Chlordiazepoxide (Librium)

Class

Benzodiazepine

Mechanism

Potentiates GABA-A receptor-mediated inhibitory neurotransmission, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.

FDA-Approved Use

Acute alcohol withdrawal, short-term relief of anxiety symptoms

Off-Label Use

Benzodiazepine taper, catatonia, preoperative anxiety

Formulation

Oral tablets, liquid

Titration

5–25 mg p.o. three to four times daily; higher doses initially for alcohol withdrawal with gradual taper

Dose Range

Varies widely by indication; commonly 30–200 mg/day divided doses for alcohol withdrawal

Kinetics

Chlordiazepoxide is extensively metabolized in the liver primarily by CYP3A4 and CYP2C19 enzymes to active metabolite, which contribute to its long half-life (5–30 hours) and prolonged clinical effects. The active metabolites have half-lives ranging from 36 to 200 hours, leading to accumulation with repeated dosing and smoother withdrawal profiles.

Common AEs

Sedation, impaired coordination, slurred speech, confusion

Serious/Rare AEs

Respiratory depression, paradoxical agitation, dependence, withdrawal seizures

Monitoring

Clinical monitoring for sedation, respiratory status during withdrawal treatment, hepatic function if indicated, fall risk assessment especially in elderly

Black Box Warning

Risk of profound sedation, respiratory depression, coma, and death when used with opioids. Risk of dependence, misuse, and withdrawal with prolonged use.

Considerations

Chlordiazepoxide is often used in individuals with alcohol use disorder and seizure risk, including those with traumatic brain injury (TBI) or underlying cognitive conditions. It should be avoided in individuals with hepatic impairment and used cautiously in the elderly due to fall risk and prolonged sedation