Reversal agent · Antidote
Flumazenil
Indications
- Reversal of benzodiazepine sedation after procedures or general anesthesia
- Pure benzodiazepine overdose in a patient known not to be dependent, such as a child's accidental ingestion (labeled for overdose, used selectively)
- Paradoxical agitation from midazolam (off-label)
Dosing
| Where | Dose |
|---|---|
| Reversal and antidotes | Flumazenil: 0.2 mg IV over 15 s, repeat to 1 mg; avoid in chronic benzodiazepine use or TCA overdose (seizures) |
On the quick cards
Mechanism of action
Flumazenil is a competitive antagonist at the benzodiazepine site of the GABA-A receptor, the interface between α and γ₂ subunits. It occupies the site without changing chloride channel function, so it blocks the positive allosteric effect of benzodiazepines, and of Z-drugs such as zolpidem, while leaving GABA's own action intact. It does not reverse drugs acting at other sites, such as propofol, barbiturates, alcohol or opioids.
Pharmacology
- CNS: reverses benzodiazepine sedation within minutes, amnesia less reliably; can unmask withdrawal or a proconvulsant co-ingestant and cause seizures, agitation or panic
- Respiratory: reversal of benzodiazepine-induced hypoventilation is partial and unreliable (label)
- Cardiovascular: little effect alone; arrhythmias with cyclic antidepressant co-ingestion
- Other: nausea, vomiting, dizziness, injection-site pain
Pharmacokinetics
| Onset | 1–2 min IV; 80% of the response by 3 min (label) |
|---|---|
| Peak | 6–10 min (label) |
| Duration | Set by its dose and the benzodiazepine level; resedation in 3–9% after procedural sedation (label) |
| Half-life | About 54 min, range 41–79 (label) |
| Distribution | Initial Vd 0.5 L/kg, steady state 0.9–1.1 L/kg (label) |
| Protein binding | About 50%, two-thirds to albumin (label) |
| Metabolism | Liver, 99%: ester cleavage to an inactive carboxylic acid, then glucuronidation; food raises clearance 50% by raising liver blood flow (label) |
| Clearance | 0.8–1.0 L/h/kg (label) |
| Elimination | Urine 90–95% as metabolites, feces 5–10% (label) |
| Organ failure | Clearance falls to 40–60% of normal in moderate and 25% in severe liver impairment; kidney failure changes little (label) |
Chemistry
- Imidazobenzodiazepine (ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate) that fits the benzodiazepine site without activating it
- Achiral weak lipophilic base: octanol:buffer partition 14 at pH 7.4; insoluble in water, slightly soluble in acid (label)
- 0.1 mg/mL with parabens, edetate and acetic acid, pH 3.8–4.3; give into a running IV in a large vein; discard 24 h after drawing up or diluting (label)
Adverse effects and cautions
In the one-pagers
- Toxins, Stings and Anaphylaxis in the FieldOpioids and sedatives: GHB ("G"): Sudden coma, slow breathing, no naloxone response: Bag-mask, capnography; expect abrupt waking within hours; no flumazenil
- Toxidromes and AntidotesReversal antidotes: Benzodiazepines: Flumazenil 0.2 mg IV, titrated to 1 mg: Rarely used; no role in arrest
Practice Toxins, Stings and Anaphylaxis in the Field questions free62 exam-style questions with rationales on the topic where Flumazenil comes up most. No account or download needed.
Other reversal agent drugs
Practice free in your browser2,450+ exam-style questions with rationales. No account, no ads. Also free on the App Store and Google Play.
Sources
- FDA label: Flumazenil Injection, Fresenius Kabi (2025)
- Penninga 2016 (flumazenil adverse events)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.