| Item |
Information |
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Drug Groups
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approved |
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Description
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Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system. |
| Indication |
For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures. |
| Pharmacology |
Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids. |
| Toxicity |
In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects. |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate. |
| Half Life |
Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes). |
| Protein Binding |
Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis. |
| Elimination |
Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces. |
| Distribution |
* 0.9 to 1.1 L/kg |
| Clearance |
* 1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg] |
| References |
| • |
Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalam R: Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? Resuscitation. 2007 Jul;74(1):27-37. Epub 2007 Feb 15.
[Pubmed]
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| • |
Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60.
[Pubmed]
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Maeda S, Miyawaki T, Higuchi H, Shimada M: Effect of flumazenil on disturbance of equilibrium function induced by midazolam. Anesth Prog. 2008 Fall;55(3):73-7.
[Pubmed]
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| External Links |
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