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The Spokesman-Review Newspaper
Spokane, Washington  Est. May 19, 1883

‘Fen-Phen’ Suspicions Not Disclosed Reports To Fda Suspect Drugs In At Least 70 Deaths Since ‘74

Kathleen Kerr Newsday

Two diet drugs sometimes used together as “fen-phen” were named as suspect medications in at least 70 deaths reported to the Food and Drug Administration between 1974 and 1997, but the agency never disclosed those reports publicly.

FDA records obtained under several Freedom of Information Act requests filed by Newsday this summer reveal for the first time that people outside the agency - drug manufacturers, pharmacists and doctors - filed at least 70 “adverse reaction” reports that detailed deaths in patients who took the drugs, phentermine and fenfluramine, either in combination or separately.

Reports can be filed by anyone suspecting a problem with a drug.

FDA officials said nothing in the individual reports triggered an investigation under the FDA’s drug-surveillance program. There are no specific criteria to trigger a retrospective investigation of drug problems, the officials said. Rather, each complaint is reviewed separately on its own merits and a number of complaints about one drug could touch off further evaluation. Their preliminary evaluation of the reports did not identify the drugs specifically as a cause of death, the officials said, or rule them out.

But critics say the agency needs a system that automatically looks beyond individual reports in order to establish whether patterns exist that may signal problems with drugs like fenfluramine, which was removed from the market in September after it was connected to reports of heart-valve damage, including one recently revealed death.

“My guess is if people knew about the adverse-reaction reports, then things could be found out sooner,” said Dr. Louis Aronne, a specialist in obesity treatment at New York Hospital-Cornell Medical Center in Manhattan. “If instead of reporting something in a blind manner, you could see what had been reported before, you could know if what you’re seeing (in a patient) is significant or not.”

Additionally, Newsday has learned that the FDA sometimes asks manufacturers to investigate reports of adverse reactions to their own products. FDA officials said their 14 safety evaluators can’t handle all the drug-reaction reports the agency receives - 170,000 in 1996 alone.

“Rarely do you get reports where it’s sort of crystal clear,” said Dr. David Graham, acting chief of epidemiology in the FDA Division of Pharmacovigilance and Epidemiology. “Usually the patients who are taking various drugs have illness and diseases.”

But Graham admitted that because warning flags seldom are hoisted in individual cases, no automatic system is in place to detect a pattern of problems linked to any specific drug, once it receives final FDA approval.

Graham said the FDA makes a diligent effort to evaluate all drug-reaction reports.

The FDA does look back on occasion at drug-reaction reports in cases where a problem comes to the agency’s attention, officials said. Safety evaluators check information at their disposal concerning the drug’s safety record and they also consult a Medicare database for possible known problems.

People familiar with the FDA drug-monitoring system said that if officials had looked back at the reports in order to establish patterns, it might have found the heart-valve problem sooner. Others, however, said the FDA does a good job, given its resources, and said perhaps what is needed to monitor drug safety is a separate, nongovernment body - also without industry ties.

Because adverse drug-reaction reports are preliminary observations and not final determinations, Newsday asked the FDA for its subsequent findings regarding the reports on phentermine and fenfluramine. The FDA provided no records.

As the number of reported deaths and other serious reactions to phentermine and fenfluramine grew over the years, the FDA apparently conducted initial reviews and filed them - but did not do a retrospective look at the reports as they accumulated.

And as the reports continued to land on FDA desks, unknowing diet doctors kept prescribing the drugs to patients, many regarding them as a miraculous elixir in the battle against obesity.

Then, in July, the Mayo Clinic and the MeritCare Medical Center of Fargo, N.D., revealed findings linking fen-phen and heart-valve disease in women with an average age of 43. And on Sept. 15, Wyeth-Ayerst Laboratories took fenfluramine - which goes by the trade name Pondimin - off the market along with its sister diet drug, Redux. Redux, the trade name for dexfenfluramine, is chemically related to Pondimin. The other half of the fen-phen duo, phentermine, is marketed under several trade names and remains on pharmacy shelves. About 4 million Americans have taken Pondimin since 1973 and more than 2 million have taken Redux since June 1996, according to Wyeth-Ayerst Laboratories.