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| {{drugbox |
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| | IUPAC_name = ''Potassium 7-chloro-2,3-dihydro-2-oxo-5-phenyl-<BR>1''H''-1,4-benzodiazepine-3-carboxylate with potassium hydroxide''
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| | image = Clorazepate.svg
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| | image2 = Clorazepate3d.png
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| | width = 200
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| | CAS_number = 57109-90-7
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| | ATC_prefix = N05
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| | ATC_suffix = BA05
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| | PubChem = 22312
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| | DrugBank = APRD00881
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| | C=16 | H=11 | Cl=1 | K=2 | N=2 | O=4
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| | molecular_weight = 408.9 (Dipotassium salt)
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| | bioavailability = 91%
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| | metabolism = [[Liver|Hepatic]]
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| | elimination_half-life = 48 hours
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| | excretion = [[Kidney|Renal]]
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| | pregnancy_US = D
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| | legal_status = [[Schedule IV controlled substance|Schedule IV]](US)
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| | routes_of_administration = Oral
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| }}
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| <!-- Commented out because image was deleted: [[Image:TranxeneAd.png|thumb|300px|left]] -->
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| '''Clorazepate''' (marketed under the brand names '''Tranxene®''' and '''Tranxilium®''') is a drug which is a [[benzodiazepine]] derivative. It possesses [[anxiolytic]], [[anticonvulsant]], [[sedative]] and [[skeletal muscle relaxant]] properties.
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| Clorazepate has been discontinued since February 2006 in the United Kingdom.
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| ==Pharmacology==
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| Clorazepate is a long acting benzodiazepine drug.<ref>{{cite journal | author = The Committee on the Review of Medicines (CRM) | coauthors = | year = 1980 | month = Mar | date = 29 | title = Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. | journal = Br Med J. | volume = 280 | issue = 6218 | pages = 910-2 | pmid = 7388368 }}</ref> The half life of Clorazepate is 36 - 200 hours.<ref>{{cite web | url = http://www.bcnc.org.uk/equivalence.html | title = BENZODIAZEPINE EQUIVALENCY TABLE | accessmonthday = Sept 23 | accessyear = 2007 | author = Professor heather Ashton | year = 2007 | month = April }}</ref>
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| ==Indications==
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| Clorazepate is used in the treatment of [[anxiety disorder]]s and [[insomnia]]. It may also be prescribed as an [[anticonvulsant]] or [[muscle relaxant]].
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| Clorazepate is principally prescribed in the treatment of [[alcoholism|alcohol withdrawal]] and [[epilepsy]], although it is also a useful [[anxiolytic]] because of its long half-life. The normal starting dosage range of Clorazepate is 15 to 60 mg per day. The drug is to be taken two to four times per day. Dosages as high as 90 to 120 mg per day may be used in the treatment of acute alcohol withdrawal. In the United States and Canada, Clorazepate is available in 3.75, 7.5, and 15 mg capsules or tablets. In Europe, tablet formations are 5 mg, 10 mg, 20 mg and 50 mg.<ref>[http://www.ziekenhuis.nl/index.php?cat=medicijngids&medgids=item&id=51600 Tranxene prescribing information in the Netherlands (Dutch language)]; accessed [[2007-03-08]]</ref> Clorazepate SD (controlled release) is available in 11.25 and 22.5 mg tablets. Clorazepate SD is only prescribed when the patient has become adjusted to a certain dosage, and is taken once a day. Clorazepate is available in generic form. Clorazepate begins to act on the [[central nervous system]] within one or two hours, and its effects may be felt for an entire day or longer in some individuals. It is contraindicated for those with impaired renal or hepatic function. Clorazepate is listed under [[Controlled Substances Act#Schedule IV drugs|Schedule IV]] of the [[Controlled Substances Act]]. Clorazepate was approved for use in the United States by the [[Food and Drug Administration]] in 1972.
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| ==Tolerance and dependence==
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| '''The Committee on the Review of Medicines'''
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| The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, [[drug dependence]] and [[benzodiazepine withdrawal]] problems and other adverse effects. The committee found that benzodiazepines do not have any [[antidepressant]] or [[analgesic]] properties and are therefore unsuitable treatments for conditions such as depression, [[tension headaches]] and [[dysmenorrhoea]]. Benzodiazepines are also not beneficial in the treatment of [[psychosis]] due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of [[anxiety]] or [[insomnia]] in children. The committee was in agreement with the [[Institute of Medicine]] (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the [[National Institute on Drug Abuse]] (USA) that there was little evidence that long term use of benzodiazepine hypnotics were benefitial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the [[benzodiazepine withdrawal syndrome]] including symptoms such as [[anxiety]], [[apprehension]], [[tremor]], [[insomnia]], [[nausea]], and [[vomiting]] upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more short acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the [[central nervous system]] depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the [[neonate]] high single doses or repeated low doses have been reported to produce [[hypotonia]], poor sucking, and [[hypothermia]] in the [[neonate]] and irregularities in the [[fetal]] heart. Benzodiazepines should be avoided in [[lactation]]. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause [[confusion]], [[toxic psychosis]], [[convulsions]], or a condition resembling [[delirium tremens]]. Abrupt withdrawal from lower doses may cause depression, [[nervousness]], [[rebound insomnia]], [[irritability]], [[sweating]], and [[diarrhoea]].<ref>{{cite journal | author = Committee on the Review of Medicines | year = 1980 | month = Mar | date = 29 | title = Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. | journal = Br Med J. | volume = 280 | issue = 6218 | pages = 910-2 | pmid = 7388368 | url = http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1601049&blobtype=pdf | format = pdf }}</ref>
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| ==Pregnancy==
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| Chlorazepate if taken in early pregnancy may result in reduced IQ, neurodevelopmental problems, physical malformations in cardiac or facial structure as well as other malformations, however the data is inconclusive. Chlorazepate if used late in pregnancy, the [[third trimester]], causes a definite risk a severe [[benzodiazepine withdrawal syndrome]] in the neonate with symptoms including [[hypotonia]], and reluctance to suck, to [[apnoeic]] spells, [[cyanosis]], and impaired [[metabolic]] responses to cold stress. Floppy infant syndrome and sedation in the new born may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.<ref>{{cite journal | author = McElhatton PR. | coauthors = | year = 1994 | month = Nov-Dec | title = The effects of benzodiazepine use during pregnancy and lactation. | journal = Reprod Toxicol. | volume = 8 | issue = 6 | pages = 461-75 | pmid = 7881198 }}</ref>
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| ==Interactions==
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| All sedatives are likely to magnify the effects of Clorazepate on the central nervous system. [[Cimetidine]], trade name Tagamet, inhibits breakdown of Clorazepate, and leads to increased levels of the drug in the system.
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| [[Image:Clorazepate_DOJ.jpg|frame|right]]
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| ==References==
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| <references/>
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| ==External links==
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| * [http://www.rxlist.com/cgi/generic2/clorazepate.htm Rx-List.com - Clorazepate]
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| * [http://www.inchem.org/documents/pims/pharm/pim327.htm Inchem.org - Clorazepate]
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| {{Benzodiazepines}}
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| {{Anticonvulsants}}
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| [[Category:Benzodiazepines]]
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| [[Category:Hypnotics]]
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| [[de:Clorazepat]]
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| [[es:Clorazepato]]
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| [[gl:Clorazepate]]
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| [[nl:Clorazepaat]]
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| [[ja:クロラゼプ酸二カリウム]]
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| [[pt:Clorazepato dipotássico]]
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