Brotizolam
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Clinical data | |
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Trade names | Lendormin |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Oral |
ATC code | |
Legal status | |
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Pharmacokinetic data | |
Bioavailability | 48–95% |
Metabolism | Hepatic |
Elimination half-life | 4.4 hours (range, 2.6–6.9 h) |
Excretion | Renal |
Identifiers | |
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JSmol) | |
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Brotizolam
It was patented in 1974[9] and came into medical use in 1984.[10] Brotizolam is not approved for sale in the UK, United States or Canada. It is approved for sale in the Netherlands, Germany, Spain, Belgium, Luxembourg, Austria, Portugal, Israel, Italy, Taiwan and Japan.
Medical uses
Brotizolam is prescribed for the short-term treatment, 2–4 weeks only of severe or debilitating insomnia. Insomnia can be described as a difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Brotizolam is a short-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep or getting to sleep. Hypnotics should only be used on a short-term basis or in those with chronic insomnia on an occasional basis.[11]
Brotizolam, in a dose of 0.25 mg can be used as a premedication prior to surgery, this dose was found to be comparable in efficacy to 2 mg flunitrazepam as a premedicant prior to surgery.[12]
Side effects
Common side effects of brotizolam are typical of hypnotic benzodiazepines and are related to
Less common side effects include
Brotizolam can cause residual side effects the next day such as impaired cognitive and motor functions as well as drowsiness. Disruption of sleep patterns may also occur such as suppression of
In clinical trials brotizolam 0.125 to 0.5 mg improved sleep in insomniacs similarly to nitrazepam 2.5 and 5 mg, flunitrazepam 2 mg and triazolam 0.25 mg, whilst brotizolam 0.5 mg was shown to be superior to flurazepam 30 mg, but inferior to temazepam 30 mg in some studies. Brotizolam at dosages below 0.5 mg at night usually produced minimal morning drowsiness; no residual impairment of psychomotor performance occurs following dosages within the recommended range of 0.125 to 0.25 mg. No serious side effects have been reported to date and the most frequently observed adverse experiences are drowsiness, headache and dizziness. Mild rebound insomnia may occur in some patients when treatment is stopped.[8]
Contraindications and special caution
Thienodiazepines and benzodiazepines require special precaution if used in the elderly, during pregnancy, in children,
Pharmacology
Brotizolam has been shown in animal studies to be a very high potency thienodiazepine. The
Brotizolam increases the slow wave light sleep (SWLS) in a dose-dependent manner whilst suppressing deep sleep stages. Less time is spent in stages 3 and 4, which are the deep sleep stages, when GABAergics such as brotizolam are used. Benzodiazepines and thienodiazepines are therefore not ideal hypnotics in the treatment of insomnia. The suppression of deep sleep stages by either may be especially problematic to the elderly as they naturally spend less time in the deep sleep stage.[16]
Abuse
Brotizolam is a drug with a potential for abuse. Drug misuse is defined as taking the drug to achieve a 'high', or continuing to take the drug in the long term against medical advice.[17]
Abuse of brotizolam, although not widespread, was a problem in Hong Kong back in the late 1980s and 1990s. To control benzodiazepine abuse in Hong Kong, the Government's Pharmacy and Poisons Board reclassified benzodiazepines as Dangerous Drugs in October 1990. Apart from formal prescriptions, detailed records were then required for the supply and dispensing of these drugs. These regulations were applied initially only to brotizolam, triazolam and flunitrazepam as they were the major benzodiazepines of abuse. The impact of these regulatory changes on benzodiazepine use has been studied by analyzing the sales patterns of seven benzodiazepines between 1990 and 1993. In 1991, the sales of flunitrazepam and triazolam fell, but the sales of five unrestricted benzodiazepines increased.[18] Particular problems arose with the trafficking and abuse of nimetazepam and the abuse of temazepam within that same year in 1991. The regulations that were originally only applied to brotizolam, triazolam and flunitrazepam were now being extended to include all benzodiazepines by January 1992. A regulation requiring the use of proper prescriptions and detailed records for the supply and dispensing of benzodiazepines, appears to have curbed, at least partially, their abuse in Hong Kong. There are still some problems with temazepam, nimetazepam, triazolam, and brotizolam, but they are not major.
Commercial names
Name | Countries |
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Bondormin, Brotizolam | Israel |
Dormex | Chile |
Lendorm | Austria, Denmark |
Lendormin | South Africa, Belgium, Germany, Hungary, Italy, Japan, Netherlands, Portugal, Taiwan |
Lendormine | Switzerland |
Lindormin | Mexico |
Noctilan | Chile |
Sintonal | Spain |
See also
- Benzodiazepines
- Thienodiazepines
- Benzodiazepine dependence
- Benzodiazepine withdrawal syndrome
- Long-term effects of benzodiazepines
- Midazolam
- Triazolam
- Loprazolam
- Flubrotizolam
- Fluclotizolam
- Flurazepam
- Responsible drug use, recreational drug use
- GABA
References
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- ^ "DEA Diversion Control Division" (PDF). Archived from the original (PDF) on 2019-10-17. Retrieved 2015-12-10.
- ^ US 4094984 6-Phenyl-8-bromo-4H-s-triazolo-[3,4C]-thieno-[2,3E]-1,4-diazepines and salts thereof
- S2CID 30788171.
- .
- ^ PMID 6140948.
- PMID 18855614.
- ^ S2CID 243228878.
- ^ US4094984 6-Phenyl-8-bromo-4H-s-triazolo-[3,4C]-thieno-[2,3E]-1,4-diazepines and salts thereof
- ISBN 9783527607495.
- S2CID 46560074.
- S2CID 24584685.
- PMID 7397057.
- PMID 19900604.
- PMID 16045197.
- PMID 15037809.
- PMID 16336040.
- PMID 8523479.
Further reading
- Greenblatt DJ, Locniskar A, Shader RI (1983). "Pilot pharmacokinetic study of brotizolam, a thienodiazepine hypnotic, using electron-capture gas-liquid chromatography". Sleep. 6 (1): 72–6. PMID 6844800.
- Langley MS, Clissold SP (February 1988). "Brotizolam. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an hypnotic". Drugs. 35 (2): 104–22. S2CID 243228878.
- Bechtel WD (1983). "Pharmacokinetics and metabolism of brotizolam in humans". British Journal of Clinical Pharmacology. 16 (Suppl 2): 279S–283S. PMID 6661373.
- Jochemsen R, Wesselman JG, Hermans J, van Boxtel CJ, Breimer DD (1983). "Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration". British Journal of Clinical Pharmacology. 16 (Suppl 2): 285S–290S. PMID 6661374.