Nefazodone liver failure with

No risk factor yet predicts who will develop irreversible liver failure with nefazodone and no clinical strategy. 

A black box warning for life-threatening liver failure was added to the prescribing information for nefazodone. Treatment with nefazodone should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. 

Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,000 patient-years of nefazodone treatment. 

There have been several reports of serious hepatotoxicity associated with nefazodone, in some cases leading to liver failure. 

Four women, aged 16-73 years, developed catastrophic liver failure while taking nefazodone (8,9). Nefazodone was given for 14—28 weeks before the onset of symptoms. The cases had similar histological appearances, with prominent centrilobular necrosis. Three died, one survived after liver transplantation, and one improved sufficiently to obviate the need for transplantation. The duration of nefazodone treatment before the onset of symptoms was 7-28 weeks. The patients had no history of liver disease and other causes were excluded as far as possible. 

A 52-year-old man with a 10-day history of fatigue and jaundice had been taking nefazodone (300 mg/day) for depression for about 6 weeks. Biochemical investigations showed acute liver failure. Infective hepatitis and immune disorders were excluded. He failed to respond to medical treatment, and hepatic transplantation was performed. Histological examination of the liver showed parenchymal necrosis, particularly in centrilobular areas, together with lymphocytic infiltration (10). 

Lucena MI, Andrade RJ, Gomez-Outes A, Rubio M, Cabello MR. Acute liver failure after treatment with nefazodone. Dig Dis Sci 1999 44(12) 2577-9. 

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