Беротек® H

General characteristics. Structure:

Active ingredient: 100 mkg of Fenoterolum of hydrobromide in 1 inhalation dose.

Excipients: citric acid anhydrous, the water purified absolute ethanol. Propellant: 1,1,1,2 - тетрафторэтан (HFA 134a).

Pharmacological properties:

Pharmacodynamics. Fenoterolum hydrobromide - the selection stimulator of beta2-adrenoceptors. Activates adenylatecyclase through stimulyatorny Gs-protein with the subsequent increase in formation of tsAMF which in turn activates A. Poslednyaya's protein kinase 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 relaxes smooth muscles of bronchial tubes and vessels, and also prevents development of the bronchospasm caused by influence of 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.

Higher concentration of drug in a blood plasma reached after peroral or are more often, after intravenous administration, inhibit sokratitelny ability of a uterus. At reception of high doses of drug 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 of drug 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 r2-adrenoceptors of heart, and at administration of drug in the doses exceeding therapeutic, stimulation of r1-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 (an exercise stress, cold air, the early response to allergen influence).

The beginning of action after inhalation - in 5 min., action duration - 3-5 hour.

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 in a mouth. As a result a quantity of the inhalated Fenoterolum gets into digestive tract. After inhalation of one dose of drug of Berotek of N 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". Long (3-5 hour) the 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 intake about 60% of Fenoterolum of hydrobromide are soaked up. This part of active ingredient is exposed to biotransformation owing to "effect of primary passing" through a liver. As a result 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.

In not changed type of Fenoterolum hydrobromide can get through a placental barrier and 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 the patients with bronchial asthma and a chronic obstructive pulmonary disease answering steroids it is necessary to consider need of the accompanying antiinflammatory therapy.

Route of administration and doses:

Doses for adults and children are more senior than 6 years. Bad attack of bronchial asthma. In most cases for stopping of a bronchospasm one inhalation dose suffices; if within 5 min. simplification of breath did not come, it is possible to repeat inhalation. If the effect is absent after two inhalations, and additional inhalations are required, it is necessary to ask immediately for medical care in the nearest hospital.

Prevention of asthma of physical effort. 1-2 inhalation doses on one reception, to 8 inhalations a day.

The bronchial asthma and other states which are followed by reversible narrowing of respiratory tracts
1-2 inhalation doses on one reception if repeated inhalations, then no more than 8 inhalations a day are required.

Doses for children from 4 to 6 years the Bad attack of bronchial asthma 1 inhalation dose Berotek N.

Prevention of asthma of physical effort 1 inhalation dose on one reception.

The bronchial asthma and other states which are followed by reversible narrowing of respiratory tracts 1 inhalation dose Berotek in N to 4 times a day. Interval between inhalations not less 3rd hour. The maximum daily dose - 4 inhalations. No more than 2 inhalations on one reception since higher doses do not increase therapeutic effect, but can cause development of side effects.

The dosed aerosol is not convenient for use for children up to 4 years. Route of administration. For achievement of the maximum effect it is necessary to use correctly dosed aerosol. Before use of the dosed aerosol for the first time press a barrel bottom twice. Every time when using of the dosed aerosol it is necessary to follow the following rules:

1. To remove a protective cap.
2. To make a slow, full exhalation.
3. Holding a barrel densely to clasp with lips a mouthpiece. The barrel has to be directed by a bottom up.

Fig. 1
 
4. Making the deepest breath, to press at the same time quickly a barrel bottom before release of an inhalation dose. For several seconds to hold the breath, then to take out a mouthpiece from a mouth and to exhale slowly.
5. To put on a protective cap

If the aerosol barrel was not used more than three days, before use it is necessary to press a barrel bottom once.

The cylinder is counted on 200 inhalations. After that the cylinder should be replaced. In spite of the fact that in a cylinder there can be a drug quantity, amount of the medicinal substance which is released at inhalation can be reduced.

The cylinder is opaque therefore the amount of drug in a cylinder can be defined only in the next way: having removed a protective cap, the cylinder is immersed in the capacity filled with water. The amount of drug is defined depending on a cylinder position in water. (see fig. 2)

Fig. 2
The mouthpiece should be kept clean, in need of it it is possible to wash out in warm water. After use of soap or detergent, it is necessary to wash out carefully a mouthpiece clear water.

PREVENTION: the plastic mouthpiece is developed for a mouth especially for Berotek by N and serves for an exact drug dosing. The mouthpiece should not be used with other dosed aerosols. Also it is impossible to use Berotek N with any other adapters, except the mouthpiece delivered together with drug.

Contents of a cylinder are under pressure. The cylinder cannot be opened and subjected to heating above 50 °C.

Features of use:

At the first use of the dosed aerosol Berotek of N patients can note that the new aerosol has a bit different taste in comparison with the former aerosol containing freon. It is necessary to warn patients about it upon transition from one formula of drug to another. Patients need to know that both formulas of drug are completely interchanged, and change of taste does not exert impact on efficiency and safety of a new formula of an aerosol.

Other    sympathomimetic    bronchodilators    it is possible    to appoint along with Berotek N only under medical observation. Perhaps simultaneous use of Fenoterolum and anticholinergic bronchodilators.

In case of sudden development and bystry progressing of an asthma it is necessary to see a doctor immediately.

Prolonged use of drug:
- treatment on requirement (oriented to symptoms) is more preferable than regular use of drug;
- it is necessary to conduct regular examination of patients for the purpose of definition of need of additional or more intensive antiinflammatory treatment (for example, inhalations of corticosteroids).

Regular use of the increasing doses of the drugs containing beta2-adrenomimetik such as Berotek of N, for stopping of bronchial obstruction can cause uncontrollable deterioration in a course of a disease. In case of strengthening of bronchial obstruction simple increase in a dose of beta2-adrenomimetik, including Beroteka of N, is more recommended for a long time, not only is not justified, but also it is dangerous. For prevention of life-threatening deterioration in a course of a disease, it is necessary to consider a question of review of treatment planning of the patient and adequate antiinflammatory therapy by inhalation corticosteroids.

At purpose of beta2-adrenomimetik development of a serious hypopotassemia is possible. In this regard extra care is required at heavy asthma as in this case the hypopotassemia can result from co-administration of beta2-adrenomimetik, ksantinovy derivatives, glucocorticoids and diuretics. Besides, at a hypoxia strengthening of influence of a hypopotassemia on a cordial rhythm is possible. It is recommended to carry out monitoring of level of potassium in a blood plasma.

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

Influence on ability to drive the car and machine equipment is not installed.

Pregnancy and lactation. Negative influence of drug on the course of pregnancy was not revealed. Nevertheless, to pregnant women (especially in the I trimester) drug is appointed only when the expected advantage for mother exceeds any possible risk for a fruit. It is necessary to remember the oppressing action of Fenoterolum on a sokratitelny uterine activity. It is known that Fenoterolum gets into breast milk. Safety of use of drug in the period of a lactation is not established. Use of drug during feeding by a breast perhaps only in cases when the expected advantage for mother surpasses possible risk for the child.

Side effects:

The most frequent undesirable effects of Berotek of N are the small tremor of skeletal muscles, nervousness,   a headache,  dizziness, tachycardia and heartbeat. Development of a serious hypopotassemia is possible.

        Developing  of cough,   local irritation, seldom paradoxical bronkhospastichesky reactions is in certain cases observed. Berotek of N can make sick, vomiting, perspiration, weakness, muscular pains, spasms, a hyperglycemia.

In rare instances, usually when using high doses, stenocardia, decrease in diastolic pressure, increase in systolic pressure, arrhythmia are noted.

Seldom there are local inflammatory and allergic reactions, especially at patients with hypersensitivity.

It was in some cases reported about development of changes of mentality under the influence of inhalation therapy by beta-adrenergic agonists.

Interaction with other medicines:

Beta and adrenergic, anticholinergics, ksantinovy derivatives (for example, theophylline), kromoglitsiyevy acid, glucocorticosteroids can strengthen action of Fenoterolum. Co-administration with Beroteky N of other beta-adrenergic agonists, anticholinergics, ksantinovy derivatives (for example, theophylline), the glucocorticosteroids, diuretics getting to a system blood stream can strengthen side effects.

Perhaps considerable decrease in bronchodilatory action of Berotek of N at co-administration of beta adrenoblockers.

The hypopotassemia connected using beta-adrenergic agonists can be strengthened by co-administration of ksantinovy derivatives, steroids and diuretics.

It is necessary to appoint with care beta and adrenergic means to the patients receiving monoaminooxidase inhibitors, tricyclic antidepressants as these drugs are capable to strengthen action of Fenoterolum.

Inhalations of the halogenated hydrocarbon anesthetics, for example a halothane, Ftorotanum, trichloroethylene or an enfluran, sensibilize a myocardium to action of Fenoterolum that promotes development of arrhythmia.

Contraindications:

- Hypersensitivity to Fenoterolum to hydrobromide or any other component of drug;

- Hypertrophic subaortic stenosis;

- Tachyarrhythmias;

- Children's age up to 4 years.

With care. The Dekompensirovanny diabetes mellitus, recently postponed myocardial infarction, a serious illness of cardiovascular system, uncontrollable arterial hypertension, a hyperthyroidism, a pheochromocytoma.

Overdose:

Symptoms. Emergence of the symptoms connected with excess stimulation of beta adrenoceptors is possible. Development of tachycardia, heartbeat, a tremor, hypertensia, hypotension, increase in pulse pressure, stenocardia, arrhythmia, a hyperemia of the person is the most probable.

Treatment. Purpose of sedatives, tranquilizers, in hard cases intensive symptomatic care is shown.

As specific antidotes r-adrenoblockers, especially the beta1-selection are recommended (атенолол, etc.). However it is necessary to consider a possibility of strengthening of bronchial obstruction and to carefully select a dose of these drugs to the patients having bronchial asthma.

Storage conditions:

At a temperature not above 25 °C in the place, unavailable to children. Period of validity 3 years. Not to use drug after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 ml in a barrel from stainless steel with the dosing valve. Each barrel with the application instruction is placed in a pack from a cardboard.