Nefazodone Hydrochloride and Liver disease

In general, treatment with nefazodone should not be initiated in patients with active liver disease or elevated baseline serum transaminase levels. Cases of hepatic failure resulting in death or liver transplant, at an estimated rate of 1 per 250,000 to 300,000 patient-years of nefazodone treatment in the U.S. (approximately 3 to 4 times the background rate), have been reported during postmarketing use. The time to liver injury for the reported cases typically ranged from 2 weeks to 6 months of use. Dark urine and nonspecific prodromal symptoms (e.g., nausea, anorexia, malaise, gastrointestinal complaints) were reported in some, but not all, cases prior to the onset of jaundice. There is no evidence that preexisting liver disease increases the likelihood of developing liver failure. However, baseline abnormalities can delay the recognition or confound the diagnosis of a drug-induced hepatotoxic effect, thus use of nefazodone is discouraged in this population. In patients who do receive nefazodone therapy, routine liver function testing should be considered to permit early detection of hepatic injury. Nefazodone therapy should be promptly discontinued if clinical signs or symptoms suggestive of liver injury occur, or if serum transaminase levels exceed 3 times the upper limit of normal. Therapy should be permanently discontinued in patients with presumed or confirmed drug-induced hepatotoxicity. In addition, the use of nefazodone is contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury.