DIET DRUG WITH PROZAC MAY BE RISKY

A new study of the diet drug phentermine suggests that combining it
with Prozac -- a strategy some tout as safer than the ``fen-phen''
combination -- might be risky.

Phentermine was half the fen-phen combination, and the study's authors
also say doctors would have avoided prescribing that combination if
phentermine's label reflected information reported in the 1970s.

The study also suggests it might be hazardous to combine some
over-the-counter medications for colds or obesity with Prozac or
similar drugs like Paxil and Zoloft. But Dr. Richard J. Wurtman, one
of the authors, said he suspected the risk with occasional use of the
nonprescription medicines would be slight.

Wurtman said people taking the drug combinations his study suggested
might be hazardous should discuss it with their doctors.

The study doesn't document any harm from the drug combinations and
gives no direct evidence of risk. It focused only on the behavior of
phentermine and the over-the-counter ingredients pseudoephedrine,
phenylpropanolamine and ephedrine.

Obesity experts were cautious about the study, and drug industry
spokesmen said there's been no sign of harm from combining phentermine
or the over-the-counter drugs with Prozac or its chemical cousins.

Medeva Pharmaceuticals Inc., which sells the phentermine product
Ionamin, dismissed the study and said prior work actually indicated
phentermine would not pose the hazard suggested in the new study.
However, the company doesn't recommend combining Ionamin with
Prozac-like drugs, a spokeswoman said.

Obesity experts said phentermine is being combined with Prozac for
weight loss, but that it's hard to say how common the practice is.
Prozac's maker, Eli Lilly and Co., said last year it doesn't support
combining its drug with phentermine.

The new work is to be presented Wednesday in Paris at the
International Congress of Obesity. The authors include Wurtman, of the
Massachusetts Institute of Technology, and Timothy J. Maher of the
Massachusetts College of Pharmacy and Allied Health Sciences.

``Fen-phen'' is the combination of phentermine with fenfluramine.
Fenfluramine, known as Pondimin, and its chemical cousin
dexfenfluramine, known as Redux, were pulled off the market last
September after doctors reported heart valve damage in some people
taking fen-phen. Previously, Redux and fen-phen had been associated
with a rare lung problem, primary pulmonary hypertension.

Wurtman has a financial interest in Redux but said that didn't
influence his new study.

The study's conclusions are based on how the body controls levels of
the substance serotonin in the blood. It has two mechanisms, either of
which can do the job by itself. Drugs called MAO inhibitors can block
one mechanism, and Prozac or its ``SSRI'' chemical cousins impair the
other. Mixing drugs from both of these classes might let serotonin
levels rise enough to cause a medical emergency that includes fever
and rapid heartbeat. So an SSRI isn't supposed to be taken with a MAO
inhibitor.

Fen-phen may have made some people's blood serotonin levels rise
dangerously too, because fenfluramine acts like an SSRI, and the new
work found evidence that phentermine is an MAO inhibitor, the
researchers said. They noted that a rare disorder that produces high
serotonin levels can lead to heart-valve damage and the lung problem.
So fen-phen may have produced those problems in susceptible people by
hindering both mechanisms for controlling serotonin, the researchers
suggested.

It's worth investigating whether phentermine plus Prozac might pose a
similar risk, Maher said.

Maher said studies from the 1970s indicated phentermine was an MAO
inhibitor, but that it's not classified that way in standard texts or
the drug's labeling. Medeva Pharmaceuticals said the only 1970s report
it could find was rat research indicating phentermine was far too weak
an inhibitor to be hazardous in people.

Maher's study also indicated that the over-the-counter drug
ingredients were MAO inhibitors. But Joe Doss, spokesman for the
Nonprescription Drug Manufacturers Association, said animal studies
suggested their inhibiting action is far too weak to pose a potential
hazard at the doses people use.