clonazepam KLONOPIN
Class: Benzodiazepine/NitroFDA Indications: Panic Disorder, Seizure Disorders
Off-Label Use: Alcohol Withdrawal, Insomnia, Catatonia, Bipolar Mania, Akathisia, Restless Leg Syndrome, Agitation/aggression, Lewy Body Dementia
Prescribing
FDA Schedule IVForms: 0.25, 0.5, 1, 2mg tablet
Dose Range: 0.25-6 mg/day
Starting: 0.25 mg bid; ↑ in increments of 0.125 to 0.25 mg bid q3 days
Stopping: Taper by 0.25 mg q3 days, slower for difficult-to-taper patients
Precautions
Contraindications: Sleep apnea, significant hepatic impairmentSerious 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, constipation, increased appetite, weight gain
Pharmacodynamics
1° MOA: GABAAR PAM2° MOA: May enhance serotonergic neurotransmission
Target: GABAA: α2, α3, γ2 (high); α1 (low to moderate)
Pharmacokinetics
t½: 34 (19-60)° TMAX: 1-4°Absorption Rate: Rapid
Lipid Solubility: Low
Substrate of: 3A4; 2B4, 2E1
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - CNS depression with combined use of opioids
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
Misc
- - moderate degree of sedation
- - longer t½ makes it easier to taper
- - better tolerability profile ie ↓ euphoria and abuse potential
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
RID 1.5-3%; ∅ AE's have been reported
Initiate with low doses and observe closely
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.
Metabolites may accumulate in patients with renal impairment
There are no dosage adjustments provided in the manufacturer's labeling