Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
ADVERSE REACTIONS 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) (see WARNINGS ).
Two of the 446 patients who received flumazenil in controlled clinical trials for the management of a benzodiazepine overdose had cardiac dysrhythmias (1 ventricular tachycardia,1 junctional tachycardia).
Adverse Events in Clinical Studies The following adverse reactions were considered to be related to flumazenil administration (both alone and for the reversal of benzodiazepine effects) and were reported in studies involving 1875 individuals who received flumazenil in controlled trials.
Adverse events most frequently associated with flumazenil alone were limited to dizziness, injection site pain, increased sweating, headache, and abnormal or blurred vision (3% to 9%).
Body as a Whole: fatigue (asthenia, malaise), headache, injection site pain*, injection site reaction (thrombophlebitis, skin abnormality, rash) Cardiovascular System: cutaneous vasodilation (sweating, flushing, hot flushes) Digestive System: nausea, vomiting (11%) Nervous System: agitation (anxiety, nervousness, dry mouth, tremor, palpitations, insomnia, dyspnea, hyperventilation)*, dizziness (vertigo, ataxia) (10%), emotional lability (crying abnormal, depersonalization, euphoria, increased tears, depression, dysphoria, paranoia) Special Senses: abnormal vision (visual field defect, diplopia), paresthesia (sensation abnormal, hypoesthesia) All adverse reactions occurred in 1% to 3% of cases unless otherwise marked.
* indicates reaction in 3% to 9% of cases.
Observed percentage reported if greater than 9%.
WARNINGS 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.
Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation.
In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided.
Treatment with flumazenil has no known benefit to the seriously ill mixed-overdose patient other than reversing sedation and should not be used in cases where seizures (from any cause) are likely.
Like all medications, Flumazenil can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: