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Revision as of 12:31, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 455388546 of page Flumazenil for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 18:15, 26 December 2024 edit Dzikiłoś (talk | contribs)182 edits →External links: Changing a URL into an active linkTag: Visual edit
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			{{Short description|GABA receptor antagonist drug and benzodiazepine antidote}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
	{{Drugbox		{{Drugbox
			| Watchedfields = changed
	| verifiedrevid = 443821856
			| verifiedrevid = 461101379
	| IUPAC_name = ethyl 12-fluoro- 8-methyl- 9-oxo- 2,4,8- triazatricyclo tetradeca- 1(10),3,5,11,13- pentaene- 5-carboxylate
			| IUPAC_name = Ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4''H''-benzoimidazodiazepine-3-carboxylate
	| image = Flumazenil.svg		| image = Flumazenil.svg
	| width = 159		| width = 222
	| image2 = Flumazenil3d.png		| image2 = Flumazenil ball-and-stick model.png
	<!--Clinical data-->		<!--Clinical data-->| tradename = Anexate, Lanexat, Mazicon, others
	| tradename = Romazicon
	| Drugs.com = {{drugs.com|monograph|flumazenil}}		| Drugs.com = {{drugs.com|monograph|flumazenil}}
	| pregnancy_AU = B3		| pregnancy_AU = B3
	| pregnancy_category = C		| pregnancy_US = C
	| legal_status =		| legal_AU = S4
			| legal_BR = C1
	| routes_of_administration = Intravenous
			| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
			| legal_CA = Rx-only
			| legal_UK = POM
			| legal_US = Rx-only
			| legal_status = Rx-only
			| routes_of_administration = ], ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->| bioavailability =
	| bioavailability =		| protein_bound =
	| protein_bound =
	| metabolism = Hepatic		| metabolism = Hepatic
	| elimination_half-life = 7-15 min (initial) <br> 20-30 min (brain) <br> 40-80 min (terminal)		| elimination_half-life = 7–15 min (initial) <br /> 20–30 min (brain) <br /> 40–80 min (terminal)
	| excretion = Urine 90-95% <br> Feces 5-10%		| excretion = Urine 90–95% <br /> Feces 5–10%
	<!--Identifiers-->		<!--Identifiers-->| IUPHAR_ligand = 4192
	| CASNo_Ref = {{cascite|correct|CAS}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 78755-81-4		| CAS_number = 78755-81-4
	| ATC_prefix = V03		| ATC_prefix = V03
	| ATC_suffix = AB25		| ATC_suffix = AB25
	| ATC_supplemental =		| ATC_supplemental =
	| PubChem = 3373		| PubChem = 3373
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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	| ChEMBL = 407		| ChEMBL = 407
	<!--Chemical data-->		<!--Chemical data-->| C = 15
			| H = 14
	| C=15 | H=14 | F=1 | N=3 | O=3
			| F = 1
	| molecular_weight = 303.288 g/mol
			| N = 3
	| smiles = Fc2cc1C(=O)N(C)Cc3c(ncn3c1cc2)C(=O)OCC
			| O = 3
	| InChI = 1/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3
			| smiles = Fc(c1)ccc-2c1C(=O)N(C)Cc3n2cnc3C(=O)OCC
	| InChIKey = OFBIFZUFASYYRE-UHFFFAOYAD
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3		| StdInChI = 1S/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3
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	| synonyms = <small>ethyl 8-fluoro- 5,6-dihydro- 5-methyl- 6-oxo- 4''H''- imidazo benzodiazepine- 3-carboxylate</small>		| synonyms = <small>ethyl 8-fluoro- 5,6-dihydro- 5-methyl- 6-oxo- 4''H''- imidazo benzodiazepine- 3-carboxylate</small>
	}}		}}
			]
			'''Flumazenil''' (also known as '''flumazepil''', code name '''] 15-1788'''<ref>{{cite journal | vauthors = Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W | display-authors = 6 | title = Selective antagonists of benzodiazepines | journal = Nature | volume = 290 | issue = 5806 | pages = 514–516 | date = April 1981 | pmid = 6261143 | doi = 10.1038/290514a0 | s2cid = 4340263 | bibcode = 1981Natur.290..514H }}</ref>) is a selective ] ]<ref>{{cite journal | vauthors = Whitwam JG, Amrein R | title = Pharmacology of flumazenil | journal = Acta Anaesthesiologica Scandinavica. Supplementum | volume = 108 | pages = 3–14 | date = 1995-01-01 | pmid = 8693922 | doi = 10.1111/j.1399-6576.1995.tb04374.x | s2cid = 24494744 }}</ref> administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (particularly in cases of overdose), through ].
			It was first characterized in 1981,<ref>{{cite journal | vauthors = Whitwam JG | title = Flumazenil: a benzodiazepine antagonist | journal = BMJ | volume = 297 | issue = 6655 | pages = 999–1000 | date = October 1988 | pmid = 2903780 | pmc = 1834756 | doi = 10.1136/bmj.297.6655.999 }}</ref> and was first marketed in 1987 by ] under the trade name '''Anexate'''. However, it did not receive FDA approval until December 20, 1991. The developer lost its exclusive patent rights in 2008; so at present, generic formulations of this drug are available. ] flumazenil is primarily used to treat ] and to help reverse anesthesia. Administration of flumazenil by ] lozenge and topical cream has also been tested.<ref name="ref-orig-13">{{cite journal | vauthors = Rye DB, Bliwise DL, Parker K, Trotti LM, Saini P, Fairley J, Freeman A, Garcia PS, Owens MJ, Ritchie JC, Jenkins A | display-authors = 6 | title = Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABAA receptors | journal = Science Translational Medicine | volume = 4 | issue = 161 | pages = 161ra151 | date = November 2012 | pmid = 23175709 | doi = 10.1126/scitranslmed.3004685 | s2cid = 44236050 }}</ref><ref>{{ClinicalTrialsGov|NCT01183312|Flumazenil for the Treatment of Primary Hypersomnia}}</ref>
			==Medical uses==
			Flumazenil benefits patients who become excessively drowsy after use of ]s for either ] or ] procedures.<ref name=gold2002>{{cite book | vauthors = Goldfrank LR |title=Goldfrank's toxicologic emergencies |publisher=McGraw-Hill Medical Publ. Division |location=New York |year=2002 |isbn=978-0-07-136001-2 |url=https://books.google.com/books?id=HVYyRsuUEc0C&q=flumazenil+not+to+be+used+in+overdose&pg=PA948}}</ref>
			The drug has been used as an ] in the treatment of benzodiazepine overdoses.<ref name=gold2002/> It reverses the effects of benzodiazepines by ] at the benzodiazepine (BZ) recognition site on the ]/benzodiazepine receptor complex. There are many complications that must be taken into consideration when used in the ] setting.<ref name=gold2002/> These include lowered seizure threshold, agitation, and anxiousness. Flumazenil's short half-life requires multiple doses. Because of the potential risks of withdrawal symptoms and the drug's short half-life, patients must be carefully monitored to prevent recurrence of overdose symptoms or adverse side effects.
			Flumazenil is also sometimes used after surgery to reverse the sedative effects of benzodiazepines. This is similar to ]'s application to reverse the effect of ] and ] following surgery. Administration of the drug requires careful monitoring by an anesthesiologist due to potential side effects and serious risks associated with over-administeration. Likewise, post-surgical monitoring is also necessary because flumazenil can mask the apparent metabolization ("wearing off") of the drug after removal of patient life-support and monitoring equipment.
			Flumazenil has been effectively used to treat overdoses of non-benzodiazepine hypnotics, such as ], ] and ] (also known as the "Z-drugs").<ref>{{cite book | vauthors = Nelson LH, Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA |title=Goldfrank's toxicologic emergencies |publisher=McGraw-Hill, Medical Pub. Division |location=New York |year=2006 |isbn=978-0-07-147914-1 }}</ref>
			It may also be effective in reducing ] while improving ] in primary ], such as ].<ref name="ref-orig-13"/>
			The drug has also been used in ]. It may have beneficial short‐term effects in people with ], but there is no evidence for long-term benefits.<ref>{{cite journal | vauthors = Goh ET, Andersen ML, Morgan MY, Gluud LL | title = Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 8 | pages = CD002798 | date = August 2017 | pmid = 28796283 | pmc = 6483298 | doi = 10.1002/14651858.CD002798.pub4 }}</ref>
			The onset of action is rapid, and effects are usually seen within one to two minutes. The peak effect is seen at six to ten minutes. The recommended dose for adults is 200&nbsp;μg every 1–2 minutes until the effect is seen, up to a maximum of 3&nbsp;mg per hour. It is available as a clear, colourless solution for ], containing 500&nbsp;μg in 5 mL.{{citation needed|date=December 2022}} Additional doses may be needed within 20 to 30 minutes if evidence of oversedation reappears.<ref name=Mihic2023>{{cite book | vauthors = Mihic S, Mayfield J | date = 2023 | chapter = Hypnotics and sedatives. | veditors = Brunton LL, Knollmann BC | title = Goodman & Gilman's: The Pharmacological Basis of Therapeutics | edition = 14th | publisher = McGraw Hill | chapter-url = https://accessanesthesiology.mhmedical.com/content.aspx?bookid=3191&sectionid=269719266 | isbn = 978-1-264-25807-9 }}</ref>
			Many benzodiazepines (including ]) have longer ] than flumazenil. Therefore, in cases of overdose, repeated doses of flumazenil may be required to prevent recurrent ]s once the initial dose of flumazenil wears off.{{cn|date=June 2023}}
			It is hepatically metabolised to inactive compounds which are excreted in the urine. Individuals who are physically dependent on benzodiazepines may experience ] symptoms, including ]s, upon rapid administration of flumazenil.
			It is not recommended for routine use in those with a decreased ].<ref>{{cite book | vauthors = Wood LD, Hall JB, Schmidt GD |title=Principles of critical care |publisher=McGraw-Hill Professional |year=2005 |isbn=978-0-07-141640-5 |url=https://books.google.com/books?id=Ss7gzGwk78gC&q=flumazenil+not+recommended+in+overdose&pg=RA11-PA1505 }}</ref>
			In terms of drug enforcement initiatives, diversion control programs and required post-marketing surveillance of adverse events, orders for flumazenil may trigger a prescription audit to the search for benzodiazepine misuse and for clinically significant adverse reactions related to their use.<ref>{{cite journal | vauthors = Kawano DF, Ueta J, Sankarankutty AK, Pereira LR, de Freitas O | title = Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital | journal = Journal of Patient Safety | volume = 5 | issue = 2 | pages = 69–74 | date = June 2009 | pmid = 19920444 | doi = 10.1097/PTS.0b013e3181a5dafa | s2cid = 12973546 }}</ref>
			===PET radioligand===
			Radiolabeled with the radioactive isotope ], flumazenil may be used as a ] in ] with ] to visualize the distribution of ] in the human brain.<ref>{{cite journal | vauthors = Hammers A, Koepp MJ, Richardson MP, Hurlemann R, Brooks DJ, Duncan JS | title = Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients | journal = Brain | volume = 126 | issue = Pt 6 | pages = 1300–1318 | date = June 2003 | pmid = 12764053 | doi = 10.1093/brain/awg138 | name-list-style = amp | doi-access = free }}</ref>
			===Treatment for benzodiazepine dependence & tolerance===
			Epileptic patients who have become tolerant to the anti-seizure effects of the benzodiazepine clonazepam became seizure-free for several days after treatment with 1.5&nbsp;mg of flumazenil.<ref name="Savic1991">{{cite journal | vauthors = Savic I, Widén L, Stone-Elander S | title = Feasibility of reversing benzodiazepine tolerance with flumazenil | journal = Lancet | volume = 337 | issue = 8734 | pages = 133–137 | date = January 1991 | pmid = 1670787 | doi = 10.1016/0140-6736(91)90799-U | s2cid = 41180892 }}</ref> Similarly, patients who were dependent on high doses of benzodiazepines (median dosage 333&nbsp;mg diazepam-equivalent) were able to be stabilised on a low dose of clonazepam after 7–8 days of treatment with flumazenil.<ref name="QuaglioPattaro2012">{{cite journal | vauthors = Quaglio G, Pattaro C, Gerra G, Mathewson S, Verbanck P, Des Jarlais DC, Lugoboni F | title = High dose benzodiazepine dependence: description of 29 patients treated with flumazenil infusion and stabilised with clonazepam | journal = Psychiatry Research | volume = 198 | issue = 3 | pages = 457–462 | date = August 2012 | pmid = 22424905 | doi = 10.1016/j.psychres.2012.02.008 | s2cid = 28979824 }}</ref>
			Flumazenil has been tested against placebo in benzodiazepine-dependent subjects. Results showed that typical benzodiazepine withdrawal effects were reversed with few to no symptoms.<ref>{{cite journal | vauthors = Gerra G, Giucasto G, Zaimovic A, Fertonani G, Chittolini B, Avanzini P, Caccavari R, Delsignore R | display-authors = 6 | title = Intravenous flumazenil following prolonged exposure to lormetazepam in humans: lack of precipitated withdrawal | journal = International Clinical Psychopharmacology | volume = 11 | issue = 2 | pages = 81–88 | date = June 1996 | pmid = 8803645 | doi = 10.1097/00004850-199611020-00002 | name-list-style = amp }}</ref> Flumazenil was also shown to produce significantly fewer withdrawal symptoms than saline in a randomized, placebo-controlled study with benzodiazepine-dependent subjects. Additionally, relapse rates were much lower during subsequent follow-up.<ref name="GerraZaimovic2002">{{cite journal | vauthors = Gerra G, Zaimovic A, Giusti F, Moi G, Brewer C | title = Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo-controlled study | journal = Addiction Biology | volume = 7 | issue = 4 | pages = 385–395 | date = October 2002 | pmid = 14578014 | doi = 10.1080/1355621021000005973 | s2cid = 21255719 }}</ref>
			] studies of tissue cultured cell lines have shown that chronic treatment with flumazenil enhanced the benzodiazepine binding site where such receptors have become more numerous and uncoupling/down-regulation of GABA<sub>A</sub> has been reversed.<ref>{{cite journal | vauthors = Pericić D, Lazić J, Strac DS | title = Chronic treatment with flumazenil enhances binding sites for convulsants at recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors | journal = Biomedicine & Pharmacotherapy | volume = 59 | issue = 7 | pages = 408–414 | date = August 2005 | pmid = 16084060 | doi = 10.1016/j.biopha.2005.02.003 | name-list-style = amp }}</ref><ref>{{cite journal | vauthors = Pericić D, Jazvinsćak Jembrek M, Svob Strac D, Lazić J, Spoljarić IR | title = Enhancement of benzodiazepine binding sites following chronic treatment with flumazenil | journal = European Journal of Pharmacology | volume = 507 | issue = 1–3 | pages = 7–13 | date = January 2005 | pmid = 15659288 | doi = 10.1016/j.ejphar.2004.10.057 | name-list-style = amp }}</ref><ref>{{cite journal | vauthors = Pericić D, Lazić J, Jembrek MJ, Strac DS, Rajcan I | title = Chronic exposure of cells expressing recombinant GABAA receptors to benzodiazepine antagonist flumazenil enhances the maximum number of benzodiazepine binding sites | journal = Life Sciences | volume = 76 | issue = 3 | pages = 303–317 | date = December 2004 | pmid = 15531382 | doi = 10.1016/j.lfs.2004.07.013 | name-list-style = amp }}</ref> After long-term exposure to benzodiazepines, GABA<sub>A</sub> receptors become down-regulated and uncoupled. Growth of new receptors and recoupling after prolonged flumazenil exposure has also been observed. It is thought this may be due to increased synthesis of receptor proteins.<ref>{{cite journal | vauthors = Jazvinsćak Jembrek M, Svob Strac D, Vlainić J, Pericić D | title = The role of transcriptional and translational mechanisms in flumazenil-induced up-regulation of recombinant GABA(A) receptors | journal = Neuroscience Research | volume = 61 | issue = 3 | pages = 234–241 | date = July 2008 | pmid = 18453026 | doi = 10.1016/j.neures.2008.03.005 | name-list-style = amp | s2cid = 9033302 }}</ref>
			Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks.<ref>{{cite journal | vauthors = Saxon L, Borg S, Hiltunen AJ | title = Reduction of aggression during benzodiazepine withdrawal: effects of flumazenil | journal = Pharmacology, Biochemistry, and Behavior | volume = 96 | issue = 2 | pages = 148–151 | date = August 2010 | pmid = 20451546 | doi = 10.1016/j.pbb.2010.04.023 | name-list-style = amp | s2cid = 41351863 }}</ref> This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.
			Low-dose, slow ] flumazenil administration is a safe procedure for patients withdrawing from long-term, high-dose benzodiazepine dependency.<ref>{{cite journal | vauthors = Faccini M, Leone R, Opri S, Casari R, Resentera C, Morbioli L, Conforti A, Lugoboni F | display-authors = 6 | title = Slow subcutaneous infusion of flumazenil for the treatment of long-term, high-dose benzodiazepine users: a review of 214 cases | journal = Journal of Psychopharmacology | volume = 30 | issue = 10 | pages = 1047–1053 | date = October 2016 | pmid = 27166362 | doi = 10.1177/0269881116647505 | s2cid = 27167585 }}</ref> It has a low risk of seizures even amongst those who have experienced convulsions when previously attempting benzodiazepine withdrawal.<ref>{{cite journal | vauthors = Tamburin S, Faccini M, Casari R, Federico A, Morbioli L, Franchini E, Bongiovanni LG, Lugoboni F | display-authors = 6 | title = Low risk of seizures with slow flumazenil infusion and routine anticonvulsant prophylaxis for high-dose benzodiazepine dependence | journal = Journal of Psychopharmacology | volume = 31 | issue = 10 | pages = 1369–1373 | date = October 2017 | pmid = 28613124 | doi = 10.1177/0269881117714050 | s2cid = 42432213 }}</ref>
			In Italy, the gold standard for treatment of high-dose benzodiazepine dependency is 8–10 days of low-dose, slowly infused flumazenil.<ref name="LugoboniFaccini2011">{{cite journal | vauthors = Lugoboni F, Faccini M, Quaglio G, Casari R, Albiero A, Pajusco B | title = Agonist substitution for high-dose benzodiazepine-dependent patients: let us not forget the importance of flumazenil | journal = Addiction | volume = 106 | issue = 4 | pages = 853 | date = April 2011 | pmid = 21320225 | doi = 10.1111/j.1360-0443.2010.03327.x | doi-access = free }}</ref> One addiction treatment centre in Italy has used flumazenil to treat over 300 patients who were dependent on high doses of benzodiazepines (up to 70 times higher than conventionally prescribed) with physicians being among the clinic's most common patients.<ref name="LugoboniLeone2012">{{cite journal | vauthors = Lugoboni F, Leone R | title = What is stopping us from using flumazenil? | journal = Addiction | volume = 107 | issue = 7 | pages = 1359 | date = July 2012 | pmid = 22509854 | doi = 10.1111/j.1360-0443.2012.03851.x | doi-access = free }}</ref>
			==Pharmacology==
			]
			Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the ].<ref>{{cite journal | vauthors = Hood SD, Norman A, Hince DA, Melichar JK, Hulse GK | title = Benzodiazepine dependence and its treatment with low dose flumazenil | journal = British Journal of Clinical Pharmacology | volume = 77 | issue = 2 | pages = 285–294 | date = February 2014 | pmid = 23126253 | pmc = 4014019 | doi = 10.1111/bcp.12023 }}</ref> It also exhibits weak partial agonism of GABA<sub>A</sub> receptor complexes that contain ]; the clinical relevance of this is unknown.<ref>{{cite journal | vauthors = Hadingham KL, Garrett EM, Wafford KA, Bain C, Heavens RP, Sirinathsinghji DJ, Whiting PJ | title = Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors | journal = Molecular Pharmacology | volume = 49 | issue = 2 | pages = 253–259 | date = February 1996 | pmid = 8632757 }}</ref>
			Flumazenil does not antagonize all of the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, and most anesthetics) and does not reverse the effects of opioids. It will however antagonize the action of non-benzodiazepine ]s, such as ] and ], because they act via the ] of the GABA receptor<ref name="Gunja 155–162">{{cite journal | vauthors = Gunja N | title = The clinical and forensic toxicology of Z-drugs | journal = Journal of Medical Toxicology | volume = 9 | issue = 2 | pages = 155–162 | date = June 2013 | pmid = 23404347 | pmc = 3657020 | doi = 10.1007/s13181-013-0292-0 }}</ref> - it has been used to successfully treat z-drug overdose.<ref name="Gunja 155–162"/><ref>{{cite journal | vauthors = Thornton SL, Negus E, Carstairs SD | title = Pediatric zolpidem ingestion demonstrating zero-order kinetics treated with flumazenil | journal = Pediatric Emergency Care | volume = 29 | issue = 11 | pages = 1204–1206 | date = November 2013 | pmid = 24196090 | doi = 10.1097/PEC.0b013e3182aa139c | s2cid = 34655918 }}</ref><ref>{{cite journal | vauthors = Lheureux P, Debailleul G, De Witte O, Askenasi R | title = Zolpidem intoxication mimicking narcotic overdose: response to flumazenil | journal = Human & Experimental Toxicology | volume = 9 | issue = 2 | pages = 105–107 | date = March 1990 | pmid = 2111156 | doi = 10.1177/096032719000900209 | bibcode = 1990HETox...9..105L | s2cid = 34525063 }}</ref>
			===Pharmacodynamics===
			Intravenous flumazenil has been shown to antagonize ], impairment of recall, psychomotor impairment and ventilatory depression produced by benzodiazepines in healthy human volunteers.
			The duration and degree of reversal of ] benzodiazepine effects are related to the dose and plasma concentrations of flumazenil.
			== Availability ==
			Flumazenil is sold under a wide variety of brand names worldwide like Anexate, Lanexat, Mazicon, Romazicon. In India it is manufactured by Roche Bangladesh Pharmaceuticals and USAN Pharmaceuticals.{{cn|date=March 2024}}
			== See also ==
			* ]
			* ]
			* ]
			* ]
			== References ==
			{{Reflist|colwidth=30em}}
			== External links ==
			* {{Commons category-inline}}
			* {{DailyMed|1053|Flumazenil}}
			* , Roche USA
			{{Benzodiazepines}}
			{{Antidotes}}
			{{GABA receptor modulators}}
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