A benzodiazepine derivative having anticonvulsant, muscle relaxant, and very potent anxiolytic properties.
Has a long half-life of 18-50 hours, making it a long-acting benzodiazepines.
Has a fast onset of action and high effectiveness rate and low toxicity in overdose.
Adverse reactions including paradoxical effects, drowsiness, and cognitive impairment.
Cognitive impairment can persist for at least 6 months after withdrawal of clonazepam.
Long-term effects of benzodiazepines include tolerance, a benzodiazepine dependence as well as a benzodiazepine withdrawal syndrome occurs in a third of people treated with clonazepam for longer than 4 weeks.
High potency agent and is sometimes used as a second line treatment of epilepsy.
Not a first line for the long-term treatment of seizures due to the development of tolerance to anticonvulsant effects.
Used for the treatment of panic disorder.
As with other benzodiazepines is the enhancement of the neurotransmitter GABA via modulation of the GABAA receptor.
May be prescribed for epilepsy, anxiety disorders, panic disorder, mania or acute psychosis together with firstline drugs, insomnia, restless leg syndrome, rapid eye movement behavior disorder, akathisia, spsticity disorders, acute mania and bruxism.
Not recommended for long-term managment of epilepsy due to the development of tolerance.
The side effects of hypotonia and drowsiness are common with clonazepam therapy.
Effective as a short-term adjunct to SSRI treatment in obsessive-compulsive disorders and clinical depression.
Available as tablets and orally disintegrating tablets (0.5mg, 1 mg), oral solution, as well as solution for injection or intravenous infusion.
PREPARATIONS: Tablets: 0.5, 1, and 2 mg; disintegrating tablets: 0.125, 0.25, 0.5, 1, and 2 mg.
Common adverse reactions include drowsiness, cognitive impairment, motor function impairment, irritability, aggression, psychomotor agitation, loss of libido, lack of motivation, impaired coordination, dizziness, impaired balance, hallicinations, short term-memory loss, amnesia, and headache.
Suppresses REM sleep, and may cause worsening of depression, disinhibition, ans sexual dysfunction.
Long-term use and withdrawal may lead to delirium tremens.
Sudden drug withdrawal can lead to severe and even fatal symptoms including status epilepticus.
Should be reduced slowly and gradually when discontinuing the drug to reduce withdrawal effects.
The elderly metabolize benzodiazepines more slowly than younger individuals.
The elderly are more sensitive to the effects of benzodiazepines even at similar blood plasma in younger patients.
Dosage for the elderly are recommended to be about half of that given to younger adults.
Treatment in the elderly should be for no longer than 2 weeks.
This agent is not recommended for the elderly due the risk of drug accumulation.
Caution in the elderly becuae of increased risk of falls.
May aggravate hepatic porphyria.
Increases violent behavior in individuals with chronic schizophrenia.
Decreases the levels of carbamazepine, and its serum level is reduced by carbamazepine.
Azole antifungals may inhibit the metabolism of clonazepam.
May decrease or increse phenytoin levels when utilized together.
Phenytoin may lower clonazepam plasma levels, by increasing the clearance by approximately 50% and decreasing its half life by 31%.
Increases primidone and phenobarbital levels.
Combined with antidepressants, sedative antihistamines, opiates, antipsychotics and alcohol may result in enhanced sedative effects.
Can cause both psychological and physical dependence.
When used late in pregnancy may result in the development of a severe withdrawal syndrome in the neonate.
Possible adverse effects during pregnancy include; abortion, malformation, intrauterine growth retardation, functional deficits, floppy infant syndrome, carcinogenesis and mutagenesis.
Primary mechanism of action is via modulating GABA function in the brain, via a receptor, located on GABAA receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing.
Enhances the effect of GABA at the GABAA receptor by increasing the opening frequency of chloride ion channels which leads to increased inhibitory effects with resultant central nervous system depression.
Lipid soluble, and rapidly crosses the blood-brain barrier and penetrates the placenta and into breast milk.
Metabolized extensively via nitroreduction by cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19.
The metabolism of benzodiazepines can be affected by inhibitors of CYP34A including erythromycin, clarithromycin, antifungal agents, ritonavir, and grapefruit juice.
Has a half life of 19-60 hours.
Peak blood concentrations of 6.5–13.5 ng/mL are usually reached within 1–2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults, and rapidly enters the CNS via the blood-brain barrier.
Plasma levels can vary as much as tenfold between different individuals.
Clonazepam is largely bound to plasma proteins.