flumazenil (Romazicon, Mazicon)

Introduction

Tradenames: Mazicon, Romazicon.

Indications

• benzodiazepine sedation reversal:
  • 0.2 mg IV over 15 sec, then 0.2 mg every 1 min PRN
  • up to 1 mg.
• benzodiazepine overdose reversal:
  • 0.2 mg IV over 30 sec, then 0.3-0.5 mg every 30 sec PRN
  • up to 3 mg.

* Note: 1/2 life 40-80 minutes is considerably less than that of most benzodiazepines

Contraindications

• patients with serious signs of tricyclic antidepressant overdose
• patients given benzodiazepines for control of potentially life-threatening conditions
  • status epilepticus
  • control of intracranial pressure

pregnancy category = c

safety in lactation = ?

Pharmacokinetics

• rapidly inactivated by the liver by hydroxylation
• 1/2life is 1 hour
• reversal of benzodiazepine may take effect in 1-3 minutes & last 1-5 hours

elimination via liver

elimination via kidney

1/2life = 40-80 minutes

Adverse effects

• common (> 10%)
  • nausea/vomiting
  • dizziness
• less common (1-10%)
  • headache, pain at injection site, increased sweating, asthenia, malaise, hot flashes, anxiety, nervousness, dry mouth, tremor, insomnia, dyspnea, hyperventilation, abnormal crying, euphoria, depression, vision disorders
• uncommon (< 1%)
  • shivering, hearing disorder, bradycardia, tachycardia, chest pain, hypertension, variations in blood pressure, hiccups, somnolence, thick tongue, ventricular asystoles, anxiety, sensation of coldness, generalized convulsions*, withdrawal syndrome
• other
  • may precipitate seizures*
  • resedation may occur

* Be prepared to manage seizures prior to administration.

Drug interactions

• toxic effects of tricyclic antidepressant overdose may emerge with reversal of benzodiazepine effect

Mechanism of action

• competitively antagonizes the effects of benzodiazepines on GABA-mediated inhibitory pathways in the CNS

More general terms

• antidote

Additional terms

• benzodiazepine
• tricyclic antidepressant (TCA)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3373