The Food and Drug Administration has linked the antibiotic Trovan to 14 cases of acute liver failure and six deaths, and warned doctors yesterday to limit its use to patients suffering from infections serious enough to require hospitalization.
"In general, therapy with Trovan should not continue for longer than 14 days," the FDA said in an advisory, and should be discontinued "sooner if the patient experiences any clinical signs of liver dysfunction, including fatigue, loss of appetite, yellowing of the skin and eyes, severe stomach pain . . . or dark urine."
The advisory said Pfizer Inc., which makes Trovan, has agreed to halt distribution of the drug except to hospitals and nursing homes, and "will be communicating in the near future" with pharmacists about possibly returning their inventories.
Pfizer's senior vice president, Joe Feczko, said the company has a "difference of opinion" over reports of liver problems associated with Trovan, but "believes it prudent" to ask doctors to "limit voluntarily" the use of the drug while further analysis is underway.
The use of Trovan, one of several antibiotics known as quinolones, was approved by the FDA in February 1998 as a treatment for 14 types of infections ranging from peritonitis to sinus trouble. An estimated 2.5 million prescriptions have been written for the drug since it was approved, the FDA said.
Sandra Kweder, the acting director of the FDA's Office of Drug Evaluation, said pre-approval testing showed "some signs of liver toxicity, but they weren't serious or unusual."
"It has unique properties," Kweder said. "It has a very broad spectrum of activity," and is extremely useful in treating serious infections whose exact cause may not be known.
But Public Citizen's Health Research Group, a consumer advocacy organization, charged that pre-approval testing of Trovan had shown unacceptably high levels of liver toxicity. Last week, it petitioned the FDA to ban the drug altogether.
"There really is nothing unique about Trovan," Public Citizen attorney Peter Lurie said yesterday. "This is the ninth quinolone on the market, so there were alternatives."
Kweder said the FDA decided to act yesterday after reports of deaths linked to Trovan started to come in "over the last couple of months." The FDA said it knew of 14 cases of acute liver failure associated with Trovan. Five patients died of liver failure, as did one of four liver transplant patients.
If doctors heed the FDA's warning, Kweder predicted that oral use of Trovan would all but end. Instead of having 14 uses, the drug would be administered to treat only five life- or limb-threatening conditions: two kinds of pneumonia; serious abdominal infections; serious gynecological and pelvic infections; and complicated skin and soft-tissue infections.
In addition, the FDA urged doctors to confine the use of Trovan to patients who begin their treatments in hospitals or nursing homes, and to proceed only after they have concluded "that the benefit of the product outweighs the risks."