social problems, the Internet played its role. Fen-phen mills used the Web to reach the gullible and desperate. Indeed, more than a month after the "fen" drugs were withdrawn, we searched the Web and found an unrepentant fen-phen dispenser still claiming that "There are clear and convincing clinical studies that these drugs are effective and safe."
Ironically enough, the next item in our search announced an FDA "health advisory" on fenfluramine and dexfenfluramine.
But trust the Internet to bring out the best: one web site was already offering an "herbal phen-fen alternative" that included ma huang, an herb containing the stimulant ephedrine.
Ephedrine can cause high blood pressure, insomnia, seizures, heart attacks and stroke. On Nov. 6, the FDA told a Pennsylvania maker of herbal phen-fen that its products might be seized as illegal drugs.
What should I do?
Should those who have taken fen-phen be concerned? Apparently so. Heart valve defects can not only lead to a devastating infection of the valve or heart lining, but also can cause fatigue, shortness of breath, and even heart failure. The problem usually shows up on a stethoscope examination, and then is nailed down with echocardiography -- ultrasound of the heart.
But understanding the full impact of fen-phen is complicated, since valve defects are present in a small percentage of the population from unknown causes.
On Nov. 13, the Centers for Disease Control and Prevention issued new statistics on fen-phen. The same day, the government issued a warning and recommendations to anyone who has taken either "fen" drug. According to the Centers for Disease Control, up to 30 percent of these people may have heart valve defects associated with using the drug and should get a medical examination for heart or lung disease.
Any of these people with symptoms of heart or lung disease should then get an echocardiogram -- a sound picture of the beating heart. And they should take medical precautions before certain dental and medical procedures, which could introduce infection into the body. See "Heart Checks Urged" in the bibliography.
This kind of disaster -- if that's not too strong a word -- makes us think we need to give more attention to long-term testing of drugs, and to testing them in the combinations that are used in the real world. (See "Medicine Remains as Much Art..." in the bibliography).
In the headlong rush to find a quick fix for fat, the story of fen-phen should stand as a "slow down" billboard. Could leptin, the latest quick fix for fat, be a rerun of fen-phen?

I'm thinking about cheese cake
right now.
The publication of a
single study in
1992
loosed a floodgate of desire to be young, beautiful, or at least
thinner. The sad saga of "fen-phen"
A miracle. A diet drug that finally worked. A quick fix to end all quick fixes. can't always believe
what
you read That was the word on fen-phen -- a combination of fenfluramine or dexfenfluramine, plus phentermine. Each drug acted on a different part of the brain to reduce hunger pangs.
By themselves, the drugs were unspectacular, but combined they were almost miraculous. In the one (as in single, only, lone, isolated, solo, unique) test of their efficacy, 121 obese patients lost an average of 30 pounds apiece.
Caution: If you've taken either of the "fen" drugs (fenfluramine or dexfenfluramine) -- alone or in the fen-phen cocktail -- read this warning from the federal government.
The publication of that study in 1992 loosed a floodgate of desire to be young, beautiful, or at least thinner. In 1996, an estimated 6 million American patients, mainly women, and not all of them obese, took the combination -- dubbed fen-phen -- on the basis of that one study. After years of disrepute, diet drugs were as popular as ice-cream cake at a birthday party.
Doctors noted a few side effects, including a rare but deadly lung complication, and a woozy feeling attributable to phentermine, an amphetamine. But it was a price worth paying, apparently, and "fen-phen mills," as pundits branded the clinics that specialized in the drugs, flourished. At one of these mills, there was a frightening lack of medical supervision; doctors gave "very cursory exams" to six new patients every hour (see "How Fen-Phen..." in the bibliography).
Losing more than just bulk
Fen-phen lost its allure on Sept. 15, when manufacturers withdrew fenfluramine and dexfenfluramine from the market, in response to a July Food and Drug Administration advisory. The problem, noted in 100 patients and counting, was damage to heart valves. This little snafu can lead to endocarditis, a sometimes-fatal infection of the lining of the heart. (The Why Files covered heart bypass surgery and the health effects of obesity.)

Update
15 JULY 1998. On June 22, the Food and Drug Administration (FDA) removed a pain killer from the market after four patients who took it died from liver failure. The drug, Duract, made by Wyeth-Ayerst Laboratories, had been known to cause liver problems in patients who took it for longer than 10 days. Despite warnings on the package, some doctors did prescribe it for longer than that.
The move was seen as a humiliation for the FDA, which is widely regarded as the most effective drug regulator in the world. Four withdrawn drugs (fenfluramine, dexfenfluramine, Duract, and Posicor, a high blood pressure medicine) in nine months is "the worst record we have ever had; it's unprecedented," Thomas Moore told The New York Times (see "New Painkiller Is Withdrawn... " in the bibliography). Moore, a senior fellow in health policy at George Washington University Medical Center, studies drug safety, said, "We are paying the wages of the one-sided debate that we have had in this country that the speed of FDA approval is the only issue." Although those who favor rapid drug acceptances say lives will be lost because the agency is too sluggish, critics have pointed out that Duract, like fen-phen, was a "me-too" drug rather than a life-saving breakthrough.

.
Michael Weintraub, a University of Rochester professor of clinical pharmacology who'd done the only study of fen-phen, professed dismay at the way his work had been interpreted. "I never thought of it as a magic pill," he told the New York Times (see "How Fen-Phen..." in the bibliography). "Every time I hear that word I sort of cringe."
As with so many current social problems, the Internet played its role. Fen-phen mills used the Web to reach the gullible and desperate. Indeed, more than a month after the "fen" drugs were withdrawn, we searched the Web and found an unrepentant fen-phen dispenser still claiming that "There are clear and convincing clinical studies that these drugs are effective and safe."
Ironically enough, the next item in our search announced an FDA "health advisory" on fenfluramine and dexfenfluramine.
But trust the Internet to bring out the best: one web site was already offering an "herbal phen-fen alternative" that included ma huang, an herb containing the stimulant ephedrine.
Ephedrine can cause high blood pressure, insomnia, seizures, heart attacks and stroke. On Nov. 6, the FDA told a Pennsylvania maker of herbal phen-fen that its products might be seized as illegal drugs.
What should I do?
Should those who have taken fen-phen be concerned? Apparently so. Heart valve defects can not only lead to a devastating infection of the valve or heart lining, but also can cause fatigue, shortness of breath, and even heart failure. The problem usually shows up on a stethoscope examination, and then is nailed down with echocardiography -- ultrasound of the heart. More attention should be given to long-term testing of drugs.
But understanding the full impact of fen-phen is complicated, since valve defects are present in a small percentage of the population from unknown causes.
On Nov. 13, the Centers for Disease Control and Prevention issued new statistics on fen-phen. The same day, the government issued a warning and recommendations to anyone who has taken either "fen" drug. According to the Centers for Disease Control, up to 30 percent of these people may have heart valve defects associated with using the drug and should get a medical examination for heart or lung disease.
Any of these people with symptoms of heart or lung disease should then get an echocardiogram -- a sound picture of the beating heart. And they should take medical precautions before certain dental and medical procedures, which could introduce infection into the body. See "Heart Checks Urged" in the bibliography.
This kind of disaster -- if that's not too strong a word -- makes us think we need to give more attention to long-term testing of drugs, and to testing them in the combinations that are used in the real world. (See "Medicine Remains as Much Art..." in the bibliography).
In the headlong rush to find a quick fix for fat, the story of fen-phen should stand as a "slow down" billboard. Could leptin, the latest quick fix for fat, be a rerun of fen-phen?

nothing

nothing [CLA] [Fen-phen] [Leptin] [F_2alpha] [DHEA]
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