II. Indication

  1. Benzodiazepine sedation reversal

III. Contraindications

  1. Mixed drug Overdose with compounds that may cause Seizure (e.g. Tricyclic Antidepressants, Cocaine)
  2. Chronic Benzodiazepine use (dependence)
  3. Seizure Disorder

IV. Dosing: Adults

  1. Benzodiazepine Sedation Reversal
    1. Initial: 0.2 mg IV over 15 seconds
    2. Titrate: 0.2 mg each minute to 1 mg total
  2. Overdose Reversal
    1. Initial: 0.2 mg IV over 30 seconds to 2 minutes
    2. Titrate: 0.3-0.5 mg every 1 to 2 minutes to 3 mg total
  3. Repeat dosing protocol
    1. Repeat Dose: 0.005 mg/kg q1-2 minutes
    2. Maximum cumulative dose: 1 mg
    3. May repeat regimen every 20 minutes

V. Dosing: Children

  1. Overdose Reversal
    1. Start: 0.01 mg/kg slow IV push over 1 to 2 minutes (maximum 0.2 mg)
    2. May repeat at 1 minute intervals up to 4 doses at 0.0005 to 0.01 mg/kg
      1. Maximum total 0.05 mg/kg (or 1 mg)
      2. Ttrate to effect

VI. Precautions

  1. Avoid in patients with chronic use (risks of severe withdrawal including Seizures)
    1. Most toxicology guidelines do not recommend Flumazenil in Overdose
    2. Potential harms appear to outweigh benefits in most cases
    3. Penningo (2016) Basic Clin Pharmacol Toxicol 118(1): 37-44 +PMID:26096314 [PubMed]
  2. May cause acute withdrawal if physically dependent
  3. Do not give routinely to comatose patients
    1. Only use if identity of drug is known, and certain that the patient has not used chronically
  4. Reverses Seizure protection of Benzodiazepines
    1. Increases risk of drugs that lower Seizure threshold (Cocaine, Tricyclic Antidepressants)

VII. Pharmacokinetics

  1. Onset: 1 to 2 minutes
  2. Peak: 6 to 10 minutes

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