Anexat - instructions for use, doses, side effects, contraindications

Active substanceFlumazenilFlumazenil

Similar drugsTo uncover

Anexat®

solution in / in

Chaplafarm Artsynmittel GmbH Germany

Dosage form: & nbspRAsterol for intravenous administration

Composition:

One ampoule (5 ml) with a solution for intravenous administration contains:

active substance: flumazenil - 0.5 mg;

Excipients: disodium edetate - 0.5 mg, glacial acetic acid - 0.5 mg, sodium chloride - 46.5 mg, sodium hydroxide 0.1 M solution - q.s. up to pH 4.0. water for injection up to 5 ml.

Description:

Transparent colorless or almost colorless liquid.

Pharmacotherapeutic group:Benzodiazepine antagonist

ATX: & nbsp

V.03.A.B Antidotes

Pharmacodynamics:

Flumazenil, an imidazobenzodiazepine derivative, is an antagonist of bisodiazepines. Specifically suppresses the effects of drugs acting on the benzodiazepine receptors of the central nervous system. Eliminates sedation, amnesia and psychomotor disorders caused by benzodiazepine receptor agonists. The hypnotic and sedative effect of benzodiazepines disappears 1-2 minutes after intravenous injection of flumazsnil, but may gradually reappear over the next several hours, depending on the half-life and the dose of the agonist and antagonist.

Flumazenil may have its own weak agonistic (eg, anticonvulsant) activity.

In adult patients who received large doses of benzodiazepines for several weeks, the administration of flumaznil was accompanied by withdrawal symptoms of benzodiazepines, including convulsions.

Pharmacokinetics:

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

Distribution

Flumazenil, a weak lipophilic base, binds approximately 50% to plasma proteins. Two thirds of the binding to proteins is accounted for by albumin. Flumazenil intensively distributed in the extravascular space. The concentrations of flumazeil in plasma decrease with a half-life of 4-11 minutes during the distribution phase. The volume of distribution when the equilibrium concentration is reached is 0.9-1.1 l / kg.

Metabolism

Flumazenil undergoes intensive metabolism in the liver. The main inactive metabolite in plasma (free form) and urine (free form and pnukuronid) is carboxylic acid. The main metabolite does not have agonistic or antagonistic benzodiazepine activity according to the results of pharmacological tests.

Excretion

The total clearance of flumaze is 0.8-1.0 l / h / kg, carried out mainly by the liver (99%) and depends on the magnitude and speed of the hepatic blood flow. The elimination of flumazeil is almost complete after 72 hours, 90-95% is detected in urine and 5-10% in feces. Elimination occurs quickly, as evidenced by a short half-life of 40-80 minutes.

Admission to the hospital during intravenous infusion of flumazepil leads to a 50% increase in clearance, most likely due to increased hepatic blood flow that accompanies the ingestion of food.

Pharmacokinetics in specific patient groups

In patients with hepatic insufficiency, the half-life of flumazepil is longer (1.3 hours in patients with moderate hepatic impairment and 2.4 hours in patients with severe hepatic impairment) and the overall clearance is lower than in healthy volunteers. The pharmacokinetics of flumazepil does not change significantly in elderly and senile individuals, does not depend on sex, hemodialysis or renal failure.

In children older than 1 year, the half-life period is more susceptible to fluctuations than in adults, and is, on average, 40 minutes (range 20-75 minutes).The clearance and volume of distribution, correlated with body weight, are in the same range as in adults.

Indications:

Complete or partial elimination of central sedative effects of benzodiazepines. The drug is used in anesthesiology and intensive care for the following indications.

Anesthesiology:

- induction of inpatients from general anesthesia initiated and maintained with benzodiazepines;

- elimination of sedative effect of benzodiazepines during short-term diagnostic and therapeutic procedures in inpatient and outpatient patients;

- elimination of sedation with preservation of consciousness caused by benzodiazepines, in children older than 1 year.

Intensive therapy and management of patients with loss of consciousness of unclear zthiology:

-differential diagnosis in the loss of consciousness of unknown etiology; the formulation or exclusion of a diagnosis of benzodiazepine poisoning;

-reduction of 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).

Contraindications:

Hypersensitivity to the drug or any of its components.

Anexat® is contraindicated in patients receiving bezodiazepines to treat a condition potentially life threatening (eg, with epileptic status or for monitoring intracranial pressure).

Poisoning by cyclic antidepressants.

Pregnancy and lactation:

Although in animal experiments flumazenil in large doses, nc had mutagenicity, embryotoxicity, teratogenicity and nc influenced fertility, the safety of its use in pregnant women is not established. Therefore, when it is appointed, the benefits of using it for the mother with a possible risk to the fetus should be carefully compared. During the period of breastfeeding, parenteral administration of flumazepil in emergency cases is not contraindicated.

Dosing and Administration:

Standard dosing regimen

Anexat® is administered only intravenously (bolus or infusion) under the supervision of a qualified anesthesiologist or therapist. The drug is compatible with 5% dextrose solution or 0.9% sodium chloride solution. To maintain sterility, Anexat® should be recruited from the ampoule just before use.After dialing into a syringe or diluting with 5% dextrose solution or 0.9% sodium chloride solution, the drug should be used within 24 hours.

The dose should be titrated until the desired effect is obtained. Since the duration of action of some benzodiazepines may exceed that of flumazepil, it may be necessary to re-administer the drug in the event that, after restoration of consciousness, the sedation reappears.

Anesthesiology

The recommended initial dose is 0.2 mg IV in 15 seconds. If 60 seconds after the first intravenous dose of the desired recovery of consciousness does not occur, then you can enter a second dose (0.1 mg). If necessary, this procedure can be carried out at 60-second intervals until a total dose of 1 mg is achieved. Usually the dose is 0.3-0.6 mg, but the individual requirement can vary significantly, depending on the dose and duration of action of the previously administered benzodiazepine and the characteristics of the patient.

Intensive therapy and management of patients with unclear etiology

The recommended initial dose is 0.3 mt IV. If the desired level of restoration of consciousness does not occur, flumazenil can be re-introduced as described above, until the total dose of nc is more than 2 mg.When recrudescence of confusion is recommended to inject the drug intravenously again: either bolus, or as an intravenous infusion at a rate of 0.1-0.4 mg per hour. The rate of infusion is selected individually to achieve the required level of recovery of consciousness.

If, after repeated administration of flumazenil, the consciousness or respiratory function is not restored enough, it is necessary to assume the non-benzodiazepine etiology of impaired consciousness.

In patients in intensive care units, as well as in patients who received long doses of benzodiazepines, the individually selected doses of flumazenil with slow administration should not cause withdrawal symptoms. When there are undesirable symptoms of hyperstimulation, intravenously injected diazepam or midazolam, carefully titrating their dose depending on the patient's reaction.

Dosing in special cases

Children over 1 year old

To eliminate sedation with conserved consciousness caused by benzodiazepines, the recommended initial dose is 0.01 mg / kg (up to 0.2 mg) IV in 15 seconds. If after 45 seconds the desired level of recovery of consciousness does not occur,can be administered additionally at 0.01 mg / kg (up to 0.2 mg) at 60-second intervals (no more than 4 times) up to a maximum total dose of 0.05 mg / kg, but not more than 1 mg. The dose is selected individually depending on the patient's response. At the moment, there is no data on the efficacy and safety of the repeated administration of the drug Anexat® to children in case of need of re-assignment.

Patients with hepatic insufficiency

As flumazenil is subjected to primary metabolism in the liver, it is recommended to be cautious in selecting the dose of the drug Anexat ® in patients with hepatic insufficiency (see section "Special instructions").

Side effects:

Adults and children are well tolerated flumazenil. Adults well tolerate even higher doses than recommended.

In the post-marketing application, hypersensitivity reactions were observed, including anaphylaxis.

After rapid administration of flumazenil, anxiety, palpitation, and a sense of fear rarely arose. These undesirable effects usually do not require special treatment.

Cases of seizures in patients suffering from epilepsy or severe liver damage are described, especially after prolonged benzodiazepine treatment or in the case of mixed drug overdose.

In the case of mixed drug overdose, especially cyclic antidepressants, toxic effects (eg, seizures and arrhythmias) are possible after elimination of the effects of benzodiazepines.

In patients who received benzodiazepines for a long time and who stopped taking them several weeks before the administration of the drug Anexat®, symptoms of withdrawal can be developed with the rapid administration of the drug Anexat®.

In patients with panic disorders in history, the administration of flumazenil may trigger a panic attack.

Adverse reactions associated with taking flumazenil, occurring in 3-9% of cases: dizziness, headache, blurred vision, agitation, anxiety, nervousness, dry mouth, tremor, insomnia, ataxia (10%), dyspnea, hyperventilation, palpitations, pain at the injection site, sweating.

From the gastrointestinal tract: nausea, vomiting (1 1%).

Adverse reactions associated with taking flumazenil, found in 1-3% of cases:

on the part of the body as a whole: asthenia, local reactions (thrombophlebitis, rash);

from the cardiovascular system: dilatation of skin vessels, sensation of "hot flashes";

from the central nervous system: paresthesia (impaired sensitivity, gyneesthesia), emotional lability (tearfulness, depersonalization, euphoria, dysphoria, depression, paranoia);

sensory organs: impaired vision (diplopia, visual field defect).

Side effects, occurring in less than 1% of cases, possibly associated with taking flumazenil or abolishing benzodiazpines:

from the nervous system: violation of concentration of attention, delirium, cramps, drowsiness;

sensory organs: transient hearing loss, hyperacusis, tinnitus.

Overdose:

Data on acute overdose of flumazenil are limited. There is no specific antidote. In case of an overdose, treatment should consist of general supportive measures, monitoring vital signs and monitoring the clinical status of the patient.

Even with intravenous doses above recommended symptoms, an overdose was not observed.

Interaction:

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

There was no pharmacokinetic interaction between flumazenil and benzodiazepine receptor agonists, ethyl alcohol.

The pharmacokinetics of benzodiazepine agonists in the presence of flumazenil does not change, as does the pharmacokinetics of flumazenil in the presence of benzodiazepine agonists. The pharmacokinetic interaction between flumazenil and ethyl alcohol is absent.

Special instructions:

Particular caution is needed in the appointment of flumazenil in cases of mixed overdose of drugs, since after elimination of benzodiazenine effects, toxic effects (eg, seizures and cardiac arrhythmias) of other drugs taken in excessive doses (especially cyclic antidepressants) may appear.

It is not recommended to apply flumazenil In patients with epilepsy, who received long-term therapy with benzodiazenines. Although flumazenil it has its own weak anti-seizure action, a sharp decrease in the effect of benzodiazepine in patients with epilepsy can provoke convulsions.

Patients to whom Anexat® was administered to eliminate the effect of benzodiazepines should be monitored for repeated sedation, respiratory depression and other residual effects of benzodiazepines over a period of time, given the dose and duration of previously administered benzodiazepines. Due to the possible delay in the onset of the effect of benzodiazepines (as described above), patients with hepatic insufficiency may need a longer follow-up period.

Anexat® is not used until the end of the action of peripheral muscle relaxants and the complete disappearance of the neuromuscular blockade.

Flumazenil is used with caution in patients with craniocerebral trauma, as it can cause seizures or alter the cerebral blood flow in patients who have received beizodiazepines.

The rapid administration of flumazenil should be avoided in patients who have long received benzodiazepines and who have completed treatment within a few weeks prior to flumazenil, since withdrawal symptoms may occur, including psychomotor agitation, anxiety, emotional lability, and mild confusion and sensory disturbances.

Flumazenil is not recommended for the treatment of dependence on benzodiazepines or for the relief of long-persisting symptoms of benzodiazenine abstinence. Flumazenil should be used with caution in order to eliminate the persistence of consciousness with children under 1 year of age, to treat benzodiazepine overdoses in children during resuscitation in newborns and to eliminate the sedative effects of benzodiazepines, which were used when anesthetized in children, because the experience of using the drug in such situations is limited.

Effect on the ability to drive transp. cf. and fur:

During the first 24 hours after the administration of flumazenil, it is necessary to refrain from activities requiring increased attention (work with machines and mechanisms, driving vehicles), since the previously taken or injected benzodiazepines may resume.

Form release / dosage:

Solution for intravenous administration 0.5 mg / 5 ml

Packaging:

5 ml of the drug in ampoules made of hydrolytic class 1 glass (EF), hermetically sealed.The ampoule has a blue dot; on the tip of the ampoule, two rings-purple and green.

5 ampoules are placed in a cardboard tray with septa, which, together with the instructions for use, are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014737 / 01

Date of registration:29.01.2009 / 04.04.2017

Expiration Date:Unlimited

The owner of the registration certificate:Chaplafarm Artsynmittel GmbHChaplafarm Artsynmittel GmbH Germany

Manufacturer: & nbsp

CENEXI, SAS France

Representation: & nbspFARMAGATE, LLCFARMAGATE, LLC

Information update date: & nbsp05.09.2017

Illustrated instructions

Instructions

Anexat® (Anexate®)