Bromazepam (marketed under several brand names, [1] including Lectopam, Lexotan, Lexilium, Lexaurin, Brazepam, Rekotnil, Bromaze

andLexotanil) is [2] a benzodiazepine derivative drug, patented by Roche in 1963 and developed clinically in the [3][4] 1970s. It has mainly anxiolyticproperties and at higher doses of 12 milligrams or more also [5] shows sedative, hypnotic and skeletal muscle relaxant properties.
Contents
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1 Indications 2 Side-effects 3 Tolerance, dependence and withdrawal 4 Contraindications and special precautions

4.1 Special populations

4.1.1 Elderly 4.1.2 Driving 4.1.3 Pregnancy and breast feeding

5 Interactions 6 Pharmacology 7 Pharmacokinetics 8 Overdose 9 Drug misuse 10 Legal status 11 See also 12 References 13 External links

Indications[edit]
Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required. Premedication to alleviate anxiety before surgery.
[7] [6]

Side-effects[edit]
All common side-effects of benzodiazepines have been noted. Consult the article under diazepam. Bromazepam 6 mg 3 times daily for 2 weeks taken alone impaired learning capacities significantly in humans in an experiment. In combination with alcohol the impairments of learning capacity became even [8] more pronounced. Impairments to memory functions are common with bromazepam and include a [9][10][11] reduced working memory and reduced ability to process environmental information. Impaired memory, visual information processing and sensory data and impaired psychomotor

performance. Deterioration of cognition including attention capacity and impaired co-ordinative [15][16] skills. Unsteadiness after taking bromazepam is however less pronounced than other [17] benzodiazepines such as lorazepam. Impaired reactive and attention performance, which can impair [18] driving skills. Drowsiness and decrease in libido. On occasion, benzodiazepines can induce extreme alterations in memory such as anterograde amnesiaand amnesic automatism, which may have medico-legal [21] consequences. Such reactions occur usually only at the higher dose end of the prescribing spectrum. Very rarely, dystonia can develop.
[22] [19][20]

[12][13][14]

Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the medication without experiencing physical and/or psychological benzodiazepine withdrawal symptoms. Leukopenia and liver-damage of the cholostatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Rocherecommends regular laboratory examinations to be performed routinely. Ambulatory patients should be warned that Bromazepam may impair the ability to drive vehicles and to operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants. During the course of therapy, tolerance to the sedative effect usually develops.

Tolerance, dependence and withdrawal[edit]

Bromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological [23][24] dependence and/or physical dependence. A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks [25] chronic use. Those whose dose was gradually reduced experienced no withdrawal. Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms [26] when abruptly withdrawn from bromazepam. Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome [27][28][29] including status epilepticus and a condition resembling delerium tremens. Animal studies have shown that chronic administration of diazepam or bromazepam causes a decrease in spontaneous locomotor activity and the turnover of noradrenaline and dopamine and serotonin, decreased activity of tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal of bromazepam or diazepam a fall in tryptophan, 5-hydroxytryptamine levels occurs as part of [30] the benzodiazepine withdrawal syndrome.

Contraindications and special precautions[edit]

Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug[31] dependent individuals and individuals with comorbid psychiatric disorders.

Special populations[edit]
Elderly[edit]

In 1987, a team of scientists led by Ochs reported that the elimination half-life, peak serum concentration, and serum free fraction are significantly elevated and the oral clearance and volume of [32] distribution significantly lowered in elderly subjects. The clinical consequence is that the elderly should be treated with lower doses than younger patients.

Driving[edit]
Bromazepam may affect driving and ability to operate machinery.
[33]

Pregnancy and breast feeding[edit]

Bromazepam is pregnancy category D, a classification that means that bromazepam has been shown to cause harm to the unborn child. The Hoffman LaRoche product information leaflet warns against breast feeding while taking bromazepam. There has been at least one report of sudden infant death [34][35] syndrome linked to breast feeding while consuming bromazepam.

Interactions[edit]
Cimetidine, fluvoxamine and propranolol causes a marked increase in the half-life of bromazepam leading [36][37][38] to increased accumulation of bromazepam.

Pharmacology[edit]

50 Pills of Lexotanil (containing 6 mg of Bromezepam apiece) as sold by Hoffmann-La Roche in Germany

Bromazepam is a "classical" benzodiazepine; other classical benzodiazepines [39] include; diazepam, clonazepam, oxazepam, lorazepam, nitrazepam,flurazepam, and clorazepate. Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring, the [40] benzene ring having a bromine atom attached to it. It is a 1,4-benzodiazepine, which means that the nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions. Bromazepam binds to the GABA receptor GABAA, causing a conformational change and increasing inhibitory effects of GABA. Other neurotransmitters are not influenced. Bromazepam is a long-acting

benzodiazepine and is lipophilic and metabolised hepatically via oxidative pathways. [42] possess any antidepressant or antipsychotic qualities.

[41]

It does not

After night time administration of bromazepam a highly significant reduction of gastric acid secretion [43] occurs during sleep followed by a highly significant rebound in gastric acid production the following day. Bromazepam alters electrical status of the brain causing an increased beta activity and a decrease in [44] alpha activity in the EEG recordings.

Pharmacokinetics[edit]
Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes. In 2003, a team led by Dr. Oda Manami at Oita Medical University reported that CYP3A4 was not the responsible enzyme, seeing as itraconazole, a known inhibitor of CYP3A4, did [45] not affect its metabolism. In 1995, J. van Harten at Solvay Duphar B.V.'s Department of Clinical Pharmacology in Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less [38] potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism. The active metabolite of bromazepam is hydroxybromazepam, which has half-life approximately equal to [citation needed] that of bromazepam.

Overdose[edit]
Main article: Benzodiazepine overdose Bromazepam is commonly involved in drug overdoses. A severe bromazepam benzodiazepine [47] overdose may result in an alpha pattern coma type. The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic [48] drugs. Bromazepam is the most common benzodiazepine involved in intentional overdoses [49] inFrance.
[46]

Drug misuse[edit]
See also: Benzodiazepine drug misuse Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam. In France car accidents involving psychotropic drugs in combination found benzodiazepines, mainlydiazepam, nordiazepam, and bromazepam, to be the most common drug, almost twice that of the [51] next-most-common drug cannabis. Bromazepam has also been used for serious criminal offences [52][53][54] including, robbery and homicide and to carry out sexual assaults.
[50]

Legal status[edit]
Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.
[55]

See also[edit]
Benzodiazepine Benzodiazepine dependence

Benzodiazepine withdrawal syndrome

References[edit]
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