Study Suggests Generic Drug's Role in 'Fen-Phen' Risk (Update4)
Bloomberg News
August 28, 1998, 2:49 p.m. ET
Study Suggests Generic Drug's Role in 'Fen-Phen' Risk (Update4)
(Adds Warner-Lambert comment in 20th paragraph.)
Paris, Aug. 28 (Bloomberg) -- New research may explain how
the once-popular ''fen-phen'' combination of diet drugs caused
heart-valve damage that led to the withdrawal of two drugs used
in the combination.
The research -- which sheds light on the role the still-
available generic drug phentermine may play in dangerous
interactions -- comes from the scientist who helped develop one
of the drugs that was pulled from the market, Interneuron
Pharmaceuticals Inc.'s diet pill Redux.
Interneuron and partner American Home Products Corp.
withdrew Redux in September 1997 after research linked it to
heart-valve problems in the ''fen-phen'' combination. In ''fen-
phen,'' Redux and American Home's similar drug Pondimin were
taken with phentermine, made by SmithKline Beecham Plc, among
others.
The research suggests that patients who took phentermine in
combination with Redux were unknowingly blocking the body's two
main ways of controlling a chemical that, when allowed to build
up unchecked, can cause damage to the heart.
Richard Wurtman, the scientist responsible for the new
findings, said 20-year-old research on phentermine should have
alerted the medical community of the potential for dangerous
interactions.
''They should never have been prescribed together,'' said
Wurtman, who is an Interneuron director and owns about 700,000
shares. ''You have to be extremely careful when you combine two
drugs for the first time, especially when one of them has a label
that's 20 years out of date.''
Labeling for phentermine was never updated to reflect
studies done in the 1970s that showed the drug blocked one of the
body's two main methods for mopping up serotonin, a chemical the
body makes that helps control mood and appetite, said Wurtman,
who is also a professor at the Massachusetts Institute of
Technology.
Findings Challenged
Redux works by blocking the body's other main mechanism for
keeping serotonin in balance. Interneuron, an unprofitable
Lexington, Massachusetts based biotechnology company, introduced
Redux, its biggest drug, in 1996.
Interneuron shares rose 1/32 to 3 1/16 in midafternoon
trading. Its stock has dropped 83 percent in the past year on the
withdrawal of Redux. It traded at 39 3/8 in April 1996. Shares of
American Home, the world's seventh-largest drugmaker, fell 7/8 to
56 1/16.
Lawsuits filed over the use of Redux and Pondimin with
phentermine could expose the drugmakers to damages topping $4
billion, plaintiffs' lawyers say.
Makers of phentermine, including SmithKline Beecham Plc and
smaller U.K. drug company Medeva Plc, challenged the findings.
''Phentermine has been used safely and effectively for nearly 40
years and remains on the market,'' SmithKline said in a
statement.
Phentermine is still widely prescribed for weight loss. In
the week ended August 14, U.S. pharmacies filled 71,905
prescriptions for phentermine, including 57,770 new
prescriptions, according to IMS Health Inc., a Westport,
Connecticut company that provides research and technical services
to the health care industry.
The U.S. Food and Drug Administration hasn't yet received
study done by Wurtman and colleagues, said spokeswoman Ivy Kupec.
''We're very interested in seeing this information,'' she said.
''We'll review it very carefully.'' She declined to comment
further.
The U.S. Food and Drug Administration never approved use of
the ''fen-phen'' combination.
The research done by Wurtman and colleagues looked at
phentermine in rats and in 17 healthy volunteers, a small sample.
Larger studies also are looking at the possible effects of diet
drugs on heart valves.
At this point, the medical community and analysts are
looking for more data, said Barney Rosen, an analyst with Argus
Research, who has a ''buy'' rating on American Home, the seventh-
largest U.S. drug maker.
''These guys might be onto something, but it's more fat to
chew on, not a clearing of the clouds,'' said Rosen, who is a
medical doctor.
Wurtman's findings suggest the same concerns about heart
damage could apply when phentermine is combined with some of the
most commonly prescribed drugs, antidepressants such as Eli Lilly
& Co.'s Prozac and Pfizer Inc.'s Zoloft.
Dangerous Combinations?
The same problem that applies to phentermine could also
apply to related compounds found in such common over-the-counter
medications such as Warner-Lambert Co.'s cold medicine Sudafed,
Wurtman and his fellow researchers said. That could point to
dangerous interactions between Sudafed and Prozac or Sudafed and
Zoloft.
Warner-Lambert said that's unilkely.
''We have been monitoring Sudafed for adverse
reactions for over 30 years,'' said Judith Sills, senior director
of U.S. regulatory affairs at the Morris Plains, New Jersey-based
company. ''We haven't seen any evidence that there's any
interaction between Sudafed and Prozac-type antidepressants.''
Prozac and Zoloft, like Redux, work by keeping serotonin
from being absorbed into platelets, blood cells needed for
clotting -- one of the body's two main mechanisms for removing
serotonin. Serotonin's functions are varied and include helping
regulate moods and appetite as well as blood clotting.
Lilly, maker of Prozac, cautioned against drawing
conclusions from the researcher's early work, especially comments
about a possible effect on Sudafed on serotonin.
''It's nothing but a theory at this point in time,'' said
Greg Kueterman, a Lilly spokesman. ''About 35 million people have
taken Prozac since it first came to market and there's no
evidence that there's any kind of interaction with Prozac and the
over-the-counter remedy.''
Still, Lilly has recommended against combination of Prozac
and phentermine because the use of the two drugs together hasn't
been studied, he said.
The research, presented at the Eighth International
Conference on Obesity in Paris, is the work of Wurtman, a
professor at the Massachusetts Institute of Technology, Timothy
Maher, director of pharmaceutical sciences at the Massachusetts
College of Pharmacy, and Ismail Ulus, a visiting MIT professor.
Redux was the result of research Wurtman did at MIT with his
wife, obesity researcher Judith Wurtman, he said.
--Kerry Dooley in the Princeton newsroom (609) 279-4016 with
quote.bloomberg.com |
