Dosing and uses of Romazicon (flumazenil)
Adult dosage forms and strengths
injectable solution
- 0.1mg/mL
Reversal of Conscious Sedation and General Anesthesia
0.2 mg IV over 15 sec
IF after 45 sec no response, administer 0.2 mg again over 1 min; may repeat at 1 min intervals; not to exceed 4 doses (1 mg)
IF resedation occurs, may repeat doses at 20-min intervals; not to exceed 1 mg/dose or 3 mg/hr
Benzodiazepine Overdose
0.2 mg IV over 15-30 sec
IF no response after 30 sec, administer 0.3 mg over 30 sec 1 min later; IF no response, repeat dose of 0.5 mg IV over 30 sec at 1-min intervals to max cumulative dose of 3 mg/hr
In the event of resedation, may repeat dose at 20-min intervals if needed; not to exceed 1 mg (administered as 0.5 mg/min) administered at any one time and no more than 3 mg/hr
Rarely patient may require titration up to total dose 5 mg; IF no response after 5 min, sedation unlikely to be secondary to benzodiazepines
Dosing Considerations
Slow infusion of lowest dose required to decrease adverse effects
Dosing Modifications
Renal impairment: Not studied
Hepatic impairment: Initial dose adjustment not necessary; reduce dose or frequency of subsequent doses
Pediatric dosage forms and strengths
injectable solution
- 0.1mg/mL
Reversal of Benzodiazepine Sedation
Initial dose: 0.01 mg/kg IV x1 dose over 15 sec
May repeat after 45 sec and then every minute; not to exceed 4 doses for a maximum 0.05 mg/kg or 1 mg, whichever is lower
Romazicon (flumazenil) adverse (side) effects
>10%
Nausea and vomiting (11%)
1-10%
Dizziness (10%)
Abnormal/blurred vision (3-9%)
Agitation (3-9%)
Dyspnea (3-9%)
Hyperventilation (3-9%)
Pain at injection site (3-9%)
Xerostomia (3-9%)
Diaphoresis (1-3%)
Emotional lability (1-3%)
Fatigue (1-3%)
Headache (1-3%)
Paresthesia (1-3%)
Tremor (1-3%)
Weakness (1-3%)
<1%
Delirium
Abnormal hearing
Junctional tachycardia
Thick tongue
Tinnitus
Coldness sensation
Generalized seizure
Warnings
Black box warnings
The use of flumazenil has been associated with seizures. These are most frequent in patients who have been on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic antidepressant overdose. Practitioners should individualize the dosage of flumazenil and be prepared to manage seizures.
Contraindications
Hypersensitivity to flumazenil or benzodiazepines
Possible concomitant: Cyclic antidepressant overdose
Chronic benzodiazepine user; patients receiving a benzodiazepine for life-threatening condition (eg, intracranial pressure control, status epilepticus)
Cautions
Head trauma
History of seizures
Chronic alcoholism
Not for reversal of respiratory depression (need to establish an airway, assist ventilation, and continue to observe patient)-monitor for return of respiratory depression/sedation
May not reverse amnesia
May cause CNS depression and impair ability to perform hazardous tasks
Resedation occurs frequently in patients who have received a large single dose or cumulative dose of a benzodiazepine administered along with a neuromuscular blocker and multiple anesthetic agents
Agitation produced in some patients
Patients rarely seize with 0.2 mg dose
If seizure after flumazenil, recommend valium 20-30 mg, then immediately to barbiturates
Use caution in patients with head injury
Use caution in patients with hepatic dysfunction
Use caution in patients with panic disorder
Unmasking of seizures, precipitation of benzodiazepine withdrawaL
Not for diagnosis of benzodiazepine-induced sedation
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Romazicon (flumazenil)
Mechanism of action
Competitive benzodiazepine receptor antagonist; inhibits activity at the benzodiazepine receptor site on the GABA/benzodiazepine receptor complex; does not reverse the effect of opioids
Absorption
Onset of action: 1-2 min; 80% response within 3 min
Peak effect: 6-10 min
Distribution
Protein bound: 40-50%
Vd: 0.5 L/kg
Elimination
Half-life: 53 min
Excretion: Feces, urine
First order elimination
Administration
IV Administration
Over 15-30 sec
To minimize pain, administer through a freely running IV infusion line into a large vein
Avoid extravasation
