Flumazenil - Uses

Uses

Flumazenil is of benefit in patients who become excessively drowsy after benzodiazepines are used for either diagnostic or therapeutic procedures.

It has been used as an antidote in the treatment of benzodiazepine overdoses. It reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine binding site on the GABA_A receptor. There are many complications that must be taken into consideration when used in the acute care setting.

It has been found to be effective in overdoses of non-benzodiazepine sleep enhancers, namely zolpidem and zaleplon.

There is some evidence that flumazenil is effective for protracted benzodiazepine withdrawal (or benzodiazepine post-withdrawal syndrome) with promising results, though larger studies with more regular dosing intervals are needed to confirm this. There have also been some studies investigating the drug's effect in reducing benzodiazapine tolerance, with promising results. In binding to the benzodiazepine receptor, flumazenil may reset the receptors sensitivity, restoring the receptor to its pre-drug affinity.

It has also been used in hepatic encephalopathy, though results have been mixed.

The onset of action is rapid and usually effects are seen within one to two minutes. The peak effect is seen at six to ten minutes. The recommended dose for adults is 200 μg every 1–2 minutes until the effect is seen, to a maximum of 3 mg per hour. It is available as a clear, colourless solution for intravenous injection, containing 500 μg in 5 mL.

Many benzodiazepines (including midazolam) have longer half-lives than flumazenil. Therefore, repeat doses of flumazenil may be required to prevent recurrent symptoms of overdosage once the initial dose of flumazenil wears off. It is hepatically metabolised to inactive compounds which are excreted in the urine. Subjects who are physically dependent on benzodiazepines may suffer benzodiazepine withdrawal symptoms, including seizure, upon administration of flumazenil.

It is not recommended for routine use in those with a decreased level of consciousness.

Considering its use as an antidote in benzodiazepine overdoses, orders for flumazenil may serve as a clue or trigger to initiate a more detailed prescription audit in the search for adverse drug events and clinically significant drug interactions related to the use of benzodiazepines.