What is the dose of flumazenil (Flumazenil) for reversal of benzodiazepine (Benzodiazepine) overdose?

From the Guidelines

The recommended dose for flumazenil reversal of benzodiazepine overdose is 0.01-0.02 mg/kg (maximum: 0.2 mg) IV, repeated at 1-min intervals to a maximum cumulative dose of 0.05 mg/kg or 1 mg, whichever is lower, as stated in the most recent and highest quality study 1.

Key Considerations

• The dose of flumazenil should be titrated to effect, with careful monitoring of the patient's level of consciousness and respiratory status.
• The duration of action of flumazenil is shorter than that of most benzodiazepines, so repeat dosing may be necessary to maintain reversal of sedation.
• Flumazenil should be used with caution in patients with a history of seizure disorders or those who are dependent on benzodiazepines, as it may precipitate seizures or withdrawal symptoms.

Important Safety Information

• Flumazenil is contraindicated in patients with a known hypersensitivity to the drug or in those who have ingested a tricyclic antidepressant, as it may induce seizures or arrhythmias.
• Patients who have received flumazenil should be observed continuously for at least 2 hours after the last dose, as the risk of resedation or respiratory depression may persist.

Clinical Context

• The use of flumazenil should be guided by the clinical presentation and medical history of the patient, with careful consideration of the potential risks and benefits of reversal of benzodiazepine sedation, as noted in recent guidelines 1.
• In cases where the diagnosis of benzodiazepine overdose is uncertain, or where the patient has ingested multiple substances, the use of flumazenil should be approached with caution, and alternative treatments, such as supportive care or the use of other reversal agents, should be considered.

From the FDA Drug Label

For the reversal of the sedative effects of benzodiazepines administered for conscious sedation, the recommended initial dose of flumazenil injection is 0.2 mg (2 mL) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, a second dose of 0. 2 mg (2 mL) can be injected and repeated at 60-second intervals where necessary (up to a maximum of 4 additional times) to a maximum total dose of 1 mg (10 mL).

The recommended dose for flumazenil reversal of benzodiazepine sedation is an initial dose of 0.2 mg administered intravenously over 15 seconds, with additional doses of 0.2 mg as needed, up to a maximum total dose of 1 mg 2.

• The dosage should be individualized based on the patient’s response.
• Most patients respond to doses of 0.6 mg to 1 mg.
• In the event of resedation, repeated doses may be administered at 20-minute intervals as needed.

From the Research

Dose for Flumazenil Reversal for Benzodiazepine Overdose

• The dose of flumazenil for reversal of benzodiazepine overdose varies, but most patients respond to 3 mg or less 3.
• A study found that 74% of patients with benzodiazepine-positive drug screens responded to 3 mg or less of flumazenil, while 6 additional patients responded to 4 or 5 mg, and one patient responded to 8 mg 3.
• Another study suggested that incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg are effective and well-tolerated in the diagnosis and treatment of pure benzodiazepine overdose 4.
• The same study recommended that additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma 4.
• A different study found that 75% of patients who received flumazenil awoke from coma after the injection of 0.7 +/- 0.3 mg of flumazenil 5.

Administration and Dosage

• Flumazenil can be administered intravenously, intramuscularly, orally, or rectally 4.
• The recommended dose for neonates and small children is 10 to 20 micrograms/kg intravenously 4.
• For adults, the initial dose is typically 0.2 to 0.5 mg intravenously, followed by additional doses as needed 4.
• A study used a mean dose of 0.73 mg (7.3 ml) of flumazenil to reverse sedation and psychomotor impairment after intravenous conscious sedation with diazepam 6.

Safety and Efficacy

• Flumazenil is generally safe and effective in reversing benzodiazepine overdose, but it can cause adverse effects such as agitation, gastrointestinal symptoms, and seizures 3, 7.
• A systematic review found that the use of flumazenil is associated with a significantly increased risk of adverse events compared with placebo 7.
• However, another study found that flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed overdose of benzodiazepine plus tricyclic antidepressants 5.