Brands, Medical Use, Clinical Data
- GABA Modulators
- Solution for injection (0.1 mg/mL)
Brands / Synonyms
Anexate; Flumazenil [USAN:BAN:INN]; Flumazenilo [Spanish]; Flumazenilum [Latin]; Flumazepil; Lanexat; Mazicon; Romazicon; Romazicon
For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose.
Flumazenil does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.
Mechanism of Action
Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
Biotrnasformation / Drug Metabolism
Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
ROMAZICON is contraindicated:
· in patients with a known hypersensitivity to flumazenil or
· in patients who have been given a benzodiazepine for control of a potentially
life- threatening condition (eg, control of intracranial pressure or status epilepticus).
· in patients who are showing signs of serious cyclic antidepressant
Interaction with central nervous system depressants other than benzodiazepines has not been
specifically studied; however, no deleterious interactions were seen when ROMAZICON was administered after narcotics,
inhalational anesthetics, muscle relaxants and muscle relaxant antagonists administered in conjunction with sedation
Particular caution is necessary when using ROMAZICON in cases of mixed drug overdosage since the toxic
effects (such as convulsions and cardiac dysrhythmias) of other drugs taken in overdose (especially cyclic
antidepressants) may emerge with the reversal of the benzodiazepine effect by flumazenil.
The use of ROMAZICON is not recommended in epileptic patients who have been receiving benzodiazepine
treatment for a prolonged period. Although ROMAZICON exerts a slight intrinsic anticonvulsant effect, its abrupt
suppression of the protective effect of a benzodiazepine agonist can give rise to convulsions in epileptic
ROMAZICON blocks the central effects of benzodiazepines by competitive interaction at the receptor
level. The effects of nonbenzodiazepine agonists at benzodiazepine receptors, such as zopiclone, triazolopyridazines
and others, are also blocked by ROMAZICON.
The pharmacokinetics of benzodiazepines are unaltered in the presence of flumazenil and vice
There is no pharmacokinetic interaction between ethanol and flumazenil.
Use in Ambulatory Patients
The effects of ROMAZICON may wear off before a long-acting benzodiazepine is completely cleared from
the body. In general, if a patient shows no signs of sedation within 2 hours after a 1-mg dose of flumazenil, serious
resedation at a later time is unlikely. An adequate period of observation must be provided for any patient in whom
either long-acting benzodiazepines (such as diazepam) or large doses of short-acting benzodiazepines (such as >10
mg of midazolam) have been used.
Because of the increased risk of adverse reactions in patients who have been taking benzodiazepines on
a regular basis, it is particularly important that physicians query patients or their guardians carefully about
benzodiazepine, alcohol and sedative use as part of the history prior to any procedure in which the use of ROMAZICON