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Unforeseen Side Effects Ruined One Blockbuster

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August 27, 2000, Section 3, Page 11Buy Reprints
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PFIZER'S marketers were turning an antibiotic called Trovan into a blockbuster when misfortune struck last year.

Doctors were prescribing Trovan at a rate of 300,000 patients a month when regulators forced Pfizer to take the drug off the shelves of most pharmacies. At least 14 people taking Trovan had suffered from acute liver failure, including 6 who died.

Pfizer lost a potential billion-dollar drug -- and one that had cost hundreds of millions of dollars to develop.

The case showed how a new drug, marketed by an expert like Pfizer, could be swiftly prescribed to thousands of patients before all the side effects were known. Pfizer said its tests of Trovan had not revealed any serious problems.

All drug companies have become more adept at getting out the word about new drugs to physicians and consumers. The companies, watched eagerly by investors, are under pressure to generate strong sales as soon as a drug is introduced.

With Trovan, Wall Street analysts were betting that Pfizer could generate up to $1 billion in sales in a year.

To maximize Trovan's potential, Pfizer had conducted clinical studies -- enough so that regulators had approved Trovan for 14 different uses, the largest number ever for a drug's initial approval.

When Trovan went on the market in February 1998, Pfizer's thousands of sales representatives were ready. A year later, the company said more than a million prescriptions of Trovan had been written.

But serious possible side effects that were never apparent in clinical trials surfaced quickly when the drug was prescribed widely. Patients began experiencing liver toxicity just months after the drug first became available. In July 1998, the F.D.A. asked Pfizer to add information about possible liver toxicity in the information provided in each Trovan package.

By June 9, 1999, regulators had received reports of more than 100 cases in which patients taking Trovan had suffered liver problems. That day, the F.D.A. warned doctors that Trovan should be used only in rare cases and only in hospitals. And Pfizer sent letters to doctors and pharmacies, telling them that Trovan's use was restricted. It offered to reimburse the pharmacies for any Trovan they had in stock.

But not all doctors and pharmacies immediately received the news. And some patients were given Trovan after the F.D.A.'s warning. On Jan. 19 of this year, Kenneth Madding, a machinist in Marion, Ill., received a prescription for Trovan from a local pharmacy. Mr. Madding, who was 34, had developed a lung infection after having surgery.

Mr. Madding's wife, Betty, said that her husband's condition worsened immediately after taking the drug. Five days later, he died. His wife, and the lawyers she has hired, say Trovan caused his death. Mrs. Madding filed a lawsuit on Friday.

Pfizer said on Friday that it had not seen the lawsuit and could not comment.

Dr. John F. Niblack, Pfizer's top scientist, said earlier this month that the company had argued with the F.D.A., contending that Trovan's advantages outweighed its risks.

Dr. Niblack said that all drugs had some risks associated with them. ''What if a medicine helped 9,999 people, but hurt one?'' he asked. ''What risks are we willing to accept?''

In Trovan's case, he said, the data seems to show that it hurt one patient in every 50,000.

In the clinical trials Pfizer conducted to receive F.D.A. approval, William C. Steere Jr., the chairman of Pfizer, said that there was no evidence that Trovan could cause liver problems. As in all drug trials, the patients involved are carefully screened, he said, and many with complicated health problems are ruled out. That means that some side effects do not show up until after a drug is approved.

''You put the drug in the general population, and then everyone is taking it,'' Mr. Steere said. ''We just hold our breath and wait to see if there is something unique with the drug.''

In the case of Trovan, he said, ''it turned out there was.''

A version of this article appears in print on  , Section 3, Page 11 of the National edition with the headline: Unforeseen Side Effects Ruined One Blockbuster. Order Reprints | Today’s Paper | Subscribe

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