diazepam VALIUM
Class: Benzodiazepine/2-KetoFDA Indications: Anxiety Disorders, Acute Alcohol Withdrawal, Muscle Spasm, Seizure Disorders, Status Epilepticus (IM Only), Preanesthetic (IM Only), Cardioversion (IM Only)
Off-Label Use: Muscle Relaxation, Preanesthetic, Tetanus, Catatonia, Delirium Tremens, Insomnia
Prescribing
FDA Schedule IVForms: 2, 5, 10mg tablet; 5 mg/mL injectable
Dose Range: 2-40 mg/day
Starting: 2-10 mg, 2-4 times/day
Stopping: Taper by 2 mg q3 days, slower for difficult-to-taper patients
Precautions
Contraindications: Sleep apneaSerious 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: 20 (20-80)° TMAX: 1-2°Absorption Rate: Rapid
Lipid Solubility: High
Substrate of: 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: oxazepam, N-desmethyldiazepam (100° t½), temazepam
DDIs
- - CNS depression with combined use of opioids
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
- - valproate causes twofold ↑ of unbound serum diazepam (via displacement from plasma protein-binding sites)
Misc
- - ↓ stage 4 sleep
- - available in rectal gel and oral liquid formulations
- - longer t½ makes it easier to taper
- - t½ ↑ by ~1h for each year >40
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
Diazepam's high RID (2.8-7.1%) and its long t½ make it the worst choice of among the benzodiazepines for nursing mothers
2-2.5 mg, 1-2 times/day; ↑ gradually as needed; use with caution; active metabolites with ↑ t½ may lead to accumulation
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.
There are no dosage adjustments provided in the manufacturer's labeling
There are no dosage adjustments provided in the manufacturer's labeling
References
Use Of Psychiatric Medications During Pregnancy And LactationValium Package Insert
Essential Psychopharmacology. The Prescriber's Guide. Third Edition
An Updated Unified Pharmacophore Model Of The Benzodiazepine Binding Site On GABAAR
UpToDate
Neonatal Benzodiazepines Exposure During Breastfeeding