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==Overdose==
==Overdose==
Bromazepam is a drug sometimes used in [[suicide attempts]].<ref>{{cite journal |author=Michaud K, Romain N, Giroud C, Brandt C, Mangin P |title=Hypothermia and undressing associated with non-fatal bromazepam intoxication |journal=Forensic Sci. Int. |volume=124 |issue=2-3 |pages=112–4 |year=2001 |month=December |pmid=11792498 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0379073801005849}}</ref> A severe bromazepam [[drug overdose]] may result in a alpha pattern coma type.<ref>{{ cite journal |pmid=6140613 |url= |year=1983 |month=Apr |author=Pasinato, E; Franciosi, A; De, Vanna, M |title="Alpha pattern coma" after poisoning with flunitrazepam and bromazepam. Case description |volume=24 |issue=2 |pages=69–74 |issn=0374-9320 |journal=Minerva psichiatrica |format= }}</ref> The effects of a bromazepam overdose can be severe life threatening and very prolonged lasting days or in the case of the elderly or debilitated well over a week.<ref>{{cite journal |author=Rudolf J, Käferstein H, Neveling M, Stenzel C |title=[Protracted course of bromazepam poisoning in advanced age] |language=German |journal=Dtsch. Med. Wochenschr. |volume=123 |issue=27 |pages=832–4 |year=1998 |month=July |pmid=9685842 |doi= |url=}}</ref> The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as [[ethanol|alcohol]] or sedative hypnotic drugs.<ref>{{cite journal |author=Marrache F, Mégarbane B, Pirnay S, Rhaoui A, Thuong M |title=Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow |journal=Hum Exp Toxicol |volume=23 |issue=10 |pages=503–5 |year=2004 |month=October |pmid=15553176 |doi= |url=}}</ref> Bromazepam is the most common benzodiazepine involved in overdoses in [[France]].<ref>{{cite journal |author=Staikowsky F, Theil F, Candella S |title=[Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room] |language=French |journal=Presse Med |volume=34 |issue=12 |pages=842–6 |year=2005 |month=July |pmid=16097205 |doi= |url=}}</ref>
Bromazepam is commonly involved in drug overdoses.<ref>{{cite journal |author=Gandolfi E, Andrade Mda G |title=[Drug-related toxic events in the state of São Paulo, Brazil] |language=Portuguese |journal=Rev Saude Publica |volume=40 |issue=6 |pages=1056–64 |year=2006 |month=December |pmid=17173163 |doi= |url=}}</ref> Bromazepam is a drug sometimes used in [[suicide attempts]].<ref>{{cite journal |author=Michaud K, Romain N, Giroud C, Brandt C, Mangin P |title=Hypothermia and undressing associated with non-fatal bromazepam intoxication |journal=Forensic Sci. Int. |volume=124 |issue=2-3 |pages=112–4 |year=2001 |month=December |pmid=11792498 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0379073801005849}}</ref> A severe bromazepam [[drug overdose]] may result in a alpha pattern coma type.<ref>{{ cite journal |pmid=6140613 |url= |year=1983 |month=Apr |author=Pasinato, E; Franciosi, A; De, Vanna, M |title="Alpha pattern coma" after poisoning with flunitrazepam and bromazepam. Case description |volume=24 |issue=2 |pages=69–74 |issn=0374-9320 |journal=Minerva psichiatrica |format= }}</ref> The effects of a bromazepam overdose can be severe life threatening and very prolonged lasting days or in the case of the elderly or debilitated well over a week.<ref>{{cite journal |author=Rudolf J, Käferstein H, Neveling M, Stenzel C |title=[Protracted course of bromazepam poisoning in advanced age] |language=German |journal=Dtsch. Med. Wochenschr. |volume=123 |issue=27 |pages=832–4 |year=1998 |month=July |pmid=9685842 |doi= |url=}}</ref> The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as [[ethanol|alcohol]] or sedative hypnotic drugs.<ref>{{cite journal |author=Marrache F, Mégarbane B, Pirnay S, Rhaoui A, Thuong M |title=Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow |journal=Hum Exp Toxicol |volume=23 |issue=10 |pages=503–5 |year=2004 |month=October |pmid=15553176 |doi= |url=}}</ref> Bromazepam is the most common benzodiazepine involved in overdoses in [[France]].<ref>{{cite journal |author=Staikowsky F, Theil F, Candella S |title=[Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room] |language=French |journal=Presse Med |volume=34 |issue=12 |pages=842–6 |year=2005 |month=July |pmid=16097205 |doi= |url=}}</ref>


==Drug misuse==
==Drug misuse==

Revision as of 13:13, 22 December 2008

Bromazepam
Clinical data
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability84%
MetabolismHepatic
Elimination half-life12-20 hours
ExcretionRenal
Identifiers
  • 9-bromo-6-pyridin-2-yl-
    2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.015.748 Edit this at Wikidata
Chemical and physical data
FormulaC14H10BrN3O
Molar mass316.2 g·mol−1

Bromazepam (marketed under brand names Calmepam, Compendium, Creosedin, Durazanil, Lectopam, Lexaurin, Lexilium, Lexomil, Lexotan, Lexotanil, Normoc, Novepam, Somalium, Lexatin)[1] is a potent benzodiazepine derivative drug, developed in 1970s.[2][3] It has mainly anxiolytic and at higher doses also sedative, hypnotic and skeletal muscle relaxant properties.[4]

Pharmacology

Bromazepam is a "classical" benzodiazepine; other classical benzodiazepines include; diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, flurazepam and clorazepate.[5] Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring, the benzene ring having a bromine atom attached to it.[6] 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 intermediate-short acting benzodiazepine and is lipophilic, is metabolised hepatically via oxidative pathways.[7] It does not possess any antidepressant or antipsychotic qualities.[8]

After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.[9]

Bromazepam alters electrical status of the brain causing an increased beta activity and a decrease in alpha activity in the EEG recordings.[10]

Pharmacokinetics

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 not effect its metabolism.[11] 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 potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism.[12]

The active metabolite of bromazepam is hydroxybromazepam, which has half life approximately equal to bromazepam.

Tolerance, dependence and withdrawal

Bromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological dependence and/or physical dependence.[13][14] A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks chronic use. Those whose dose was gradually reduced experienced no withdrawal.[15]

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 when abruptly withdrawn from bromazepam.[16][17] Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses may lead to a severe withdrawal syndrome including status epilepticus and a condition resembling delerium tremens.[18][19][20]

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 the benzodiazepine withdrawal syndrome.[21]

Indications

Availability

Bromazepam is available as a generic in Belgium and Japan (as Lexotan), Bosnia, Bulgaria, Canada, Chile, Denmark (as Bromam), Estonia, France, Germany, Israel (Lenitin, by Teva), Italy, Kosovo province, the Republic of Macedonia, The Netherlands, Latvia, (as Lexotanil), Poland, Portugal and Switzerland. It is available as Lexaurin in Croatia. It is also available as Lexotanil in Bangladesh, Colombia, Greece, Pakistan, United Arab Emirates and Venezuela. It is available as Lexotan and Somalium in Australia, Brazil, Portugal, Singapore, and the Philippines. It is available as Lexilium in the Republic of Macedonia and Serbia and Bosnia (also as a generic, produced by ZORKA Pharma). Bromazepam is also available in Canada as Lectopam. Bromazepam is available in Yemen as Novepam and in Cambodia as Lexomil. And it is also available in Spain as Lexatin.

Dosage

Usually, 3 mg to 6 mg at bedtime, with additional 1.5 mg to 3 mg during the next day if needed. Malnourished patients, patients with compromised cardiovascular, liver or renal function, and elderly patients should receive lower doses. In hospitalized patients with severe agitation and/or anxiety, daily doses of up to 24 mg have been given and tolerated for a limited period of time. A 3 mg dose of bromazepam is equivalent to a 5 mg dose of diazepam.

Side-effects

All common side-effects of benzodiazepines have been noted. Consult the article under diazepam. Euphoria, leading to a high abuse potential, is quite often reported.[24]

Bromazepam taken alone impairs learning capacities significantly in humans. In combination with alcohol the impairments of learning capacity become even more pronounced.[25] Dramatic impairments memory functions are common with bromazepam and include an reduced ability to process environmental information.[26][27] Impaired memory, prosessing of sensory data and psychomotor performance.[28][29] Deterioration of cognition including attention capacity and impaired co-ordinative skills.[30][31] Unsteadiness after taking bromazepam is however less pronounced than other benzodiazepines such as lorazepam.[32] Impaired reactive and attention performance, which may impair driving skills.[33]

A decrease in libido and drowsiness.[34][35] Altered skin conduction.[36]

Occasionally benzodiazepines can induce extreme alterations in memory such as anterograde amnesia and amnesic automatism which may have medico-legal consequences. Such reactions usually only occur at the higher dose end of the prescribing spectrum.[37]

Very rarely dystonia can develop.[38]

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 Roche recommends 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.

Contraindications

The general contraindications for benzodiazepines apply. Consult the section under diazepam.

Special Populations

Elderly

In 1987, a team of scientists lead 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 distribution significantly lowered in elderly subjects.[39] The clinical consequence is that the elderly should be treated with lower doses than younger patients.

Bromazepam may effect driving and ability to operate machinery.[40]

Pregnancy and breast feeding

Bromazepam is pregnancy category C, a classification which means that bromazepam has been shown to cause harm to the unborn child. The Hoffman LaRoche product information leaflet warns against breast feeding whilst taking bromazepam. There has been at least one report of sudden infant death syndrome linked to breast feeding whilst consuming bromazepam.[41][42]

Interactions

Cimetidine, fluvoxamine and propranolol causes a marked increase in the half life of bromazepam leading to increased accumulation of bromazepam.[43][44][45]

Overdose

Bromazepam is commonly involved in drug overdoses.[46] Bromazepam is a drug sometimes used in suicide attempts.[47] A severe bromazepam drug overdose may result in a alpha pattern coma type.[48] The effects of a bromazepam overdose can be severe life threatening and very prolonged lasting days or in the case of the elderly or debilitated well over a week.[49] The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic drugs.[50] Bromazepam is the most common benzodiazepine involved in overdoses in France.[51]

Drug misuse

Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam.[52] In France car accidents involving psychotropic drugs in combination found benzodiazepines, mainly diazepam nordiazepam and bromazepam to be the most common drug, almost twice that of the next commonest drug cannabis.[53] Bromazepam has been also been used for serious criminal offences including homicide and to carry out sexual assaults.[54][55]

Legal Status

Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[56]

See also

References

  1. ^ PubChem Substance: Bromazepam National Center of Biotechnology Information.
  2. ^ "Bromazepam, a new anxiolytic: a comparative study with diazepam in general practice".
  3. ^ Fontaine, R; Annable, L; Beaudry, P; Mercier, P; Chouinard, G (1985). "Efficacy and withdrawal of two potent benzodiazepines: bromazepam and lorazepam". Psychopharmacology bulletin. 21 (1): 91–2. ISSN 0048-5764. PMID 2858908. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
  4. ^ "Bromazepam prescribing information (Roche)" (PDF).
  5. ^ Braestrup C (1978). "Pharmacological characterization of benzodiazepine receptors in the brain". Eur J Pharmacol. 48 (3): 263–70. doi:10.1016/0014-2999(78)90085-7. PMID 639854. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)
  6. ^ Bromazepam Eutimia.com - Salud Mental. © 1999-2002.
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  11. ^ Oda M, Kotegawa T, Tsutsumi K, Ohtani Y, Kuwatani K, Nakano S. "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers." European Journal of Clinical Pharmacology. 2003 Nov;59(8-9):615-9. Epub 2003 Sep 27. PMID 14517708 English Fulltext (registration required) Japanese Fulltext (PDF, no registration)
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  17. ^ Chouinard, G; Labonte, A; Fontaine, R; Annable, L (1983). "New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines". Progress in neuro-psychopharmacology & biological psychiatry. 7 (4–6): 669–73. doi:10.1016/0278-5846(83)90043-X. ISSN 0278-5846. PMID 6141609. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
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  19. ^ Thomas P, Lebrun C, Chatel M (1993). "De novo absence status epilepticus as a benzodiazepine withdrawal syndrome". Epilepsia. 34 (2): 355–8. PMID 8384109.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  21. ^ Agarwal RA (1977). "Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam". Br J Pharmacol. 60 (1): 3–9. PMID 18243. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
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  23. ^ Chalmers, P; Horton, Jn (1984). "Oral bromazepam in premedication. A comparison with diazepam". Anaesthesia. 39 (4): 370–2. doi:10.1111/j.1365-2044.1984.tb07280.x. ISSN 0003-2409. PMID 6143514. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Laxenaire, M; Kahn, Jp; Marchand, P (1982). "A clinical trial of bromazepam (author's transl)". La Nouvelle presse medicale. 11 (22): 1699–701. ISSN 0301-1518. PMID 6124936. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  25. ^ Liljequist R (1975). "Effect of two weeks' treatment with thioridazine, chlorpromazine, sulpiride and bromazepam, alone or in combination with alcohol, on learning and memory in man". Psychopharmacologia. 44 (2): 205–8. doi:10.1007/BF00421011. PMID 710. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  26. ^ Münte TF, Gehde E, Johannes S, Seewald M, Heinze HJ (1996). "Effects of alprazolam and bromazepam on visual search and verbal recognition memory in humans: a study with event-related brain potentials". Neuropsychobiology. 34 (1): 49–56. PMID 8884760.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Montenegro M, Veiga H, Deslandes A; et al. (2005). "[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study.]". Arq Neuropsiquiatr. 63 (2B): 410–5. doi:/S0004-282X2005000300009. PMID 16059590. {{cite journal}}: Check |doi= value (help); Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Stacher G (1976). "Gastric acid secretion, serum-gastrin levels and psychomotor function under the influence of placebo, insulin-hypoglycemia, and/or bromazepam". Int J Clin Pharmacol Biopharm. 13 (1): 1–10. PMID 2560. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  29. ^ . PMID 2577220. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  30. ^ Saario I (1976). "Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol". Ann Clin Res. 8 (2): 117–23. PMID 7178. {{cite journal}}: Unknown parameter |month= ignored (help)
  31. ^ . PMID 2908134. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  32. ^ Patat, A; Foulhoux, P (1985). "Effect on postural sway of various benzodiazepine tranquillizers" (PDF). British journal of clinical pharmacology. 20 (1): 9–16. ISSN 0306-5251. PMC 1400619. PMID 2862898. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ Seppälä T (1976). "Two weeks' treatment with chlorpromazine, thioridazine, sulpiride, or bromazepam: actions and interactions with alcohol on psychomotor skills related to driving". Mod Probl Pharmacopsychiatry. 11: 85–90. PMID 9581. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  34. ^ Horseau, C; Brion, S (1982). "Clinical trial of bromazepam. Thirty-four cases (author's transl)". La Nouvelle presse medicale. 11 (22): 1741–3. ISSN 0301-1518. PMID 6124948. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ Perret, J; Zagala, A; Gaio, Jm; Hommel, M; Meaulle, F; Pellat, J; Pollak, P (1982). "Bromazepam in anxiety. Clinical evaluation (author's transl)". La Nouvelle presse medicale. 11 (22): 1722–4. ISSN 0301-1518. PMID 6124942. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ Lapierre, Yd; Butter, Hj; Oyewumi, Lk (1983). "Benzodiazepine effect on information processing in generalized anxiety disorder". Neuropsychobiology. 9 (2–3): 88–93. doi:10.1159/000117943. ISSN 0302-282X. PMID 6137786. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
  37. ^ Rager, P; Bénézech, M (1986). "Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects". Annales medico-psychologiques. 144 (1): 102–9. ISSN 0003-4487. PMID 2876672. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Pérez Trullen JM, Modrego Pardo PJ, Vázquez André M, López Lozano JJ (1992). "Bromazepam-induced dystonia". Biomed. Pharmacother. 46 (8): 375–6. PMID 1292648.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ Ochs HR, Greenblatt DJ, Friedman H, Burstein ES, Locniskar A, Harmatz JS, Shader RI. "Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol." Clinical Pharmacology & Therapeutics. 1987 May;41(5):562-70. PMID 2882883
  40. ^ Hobi, V; Kielholz, P; Dubach, Uc (1981). "The effect of bromazepam on fitness to drive (author's transl)". MMW, Munchener medizinische Wochenschrift. 123 (42): 1585–8. ISSN 0341-3098. PMID 6118830. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Hoffman LaRoche Pharmaceuticals (3 April 2008). "NAME OF THE MEDICINE LEXOTAN" (PDF). Australia: roche-australia.com. Retrieved 16 December 2008.
  42. ^ Martens PR (1994). "A sudden infant death like syndrome possibly induced by a benzodiazepine in breast-feeding". Eur J Emerg Med. 1 (2): 86–7. PMID 9422145. {{cite journal}}: Unknown parameter |month= ignored (help)
  43. ^ Ochs HR, Greenblatt DJ, Friedman H; et al. (1987). "Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol". Clin. Pharmacol. Ther. 41 (5): 562–70. PMID 2882883. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ Perucca E, Gatti G, Spina E (1994). "Clinical pharmacokinetics of fluvoxamine". Clin Pharmacokinet. 27 (3): 175–90. PMID 7988100. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  45. ^ van Harten J (1995). "Overview of the pharmacokinetics of fluvoxamine". Clin Pharmacokinet. 29 Suppl 1: 1–9. PMID 8846617.
  46. ^ Gandolfi E, Andrade Mda G (2006). "[Drug-related toxic events in the state of São Paulo, Brazil]". Rev Saude Publica (in Portuguese). 40 (6): 1056–64. PMID 17173163. {{cite journal}}: Unknown parameter |month= ignored (help)
  47. ^ Michaud K, Romain N, Giroud C, Brandt C, Mangin P (2001). "Hypothermia and undressing associated with non-fatal bromazepam intoxication". Forensic Sci. Int. 124 (2–3): 112–4. PMID 11792498. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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External links

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