clorazepate TRANXENE
Class: BenzodiazepineFDA Indications: Anxiety Disorders, Acute Alcohol Withdrawal, Adjunct Therapy For Partial Seizures In Adults With Epilepsy
Off-Label Use: Insomnia
Prescribing
FDA Schedule IVForms: 3.75, 7.5, 15mg tablet
Dose Range: 15-60 mg/day
Starting: 30 mg/day in divided doses (range: 15 to 60 mg/day) or 15 mg at bedtime; adjust dose based on patient response
Precautions
Contraindications: Sleep apnea, acute narrow-angle glaucomaSerious Side Effects: Overdose can result in hypotension, respiratory depression, and coma
Side Effects: sedation/somnolence, dizziness, confusion, disequilibrium, ataxia, lightheadedness, weakness/asthenia, decreased libido, dysarthria, increased appetite, weight gain
Pharmacokinetics
t½: 48 (20-179)° TMAX: 0.5-1°Absorption Rate: Fast
Lipid Solubility: High
Substrate of: Rapidly decarboxylated → desmethyldiazepam → (via 3A4 & 2C19) oxazepam
Inhibits: ∅ ; Induces: ∅
Active Metabolites: oxazepam (5-15° t½), N-desmethyldiazepam (30-200° t½)
DDIs
- - CNS depression with combined use of opioids
- - antacids ↓ levels
Misc
- - lacking any intrinsic pharmacological activity, clorazepate is a prodrug for desmethyldiazepam
- - decarboxylated by stomach acid to desmethyldiazepam, which is also the major active metabolite of diazepam and ∴ clorazepate exhibits the profile and properties of diazepam
Special Populations
Category D—The effects of benzodiazepines on the human embryo and fetus are controversial. Although some studies have reported an association with various types of congenital defects, other studies have not found such associations. Maternal denial of exposure and concurrent exposure to other toxic drugs and substances (e.g., alcohol and smoking) may be confounding factors. If the maternal condition requires use of the drug during pregnancy, the lowest possible dose should be taken.
No reports describing the use of clorazepate during human lactation have been located. Other benzodiazepines accumulate in human milk, and adverse effects in the nursing infant have been reported. In 2001, the American Academy of Pediatrics classified other benzodiazepines as drugs whose effect on the nursing infant is unknown but may be of concern.
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.
No dosage adjustment necessary
No dose adjustment necessary with mild-moderate liver dz; use with caution if severe insufficiency