clonazepam (Klonopin)

Dosing and uses of Klonopin (clonazepam)

• Adult
• Pediatric

 

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of treatment: Withdraw treatment gradually; decrease the dose q3Days by 0.125 mg PO q12hr until completely withdrawn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10 years: Treatment should be withdrawn gradually, as necessary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10 years: Withdraw treatment gradually; decrease the dose q3Days by 0.125 mg PO q12hr until completely withdrawn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