What is flumazenil?

Flumazenil is a medicine used to reverse the effects of benzodiazepines. Benzodiazepines (diazepam and temazepam) are often used to induce sedation prior to minor surgical procedures.

Flumazenil reverses the effects of benzodiazepines by competing with them for the GABA receptors. Flumazenil binds to the receptors, preventing benzodiazepines from acting on them. This blocks their effects and causes sedation to be reversed.

How does flumazenil work?

The benzodiazepines work by acting on receptors in the brain (GABA receptors) causing the release of a chemical called GABA (gamma amino butyric acid). GABA is a major inhibitory chemical in the brain involved in inducing sleep and control of anxiety and fits. Benzodiazepines act by increasing the activity of GABA, thereby reducing the functioning of certain areas of the brain. This results in sleepiness, a decrease in anxiety and relaxation of muscles. Flumazenil is used to reverse general anaesthesia induced by benzodiazepines, sedation induced by benzodiazepines for short term procedures and sedation of patients in intensive care.

Chemically, flumazenil is ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a)(1,4) benzodiazepine-3-carboxylate. Flumazenil has an imidazobenzodiazepine structure and calculated molecular weight of 303.3.

What is flumazenil for?

Flumazenil reverses the sedative effects of certain medications. It is used to counteract effects of certain anesthetics. It may also be used in the treatment of drug overdose.

Uses of flumazenil

Complete or partial reversal of benzodiazepine-induced depression of the ventilatory responses to hypercapnia and hypoxia. Situations include cases where general anesthesia has been induced or maintained by benzodiazepines, where sedation has been produced by benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdosage.

Contraindications of flumazenil

Use in clients given a benzodiazepine for control of intracranial pressure or status epilepticus. In clients manifesting signs of serious cyclic antidepressant overdose. Use during labor and delivery or in children as the risks and benefits are not known. To treat benzodiazepine dependence or for the management of protracted benzodiazepine abstinence syndrome. Use until the effects of neuromuscular blockade have been fully reversed.

Potential flumazenil side effects

Headache, sweating, irritation at the injection site, blurred vision, flushing, nausea, vomiting or dizziness may occur. If any of these effects continue or become bothersome, inform your doctor. Notify your doctor immediately if you develop a rapid heart rate, skin rash, mood changes, irritability, anxiety, mental confusion, nervousness, tremor, abnormal or jerky muscle movements or depression while taking flumazenil. Avoid intake of alcoholic beverages or any prescription or nonprescription medication for at least one day unless directed to do so by your doctor. Be aware that sedation may persist and that your memory and judgment may be impaired for up to one day. Therefore, avoid driving and do not perform tasks requiring alertness until you no longer feel dizzy. Deaths have occurred in clients receiving flumazenil, especially in those with serious underlying disease or in those who have ingested large amounts of nonbenzodiazepine drugs (usually cyclic antidepressants) as part of an overdose. Seizures are the most common serious flumazenil side effect noted.

Precautions for taking flumazenil

Tell your doctor if you have a history of seizures, panic attacks, alcohol or drug dependency, breathing disorders, heart disease, liver disease, head injury or if you have any allergies. This drug should be used only if clearly needed during pregnancy. Discuss the risks and benefits with your doctor. It is not known if flumazenil appears in breast milk. Consult your doctor before breast-feeding. This drug is not recommended for use in children.

Flumazenil should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.  If you feel you have experienced an allergic reaction, stop using flumazenil and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding while taking flumazenil

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby.Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

Flumazenil should be used with caution during pregnancy, and only if the expected benefit to the mother is greater than any possible risk to the foetus. Seek medical advice from your doctor. 

Small amounts of flumazenil may pass into breast milk. Seek medical advice from your doctor before breastfeeding while using flumazenil.

Flumazenil intrinsic clinical properties

Dentists should be aware that flumazenil does possess its own intrinsic clinical properties 

At clinical doses (5 mg), flumazenil can cause cardiovascular depression and amnesia 

Flumazenil should be reserved for use in sedation-related emergencies and not simply to expedite recovery. 

Patients receiving flumazenil must be discharged with written post-sedation instructions into the care of a responsible adult. 

Special concerns for flumazenil

The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk clients (e.g., concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to administration of flumazenil in cases of overdose, and concurrent cyclic antidepressant overdosage). Use with caution in clients with head injury as the drug may precipitate seizures or alter cerebral blood flow in clients receiving benzodiazepines. Use with caution in clients with alcoholism and other drug dependencies due to the increased frequency of benzodiazepine tolerance and dependence. Use with caution during lactation.

Flumazenil may precipitate a withdrawal syndrome if the client is dependent on benzodiazepines. Flumazenil may cause panic attacks in clients with a history of panic disorder.

Use with caution in mixed-drug overdosage as toxic effects (e.g., cardiac dysrhythmias, convulsions) may occur (especially with cyclic antidepressants).

How can flumazenil affect other medicines?

Flumazenil blocks the effects of benzodiazepines in the brain and also blocks the effects of non-benzodiazepines, such as zopiclone, which act at the same receptors.

Warning!

As benzodiazepines have potential for dependance when used long term, symptoms of benzodiazepine withdrawal such as depression, nervousness, rebound insomnia, sweating and irritability may occur with flumazenil if patients have been treated with high doses of benzodiazepines for prolonged periods. This may also occur mildly if benzodiazepine treatment is reversed after a short period.

People who have received flumazenil should not drive or operate machinary for at least 24 hours after treatment, as the effect of the benzodiazepine may return temporarily, decreasing mental and physical ability.

Flumazenil Clinical trials                Flumazenil Patents 1                Flumazenil Patents 2

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.