FLUMAZENIL Solution for injection or infusion Ref.[9518] Active ingredients: Flumazenil

Posology

Adults

Anaesthesia

The recommended starting dose is 200 micrograms administered intravenously over 15 seconds. If the required level of consciousness is not obtained within 60 seconds, a further dose of 100 micrograms can be injected and repeated at 60-second intervals, up to a maximum dose of 1000 micrograms. The usual dose is 300 to 600 micrograms, but may deviate depending on the patient’s characteristics and the benzodiazepine used.

Intensive Care

The recommended starting dose is 300 micrograms administered intravenously. If the required level of consciousness is not obtained within 60 seconds, a further dose of 100 micrograms can be injected and repeated at 60-second intervals, up to a total dose of 2000 micrograms or until the patient awakes.

If drowsiness recurs, a second bolus injection of flumazenil may be administered. An intravenous infusion of 100 – 400 micrograms/hour may be useful.

The dosage and rate of infusion should be adjusted individually to achieve the desired level of consciousness.

If a significant improvement in consciousness or respiratory function is not obtained after repeated doses of flumazenil, a non-benzodiazepine aetiology must be assumed.

Infusion should be discontinued every 6 hours to verify whether re-sedation occurs.

To avoid withdrawal symptoms in patients treated for a long period of time with high doses of benzodiazepines in the intensive care unit, the dosage of flumazenil has to be titrated individually and the injection has to be administered slowly (see section 4.4).

Special Populations

Elderly

In the absence of data on the use of flumazenil in elderly patients, it should be noted that this population is generally more sensitive to the effects of medicinal products and should be treated with due caution.

Patients with renal or hepatic impairment

Since flumazenil is primarily metabolised in the liver, careful titration of dosage is recommended in patients with impaired hepatic function. No dosage adjustments are required in patients with renal impairment.

Paediatric population

Children above 1 year of age: For the reversal of conscious sedation induced with benzodiazepines in children above 1 year of age, the recommended initial dose is 10 micrograms/kg (up to 200 micrograms) administered intravenously over 15 seconds. If the desired level of consciousness is not obtained after waiting an additional 45 seconds, further injection of 10 micrograms/kg may be administered (up to 200 micrograms) and repeated at 60 second intervals where necessary (a maximum of 4 times) to a maximum total dose of 50 micrograms/kg or 1000 micrograms, whichever is lower. The dose should be individualised based on the patient’s response. No data are available on the safety and efficacy of repeated administration of flumazenil to children for re-sedation.

Children under the age of 1 year: There are insufficient data on the use of flumazenil in children younger than 1 year.

Therefore, flumazenil should only be administered in children younger than 1 year if the potential benefits to the patient outweigh the possible risk.

Method of administration

Flumazenil must be administered intravenously by an anesthetist or a doctor with experience in anesthesiology.

Flumazenil may be administered as an infusion – for instructions on dilution of the medicinal product before administration, see section 6.6.

Flumazenil may be used concomitantly with other resuscitative measures.

In cases of mixed-drug overdose, particularly with cyclic antidepressants, toxic effects (such as convulsions and cardiac dysrhythmias) may emerge with the reversal of benzodiazepine effects by flumazenil.

There is very limited experience of acute overdose in humans with flumazenil.

There is no specific antidote for overdose with Flumazenil. Treatment should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

Even when administered intravenously at doses of 100 mg, no symptoms of overdose attributable to flumazenil have been observed.

Shelf life: 3 years.

Shelf life after first opening: After first opening the medicinal product should be used immediately.

Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Do not store above 25°C. Do not freeze.

Keep the ampoules in the outer carton in order to protect from light.

Carton boxes with 5 or 10 ampoules (glass Type I) containing 5 ml solution for injection/infusion.

Carton boxes with 5 or 10 ampoules (glass Type I) containing 10 ml solution for injection/infusion.

Not all pack sizes may be marketed.

This medicinal product is for single use only and any unused solution should be discarded.

Please inspect the medicinal product visually. It should only be used if the solution is clear and practically free from particles.

When flumazenil is to be used in infusion, it must be diluted prior to infusion. Flumazenil should only be diluted with sodium chloride 9 mg/ml (0.9%) solution, dextrose 50 mg/ml (5%) solution or sodium chloride 4.5 mg/ml (0.45%) + dextrose 25 mg/ml (2.5%) solution (10, 20, 50 ml Flumazenil 100 micrograms/ml in 500 ml solution). Compatibility between flumazenil and other solutions for injection has not been established.

Intravenous infusion solutions should be discarded after 24 hours.

Any unused product or waste material should be disposed of in accordance with local requirements.