Беродуал® H

General characteristics. Structure:

Active ingredients: 0,021 mg (21 mkg) a monohydrate bromide ipratropiya (that there corresponds the ipratropiya of bromide of 0,020 mg (20 mkg)), 0,05 mg (50 mkg) of Fenoterolum hydrobromide of 0,050 mg (50 mkg) in 1 inhalation dose.

Excipients: absolute ethanol; the water purified; citric acid, тетрафторэтан (HFA 134a, propellant).

The combined drug containing two components having broncholitic activity.

Pharmacological properties:

Pharmacodynamics. Berodual - the combined drug, contains two components having broncholitic activity: an ipratropiya bromide - m-holinoblokator, and Fenoterolum hydrobromide - beta2-adrenomimetik.

Bronchodilatation at inhalation introduction an ipratropiya of bromide is caused, mainly, by local, but not systemic anticholinergic action.

Ipratropiya bromide is to quarternary derivatives of ammonium, it has anticholinergic (parasympatolytic) properties. Ipratropy brakes the reflexes mediated by a vagus nerve, counteracting effect of acetylcholine - the neurotransmitter which is released from this nerve. Anticholinergics prevent increase in intracellular concentration cyclic гуанезин monophosphate (cyclic GMF) in unstriated muscles of bronchial tubes, arising at interaction of acetylcholine with muskarinovy receptors.

Considerable improvement of function of lungs (increase in volume of the forced exhalation for 1 sec. (OFV1) and the average volume speed of the forced exhalation for 15% and more) at patients with a chronic obstructive pulmonary disease with attacks of a bronchospasm occurs within 15 minutes, the maximum effect is reached in 1-2 hours and proceeds at most of patients till 6 o'clock after introduction.

At 40% of patients with the bronchospasm connected with bronchial asthma considerable improvement of function of lungs is noted (increase in OFV1 by 15% and more).

Ipratropiya bromide does not exert negative impact on secretion of slime in respiratory tracts, mukotsiliarny clearance and gas exchange.

Fenoterolum hydrobromide has direct sympathomimetic effect. It selectively stimulates beta2-adrenoceptors of bronchial tubes in therapeutic doses. In higher doses it has ability to stimulate beta1-adrenoceptors. Linkng with beta2-adrenoceptors activates adenylatecyclase with the participation of the stimulating Gs-protein. The increased level of cyclic AMF activates a protein kinase And which then phosphorylates proteins target in smooth muscle cells. It, in turn, leads to phosphorylation of a light chain of a miozinkinaza, inhibition of hydrolysis of a fosfoinozitid and opening of the potassium channels activated by calcium.

Fenoterolum relaxes smooth muscles of bronchial tubes and vessels and counteracts development of the bronkhospastichesky reactions caused by influence of a histamine, metasincaline, cold air and allergens (reaction of immediate hypersensitivity). Right after appointment Fenoterolum blocks release of bronkhokonstriktorny mediators of an inflammation from mast cells. Use of higher doses of Fenoterolum increases mukotsiliarny clearance.

At higher concentration of Fenoterolum in plasma, contractility of a uterus is inhibited. Also when using higher doses metabolic effects are observed: lipolysis, glycogenolysis, hyperglycemia and hypopotassemia. The hypopotassemia is caused, mainly, by the increased inclusion of potassium ions in skeletal muscles. Beta and adrenergic impacts on heart, such as increase in frequency and force of cordial reductions are a consequence of influence of Fenoterolum on vessels, stimulations of beta2-adrenoceptors of a myocardium and, when using the doses exceeding therapeutic, beta1-adrenoceptors.

As well as when using other beta and adrenergic drugs lengthening of an interval of OTS when using high doses was noted. The most often observed effect of beta2-agonists is the tremor. Unlike impact on unstriated muscles of bronchial tubes to system influences of beta2-agonists   tolerance can develop.

Fenoterolum prevents development of the bronkhokonstriktion caused by various incentives, such as an exercise stress, cold air and allergens (reaction of immediate hypersensitivity).

At combined use an ipratropiya of bromide and Fenoterolum the bronchodilatory effect is reached by impact on various pharmacological targets. The specified substances supplement each other, the broncholitic effect as a result amplifies and the big width of therapeutic action at the bronchopulmonary diseases which are followed by a konstriktion of respiratory tracts is provided. Complementary action such is that for achievement of desirable effect is required lower dose of a beta and adrenergic component that facilitates an individual drug dosing and promotes minimization of undesirable reactions.

Indications to use:

Prevention and symptomatic treatment of obstructive respiratory diseases with a reversible bronchospasm: a chronic obstructive pulmonary disease, bronchial asthma, the chronic bronchitis complicated or uncomplicated emphysema.

Route of administration and doses:

The dose should be selected individually. In the absence of other recommendations of the doctor use of the following doses is recommended:

Adults and children are more senior than 6 years. Treatment of attacks. In most cases for stopping of symptoms there are enough two inhalation doses of an aerosol. If within 5 minutes of simplification of breath did not come, it is possible to use in addition 2 inhalation doses. If the effect is absent after four inhalation doses, and additional inhalations are required, it is necessary to ask for medical care immediately.

Discontinuous and long therapy. On 1-2 inhalations on one reception, to 8 inhalations a day (on average on 1-2 inhalations 3 times a day).

The dosed aerosol Berodual the N at children should be applied only on doctor's orders and under control of adults.

Route of administration. Patients have to be instructed about the correct use of the dosed aerosol. Before use of the dosed aerosol for the first time stir up a cylinder and press the aerosol valve 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 cylinder densely to clasp with lips a mouthpiece. The cylinder has to be directed by a bottom up.

Fig. 1
 
4. Making the deepest breath, to press at the same time quickly a cylinder bottom before release of one inhalation dose. On несколькосекунд to hold the breath, then to take out a mouthpiece from a mouth and to exhale slowly. To repeat actions for receiving the second inhalation dose.
5. To put on a protective cap.
6. If the aerosol barrel was not used more than three days, before use it is necessary to press once a barrel bottom before emergence of a cloud of an aerosol.

Since a container opaque, it is impossible to define, whether an empty cylinder. The cylinder is counted on 200 inhalations. After use of this quantity of doses in a container there can be a small amount of solution. Nevertheless, it is necessary to replace a container as differently it is possible not to receive a necessary medical dose.

The amount of the drug which remained in a container can be checked as follows. Remove a plastic mouthpiece from a container and place a container in a vessel with water. Contents of a container can be determined by its situation 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, carefully to wash out a tip clear water.

PREVENTION: the plastic mouthpiece is developed especially for the dosed aerosol Berodual 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 an aerosol Berodual of N with any other adapters, except the mouthpiece delivered together with a cylinder.

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

Features of use:

In case of sudden emergence and bystry progressing of an asthma (the complicated breath) it is necessary to see a doctor immediately.

Prolonged use:
• at the patients having bronchial asthma or easy and medium-weight forms of a chronic obstructive pulmonary disease the symptomatic treatment can be more preferable than regular use.
• at patients with bronchial asthma or steroido-dependent forms of the chronic obstructive pulmonary disease (COPD) it is necessary to remember need of carrying out or strengthening of antiinflammatory therapy for control of inflammatory process of respiratory tracts and the course of a disease.

Regular use of the increasing doses of the drugs containing beta2-agonists such as Berodual 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-agonists, including Beroduala 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 glucocorticosteroids.

It is necessary to appoint other sympathomimetic bronchodilators along with Berodualy N only under medical observation.

Patients should be instructed in detail concerning rules of use of the dosed aerosol inhaler Berodual of N! Eye pain, indistinct sight, feeling of emergence of an aura or color spots before eyes in combination with reddening of an eye in the form of a conjunctival or corneal injection can be signs of a bad attack of closed-angle glaucoma. At emergence of the listed symptoms in any combination it is necessary to begin treatment with the eye drops causing narrowing of a pupil and to ask immediately for specialized medical care.

At the patients having a mucoviscidosis in the anamnesis disturbances of motility of digestive tract are possible.

Expediency of the accompanying antiinflammatory therapy has to be considered at the patients with the chronic obstructive pulmonary disease (COPD) answering glucocorticosteroids and bronchial asthma.

Pregnancy and lactation. The existing clinical experience showed that Fenoterolum and an ipratropiya bromide have no negative effect on pregnancy. Nevertheless, when using these drugs during pregnancy usual precautionary measures, especially in the first trimester have to be observed. It is necessary to take the inhibiting Berodual's influence on contractility of a uterus into account. Fenoterolum hydrobromide can get into breast milk. In the relation an ipratropiya such data are not obtained. Essential influence an ipratropiya on the baby, especially in case of use of drug in the form of an aerosol, is improbable. Nevertheless, considering ability of many medicines to get into breast milk, at Berodual's appointment the women nursing should be careful.

Side effects:

The most frequent undesirable effects of Berodual of N is the small tremor of skeletal muscles, nervousness and dryness in a mouth; less often the headache, dizziness, tachycardia and heartbeat, especially occur at patients with the burdening factors.

At purpose of beta2-agonists development of the expressed hypopotassemia is possible.

As well as at other inhalation therapy, developing of cough, local irritation (pharyngitis), seldom bronkhospastichesky reactions was in certain cases observed.

As well as other beta2-adrenomimetik, Berodual of N can make sick, vomiting, perspiration, weakness, muscular pains and spasms. In rare instances, usually when using high doses, decrease in diastolic pressure, increase in systolic pressure, arrhythmia, fibrillation and supraventricular tachycardia was noted.

It is in some cases reported about development of changes of mentality under the influence of inhalation therapy of a beta2-adrenomimetikama.

Disturbances of accommodation of eyes, disturbances of motility of digestive tract (vomiting, a lock, a diarrhea) and an ischuria meet seldom and have reversible character.

There are messages on undesirable effects from eyes, such as a mydriasis, increase in intraocular pressure, closed-angle glaucoma, pain in an eyeglobe.

Skin reactions and allergic reactions such as rash, Quincke's disease (a paraglossa, lips and a face), a small tortoiseshell, a bronchospasm, a laryngospasm, hypostasis of a stomatopharynx and an acute anaphylaxis are in rare instances possible.

Interaction with other medicines:

Beta and adrenergic and anticholinergics, ksantinovy derivatives (for example, theophylline) can strengthen bronchodilatory action of Berodual N. Co-administration of other beta-adrenergic agonists getting to a system blood stream of anticholinergics or ksantinovy derivatives (for example, theophylline) can lead to strengthening of side effects.

Perhaps considerable weakening of bronchodilatory action of Berodual of N at co-administration of beta adrenoblockers.

The hypopotassemia connected using beta-adrenergic agonists can be strengthened by co-administration of ksantinovy derivatives, glucocorticosteroids and diuretics. It should pay special attention at treatment of patients with severe forms of obstructive respiratory diseases.

The hypopotassemia can lead to increase in risk of developing of arrhythmias at the patients receiving digoxin. Besides, the hypoxia can strengthen a negative impact of a hypopotassemia on a cordial rhythm. In similar cases it is recommended to carry out monitoring of potassium concentration in blood serum.

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

Inhalations of the halogenated hydrocarbon anesthetics, for example a halothane, trichloroethylene or an enfluran, can strengthen adverse influence of beta and adrenergic funds for cardiovascular system.

Contraindications:

Hypertrophic subaortic stenosis, tachyarrhythmia; hypersensitivity to Fenoterolum to hydrobromide, atropinopodobny substances or any other components of drug, the first trimester of pregnancy, children's age up to 6 years.

With care: closed-angle glaucoma, coronary insufficiency, arterial hypertension, insufficiently controlled diabetes mellitus, recently postponed myocardial infarction, heavy organic heart diseases and vessels, a hyperthyroidism, a pheochromocytoma, a prostatauxe, obstruction of a neck of a bladder, a mucoviscidosis, children's age.

Overdose:

Symptoms. Symptoms of overdose are usually connected preferential with action of Fenoterolum. Emergence of the symptoms connected with excess stimulation of beta adrenoceptors is possible. Emergence of tachycardia, serdtsebiyeniye, a tremor, arterial hypertension or arterial hypotension, increase in pulse pressure, anginal pains, arrhythmias and inflows is the most probable.

Overdose symptoms a bromide ipratropiya (such as dryness in a mouth, disturbance of accommodation of eyes), considering the big width of therapeutic effect of drug and a local route of administration, usually malovyrazhena also have passing character.

Treatment. Sedative drugs, tranquilizers, in hard cases - an intensive care are shown. As a specific antidote use of beta adrenoblockers, preferably the beta1-selection adrenoblockers is possible.

However it is necessary to remember possible strengthening of bronchial obstruction under the influence of beta adrenoblockers and to carefully select a dose for the patients having bronchial asthma or a chronic obstructive pulmonary disease in connection with danger of a heavy bronchospasm which can lead to death.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place unavailable to children. Period of validity 3 years. Not to use drug after expiry date.

Issue conditions:

According to the recipe

Packaging:

Aerosol for inhalations dosed 20 mkg + 50mkg/dose - 200 doses On 10 ml in a metal barrel with the dosing valve and a mouthpiece with a protective cover. The barrel with the application instruction is placed in a cardboard pack.