Special Warning : אזהרת שימוש

Warnings
Since flumazenil often has a shorter duration of action than benzodiazepines, a reappearance of sedation, respiratory depression or any other benzodiazepine residual effect could occur. Therefore, the patients must be monitored until the benzodiazepines effects disappear.

Flumazenil only opposes benzodiazepines, it is ineffective when the absence of waking is due to other products.

In the treatment of patients who received high doses of benzodiazepines and/or where treated in the long term, the benefit of the use of flumazenil must be carefully evaluated against the possible risk of triggering benzodiazepines withdrawal symptoms. In such cases, a rapid injection of high doses of flumazenil (more than 1 mg) could provoke the appearance of these symptoms. If in spite of careful adjustment of the doses, benzodiazepine withdrawal symptoms appear, this may be remedied by administering low doses of an injectable benzodiazepine.

In patients presenting a probable multidrug (especially with tricyclic antidepressants or other medicines that decrease the epileptogenic threshold) intentional or accidental overdose, the antagonism of the benzodiazepine effects by flumazenil could favour the appearance of seizures.

In these patients, a sudden removal of the benzodiazepine effect could also favour the occurrence of rhythm disorders (especially ventricular). The latter could be due to an increase in the sympathetic tonus and occur in particular in case of seizures and cardiovascular history and under heavy intensive care conditions.
Flumazenil will only be used after carrying out a directed interrogation of relations, a complete clinical examination as well as an electrocardiogram. It is not recommended to use flumazenil, in the presence of signs indicative of a multidrug intoxication (for example with tricyclic antidepressants) such as agitated or hypertonic coma, pyramidal or anticholinergic signs (mydriasis, tachycardia), electrical anomalies (lengthening of QT, broadening of QRS).

Flumazenil must not be used in case of hypothermia and/or collapse potentially associated with antidepressants.

The use of the antagonist is not recommended in epileptic patients who received a prolonged benzodiazepine treatment, or in patients who received benzodiazepines to control convulsions, a sudden suppression of the protective effect of benzodiazepines provoked could trigger convulsions.

Flumazenil must not be used for the treatment of benzodiazepine dependence syndrome, due to the risk of a withdrawal syndrome.

Precautions for use

In case of a concomitant use with curare, the neuromuscular blockage must be completely neutralised before administering flumazenil.

Due to a limited experience, flumazenil must be used with precaution: • in children under 6 months, during reversal of conscious sedation in a hospital setting, • in children under 6 years, during reversal of conscious sedation in a medical transport or emergency situation,
• in paediatrics, during treatment of an overdose and reversion of the sedative effect induces by the benzodiazepines used for the induction of a general anaesthesia,
• in intensive care of newborns.

In patients presenting a severe cranial trauma (and/or unstable intracranial pressure), flumazenil could favour an increase of the intracranial pressure.

This medicine contains 4.24 mg of sodium per ml of injectable solution: to be taken into account in persons who follow a strict low sodium diet.

Effects on Driving

4.7 Effects on ability to drive and use machines

Even though intravenous administration of flumazenil does not cause somnolence, patients should be warned against any activity requiring constant attention, for example running machines or driving vehicles, within the 24 hours following the administration of this product, the effect of the benzodiazepines ingested or administered previously could reappear.