Liver injury due to tetrabamate (Atrium (R)): an analysis of 11 cases

Background Tetrabamate (Atrium(R)), widely used in the treatment of tremor and ethanol-withdrawal symptoms, has been incriminated as a potential cause of reversible acute hepatitis. Objective We report here on 11 patients who experienced tetrabamate-related liver injury, in order to evaluate their clinical, histopathological and e volutive features. Patients and methods Between 1987 and 1998, 34 cases of tetrabamate-associa ted acute hepatitis were spontaneously reported to the regional pharmacovig ilance center of Lyon. Eleven cases were considered probably to be drug-ind uced. Results There were three males and eight females aged 31-82 years (mean, 57 years). The duration of treatment ranged from 33 to 206 days, and indicati on for treatment was depressive disorders, tremor or prevention of alcohol withdrawal symptoms. Clinical symptoms were asthenia (n = 9), jaundice (n = 3) and/or diffuse rash (n = 3). The pattern of liver injury was cytolytic (n = 10) or cholestatic (n = 1). Three patients presented biological featur es of hepatic failure. A percutaneous liver biopsy was performed in six pat ients. Histological examination of the liver specimen showed a large spectr um of lesions: massive hepatocellular necrosis (n = 1), centrilobular and n onconfluent hepatocyte necrosis (n = 2), intracellular cholestasis (n = 3), and granulomatous hepatitis (n = 1), Tetrabamate was discontinued in all p atients. In seven patients, a complete recovery was observed 3 weeks to 3 m onths after drug withdrawal. Two patients, despite a rapid improvement of l iver function tests, died from unrelated causes. The remaining two patients died from irreversible hepatic failure. Conclusions Our data strongly suggest that tetrabamate may induce acute liv er injury, which may eventually result in life-threatening liver failure, ( C) 2000 Lippincott Williams & Wilkins.