Risk of prolonged sedation with the use of chlordiazepoxide in alcohol withdrawal treatment

Summary The use of chlordiazepoxide in the treatment of alcohol withdrawal symptoms poses a risk of prolonged sedation with the need of weeks lasting antidote treatment, and extended hospitalization due to active metabolites with very long half-lives. We present four case stories to elucidate this issue. One patient received 800 mg chlordiazepoxide and was treated with flumazenil for 42 days. Another patient was treated with 100 mg chlordiazepoxide. 5 days after administration of chlordiazepoxide, concentrations of chlordiazepoxide and its active metabolite demoxepam, were within therapeutic range, the patient was treated with flumazenil for 6 days. He died after palliative care. The great individual variation in the clinical effect of chlordiazepoxide depends on the activity of the CYP P450 system, especially CYP3A4/A5 and CYPS2C19, which can be impaired in cirrhotic and elderly patients.