oston researchers said yesterday that they have discovered why the discredited diet-drug combination called fen-phen apparently caused heart-valve damage in some users. The researchers also warned 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 yesterday 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.
Obesity specialists say the number of such patients may be legion.
Many weight-loss clinics started prescribing Prozac and related drugs with phentermine, a combination popularly called ``phen-Pro,'' when the fen-phen regimen came under suspicion last year as a possible cause of heart-valve damage.
The makers of Redux, or dexfenfluoramine, the ``fen'' in fen-phen, withdrew it from the market a year ago under pressure from the US Food and Drug Administration. Phentermine, the other half of the combination, remains on the market.
The new data, to be presented next week in Paris at the International Congress on Obesity, found that serotonin levels rose in the blood of 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 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 if 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 coauthor of the study with Ismail H. Ulus of the University of Uludag in Turkey. ``The fact that phentermine is an MAO inhibitor should have been stated on the label.''
Wurtman said that 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.
