LIBRIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIBRIUM (LIBRIUM).
Binds to benzodiazepine site on GABA-A receptor, potentiating GABAergic inhibition and increasing chloride ion conductance.
| Metabolism | Hepatic via oxidative N-dealkylation (CYP3A4) to active metabolite (desmethyldiazepam) and subsequent hydroxylation. |
| Excretion | Renal excretion of unchanged drug and metabolites (primarily glucuronide conjugates of chlordiazepoxide and demoxepam, <2% unchanged); approximately 60-70% of a dose appears in urine as metabolites, with 4-9% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life of chlordiazepoxide is 24-48 hours; active metabolite desmethyldiazepam has half-life of 36-200 hours; with repeated dosing, effective half-life extends due to accumulation of active metabolites. |
| Protein binding | 96-98% bound, primarily to albumin. |
| Volume of Distribution | 0.3-0.5 L/kg; distributes widely into tissues; crosses blood-brain barrier and placenta. |
| Bioavailability | Oral: 90-100% (well absorbed); IM: 80-100% but absorption slow and erratic; IV: 100%. |
| Onset of Action | Oral: 30-60 minutes (anxiolytic); IM: 15-30 minutes (peak plasma levels at 30-60 min); IV: 1-5 minutes (sedation); delayed onset in IM due to erratic absorption. |
| Duration of Action | Oral: 6-8 hours for single dose, but prolonged with repeated dosing due to long-acting metabolites; IV: 15-30 minutes for acute effects; clinical duration extends to 24-48 hours for anxiolytic/sedative effects. |
5-25 mg orally 3-4 times daily; or 50-100 mg intramuscularly or intravenously initially, then 25-50 mg 3-4 times daily as needed.
| Dosage form | CAPSULE |
| Renal impairment | CrCl <10 mL/min: administer at 50% of normal dose; CrCl ≥10 mL/min: no adjustment required. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: not recommended. |
| Pediatric use | Children 6-12 years: 5 mg orally 2-4 times daily; 5-10 mg intramuscularly or intravenously every 6-8 hours. Children >12 years: adult dosing. |
| Geriatric use | Initiate at 5 mg orally once or twice daily; avoid doses >10 mg/day; reduce parenteral dose by 50%. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIBRIUM (LIBRIUM).
| Breastfeeding | Chlordiazepoxide and its active metabolite nordiazepam are excreted in breast milk. M/P ratio not available for chlordiazepoxide; for nordiazepam, approximately 0.5. Infant serum levels can reach 1-10% of maternal levels. Risk of sedation and feeding difficulties; use with caution and monitor infant for drowsiness, poor feeding, and weight gain. |
| Teratogenic Risk | First trimester: Increased risk of oral clefts (odds ratio ~2.0). Late third trimester or labor: Risk of neonatal withdrawal syndrome (irritability, hypertonia, feeding difficulties) and floppy infant syndrome (hypotonia, lethargy, respiratory depression). |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Serious Effects |
["Hypersensitivity to chlordiazepoxide or any benzodiazepine","Narrow-angle glaucoma","Severe hepatic impairment","Concurrent use with opioids (except alternative treatments considered)"]
| Precautions | ["Risk of respiratory depression","Dependence and withdrawal reactions","Abuse potential","CNS depressant effects (impaired cognition/motor function)","Elderly/debilitated patients at increased risk of toxicity","Neonatal withdrawal syndrome during pregnancy"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, respiratory rate, and sedation level. In late pregnancy, assess fetal heart rate and consider ultrasound for growth if chronic use. For neonates, monitor for signs of withdrawal (e.g., poor feeding, irritability) and respiratory depression. |
| Fertility Effects | No well-documented adverse effects on fertility in humans. Animal studies high doses may affect reproductive organs, but clinical relevance unknown. |