Flumazenil

[SH4:p152]

• Specific and competitive benzodiazepine antagonist
• High affinity for benzodiazepine receptors
  * Minimal agonist activity
• Metabolised by hepatic microsomal enzymes to inactive metabolites

Structure

• 1,4-imidazobenzodiazepine derivative

Pharmacodynamics

Side effect

• May precipitate acute withdrawal seizures
  * Administration to patients on antiepileptic drugs is not recommended
• Does NOT cause acute anxiety, increased HR or BP
• Does NOT alter MAC
• No agonist effect on resting ventilation or psychomotor function in normal individual

Pharmacokinetics

Metabolism

• Metabolism of flumazenil is by hepatic microsomal enzymes to inactive metabolites

Action profile

• Duration of action = 30 to 60 minutes
• Additional doses may be needed

Pharmaceutics

Presentation

• 0.5mg / 5 mL

Composition

• Active = Flumazenil (0.01%)
• Inactive
  * Disodium edetate
  * Acetid acid
• pH = 4.0

NB:

• Aqueous solution, NOT in propylene glycol [PI]

Clinical

Administration

• Initial IV dose of 0.2mg (8-15 microgram/kg)
  --> Reverse CNS effect within 2 minutes
• Further doses of 0.1 mg IV can be given every 60 seconds
  * Up to a total of 1 mg IV
  * Usual total dose = 0.3 - 0.6 mg IV
• Alternatively, continuous infusion at 0.1-0.4 mg/hour

NB:

• In overdose of unknown drugs, failure to respond to more than 5 mg of flumazenil IV indicates intoxicants other than benzodiazepines

Overdose

• Even when given at a dose of 100mg IV --> no symptoms of overdose were observed
  * [PI on MIMs]

Trivia

Brand name = anexate