Librax (Chlordiazepoxide) Dosing
For adults with mild to moderate anxiety, start with 5-10 mg three to four times daily; for severe anxiety, use 20-25 mg three to four times daily, with a maximum total daily dose of 300 mg in acute situations such as alcohol withdrawal. 1
Standard Adult Dosing
Anxiety Disorders
- Mild to moderate anxiety: 5-10 mg orally, 3-4 times daily 1
- Severe anxiety: 20-25 mg orally, 3-4 times daily 1
- The FDA-approved dosing allows for individualized titration based on symptom severity and patient response 1
Special Populations
- Geriatric patients or debilitated patients: Reduce dose to 5 mg, 2-4 times daily due to increased sensitivity and altered pharmacokinetics 1
- Elderly patients show reduced clearance and prolonged elimination half-life, necessitating lower doses 2
Preoperative Anxiety
- Days before surgery: 5-10 mg orally, 3-4 times daily 1
- Immediate preoperative: 50-100 mg IM one hour prior to surgery 1
Alcohol Withdrawal
- Initial oral dosing: 50-100 mg, followed by repeated doses as needed until agitation is controlled, up to 300 mg per day 1
- Maintenance: Reduce to lower maintenance levels once acute symptoms are controlled 1
- Important caveat: In patients with hepatic insufficiency, chlordiazepoxide carries significant risk of dose-stacking and delayed, prolonged sedation due to slow metabolism and accumulation of active metabolites 3
Pediatric Dosing
- Children over 6 years: 5 mg, 2-4 times daily; may increase to 10 mg, 2-3 times daily in some children 1
- Children under 6 years: Not recommended due to limited clinical experience 1
- For pediatric sedation/anxiolysis in emergency settings, benzodiazepines like midazolam (0.05-0.10 mg/kg IV or 0.25-0.50 mg/kg PO) are more commonly used 4
Pharmacokinetic Considerations
Metabolism and Active Metabolites
- Chlordiazepoxide undergoes complex hepatic metabolism producing multiple active metabolites: desmethylchlordiazepoxide, demoxepam, desmethyldiazepam, and oxazepam 2
- Elimination half-life: 5-30 hours for parent compound, but demoxepam has a markedly longer half-life of 14-95 hours 2, 3
- Active metabolites accumulate during chronic dosing and may exceed parent compound concentrations at steady state 5
Factors Affecting Blood Levels
- Weight: Negative correlation—higher weight associated with lower blood concentrations 6
- Age: Reduced clearance and prolonged half-life in elderly patients 2
- Sex: Female patients may have lower drug levels 6
- Hepatic disease: Dramatically reduced clearance and risk of severe dose-stacking 3
Critical Clinical Pitfalls
Hepatic Insufficiency Warning
Chlordiazepoxide should be avoided in patients with hepatic insufficiency due to the unique risk of dose-stacking: the parent compound has minimal sedative activity, requiring metabolism to active metabolites for therapeutic effect. 3 In liver disease, slow metabolism leads to:
- Delayed onset of action requiring higher cumulative doses
- Accumulation of unmetabolized drug ("dose-stacking")
- Subsequent delayed, profound, and prolonged sedation from slow conversion to long-acting metabolites 3
Onset of Action
- Therapeutic effects: May take 2-4 weeks for full anxiolytic effects, requiring patient education about delayed onset 7
- This delayed response differs from acute sedative effects and is important for managing patient expectations 7
Drug Interactions
- Disulfiram: Concurrent use reduces chlordiazepoxide clearance and prolongs half-life 2
- Avoid combining with other CNS depressants due to additive sedation 1
Overdose Management
- Manifestations include somnolence, confusion, coma, and diminished reflexes 1
- Flumazenil (benzodiazepine antagonist) may be used for reversal, but monitor for resedation and seizure risk, especially in chronic users 1
- Barbiturates should NOT be used if excitation occurs 1