Беротек®

General characteristics. Structure:

Active ingredient: 1 mg of Fenoterolum of hydrobromide in 1 ml of solution for inhalations (20 drops).

Excipients: a benzalkoniya chloride, dinatrium эдетат a dihydrate, sodium chloride, 1 N Acidum hydrochloricum, the distilled water.

Pharmacological properties:

Pharmacodynamics. Fenoterolum hydrobromide - the selection stimulator of beta2-adrenoceptors. Stimulation of beta1-adrenoceptors happens at use of drug in higher doses. Binding of beta2-adrenoceptors activates adenylatecyclase through stimulyatorny Gs-protein with the subsequent increase in formation of tsAMF which in turn activates a protein kinase And which then phosphorylates proteins target in cells of unstriated muscles. It in turn leads to phosphorylation of a kinase of a light chain of a myosin, inhibition of hydrolysis of phosphoinosine and opening of kaltsiyaktiviruyemy bystry potassium channels.

Thus, Fenoterolum causes a relaxation of smooth muscles of bronchial tubes and vessels, and also protects it from such bronkhokonstriktorny factors as a histamine, metasincaline, cold air and allergens (reaction of immediate type). After administration of drug release from mast cells of mediators of an inflammation is inhibited. Besides, after reception of Fenoterolum in high doses strengthening of mukotsiliarny transport is observed. Fenoterolum shows also properties of a stimulator of breath.

Higher concentration of drug in a blood plasma, a thicket reached after peroral and especially after intravenous administration, inhibit sokratitelny ability of a uterus. At reception of high doses of drug also effects at the level of a metabolism are observed: a lipolysis, a glycogenolysis, a hyperglycemia and a hypopotassemia (the last is caused by the increased absorption of K+ skeletal muscles).

Beta and adrenergic effects at the level of a cardiac muscle, such as increase in heart rate and strengthening of contractility of a myocardium, are explained by action of Fenoterolum on vessels, stimulation of beta2-adrenoceptors and (at administration of drug in doses over therapeutic range) stimulation of beta1-adrenoceptors. Often observed effect of agonists of r-adrenoceptors is the tremor. Unlike action on smooth muscles of bronchial tubes system effects of agonists of r-adrenoceptors are associated with tolerance development.

Fenoterolum warns and quickly stops a bronchospasm of various genesis. The beginning of action after inhalation - in 5 min., at most - 30k90 min., duration - 3-6 hour.

There are no sufficient data about influence of Fenoterolum of hydrobromide on a metabolism at a diabetes mellitus.

Pharmacokinetics. Depending on a method of inhalation and the used inhalation system about 10-30% of the active agent released from aerosol drug after inhalation reach the lower respiratory tracts, and other part is deposited in upper respiratory tracts and swallowed. As a result a quantity of the inhalated Fenoterolum gets into digestive tract. After inhalation of one dose of drug Berotek extent of absorption makes 17% of the entered dose. Absorption has two-phase character - 30% of Fenoterolum of hydrobromide are quickly soaked up with an elimination half-life of 11 min., and 70% are soaked up slowly with an elimination half-life of 120 min.

There is no correlation between the concentration of Fenoterolum in a blood plasma reached after inhalation and a pharmakodinamichesky curve "time - effect". The long-term bronchodilatory effect of drug after inhalation, comparable with the corresponding effect reached after intravenous administration is not supported by high concentration of active agent in a system blood-groove. After introduction about 60% of Fenoterolum of hydrobromide are inside soaked up. Time of achievement of the maximum concentration in a blood plasma of the CU of max - the 2nd hour. Communication with proteins of plasma of 40-55%.

It is metabolized in a liver. It is removed by kidneys and with bile in the form of inactive sulphatic conjugates. In 24 h 60% from entered into doses and 35% of peroral it is excreted with urine. This share of active agent is exposed to biotransformation owing to "effect of primary passing" through a liver therefore bioavailability of drug after introduction inside falls approximately to 1,5%. The fact that the swallowed amount of drug practically does not affect the level of active agent in a blood plasma reached after inhalation in any way is explained by it.

At parenteral administration of Fenoterolum hydrobromide is removed according to three-phase model with elimination half-lives - 0,42 min., 14,3 min. and 3,2 h. Hydrobromide Fenoterolum biotransformation at the person proceeds only by conjugation with sulfates preferential in an intestines wall.

Fenoterolum hydrobromide can get in not changed look through a placental barrier and to get to breast milk.

Indications to use:

- Stopping of attacks of suffocation of bronchial asthma.
- Prevention of attacks of bronchial asthma owing to physical tension.
- A symptomatic treatment of bronchial asthma or other states with reversible narrowing of pneumatic ways (for example, chronic obstructive bronchitis). At patients with the bronchial asthma and a chronic obstructive pulmonary disease answering steroids it is necessary to consider need of antiinflammatory treatment.
- As bronchodilatory means before inhalation of other medicines (antibiotics, mucolytic means, glucocorticosteroids)
- Carrying out bronkhodilyatatsionny tests at a research of function of external respiration.

Route of administration and doses:

It is inhalation. (20 drops = 1 ml, 1 drop = 50 mkg of Fenoterolum of hydrobromide)
Doses should be selected according to individual needs of the patient; besides, during treatment of the patient has to be under observation of the doctor. In the absence of other instructions the following mode of dosing is recommended.

Adults (including patients of senile age) and teenagers are more senior than 12 years. Attacks of bronchial asthma: 0,5 ml (10 drops = 0,5 mg of Fenoterolum of hydrobromide) happen in many cases enough for immediate stopping of a symptom; in hard cases when most of patients needs the emergency medical care, higher doses from 1 to 1,25 ml can be required (20-25 drops = 1-1,25 mg of Fenoterolum of hydrobromide); in exclusively hard cases it is possible to enter under observation of the doctor to 2 ml (40 drops = 2 mg of Fenoterolum of hydrobromide);

Prevention of attacks of bronchial asthma owing to physical tension: 0,5 ml (10 drops = 0,5 mg of Fenoterolum of hydrobromide) on reception to 4 times a day;

Bronchial asthma and other states with reversible narrowing of pneumatic ways: in need of repeated administration of drug accept on 0,5 ml (10 drops = 0,5 mg of Fenoterolum of hydrobromide) to 4 times a day;

Children from 6 to 12 years (with body weight about 22-36 kg). Attacks of bronchial asthma: 0,25-0,5 ml (5-10 drops = 0,25-0,5 mg of Fenoterolum of hydrobromide) happen in many cases enough for immediate stopping of a symptom; in hard cases higher doses to 1 ml can be required (20 drops = 1 mg of Fenoterolum of hydrobromide); in exclusively hard cases it is possible to enter under observation of the doctor to 1,5 ml (30 drops = 1,5 mg of Fenoterolum of hydrobromide);

Prevention of attacks of bronchial asthma owing to physical tension: 0,5 ml (10 drops = 0,5 mg of Fenoterolum of hydrobromide) on reception to 4 times a day;

Bronchial asthma and other states with reversible narrowing of pneumatic ways: in need of repeated administration of drug accept on 0,5 ml (10 drops = 0,5 mg of Fenoterolum of hydrobromide) to 4 times a day;

Children up to 6 years (with body weight less than 22 kg): because of limitation of information on this age group treatment is carried out only under observation of the doctor, appointing drug in the following dose: about 50 mkg/kg on reception (5-20 drops = 0,25-1 mg) to 3 times a day.

Treatment is begun, as a rule, with the smallest recommended dose. The recommended dose is parted with normal hydrochloric saline solution up to the final volume of 3-4 ml, sprayed and inhalated before full consumption of the received cultivation. Berotek 0,1% solution cannot be parted with the distilled water.
Solution part every time again before use; the remains of divorced solution are thrown out.
The mode of dosing can depend on a way of inhalation and characteristics of an inhaler. Duration of inhalation can be controlled cultivation volume. Berotek 0,1% solution can be applied with use of the inhalation devices which are available on sale. In the presence of the oxygen and respiratory equipment solution is the best of all to inhalate 6-8 l/min at a flow rate.

Berotek 0,1% solution can be inhalated along with well-cared and mucolytic means, compatible to it. It concerns first of all the drugs Atrovent®, Мукозолван® and Бизолвон® in the form of solutions for inhalation and/or in aerosol cans with the dosing valve.
If necessary the subsequent inhalations carry out not less than 4 p with intervals.

Features of use:

At patients with a diabetes mellitus during treatment it is necessary to carry out regular control of the content of glucose in plasma.

Other sympathomimetic bronchodilators can be applied together with drug Berotek of 0,1% solution only under observation of the doctor.

At acute, quickly amplifying диспноэ (the complicated breath) it is necessary to consult immediately with the doctor.

Prolonged use:
• treatment on requirement (oriented to a symptom) can be more preferable than regular use of drug;
• patients have to be inspected regarding performing additional or more intensive antiinflammatory treatment (for example, inhalations of corticosteroids) for the purpose of control of an inflammation of pneumatic ways and the prevention of long exacerbations of bronchial asthma.

In case of strengthening of obstruction of bronchial tubes it is considered unacceptable and there can be even risky a simple increase in reception of agonists of the beta2-adrenoceptors which are contained in such drugs as Berotek of 0,1% solution over the recommended doses and the recommended use duration. Reception in high doses of agonists of the beta2-adrenoceptors which are contained in such drugs as Berotek of 0,1% solution for the purpose of control of symptoms of bronchial obstruction, can cause uncontrollable deterioration in a course of a disease. In such situation it is necessary to reconsider treatment planning and, especially, adequacy of antiinflammatory therapy.

At treatment by agonists of beta2-adrenoceptors development of the expressed hypopotassemia is possible. Extra care should be shown at heavy bronchial asthma as this effect can be strengthened by the accompanying use of derivatives of xanthine, glucocorticosteroids and diuretics. Besides, at a hypoxia strengthening of influence of a hypopotassemia on a cordial rhythm is possible. In such situations regular control of level of potassium in blood serum is recommended.

Pregnancy and period of a lactation. Results of preclinical trials in combination with the available experience of a clinical use of drug demonstrate that it does not cause any undesirable phenomena during pregnancy. Nevertheless, it is necessary to show usual care concerning use of medicines during pregnancy (especially in its first third). It is worth to remember that Fenoterolum inhibits sokratitelny function of a uterus. Preclinical trials showed that Fenoterolum gets into breast milk. Safety of drug in the lactation period is still not established.

Side effects:

The melkorazmashisty tremor of skeletal muscles and nervousness, headache, dizziness, tachycardia and the strengthened heartbeat belong to frequent undesirable effects of drug Berotek of 0,1% solution. In rare instances stenokardichesky pains, decrease in diastolic pressure, increase in systolic pressure, heart arrhythmia, especially after introduction of high doses of drug can be observed.

Treatment by means of agonists of r-adrenoceptors can lead to a serious hypopotassemia. As well as at inhalation of other medicines, cough, local irritation and smaller, than usually, probability of development of a paradoxical bronchospasm can be noted.

As well as at use of others beta адреномиметических means, nausea, vomiting, perspiration, weakness, and also a mialgiya and muscular spasms, a hyperglycemia, easing of motility of upper parts of urinary tract, a tolerantost can take place.

There are rare messages on skin or allergic reactions, especially for patients with hypersensitivity.

Interaction with other medicines:

Beta and adrenergic drugs, anticholinergics, xanthine derivatives (such as theophylline), sodium кромогликат, glucocorticosteroids and diuretics can strengthen action and side effects of Fenoterolum.

Considerable decrease in a bronkhodilatation can be observed during simultaneous use of Fenoterolum and blockers of r-adrenoceptors.

It is necessary to appoint agonists of beta adrenoceptors with care the patient receiving MAO inhibitors or tricyclic antidepressants which are capable to strengthen action of agonists of beta adrenoceptors.

Inhalation of such fluorinated hydrocarbon anesthetics as halothane, Ftorotanum, trichloroethylene and энфлуран, can increase probability of action of agonists of r-adrenoceptors at the level of cardiovascular system. Ftorotanum sensibilizes a myocardium to action of Fenoterolum, promotes development of arrhythmia. Co-administration of bronchial spasmolytics with the similar mechanism of action results in the additive effect and the phenomena of overdose.

Contraindications:

- Hypersensitivity to Fenoterolum to hydrobromide or to other ingredients of drug.
- Hypertrophic subaortic stenosis, tachyarrhythmia.

With care: a hyperthyroidism, arterial hypotension, arterial hypertension, an intestines atony, a hypopotassemia, a diabetes mellitus, recently postponed myocardial infarction, a serious illness of cardiovascular system, a pheochromocytoma.

Overdose:

Symptoms. The same overdoses expected symptoms, as at excessive stimulation of adrenergic r-receptors, including the known, but excessively strengthened pharmacological effects (for example, some symptoms given in the section "Side effects"); the most noticeable of them are tachycardia, the strengthened heartbeat, a tremor, arterial hypertension, arterial hypotension, increase in pulse arterial pressure, anginal pain, arrhythmias of heart and a hyperemia of the person.

Treatment. Usually appoint sedative drugs, tranquilizers, in hard cases carry out intensive sympathomimetic care. As specific antidotes it is possible to appoint blockers of adrenergic beta receptors (preferably the selection blockers of beta1-adrenoceptors); at the same time it is necessary to consider a possibility of strengthening of obstruction of bronchial tubes and to carefully select doses of these drugs at the patients having bronchial asthma.

Storage conditions:

To store at a temperature not above 30 °C. Not to subject to freezing. To store in the place, unavailable to children. Period of validity of 5 years. Not to use drug on the termination of the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 20 ml, 40 ml or 100 ml in glass bottles from amber glass with a polyethylene dropper and the screwing-up polypropylene cover. The bottle together with the instruction is placed in a cardboard pack.