Each mL contains: Flumazenil 100 mcg.
Pharmacology: Pharmacokinetics: Flumazenil is well absorbed from the gastrointestinal tract but undergoes extensive first-pass hepatic metabolism and has a systemic bioavailability of about 20%. It is about 50% bound to plasma proteins. After intravenous administration, it is extensively metabolised in the liver to the inactive carboxylic acid form, which is excreted mainly in the urine. The elimination half-life is about 40 to 80 minutes. In patients with hepatic impairment the clearance of flumazenil is decreased with a resultant prolongation of half-life.
Flumazenil is a benzodiazepine antagonist that acts competitively at CNS benzodiazepine receptors. It is used in anaesthesia and intensive care to reverse benzodiazepine-induced sedation; it may also be used to treat benzodiazepine overdosage.
Flumazenil should be given by slow intravenous injection or infusion. The usual initial dose for the reversal of benzodiazepine- induced sedation is 200 micrograms, followed at intervals of 60 seconds by further doses of 100 to 200 micrograms if required, to a maximum total dose of 1 mg or occasionally 2 mg (usual range, 0.3 to 1 mg); each dose should be given over 15 seconds, and further doses should only be given if an adequate response has not occurred 45 seconds after completion of the injection. If drowsiness recurs an intravenous infusion may be used, at a rate of 100 to 400 micrograms/hour, adjusted according to response.
Alternatively, further doses of up to 1 mg, in boluses of 200 micrograms as above, may be given at 20-minute intervals to a maximum of 3 mg in one hour. Patients at risk from the effects of benzodiazepine reversal, such as those dependent on benzodiazepines, should receive smaller bolus injections of 100 micrograms. The dose for children is 10 micrograms/kg, repeated at 60-second intervals up to a maximum of 50 micrograms/kg or 1 mg, whichever is lower; doses are given intravenously over 15 seconds, with further doses if an adequate response has not occurred 45 seconds after completion of the injection, as for adults.
The usual initial dose for the management of benzodiazepine overdose is 200 micrograms given intravenously over 30 seconds. A further dose of 300 micrograms can be given after another 30 seconds and can be followed by doses of 500 micrograms at one-minute intervals if required, to a total dose of 3 mg or occasionally 5 mg. If a dose of up to 5 mg produces no response then further doses are unlikely to be effective.
If symptoms of intoxication recur, repeated doses may be given at 20-minute intervals; not more than 1 mg should be given at any one time and not more than 3 mg in one hour. As before, a slower rate of administration may be used for 'at risk' patients. If signs of overstimulation occur during the use of flumazenil, then diazepam or midazolam may be given by slow intravenous injection.
Flumazenil labeled with carbon-11 has been used for studying GABA receptors by positron emission tomography.
Flumazenil should not be given to patients who have received neuromuscular blockers until the effects of neuromuscular blockade have fully cleared. Dosage should be adjusted individually; in high-risk or anxious patients, and after major surgery, it may be preferable to maintain some sedation during the early postoperative period. Flumazenil should be used with caution in patients with head injury since it may precipitate seizures or alter cerebral blood flow. Careful titration of dosage is recommended in hepatic impairment.
Flumazenil is contra-indicated in patients who are receiving benzodiazepines to control potentially life-threatening conditions and should not be given to epileptic patients who have been receiving benzodiazepines for a prolonged period to control seizures. In cases of mixed overdose, flumazenil may unmask adverse effects of other psychotropic drugs. In particular, it should not be used in the presence of severe intoxication with tricyclic and related antidepressants.
The adverse effects experienced during use of flumazenil are generally due to the reversal of benzodiazepine effects and resemble benzodiazepine withdrawal symptoms. Nausea, vomiting, dizziness, blurred vision, headache, and flushing may occur. Anxiety, fear, and agitation have been reported after too rapid reversal of sedation. There have been reports of seizures, especially in epileptics. Transient increases in blood pressure and heart rate have been observed. Hypersensitivity reactions have occurred rarely. Patients who have received benzodiazepines for prolonged periods are particularly at risk of experiencing withdrawal symptoms and rapid injection of flumazenil should be avoided in such patients. Because of its short duration of action, patients given flumazenil to reverse benzodiazepine-induced sedation should be kept under close observation; further doses of flumazenil may be necessary.
Cyclic Antidepressants: Flumazenil should not be used in patients exhibiting manifestations of serious concurrent cyclic antidepressant overdosage, such as motor abnormalities (e.g. twitching, rigidity, focal seizures), arrhythmias, (e.g. wide QRS complexes, ventricular arrhythmias, heart block), anticholinergic effects (e.g. mydriasis, dry mucosa, hypoperistalsis), or cardiovascular collapse. In such cases, the patient should be managed ventilator and circulatory supportive measures until the signs of antidepressant toxicity have subsided.
Benzodiazepines: Pharmacokinetics interaction unlikely. However, Flumazenil may precipitate dose-dependent manifestations of withdrawal in patients with established physical dependence on benzodiazepines.
Other Drugs: Interactions of Flumazenil with CNS depressants other than benzodiazepines have not been studied. However, deleterious interactions have been observed when flumazenil was administered with opiates, inhalational anesthetics, skeletal muscle relaxants, or muscle relaxant antagonist administered in conjunction with sedation or anesthesia. Flumazenil should not be administered until the effects of neuromuscular blockade have been fully reserved.
Single use only, discard any remaining portion.
Store at temperatures not exceeding 30°C.
V03AB25 - flumazenil ; Belongs to the class of antidotes. Used in the management of hypnotics and sedatives overdose.
Soln for infusion (amp) 100 mcg/mL x 5 mL x 5's.