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Clonazepam



Clonazepam Drug
Clonazepam (marketed by Roche under the trade-name Klonopin in the United States and Rivotril in Canada and Europe) is a drug which is a benzodiazepine derivative. It is a highly potent and powerful sedative, hypnotic, anticonvulsant, amnestic and anxiolytic.


Pharmacology


Like other benzodiazepines, clonazepam is believed to act by simulating the action of GABA on the central nervous system. Because of strong anxiolytic properties and euphoriant side-effects it is said to be among the class of 'highly potent' benzodiazepines with a higher risk of abuse, misuse and dependence than other benzodiazepines. The sedative effects of Clonazepam are relatively weak, compared to its strong anxiolytic and anticonvulsant effects. One quarter of a milligram (0.25mg) of Clonazepam is equivalent to five milligrams (5.00mg) of Diazepam.

Indications
Clonazepam is commonly prescribed for:

Epilepsy
Anxiety disorder
Panic attacks
Restless leg syndrome (RLS)
Inital treatment of mania, together with firstline-drugs such as lithium, haloperidol or risperidone
Hallucinogen persisting perception disorder (off-label use)
Chronic fatigue syndrome
Night terrors
Clonazepam is rarely used as a treatment for insomnia, because its sedative effects are relatively weak compared to other benzodiazepines.

Availability
Clonazepam was approved in the United States as a generic medication in 1997 and is now manufactured and marketed by several companies.

Clonazepam is available in the following forms:

Tablets: 0.25, 0.5, 1.0, and 2mg
Liquid concentrate: 2.5mg per ml
Oral wafers: 0.25, 0.5, 1.0 mg
Injection concentrate: 1mg per ml

Dosage

Epilepsy
Status epilepticus - 1mg is given slowly by I.V.; if seizures persist additional doses of 1mg may be given in intervals of 10 to 20 minutes.

Clonazepam can be useful for long-term treatment of some petit-mal forms of epilepsy in children and adolescents (adults may also respond well).

Up to 30% of epileptic patients treated with clonazepam develop a serious tolerance to the anticonvulsant effects. This may require dose increases or gradual withdrawal and replacement of the drug.

Oral doses in long term treatment of epilepsy vary from 1mg to 20mg, depending upon the severity of case and the weight of the patient. Treatment should be initiated at a low dose, and can be increased gradually if necessary.

Other
Anxiety and panic disorders - 1mg to 10mg daily, in divided doses
Restless Leg Syndrome - 1mg to 2mg at bedtime
Mania - Up to 20mg daily, in divided doses

Side effects
Because Clonazepam can impair both mental and motor function, those taking it are advised to use caution when operating motor vehicles or machinery, or engaging in hazardous occupations requiring mental alertness. Side effects include:

Drowsiness
Depression
Impaired motor function
Impaired coordination
Impaired balance
Dizziness
Nervousness
Anterograde amnesia (common with higher doses)
It should be noted that up to 30% of individuals treated on a long-term basis develop a form of dependence known as "low-dose-dependence". These patients do not develop a tolerance, and do not need increasingly large doses to experience the euphoric side effects of the drug.

Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side effects) of the drug.

Interactions
See Diazepam#Interactions.

Contraindications
Use of clonazepam should be avoided in individuals with the following conditions:

Myasthenia gravis
Acute intoxication with alcohol, narcotics, or other psychoactive substances
Ataxia
Severe hypoventilation
Acute narrow-angle glaucoma
Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
Severe sleep apnea
Hypersensitivity or allergy to any drug in the benzodiazepine class

Special Caution Needed
Children and adolescents (less than 18 years of age) - Treatment usually not indicated, except treatment of epilepsy, and pre-/postoperative treatment; extended clinical data for this age group is currently lacking.
I.V. or I.M. injections in hypotensive individuals or those in shock should be administered carefully and vital signs should be monitored.

Patients at a High Risk for Abuse and Dependence
At a particularly high risk for misuse, abuse, and dependence are:

Patients with a history of alcohol or drug abuse or dependence
Emotionally unstable patients
Patients with severe personality disorders, such as Borderline Personality Disorder
Patients with chronic pain or other physical disorders
Patients from the aforementioned group should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.

Long-term treatment with clonazepam should never be discontinued abruptly. It should be withdrawn gradually over a period of weeks or months.

Overdose
An individual who has consumed too much clonazepam will display one or more of the following symptoms:

Somnolence (difficulty staying awake)
Mental confusion
Hypotension
Impaired motor functions
Impaired reflexes
Impaired coordination
Impaired balance
Dizziness
Coma
Clonazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of clonazepam (or any other benzodiazepine) is flumazenil (Anexate).

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