clonazepam

Pregnancy Category D

Controlled Substance C-IV

Drug classes

Benzodiazepine

Antiepileptic

Therapeutic actions

Exact mechanisms not understood; benzodiazepines potentiate the effects of GABA, an inhibitory neurotransmitter.

Indications

· Used alone or as adjunct in treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures; may be useful in patients with absence (petit mal) seizures who have not responded to succinimides; up to 30% of patients show loss of effectiveness of drug, often within 3 mo of therapy (may respond to dosage adjustment), treatment of panic disorder with or without agoraphobia

· Unlabeled uses: Periodic leg movements during sleep, hypokinetic dysarthria, acute manic episodes, multifocal tic disorders, neuralgias

Contraindications and cautions

· Contraindicated with hypersensitivity to benzodiazepines, psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication with depression of vital signs; pregnancy (risk of congenital malformations, neonatal withdrawal syndrome), labor and delivery ("floppy infant" syndrome), lactation (infants become lethargic and lose weight).

· Use cautiously with impaired liver or kidney function, debilitation.

Available forms

Tablets—0.5, 1, 2 mg; orally disintegrating tablets—0.125, 0.25, 0.5, 1, 2 mg

Dosages

Individualize dosage; increase dosage gradually to avoid adverse effects; drug is available only in oral dosage forms.

ADULTS

Seizure disorders: Initial dose should not exceed 1.5 mg/day PO divided into three doses; increase in increments of 0.5–1 mg PO every 3 days until seizures are adequately controlled or until side effects preclude further increases. Maximum recommended dosage is 20 mg/day.

Panic disorders: Initial dose 0.25 mg PO bid; gradually increase to a target dose of 1 mg/day.

PEDIATRIC PATIENTS > 10 YR OR 30 KG

Initially, 0.01–0.03 mg/kg/day PO; do not exceed 0.05 mg/kg/day PO, given in two or three doses. Increase dosage by not more than 0.25–0.5 mg every third day until a daily maintenance dose of 0.1–0.2 mg/kg has been reached, unless seizures are controlled by lower dosage or side effects preclude increases. Whenever possible, divide daily dose into three equal doses, or give largest dose hs.

Pharmacokinetics

Route	Onset	Peak	Duration
Oral	Varies	1–2 hr	Weeks

Metabolism: Hepatic; T_1/2: 18–50 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

· CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, anger, hostility, episodes of mania and hypomania, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions during first 2 weeks of treatment

· CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema

· Dermatologic: Urticaria, pruritus, rash, dermatitis

· EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion

· GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction, encoporesis

· GU: Incontinence, urinary retention, changes in libido, menstrual irregularities

· Hematologic: Elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; blood dyscrasias: agranulocytosis, leukopenia

· Other: Hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia. Drug dependence with withdrawal syndrome when drug is discontinued; more common with abrupt discontinuation of higher dosage used for longer than 4 mo

Interactions

Drug-drug

· Increased CNS depression with alcohol

· Increased effect with cimetidine, disulfiram, omeprazole, hormonal contraceptives

· Decreased effect with theophylline

· Risk of increased digoxin levels and toxicity; monitor patient carefully

Nursing considerations

CLINICAL ALERT!

Name confusion has been reported between Klonopin (clonazepam) and clonidine; use caution.

Assessment

· History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication; pregnancy; lactation; impaired liver or kidney function, debilitation.

· Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic examination; P, BP; R, adventitious sounds; liver evaluation, abdominal examination, bowel sounds, normal output; CBC, liver and renal function tests.

Interventions

· Monitor addiction-prone patients carefully because of their predisposition to habituation and drug dependence.

· Monitor liver function and blood counts periodically in patients on long-term therapy.

· WARNING: Taper dosage gradually after long-term therapy, especially in patients with epilepsy; substitute another antiepileptic.

· Monitor patient for therapeutic drug levels: 20–80 ng/mL.

· Arrange for patient to wear medical alert ID indicating the patient has epilepsy and is receiving drug therapy.

Teaching points

· Take drug exactly as prescribed; do not stop taking drug (long-term therapy) without consulting health care provider.

· Avoid alcohol, sleep-inducing, or OTC drugs.

· Avoid pregnancy; serious adverse effects can occur. Use of barrier contraceptives is advised while taking this drug.

· You may experience these side effects: Drowsiness, dizziness (may become less pronounced; avoid driving or engaging in other dangerous activities); GI upset (take drug with food); fatigue; dreams; crying; nervousness; depression, emotional changes; bed-wetting, urinary incontinence.

· Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, difficulty voiding, palpitations, swelling in the extremities.

Adverse effects in Italic are most common; those in Bold are life-threatening.