What to Know About Flumazenil

Flumazenil is a drug used to reverse certain kinds of sedation given for diagnostic or surgical procedures. It can also be a lifesaving treatment for benzodiazepine drug overdose.

What Are Benzodiazepines?

To understand the uses of flumazenil, it’s helpful to understand a little about benzodiazepines. Benzodiazepines are a class of drugs that activate a type of receptor found on many cells of the nervous system, called the GABA receptor. In general, binding to these receptors produces a calming effect on the brain.

These drugs are sometimes prescribed for a variety of different health conditions. Some examples are:

• Insomnia
• Anxiety
• Epilepsy
• General muscle relaxation
• Muscle spasticity (from a central nervous system problem)

These drugs are also used for sedation and relaxation during medical procedures (often in addition to other types of drugs).

Many drugs that end with “pam” or “lam” are benzodiazepines. Some examples include:

• Diazepam (Valium)
• Lorazepam (Ativan)
• Clonazepam (Klonopin)
• Alprazolam (Xanax)
• Flurazepam (Dalmane)

While benzodiazepines have positive uses, they can produce undesirable side effects in certain situations. More importantly, they can be life-threatening when taken in too large doses, or when taken in combination with certain other drugs. That’s why flumazenil is such an important drug.

What Is Flumazenil?

Flumazenil (trademarked as Romazicon and Anexate) is a benzodiazepine antagonist, a type of drug that counteracts the effects of benzodiazepines. It does this by helping block the binding of benzodiazepine drugs to the GABA receptor. It can be given as an intravenous injection or a continuous intravenous infusion. Flumazenil is approved for use in both adults and in children.

Who Might Need It

Typically, flumazenil is not a drug that people take over the long term. Most commonly it is used in one of two situations: after a medical procedure or in response to a benzodiazepine overdose.

After a Medical Procedure

Benzodiazepines and related drugs are frequently used as part of diagnostic or surgical procedures. For example, you might be given a benzodiazepine as part of sedation for a colonoscopy to reduce discomfort. This is sometimes called “conscious sedation” because you aren’t completely unconscious during the procedure.

Other times you might need general anesthesia, which provides deep sedation for a more involved surgical procedure. In this case, you won’t have any consciousness at all during the procedure. The various drugs used during anesthesia (which may include benzodiazepines) will ensure that you don’t experience pain while it is happening.

People who receive conscious sedation or general anesthesia feel groggy and sedated afterward because it takes a while for the medications used during the procedure to wear off. This can take several hours or more. During this time, it isn’t safe to drive or do other activities that require full alertness. In some cases, flumazenil can help decrease the recovery time needed to feel normal. People taking flumazenil may feel more alert more quickly, compared to people who don’t take flumazenil. Flumazenil is not as effective at reducing sedation if you have received non-benzodiazepine drugs for sedation as well as benzodiazepines.

Benzodiazepine Overdose

Flumazenil is also an essential treatment for people who have overdosed on benzodiazepine drugs. This might happen if a person accidentally takes too much of a prescribed drug, or if a person is suicidal.

Currently, the only uses of flumazenil approved by the Food and Drug Administration (FDA) are for reversal of post-procedural sedation and for treatment of benzodiazepine overdose. However, it is sometimes prescribed for other medical problems “off-label.” That is, your healthcare provider may think there are good reasons that the medicine might be helpful, but the FDA hasn’t done all the studies needed to approve the drug in that setting. Some of these other conditions include:

• Alcohol withdrawal syndrome
• Hepatic encephalopathy
• Drug action reversal of other drugs (such as baclofen)
• Stupor of unknown origin

Flumazenil may also be of benefit in helping people who have become dependent on benzodiazepines come off these drugs more comfortably and easily.

How Quickly Does It Work?

Flumazenil acts quickly—it only takes a minute or two to start to work, and its peak effect occurs in less than 10 minutes. Because of this, it’s sometimes necessary to carefully monitor someone who has been given flumazenil. On the one hand, a patient might end up needing more than one dose (for example, to counteract overdose symptoms). On the other hand, if a person is given too much flumazenil, this can cause other serious problems, like seizures. Your healthcare provider will only administer flumazenil if the potential benefits outweigh the risks.

Possible Side Effects

In certain circumstances, flumazenil may cause side effects. The most serious potential reactions are:

• Seizure
• Neurological Effects
• Dangerous heart rhythms

Other possible problems include:

• Re-sedation
• Nausea and vomiting
• Confusion
• Headache
• Dizziness
• Impaired thinking
• Chest pain
• Heart rate that is too slow or too fast
• Elevated blood pressure
• Blurred vision
• Reaction at the injection site
• Anxiety or agitation
• Increased sweating

Seizures are much more common in people who have been taking benzodiazepines for a long period of time, especially if those people have ever had a seizure in the past. These people need to be monitored carefully for at least two hours after they receive the drug. They should only be given the drug if it is deemed safe to do so. Healthcare professionals will use the minimum necessary dose, to lower possible risks.

Who Shouldn't Take It

There are some contraindications that preclude some people from safely taking flumazenil. The drug should never be taken by:

• People who are hypersensitive to flumazenil or benzodiazepines
• People taking benzodiazepines to control a life-threatening condition (like elevated pressure inside the skull)
• Patients who have overdosed on cyclic antidepressant drugs (like amitriptyline)

Flumazenil has also not been studied for safety during pregnancy, so it should only be given if the potential benefits for an expecting mother outweigh potential harms.