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Pronunciationkloe' ba zam[1]
Trade namesFrisium, Urbanol, Onfi, others[1]
  • 7-chloro-1-methyl-5-phenyl-1,5-benzodiazepine-2,4-dione
Clinical data
Drug classBenzodiazepine[1]
Main usesAnxiety, epilepsy[2]
Side effectsSedation, drooling, vomiting, constipation, pneumonia, poor coordination, appetite change[3]
  • AU: C
  • US: C (Risk not ruled out)
Routes of
By mouth
Onset of action0.5–4 hours
External links
License data
Legal status
Bioavailability87% (by mouth)
Protein binding80–90%
    • N-desmethylclobazam
    • 4′-hydroxyclobazam
Elimination half-life
    • clobazam: 36–42 hours
    • N-desmethylclobazam: 59–82 hours
Chemical and physical data
Molar mass300.74 g·mol−1
3D model (JSmol)
  • ClC1=CC(N(C2=CC=CC=C2)C(CC(N3C)=O)=O)=C3C=C1
  • InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3 checkY

Clobazam, sold under the brand names Frisium among others, is a medication used to treat anxiety and epilepsy.[2] This includes Lennox-Gastaut and Dravet syndrome.[3] For anxiety it should only be used short term.[2] It is taken by mouth.[2]

Common side effects include sedation, drooling, vomiting, constipation, pneumonia, poor coordination, and appetite change.[3] Other side effects may include misuse, suicide, Stevens-Johnson syndrome, and infertility.[3] Use during pregnancy may harm the baby.[3] It is a benzodiazepine that is believed to work by enhancing gamma-aminobutyric acid (GABA).[1]

Clobazam was patented in 1968 and come into medical use in 1975.[4] It is available as a generic medication.[2] In the United Kingdom 30 pills of 10 mg costs the NHS about £4 as of 2021.[2] This amount in the United States is about 20 USD.[5] In the United States it is a schedule IV controlled substance.[3]

Medical uses

Clobazam is used for anxiety and epilepsy.


In the United Kingdom clobazam is approved for short-term (2–4 weeks) relief of acute anxiety in patients who have not responded to other drugs, with or without insomnia and without uncontrolled clinical depression.[6] Clobazam is also approved as a short-term (2–4 weeks) adjunctive agent in schizophrenia and other psychotic disorders to manage anxiety or agitation.[6]


Clobazam is approved in Canada for add-on use in tonic-clonic, complex partial, and myoclonic seizures.[7] Clobazam is approved for adjunctive therapy in complex partial seizures,[8] certain types of status epilepticus, specifically the mycolonic, myoclonic-absent, simple partial, complex partial, and tonic varieties,[9] and non-status absence seizures.

In India, clobazam is approved for use as an adjunctive therapy in epilepsy, and in acute and chronic anxiety.[10] In Japan, clobazam is approved for adjunctive therapy in treatment-resistant epilepsy featuring complex partial seizures.[11] In New Zealand, clobazam is marketed as Frisium[12] It was not approved in the United States until October 25, 2011, when it was approved for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age or older.[13]

As an adjunctive therapy in epilepsy, it is used in people who have not responded to first-line drugs and in children who are refractory to first-line drugs. It is unclear if there are any benefits to clobazam over other seizure medications for children with Rolandic epilepsy or other epileptic syndromes.[14] It is not recommended for use in children between the ages of six months and three years, unless there is a compelling need.[6]

Clobazam is sometimes used for refractory epilepsies. However, long-term prophylactic treatment of epilepsy may have considerable drawbacks, most importantly decreased antiepileptic effects due to drug tolerance which may render long-term therapy less effective.[15] Other antiepileptic drugs may therefore be preferred for the long-term management of epilepsy. Furthermore, benzodiazepines may have the drawback, particularly after long-term use, of causing rebound seizures upon abrupt or over-rapid discontinuation of therapy forming part of the benzodiazepine withdrawal syndrome.


In adults it is often started at 20 to 30 mg per day, which may be increased to 60 mg per day.[2] Smaller doses should be used in older people.[2]


Clobazam should be used with great care in patients with the following disorders:

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals, and individuals with comorbid psychiatric disorders.[17]

Side effects

Common side effects include fever, drooling, and constipation.[18]

Other side effects include hives and other rashes. In December 2013, the FDA added warnings to the label, that it can cause serious skin reactions, Stevens–Johnson syndrome, and toxic epidermal necrolysis, especially in the first eight weeks of treatment.[19]


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.[20]

Classic (non-anxioselective) benzodiazepines in animal studies have been shown to increase reward-seeking behaviours which may suggest an increased risk of addictive behavioural patterns.[21] Clobazam abuse has been reported in some countries, according to a 1983 World Health Organisation report.[22]


In humans, tolerance to the anticonvulsant effects of clobazam may occur[23] and withdrawal seizures may occur during abrupt or overrapid withdrawal.[24]

Clobazam as with other benzodiazepine drugs can lead to physical dependence, addiction, and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from clobazam or other benzodiazepines after regular use often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dosage and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Benzodiazepine treatment should only be discontinued via a slow and gradual dose reduction regimen.[25]


Overdose and intoxication with benzodiazepines, including clobazam, may lead to CNS depression, associated with drowsiness, confusion, and lethargy, possibly progressing to ataxia, respiratory depression, hypotension, and coma or death. The risk of a fatal outcome is increased in cases of combined poisoning with other CNS depressants, including alcohol.[26]


  • Alcohol increases bioavailability by 50%; compounded depressant effect may precipitate life-threatening toxicity.
  • Cimetidine increases the effects of clobazam.
  • Valproate.


Clobazam is predominantly a positive allosteric modulator at the GABAA receptor with some speculated additional activity at sodium channels and voltage-sensitive calcium channels.[27]

Like other 1,5-benzodiazepines (for example, arfendazam, lofendazam, or CP-1414S), the active metabolite N-desmethylclobazam has less affinity for the α1 subunit of the GABAA receptor compared to the 1,4-benzodiazepines. It has higher affinity for α2 containing receptors, where it has positive modulatory activity.[28][29]

In a double-blind placebo-controlled trial published in 1990 comparing it to clonazepam, 10 mg of clobazam was shown to be less sedative than either 0.5 mg or 1 mg of clonazepam.[30]

The α1 subtype of the GABAA receptor, was shown to be responsible for the sedative effects of diazepam by McKernan et al. in 2000, who also showed that its anxiolytic and anticonvulsant properties could still be seen in mice whose α1 receptors were insensitive to diazepam.[31]

In 1996, Nakamura et al. reported that clobazam and its active metabolite, N-desmethylclobazam (norclobazam), work by enhancing GABA-activated chloride influx at GABAA receptors,[32] creating a hyperpolarizing, inhibitory postsynaptic potential.[33] It was also reported that these effects were inhibited by the GABA antagonist flumazenil, and that clobazam acts more efficiently in GABA-deficient brain tissue.[32]


Clobazam has two major metabolites: N-desmethylclobazam and 4′-hydroxyclobazam, the former of which is active.[34] The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4-hydroxyclobazam by CYP2C18 and CYP2C19.[35]


Clobazam is a 1,5-benzodiazepine, meaning that its diazepine ring has nitrogen atoms at the 1 and 5 positions (instead of the usual 1 and 4).[36]

It is not soluble in water and is available in oral form only.[27][26]


Clobazam was discovered at the Maestretti Research Laboratories in Milan and was first published in 1969;[37] Maestretti was acquired by Roussel Uclaf[38] which became part of Sanofi.


  1. 1.0 1.1 1.2 1.3 "Clobazam". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 6 May 2021. Retrieved 5 January 2022.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 355. ISBN 978-0857114105.
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External links

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