Clonazepam

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Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and akathisia.<ref name="AHFS2015">Template:Cite web</ref> It is a long-acting<ref>Template:Cite book</ref> benzodiazepine.<ref name="AHFS2015" /> It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally (swallowed by mouth) but is also used intravenously.<ref name="AHFS2015" /><ref>Template:Cite journal</ref> Effects begin within one hour and last between eight and twelve hours in adults.<ref name="Coop2007">Template:Cite book</ref><ref name="Paxam_Data_Sheet">Template:Cite web</ref>

Common side effects may include sleepiness, weakness, poor coordination, difficulty concentrating, and agitation. Clonazepam may also decrease memory formation.<ref name=AHFS2015/> Long-term use may result in tolerance, dependence, and life-threatening withdrawal symptoms if stopped abruptly.<ref name=AHFS2015/><ref>Template:Cite journal</ref> Dependence occurs in one-third of people who take benzodiazepines for longer than four weeks.<ref name="Riss-2008"/> The risk of suicide increases, particularly in people who are already depressed.<ref name=AHFS2015/><ref name=Dodd2017/> Use during pregnancy may result in harm to the fetus.<ref name=AHFS2015/> Clonazepam binds to GABA_A receptors, thus increasing the effect of the chief inhibitory neurotransmitter γ-aminobutyric acid (GABA).<ref name="Riss-2008">Template:Cite journalTemplate:Cbignore</ref>

Clonazepam was patented in 1960, marketed in 1964, and went on sale in 1975 in the United States from Roche.<ref name=Fis2006>Template:Cite book</ref><ref>Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2015/> In 2023, it was the 62nd most commonly prescribed medication in the United States, with more than 10Template:Nbspmillion prescriptions.<ref name="Top300Drugs">Template:Cite web</ref><ref>Template:Cite web</ref> In many areas of the world, it is commonly used as a recreational drug.<ref>Template:Cite book</ref><ref>Template:Cite book</ref>

Medical uses

Clonazepam is prescribed for short-term management of epilepsy, anxiety, obsessive–compulsive disorder (OCD), and panic disorder with or without agoraphobia.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite web</ref>

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.<ref name="pmid 12657420">Template:Cite journal</ref> As a result, clonazepam is sometimes used for certain rare childhood epilepsies, but it is ineffective in the control of infantile spasms.<ref>Template:Cite journal</ref> Clonazepam is mainly prescribed for the acute management of epilepsy. Clonazepam is effective in the acute control of non-convulsive status epilepticus; the benefits, though, tended to be transient in many people, and the addition of phenytoin for lasting control was required in these patients.<ref>Template:Cite journal</ref>

It is also approved for the treatment of typical and atypical absences (seizures) and infantile myoclonic and akinetic seizures.<ref name="Clonazepam. A review of a new antic">Template:Cite journal</ref> 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.<ref name="Riss-2008"/><ref>Template:Cite journal</ref>

Anxiety disorders

• Panic disorder with or without agoraphobia.<ref>Template:Cite journal</ref>
• Clonazepam has also been found effective in treating other anxiety disorders, such as social phobia, but this is an off-label use.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

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.<ref>Template:Cite journal</ref> Clonazepam is also effective in the management of acute mania.<ref>Template:Cite journal</ref>

Muscle disorders

Restless legs syndrome can be treated using clonazepam as a third-line treatment option, as the use of clonazepam is still investigational.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Bruxism also responds to clonazepam in the short term.<ref name="Huynh-">Template:Cite journal</ref> REM sleep behavior disorder responds well to low doses of clonazepam.<ref name="Ferini-Strambi">Template:Cite journal</ref> It is also used for:

• The treatment of acute and chronic akathisia induced by neuroleptics, also called antipsychotics<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Spasticity related to amyotrophic lateral sclerosis (ALS)<ref>Template:Cite journal</ref>

Other

• Benzodiazepines, such as clonazepam, are sometimes used for the treatment of mania or acute psychosis-induced aggression. In this context, benzodiazepines are given either alone or in combination with other first-line drugs such as lithium, haloperidol, or risperidone.<ref>Template:Cite journal</ref><ref name=":Gillies2013">Template:Cite journal</ref> The effectiveness of taking benzodiazepines along with antipsychotic medication is unknown, and more research is needed to determine if benzodiazepines are more effective than antipsychotics when urgent sedation is required.<ref name=":Gillies2013" />
• Hyperekplexia<ref>Template:Cite journal</ref>
• Many forms of parasomnia and other sleep disorders are treated with clonazepam.<ref>Template:Cite journal</ref>
• It is not effective for preventing migraines.<ref>Template:Cite journal</ref>

Contraindications

• Coma
• Current alcohol use disorder
• Current substance use disorder
• Respiratory depression<ref>Template:Cite web</ref>

Adverse effects

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.<ref>Template:Cite web Template:PD-notice</ref>

Common

• Sedation<ref>Template:Cite journal</ref>
• Euphoria
• Motor impairment

Less common

• Confusion<ref name="Riss-2008"/>
• Irritability and aggression<ref>Template:Cite journal</ref>
• Psychomotor agitation<ref>Template:Cite journal</ref>
• Lack of motivation<ref>Template:Cite journal</ref>
• Increased libido<ref>Template:Cite web</ref>
• Loss of libido
• Impaired motor function
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Cognitive impairmentsTemplate:Vague<ref name="meylers_side_effects_of_psychiatric_drugs">Template:Cite book</ref>
  • Hallucinations.<ref>Template:Cite web</ref>
  • Short-term memory loss<ref name="the_interface_of_neurology_internal_medicine">Template:Cite book</ref>
  • Anterograde amnesia (common with higher doses)<ref name="the_american_psychiatric_publishing_textbook_of_psychoph_a01">Template:Cite book</ref>
• Some users report hangover-like symptoms of drowsiness, headaches, sluggishness, and irritability upon waking up if the medication was taken before sleep. This is likely the result of the medication's long half-life, which continues to affect the user after waking up.<ref>Template:Cite web</ref><ref name="narcolepsy_a05">Template:Cite book</ref><ref name="principles_of_psychopharmacology_for_mental_health_profession">Template:Cite book</ref> While benzodiazepines induce sleep, they tend to reduce the quality of sleep by suppressing or disrupting REM sleep.<ref name="sleep_medicine_a04">Template:Cite book</ref> After regular use, rebound insomnia may occur when discontinuing clonazepam.<ref name="katzung_trevors_review_of_pharmacology">Template:Cite book</ref>
• Benzodiazepines may cause or worsen depression.<ref name="Riss-2008"/>

Occasional

• Dysphoria<ref>Template:Cite journal</ref>
• Induction of seizures<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> or increased frequency of seizures<ref>Template:Cite journal</ref>
• Personality changes<ref name="clonepi">Template:Cite journal</ref>
• Behavioural disturbances<ref>Template:Cite journal</ref>
• Ataxia<ref name="Riss-2008"/>

Rare

• Suicide through disinhibition<ref name=Dodd2017>Template:Cite journal</ref>
• Psychosis<ref>Template:Cite journal</ref>
• Incontinence<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Paradoxical behavioural disinhibition<ref name="Riss-2008"/><ref name="pmid2019899">Template:Cite journal</ref> (most frequently in children, the elderly, and in persons with developmental disabilities)
  • Rage
  • Excitement
  • Impulsivity

The long-term effects of clonazepam can include depression,<ref name="Riss-2008"/> disinhibition, and sexual dysfunction.<ref>Template:Cite journal</ref>

Drowsiness

Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, so alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms.

Withdrawal-related

• Anxiety
• Irritability
• Insomnia
• Tremors
• Headaches
• Stomach pain
• Hallucinations
• Suicidal thoughts or urges
• Depression
• Fatigue
• Dizziness
• Sweating
• Confusion
• Potential to exacerbate existing panic disorder upon discontinuation
• Seizures<ref>Template:Cite journal</ref> similar to delirium tremens (with long-term use of excessive doses)

Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior.<ref>Template:Cite journal</ref> Many individuals treated on a long-term basis develop a dependence. Physiological dependence was demonstrated by flumazenil-precipitated withdrawal.<ref>Template:Cite journal</ref> Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects, including side effects, of the drug.

A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms.<ref>Template:Cite book</ref>

Tolerance and withdrawal

Template:Main Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding.<ref name="Riss-2008"/>

Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide.<ref>Template:Cite journal</ref> In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy.<ref>Template:Cite journal</ref> Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant.<ref name="Clonazepam. A review of a new antic"/>

Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects.<ref name="clonepi"/> Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring.<ref>Template:Cite journal</ref>

Overdose

Template:Main Excess doses may result in:

• Difficulty staying awake
• Mental confusion
• 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 four-year-old boy who overdosed on clonazepam.<ref>Template:Cite journal</ref> The combination of clonazepam and certain barbiturates (for example, amobarbital), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression.<ref>Template:Cite journal</ref>

Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting.<ref>Template:Cite web</ref>

Detection in biological fluids

Clonazepam and 7-aminoclonazepam may be quantified in plasma, serum, or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses.<ref>R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 335-337.</ref>

Special precautions

The elderly metabolize benzodiazepines more slowly than younger people and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as clonazepam are not generally recommended for the elderly due to the risk of drug accumulation.<ref name="Riss-2008"/>

The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders.<ref name="Authier-2009">Template:Cite journal</ref> Clonazepam is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines.<ref>Template:Cite journal</ref>

Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital.<ref name="Authier-2009"/><ref>Template:Cite journal</ref>

Doses higher than 0.5–1 mg per day are associated with significant sedation.<ref>Template:Cite journal</ref>

Clonazepam may aggravate hepatic porphyria.<ref name="Bonkowsky">Template:Cite journal</ref><ref>Template:Cite journal</ref>

Clonazepam is not recommended for patients with chronic schizophrenia. A 1982 double-blinded, placebo-controlled study found clonazepam increases violent behavior in individuals with chronic schizophrenia.<ref>Template:Cite journal</ref>

Clonazepam has similar effectiveness to other benzodiazepines at often a lower dose.<ref>Template:Cite web</ref>

Interactions

Clonazepam decreases the levels of carbamazepine,<ref name="pmid2912">Template:Cite journal</ref><ref>Template:Cite journal</ref> and, likewise, clonazepam's level is reduced by carbamazepine. Azole antifungals, such as ketoconazole, may inhibit the metabolism of clonazepam.<ref name="Riss-2008"/> Clonazepam may affect levels of phenytoin (diphenylhydantoin).<ref name="pmid2912"/><ref>Template:Cite journal</ref><ref name="inter">Template:Cite journal</ref><ref>Template:Cite journal</ref> In turn, Phenytoin may lower clonazepam plasma levels by increasing the speed of clonazepam clearance by approximately 50% and decreasing its half-life by 31%.<ref>Template:Cite journal</ref> Clonazepam increases the levels of primidone<ref name="inter"/> and phenobarbital.<ref>Template:Cite journal</ref>

Combined use of clonazepam with certain antidepressants, anticonvulsants (such as phenobarbital, phenytoin, and carbamazepine), sedative antihistamines, opiates, and antipsychotics, nonbenzodiazepines (such as zolpidem), and alcohol may result in enhanced sedative effects.<ref name="Riss-2008"/>

Pregnancy

Template:See also There is some medical evidence of various malformations (for example, cardiac or facial deformations when used in early pregnancy); however, the data is not conclusive. The data are also inconclusive on whether benzodiazepines such as clonazepam cause developmental deficits or decreases in IQ in the developing fetus when taken by the mother during pregnancy. Clonazepam, when used late in pregnancy, may result in the development of a severe benzodiazepine withdrawal syndrome in the neonate. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress.<ref>Template:Cite journal</ref>

The safety profile of clonazepam during pregnancy is less clear than that of other benzodiazepines, and if benzodiazepines are indicated during pregnancy, chlordiazepoxide and diazepam may be a safer choice. The use of clonazepam during pregnancy should only occur if the clinical benefits are believed to outweigh the clinical risks to the fetus. Caution is also required if clonazepam is used during breastfeeding. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis. Neonatal withdrawal syndrome associated with benzodiazepines include hypertonia, hyperreflexia, restlessness, irritability, abnormal sleep patterns, inconsolable crying, tremors, or jerking of the extremities, bradycardia, cyanosis, suckling difficulties, apnea, risk of aspiration of feeds, diarrhea and vomiting, and growth retardation. This syndrome can develop between three days to three weeks after birth and can have a duration of up to several months. The pathway by which clonazepam is metabolized is usually impaired in newborns. If clonazepam is used during pregnancy or breastfeeding, it is recommended that serum levels of clonazepam are monitored and that signs of central nervous system depression and apnea are also checked for. In many cases, non-pharmacological treatments, such as relaxation therapy, psychotherapy, and avoidance of caffeine, can be an effective and safer alternative to the use of benzodiazepines for anxiety in pregnant women.<ref>Template:Cite journal</ref>

Pharmacology

Mechanism of action

Clonazepam enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system to give its anticonvulsant, skeletal muscle relaxant, and anxiolytic effects.<ref>Template:Cite web</ref> It acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. This further results in an inhibition of synaptic transmission across the central nervous system.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Benzodiazepines do not have any effect on the levels of GABA in the brain.<ref>Template:Cite journal</ref> Clonazepam has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase. Clonazepam does, however, affect glutamate decarboxylase activity. It differs from other anticonvulsant drugs it was compared to in a study.<ref>Template:Cite journal</ref>

Clonazepam's primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABA_A receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABA_A receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA's inhibitory effects and resultant central nervous system depression.<ref name="Riss-2008"/> In addition, clonazepam decreases the utilization of 5-HT (serotonin) by neurons<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and has been shown to bind tightly to central-type benzodiazepine receptors.<ref>Template:Cite journal</ref> Because clonazepam is effective in low milligram doses (0.5 mg clonazepam = 10 mg diazepam),<ref>"Benzodiazepine Equivalency Table" based on NRHA Drug Newsletter, April 1985 and Benzodiazepines: How they Work & How to Withdraw (The Ashton Manual), 2002.[1] Template:Webarchive</ref><ref>Template:Cite web</ref> it is said to be among the class of "highly potent" benzodiazepines.<ref>Template:Cite journal</ref> The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and the inhibition of sustained, high-frequency repetitive firing.<ref>Template:Cite journal</ref>

Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Clonazepam decreases release of acetylcholine in the feline brain<ref>Template:Cite journal</ref> and decreases prolactin release in rats.<ref>Template:Cite journal</ref> Benzodiazepines inhibit cold-induced thyroid-stimulating hormone (also known as TSH or thyrotropin) release.<ref>Template:Cite journal</ref> Benzodiazepines act via micromolar benzodiazepine binding sites as Ca²⁺ channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as a mechanism for high-dose effects on seizures in the study.<ref>Template:Cite journal</ref>

Clonazepam is a 2'-chlorinated derivative of nitrazepam, which increases its potency due to electron-attracting effect of the halogen in the ortho-position.<ref>Template:Cite book</ref><ref name="Coop2007"/>

Pharmacokinetics

Clonazepam is lipid-soluble, rapidly crosses the blood–brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine.<ref name="auto1">Template:Cite web</ref> 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.<ref>Template:Cite journal</ref> It has an elimination half-life of 19–60 hours.<ref name="Riss-2008"/> 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.<ref>Template:Cite web</ref>

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

Clonazepam has plasma protein binding of 85%.<ref>Template:Cite journal</ref><ref name="auto1"/> Clonazepam passes through the blood–brain barrier easily, with blood and brain levels corresponding equally with each other.<ref>Template:Cite journal</ref> The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam.<ref name="auto"/><ref>Template:Cite journal</ref> These metabolites are excreted by the kidney.<ref name="auto1"/>

It is effective for 6–8 hours in children, and 8–12 hours in adults.<ref>Template:Cite book</ref><ref name="Paxam_Data_Sheet" />

Society and culture

Recreational use

Template:See also A 2006 US government study of hospital emergency department (ED) visits found that sedative-hypnotics were the most frequently implicated pharmaceutical drug in visits, with benzodiazepines accounting for the majority of these. Clonazepam was the second most frequently implicated benzodiazepine in ED visits. Alcohol alone was responsible for over twice as many ED visits as clonazepam in the same study. The study examined the number of times the non-medical use of certain drugs was implicated in an ED visit. The criteria for non-medical use in this study were purposefully broad, and include, for example, drug abuse, accidental or intentional overdose, or adverse reactions resulting from legitimate use of the medication.<ref name=dawn2neodredv>Template:Cite web</ref>

Formulations

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

Clonazepam is available as tablets and orally disintegrating tablets (wafers) an oral solution (drops), and as a solution for injection or intravenous infusion.<ref name=":0">Template:Cite book</ref>

Crime

In some countries, clonazepam is used by criminals to subdue their victims.<ref>Template:Cite web</ref>

Brand names

File:Rivotril.jpg

Brand name clonazepam tablets

It is marketed under the brand name Rivotril by Roche in Argentina, Australia, Austria, Bangladesh, Belgium, Brazil, Canada, Colombia, Costa Rica, Croatia, the Czech Republic, Denmark, Estonia,<ref>Template:Cite web</ref> Germany, Hungary, Iceland, Ireland, Italy, China, Mexico, the Netherlands, Norway, Portugal, Peru, Pakistan, Romania, Serbia, South Africa, South Korea, Spain, Turkey, and the United States; Emcloz, Linotril, Lonazep, Clotrin and Clonotril in India and other parts of Europe; under the name Riklona in Indonesia and Malaysia; and under the brand name Klonopin by Roche in the United States. Other names, such as Antelepsin, Clonoten, Ravotril, Rivotril, Iktorivil, Clonex (Israel), Paxam, Petril, Naze, Zilepam and Kriadex, are used throughout the world.<ref name="Clonazepam International" /><ref name=":0" /> In August 2021, Roche Australia transferred Rivotril to Pharmaco Australia Ltd.<ref>Template:Cite web</ref>

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  Klonopin 0.5 mg tablet
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  Klonopin 1 mg tablet
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  Klonopin 2 mg tablet
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  Clonazepam orally disintegrating tablet, 0.25 mg

Further reading

• Poisons Information Monograph - Clonazepam