clonazepam (Klonopin)
Classes: Anticonvulsants, Other; Antianxiety Agents; Anxiolytics, Benzodiazepines
Dosing and uses of Klonopin (clonazepam)
Adult dosage forms and strengths
tablet dispersible: Schedule IV
- 0.125mg
- 0.25mg
- 0.5mg
- 1mg
- 2mg
tablet: Schedule IV
- 0.5mg
- 1mg
- 2mg
Panic Disorder
0.25 mg PO q12hr initially; may increase to 1 mg/day after 3 days (up to 4 mg/day in some patients)
Seizure Disorders
1.5 mg/day PO divided q8hr; increase by 0.5-1 mg q3Days until desired effect achieved; not to exceed 20 mg/day
Maintenance: 2-8 mg PO; not to exceed 20 mg/day
Essential Tremor (Off-label)
0.5 mg PO at bedtime; increase dose by 0.5 mg q3-4days; not to exceed 6 mg/day
REM Sleep Behavior Disorder (Off-label)
0.25-2 mg PO 30 min prior to bedtime; not to exceed 4 mg
Burning Mouth Syndrome (Off-label)
0.25 mg PO at bedtime for 1 week; increase dose by up to 0.25 mg qweek; not to exceed 3 mg daily in 3 divided doses
Alternatively, 1 mg topirally three times daily after each meal; suck on the tablet, retain salive in mouth near pain sites without swallowing for 3 min, then expectorate saliva
Hyperekplexia (Orphan)
Orphan indication sponsor
- Hoffmann-La Roche, Inc; 340 Kingsland Street; Nutley, NJ 07110
Recurrent, Acute, Repetitive Seizures (Orphan)
Administration: Intranasal spray
Orphan indication sponsor
- Jazz Pharmaceuticals, Inc; 3180 Porter Drive; Palo Alto, CA 94304
Dosing Considerations
Discontinuation of treatment: Withdraw treatment gradually; decrease the dose q3Days by 0.125 mg PO q12hr until completely withdrawn
Dosing Modifications
Renal impairment: Supplemental dose in hemodialysis not necessary
Pediatric dosage forms and strengths
tablet: Schedule IV
- 0.125mg
- 0.25mg
- 0.5mg
- 1mg
- 2mg
Seizure Disorders
<6 years
- Potential toxic dose: 0.05 mg/kg
<10 years or <30 kg
- 0.01-0.03 mg/kg/day PO divided q8hr; increase by 0.25-0.5 mg/day q3Days to maximum 0.1-0.2 mg/kg/day PO divided q8hr
- Maintenance dose: 0.1-0.2 mg/kg/day PO divided q8hr; not to exceed 0.2 mg/kg/day
>10 years or >30 kg
- 1.5 mg/day PO divided q8hr; increase by 0.5-1 mg q3Days until desired effect achieved; not to exceed 20 mg/day
- Maintenance: 2-8 mg PO; not to exceed 20 mg/day
Dosing Considerations
Discontinuation of treatment
- <10 years: Treatment should be withdrawn gradually, as necessary
- >10 years: Withdraw treatment gradually; decrease the dose q3Days by 0.125 mg PO q12hr until completely withdrawn
Klonopin (clonazepam) adverse (side) effects
>10%
Somnolence (37%)
1-10%
Abnormal coordination (5-10%)
Ataxia (5-10%)
Depression (5-10%)
Dizziness (5-10%)
Fatigue (5-10%)
Memory impairment (5-10%)
Upper respiratory infection (5-10%)
Confusion (1-5%)
Dysarthria (1-5%)
Rhinitis (1-5%)
Coughing (1-5%)
Urinary frequency (1-5%)
Impotence (1-5%)
Decreased libido (1-5%)
Frequency not defined
Increased salivation
Worsening tonic-clonic seizures
Warnings
Contraindications
Significant hepatic impairment
Documented hypersensitivity
Acute narrow angle glaucoma
Cautions
Withdraw gradually when used for panic disorder
Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicidal ideation
Not recommended in patients with depressed neuroses, psychotic reactions, severe respiratory depression, myasthenia gravis (allowable in limited circumstances), acute alcohol intoxication
Anterograde amnesia reported benzodiazepine use
May cause CNS depression and impairs ability to perform hazardous tasks
Hyperactive or aggressive behavior reported with benzodiazepines in pediatric/adolescent patients and in psychiatric patients
Increased risk of suicidal thoughts/behavior reported with antiepileptic agents; monitor patient for suicidal behavior and notify health-care provider immediately
Use with caution in patients with a history of drug abuse or acute alcoholism; drug dependency possible; prolonged use may result in psychological and physical dependence
Use with caution in patients with compromised respiratory function
May have porphyrogenic effect; use with caution in patients with porphyria
Not for concomitant administration with alcohol or other CNS-depressant drugs
When used in patients in whom several different types of seizure disorders coexist, clonazepam may increase incidence or precipitate onset of generalized tonic-clonic seizures (grand mal); may require addition of appropriate anticonvulsants or increase in dosages; concomitant use of valproic acid and clonazepam may produce absence status
Abrupt withdrawal, particularly in patients on long-term, high-dose therapy, may precipitate status epilepticus; when discontinuing clonazepam, gradual withdrawal essential; while being gradually withdrawn, simultaneous substitution of another anticonvulsant may be indicated
May produce increase in salivation; consider before giving drug to patients who have difficulty handling secretions
Pregnancy and lactation
Pregnancy category: d
Lactation: Excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Klonopin (clonazepam)
Mechanism of action
Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters
Suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in motor cortex
Absorption
Bioavailability: 90%
Onset: 20-40 min
Peak plasma time: 1-4 hr; 5-7 days (steady state)
Distribution
Protein bound: 85%
Vd: 1.5-3 L/kg
Metabolism
Metabolized by CYP3A4 (minor), glucuronic acid conjugation
Metabolites: Inactive
Elimination
Half-life: 17-60 hr (adults); 22-33 hr (children)
Excretion: Urine