Clonazepam
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Clonazepam
Klonopin
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Summary
Common uses
Panic disorder (FDA)0, Lennox-Gastaut syndrome (FDA)0, Akinetic and myoclonic seizures (FDA)0, Social anxiety disorder (off-label)0, REM sleep behavior disorder (off-label, evidence-supported)0, Restless legs syndrome (off-label, second-line)0, Acute mania adjunct (off-label)0
Pharmacy
Starting dose
Anxiety: 0.25 mg PO BID, titrate by 0.125-0.25 mg every 3 days to target 1-4 mg/day divided. Seizures: 1.5 mg/day divided TID, titrate by 0.5-1 mg every 3 days
Preparations
Tablets 0.5, 1, 2 mg; orally disintegrating tablets 0.125, 0.25, 0.5, 1, 2 mg
US FDA Max
20 mg/day (seizures); commonly limited to 4 mg/day for anxiety in current practice
Pharmacology
Routes
Oral
Onset
20-60 minutes
Duration
6-12 hours (long-acting among benzodiazepines)
Half-life
30-40 hours (long; accumulates with chronic dosing)[1]
Bioavailability
~90% (oral)[1]
Pregnancy
Limited human data; some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[citation needed]
Legal status
Schedule IV controlled substance in US. Carries the benzodiazepine class Boxed Warning for risk of fatal respiratory depression, coma, and death when combined with opioids[1]
Purported mechanism
Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The long elimination half-life is the clinical signature: smoother symptom coverage than short-acting alternatives but greater accumulation, longer next-day sedation, and longer protracted withdrawal.0 Strong CYP3A4 substrate; CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, grapefruit juice) substantially raise plasma exposure. Tolerance to anxiolytic effect, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use[1].
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, Klonopin (clonazepam), Genentech/Roche, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017533s055lbl.pdf