Antidepressent
Nefazodone (SERZONE) Pulled
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 The drug was withdrawn from the Swedish market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.
Last Updated on
04/14/04
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