Flumazenil
Classification
Antidote
Indications
CCP: Benzodiazepine overdose
Contraindications
- Hypersensitivity
- Benzodiazepine reversal in patients requiring benzodiazepines for control of life-threatening conditions.
- Patients who may have ingested or showing signs of cyclic-antidepressant overdose.
Adult dosages
CCP: Benzodiazepine overdose
- Initial dose: 0.2 mg IV over 30 seconds
- Repeat dose: 0.3 mg IV repeated at 1-minute intervals
- Max dose 3 mg
Pediatric Considerations And Dosing
CCP: Benzodiazepine overdose
- Initial dose: 0.01 mg/kg to a max of 0.2 mg IV
- Repeat dose: 0.01 mg/kg to a max of 0.2 mg IV
- Total max dose of 1 mg
Mechanism Of Action
Competitively inhibits the activity at the benzodiazepine receptor site on the GABA receptor complex. Flumazenil does not antagonize the CNS effect of drugs affecting GABA neurons by means other than the benzodiazepine receptor. It also does not reverse the effects of opioids.
Pharmacokinetics
Onset: 1-2 minutes
Peak effect: 6-10 minutes
Duration: 19-50 minutes
Half-life: 54 minutes
Adverse Effects
Gastrointestinal
- Vomiting
- Xerostomia, nausea
Cardiovascular
- Palpitation, flushing, thrombophlebitis, vasodilation
- Atrial tachycardia (paroxysmal), bradycardia, tachycardia, cardiac arrhythmia, chest pain
- Decreased blood pressure, increased blood pressure, ventricular tachycardia
Central nervous system
- Ataxia, dizziness, vertigo, agitation, anxiety, insomnia, nervousness, depersonalization, depression, dysphoria, emotional lability, euphoria, fatigue, headache, hypoesthesia, malaise, paranoia, paresthesia
- Weakness, tremor, confusion, delirium, fear, panic attack, seizures
Dermatologic
- Dermatological disease, diaphoresis, skin rash
Endocrine & metabolic
- Hot flash
Local
- Pain at injection site, injection site reaction
Ophthalmic
- Blurred vision, lacrimation, visual disturbance
Respiratory
- Dyspnea, hyperventilation
Auditory
- Reversible hearing loss, tinnitus
Warning And Precautions
- Does not consistently reverse amnesia.
- May impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness.
- Resedation may occur more frequently in patients where a large single dose or cumulative dose of a benzodiazepine has been administered along with a neuromuscular-blocking agent and multiple anesthetic agents.
- Should not be relied upon to reverse respiratory depression/hypoventilation.
- Benzodiazepine reversal may result in seizures. Seizures may occur more frequently in patients on benzodiazepines for long-term sedation or following tricyclic antidepressant overdose.
- May alter cerebral blood flow or precipitate convulsions in patients receiving benzodiazepines.
- Use with caution in patients with hepatic dysfunction.
- Use with caution in patients with mixed drug overdoses; toxic effects of other drugs taken may emerge once benzodiazepine effects are reversed.
Drug Interactions
- Amitriptyline
- Clomipramine
- Desipramine
- Doxepin
- Nortriptyline
- Protriptyline
- Trimipramine