chlordiazepoxide LIBRIUM
Class: BenzodiazepineFDA Indications: Acute Alcohol Withdrawal, Anxiety Disorders, Preoperative Apprehension And Anxiety
Off-Label Use: IBS
Prescribing
FDA Schedule IVForms: 5, 10, 25mg capsule
Dose Range: 10-300 mg/day
Starting: Acute alcohol withdrawal: 50-100 mg; dose may be repeated as necessary to a maximum of 300 mg/day
Anxiety: 5-25 mg tid-qid
Precautions
Serious Side Effects: Overdose can result in hypotension, respiratory depression, and comaSide Effects: confusion, sedation/somnolence, ataxia, decreased libido, visual changes
Pharmacodynamics
1° MOA: GABAAR PAMTarget: GABAA: α3 (moderate), α1 (low-moderate), γ2 (low-moderate), α2 (weak)
Pharmacokinetics
t½: 10 (24-48)° TMAX: 0.5-2°Absorption Rate: Medium
Lipid Solubility: High
Substrate of: 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: Desmethylchlordiazepoxide, demoxepam (t½ 28-63°), desmethyldiazepam (nordiazepam) (t½ 30-200°), and oxazepam (t½ 5-15°).
DDIs
- - CNS depression with combined use of opioids
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
Misc
- - the first compound synthesized in the benzodiazepine class and the first marketed in 1960, initially with a primary indication for use in alcohol withdrawal
- - its relatively long t½ is an advantage as it contributes to a smooth course of alcohol withdrawal
- - since chlordiazepoxide has 4 active metabolites, accumulation of the metabolites occurs, and it can take 2-3 weeks to reach steady state
Special Populations
Category D—↑ risk of oral cleft by 0.01%, use just before delivery associated with floppy infant syndrome, 3rd trimester use can cause withdrawal in newborns
Excreted in breast milk. Drowsiness, lethargy, or weight loss in nursing infants have been observed in case reports following maternal use of some benzodiazepines
Avoid use; however, use may be appropriate in older adults when used for seizure disorders, rapid eye movement disorders, benzodiazepine or ethanol withdrawal, severe generalized anxiety disorder, or periprocedural anesthesia (Beers Criteria [AGS 2015])
2019 BEE℞S Recommendation: Avoid. Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long- acting agents; in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults. May be appropriate for seizure disorders, RBD, benzodiazepine withdrawal, EtOH withdrawal, severe GAD, and periprocedural anesthesia.
CrCl ≤10 mL/min: No dosage adjustment necessary; CrCl <10 mL/minute: Administer 50% of dose;
There are no dosage adjustments provided in the manufacturer's labeling; however, chlordiazepoxide undergoes hepatic metabolism and should be used with caution.