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Poisoning Information for the Public & Health Care Professionals

Atlantic Canada Poison Centre
Antidote Kit Manual

1-800-565-8161 or 902-470-8161 | atlanticcanadapoisoncentre.ca
Last updated: 07/2015
Pediatric Adult
Last updated: 07/2015
Antidote
Adult

Flumazenil

Anexate®;

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Antidote
Adult

Flumazenil

Anexate®;

ALERT: The use of flumazenil as a reversal agent for intentional benzodiazepine overdose is not routinely recommended due to risk of refractory seizures.

Indications

  • Reversal of sedation due to benzodiazepines used in diagnostic or therapeutic procedures.
  • Management/diagnosis of a pure benzodiazepine overdose causing clinically significant CNS or respiratory depression meeting the following criteria: no history of seizure disorder, no chronic use of benzodiazepines, and no coingestion of a toxin that can cause seizures or cardiac dysrhythmias.
  • Management of clinically significant CNS or respiratory depression caused by overdose of zolpidem, zaleplon, or zopiclone

Dosage

      Initial dose:

  • 0.2 mg IV over 30 seconds. If no response at 60 seconds, give 0.3 mg IV. If there is still no response give 0.5 mg every 60 seconds to a maximum dose of 3 mg. 

      If resedation occurs:

  • Consider infusion of 0.1 mg — 1 mg/hour. Titrate to effect.

Administration

  • IV Direct: Administer undiluted over 15-30 seconds. Cardiac and Respiratory monitoring is required.
  • Infusion: For a final concentration of 0.04 mg/mL: add 2 mg (20 mL of a 0.1 mg/mL solution) to 30 mL of sodium chloride 0.9% or dextrose 5% in water. Cardiac and Respiratory monitoring is required.

Compatibility, Stability

  • Compatible with sodium chloride 0.9%, dextrose 5% in water or lactated ringers.
  • Stable for 24 hours at room temperature when diluted in sodium chloride 0.9%, dextrose 5% in water or lactated ringers.

Potential Hazards of Administration

  • Central benzodiazepine effects may recur due to short duration of action. Closely monitor patient. Repeat doses may be required.
  • Nausea, vomiting, flushing.
  • Hypertension and tachycardia (transient).
  • May cause agitation, anxiety and fear.
  • May precipitate benzodiazepine withdrawal symptoms (anxiety, agitation, tachycardia, dizziness, diaphoresis, seizures) in patients on long-term benzodiazepine therapy.
  • Pain at injection site.

Miscellaneous

  • The use of flumazenil should be avoided in tricyclic antidepressant, chloral hydrate, carbamazepine and multiple drug overdose as it has been associated with life-threatening complications such as seizure and arrhythmia.
  • As flumazenil has a short duration of action (half-life approximately 1 hour) patients should be monitored for recurrence of sedation for up to 3 - 4 hours after flumazenil injection.
  • Although flumazenil can reverse benzodiazepine-induced sedation it has variable effects on benzodiazepine-induced respiratory depression.

Bailey, B., Blais, R., Gaudreault, P., Gosselin, S., & Laliberte, M. (2009). Antidotes en toxicologie d'urgence (3rd ed.). Quebec, Canada: Centre antipoison du Quebec.

Goldfrank, L. R., Nelson, L. S., Lewin, N. A., Howland, M. A., Hoffman, R. S., (2015). Goldfrank's toxicologic emergencies(Tenth ed.). New York: McGraw Hill.

Gunja, N. (2013). Review article: The clinical and forensic toxicology of Z-drugs. Journal of Medical Toxicology, 9, 155-162.

Kreshak, A. A., Tomaszewski, C. A., Clark, R. F., & Cantrell, F. L. (2012). Flumazenil administration in poisoned pediatric patients. Pediatric Emergency Care, 28, 448-450.

Micromedex, T. H. A. (2014). Micromedex health care systems. Retrieved from http://www.micromedexsolutions.com

Olson, K. R. (2007). Poisoning & drug overdose (Sixth ed.). New York: McGraw Hill.

Phelps SJ, C. C. (2013).  Teddy bear, pediatric injectable drugs. Retrieved from http://www.pharmpress.com/product/MC_PED/pediatric-injectable-drugs

Shannon, M. W., Borron, S. W., & Burns, M. J. (2007). Haddad and Winchester's clinical management of poisoning and drug overdose (Fourth ed.). Philadelphia: Saunders Elsevier.

Thornton, S. L., Negus, E., & Carstairs, S. D. (2013). Pediatric zolpidem ingestion demonstrating zero-order kinetics treated with flumazenil. Pediatric Emergency Care, 29, 1204-1206.

Trissel, Lawrence, A,. (2013). Handbook on injectable drugs (17th ed.). Bethesda, Maryland: American Society of Health-System Pharmacists

Veiraiah, A., Dyas, J., Cooper, G., Routledge, P. A., & Thompson, J. P. (2012). Flumazenil use in benzodiazepine overdose in the UK: A restrospective survey of NPIS data. Emergency Medicine Journal, 29, 565-569.