The Real Controversy Behind "Fen/Phen"

Barely a year and a half after approving the use of Redux for weight loss, the FDA warned patients to stop using it. The alert included both dexfenfluramine, marketed as Redux, and fenfluramine, sold as Pondimin and often prescribed with phentermine to form the "fen/phen" duo. Wyeth-Ayerst Laboratories, the manufacturer of both drugs, immediately pulled them from the market.

Why? Because a sharp-eyed lab technician in Fargo, North Dakota, noticed heart valve irregularities in several women who had been using one of the diet drugs. A subsequent study of 291 diet pill users found 30 percent had this heart problem. Most had used the popular fen/phen" combo, but of the 20 Redux users, six showed signs of the valve problem which would require surgery to correct -- about one Redux user out of three.

But since morbid obesity also caused death from heart disease and diabetes, the FDA concluded that the benefits outweighed the risks. Thry assumed that Redux would be used only by those weighing thirty percent above their healthy weight -- an unrealistic assumption in this weight-obsessed society. Indeed, Redux was sometimes prescribed over the phone to anyone who wanted to lose a few pounds.

The FDA panel -- or at least, some of its members -- also heard testimony from Dr. George Ricaurte of John Hopkins University Medical School, who found that Redux and Pondimin both destroyed serotonin nerve endings in the brains of several species of monkeys. Interneuron, a Boston based company that holds the patent on Redux, maintained that the doses were ten times the human dose. Ricaurte insists that the monkeys got the equivalent of the average human dose per pound of body weight.

Two of the eleven panelists who voted to approve were not present when this testimony was presented. And although no reports of human brain damage have yet surfaced, Ricaurte feels that a more rigorous study of the possible brain and lung damage would have revealed the heart valve damage.

Meanwhile, three million Americans and 10 million Europeans have used at least one of the drugs. If even half took them for 6 months, possibly more than 2 million people now suffer from serious heart problems.

The lawsuit, filed on November 11, alleges that Interneuron "publicly disseminated materially false and misleading statements concerning the prospects and safety of its only commercially salable drug, Redux, which resulted in artificially inflating the stock price."

Drug user lawsuits are claiming that Wyeth and Interneuron knew of the heart valve problems in March of 1997 but didn't withdraw the drug until after the FDA's September, 1997 warning. Indeed, in an August, 1997 diet drug debate on the Online Newshour, Wurtman wrote that "the clinical evidence is this is one of the safest drugs to come along in a long time."

The FDA admits to receiving a handful of reports of heart valve damage in 1996, but didn't consider it a pattern. While it costs a drug company upwards of $200 million and many years to gain drug approval, the FDA spends only $140,000 a year on its "med-Watch" program to which doctors and pharmaceutical companies report side effects of FDA approved drugs.

This fiasco will probably leave a million Americans with heart valve damage. All long-time users of either Redux or fen/phen have been advised to undergo expensive echo cardiogram testing to determine if the heart valve needs surgical replacement.

Meanwhile, the FDA has approved another diet drug called sibutramine which Knoll Pharmaceutical will market as Meridia. Once again, the FDA has ignored the warnings of its scientific advisory council which thought the drug too risky. Meridia works by a different mechanism than the two drugs recently recalled. Redux and fen/phen work by increasing the release of the neurotransmitter serotonin, while Meridia just prevents the serotonin already present in the brain from being broken down and recycled.

Studies on Meridia have shown no sign of heart valve damage or pulmonary hypertension, both serious side effects of the recalled drugs. But Meridia has been found to increase blood pressure in some users, a potential danger for those with hypertension, heart disease or irregular heartbeat or anyone who has had a stroke. Meridia should reach the market in 1998. The company has stressed that it should be used only for those with serious obesity -- and not for cosmetic reasons.