Anexat
Anexat: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Anexate
ATX code: V03AB25
Active ingredient: flumazenil (Flumazenil)
Manufacturer: Senexi SAS (Cenexi, SAS) (France)
Description and photo update: 2019-23-04
Prices in pharmacies: from 7929 rubles.
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Anexat is a drug that blocks benzodiazepine receptors.
Release form and composition
The drug is available in the form of a solution for intravenous administration, which is a colorless or almost colorless transparent liquid (5 ml each in hermetically sealed glass ampoules with a blue dot and two colored rings at the tip of the ampoule, 5 ampoules each in cardboard trays with partitions, in a cardboard box one pallet and instructions for use of Anexat).
Composition for one ampoule (5 ml):
- active substance: flumazenil - 0.5 mg;
- auxiliary components: glacial acetic acid, sodium hydroxide 0.1 M solution (up to pH 4.0), disodium edetate, sodium chloride, water for injection.
Pharmacological properties
Pharmacodynamics
Flumazenil refers to derivatives of imidazobenzodiazepines and is a benzodiazepine antagonist. It specifically inhibits the action of drugs that affect the benzodiazepine receptors in the central nervous system.
Anexat eliminates amnesia, sedation and psychomotor disorders caused by benzodiazepine receptor agonists. The sedative and hypnotic effects of benzodiazepines disappear within 1-2 minutes after the intravenous injection of the drug, but in the next few hours they may gradually develop again. It depends on the half-lives and the doses of the antagonist and agonist taken.
Flumazenil itself is capable of exerting a slight agonist effect (eg, anticonvulsant).
In patients who received high doses of benzodiazepines for several weeks, with the introduction of Anexat, symptoms of benzodiazepine withdrawal, including convulsions, occurred.
Pharmacokinetics
Pharmacokinetic parameters of flumazenil in any dose range (up to 100 mg) are dose-dependent.
The drug is about 50% bound to plasma proteins (of which 2/3 are albumin). Flumazenil is actively distributed in tissues and organs in the extravascular space. Its plasma concentration decreases during the distribution phase with an elimination half-life of 4 to 11 minutes. When the equilibrium concentration is reached, the volume of distribution of the substance is 0.9–1.1 l / kg.
Flumazenil is extensively metabolized in the liver. The main inactive metabolite is carboxylic acid. In blood plasma it is present in free form, in urine - in the form of glucuronide and in free form.
Excretion of flumazenil is 99% carried out by the liver. The total clearance depends on the rate and size of the hepatic blood flow and is 0.8–1 l / h / kg. The elimination of the drug is completed in almost 72 hours. About 90–95% of flumazenil is found in urine and a small amount (5–10%) in feces. Elimination is fast, as evidenced by the short half-life, which is only 40–80 minutes.
If during the intravenous infusion of Anexat the patient takes food, the clearance of flumazenil increases by 50%, which is most likely due to increased hepatic blood flow due to food intake.
In hepatic failure, the half-life of the drug is lengthened and is 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severe liver impairment. The total clearance of flumazenil is reduced.
In elderly and senile patients, regardless of gender, degree of renal failure and hemodialysis, the pharmacokinetic parameters of Anexat do not significantly change.
In children aged 1 year and older, the half-life of flumazenil fluctuates more than in adults, and ranges from 20 to 75 minutes (40 minutes on average). The volume of distribution and clearance, taking into account body weight, are within the limits typical for adult patients.
Indications for use
Anexat is used to completely or partially eliminate the central sedative effects of benzodiazepine drugs.
In anesthesiology, flumazenil is indicated for use in the following cases:
- elimination of sedation caused by benzodiazepines in short-term therapeutic and diagnostic procedures in outpatients and inpatients;
- elimination of the sedative effect with preservation of consciousness caused by benzodiazepine drugs in children aged 1 year and older;
- removal of inpatients from general anesthesia, initiated and maintained with benzodiazepines.
Anexat is also used in intensive care and in the management of patients with loss of consciousness of unknown origin:
- intoxication with benzodiazepine drugs: in order to eliminate the central effects of benzodiazepines in case of poisoning with them (to restore consciousness and spontaneous breathing, which helps to avoid intubation or allows the patient to be extubated);
- statement or exclusion of the diagnosis of benzodiazepine overdose;
- differential diagnosis in patients with loss of consciousness of unknown origin.
Contraindications
- poisoning with mono-, di-, tri-, tetracyclic and atypical cyclic antidepressants;
- simultaneous therapy with benzodiazepines for conditions that potentially pose a threat to the patient's life (for example, to control intracranial pressure or status epilepticus);
- increased individual sensitivity to Anexat.
Anexat, instructions for use: method and dosage
Normal dosing regimen
Anexat solution in ampoules is intended only for intravenous administration (infusion or bolus) under the supervision of a qualified anesthesiologist or therapist. To prepare the infusion solution, you can use 0.9% sodium chloride solution or 5% dextrose solution. In order to maintain sterility, the drug should be taken from the ampoule immediately before administration. After dilution or a set of Anexat in a syringe, it must be used within 24 hours.
The dose of the drug should be titrated until the expected effect is obtained. Since the duration of action of individual benzodiazepines exceeds that of flumazenil, in some cases it may be necessary to re-administer Anexat (if sedation reappears after the achieved recovery of consciousness).
Anesthesiology
In anesthesiology, Anexat is used in an initial dose of 0.2 mg (it is administered intravenously for 15 seconds). If after 1 minute after the first administration of the drug the desired result is not achieved, then a second dose of 0.1 mg can be administered. If necessary, this procedure is repeated at intervals of 1 minute until a total dose of 1 mg is reached. On average, a single dose of flumazenil is 0.3-0.6 mg, but in practice it can vary greatly, depending on the dose of benzodiazepine taken or administered earlier, the duration of its action and the individual characteristics of the patient.
Intensive care and case management for unclear loss of consciousness
Intravenous administration of Anexat is recommended at an initial dose of 0.3 mg. In the absence of the desired recovery of consciousness, the drug is re-administered at intervals of 1 minute until the maximum total dose of 2 mg is reached. If the patient has a relapse of confusion, flumazenil is re-injected (as an infusion at a rate of 0.1–0.4 mg per hour or bolus). The infusion rate is selected individually.
If repeated administration of Anexat does not lead to sufficient restoration of respiratory function or consciousness, it can be assumed that the impairment of consciousness is of non-benzodiazepine origin.
Patients who have received high doses of benzodiazepines for a long time, as well as patients who are in intensive care units, should not experience withdrawal symptoms with an individual selection of the dose of Anexat and its slow intravenous administration. If undesirable signs of hyperstimulation appear, intravenous administration of midazolam or diazepam is recommended (it is necessary to carefully titrate their doses and take into account the patient's response).
Dosing regimen in special cases
For children over the age of 1 year, to eliminate the sedative effect while preserving consciousness, Anexat is recommended to be administered at an initial dose of 0.01 mg per kg of body weight (up to 0.2 mg) intravenously for 15 seconds. In the absence of the desired recovery of consciousness after 45 seconds, additional administration of flumazenil at a dose of 0.01 mg / kg (up to 0.2 mg) is possible. Then the procedure is repeated with an interval of 1 minute (but not more than 4 times) until the desired result or the maximum total dose of 0.05 mg / kg (not more than 1 mg) is achieved. To date, there are no data on the efficacy and safety of administering Anexat repeatedly (in the event of repeated sedation after recovery of consciousness).
In patients with hepatic impairment, the dose of flumazenil should be carefully selected.
Side effects
Patients of any age tolerate Anexat well. In adults, even at doses higher than recommended, the response to the drug is usually good.
During the post-registration use of flumazenil, hypersensitivity was sometimes observed up to anaphylaxis.
After the rapid administration of the drug, in rare cases, there were such undesirable phenomena as palpitations, anxiety and a feeling of fear, which did not require special therapy.
Isolated cases of seizures have been described, but mainly in patients with severe liver damage or epilepsy and after prolonged use of benzodiazepines or with a mixed drug overdose.
Persons with a history of panic disorder may develop a panic attack as a result of the administration of Anexat.
In 3-9% of cases, there are the following side effects associated with taking the drug: headache, dry mouth, dizziness, agitation, nervousness, insomnia, palpitations, sweating, anxiety, blurred vision, hyperventilation, tremor, shortness of breath, pain in the place injections, violation of the coordination of movements of various muscles (10%).
In 1–3% of cases, adverse reactions from the following systems and organs are possible:
- digestive system: vomiting, nausea;
- cardiovascular system: sensation of rushes of blood to the skin, expansion of skin vessels;
- central nervous system: unstable emotional state (euphoria, tearfulness, dysphoria, paranoia, depersonalization, depression), impaired sensitivity, decreased sensitivity to stimuli;
- sense organs: visual field defect, diplopia;
- general disorders: asthenia, skin rash, thrombophlebitis.
Adverse reactions that occur in less than 1% of cases and are apparently due to the intake of Anexat or the withdrawal of benzodiazepines:
- nervous system: drowsiness, delirium, impaired concentration, convulsions;
- sensory organs: tinnitus, perverse perception of sounds, transient hearing loss.
Overdose
There are insufficient data on acute drug overdose. There is no specific antidote. Treatment consists of general supportive measures, monitoring the patient's clinical status and monitoring vital signs.
Overdose symptoms of Anexat did not develop even in the case of intravenous administration of large doses of the drug, significantly exceeding the recommended ones.
special instructions
In the case of prescribing flumazenil in case of a mixed drug overdose, special care must be taken, since after the elimination of the effects of benzodiazepines, the toxic effect of other drugs that were taken in excessive doses may manifest itself (for example, the appearance of cardiac arrhythmias and seizures due to an overdose of cyclic antidepressants).
Anexat is not recommended for use in patients with epilepsy and long-term benzodiazepine therapy. Despite the fact that flumazenil has its own weak anticonvulsant effect, with a sharp elimination of benzodiazepine effects in patients with epilepsy, seizures may develop.
It is necessary to establish monitoring of patients who received flumazenil in order to eliminate the effects of benzodiazepine drugs. Respiratory function, re-occurrence of sedation and other residual effects of benzodiazepines should be monitored for a certain time (taking into account the doses and duration of action of previously administered benzodiazepines). Patients with impaired liver function may require longer monitoring.
Anexat should not be used until the neuromuscular blockade of conduction completely disappears and the effect of peripheral muscle relaxants ends.
The drug is prescribed with caution to patients with craniocerebral trauma, as it can alter cerebral blood flow and provoke seizures in persons receiving benzodiazepine drugs.
Flumazenil should be administered slowly to patients who have previously received benzodiazepines for a long time and finished taking them several weeks before the appointment of Anexat, since withdrawal symptoms (anxiety, emotional instability, psychomotor agitation, sensory disturbances and mild confusion) may appear.
It is not recommended to use the drug in patients with dependence on benzodiazepines, as well as for the relief of symptoms of benzodiazepine withdrawal.
Flumazenil is used with caution to eliminate sedative effects while maintaining consciousness in infants under 1 year of age, for the treatment of benzodiazepine overdose during resuscitation of newborns and in children of any age in order to eliminate sedation when using benzodiazepine anesthesia, since in these situations the experience of using Anexat is limited.
Influence on the ability to drive vehicles and complex mechanisms
On the first day after the administration of Anexat, one should refrain from any activities associated with increased concentration of attention, since it is possible to resume the sedative effect of previously administered or taken benzodiazepine drugs.
Application during pregnancy and lactation
In experiments conducted on animals, it was shown that flumazenil, even in large doses, does not have embryotoxicity, mutagenicity, teratogenicity and does not affect fertility. However, when prescribing Anexat to pregnant women, it is necessary to carefully assess the benefits of using the drug for the mother and the potential risk to the fetus.
In urgent situations, the administration of flumazenil to lactating women is not contraindicated.
Pediatric use
Anexat can be used at any age, but in some cases special care is required (when eliminating sedation with preservation of consciousness in infants up to 1 year old, during resuscitation of newborns, in order to treat an overdose of benzodiazepine drugs in children at any age, as well as to eliminate sedation, caused by benzodiazepine anesthesia).
Drug interactions
Anexat suppresses the central effects of benzodiazepine drugs by competitive inhibition of benzodiazepine receptors. In addition, it blocks the effect of non-benzodiazepine agonists on benzodiazepine receptors (for example, the effects of zopiclone and triazole pyridazines).
Pharmacokinetic interaction between Anexat and ethanol, as well as benzodiazepine receptor agonists, has not been identified.
Analogs
There is no information about analogues of Anexat.
Terms and conditions of storage
The drug belongs to the list B. Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
The shelf life is 5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Anexat
There are very few reviews of Anexat, since only specially trained anesthesiologists or therapists can use the drug. The tool is very powerful and effective and is often used in surgical departments. It is noted that Anexat can be administered exclusively under the supervision of a specialist, and after administration, the patient must be carefully monitored.
Price for Anexat in pharmacies
The approximate price for Anexat in ampoules (5 pieces per package) is from 5498 to 5700 rubles.
Anexat: prices in online pharmacies
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Drug name Price Pharmacy |
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Anexat 0.1 mg / ml solution for intravenous administration 5 ml 5 pcs. 7929 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
