UMEM Educational Pearls


Flumazenil is a reversal agent for benzodiazepine overdose.  Adverse events including seizure, agitation and cardiac arrhythmias have been reported but the frequency of adverse events is unknown.

AE and serious AEs were defined as:


  • Aggressive behavior, agitation, screaming, restlessness
  • Nausea/vomiting, abdominal cramps
  • Sweating, shivering, chills, hot flashes
  • Headache, dizziness
  • Anxiety, distress, depressed mood, abnormal crying
  • Tremors 

Serious AE (SAE):

  • Seizures
  • Supraventricular arrhythmia
  • Multiple ventricular beats
  • Tachycardia
  • Sudden fall in systolic BP

A systematic review/meta-analyses of 13 randomized controlled trials showed

  • AEs more common in flumazenil group vs. placebo (risk ratio: 2.85; 95% CI: 2.11-3.84)
  • SAEs more common in flumazenil group vs. placebo (risk ratio: 3.81; 95% CI: 1.28-11.39) 

Most common AEs

  • Aggressive behavior, agitation, screaming: 26.2% (n=33/126)
  • Nausea/vomiting, abdominal cramps: 20.6% (n=26/126)
  • Anxiety, distress, depressed mood: 15.7% (n=19/126)

Most common SAEs

  • Supraventricular arrhythmia: 30% (n=4/12)
  • Seizure: 25% (n=3/12)
  • Tachycardia: 25% (n=3/12)


  • Administration of flumazenil to patients with known or suspected benzodiazepine overdose is associated with increased risk of AEs


PENNINGA E ET AL.Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomized Trials. Basic Clin Pharmacol Toxicol. 2016

DOI:       10.1111/bcpt.12434