Detail:

        Clonazepam, sold under the brand name Klonopin among others, is a medication used to prevent and treat seizures, panic disorder, and for the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine class. It is taken by mouth. It begins having an effect within an hour and lasts between 6 and 12 hours.

        Common side effects include sleepiness, poor coordination, and agitation. Long-term use may result in tolerance, dependence, and withdrawal symptoms if stopped abruptly. Dependence occurs in one-third of people who take clonazepam for longer than four weeks. It may increase risk of suicide in people who are depressed. If used during pregnancy it may result in harm to the baby. It binds to GABAA receptors and increases the effect of the neurotransmitter gamma-Aminobutyric acid (GABA).

        Clonazepam was initially patented in 1964 and went on sale in 1975 in the United States from Roche. It is available as a generic medication. The wholesale cost in the developing world is between US$0.01 and US$0.07 per pill. In the United States, the pills are about US$0.40 each.In many areas of the world it is commonly used as a recreational drug.

Medical uses:

        Clonazepam is prescribed for epilepsy and panic disorder with or without agoraphobia.

Seizures:

        Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to the anticonvulsant effects.

        Clonazepam has been found effective in treating epilepsy in children, and the inhibition of seizure activity seemed to be achieved at low plasma levels of clonazepam. As a result, clonazepam is sometimes used for certain rare childhood epilepsies; however, it has been found to be ineffective in the control of infantile spasms. Clonazepam is mainly prescribed for the acute management of epilepsies. Clonazepam has been found to be effective in the acute control of non-convulsive status epilepticus; however, the benefits tended to be transient in many of the people, and the addition of phenytoin for lasting control was required in these patients.

         It is also approved for treatment of typical and atypical absences, infantile myoclonic, myoclonic and akinetic seizures. A subgroup of people with treatment resistant epilepsy may benefit from long-term use of clonazepam; the benzodiazepine clorazepate may be an alternative due to its slow onset of tolerance.

Anxiety disorders:

        Panic disorder with or without agoraphobia.

        Clonazepam has also been found effective in treating other anxiety disorders, such as social phobia, but this is an off-label use.

        The effectiveness of clonazepam in the short-term treatment of panic disorder has been demonstrated in controlled clinical trials. Some long-term trials have suggested a benefit of clonazepam for up to three years without the development of tolerance but these trials were not placebo-controlled.[citation needed] Clonazepam is also effective in the management of acute mania.

Muscle disorders:

        Restless legs syndrome can be treated using clonazepam as a third-line treatment option as the use of clonazepam is still investigational. Bruxism also responds to clonazepam in the short-term. Rapid eye movement behavior disorder responds well to low doses of clonazepam.

        The treatment of acute and chronic akathisia induced by neuroleptics, also called antipsychotics.

        Spasticity related to amyotrophic lateral sclerosis.

        Alcohol withdrawal syndrome

Overdose:

        Excess doses may result in:

        Difficulty staying awake

        Mental confusion

        Nausea

        Impaired motor functions

        Impaired reflexes

        Impaired coordination

        Impaired balance

        Dizziness

        Respiratory depression

        Low blood pressure

        Coma

        Coma can be cyclic, with the individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a 4-year-old boy who suffered an overdose of clonazepam. The combination of clonazepam and certain barbiturates, e.g. amobarbital, at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression.

        Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting.

Pharmacokinetics:

        Clonazepam is lipid-soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites. Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. It has an elimination half-life of 19–60 hours. Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4–8 hours.

        Clonazepam passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound clonazepam in the blood serum. Clonazepam plasma levels are very unreliable amongst patients. Plasma levels of clonazepam can vary as much as tenfold between different patients.

        Clonazepam is largely bound to plasma proteins. Clonazepam passes through the blood–brain barrier easily, with blood and brain levels corresponding equally with each other. The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam.

        It is effective for 6–8 hours in children, and 6–12 in adults.

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