flumazenil

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.

Metabolism/Excretion: Primarily metabolized in the liver. Primarily excreted in feces and urine (<1% as unchanged drug).

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.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to flumazenil or benzodiazepines;
Patients receiving benzodiazepines for life-threatening medical problems, including status epilepticus or ↑ intracranial 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 ↑ intracranial pressure and risk of seizures);
Severe hepatic impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <1 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, chest pain, hypertension

Derm: flushing, sweating

EENT: abnormal hearing, abnormal vision, blurred vision

GI: nausea, vomiting, hiccups

Local: pain/injection-site reactions, phlebitis

Neuro: dizziness, agitation, confusion, drowsiness, emotional lability, fatigue, headache, paresthesia, SEIZURES, sleep disorders

Misc: rigors, shivering

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Reversal of Conscious Sedation or General Anesthesia

IV (Adults ): 0.2 mg initially. 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 1-min intervals when necessary (up to a max of 4 additional times) to a max 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 initially. 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 min 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)

Solution for injection: 0.1 mg/mL

Assessment ⬆ ⬇

Assess level of consciousness and respiratory status before and during therapy. Observe patient for ≥2 hr after administration for the appearance of resedation. Hypoventilation may occur.
Overdose: Attempt to determine time of ingestion and amount and type of benzodiazepine taken. Knowledge of agent ingested allows an estimate of duration of CNS depression.
Monitor for seizure activity associated with benzodiazepine withdrawal. Institute seizure precautions as indicated. Seizures are more likely to occur in patients who are experiencing sedative/hypnotic withdrawal, those who have recently received repeated doses of benzodiazepines, or those who have a previous history of seizure activity. Seizures may be treated with benzodiazepines, barbiturates, or phenytoin. Larger than normal doses of benzodiazepines may be required.

Implementation ⬆ ⬇

Do not confuse flumazenil with influenza virus vaccine.
Ensure that patient has a patent airway before administration of flumazenil.
- Observe IV site frequently for redness or irritation. Administer through a free-flowing IV infusion into a large vein to minimize pain at the injection site.
- Optimal emergence should be undertaken slowly to decrease undesirable effects including confusion, agitation, emotional lability, and perceptual distortion.
Suspected Benzodiazepine Overdose: If no effects are seen after administration of flumazenil, consider other causes of decreased level of consciousness (alcohol, barbiturates, opioid analgesics).

IV Administration:

IV Push: Diluent: May be administered undiluted or diluted in syringe with D5W, 0.9% NaCl, or LR. Diluted solution should be discarded after 24 hr. Concentration: Up to 0.1 mg/mL.
Rate: Administer 0.1 mg over 15–30 sec into free-flowing IV in a large vein. Do not exceed 0.2 mg/min in children or 0.5 mg/min in adults.
Y-Site Compatibility:
- esomeprazole
- remimazolam

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects. Flumazenil does not consistently reverse the amnestic effects of benzodiazepines. Provide patient and family with written instructions for postprocedure care.
Inform family that patient may appear alert at the time of discharge but the sedative effects of the benzodiazepine may recur. Instruct patient to avoid driving or other activities requiring alertness for ≥24 hr after discharge.
Instruct patient not to take any alcohol or nonprescription drugs for at least 18–24 hr after discharge.
Resumption of usual activities should occur only when no residual effects of the benzodiazepine remain.
Advise patient to notify health care provider if dizziness, headache, upset stomach, vomiting, blurred eyesight, dry mouth, sweating a lot, feeling nervous and excitable, shakiness, or trouble sleeping occur.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇