Originally created 08/29/98

Diet drug, Prozac combo may be risky



People who combine the diet drug phentermine with Prozac, a strategy touted by some as safer than the "fen-phen" combination, may be at risk for the very hazard they're trying to avoid, a study suggests.

The study authors also say fen-phen, which was associated with heart valve damage and a serious lung problem, wouldn't have been prescribed in the first place if phentermine's label reflected information reported in the 1970s.

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

Wurtman said people taking combinations cited in his study should discuss it with their physicians.

The study doesn't document any harm from the drug combinations and gives no direct evidence of risk. It focused 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. Prozac's maker, Eli Lilly & Co., said last year that it did not support combining Prozac with phentermine, but obesity experts said some doctors are prescribing the combination anyway.

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. A Medeva spokeswoman said the company does not recommend using its product with Prozac or similar drugs.

The new work is to be presented next 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 the rare lung problem, primary pulmonary hypertension.

It's worth investigating whether phentermine plus a Prozac-like drug might pose a risk of such problems by boosting blood levels of the substance serotonin dangerously high, Maher said.

He said research reported in the 1970s indicated phentermine was an MAO inhibitor, which would indicate it would be hazardous to combine with fenfluramine or Prozac-like drugs. But Medeva said the only 1970s report it could find on the topic was rat research indicating phentermine was far too weak an inhibitor to be hazardous in people.

Maher's study also implicated the over-the-counter drug ingredients as MAO inhibitors through test-tube studies, suggesting a hazard when combined with drugs like Prozac. But Joe Doss, spokesman for the Nonprescription Drug Manufacturers Association, said animal studies suggested their action is far too weak to pose a risk at the doses people use.

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