Hepatic adverse reactions associated with nefazodone.
OBJECTIVE
Since 1999, international reports of hepatotoxicity associated with the antidepressant nefazodone (Serzone) have increased. In June 2001, a manufacturer's safety advisory notified Canadian physicians of "very rare reports of severe liver injury temporally associated with the use of nefazodone HC1." We undertook this study to determine the prevalence of adverse drug reactions to nefazodone reported in a Canadian database.


METHODS
We requested the Canadian Adverse Drug Reaction Monitoring Programme (CADRMP) database for nefazodone and analyzed it for suspected hepatic complications reported and entered from the time of marketing to June 30, 2001.


RESULTS
We found 32 cases of liver injury associated with nefazodone, with 26 (81.3%) classified as "severe." Patients ranged in age from 30 to 69 years and took 100 to 600 mg of nefazodone daily. Most (68.8%) of the patients were women. Eleven patients were prescribed only nefazodone, and 20 took it concomitantly with other drugs. Of affected patients, 88% developed liver injury within 6 months of starting nefazodone. At the time of reporting, 17 patients recovered without sequelae, 12 patients had not yet recovered, and the outcomes for 3 were unknown. There were 3 cases of hepatic failure, 1 of hepatocellular degeneration, 1 of hepatic necrosis, and 1 of fulminant hepatitis.


CONCLUSIONS
In common with similar databases, the CADRMP database includes only a small proportion of suspected drug reactions. In view of 32 reported cases of hepatotoxicity associated with nefazodone in Canada, 81.3% of which were severe, caution should be exercised if nefazodone is prescribed with other drugs, especially those metabolized by CYP4503A4. Nefazodone should not be prescribed to patients with preexisting liver disease. Baseline and regular liver function tests should be obtained in all patients on nefazodone therapy in the first 6 months, and the drug should be discontinued if abnormalities are found. Patients should be advised of symptoms of hepatotoxicity, and to report them immediately to their physician.
Stewart
Donna E
DE
University Health Network, University of Toronto, Toronto, Ontario. donna.stewart@uhn.on.ca
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D002170:Canada; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone