Anti-anxiety: clonazepam, Klonopin, Leponex, Rivotril

Generic Name: clonazepam
Brand Name(s): Klonopin, Leponex, Rivotril
Common Use: Antianxiety agent

Clonazepam's pharmacological profile is similar to other anxiolytic/sedative benzodiazepines. Its basic anticonvulsive properties are also similar to those of other diazepines.

Alone or as an adjunct in the management of myoclonic and akinetic seizures and petit mal variant (Lennox-Gastaut syndrome). May also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides.

Contraindications

Significant liver disease, narrow angle glaucoma, sensitivity to benzodiazepines.

Although simultaneous administration of several anticonvulsants may be considered with clonazepam, such combined therapy may result in an increase of central depressant adverse effects. In addition, the dosage of each drug may be required to be adjusted to obtain the optimum effect. Abrupt withdrawal of clonazepam particularly in those patients on long-term, high dose therapy, may precipitate status epilepticus. Therefore, as with any other anticonvulsants, gradual withdrawal is essential when discontinuing clonazepam. While clonazepam is being gradually withdrawn, the simultaneous substitution of incremental doses of another anticonvulsant may be indicated.

Caution patients receiving clonazepam against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.

They also should be warned against the concomitant use of alcohol and other CNS depressant drugs. The CNS depressant action of benzodiazepines may be potentiated by other drugs such as alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, anxiolytics, phenothiazines, thioxanthene and butyrophenone antipsychotic agents, MAO inhibitors and tricyclic antidepressants.Benzodiazepines have produced habituation, dependence and withdrawal symptoms similar to those noted with barbiturates and alcohol. Therefore, patients who may be prone to increasing the dose of drugs on their own initiative should be under careful monitoring when receiving clonazepam. Periodic liver function tests and blood counts are recommended during long-term clonazepam therapy.

Adverse Side Effects

The most frequently occurring adverse reactions to clonazepam are referable to CNS depression. Drowsiness occurs in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time. Behaviour problems have been noted in approximately 25% of patients and increased salivation in 7%.

Others are:
Alterations in behaviour, which have been variously reported as aggressiveness, argumentative behaviour, hyperactivity, agitation, depression, euphoria, irritability, forgetfulness and confusion. These behavioural reactions are particularly likely to occur in patients with a prior history of psychiatric disturbances and are known to occur in patients with chronic seizure disorders.

Other adverse reactions involving the CNS have included nystagmus, unsteady gait, slurred speech, dysarthria, vertigo, insomnia, and diplopia. Isolated reports of akinesia, hemiparesis, tremor, hypotonia, headache and choreiform movements have been received. Minor changes in EEG patterns specifically low-voltage fast activity.Increased salivation, nausea, vomiting, anorexia, constipation, diarrhea, encopresis, dry mouth, increased appetite, abdominal pain, hepatomegaly.Rare instances of dysuria, nocturia, incontinence, urinary retention, enuresis. Nonspecific erythematous, papular and maculopapular rashes, swelling of the face and eyelids, urticaria, pruritus. Hirsutism and hair loss have also been reported, but drug relationship has not been established. Muscle weakness, low back pain. Hypersecretion in the upper respiratory passages, rhinorrhea, dyspnea, respiratory depression.Anemia, leukopenia (WBC below 4000/mm(3)), thrombocytopenia, eosinophilia. Slight, transient elevations of transaminase and alkaline phosphatase. Palpitations, coated tongue, dehydration, fever, lymphadenopathy, weight gain or loss, changes in libido, gynecomastia, hallucinations, dysdiadochokinesis, coma, aphonia.

Overdose

The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimal effects on respiration, pulse and blood pressure, unless the overdosage is extreme. When the effects of the drug overdosage begin to wear off, the patient exhibits some jitteriness and over stimulation.

Gastric lavage may be beneficial if performed soon after ingestion of clonazepam.

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