Serzone Side Effects and Potential Interactions

Public Citizen Petitions FDA to Ban Serzone

In response to reports of liver damage and liver failure worldwide, the consumer advocacy group Public Citizen petitioned the FDA to remove Serzone (nefazodone) from the market on March 6, 2003. The petition cites the following as conclusive evidence that more than a black box warning is needed to protect the public from the dangers of Serzone:

• Bristol-Myers Squibb voluntarily withdrew nefazodone from the European market on January 8, 2003
• Public Citizen analysis, based on adverse reaction reports to the FDA, estimated that Serzone was associated with "at least 53 cases of liver injury, including 21 cases of liver failure from which 11 people died"
• Bristol-Myers Squibb acknowledged a total of 28 reports of liver failure leading to necrosis or death
• Australian reports in 1998 of hepatic dysfunction, cases of jaundice, and a liver biopsy being required for one patient following drug-induced hepatitis
• Reports in the FDA adverse events database of patients requiring liver transplants
• Independent Spanish research report evidence that of 13 antidepressants studied, Serzone had the highest incidence of hepatic injury
• Numerous advisories and Dear Doctor letters issued by Bristol-Myers

According to the petition, the potential dangers of Serzone have not been made clear enough to patients or prescribing doctors:

One of the reasons for the increased toxicity of nefazodone is that it is both metabolized by and inhibits a key enzyme in the liver that detoxifies drugs (cytochrome P450 3A4). CYP3A4 is thought to be involved in the metabolism of about 50% of all the drugs currently prescribed. Thus, any change in the activity of this enzyme is a key predictor of drug responsiveness and toxicity both for nefazodone itself and any drugs administered simultaneously.

Because of CYP3A4 inhibition, nefazodone can cause dramatic increases in plasma levels of other drugs that rely on CYP3A4 for their removal from the body... There are also warnings in the nefazodone label of many other dangerous drug interactions: alprazolam (Xanax), triazolam (Halcion), cisapride (Propulsid), pimozide (Orap), fluoxetine (Prozac), haloperidol (Haldol), desipramine (Norpramine), carbamazepine (Tegretol), monoamine oxidase inhibitors, 'general anesthetics and other CNS-active drugs,' digoxin, HMG-CoA reductase inhibitors (statins), alcohol, and immunosuppressive agents. In addition, by inhibiting its own metabolism, nefazodone can increase its own concentration with potentially toxic results.

There is no rationale for allowing Serzone to remain on the market, concludes Public Citizen in its petition.