Flumazenil
1,4-imidazobenzodiazepine derivative
Also known as: Romazicon · Anexate · Fadaflumaz · Flumage · Flumanovag · Fluxifarm · Lanexat · flumazenilum · flumazepil · Ro-15-1788/000
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (3)
Evidence only — not for automatic calculation
Crocodilians, chelonians/reversal of zolazepam
TABLE 127.5. Agent: Flumazenil (Romazicon, Hoffman-LaRoche). Dosage: 1 mg/20 mg of zolazepam187 IM, IV275. Species/Comments: Crocodilians, chelonians/reversal of zolazepam.
Evidence only — not for automatic calculation
All species/reversal of midazolam; extrapolated from mammals and birds
TABLE 127.5. Agent: Flumazenil (Romazicon, Hoffman-LaRoche). Dosage: 0.05 mg/kg IM, SC, IV207. Species/Comments: All species/reversal of midazolam; extrapolated from mammals and birds.
Evidence only — not for automatic calculation
All species/reversal of benzodiazepines, including diazepam and midazolam; seldom indicated
TABLE 127.5. Agent: Flumazenil (Romazicon, Hoffman-LaRoche). Dosage: —. Species/Comments: All species/reversal of benzodiazepines, including diazepam and midazolam; seldom indicated.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Flumazenil is a highly specific benzodiazepine antagonist used primarily in veterinary medicine to reverse the central nervous system (CNS) depressant effects of benzodiazepines (e.g., diazepam, midazolam, zolazepam) following therapeutic use or accidental overdose.
Key Clinical Applications:
- Reversal of Sedation/Anesthesia: Rapidly reverses benzodiazepine-induced sedation.
- Hepatic Encephalopathy: May be used as an adjunctive therapy to temporarily improve neurologic function in patients with severe hepatic failure by antagonizing endogenous benzodiazepine-like substances.
- Toxicity/Overdose: Effective for overdoses of benzodiazepines and certain non-benzodiazepine hypnotics like zolpidem (Ambien®).
Clinical Pearl: When used to reverse the anesthetic combination tiletamine-zolazepam (Telazol®), flumazenil successfully reverses the zolazepam component (analgesia, posture, auditory effects) but does not reverse tiletamine (a dissociative anesthetic). This can lead to a rough recovery characterized by residual dissociative effects (e.g., muscle rigidity, dysphoria) without the smoothing effect of the benzodiazepine.
Mechanism of action
Flumazenil acts as a competitive antagonist at the benzodiazepine recognition site on the GABA-A/benzodiazepine receptor complex in the central nervous system.
Mechanism Pathway: Flumazenil binds to the receptor → competitively displaces benzodiazepine molecules → prevents the allosteric enhancement of GABA → prevents the opening of chloride (Cl-) channels → reverses GABAergic inhibitory effects (sedation, amnesia, muscle relaxation).
Safety & warnings
Contraindications
- Known hypersensitivity to flumazenil or other benzodiazepines
- Patients receiving benzodiazepines for life-threatening conditions (e.g., status epilepticus, increased intracranial/CSF pressure)
- Serious tricyclic antidepressant (TCA) overdose
- Mixed overdoses where benzodiazepine reversal may precipitate seizures
- Baclofen or carisoprodol overdoses (may worsen clinical signs)
- Suspected tricyclic antidepressant overdose (can precipitate seizures)
- Patients receiving long-term benzodiazepine administration for seizure control or sedation (relative contraindication)
Adverse effects
- Injection site reactions
- Vomiting
- Cutaneous vasodilatation
- Vertigo
- Ataxia
- Blurred vision
- Seizures (especially in patients with a history of chronic benzodiazepine use or tricyclic antidepressant toxicity)
- Potentially teratogenic at high dosages
- Seizures (especially in patients receiving long-term benzodiazepine therapy)
- Re-sedation (due to short half-life)
- Agitation or anxiety upon rapid awakening
Precautions
Important Warnings:
- Short Half-Life: Flumazenil has a shorter half-life (~1 hour) than many of the benzodiazepines it reverses. Re-sedation can occur once flumazenil wears off, requiring repeated dosing.
- Seizure Risk: Use with extreme caution in patients with mixed drug overdoses or those dependent on benzodiazepines for seizure control, as rapid reversal can precipitate intractable seizures.
- Not a Universal Antidote: It does not alter benzodiazepine pharmacokinetics (clearance/metabolism) and does not reverse opioids, alpha-2 agonists, or dissociative anesthetics.
Drug interactions
Increased risk for seizures; concurrent use is contraindicated.
Not recommended to use flumazenil until neuromuscular blockade has been fully reversed.
Can precipitate seizures in patients with suspected TCA overdose
Antagonizes therapeutic effects (intended interaction)
Increased risk of seizures if flumazenil is administered during a TCA overdose.
Monitoring
- Efficacy of reversal (level of consciousness, respiratory rate)
- Monitor for re-sedation after 1-2 hours due to short half-life
- Monitor for seizures in susceptible patients
- Respiratory rate and depth
- Level of consciousness and sedation (monitor for re-sedation after 1 hour)
- Seizure activity
Pharmacokinetics
Half-life
Absorption
Administered by rapid IV injection. Therapeutic effects are very rapid, typically occurring within 1-2 minutes of administration.
Distribution
Rapidly distributed throughout the body and into the CNS.
Metabolism
Rapidly metabolized in the liver.
Elimination
Cleared primarily via hepatic metabolism.
Overdose
Large IV overdoses have rarely caused symptoms in otherwise healthy humans. If seizures are precipitated by an overdose or rapid reversal, they have been successfully treated with barbiturates, benzodiazepines, and phenytoin, usually with prompt responses.
Available products
Formulations
- Injection
- Injectable: 0.1 mg/ml solution (5 ml and 10 ml vials)
Human-labeled
- Flumazenil Injection: 0.1 mg/mL in 5 mL & 10 mL vials (Romazicon®, generic)
- Romazicon 0.1 mg/ml injectable solution
Regulatory status
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at 25°C (77°F); excursions are permitted from 15° to 30°C (59° to 86°F). Once drawn into a syringe or mixed with compatible IV solutions (Lactated Ringer's, D5W, or normal saline), discard after 24 hours.
Client information
What Pet Owners Should Know:
- Hospital Use Only: Flumazenil is an emergency and anesthetic reversal drug used strictly in a controlled veterinary hospital environment by trained professionals.
- Purpose: It is used to quickly "wake up" pets who have been given benzodiazepine sedatives (like Valium/diazepam) or to treat accidental overdoses of these medications or human sleep aids like Ambien.
- Monitoring: Because the drug wears off quickly (in about an hour), your pet will be closely monitored in the hospital to ensure they do not become sleepy again once the reversal agent wears off.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.