The antidepressant Serzone, about to be pulled off the market in Canada and long gone in Europe, should be banned in the United States because of cases of deadly liver failure, a consumer advocacy group told the government Wednesday.
It’s impossible to predict which patient will develop liver failure, an unacceptable risk considering Serzone works no better than older antidepressants that don’t come with that side effect, Dr. Sidney Wolfe of Public Citizen told the Food and Drug Administration.
The United States is “lagging behind other countries in drug safety,” Wolfe wrote the FDA. “Remove this drug from the market before more people are injured or killed.”
Wolfe’s petition details 55 cases of liver failure, including 20 deaths, and another 39 cases of less severe liver injury reported to the FDA since Serzone began selling in 1994. Rather than trickling off as the years passed, side-effect reports are increasing since the FDA two years ago placed its strongest possible warning on Serzone’s label to alert patients to the risk, Wolfe said.
The FDA estimates its monitoring system counts fewer than 10 percent of the side effects caused by medications, meaning far more Serzone users may have been harmed, Wolfe said.
Public Citizen first asked FDA to ban Serzone in March, and the agency refused. Wednesday, the consumer advocacy group asked again, citing international concern:
Earlier this month, Canadian authorities announced Serzone would be pulled off the market, saying, “to date, no risk factor to predict patients who will develop irreversible liver failure has been identified.” Nor have traditional measures, like routine liver tests, reduced that risk, Health Canada concluded.
To give patients time to switch to another medicine, Serzone sales in Canada will end on Nov. 27.
The World Health Organization and Health Canada recently compared a number of popular antidepressants and found only Serzone linked to an increased risk for serious liver injury, Wolfe said.
While the FDA will examine Wolfe’s petition, for now it contends that warning patients about the risk is adequate, particularly as liver failure is a rare risk.
“Depression is a serious illness. Not all patients respond to all drugs,” said Dr. Thomas Laughren, FDA’s antidepressant chief. “We think clinicians and patients should have options.”
Manufacturer Bristol-Myers Squibb Co. says cases of liver failure among Serzone users are very rare and side-effect rates haven’t changed, suggesting no need for renewed concern.
“We respectfully disagreed with Health Canada” about the liver risk, but ultimately bowed to regulators’ wishes to end sales there, said Bristol-Myers spokesman Rob Hutchinson. Here, “there is no new data that would alter the risk-benefit assessment of the product.”
Bristol-Myers quit selling Serzone in Europe last January, saying it made the decision because of low sales, not safety questions. But some foreign regulators cited concern about fatal liver failure at the time, and Wolfe said sales in Scandinavia and Turkey have since ended, too.
Wolfe said Serzone, known chemically as nefazodone, inhibits an enzyme key to drug metabolism, allowing the antidepressant to sometimes build to toxic levels in the liver. That enzyme also metabolizes numerous other drugs, meaning patients taking multiple medications could be at higher risk, he said.