Flumazenil

Flumazenil is a benzodiazepine-site antagonist used to reverse selected benzodiazepine effects. Veterinary applications include reversal of excessive sedation or delayed recovery after diazepam, midazolam or related drugs, and selected benzodiazepine intoxications. Its action is specific to the benzodiazepine component of sedation in patients receiving multiple classes of centrally acting medication.

Group

Benzodiazepine antagonist

Mechanism of Action

Flumazenil competitively binds the benzodiazepine site on GABA-A receptor complexes with little intrinsic agonist activity. It displaces benzodiazepines and reduces their enhancement of GABA-mediated chloride conductance. This can reverse benzodiazepine-associated sedation, impaired coordination and some respiratory effects. Reversal depends on the relative receptor occupancy and persistence of both antagonist and agonist.

Dose Rates

Dog

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV
Benzodiazepine reversal	0.2 mg/animal	IV	As needed	Alternative fixed regimen in the source.
Hepatic encephalopathy adjunct	0.02 mg/kg	IV		May repeat if a neurologic response is demonstrated; duration of antagonism can be short.

Cat

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV
Benzodiazepine reversal	0.2 mg/animal	IV	As needed	Alternative fixed regimen in the source.

Horse

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV

Cattle

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV

Pig

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV

Sheep

Use / stage	Dose	Route	Schedule	Instructions
Benzodiazepine reversal	0.02 mg/kg	IV

Indications

Reversal of excessive or prolonged benzodiazepine-associated sedation in veterinary patients.
Treatment of selected benzodiazepine overdoses or intoxications when receptor antagonism is appropriate.
Reversal of the benzodiazepine contribution to delayed recovery after a balanced anesthesia or sedation protocol.

Contraindications

Use cautiously with seizure disorders or mixed poisoning involving proconvulsants.

Interactions

Tricyclic antidepressants and other seizure-threshold-lowering drugs increase risk.

Adverse effects

Seizures may be precipitated in susceptible patients.

Preparations

Preparation	Form	Strength	Route
Flumazenil injection 0.1 mg/mL	Injection	0.1 mg / mL	IV

Monitoring and Administration

Monitor consciousness, respiration and recurrence of sedation. Oral delivery is ineffective because of first-pass metabolism.