DO NOT USE! Dangerous Antidepressant Nefazodone (SERZONE) Withdrawn From The Market In Canada HRG Files Second Petition to Ban Nefazadone

Nefazodone (SERZONE), a dangerous antidepressant long linked to liver toxicity and deaths, was withdrawn from the Canadian market effective November 27, 2003. The drug is produced by Bristol-Myers Squibb in both Canada and the U.S.

In the notification of the drug’s withdrawal it was stated “...no risk factor to predict patients who will develop irreversible liver failure with nefazodone has been identified,” and that “...no clinical strategy, such as routine liver function tests, could be identified to reduce the risk of liver failure.” In other words, there is no way to ensure that this drug can be used safely.

Since its introduction in Canada in 1994, nefazodone has been associated with liver adverse events such as jaundice, hepatitis (inflammation of the liver) and hepatocellular necrosis (liver cell death) in patients receiving the drug. As of December 2002, there were 51 Canadian reports of liver toxicity associated with the use of nefazodone. Two patients required liver transplantation, one of whom died. In the Canadian reports, liver injury occurred as early as a few weeks after starting the drug or after continuous use for up to three years.

Serzone’s U.S. professional product labeling, or package insert, states that “The physician may consider the value of liver function testing.” It also adds that, “Periodic serum transaminase [liver function] testing has not been proven to prevent serious injury.” As a result, there is no means available to reliably monitor and protect patients’ health.

Nefazodone was listed as a Do Not Use drug in February 2002 after the Food and Drug Administration (FDA) required a black box warning in the drug’s professional product labeling or package insert about its liver toxicity (see Worst Pills, Best Pills News February 2002). A black box warning is the strongest type of warning that the FDA can require on a drug’s labeling.

The addition of the black box warning had only a modest effect on the prescribing of this dangerous drug. In 2001, over 4.5 million prescriptions for nafazodone were dispensed in U.S. pharmacies. The number dropped to approximately 2.8 million in 2002. Unfortunately, there is no requirement that patients see black box warnings before they receive a drug and the warning has not diminished the occurrence of life-threatening liver damage.

We warned readers again about the toxicity of the drug in March 2003 when Bristol-Myers Squibb halted the sale of nefazodone in all European countries after national drug regulatory authorities became concerned about its safety (see Worst Pills, Best Pills News March 2003). Turkish authorities banned the drug in April 2003.

On March 6, 2003, we petitioned the FDA to immediately remove nefazodone from the market. At the time, our analysis based on adverse reaction reports to the FDA revealed that from 1994, when first marketed in the U.S., through the first quarter of 2002, nefazodone was associated with at least 53 cases of liver injury, including 21 cases of liver failure from which 11 people died.

Because of the failure of the FDA to take action on our petition and the growing number of reports of liver toxicity associated with the use of nefazodone, we filed an amended petition with the FDA on October 29, 2003 again asking that the drug be immediately removed from the market. From April 1, 2002 through May 12, 2003 there have been an additional nine deaths related to the use of nefazodone reported to the FDA. This brings the total to at least 20 deaths linked to the use of nefazodone.

The numbers of injuries and deaths reported to the FDA must be placed in their proper context. Because the safety reporting system is voluntary, the FDA estimates that only one in ten serious adverse drug reactions is ever reported.

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

The FDA’s failure to ban this dangerous drug is incomprehensible. There are currently two dozen antidepressants, in at least four pharmacologic classes, available on the market in the U.S. Not one of these drugs, including nefazodone, has been shown to be superior to another in the treatment of depression in controlled clinical trials. The best way to differentiate one from another, as is the case with most families of drugs which have similar efficacy, is on the basis of their known toxicities. Clearly, nefazodone possesses a known significant toxicity, the possibility of liver failure and death, and should be removed from the market immediately.

The Canadians have taken action before the FDA on several important drug safety issues and should be commended. However, the Canadian government’s decision to allow Bristol-Myers Squibb to continue selling nefazodone until the end of November 2003 is dangerous and inexcusable.

What You Can Do

If you have never before been treated with an antidepressant, there is no medical reason why you should be started on nefazodone.

If you are currently taking nefazodone, discuss with your doctor switching to one of the numerous other, safer antidepressant drugs on the market.