- October 29 - New reports of deaths and severe injuries from liver failure in patients taking the antidepressant Serzone (nefazodone) require that the U.S. Food and Drug Administration (FDA) act immediately to protect U.S. patients, Public Citizen said today. Public Citizen submitted a supplement containing new data to its March 2003 petition requesting the withdrawal of this uniquely dangerous drug from the market.
Just this month, Canada announced it would remove from the market the liver-toxic drug due to its association with "hepatic adverse events such as jaundice, hepatitis and hepatocellular necrosis." A "Dear Health Care Professional" letter posted on the Health Canada Web site makes an irrefutable case for removing the drug, Public Citizen said in its supplement.
Bristol-Myers Squibb manufactures nefazodone and markets it under the name Serzone. More than 2.8 million prescriptions were filled for Serzone in the United States in 2002.
In its original petition, Public Citizen cited 21 cases of liver failure and 11 deaths from 1994, when nefazodone was first marketed, to the spring of 2002. A new analysis of the FDA Adverse Event Reports Database found that, just from April 1, 2002, through May 12, 2003, there were 33 additional reports of liver failure including nine deaths for a total of 55 patients with liver failure, including 20 deaths.
"Typically, it is estimated that only about 10 percent of cases are reported, meaning that potentially hundreds of people have died from this drug and hundreds more have been injured," said Dr. Sidney Wolfe, director of Public Citizens Health Research Group. "This drug is no more effective than other antidepressants, but is uniquely and unpredictably toxic."
The liver toxicity dangers of nefazodone are compounded by the fact that it inhibits a key enzyme that is involved in the metabolism of about half of all prescribed drugs, so nefazodone increases the toxicity dangers of other drugs a patient may be taking. 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. This strategy has clearly failed to curb the cases of liver failure and death caused by the drug.
However, the "Dear Health Care Professional" letter posted on the Health Canada Web site makes it clear that it is not possible to manage this drug safely, saying, "To date, no risk factor to predict patients who will develop irreversible liver failure with nefazodone [Serzone] has been identified. Also, no clinical strategy, such as routine liver function tests, could be identified to reduce the risk of liver failure."
"Once again, the United States is lagging behind other countries in drug safety. Any delay by the FDA in removing this drug from the market will cause more patients to be injured or killed," Wolfe said.
Click here to view a copy of Public Citizens supplementary petition. Click here to view the original petition.