flumazenil (flu-maz-e-nil) Anexate, Romazicon

 Indications

Complete/partial reversal of effects of benzodiazepines

used as general anesthetics, or during diagnostic or

therapeutic procedures. Management of intentional or

accidental overdose of benzodiazepines.

Action

Flumazenil is a benzodiazepine derivative that antagonizes

the CNS depressant effects of benzodiazepine

compounds. It has no effect on CNS depression from

other causes, including opioids, alcohol, barbiturates,

or general anesthetics. Therapeutic Effects: Reversal

of benzodiazepine effects.

Pharmacokinetics

Absorption: IV administration results in complete

bioavailability.

Distribution: Unknown.

Protein Binding: 50% primarily to albumin.

Metabolism and Excretion: Metabolism of flumazenil

occurs primarily in the liver.

Half-life: Children: 20–75 min; Adults: 41–79 min.

TIME/ACTION PROFILE (reversal of

benzodiazepine effects)

ROUTE ONSET PEAK DURATION

IV 1–2 min 6–10 min 1–2 hr†

†Depends on dose/concentration of benzodiazepine and

dose of flumazenil.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to flumazenil

or benzodiazepines; Patients receiving benzodiazepines

for life-threatening medical problems, including status

epilepticus orqintracranial pressure; Serious cyclic

antidepressant overdosage.

Use Cautiously in: Mixed CNS depressant overdose

(effects of other agents may emerge when benzodiazepine

effect is removed); History of seizures (seizures

are more likely to occur in patients who are experiencing

sedative/hypnotic withdrawal, who have recently received

repeated doses of benzodiazepines, or who have

a previous history of seizure activity); Head injury (may

qintracranial pressure and risk of seizures); Severe

hepatic impairment; OB, Lactation: Safety not established;

Pedi: Children 1 yr (safety not established).

Adverse Reactions/Side Effects

CNS: SEIZURES, dizziness, agitation, confusion, drowsiness,

emotional lability, fatigue, headache, sleep disorders.

EENT: abnormal hearing, abnormal vision,

blurred vision. CV: arrhythmias, chest pain, hypertension.

GI: nausea, vomiting, hiccups. Derm: flushing,

sweating. Local: pain/injection-site reactions, phlebitis.

Neuro: paresthesia. Misc: rigors, shivering.

Interactions

Drug-Drug: None significant.

Route/Dosage

Reversal of Conscious Sedation or General

Anesthesia

IV (Adults): 0.2 mg. Additional doses may be given at

1-min intervals until desired results are obtained, up to

a total dose of 1 mg. If resedation occurs, regimen may

be repeated at 20-min intervals, not to exceed 3 mg/hr.

IV (Children): 0.01 mg/kg (up to 0.2 mg); if the desired

level of consciousness is not obtained after waiting

an additional 45 sec, further injections of 0.01 mg/

kg (up to 0.2 mg) can be administered and repeated at

60-sec intervals when necessary (up to a maximum of 4

additional times) to a maximum total dose of 0.05 mg/

kg or 1 mg, whichever is lower. The dose should be individualized

based on the patient’s response.

Suspected Benzodiazepine Overdose

IV (Adults): 0.2 mg. Additional 0.3 mg may be given

30 sec later. Further doses of 0.5 mg may be given at 1-

min intervals, if necessary, to a total dose of 3 mg. Usual

dose required is 1–3 mg. If resedation occurs, additional

doses of 0.5 mg/min for 2 min may be given at

20-min intervals (given no more than 1 mg at a time,

not to exceed 3 mg per hr).

IV (Children): Unlabeled—0.01 mg/kg (maximum

dose 0.2 mg) with repeat doses every minute up to a

cumulative dose of 1 mg. As an alternative to repeat

doses, continuous infusions of 0.005–0.01 mg/kg/hr

have been used.

Availability (generic available)

Injection: 0.1 mg/mL.