RESEARCHERS: MIXING PROZAC, DIET DRUGS RISKY

Combination may pose the same dangers as `fen-phen,' they warn

BOSTON -- Researchers think they've discovered why the discredited
diet-drug combination called ``fen-phen'' apparently caused heart-valve
damage in some users -- and warn that other widely used but unsuspected
drug combinations may pose the same danger.

Millions of patients on daily Prozac and related antidepressants may be at
risk, they said Thursday in interviews, if patients also take the diet drug
phentermine or possibly even over-the-counter cold remedies such as Sudafed
and the appetite suppressant Accutrim.

Many weight-loss clinics started prescribing Prozac and related drugs along
with phentermine, a combination popularly called ``phen-Pro,'' when the
fen-phen regimen came under suspicion last year as the cause of heart-valve
damage.

The manufacturers of Redux or dexfenfluoramine, the ``fen'' in fen-phen,
withdrew it from the market a year ago under pressure from the U.S. Food
and Drug Administration. Phentermine, the other half of the combination,
remains on the market.

The new data, to be presented in Paris next week at the International
Congress on Obesity, show that serotonin levels rose in the blood of normal
volunteers given two different doses of phentermine. The reason, the
researchers said, is that phentermine blocks an enzyme called monoamine
oxidase, or MAO, which is the body's principal mechanism for clearing
serotonin from the bloodstream.

Redux blocks the ability of blood cells called platelets to soak up excess
serotonin. So the combination apparently destroys some patients' ability to
control serotonin blood levels.

Too much serotonin damages heart valves and blood vessels in the lung,
which can lead to a potentially fatal disorder known as primary pulmonary
hypertension.

``If physicians had known that phentermine inhibits MAO, I believe they
never would have prescribed the two drugs together,'' said Timothy J. Maher
of the Massachusetts College of Pharmacy, principal author of the new
report.

The Boston researchers said the FDA should determine whether new warnings
or drug label changes are necessary, for phentermine and for other
MAO-blocking drugs.

``I think we need some guidance from the FDA,'' said Richard J. Wurtman,
co-inventor of Redux and a co-author of the new study along with Ismail H.
Ulus of the University of Uludag in Turkey. ``The fact that phentermine is
a MAO inhibitor should have been stated on the label.''

Wurtman said a number of drugs inhibit MAO. For instance, the researchers
called for study of pseudoephedrine in the cold remedy Sudafed and the
phenylpropanolamine found in Accutrim. Maher said the herbs St. John's wort
and ma huang, both of which are taken for mood elevation and weight loss,
may also inhibit MAO.

Dr. Robert Kushner, a weight-loss specialist at Northwestern Memorial
Hospital in Chicago, called it ``foolhardy'' to combine phentermine with
Prozac-like drugs without thorough studies.

``The finding that phentermine is an MAO inhibitor is big news with
important public-health implications,'' Kushner said.

1997 - 1998 Mercury Center.

Checked-by: Joel W. Johnson