Key points
- We recommend to consult your poison centre with the use of this antidote.
- Flumazenil is contraindicated in:
- Coma of unknown origin or coma in setting of co-ingestion of another toxic substance, particularly proconvulsants (antidepressants, cocaine, etc.)
- In epileptic patients
- In benzodiazepine-dependent patients
- In patients with an EKG consistent cyclic antidepressants poisoning (terminal R wave in aVR, QRS widening).
- Flumazenil is not recommended for intubated patients.
- The duration of action of flumazenil (1 h) is shorter than the effect of most benzodiazepines; patients will require close monitoring, as repeat doses may be needed.
- Onset of action in 1 to 3 min; peak action in 6 to 10 min; half-life of approx. 1 h.
+ Synonyms and other terms
- Anexate™
+ Indications
- Pediatric or iatrogenic exposures in adults if:
- There is coma or respiratory depression secondary to a pure benzodiazepines overdose, AND
- The patient is naïve to benzodiazepines, AND
- The patient is not epileptic.
+ Dosage
+ Pediatric Dose
- 0.01 mg/kg (max. 0.2 mg) by direct IV, repeated every 60 seconds, as needed, for up to 4 additional doses, with a maximum cumulative dose of 1 mg or 0,05mg/kg, whichever is lower.
- Relapse in sedation may occur approximately 90 minutes after the first administration. In such cases, it may be necessary to repeat dose of 0.01 mg/kg (max. 0.2 mg) by direct IV or start continuous IV infusion of 0.01 - 0.02 mg/kg/h.
+ Adult Dose
- 0.2 mg by direct IV, followed by 0.3 mg by direct IV, if needed, followed by 0.5 mg by direct IV, until a cumulative dose of 5 mg is reached. Wait 60 seconds between each injection.
- Relapse in sedation may occur approximately 90 minutes after the first administration. In such cases, it may be necessary to repeat dose of 0.2 mg by direct IV or start continuous IV infusion of 0.2 - 0.5 mg/h.
+ Renal Impairment
No data suggests that the dose should be modified for short-term use.
+ Hepatic Impairment
Flumazenil clearance may take longer. Caution is warranted with repeat administrations of flumazenil in patients with liver disease.
+ Hemodialysis Patient
No data suggests that the dose should be modified for short-term use.
+ Pregnancy
- Safety has not been demonstrated.
- However, do not hesitate to use flumazenil during pregnancy if the anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
No data suggests that the dose should be modified for short-term use.
+ Adverse effects
- Nausea, vomiting
- Agitation, tremors, seizures, arrhythmias
+ Monitoring
- Vital signs
- EKG
- Rebound sedation (duration of action of flumazenil may be shorter than that of benzodiazepine).
- Adverse effects
+ End of treatment
- Absence of signs of benzodiazepine poisoning 2 h after the last dose of flumazenil.
+ Special Notes on Administration
Intravenous Route (IV)
- Direct IV
- Administer undiluted dose IV over 30 seconds.
- Continuous IV infusion:
- Suggested preparation method:
- 2 mg (20 ml) in 80 ml of compatible solution. Final volume: 100 ml. Final concentration: 0.02 mg/ml.
- Suggested preparation method:
Subcutaneous Route (SC)
- No data available.
Intramuscular Route (IM)
- No data available.
Intraosseous Route (IO)
- No data available.
Compatibility
Partial list only. Consult the pharmacist on duty at your health care facility.
- Compatible solutions: NS, ½NS, D5W, LR.
- Y-site compatibility: aminophylline, dobutamine, dopamine, famotidine, heparin, lidocaine, procainamide, ranitidine.
- Y-site incompatibility: No data available.
Stability
- Store vials at room temperature (15°C - 30°C).
- Multidose vials. Discard any unused portion 28 days after opening the vial. Contains parabens as preservatives.
- Flumazenil solution is stable for 24 h once diluted.
+ Available products
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 10 mg.
+ References
Kreshak, Allyson, and Stephen Munday. 2016. “Flumazenil.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 9:1–8. Cham: Springer International Publishing.
Penninga, Elisabeth I., Niels Graudal, Morten Baekbo Ladekarl, and Gesche Jürgens. 2016. “Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomised Trials.” Basic & Clinical Pharmacology & Toxicology 118 (1):37–44.
Sivilotti, Marco L. A. 2016. “Flumazenil, Naloxone and the ‘coma Cocktail.’” British Journal of Clinical Pharmacology 81 (3):428–36.
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