Name: FLUMAZENIL (AnexateR)
Classification: benzodiazepine antagonist
  • used in reversal of benzodiazepine induced CNS depression (will not necessarily reverse sedation or respiratory depression)
  • used in diagnosis and/or management of benzodiazepine overdose

Maximum cumulative dose is 3 mg. Patients with a partial response at 3 mg may required additional titration up to 5 mg. If no response 5 minutes after cumulative dose of 5 mg, the sedation is not likely due to benzodiazapines.

  • Benzodiazepine associated anaesthesia/sedation:
    • 0.2 mg IV direct over 15 seconds
    • further incremental doses of 0.1 mg IV direct every 60 seconds to a maximum total dose of 1 mg
  • Benzodiazepine overdose:
    • 0.3 mg IV direct over 30 seconds
    • further incremental doses of 0.3 mg IV direct over 30 seconds repeated every 60 seconds to a cumulative dose of 3 mg
  • IV Infusion
    • 0.1 - 0.4 mg/hr, titrate to individual response. Indicated for rebound drowsiness.
Administration: IV Infusion
1 mg/100 mL dextrose 5% or sodium chloride 0.9%
Adverse Effects: Due to abrupt benzodiazepine withdrawal:
  • seizures 
  • cardiac arrhythmias including bradycardia or ventricular asystole
  • hypotension or hypertension
  • nausea, vomiting
  • agitation, discomfort, tearfulness, anxiety, emotional lability
  • dry mouth
  • blurred visions
  • injection site pain
  • hot flashes
  • hiccups
  • sensation of cold
  • contraindicated with raised ICP, seizures or tricyclic antidepression overdose
  • should be used with caution in epileptic patients 
  • should be used with caution in mixed overdoses where there has been co-ingestion of agents that decrease the seizure threshold (e.g. tricyclic antidepressents, phenothiazines) 
  • should be used with caution with a history of cardiac arrhythmias
  • in liver failure, first dose is the same as non-liver failure but subsequent doses should be reduced
Monitoring Therapy:
  • IV site
  • neurological status
  • signs of seizures
  • heart rate
  • blood pressure
  • respiratory status
NOTE: duration of benzodiazepines will exceed that of flumazenil; observe closely for recurrence of sedation or respiratory depression
Adult Critical Care Protocol:
  • May be administered IV direct or by IV infusion by a nurse in Adult Critical Care.

Lynne Kelly, Pharmacist, CCTC
Brenda Morgan, Clinical Nurse Specialist, CCTC
Last Update: September 19, 2018