Is liver failure a known side effect of Nefadar (nefazodone)?/nThe question concerns a patient with

Fråga: Is liver failure a known side effect of Nefadar (nefazodone)? The question concerns a patient with depression who has been treated with nefazodone in normal dose and now has developed fulminant and very severe hepatitis. No other drugs have been given during the last three months.

Sammanfattning: In the absence of other potentially causative agents, the treatment with nefazodone is the suspected cause of the liver necrosis in the present case.

Svar: Nefazodone is an antidepressant that shows an adverse reaction profile which includes hepatotoxicity and hepatitis is currently mentioned as a rare side effect in FASS (1). Through the representative of the producer, we have been informed that there has been one case of fulminant hepatotoxicity with lethal outcome related to the intake of the drug (2).

Out of ninety-nine reports to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC), eight concerned the hepatobiliary system (3). The WHO adverse reaction register contains 5 reports on hepatic failure, 44 reports on abnormal hepatic function, 2 reports on hepatic necrosis and 26 reports on hepatitis. Unfortunately the WHO reports cannot be further evaluated.

Nefazodone clearance is reduced in hepatic impairment and in the elderly (4). Nefazodone is partly metabolised by CYP3A4 and inhibits the metabolism of some other substances cleared through this enzyme (5). Clinically significant interactions have been reported between nefazodone and triazolam, alprazolam, cyclosporine, and carbamazepine (5). CYP3A4 occurs both in the liver and in the gut implying that the metabolism should be partially preserved during severe liver failure.

We recommend that this case be reported to SADRAC.