In healthy volunteers, flumazenil did not alter intraocular pressure when given alone and reversed the decrease in intraocular pressure seen after administration of midazolam.Īfter IV administration, plasma concentrations of flumazenil follow a two-exponential decay model. The duration and degree of reversal are related to the plasma concentration of the sedating benzodiazepine as well as the dose of flumazenil given. Eighty percent response will be reached within 3 minutes, with the peak effect occurring at 6 to 10 minutes. The onset of reversal is usually evident within 1 to 2 minutes after the injection is completed. Generally, doses of approximately 0.1 mg to 0.2 mg (corresponding to peak plasma levels of 3 to 6 ng/mL) produce partial antagonism, whereas higher doses of 0.4 to 1 mg (peak plasma levels of 12 to 28 ng/mL) usually produce complete antagonism in patients who have received the usual sedating doses of benzodiazepines. The duration and degree of reversal of sedative benzodiazepine effects are related to the dose and plasma concentrations of flumazenil as shown in the following data from a study in normal volunteers. Intravenous flumazenil has been shown to antagonize sedation, impairment of recall, psychomotor impairment and ventilatory depression produced by benzodiazepines in healthy human volunteers. A similar effect was seen in adult human subjects. In animals pretreated with high doses of benzodiazepines over several weeks, flumazenil elicited symptoms of benzodiazepine withdrawal, including seizures. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.įlumazenil does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil Injection - Clinical Pharmacologyįlumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Each mL contains 0.1 mg of Flumazenil compounded with 1.8 mg of Methylparaben, 0.2 mg of Propylparaben, 0.9% mg Sodium Chloride, 0.01% Edetate Disodium Dihydrate, and 0.1 mg Glacial Acetic Acid the pH is adjusted to 3.4 to 4.6 with Hydrochloric Acid and/or, if necessary, Sodium Hydroxide and Water for Injection q.s. Flumazenil is available as a sterile parenteral dosage form for intravenous administration. It is insoluble in water but slightly soluble in acidic aqueous solutions. Flumazenil has an imidazobenzodiazepine structure a calculated molecular weight of 303.3 and the following structural formula:įlumazenil is a white to off-white crystalline compound with an octanol:buffer partition coefficient of 14 to 1 at pH 7.4. Chemically, flumazenil is ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo (1,4) benzodiazepine-3-carboxylate. Flumazenil Injection, USP is a benzodiazepine receptor antagonist.
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