Flumazenil Mylan

/ Genmedix

In anaesthesiology
In adults: Flumazenil must be administered by an anaesthesiologist/intensive care physician.
The recommended initial dose is of 0.2 mg, administered by IV route in 15 seconds. If the consciousness level desired is not obtained within 60 seconds, a second 0.1 mg dose may be injected. If necessary, this operation may be repeated at 60 second intervals, the maximum dose is 1 mg. The usual total dose is of 0.3 to 0.6 mg, depending on inter-individual variations that may be observed as a function of the dose and duration of action of the benzodiazepine administered and the characteristics of the patient.
In children over 6 months old: The recommended initial dose is of 0.01 mg/kg (up to 0.2 mg per injection) administered by IV route in 15 seconds. If a satisfactory consciousness level is not obtained after waiting 45 additional seconds, other 0.01 mg/kg (up to 0.2 mg per injection) injections may be administered and repeated every minute, if necessary (up to 4 additional administrations), the maximum total dose is 0.05 mg/kg or 1 mg.
In intensive care: Flumazenil must be administered by an anaesthesiologist/ intensive care physician.
In adults: The recommended initial IV dose is of 0.3 mg. If the degree of consciousness desired is not obtained within 60 seconds, new injections of flumazenil of 0.2 or 0.3 mg may be performed, until obtaining signs of waking up or until attaining a maximum total dose of 2 mg. If the consciousness level of the patient and his/her respiratory function do not present a significant improvement after administration of this 2 mg total dose, it should admit that the clinical picture is not due to benzodiazepines. If waking is obtained, and to maintain it, the administration of flumazenil in one or several IV injections of 0.3 mg or in IV infusion of 0.1 to 0.4 mg per hour may be continued. The infusion rate may be adjusted individually as a function of the degree of waking desired.
In children (including infants): The recommended initial dose is of 0.01 mg/kg in slow intravenous injection every 2 minutes until obtaining signs of waking and followed, if necessary, of a continuous infusion with an hourly dose equal to the total loading dose.
For full details see prescribing information.

Flumazenil is indicated,
Benzodiazepine antagonist for reversal of benzodiazepine anesthesia, as well as for patients with Benzodiazepine intoxication.
In a hospital setting:
In anaesthesiology to neutralise the sedative effects of benzodiazepines on the central nervous system in adults and children older than 6 months:
– reversal of sedative effect during general anaesthesia induced and maintained by benzodiazepines,
– reversal of conscious sedation induced by benzodiazepines in short operations with a diagnostic or therapeutic objective.
In intensive care to neutralise the sedative effects of benzodiazepines on the central nervous system and treat a coma of unknown aetiology, in adults and children (including newborns) if the semiology is compatible with the hypothesis of a benzodiazepine or related substance-induced coma:
– diagnosis and/or treatment of intentional or accidental benzodiazepine overdose,
– aetiological diagnosis of an unexplained coma in order to differentiate what is caused by a benzodiazepine from another cause (pharmacological or neurological).
– specific cancellation of the effects on the central nervous system by excessive benzodiazepine doses (re-establishment of spontaneous ventilation to avoid intubation or interrupt ventilatory assistance).
In an emergency situation or medical transport, in adults and children older than 6 years:
– reversal of benzodiazepine-induced conscious sedation in case of respiratory depression or apnoea.

Flumazenil is contraindicated in patients with a known hypersensitivity or intolerance to this product (or to benzodiazepines and related substances) or to any ingredient of the product.
Flumazenil is contraindicated in patients who received benzodiazepines or related substances for a pathology that represents a vital risk (increase in intracranial pressure, epileptic seizure).

Attention
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.

During administration in anaesthesiology: rare cases of nausea and/or vomiting.
The following has been occasionally reported: anxiety, palpitation and anguish. Usually, the undesirable effects mentioned did not require any special treatment. Convulsions have been reported in some patients with a long term benzodiazepine treatment, in particular in epileptic subjects or in a multidrug overdose. Withdrawal symptoms may appear after a fast injection of flumazenil in patients whose long term benzodiazepine treatment was stopped in the weeks preceding the administration of flumazenil.
Flumazenil may provoke panic attacks in patients who have already suffered from them.

Not applicable.

Pregnancy: There are no reliable teratogenesis data in animals. In clinical practice, there is currently insufficient pertinent data to evaluate any possible malformation or foetotoxic effect of flumazenil when administered during pregnancy.
Therefore, the use of flumazenil during pregnancy is advised against except in emergency situations.
Breast-feeding: Breast-feeding is not a contraindication to the administration of flumazenil in an emergency context. However the continuation of the breast-feeding must take into account the intoxication treated.

No sign of overdose has been observed, even when flumazenil is administered at doses higher than those recommended.