Professional Information

Clonazepam

Pronunciation: (kloe-NAY-ze-pam)
Class: Benzodiazepine

Trade Names:
Klonopin
- Tablets 0.5 mg
- Tablets 1 mg
- Tablets 2 mg
- Tablets, orally disintegrating 0.125 mg
- Tablets, orally disintegrating 0.25 mg
- Tablets, orally disintegrating 0.5 mg
- Tablets, orally disintegrating 1 mg
- Tablets, orally disintegrating 2 mg

Apo-Clonazepam (Canada)
CO Clonazepam (Canada)
Gen-Clonazepam (Canada)
PMS-Clonazepam (Canada)
ratio-Clonazepam (Canada)
Rivotril (Canada)
Sandoz Clonazepam (Canada)

Pharmacology

Potentiates action of GABA, inhibitory neurotransmitter, resulting in increased neuronal inhibition and CNS depression, especially in limbic system and reticular formation.

Pharmacokinetics

Absorption

Rapidly absorbed. About 90% bioavailable. T _max is 1 to 4 h.

Distribution

About 85% protein bound.

Metabolism

Highly metabolized in the liver; CYP-450, including CYP3A4, may play a major role in oxidation and reduction of clonazepam.

Elimination

The t _½ is 30 to 40 h. Less than 2% is excreted in urine as unchanged drug.

Indications and Usage

Treatment of Lennox-Gastaut syndrome; management of akinetic and myoclonic seizures and absence seizures unresponsive to succinimides; panic disorders.

Unlabeled Uses

Treatment of restless legs syndrome, parkinsonian dysarthria, acute manic episodes of bipolar affective disorder, multifocal tic disorders and neuralgias; adjunctive therapy for schizophrenia.

Contraindications

Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; significant liver disease; shock; coma; acute alcohol intoxication.

Dosage and Administration

Panic Disorder
Adults

PO Start with 0.25 mg twice daily. An increase to the target dose for most patients of 1 mg/day may be made after 3 days. Dose may be increased in increments of 0.125 to 0.25 mg twice daily every 3 days until panic disorder is controlled or side effects make further undesired increases (max, 4 mg/day).

Seizure Disorders
Adults Initial dose

PO 1.5 mg/day in 3 divided doses. Increase by 0.5 to 1 mg every 3 days until seizures are adequately controlled (max, 20 mg/day).

Infants and Children (10 yr of age or younger; 30 kg or less) Initial dose

PO 0.01 to 0.03 mg/kg/day in 2 to 3 divided doses. Increase by 0.25 to 0.5 mg every 3 days until maintenance dose of 0.1 to 0.2 mg/kg has been reached.

General Advice

May be administered without regard to meals. Administer with food if GI upset occurs.

Tablets
Administer prescribed dose with water. Have patient swallow whole. Do not crush, chew, divide, or break tablet.

Tablets, orally disintegrating
Do not open pouch until immediately before dose is to be administered.
Open pouch and peel back foil on blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove the tablet and place in mouth. Tablet disintegrates rapidly in saliva and may be swallowed with or without water.

Storage/Stability

Store at controlled room temperature (59° to 86°F).

Drug Interactions

Alcohol and CNS depressants

May cause additive CNS depressant effects.

Carbamazepine, phenytoin, rifampin

May reduce clonazepam serum concentrations, decreasing the clinical effect.

Cimetidine, disulfiram, oral contraceptives

May cause effects of clonazepam to increase, with excessive sedation and impaired psychomotor function.

Digoxin

May increase serum digoxin concentrations.

Theophyllines

May antagonize sedative effects.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Seizure disorders

CV collapse; hypotension; phlebitis or thrombosis at IV sites.

CNS

Panic disorder

Somnolence (50%); dizziness (12%); abnormal coordination (9%); ataxia, depression (8%); memory disturbance (5%); nervousness, reduced intellectual ability, dysarthria (4%); decreased libido (3%); emotional lability, confusion (2%).

Seizure disorders

Drowsiness (50%); ataxia (30%); confusion; dizziness; lethargy; fatigue; apathy; memory impairment; disorientation; anterograde amnesia; restlessness; headache; slurred speech; aphonia; stupor; coma; euphoria; irritability; vivid dreams; psychomotor retardation; paradoxic reactions (eg, anger, hostility, mania, insomnia, muscle spasms).

Dermatologic

Seizure disorders

Rash.

EENT

Panic disorder

Pharyngitis, blurred vision (3%).

Seizure disorders

Visual and auditory disturbances; depressed hearing.

GI

Panic disorder

Constipation (5%); decreased appetite (3%); abdominal pain (2%).

Seizure disorders

Constipation; diarrhea; dry mouth; coated tongue; excessive salivation; nausea; anorexia; vomiting.

Genitourinary

Panic disorder

Dysmenorrhea (6% [women]); colpitis (4% [women]); impotence (men); micturition frequency, delayed ejaculation (2% [men]), UTI (2%).

Seizure disorders

Dysuria; enuresis; nocturia; urinary retention.

Hematologic

Seizure disorders

Blood dyscrasias including agranulocytosis; anemia; thrombocytopenia; leukopenia; neutropenia.

Hepatic

Seizure disorders

Hepatic dysfunction, including hepatitis and jaundice; elevated LDH, ALT, AST, and alkaline phosphatase.

Respiratory

Panic disorder

Upper respiratory tract infection (10%); sinusitis (8%); rhinitis, coughing (4%); bronchitis (2%).

Miscellaneous

Panic disorder

Fatigue (9%); influenza (5%); allergic reaction, myalgia (4%).

Seizure disorders

Dependence/withdrawal syndrome (eg, confusion, abnormal perception of movement, depersonalization, muscle twitching, psychosis, paranoid delusions, seizures).

Precautions

Monitor

CBC

Ensure that CBC with differential and liver enzymes are evaluated periodically in patient on prolonged therapy.

Response to treatment

Frequently assess patient for response to treatment. Notify health care provider if condition does not appear to improve or worsens.

Review therapy

Ensure that therapy is periodically reviewed to determine if it needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.

Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Panic disorder

Safety and efficacy not established.

Seizure disorders

Initial dose should be small and gradually increased. Long-term use may cause adverse effects such as possibly delayed mental or physical development.

Renal Function

Use drug with caution to avoid accumulation.

Hepatic Function

Use drug with caution to avoid accumulation.

Dependence

Withdrawal symptoms of the barbiturate type may occur.

Elderly or debilitated patients

Initial dose should be small and gradually increased. Give drug with extreme care to elderly or very ill patients with limited respiratory reserve.

Hypersalivation

Because an increase in salivation may occur, use with caution in patients who have difficulty handling secretions or those with chronic respiratory disease.

Psychiatric disorders

Not intended for use in patients with primary depressive disorder, psychosis, or disorders in which anxiety is not prominent.

Seizure

In patients with multiple seizure types, drug may increase incidence or precipitate onset of grand mal seizures.

Suicide

Use drug with caution in patients with suicidal tendencies; do not allow patient access to large quantities.

Withdrawal

Abrupt discontinuation, particularly in patients on long-term, high-dose therapy, may precipitate status epilepticus. If treatment is to be discontinued or the dose reduced, gradually taper the dose and monitor patient for withdrawal symptoms. If significant withdrawal symptoms develop (eg, increased anxiety, tremor, muscle or abdominal cramps, sweating), reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Overdosage

Symptoms

Somnolence, confusion, diminished reflexes, coma.

Patient Information

Advise patient or caregiver to read the patient information leaflet before starting therapy and with each refill.
Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
Caution patient that medication may be habit forming, to take as prescribed, and not to stop taking or change the dose unless advised by health care provider.
Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
Advise patient taking tablets to take each dose with water and to swallow whole. Caution patient not to crush, chew, or break tablet.
Advise patient taking orally disintegrating tablets to open pouch, peel back foil on blister, and, using dry hands, immediately remove the tablet and place in mouth. Advise patient that tablet disintegrates rapidly in saliva and may be swallowed with or without water. Caution patient not to open pouch until just before dose is needed.
Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient to never take 2 doses at the same time.
Advise patient that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
Instruct patient to contact health care provider if symptoms (eg, panic attacks, seizures) do not appear to be getting better or are getting worse, or if bothersome side effects (eg, drowsiness, memory impairment) occur.
Advise patient that drug may cause drowsiness or impair judgment, thinking, or reflexes and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Encourage patient with seizure disorder to carry medical identification (eg, card, bracelet) indicating condition and medication being used to treat.