Usual Adult Dose for Reversal of Sedation

Initial dose: 0.2 mg IV one time over 15 seconds.
Repeated doses: 0.2 mg may be given every minute until the desired level of consciousness is achieved.
Maximum total dose 1 mg.

Resedation: 0.2 mg every 20 minutes as needed
Maximum dose: 1 mg total at any one time; no more than 3 mg in any one hour

Comments:

• Individualize dose based on patient response.
• Most patients respond to doses of 0.6 to 1 mg.
• Administer as a series of small injections as described to control reversal of sedation to desired endpoint and minimize adverse effects.

Use(s): Complete or partial reversal of the sedative effects of benzodiazepines where general anesthesia has been induced and/or maintained with benzodiazepines, or where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures.

Usual Adult Dose for Benzodiazepine Overdose

Initial dose: 0.2 mg IV over 30 seconds

• If desired level of consciousness is not achieved after waiting 30 seconds, a second dose of 0.3 mg may be given over another 30 seconds.
• Further doses of 0.5 mg over 30 seconds may be given at 1 minute intervals, if needed

Maximum cumulative dose: 3 mg total

Resedation: Repeated doses may be given at 20 minute intervals as needed
Maximum dose: 1 mg total at any one time; no more than 3 mg in any one hour

Comments:

• Do not rush administration.
• Patients should have secure airway and venous access before administration, and be awakened gradually.
• Most patients with a benzodiazepine overdose will respond to a cumulative dose of 1 to 3 mg.
• Doses beyond 3 mg do not reliably produce additional effects.
• On rare occasions, patients who partially respond to 3 mg may require additional titration up to a total dose of 5 mg, given in the same manner as above.
• If a patient has not responded 5 minutes after receiving a cumulative dose of 5 mg, the major cause of sedation is unlikely to be benzodiazepines and additional doses of this drug are unlikely to help.

Use(s): Management of benzodiazepine overdose

Usual Pediatric Dose for Reversal of Sedation

1 to 17 years old:
Initial dose: 0.01 mg/kg IV over 15 seconds

• If desired level of consciousness is not achieved after an additional 45 seconds, a second 0.01 mg/kg dose may be given and repeated at 60 second intervals, if needed, up to a maximum of 4 doses

Maximum dose: 0.05 mg/kg or 1 mg, whichever is lower

Comments:

• Individualize dose based on patient response.
• Mean total dose in pediatric clinical trials was 0.65 mg (range 0.08 to 1 mg)
• About half of the patients required the maximum 5 doses.
• Resedation occurred in 7 of 60 pediatric patients who were fully alert 10 minutes after starting this medication.
• Safety and efficacy of repeated administration for resedation in pediatric patients has not been established.

Use(s): Reversal of conscious sedation induced with benzodiazepines

Renal Dose Adjustments

Data not available

• The pharmacokinetics of this drug are not significantly affected by renal failure (CrCl under 10 mL/min)

Liver Dose Adjustments

Use with caution.

• The initial dose for benzodiazepine reversal is not affected, but repeat doses should be reduced in size or frequency.

Dose Adjustments

Resedation:

• In clinical situations in adults where resedation must be prevented, physicians may wish to repeat the initial dose at 30 minutes and possibly at 60 minutes also; although not studied in clinical trials, this was effective in preventing resedation in a pharmacologic study in normal volunteers.
• Safety and effectiveness of repeated flumazenil administration in pediatric patients experiencing resedation has not been established.

Precautions

US BOXED WARNING(S):

• Use of this drug has been associated with the occurrence of seizures.
• Seizures are most frequent in patients on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic anti-depressant overdose.

Recommendation:

• Individualized the dosage, and be prepared to manage seizures.

CONTRAINDICATIONS:

• Hypersensitivity to this drug or benzodiazepines
• Patients on benzodiazepines to control a potentially life-threatening condition (e.g. control of intracranial pressure or status epilepticus)
• Signs of serious cyclic antidepressant overdose

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

• The pharmacokinetics of this drug are not significantly affected by hemodialysis

Other Comments

Administration advice:

• For intravenous use only.
• Administer through a freely running intravenous infusion into a large vein to minimize injection site pain.

Storage requirements:

• Store at controlled room temperature.
• Protect from light
• Do not freeze

Reconstitution/preparation techniques:

• Once mixed or drawn into a syringe, use within 24 hours.

IV compatibility:

• Compatible with 5% dextrose, lactated Ringer's, and normal saline.

Patient advice:

• This drug does not consistently reverse amnesia.
• Patient instructions should be reinforced in writing or given to a responsible family member as patients cannot be expected to remember information told to them in the postprocedural period.
• Although the patient may feel alert at discharge, sedation may recur.
• Memory and judgement may be impaired; do not engage in activities requiring complete alertness, and do not operate hazardous machinery or a motor vehicle during the first 24 hours after discharge.
• Do not take any alcohol or non-prescription drugs during the first 24 hours after flumazenil administration or if benzodiazepine effects persist.