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New Heart Dangers Seen With Diet Drug

Monday, August 31, 1998

Research: Phentermine, half of the once-popular fen-phen cocktail, may produce valve defects when mixed with some other drugs.

By THOMAS H. MAUGH II, Times Medical Writer

Combining the diet drug phentermine with a variety of other drugs, such as Prozac, Sudafed and Accutrim, has the potential to produce the same type of heart-valve defects previously seen in dieters who used the widely touted fen-phen combination of drugs, MIT researchers warned.
     Such combinations of drugs can lead to high levels of serotonin in the blood, a condition that has previously been shown to damage blood vessels and produce heart-valve defects, said Dr. Richard J. Wurtman, director of MIT's Clinical Research Center. Physicians have not yet found any heart-valve damage caused by such combinations, he conceded, but the potential exists.
     Most physicians are not aware of the possibility of such problems because they do not know that phentermine is part of a class of drugs called monoamine oxidase (MAO) inhibitors. That fact is not stated on phentermine's label and is not indicated in the Physicians' Desk Reference and other sources used by doctors to obtain information about drugs, according to Wurtman and his colleagues from MIT and the Massachusetts College of Pharmacy and Allied Health Sciences.
     Phentermine was not discovered to be an MAO inhibitor until long after the drug was placed on the market, they said, and the label has never been revised to reflect that fact. Had more physicians known it, the drug most likely would never have been prescribed in combination with the drug fenfluramine.
     That combination, widely known as fen-phen, was very effective at reducing appetite, but heart-valve damage was found in so many patients that fenfluramine was withdrawn from the market in 1997.
     Phentermine and the MAO inhibitors work by different mechanisms, but the effect of both is to increase the level of serotonin in the blood. Fenfluramine blocks the uptake of serotonin by platelets, which use it for clotting. MAO inhibitors block the ability of monoamine oxidase to destroy serotonin in the blood.
     Taken alone, these drugs do not produce dangerously high levels of serotonin. Together, however, they can allow serotonin levels to become quite high.
     Antidepressants, such as Prozac, Zoloft and Paxil, all have labels warning they should not be used in conjunction with MAO inhibitors.
     Over-the-counter cold remedies and diet pills also contain drugs that increase blood-serotonin levels. Those compounds include pseudoephedrine (found in Sudafed and a broad variety of other decongestants), phenylpropanolamine (found in Accutrim as well as decongestants) and ephedrine.
     Herbs such as St. John's wort and ma huang--both taken for mood elevation and weight loss--may also be MAO inhibitors, according to Timothy J. Maher, also of the Massachusetts College of Pharmacy and Allied Health Sciences.
     The team's findings will be presented Wednesday at the International Congress on Obesity in Paris.