Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Use in children for other indications than reversal of conscious sedation is not recommended as no controlled studies are available.
- The patient should be monitored for an adequate period of time (ECG, pulse, oximetry, patient alertness and other vital signs such as heart rate, respiratory rate and blood pressure).
- Flumazenil specifically reverses benzodiazepines. Therefore, if the patient does not wake up, another aetiology should be considered.
- When used in anaesthesiology at the end of surgery, flumazenil should not be given until the effects of peripheral muscle relaxants have been fully reversed.
- As the action of flumazenil is usually shorter than that of benzodiazepines and sedation may possibly recur the patient should remain closely monitored, preferably in the intensive care unit, until the effect of flumazenil has presumably worn off.
- In patients at increased risk the advantages of sedation by means of benzodiazepines should be weighed against the drawbacks of rapid awakening. In patients (e.g. with cardiac problems) maintenance of a certain level of sedation may be preferable to being fully awake.
- Rapid injection of high doses (more than 1 mg) flumazenil should be avoided. In patients who receive high dose and/or chronic treatment with benzodiazepines at any time within the weeks preceding flumazenil administration, rapid injection of doses equal or higher than 1 mg has led to withdrawal symptoms including palpitations, agitation, anxiety, emotional lability as well as mild confusion and sensory distortions.
- In patients suffering from pre-operative anxiety or having a history of chronic or episodic anxiety the dosage of flumazenil should be adjusted carefully.
- Postoperative pain must be taken into account. It may be preferable to keep the patient lightly sedated.
- In patients treated for long periods with high doses of benzodiazepines, the advantages of the use of flumazenil should be carefully weighed against the risk of withdrawal symptoms. If withdrawal symptoms occur despite careful dosing an individually titrated dose of 5 mg diazepam or 5 mg midazolam should be given by slow intravenous injection.
- Patients who have received flumazenil for the reversal of benzodiazepine effects should be monitored for resedation, respiratory depression or other residual benzodiazepine effects for an appropriate period based on the dose and duration of effect of the benzodiazepine employed. Because patients with underlying hepatic impairment may experience delayed effects as described above, an extended observation period may be required.
-   Because of the potential for resedation and respiratory depression children previously sedated with midazolam should be monitored at least 2 hours after flumazenil administration.
In case of other sedating benzodiazepines, the monitoring time must be adjusted according to their expected duration.
-   Until sufficient data are available flumazenil should not be used in children of 1 year or younger unless the risks for the patient (especially in case of accidental overdose) have been weighed against the advantages of the therapy.
-   The use of the antagonist is not recommended in patients with epilepsy, who have been treated with benzodiazepines for a prolonged period of time. Although flumazenil has some intrinsic anti-epileptic effects, the abrupt antagonising effect can cause convulsions in patients with epilepsy.
-   In patients with serious brain damage (and/or instable intracranial pressure) receiving flumazenil – to reverse the effects of benzodiazepines – an increased intracranial pressure may develop.
-   Flumazenil is not recommended for the treatment of benzodiazepine-dependence or for the treatment of long-term benzodiazepine-abstinence-syndromes.
-   Panic attacks have been reported after the use of flumazenil in patients with a history of panic disorder.
-   Due to the increased frequency of benzodiazepines tolerance and dependence in patients with alcoholism and other drug dependencies, flumazenil should be used with caution in this population.
-   Particular caution is necessary when using flumazenil in cases of mixed-drug overdose. In particular in the case of an intoxication with benzodiazepines and cyclic antidepressants, certain toxic effects such as convulsions and cardiac arrhythmias, which are caused by these antidepressants but which emerge less readily on concomitant administration with benzodiazepines, are exacerbated on administration of flumazenil.
-   Elimination may be delayed in patients with hepatic impairment.
-   Each 5 ml ampoule contains less than 1 mmol sodium (or 23 mg), that is to say essentially ‘sodium-free’.
-   Each 10 ml ampoule contains 1.61 mmol sodium (or 37 mg), equivalent to 1.9% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7 Effects on ability to drive and use machines
Patients who have received flumazenil to reverse the effects of benzodiazepine sedation should be warned not to drive, to operate machinery or to engage in other activities demanding physical or mental exertion for at least 24 hours, since the effect of the benzodiazepine may return.