Flumazenil is the antidote to benzodiazepines (diazepam, midazolam). It is used in hospital to wake patients with excessive sedation or overdose from this type of medicine.
Also known as: Anexate
Flumazenil reverses midazolam sedation but may precipitate withdrawal seizures in chronic benzodiazepine users or in mixed overdose, and sedation reappears after reversal (resedation).
Competitive antagonism at the GABA-A benzodiazepine receptor: abrupt reversal removes the depressant effect and unmasks a hyperexcitable state with a lowered seizure threshold; flumazenil has a short half-life (≈1 h), shorter than midazolam, so sedation reappears (Prontuário, Annex 7 — Flumazenil: "the benzodiazepine effect may reappear").
Consciousness, respiratory rate, SpO2 and ECG; reassess sedation over the next 2 h and advise against driving for 24 h (Prontuário, Annex 7).
Seizures, paradoxical agitation, recurrence of respiratory depression.
Use only with a precise indication (benzodiazepine overdose with respiratory depression); exclude mixed overdose with tricyclics or other proconvulsants before administration; titrate in 0.2 mg increments and monitor where airway support and rescue benzodiazepine are available.
Flumazenil Injection USP (Pfizer) label, Warnings — withdrawal seizures in benzodiazepine-dependent patients: https://labeling.pfizer.com/ShowLabeling.aspx?id=684; INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Flumazenil (benzodiazepine effect may reappear).
In mixed overdose with tricyclic antidepressants and benzodiazepines, flumazenil may precipitate potentially fatal seizures and arrhythmias.
Flumazenil removes the protective benzodiazepine effect on a seizure threshold already lowered by the tricyclic (sodium channel blockade, antimuscarinic and proconvulsant effects); the overlap precipitates seizures and ventricular arrhythmias — a situation formally excluded from flumazenil use.
ECG (QRS width), blood gases, electrolytes, neurological status, monitored cardiac rhythm.
QRS widening, seizures, ventricular arrhythmias, coma.
Do not give flumazenil when mixed tricyclic overdose is suspected; sedate with benzodiazepines, treat tricyclic cardiotoxicity with sodium bicarbonate and contact the poison centre.
Flumazenil Injection USP (Pfizer) label — use excluded in mixed overdose/patients at seizure risk: https://labeling.pfizer.com/ShowLabeling.aspx?id=684; INFARMED Prontuário Terapêutico (11th ed., 2012), Imipramine entry (tricyclic cardiovascular and convulsive toxicity).
No documented food or drink interactions.
Flumazenil precipitates seizures in benzodiazepine-dependent patients and in mixed overdose with tricyclics — NEVER use in mixed overdose with tricyclic antidepressants.
Confirm absence of tricyclics in overdose; setting with seizure support.
Site monograph (flumazenil — never use in mixed overdose with tricyclic antidepressants).
In benzodiazepine-dependent patients, flumazenil precipitates withdrawal and seizures — caution in drug addicts.
History of dependence: titrate with minimal doses; avoid if possible.
Site monograph (flumazenil — re-sedation, 2 h observation).
No documented pregnancy or breastfeeding information.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Reversal of benzodiazepine sedation and respiratory depression in 1–2 min; effect lasts 45–90 min.
Competitive antagonist at the benzodiazepine site of GABA-A; no significant intrinsic activity (weak inverse agonist at high dose).
IV: 100% bioavailability; oral: ~ 20% (first pass).
Extensive hepatic metabolism (oxidation and glucuronidation) to inactive metabolites; renal excretion.
~ 45–90 min (short half-life; re-sedation risk with long benzodiazepines).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
