Generic Medicine Info
Indications and Dosage
Reversal of benzodiazepine-induced sedation
Adult: Anaesth: Initially, 200 mcg via IV inj over 15 seconds. A 2nd dose of 100 mcg can be given if desired degree of consciousness is not obtained w/in 60 seconds. May be repeated at 60-sec intervals if necessary. Usual dose: 300-600 mcg. Max: 1,000 mcg. Intensive care: Initially, 300 mcg via IV inj over 15 sec. A repeat dose of 100 mcg may be administered if desired degree of consciousness is not obtained w/in 60 sec. May be repeated at 60-intervals if necessary. Max: 2,000 mcg. If drowsiness recurs, admin a 2nd dose via IV infusion of 100-400 mcg/hour. Adjust rate of infusion according to desired the level of consciousness.
Child: >1 year Initially, 10 mcg/kg (up to 200 mcg) via IV inj over 15 seconds. Repeat at 60-sec intervals if desired level of consciousness is not obtained after 45 sec. Max: 50 mcg/kg or 1,000 mcg, whichever is lower. Dose is individualised based on patient's response.

Benzodiazepine overdose
Adult: Initially, 200 mcg via IV  inj over 30 seconds, may give additional 300 mcg after 30 seconds, followed by 500 mcg at 60-second intervals if required. Max: 3,000 mcg or 5,000 mcg. Alternatively, may be given via IV infusion at a rate of 100-500 mcg/hr, adjusted according to response. If symptoms of intoxication recur, may repeat doses at 20-minute intervals but doses should not exceed 1,000 mcg/dose (given as 500 mcg/min) and 3,000 mcg/hr.
Hepatic Impairment
Careful titration of dosage.
Patient receiving benzodiazepines to control potentially life-threatening conditions (e.g. status epilepticus, raised intracranial pressure). Severe intoxication w/ tricyclic and related antidepressants.
Special Precautions
Patient w/ head injury, alcoholism and other drug dependencies, history of panic disorder. Not intended to treat benzodiazepine dependence or withdrawal syndrome. Should only be used until effects of neuromuscular blockade have been fully reversed. Hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Dizziness, pain at inj site, increased sweating, headache, abnormal or blurred vision, nausea, vomiting, palpitations, anxiety, fear, transient HTN, flushing, agitation, chills, sensory disturbances.
Potentially Fatal: Cardiac arrhythmias (e.g. junctional or ventricular tachycardias), seizures.
IV/Parenteral: C
Patient Counseling Information
Avoid activities that require complete alertness and do not operate hazardous machinery or drive a vehicle during the 1st 24 hr after discharge.
Monitor for recurrence of sedation, resp depression and other residual effects of benzodiazepines for at least 2 hr, until patient is stable.
Drug Interactions
Antagonises central effects of benzodiazepines and non-benzodiazepine agonists (e.g. zopiclone, triazolopyridazine) by competitive interaction at the receptor.
Potentially Fatal: Toxic effects of other psychotropic products esp TCAs taken concurrently may increase w/ the subsidence of benzodiazepine effect.
Food Interaction
Intake of food during IV infusion may increase clearance by 50%.
Description: Flumazenil, an imidazobenzodiazepine derivative, competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex.
Onset: 1-2 min.
Duration: Approx 1 hr.
Absorption: Absorb from the GI tract. Systemic bioavailability: Approx 20%.
Distribution: Volume of distribution: 0.9-1.1 L/kg. Plasma protein binding: Approx 50% (mostly albumin).
Metabolism: Undergoes extensive first-pass hepatic metabolism, mainly to the inactive carboxylic acid form.
Excretion: Mainly via urine as metabolites; faeces (small amount). Terminal elimination half-life: Approx 40-80 min.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Flumazenil, CID=3373, https://pubchem.ncbi.nlm.nih.gov/compound/Flumazenil (accessed on Jan. 21, 2020)

Store between 20-25°C.
ATC Classification
V03AB25 - flumazenil ; Belongs to the class of antidotes. Used in the management of hypnotics and sedatives overdose.
Anon. Flumazenil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/10/2015.

Buckingham R (ed). Flumazenil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/10/2015.

Flumazenil Injection Solution (Pfizer Laboratories). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/10/2015.

Joint Formulary Committee. Flumazenil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/10/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Flumazenil. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 28/10/2015.

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