Clonazepam

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Clonazepam (marketed by Roche under the trade-name Klonopin® in the United States and Rivotril® in Europe, South America and Canada) is a drug which is a benzodiazepine derivative. It is a highly potent 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 euphoric 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, excluding alprazolam which alone is considered to be the most potent. 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 approximately 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
• Tourette Syndrome - Clonazepam has shown to be helpful in reducing and dealing with the physical motor tics associated with TS, though is still considered an off-label usage by many.

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 Legs 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)

Rare side effects:

• Anger (Most frequently on children and elderly)
• Rage

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®).

Recreational Use

Owing to its availability, clonazepam is one of the most frequently abused benzodiazepines. It is often mixed with opiates, particularly heroin, to produce euphoria far in excess of that produced by either drug on its own. Illicit use of clonazepam is very common in teenagers seeking help with substance addiction.

Legal Status

Clonazepam is a Schedule IV drug in the United States, and possession is illegal without a prescription.

References

• Wallace, Christina. "Kpin, a hit drug with teens, can be deadly, officials say."] Boston Metro, Wednesday April 12, 2006. Page 2.

External links

• [Rx-List - Clonazepam]
• [Inchem - Clonazepam]
• [Clonazepam - Prescription Drug Info] Detailed Drug Profile
• [FDA prescription insert]

Anticonvulsants (N03) [http://encycl.opentopia.com/ edit]

N03AA - Barbiturates: -- Pyrimidinediones: N03AB - Hydantoins: N03AC - Oxazolidinediones: N03AD - Succinimides: N03AE - Benzodiazepines: N03AF - Carboxamides: N03AG - Fatty acid derivatives: Valproylamides: -- Carboxylic acids: -- GABA analogs: N03AX and others -- Monosaccharides: -- Aromatic allylic alcohols: -- Ureas: -- Carbamates: -- Pyrrolidines: -- Sulfonamides: -- Propionates: -- Aldehydes: -- Bromides:

 

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