Nefazodone (Serzone®, Bristol Myers Squibb), a phenylpiperazine antidepressant, was licensed in Singapore in 1996 and is indicated for the treatment of depression, including depression accompanied by anxiety or sleep disturbances. It inhibits re-uptake of serotonin and also selectively blocks serotonin receptors.

As of December 2002, worldwide data shows that there have been 28 reports of liver failure, 15 of which resulted in deaths. These were suspected to be associated with nefazodone since it became available in 1994.

In January 2002, the US FDA added a Black Box Warning and strengthened the warnings label for Serzone® to include the reports of liver failure. The reported rate in the US is about 1 case of liver failure resulting in death or transplant per 250,000 - 300,000 patient-years of Serzone® treatment.

In January 2003, Bristol Myers Squibb announced the decision to voluntarily withdraw nefazodone in all European countries for commercial reasons. The drug continues to be available in other countries such as the US and Australia.

The local package insert for Serzone® has been amended in February 2002 to include the black box and warning on hepatic adverse effect:

• Nefazodone is not recommended for use in patients with acute liver disease or elevated baseline serum transaminases.
• Patients should be advised to be alert for signs and symptoms of liver dysfunction, and to report them to their doctor immediately if they occur.
• Nefazodone should be discontinued if signs or symptoms suggest liver failure, or if patient develops evidence of hepatocellular injury. Such patients should be assumed to be at increased risk of developing liver injury if nefazodone is restarted, and therefore this should not be considered.

The PV Unit is closely monitoring the safety of nefazodone and the measures taken by the other regulatory agencies such as those in the US and Australia. Healthcare professionals are encouraged to report every case of suspected ADRs of nefazodone to the PV Unit.