Liver injury due to tetrabamate (Atrium): an analysis of 11 cases.
BACKGROUND
Tetrabamate (Atriums), 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 evolutive features.


METHODS
Between 1987 and 1998, 34 cases of tetrabamate-associated acute hepatitis were spontaneously reported to the regional pharmacovigilance center of Lyon. Eleven cases were considered probably to be drug-induced.


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 indication 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 features of hepatic failure. A percutaneous liver biopsy was performed in six patients. Histological examination of the liver specimen showed a large spectrum of lesions: massive hepatocellular necrosis (n = 1), centrilobular and nonconfluent hepatocyte necrosis (n = 2), intracellular cholestasis (n = 3), and granulomatous hepatitis (n = 1). Tetrabamate was discontinued in all patients. In seven patients, a complete recovery was observed 3 weeks to 3 months after drug withdrawal. Two patients, despite a rapid improvement of liver 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 liver injury, which may eventually result in life-threatening liver failure.
Dumortier
J
J
Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Lyon, France.
Bellemin
B
B
Jacob
P
P
Berger
F
F
Chevallier
M
M
Scoazec
J Y
JY
Vial
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001463:Barbiturates / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology*; D004338:Drug Combinations; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000009:adverse effects*; D011619:Psychotropic Drugs / Q000009:adverse effects*; D013997:Time Factors
D001463:Barbiturates; D004338:Drug Combinations; D011619:Psychotropic Drugs; C006648:difebarbamate, febarbamate, phenobarbital drug combination; D010634:Phenobarbital