Flumazenil (Flumazenilum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
Read on
Clinical and pharmacological group: & nbsp

Detoxifying agents, including antidotes

Included in the formulation
  • Anexat®
    solution in / in 
    Chaplafarm Artsynmittel GmbH     Germany
    • АТХ:

    V.03.A.B   Antidotes

    Pharmacodynamics:

    Specific antagonist of benzodiazepine derivatives. The main effects of benzodiazepines - sedative, hypnotic, anticonvulsant, anxiolytic - result from stimulation of benzodiazepine receptors and amplification in this regard GABA-ergic mechanisms in the CNS. Flumazenil blocks benzodiazepine receptors and eliminates or reduces the action of benzodiazepines. A similar effect occurs upon administration of flumazenil background "nonbenzodiazepine" benzodiazepine receptor agonists, for example, hypnotic zopiclone means.

    Neutralizes sleeping-sedative action, amnesia, psychomotor disturbances and restores self-breathing and consciousness in case of benzodiazepine overdose. Has an internal agonistic (in relation to the named receptors) activity (anticonvulsant).

    Flumazenil does not eliminate the effects of substances that depress the central nervous system, if their effects are not due to the effect on benzodiazepine receptors. By duration of action flumazenil is inferior to most of the benzodiazepine receptor agonists, and it is sometimes necessary to administer flumazenil repeatedly.

    Pharmacokinetics:

    The onset of action is within 1-2 min, the peak concentration time in the central nervous system is 1-3 min. The time to achieve the maximum effect is 6-10 minutes after intravenous administration. The duration of action depends on the dose of benzodiazepines and flumazenil, in 60-95% of patients it is possible to remove the inhibitory effect of benzodiazepines by about 3 hours.

    Rapidly absorbed with parenteral administration. In the blood, it binds to proteins by 50% (2/3 - with albumins). The average volume of distribution is 0.95 l / kg. The total plasma clearance is 1 l / min. The half-life is 50-60 minutes. The main metabolite, carboxylic acid, is inactive (neither as an agonist nor as a benzodiazepine antagonist). Completely (99%) is excreted with bile.

    Indications:
    • The induction of inpatients from general anesthesia started and maintained with benzodiazepines.
    • Elimination of the sedative effect of benzodiazepines in short-term diagnostic and therapeutic procedures in inpatient and outpatient patients.
    • Differential diagnosis in the loss of unclear etiology: setting or excluding the diagnosis of benzodiazepine poisoning.
    • Poisoning with benzodiazepines: specific elimination of central effects of benzodiazepines during their overdose (restoration of independent breathing and consciousness,which eliminates the need for intubation or allows extubation of the patient).
    ICD-10

    XIX.T36-T50.T42   Poisoning with anticonvulsant, sedative, hypnotics, and anti-Parkinsonics

    XXI.Z40-Z54.Z51.4   Preparatory procedures for subsequent treatment, not elsewhere classified

    XIX.T66-T78.T78.8   Other adverse reactions, not elsewhere classified

    XX.Y85-Y89.Y88.0   Consequences of adverse effects of medicinal products, medicines and biological substances used for therapeutic purposes

    Contraindications:

    Hypersensitivity, poisoning with cyclic antidepressants. Contraindicated in patients who receive benzodiazepines for the treatment of potentially life-threatening conditions (eg, intracranial hypertension or epileptic status).

    Poisoning by cyclic antidepressants.

    Carefully:No data.
    Pregnancy and lactation:

    Recommendations for FDA - Category C. Qualitative and well-controlled studies on humans and animals have not been conducted. In some studies on animals, the embryotoxic effect of flumazenil has been established in doses exceeding the average doses for humans by 100-200 times.

    When using the drug should carefully compare the benefits of use for the mother with a possible risk to the fetus.

    There is no data on the penetration into breast milk. During the period of breastfeeding, parenteral administration of flumazenil in emergency cases is not contraindicated.

    Dosing and Administration:Intravenously (previously diluted with 5% glucose solution or 0.9% sodium chloride solution).
    In anesthesiology:     in an initial dose of 0.2 mg for 15 seconds; if necessary, 0.1 mg every 60 seconds to a total dose of 1 mg; the usual dose is 0.3-0.6 mg.
    In intensive care:     in an initial dose of 0.3 mg; if necessary, repeat the injection every 60 seconds to a total dose of 2 mg.
    Side effects:

    From the side nervous system and sense organs: dizziness, headache, blurred vision, agitation, anxiety, nervousness, tremor, insomnia; asthenia, paresthesia, emotional lability (tearfulness), depersonalization, euphoria, dysphoria, depression, paranoia, impaired vision (diplopia, visual field defect); impaired concentration, delirium, cramps, drowsiness, transient hearing loss, hyperacusis, tinnitus; cases of convulsive seizures in patients,suffering from epilepsy or severe liver damage (especially after prolonged treatment with benzodiazepines or in case of mixed drug overdose); there are reports that in patients with panic disorders in the anamnesis, the administration of flumazenil may trigger a panic attack.

    From the side cardiovascular system and blood (hematopoiesis, hemostasis): palpitation; dilatation of skin vessels, flushing of blood to the face.

    From the side organs of the digestive tract: dry mouth, nausea, vomiting.

    Other: ataxia, dyspnea, hyperventilation, pain at the injection site, sweating; thrombophlebitis, rash; after rapid administration of flumazenil - anxiety, palpitations, a sense of fear.

    Overdose:Not described. Treatment symptomatic.
    Interaction:Tricyclic and tetracyclic antidepressants are a high risk of seizures, especially with a mixed overdose with benzodiazepines, since flumazenil removes not only the sedative, but also the anticonvulsant effect of benzodiazepines. Weakens the effects of zopiclone, triazolpyridazines, benzodiazepines.
    Special instructions:

    When anesthesia can not be administered until the end of the action of peripheral muscle relaxants.It should be borne in mind that in patients with severe craniocerebral trauma (or unstable intracranial pressure), an increase in intracranial pressure may develop.

    Do not use flumazenil in patients with epilepsy, who for a long time received drugs that are derivatives of benzodiazepine.

    Impact on the ability to drive vehicles and manage mechanisms.

    Within 24 hours after the application of flumazenil it is necessary to refrain from working with potentially dangerous mechanisms, driving the car and other activities requiring increased attention.

    Instructions
    Up