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Benzodiazepine (long-acting) Pregnancy: Avoid — neonatal floppy infant syndrome, withdrawal. If withdrawal occurs in pregnancy, lower-dose chlordiazepoxide regimen with specialist obstetric/addiction input.

Chlordiazepoxide

Brand names: Librium

Adult dose

Dose: Alcohol withdrawal (CIWA-Ar guided fixed reducing regimen — example, fit adult <65 yr, no liver disease): Day 1: 20–40 mg QDS (max 200 mg); Day 2: 15–30 mg QDS; Day 3: 10–20 mg QDS; Day 4: 10 mg QDS; Day 5: 5–10 mg QDS; Day 6: 5 mg BD–QDS. Severe anxiety (rare indication now): 10 mg TDS up to 60–100 mg/day in divided doses (max 4 weeks).
Route: Oral
Frequency: QDS for withdrawal regimens
Max: 200 mg/day day 1 (alcohol withdrawal); 100 mg/day for anxiety
Symptom-triggered (CIWA-Ar) regimens reduce total benzodiazepine exposure vs fixed regimens; preferred in inpatient settings. Reduce all doses by 50% in elderly, low body weight, or hepatic impairment.

Dose adjustments

Renal

Caution; reduce dose in severe impairment.

Hepatic

Reduce dose 50% in mild–moderate impairment. Avoid in severe cirrhosis — accumulation, encephalopathy. Use lorazepam or oxazepam (no active metabolites) instead in significant liver disease.

Clinical pearls

  • First-line for inpatient alcohol withdrawal in UK (NICE CG100, CG115) — long half-life provides smooth taper.
  • Active metabolites (desmethylchlordiazepoxide, demoxepam, desmethyldiazepam — t½ 30–200 hr) accumulate over 5 days; some clinicians prefer diazepam (similar profile, more predictable) or lorazepam (no active metabolites — safer in liver disease).
  • ALWAYS prescribe parenteral thiamine (Pabrinex 2 pairs IV/IM TDS for 3–5 days) before/with chlordiazepoxide to prevent Wernicke's encephalopathy.
  • Symptom-triggered (CIWA-Ar) regimens reduce total benzodiazepine exposure by 30–50% in randomised trials — preferred in monitored ward settings.
  • Avoid in severe liver disease — half-life >200 hours risk of encephalopathy; use lorazepam 1–2 mg q4–6h prn instead.
  • NOT recommended for chronic anxiety — high dependence/falls risk; SSRIs preferred.

Contraindications

  • Severe respiratory disease, sleep apnoea
  • Severe hepatic impairment (use lorazepam instead)
  • Myasthenia gravis
  • Acute narrow-angle glaucoma
  • Pregnancy (relative — neonatal effects), breastfeeding
  • Concurrent strong opioids (relative — dose-related respiratory depression)

Side effects

  • Sedation, drowsiness, ataxia
  • Anterograde amnesia
  • Falls and fractures (especially elderly)
  • Respiratory depression (esp. with opioids — black-box warning)
  • Tolerance and dependence (lower than alprazolam due to long half-life)
  • Withdrawal syndrome on abrupt cessation
  • Paradoxical agitation
  • Hangover effect (long t½ + active metabolites)

Interactions

  • Opioids: fatal respiratory depression — MHRA black-box warning
  • Alcohol: additive CNS depression (note: indication is alcohol withdrawal — used in patients off alcohol)
  • CYP3A4 inhibitors (cimetidine, fluconazole, ritonavir): ↑ levels
  • CYP3A4 inducers (rifampicin, phenytoin): ↓ levels
  • Other CNS depressants (gabapentinoids, antipsychotics): additive sedation/respiratory depression

Monitoring

  • CIWA-Ar score 1–4 hourly during peak withdrawal
  • Sedation score, respiratory rate
  • Glucose (often co-existing hypoglycaemia)
  • Bloods: FBC, U&Es, LFTs, INR, magnesium, B12, folate

Reference: BNF 90; SmPC Librium; NICE CG100 (Alcohol-Use Disorders Diagnosis 2010); NICE CG115 (Alcohol-Use Disorders Management); SIGN 156. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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