Chlordiazepoxide metabolite accumulation in liver disease

Chlordiazepoxide 40mg daily was used to prevent delerium tremens in a 64-year-old female with alcoholic liver disease. After 20 days, the drug was stopped because of the onset of progressive drowsiness. The kinetics of chloridazepoxide were within the predicted range for patients with liver disease, but the elimination half-lives of desmethylchlordiazepoxide and demoxepam were greatly prolonged at 346 hours and 150 hours, respectively. It is suggested that metabolite accumulation may have contributed to the coma, which is an unusual reaction to chlordiazepoxide.