Intravenous Reversal of benzodiazepine-induced sedation
Adult: Anaesthesia: Initially, 0.2 mg via IV inj over 15 seconds; followed by 0.1 mg at 1-minute intervals if needed. Usual dose: 0.3-0.6 mg. Max total dose: 1 mg. Intensive care: Initially, 0.3 mg via IV inj over 15 seconds; followed by 0.1 mg at 1-minute intervals if needed. Max total dose: 2 mg. If drowsiness recurs, give 0.1-0.4 mg/hour via IV infusion then adjust according to the desired level of consciousness. Alternatively, repeat 0.5-1 mg doses may be given at 20-minute intervals if needed up to a Max of 3 mg in any 1-hour period. Child: >1 year Initially, 0.01 mg/kg (up to 0.2 mg) via IV inj over 15 seconds; may repeat at 1-minute intervals if needed. Max total dose: 0.05 mg/kg or 1 mg (whichever is lower).
Intravenous Benzodiazepine overdose
Adult: Initially, 0.2 mg via IV inj over 30 seconds; may give further dose of 0.3 mg after 30 seconds and followed by 0.5 mg at 1-minute intervals if needed. Max total dose: 3 mg. In the event of resedation, repeated doses of up to 1 mg may be given at 20-minute intervals if needed up to Max of 3 mg in any 1-hour period.
Contraindications
Patient receiving benzodiazepines to control potentially life-threatening conditions (e.g. status epilepticus, raised intracranial pressure). Mixed intoxication with benzodiazepine and tricyclic and/or tetracyclic antidepressants. Showing signs of serious cyclic antidepressant overdose.
Special Precautions
Patient with head injury, alcoholism and other drug dependencies; pre-operative anxiety or history of chronic or episodic anxiety; treated for long periods with high doses of benzodiazepines; concurrent major sedative-hypnotic drug withdrawal; recent therapy with repeated doses of parenteral benzodiazepine; myoclonic jerking or seizure activity before administration of flumazenil in overdose case. Patient in the ICU. Should not be given in patients who have received neuromuscular blockers until the effects of neuromuscular blockade have been fully reversed. Not recommended for the treatment of benzodiazepine dependence or for the treatment of long-term benzodiazepine abstinence syndromes. Not indicated to diagnose benzodiazepine-induced sedation. Hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Seizures, CNS depression, resedation; withdrawal symptoms including agitation, anxiety, emotional lability, mild confusion, sensory distortions (rapid inj of doses ≥1 mg); panic attacks (those with history of panic disorder). Cardiac disorders: Palpitations. Ear and labyrinth disorders: Vertigo. Eye disorders: Diplopia, strabismus, increased lacrimation. Gastrointestinal disorders: Nausea, dry mouth, vomiting, hiccup. General disorders and administration site conditions: Fatigue, inj site pain. Immune system disorders: Allergic reactions. Investigations: Transient increased blood pressure (on wakening). Musculoskeletal and connective tissue disorders: Tremor. Nervous system disorders: Headache, speech disorder, paraesthesia. Psychiatric disorders: Anxiety, agitation, insomnia, somnolence. Respiratory, thoracic and mediastinal disorders: Hyperventilation, dyspnoea. Skin and subcutaneous tissue disorders: Sweating. Vascular disorders: Hypotension, orthostatic hypotension, flushing.
This drug may cause drowsiness or dizziness, if affected, do not drive or operate machinery for 24 hours after discharge.
Monitoring Parameters
Observe for recurrence of sedation, respiratory depression and other residual effects of benzodiazepines for at least 2 hours and until patient is stable. Evaluate the level of consciousness frequently. Monitor vital signs and airway.
Drug Interactions
Antagonises the effects of non-benzodiazepine agonists acting via the benzodiazepine receptor (e.g. zopiclone, triazolopyridazine). Toxic effects of other psychotropic drugs (especially cyclic antidepressants) taken in overdose may emerge with the reversal of the benzodiazepine effect by flumazenil.
Action
Description: Mechanism of Action: Flumazenil, an imidazobenzodiazepine derivative, competitively inhibits the activity at the benzodiazepine receptor site on the GABA/benzodiazepine receptor complex. Onset: 1-2 minutes. Duration: Approx 1 hour. Pharmacokinetics: Distribution: Extensively distributed in the extravascular space. Plasma protein binding: Approx 50%, mainly to albumin. Metabolism: Metabolised in the liver mainly into the inactive carboxylic acid form. Excretion: Via urine (<1% as unchanged drug); faeces. Terminal elimination half-life: Approx 40-80 minutes.
Chemical Structure
Flumazenil Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3373, Flumazenil. https://pubchem.ncbi.nlm.nih.gov/compound/Flumazenil. Accessed Oct. 23, 2023.
V03AB25 - flumazenil ; Belongs to the class of antidotes. Used in the management of hypnotics and sedatives overdose.
References
Anon. Flumazenil. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 01/06/2023.Anon. Flumazenil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/06/2023.Baxter Healthcare Ltd. Flumazenil-Baxter 0.5 mg/5 mL and 1.0 mg/10 mL Solution for Injection data sheet 29 April 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 01/06/2023.Buckingham R (ed). Flumazenil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/06/2023.Flumazenil 0.1 mg/mL Injection (Pharmaniaga Lifescience Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/06/2023.Flumazenil 0.1 mg/mL Solution for Injection (Fresenius Kabi Ltd). MHRA. https://products.mhra.gov.uk. Accessed 28/09/2023.Flumazenil Injection, Solution (Hikma Pharmaceuticals USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/06/2023.Joint Formulary Committee. Flumazenil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/06/2023.
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