Flumazenil
Flumazenil (Romazicon)
Flumazenil
(floo- MAZ-eh-nill)
Pregnancy Category: C Anexate Romazicon (Rx)

Classification: Benzodiazepine receptor antagonist

Action/Kinetics: Antagonizes the effects of benzodiazepines on the CNS by competitively inhibiting their action at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Does not antagonize the CNS effects of ethanol, general anesthetics, barbiturates, or opiates. Depending on the dose, there will be partial or complete antagonism of sedation, impaired recall, and psychomotor impairment. Onset of reversal: 1-2 min. Peak effect: 6-10 min. The duration of reversal is related to the plasma levels of the benzodiazepine and the dose of flumazenil. Distribution t 1/2, initial: 7-15 min; terminal t 1/2: 41-79 min. Metabolized in the liver with 90%-95% excreted through the urine and 5%-10% excreted in the feces. Hepatic impairment prolongs the half-life of the drug. Ingestion of food results in a 50% increase in clearance of flumazenil.

Uses: Complete or partial reversal of benzodiazepine-induced depression of the ventilatory responses to hypercapnia and hypoxia. Situations include cases where general anesthesia has been induced or maintained by benzodiazepines, where sedation has been produced by benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdosage.

Contraindications: Use in clients given a benzodiazepine for control of intracranial pressure or status epilepticus. In clients manifesting signs of serious cyclic antidepressant overdose. Use during labor and delivery or in children as the risks and benefits are not known. To treat benzodiazepine dependence or for the management of protracted benzodiazepine abstinence syndrome. Use until the effects of neuromuscular blockade have been fully reversed.

Special Concerns: The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk clients (e.g., concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to administration of flumazenil in cases of overdose, and concurrent cyclic antidepressant overdosage). Use with caution in clients with head injury as the drug may precipitate seizures or alter cerebral blood flow in clients receiving benzodiazepines. Use with caution in clients with alcoholism and other drug dependencies due to the increased frequency of benzodiazepine tolerance and dependence. Use with caution during lactation.
Flumazenil may precipitate a withdrawal syndrome if the client is dependent on benzodiazepines. Flumazenil may cause panic attacks in clients with a history of panic disorder.
Use with caution in mixed-drug overdosage as toxic effects (e.g., cardiac dysrhythmias, convulsions) may occur (especially with cyclic antidepressants).

Side Effects: Deaths have occurred in clients receiving flumazenil, especially in those with serious underlying disease or in those who have ingested large amounts of nonbenzodiazepine drugs (usually cyclic antidepressants) as part of an overdose. Seizures are the most common serious side effect noted.
CNS: Dizziness, vertigo, ataxia, anxiety, nervousness, tremor, palpitations, insomnia, dyspnea, hyperventilation, abnormal crying, depersonalization, euphoria, increased tears, depression, dysphoria, paranoia, delirium, difficulty concentrating, seizures somnolence, stupor, speech disorder. GI: N&V;, hiccoughs, dry mouth. CV: Sweating, flushing, hot flushes, arrhythmias (atrial, nodal, ventricular extrasystoles) bradycardia, tachycardia, hypertension, chest pain. At injection site: Pain, thrombophlebitis, rash, skin abnormality. Body as a whole: Headache, increased sweating, asthenia, malaise, rigors, shivering, paresthesia. Ophthalmologic: Abnormal vision including visual field defect and diplopia; blurred vision. Otic: Transient hearing impairment, tinnitus, hyperacusis.

How Supplied: Injection: 0.1 mg/mL

Dosage
?IV Only To reverse conscious sedation or in general anesthesia.
Adults, initial: 0.2 mg (2 mL) given IV over 15 sec. If the desired level of consciousness is not reached after waiting an additional 45 sec, a second dose of 0.2 mg (2 mL) can be given and repeated at 60-sec intervals, up to a maximum total dose of 1 mg (10 mL). Most clients will respond to doses of 0.6-1 mg. To treat resedation, give no more than 1 mg (given as 0.2 mg/min) at any one time and give no more than 3 mg in any 1 hr.
Management of suspected benzodiazepine overdose.
Adults, initial: 0.2 mg (2 mL) given IV over 30 sec; a second dose of 0.3 mg (3 mL) can be given over another 30 sec. Further doses of 0.5 mg (5 mL) can be given over 30 sec at 1-min intervals up to a total dose of 3 mg (although some clients may require up to 5 mg given slowly as described). If the client has not responded 5 min after receiving a cumulative dose of 5 mg, the major cause of sedation is probably not due to benzodiazepines and additional doses of flumazenil are likely to have no effect. For resedation, repeated doses may be given at 20-min intervals; no more than 1 mg (given as 0.5 mg/min) at any one time and no more than 3 mg in any 1 hr should be administered.