FDA approval of Serzone ‘endangering lives of patients’

The consumer advocacy group Public Citizen has petitioned the U.S. Food and Drug Administration (FDA) to remove from the market the popular antidepressant nefazodone, manufactured by Bristol-Myers Squibb. Nefazodone, marketed under the name “Serzone,” has no unique therapeutic benefit and has led to at least 11 deaths in the United States from liver toxicity, government records show.

In January 2003, the manufacturer removed nefazodone from the European market after the Swedish Medical Products Agency announced that it would require a warning on the drug’s label about the potential for liver toxicity. In the United States , more than 4.5 million prescriptions were filled for Serzone in 2001.

"There is no good reason to keep this drug on the market. It is no more effective than other antidepressants, and it presents a unique health hazard for patients," said Sidney Wolfe, M.D., director of Public Citizen’s Health Research Group.

In its analysis of adverse event reports from the FDA, Public Citizen found that from 1994, when it was first marketed, to the spring of 2002, nefazodone was associated with at lease 53 cases of liver injury, including 21 cases of liver failure and 11 deaths. Worldwide, Bristol-Myers Squibb itself acknowledges 28 reports of liver failure, including 18 deaths.

Additionally, while nefazodone is not more effective at treating depression than older drugs, according to research by the federal Agency for Health Care Policy and Research, it is uniquely dangerous to patients. Further, periodic liver testing has not been shown to prevent injury and there is no way to predict which patients are at higher risk for liver damage.

An analysis by researchers in Spain found that, of 13 antidepressants, nefazodone has the highest incidence of liver injury – seven to 22 times that of the other antidepressants.

The liver toxicity dangers of nefazodone are compounded by the fact that it inhibits a key enzyme that is involved in the detoxification of about half of all prescribed drugs, so nefazodone increases the toxicity dangers of other drugs a patient is taking simultaneously. Also, by inhibiting this enzyme, nefazodone can increase its own concentration with potentially toxic results.

The FDA in December 2001 notified Bristol-Myers Squibb that it must add a "black box" warning to the package insert for nefazodone warning of life-threatening liver damage and recommending that physicians advise their patients to be aware of signs of liver problems.

But the black box warning does not go far enough to protect patients, particularly because the labeling presented a confused message, the petition said. Although the black box warning recommends monitoring of patients’ liver function, a second notice on the label downplays the necessity of such tests.

In the February 2002 issue of its monthly newsletter about drug safety, Worst Pills, Best Pills News, Public Citizen labeled nefazodone as a "Do Not Use" drug because of its known liver toxicity and recommended that anyone who had been taking it consider switching to a safer antidepressant. The petition and articles from the newsletter about Serzone are posted online at www.worstpills.org, a drug information service launched this winter by Public Citizen.

"Our readers have known for a year to steer clear of this drug, and now patients in Europe are protected, too," Dr. Wolfe said. "The FDA is endangering the lives of patients in this country every day that it allows nefazodone to remain on the market."

SOURCE: Public Citizen news release, March 6, 2003 .