Anexat, 0.5mg/5ml 5 ml 5 pcs

Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist.

Pharmacological action – blocking benzodiazepine receptors.

Pharmacokinetics

The pharmacokinetics of flumazenil, both in the therapeutic and higher dose range (up to 100 mg), are dose dependent.

• Distribution

  Flumazenil, a weak lipophilic base, is approximately 50% bound to plasma proteins. Albumin accounts for two-thirds of the binding to proteins. Flumazenil is intensively distributed in the extravascular space. Plasma concentrations of flumazenil decrease with a half-life of 4-11 minutes during the distribution phase. The volume of distribution when reaching the equilibrium concentration is 0.9-1.1 L/kg.

• Metabolism

  Flumazenil is extensively metabolized in the liver. The main inactive metabolite in plasma (free form) and urine (free form and glucuronide) is carboxylic acid. The main metabolite has no agonist or antagonist benzodiazepine activity according to pharmacological tests.

• Elimation

  The total clearance of flumazenil is 0.8-1.0 L/h/kg, is primarily by the liver (99%) and depends on the magnitude and rate of hepatic blood flow. Excretion of flumazenil is practically completed after 72 hours, 90-95% is found in the urine and 5-10% in the feces. Elimination is rapid, as evidenced by a short elimination half-life of 40-80 minutes.

  Eating during an intravenous infusion of flumazenil results in a 50% increase in clearance, most likely due to the increased hepatic blood flow that accompanies eating.

• Pharmacokinetics in special clinical groups

  In patients with impaired hepatic function, the half-life of flumazenil is longer and total clearance is lower than in healthy volunteers.

  The pharmacokinetics of flumazenil are not significantly altered in elderly and senile patients and are independent of gender, hemodialysis or renal impairment.

  In children over 1 year of age, the elimination half-life is more variable than in adults and averages 40 minutes (range 20-75 minutes). Clearance and volume of distribution, correlated with body weight, are within the same limits as in adults.

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Indications

To reduce or eliminate the inhibitory effects of benzodiazepine receptor agonists (including

Active ingredient

Composition

one ampoule with 5 ml of aqueous solution for intravenous injection contains Flumazenil 0.5 mg;

auxiliary substances:

Ethylenediaminetetetraacetic acid,

acetic acid,

How to take, the dosage

It is administered by infusion.

The initial dose is 200-300 mcg.

If repeated administration is necessary, the total dose should not exceed 1-2 mg.

Interaction

Flumazenil suppresses the central effects of benzodiazepines by competitive inhibition at the receptor level. It also blocks the effects of non-benzodiazepine agonists on benzodiazepine receptors (zopiclone, triazolpyridazines, etc.).

No pharmacokinetic interaction between anexat and benzodiazepine receptor agonists, ethyl alcohol has been identified. Pharmacokinetics of benzodiazepine agonists in the presence of flumazenil does not change, as well as pharmacokinetics of flumazenil in the presence of benzodiazepine agonists does not change. There is no pharmacokinetic interaction between flumazenil and ethyl alcohol.

Special Instructions

Particular caution is needed when prescribing flumazenil in cases of mixed drug overdose, because after elimination of benzodiazepine effects the toxic effects (e.g., seizures and cardiac arrhythmias) of other drugs taken in excessive doses (especially cyclic antidepressants) may appear.

Flumazenil is not recommended for use in patients with epilepsy who have received long-term therapy with benzodiazepines. Although flumazenil has a weak anticonvulsant effect of its own, a sharp decrease in the effects of benzodiazepines in patients with epilepsy may provoke seizures.

Patients to whom flumazenil has been administered to reverse the effects of benzodiazepines should be monitored for re-sedation, respiratory depression, and other residual benzodiazepine effects over time, given the doses and duration of action of previously administered benzodiazepines.

Flumazenil should not be used until peripheral myorelaxants have completed their action and neuromuscular blockade has resolved simultaneously with neuromuscular transmission blockers and should not be administered until neuromuscular blockade has resolved.

Flumazenil is used with caution in patients with craniocerebral injuries because it may induce seizures or alter cerebral blood flow in patients who have received benzodiazepines.

The rapid administration of flumazenil should be avoided in patients who have previously received long-term benzodiazepines and have completed their treatment within a few weeks before prescribing flumazenil, as withdrawal symptoms, including agitation, anxiety, emotional lability, and mild degrees of confusion and sensory disturbances, may occur.

Flumazenil is not recommended for the treatment of benzodiazepine dependence or for the management of long-lasting symptoms of benzodiazepine withdrawal.

Flumazenil should be used with caution to relieve conscious sedation in children under 1 year of age, to treat benzodiazepine overdose in children, to treat neonatal resuscitation, and to relieve the sedative effects of benzodiazepines that have been used in anesthesia in children because experience with the drug in these situations is limited.

Impact on driving and operating machinery

In the first 24 hours after administration of flumazenil, refrain from activities requiring increased attention (operating machinery, driving vehicles) because the effects of previously taken or injected benzodiazepines may resume.

Contraindications

Anexat is contraindicated in patients who receive benzodiazepines to treat a potentially life-threatening condition (such as intracranial hypertension or epileptic status).

Side effects

In very rapid recovery of consciousness, motor agitation, anxiety, fear are possible.

Possible: nausea, vomiting, sudden reddening of the skin, transient increase in BP, tachycardia.

Rarely: seizures (especially in patients with epilepsy).

Overdose

There are no symptoms of overdose, even after IV doses higher than recommended.

Pregnancy use

Although flumazenil has not been shown to be mutagenic, embryotoxic, or teratogenic at high doses in animal experiments and has no effect on fertility, the safety of its use in human pregnancy has not been established. Therefore, when prescribing it in these cases, the benefits of its use should be carefully weighed against the possible risks to the fetus.

Parenteral administration of flumazenil in emergency cases is not contraindicated during lactation.