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Bristol-Myers Squibb of Princeton, NJ announced on January 8, 2003 that it will pull the antidepressant nefazodone (SERZONE) in all European countries where it is marketed. The drug was withdrawn from the Swedish market in early 2002 and from Denmark in December 2002 after concerns about liver toxicity. Nefazodone has been linked to liver failure and/or death in 26 patients worldwide.
In February 2002, the Food and Drug Administration (FDA) required the addition of a black box warning in the...
Bristol-Myers Squibb of Princeton, NJ announced on January 8, 2003 that it will pull the antidepressant nefazodone (SERZONE) in all European countries where it is marketed. The drug was withdrawn from the Swedish market in early 2002 and from Denmark in December 2002 after concerns about liver toxicity. Nefazodone has been linked to liver failure and/or death in 26 patients worldwide.
In February 2002, the Food and Drug Administration (FDA) required the addition of a black box warning in the drug’s professional product labeling, or “package insert,” about reports of liver toxicity in association with use of the drug. A black box warning is the strongest type of warning that the FDA can require for a prescription drug. At that time, we listed the drug as DO NOT USE (see Worst Pills, Best Pills News, February 2002).
The text of the black box warning is given below and estimates the rate of death or liver transplant due to nefazodone in the U.S. This significantly underestimates the frequency of liver damage, however, because it does not include the larger number of patients with serious nefazodone toxicity who did not die or require a liver transplant. The warning also cautions that patients with elevated liver enzyme (sometimes called serum transaminases, or abbreviated as ALT or AST) levels should not receive the drug. These liver enzyme elevations can be a sign of active liver disease. Liver enzyme elevations to levels three times the upper limit of normal or greater in patients taking nefazodone is an early sign of potential liver toxicity and the drug should be stopped.
Patients who are taking nefazodone who develop any of the following symptoms of serious liver problems should contact their prescribing physician immediately:
• Yellowing of the skin or whites of eyes (jaundice)
• Unusually dark urine
• Loss of appetite that lasts several days or longer
• Nausea
• Abdominal (lower stomach) pain
A Canadian review of reports of liver toxicity associated with the use of nefazodone was published in the May 2002 Canadian Journal of Psychiatry. From the time the drug was first marketed through November 2001, there had been 38 cases of liver injury reported to Canadian drug regulatory authorities.
Spanish physicians writing in the February 2002 issue of the Journal of Clinical Psychiatry reported that the rate of adverse drug reaction reports for liver injury associated with antidepressant use was highest with nefazodone. However, this estimate was based on only three cases of liver injury being reported to Spanish authorities.
Our review of the FDA’s adverse drug reaction database from the onset of marketing of nefazodone in the U.S. in 1994 through the first quarter of 2002, found 10 reports of death linked to liver injury associated with the use of nefazodone.
Bristol-Myers Squibb has no plans at this time to remove the drug from the market in the U.S.
What You Can Do
If you or a family member have never before been treated with an antidepressant, there is no medical reason why nefazodone should be started instead of other antidepressants.
If you or a family member are currently taking nefazodone, discuss with the prescribing physician switching to one of the numerous other, safer antidepressant drugs now on the market.
WARNING Cases of life-threatening hepatic failure have been reported in patients treated with SERZONE. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000-300,000 patient-years of SERZONE treatment. The total patient-years is a summation of each patient’s duration of exposure expressed in years. For example, 1 patient-year is equal to 2 patients each treated for 6 months, 3 patients each treated for 4 months, etc. Ordinarily, treatment with SERZONE should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. There is no evidence that pre-existing liver disease increases the likelihood of developing liver failure; however, baseline abnormalities can complicate patient monitoring. Patients should be advised to be alert for signs and symptoms of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur. SERZONE should be discontinued if clinical signs or symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels = 3 times the upper limit of normal while on SERZONE should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if SERZONE is reintroduced. Accordingly, such patients should not be considered for re-treatment. |
