clonazePAM, KlonoPIN, Rivotril

 Indications

Treatment of Lennox-Gastaut, akinetic, or myoclonic

seizures. Panic disorder with or without agoraphobia.

Unlabeled Use: Uncontrolled leg movements during

sleep. Neuralgias. Infantile spasms. Sedation. Adjunct

management of acute mania, acute psychosis, or insomnia.

Action

Anticonvulsant effects may be due to presynaptic inhibition.

Produces sedative effects in the CNS, probably by

stimulating inhibitory GABA receptors. Therapeutic

Effects: Prevention of seizures. Decreased manifestations

of panic disorder. 

Pharmacokinetics

Absorption: Well absorbed from the GI tract.

Distribution: Probably crosses the blood-brain barrier

and the placenta.

Protein Binding: 85%.

Metabolism and Excretion: Mostly metabolized

by the liver.

Half-life: 18–50 hr.

TIME/ACTION PROFILE (anticonvulsant

activity)

ROUTE ONSET PEAK DURATION

PO 20–60 min 1–2 hr 6–12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to clonazepam

or other benzodiazepines; Severe hepatic impairment;

OB: May cause fetal harm; Lactation: Use not recommended

while breast feeding.

Use Cautiously in: All patients (mayqrisk of suicidal

thoughts/behaviors); Angle-closure glaucoma;

Obstructive sleep apnea; Chronic respiratory disease;

History of porphyria; Do not discontinue abruptly; Geri:

May experience excessive sedation at usual doses;p

dosage recommended; Pedi: Children 18 yr (panic

disorder) (safety and effectiveness not established).

Adverse Reactions/Side Effects

CNS: SUICIDAL THOUGHTS, behavioral changes, drowsiness,

fatigue, slurred speech, ataxia, sedation, abnormal

eye movements, diplopia, nystagmus. Resp:qsecretions.

CV: palpitations. Derm: rash. GI:

constipation, diarrhea, hepatitis, weight gain. GU: dysuria,

nocturia, urinary retention. Hemat: anemia, eosinophilia,

leukopenia, thrombocytopenia. Neuro:

ataxia, hypotonia. Misc: fever, physical dependence,

psychological dependence, tolerance.

Interactions

Drug-Drug: Use with opioids or other CNS depressants,

including otherbenzodiazepines, nonbenzodiazepine

sedative/hypnotics, anxiolytics,

general anesthetics, muscle relaxants, antipsychotics,

and alcohol may cause profound sedation,

respiratory depression, coma, and death; reserve concurrent

use for when alternative treatment options are

inadequate. Cimetidine, hormonal contraceptives,

disulfiram, fluoxetine, isoniazid, ketoconazole,

metoprolol, propranolol, or valproic acid mayp

metabolism andqtoxicity of clonazepam. Maypefficacy

of levodopa. Rifampin or barbiturates mayq

metabolism andpeffectiveness. Sedative effects may be

pby theophylline. Mayqserum phenytoin levels.

Phenytoin mayplevels.

Drug-Natural Products: Concomitant use of

kava-kava, valerian, or chamomile canqCNS depression.

Route/Dosage

PO (Adults): 0.5 mg 3 times daily; mayqby 0.5–1 mg

q 3 days. Total daily maintenance dose not to exceed 20

mg. Panic disorder—0.125 mg twice daily;qafter 3

days toward target dose of 1 mg/day (some patients

may require up to 4 mg/day).

PO (Children 10 yr or 30 kg): Initial daily dose

0.01–0.03 mg/kg/day (not to exceed 0.05 mg/kg/day)

given in 2–3 equally divided doses;qby no more than

0.25–0.5 mg q 3 days until therapeutic blood levels are

reached (not to exceed 0.2 mg/kg/day).

Availability (generic available)

Tablets: 0.5 mg, 1 mg, 2 mg. Cost: Generic—0.5 mg

$11.77/100, 1 mg $11.25/100, 2 mg $15.59/100.

Orally disintegrating tablets: 0.125 mg, 0.25 mg,

0.5 mg, 1 mg, 2 mg. Cost: Generic—0.125 mg

$77.93/60, 0.25 mg $77.93/60, 0.5 mg $77.80/60, 1

mg $88.91/60, 2 mg $123.19/60.