Benzodiazepine Receptor Antagonist

Flumazenil

Brand names: Anexate

Flumazenil is a competitive benzodiazepine antagonist used to reverse benzodiazepine sedation, mainly after procedural sedation or iatrogenic over-sedation.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 0.2 mg (initial)

Route: Intravenous (into a freely running IV infusion in a large vein)

Frequency: 0.2 mg over 15 seconds; if desired consciousness not obtained after 45 seconds, repeat 0.2 mg at 60-second intervals (up to a maximum of 4 additional times)

Max: 1 mg maximum total per cycle. For repeat treatment no more than 1 mg (given as 0.2 mg/min) at any one time and no more than 3 mg in any one hour.

Reversal of conscious sedation (adults) — primary regimen shown; most patients respond to 0.6 to 1 mg. Reversal of general anaesthesia (adults): same regimen. Suspected benzodiazepine overdose (adults): 0.2 mg over 30 seconds, then 0.3 mg over 30 seconds, then 0.5 mg doses over 30 seconds at 1-minute intervals to a cumulative dose of 3 mg (most respond to 1 to 3 mg; rarely titrate up to 5 mg). Resedation: repeat doses at 20-minute intervals as needed. Give as a series of small injections, not a single bolus. IV use only.

Paediatric dose

Dose: 0.01 mg/kg

Route: Intravenous

Frequency: 0.01 mg/kg (up to 0.2 mg) over 15 seconds; repeat 0.01 mg/kg (up to 0.2 mg) at 60-second intervals up to a maximum of 4 additional times

Max: 0.05 mg/kg or 1 mg, whichever is lower (each individual dose up to 0.2 mg)

Children greater than 1 year of age, reversal of conscious sedation. Safety and efficacy below 1 year of age, and of repeated administration for resedation, not established.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

Patient weight (kg)

Children greater than 1 year of age, reversal of conscious sedation. Safety and efficacy below 1 year of age, and of repeated administration for resedation, not established.

Verify in a children's formulary

US labelling (FDA)

Reference — US labelling, may differ from UK

DOSAGE AND ADMINISTRATION Flumazenil injection is recommended for intravenous use only. It is compatible with 5% dextrose in water, lactated Ringer’s and normal saline solutions. If flumazenil injection is drawn into a syringe or mixed with any of these solutions, it should be discarded after 24 hours. For optimum sterility, flumazenil injection should remain in the vial until just before use. As with all parenteral drug products, flumazenil injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. To minimize the likelihood of pain at the injection site, flumazenil injection should be administered …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2025-02-14. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Known hypersensitivity to flumazenil or to benzodiazepines
Patients given a benzodiazepine for control of a potentially life-threatening condition (e.g. control of intracranial pressure or status epilepticus)
Patients showing signs of serious cyclic antidepressant overdose

Side effects

Convulsions (most common serious adverse event; especially with benzodiazepine dependence, seizure control, severe hepatic impairment or mixed-drug overdose)
Dizziness
Injection site pain
Cardiac dysrhythmias (ventricular tachycardia, junctional tachycardia)
Deaths have occurred, mainly in patients with serious underlying disease or large non-benzodiazepine (e.g. cyclic antidepressant) overdose

Clinical monograph

How it works

It competitively antagonises benzodiazepines at the GABA-A receptor benzodiazepine binding site, reversing their sedative and respiratory-depressant effects.

Prescribing in practice

It can precipitate seizures and is hazardous in benzodiazepine-dependent patients and in mixed overdoses (for example with tricyclic antidepressants or other proconvulsants), so it is not used routinely in undifferentiated overdose.
Its half-life is short, so re-sedation can occur after the effect wears off — observe and be ready to re-dose.
Avoid where benzodiazepines are being used to control seizures or raised intracranial pressure, and in long-term benzodiazepine use.

Monitoring

Monitor conscious level, respiratory rate, oxygen saturation and for any seizure activity, and observe for long enough to detect re-sedation as the drug is eliminated.

Counselling the patient

Warn the team that reversal is short-lived and that re-sedation and recurrent respiratory depression can follow.
Highlight the seizure risk and that flumazenil should not be used as a routine 'wake-up' in undifferentiated or mixed overdose.
Discuss any poisoning case with Toxbase/NPIS before considering flumazenil.

Evidence & guidelines

Reserved for selected benzodiazepine reversal; not recommended for routine overdose (Toxbase/NPIS).

Reference: MHRA SPC Anexate; TOXBASE NPIS; Hojer et al. J Toxicol Clin Toxicol 1996 (flumazenil in BZD overdose); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators