Flumazenil

Adult Patients Flumazenil Injection, USP is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose. Pediatric Patients (aged 1 to 17) Flumazenil Injection, USP is indicated for the reversal of conscious sedation induced with benzodiazepines.

Flumazenil Injection, USP is recommended for intravenous use only. It is compatible with 5% dextrose in water, lactated Ringer’s and normal saline solutions. If Flumazenil Injection, USP is drawn into a syringe or mixed with any of these solutions, it should be discarded after 24 hours. For optimum sterility, Flumazenil Injection, USP should remain in the vial until just before use. As with all parenteral drug products, Flumazenil Injection, USP should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. To minimize the likelihood of pain at the injection site, Flumazenil Injection, USP should be administered through a freely running intravenous infusion into a large vein.

Flumazenil Injection, USP is contraindicated: • in patients with a known hypersensitivity to flumazenil or benzodiazepines. • in patients who have been given a benzodiazepine for control of a potentially life-threatening condition (e.g., control of intracranial pressure or status epilepticus). • in patients who are showing signs of serious cyclic antidepressant overdose.

THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF 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. Risk of Seizures The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk populations. Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning.

Serious Adverse Reactions Deaths have occurred in patients who received flumazenil in a variety of clinical settings. The majority of deaths occurred in patients with serious underlying disease or in patients who had ingested large amounts of non-benzodiazepine drugs (usually cyclic antidepressants), as part of an overdose. Serious adverse events have occurred in all clinical settings, and convulsions are the most common serious adverse events reported. Flumazenil administration has been associated with the onset of convulsions in patients with severe hepatic impairment and in patients who are relying on benzodiazepine effects to control seizures, are physically dependent on benzodiazepines, or who have ingested large doses of other drugs (mixed-drug overdose).

Store at 20° to 25°C (68° to 77°F).