Flumazenil (Anexate®, Romazicon®)

Section 1.1

(Anexate®, Romazicon®)  Flumazenil is a benzodiazepine receptor antagonist and acts as an antidote in reversing the CNS depressant effects of benzodiazepine compounds. Flumazenil has no effect on CNS depression from other causes such as opioids, alcohol, barbiturates or general anesthetics. Flumazenil if required should be readily available for administration.

Indications for Clinical Use:

For reversal of benzodiazepine use during procedure, or known isolated benzodiazepine overdose if not taking benzodiazepines chronically.

Contraindications:

Hypersensitivity to flumazenil or benzodiazepines or to any component of the formulation.

Warnings and Precautions:

Flumazenil may not reverse respiratory depression as well when longer acting benzodiazepines have been used. There is a need to monitor in the event that respiratory depression or sedation returns. Flumazenil may not reverse amnesia. Immediately after administration physician consultation is required.

Consult physician immediately if patient takes benzodiazepines chronically but has an acute overdose – risk of seizures may occur. The indications for flumazenil in clinical use are for benzodiazepine reversal during procedure, or known isolated benzodiazepine overdose in those who are not taking benzodiazepines chronically. The number of different types of benzodiazepines does not affect efficacy of flumazenil, however flumazenil’s half-life may be shorter than the benzodiazepines used and repeated doses may be necessary.

Pregnancy:

Compatible

Although an assessment of the teratogenic risk in humans cannot be made, animal data suggests the risk is low. Human-placenta transfer to the fetus is unknown, and despite the moderate plasma protein binding capacity and inactive metabolites, the very short elimination half-life will limit exposure. The indications for flumazenil are such that the benefit should outweigh the unknown fetal risk.

Lactation:

No Data- Probably Compatible

Flumazenil may be considered suitable for use in lactation as this medication has a very short half-life, however when administering this medication to a breastfeeding client for a benzodiazepine overdose, breastfeeding may need to be withheld due to the amount of benzodiazepine in milk and the potential risk of adverse effects (respiratory depression, sedation).

Adverse Reactions:

Headache; fatigue; tremor; weakness; diaphoresis; agitation; nausea/vomiting; seizure although rare.

Dosage and Administration:

0.1 mg/ml injectable solution
IV: 0.2 mg over 30 seconds
If there is inadequate response 30 seconds after the first dose, give 0.3 mg IV over 30 seconds. If inadequate response continues, repeat doses of 0.5 mg IV over 30 seconds can be given at one (1) minute intervals to a maximum cumulative dose of 3 mg.

Onset of Action:

30-60 seconds

Half-life:

Adult – 4-11 minutes

Neonate – unknown

Elimination:

Liver