Anexate - General Information
A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.
Pharmacology of Anexate
Anexate 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.
Anexate for patients
ROMAZICON does not consistently reverse amnesia. Patients cannot be expected to remember information told to them in the postprocedure period and instructions given to patients should be reinforced in writing or given to a responsible family member. Physicians are advised to discuss with patients or their guardians, both before surgery and at discharge, that although the patient may feel alert at the time of discharge, the effects of the benzodiazepine (eg, sedation) may recur. As a result, the patient should be instructed, preferably in writing, that their memory and judgment may be impaired and specifically advised:
- Not to engage in any activities requiring complete alertness, and not to operate hazardous machinery or a motor vehicle during the first 24 hours after discharge, and it is certain no residual sedative effects of the benzodiazepine remain.
- Not to take any alcohol or non-prescription drugs during the first 24 hours after flumazenil administration or if the effects of the benzodiazepine persist.
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 or anesthesia.
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 patients.
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 versa.
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 is planned.
ROMAZICON is contraindicated:
- in patients with a known hypersensitivity to flumazenil or benzodiazepines.
- 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 overdose.
Additional information about Anexate
Anexate Indication: 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.
Mechanism Of Action: Anexate, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Anexate competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Anexate is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Flumazenil
Synonyms: Flumazenilo [Spanish]; Flumazenilum [Latin]
Drug Category: Antidotes; GABA Modulators
Drug Type: Small Molecule; Approved
Other Brand Names containing Flumazenil: Anexate; Flumazepil; Lanexat; Mazicon; Romazicon;
Absorption: Not Available
Toxicity (Overdose): In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
Protein Binding: Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.
Biotransformation: Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
Half Life: Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).
Dosage Forms of Anexate: Solution Intravenous
Chemical IUPAC Name: ethyl 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
Chemical Formula: C15H14FN3O3
Flumazenil on Wikipedia: http://en.wikipedia.org/wiki/Flumazenil
Organisms Affected: Humans and other mammals