Two diabetics taking the new oral insulin-enhancing drug Avandia had severe negative reactions to the medication, doctors reported.
The two Pennsylvania men suffered liver failure or poisoning after several weeks on the drug, and recovered after it was discontinued, the doctors wrote in today's issue of the Annals of Internal Medicine.
The Food and Drug Administration and the drug's manufacturer, SmithKline Beecham, were informed of the reactions, and both concluded the drug remains safe and effective. A spokesman for SmithKline said it was unclear whether the two cases had anything to do with Avandia.
The director of the FDA's Office of Drug Evaluation, John Jenkins, said the agency has received other reports of liver toxicity related to use of Avandia from doctors and patients, but that none had been confirmed.
"Based on what we have seen, we are not contemplating any changes to the labeling, or any warning to patients or physicians," he said.
Another popular oral medication for diabetics, Rezulin, has been associated with severe liver failure in dozens, if not hundreds of diabetics since it was approved in 1997. Both Rezulin and Avandia are thiazolidinediones, a class of compounds that helps diabetics by boosting the body's ability to absorb insulin, thereby lowering blood-sugar levels.
According to one of the journal authors, Robert H. Diamond of the Hospital of the University of Pennsylvania, the case he described occurred soon after Avandia was approved by the FDA in May. He was especially concerned when he saw what appeared to be liver failure in a diabetic taking Avandia because of the history of liver toxicity in Rezulin users, he said.
"We wanted to put the case study out there because there is the potential that there could be this toxicity again from the drug," Diamond said. "We wanted clinicians to be aware of this, and to engage in a dialogue about it."
SmithKline spokesman Brian Jones said his company believes the two cases do not necessarily point to problems with Avandia. Regarding one of the Pennsylvania cases, Jones said SmithKline researchers and three outside experts concluded the man's liver injury was the result of a heart problem rather than Avandia.
"The cases remain unresolved for us; we do not believe there is conclusive evidence to link the problems to Avandia," he said. "But the key point is that there have been no reports of death directly associated with Avandia, and both of these patients [in the journal article] resolved successfully."
Both Avandia and Rezulin have been popular with the estimated 14 million diabetics in the United States, most of whom have what is known as Type 2 diabetes. It has been especially useful for diabetics who did not respond well to other treatments. Avandia is used by more than 350,000 diabetics in the United States, according to SmithKline.
Because of the adverse reactions to Rezulin, the FDA has required stricter monitoring of patients taking it. The drug was taken off the market in Britain in 1997, and the number of prescriptions written for Rezulin in the United States declined more than 10 percent over the last year, according to IMS Health, a company that gathers pharmaceutical statistics.
The arrival of Avandia had been eagerly anticipated last year because it did not cause any liver damage in studies involving more than 4,000 patients before it was approved. FDA officials say it is common for some patients taking a new drug on the market to have unexpected reactions.