The Wall Street Journal -- August 28, 1997
Medicine:
Eminent Journal Urges
Moratorium on Diet-Drug Use
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By Robert Langreth
Staff Reporter of The Wall Street Journal
Pressure is building in the medical community to restrict the use of several
popular prescription diet medications.
An unusually blunt editorial today in the nation's most influential journal for
doctors, the New England Journal of Medicine, calls for a moratorium on the
use of prescription diet drugs Redux and a combination of two other medicines
called "phen-fen" for cosmetic weight loss.
The editorial is likely to spur further alarm over the widespread use of the
prescription diet pills, whose sales had been soaring until recent reports of
possible harmful side effects received widespread publicity. Since then,
industry sources say, sales of the three medicines have dropped between 15%
and 40%.
The New England Journal's editorial harshly criticizes the rationale the U.S.
Food and Drug Administration used last year to approve Redux, which was
developed by Interneuron Pharmaceuticals Inc. of Lexington, Mass., and
marketed by the giant U.S. drug maker, American Home Products Corp.,
Madison, N.J. The editorial argues that the obesity drug's purported
life-prolonging benefits are not proved and may not outweigh the risks of side
effects for all but the seriously obese.
Cardiologist Gregory Curfman, New England Journal deputy editor and author
of the editorial, in an interview called some of the side-effect reports "pretty
scary." He added: "It has never been shown that these drugs can make people
live longer, [but] even short-term use has been associated with serious
complications." The New England Journal editorial is all the more remarkable
as it represents a dramatic reversal from a controversial editorial last year in
the same journal touting the potential benefits of obesity drugs.
In the last couple of years, diet drugs' popularity has soared, as many doctors
and entrepreneurs opened diet clinics centered on the drugs. Critics say many
such weight-loss centers hand out the prescription drugs after only cursory
exams and dispense them to patients only trying to lose a few pounds. The
most popular diet drugs are Redux, and "phen-fen," a combination of
phentermine and fenfluramine. Fenfluramine is sold under the brand name
Pondimin, also by American Home Products, while phentermine is a generic
product sold by several companies.
Proponents of phen-fen and Redux say worries about side effects are
overblown and unproven. But concern over the diet drugs has grown in the
last few months as new research reports have linked them to an increasing
variety of serious, sometimes deadly, side effects, including a potentially lethal
lung disease called primary pulmonary hypertension and rare heart-valve
disorders.
"This scares me to death," says Gary Huber, a weight-loss expert at the Texas
Nutrition Institute in Tyler, Texas, who uses phen-fen therapy on his patients.
He says he is performing extra heart tests on his patients and plans to take
many of them off phen-fen as soon as expected new drugs become available in
the next few weeks.
In the latest side-effect report, also in today's New England Journal,
pathologists at Boston's Massachusetts General Hospital describe a
29-year-old woman who died of pulmonary hypertension after taking phen-fen
for a mere 23 days. The condition occurs when pressure builds up in blood
vessels between the heart and the lungs. Previously, pulmonary hypertension
has been associated with diet-drug usage of three months or more.
An autopsy revealed that the woman's artery damage was similar to that
caused by the notorious diet drug aminorex, which has a chemical structure
similar to that of phentermine and fenfluramine. Aminorex was popular in
Europe in the late 1960s and was banned there after it was linked to numerous
deaths.
The New England Journal is expected to stir up additional concerns by
prominently publishing provocative research from the esteemed Mayo Clinic in
Rochester, Minn. The research, informally released in July, describes 24
patients who developed a rare form of heart valve disease after taking
phen-fen. In addition, two other letters in the same issue from doctors at
Brown University and from officials at the Food and Drug Administration
discuss several dozen other patients who may have developed heart-valve
disorders related to use of Redux or phen-fen.
The FDA yesterday defended its 1996 decision to approve Redux. But the
agency in a statement said it was requiring manufacturers of all three diet drugs
to issue prominent new warnings on the drugs' labels, as well as requiring the
companies provide patient "inserts" warning users about the potential for the
drugs to cause heart-valve damage.
The FDA has also begun gathering more information on the incidence of side
effects before deciding whether to take additional steps, which could include
yet more warnings for patients or doctors, changes in the recommended
dosages or length of time the drugs can be safely prescribed.
"All options are open," said acting FDA commissioner Michael Friedman.
Proponents of the diet drugs, including Interneuron and American Home
Products, say benefits of the diet pills outweigh any small chance of serious
complications because hundreds of thousands of people die each year from
obesity-related illnesses, such as heart disease and diabetes.
However, Dr. Curfman takes issue with that argument in the New England
Journal editorial. "Weight reduction extends health benefits to overweight
people only if it is maintained for a long period. It has never been shown, and it
is highly implausible, that appetite-suppressant drugs can maintain weight loss
indefinitely. . . . Their safety if taken over a period of many years is doubtful,
since the risk of serious toxicity appears to increase with duration of use."
The new reports of dangerous heart and lung illness, the editorial continues,
"are chilling reminders that succumbing to the allure of diet pills as a quick fix
for excess weight may be courting disaster." To prevent patients from ending
up at diet clinics with improper supervision, the editorial recommends that
patients trying to lose weight should consult their own doctors, not ones they
don't know.
American Home Products says it has always recommended against using its
drugs for cosmetic weight loss. It says reports of heart-valve reports
associated with phen-fen or Redux use are inconclusive. And it says that doses
of Redux that appear to harm laboratory animal brains are far greater than
doses used in humans, contradicting a report in yesterday's Journal of the
American Medical Association arguing that doses of diet drugs thought to
cause brain damage in laboratory animals are comparable to doses used by
people.
"The safety record of [Redux and Pondimin] are as good as any drugs for
treating chronic disease," says Marc Deitch, global medical director for
American Home's Wyeth-Ayerst Laboratories unit.
Still, the company is funding studies to research unintended effects of the
drugs. One study with the Mayo Clinic will compare the hearts of hundreds of
patients on the diet drugs with those of similar patients not on the drugs.
Another study will examine the effects of Redux on the brain.
Meanwhile, some patients and doctors are already stopping the drugs. Since
the FDA released warnings about the possible heart valve side effect in early
July, weekly prescriptions of Redux have dropped 22% and Pondimin
prescriptions have plummeted 38%, according to IMS America, a
market-research firm.
However, some doctors say that many questionable diet centers are still in
operation. "I still am getting complaints about pill mills," says Richard Joseph, a
doctor in Naperville, Ill., who is chairman of the ethics committee for the
American Society of Bariatric Physicians. "I don't see a big change. In fact, it
is getting worse." As patients get hurt, he says, "there are going to be some big
bigtime lawsuits."
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Under Attack
-- April 1996: Redux becomes first new diet drug in over 20 years
-- August 1996: New England Journal of Medicine study links main ingredient
in Redux and other diet drugs to rare but deadly lung disorder
-- December 1996: 1 million prescriptions written for Redux and its chemical
cousin, Pondimin, both sold by American Home Products Corp.
-- July 1997: Mayo Clinic study links `phen-fen' diet-pill combination to heart
valve disease; FDA sends warning letter to doctors
-- Aug. 27, 1997: Report in Journal of the American Medical Association
claims diet drugs cause brain damage in animals in doses comparable to human
doses
-- Aug. 28, 1997: New England Journal of Medicine reports that a woman
died of a rare lung disorder after taking phen-fen for only 23 days; lung
damage is similar to that seen in dangerous amphetamine-like drugs. A Journal
editorial calls for moratorium on use of diet drugs for cosmetic purposes, and
criticizes logic behind approval of Redux
Sources: Staff research, medical journals, Scott-Levin |
