Berodual, inhalation solution 0.1%, 20ml

Composition

>1 ml of the solution for inhalation contains: Active ingredient: 261 mcg of ipratropium bromide monohydrate, based on anhydrous ipratropium bromide (250 mcg) and 500 mcg of fenoterol hydrobromide. auxiliary substances: benzalkonium chloride, disodium edetate dihydrate, sodium chloride, hydrochloric acid 1 N, purified water.

Pharmacological action

Combined bronchodilator drug. It contains two components with bronchodilatory activity: ipratropium bromide-m-holinoblokator and fenoterol hydrobromide-beta 2-adrenomimetic.

Bronchodilation during inhaled use of ipratropium bromide is mainly due to local, rather than systemic, anticholinergic effects.

Ipratropium bromide is a quaternary ammonium derivative with anticholinergic (parasympatholytic) properties. The drug inhibits reflexes caused by the vagus nerve, counteracting the effects of acetylcholine-a mediator released from the endings of the vagus nerve. Anticholinergic agents prevent an increase in the intracellular concentration of calcium, which occurs due to the interaction of acetylcholine with the muscarinic receptor located on the smooth muscles of the bronchi. Calcium release is mediated by a system of secondary mediators, including ITP (inositol triphosphate) and DAG (diacylglycerol).

In patients with COPD-related bronchospasm (chronic bronchitis and emphysema), a significant improvement in lung function (increased forced expiratory volume in 1 second (FEV 1) and peak expiratory velocity by 15% or more) was observed within 15 minutes, the maximum effect was achieved in 1-2 hours and lasted in most patients up to 6 hours after use.

Ipratropium bromide does not adversely affect mucus secretion in the respiratory tract, mucociliary clearance and gas exchange.

Fenoterol hydrobromide selectively stimulates beta-2-adrenergic receptors at a therapeutic dose. Stimulation of β1-adrenergic receptors occurs when using high doses (for example, when prescribed for tocolytic action).

Fenoterol relaxes the smooth muscles of the bronchi and blood vessels and counteracts the development of bronchospastic reactions caused by the influence of histamine, methacholine, cold air and allergens (immediate hypersensitivity reactions). Immediately after use, fenoterol blocks the release of inflammatory mediators and bronchial obstruction from mast cells. In addition, when using fenoterol at a dose of 600 mcg, an increase in mucociliary clearance was noted.

The beta-adrenergic effect of the drug on cardiac activity, such as an increase in heart rate and heart rate, is due to the vascular effect of fenoterol, stimulation of beta-2-adrenergic receptors of the heart, and when used in doses exceeding therapeutic ones, stimulation of beta-1-adrenergic receptors.

As with other beta-adrenergic drugs, prolongation of the QT interval was observed when using high doses. When using fenoterol with metered-dose aerosol inhalers (DAI), this effect was not constant and was noted in the case of using doses that exceeded the recommended ones. However, after using fenoterol with nebulizers (a solution for inhalation in vials with a standard dose), the systemic effect may be higher than when using the drug with DAI in the recommended doses. The clinical significance of these observations has not been established.

The most commonly observed effect of beta-adrenergic agonists is tremor. In contrast to the effects on the smooth muscles of the bronchi, tolerance can develop to the systemic effects of beta-adrenergic agonists. The clinical significance of this manifestation has not been clarified.

When combined with ipratropium bromide and fenoterol, the bronchodilator effect is achieved by acting on various pharmacological targets. These substances complement each other, as a result, the antispasmodic effect on the bronchial muscles increases and a greater breadth of therapeutic action is provided for bronchopulmonary diseases accompanied by airway constriction.

The complementary effect is such that to achieve the desired effect, a lower dose of the beta-adrenergic component is required, which allows you to individually select the effective dose with the practical absence of side effects.

Indications

Prevention and symptomatic treatment of chronic obstructive airway diseases with reversible bronchospasm, such as bronchial asthma and, especially, chronic obstructive pulmonary disease (chronic obstructive bronchitis and emphysema).

Contraindications

Hypertrophic obstructive cardiomyopathy, tachyarrhythmia, I and III trimesters of pregnancy. Hypersensitivity to fenoterol or atropine-like drugs or other components of this drug.

With caution: angle-closure glaucoma, arterial hypertension, diabetes mellitus, recent myocardial infarction (within the last 3 months), heart and vascular diseases such as chronic heart failure, coronary heart disease, heart disease, aortic stenosis, severe lesions of the cerebral and peripheral arteries.

Hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, cystic fibrosis, second trimester of pregnancy, breastfeeding.

Side effects

Many of these undesirable effects may be due to the anticholinergic and beta-adrenergic properties of Berodual. As with any inhalation therapy, the use of Berodual may cause local irritation. Adverse reactions of the drug were determined based on data obtained in clinical studies and during pharmacological supervision of the use of the drug after its registration.

The most common side effects reported in clinical trials were cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, increased systolic blood pressure, and nervousness.

Immune system disorders: anaphylactic reaction, hypersensitivity.

From the side of metabolism: hypokalemia.

From the nervous system and psyche: nervousness, agitation, mental disorders, headache, tremor, dizziness.

From the side of the visual organ: glaucoma, increased intraocular pressure, accommodation disorders, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, the appearance of a halo around objects.

From the cardiovascular system: tachycardia, palpitation, arrhythmias, atrial fibrillation, supraventricular tachycardia, myocardial ischemia, increased systolic blood pressure, increased diastolic blood pressure.

Respiratory system disorders: cough, pharyngitis, dysphonia, bronchospasm, pharyngeal irritation, pharyngeal edema, laryngospasm, paradoxical bronchospasm, dry throat.

From the digestive system: vomiting, nausea, dry mouth, stomatitis, glossitis, gastrointestinal motility disorders, diarrhea, constipation, oral edema.

Skin and subcutaneous tissue disorders: urticaria, pruritus, angioedema, hyperhidrosis.

Musculoskeletal disorders: muscle weakness, muscle spasms, myalgia.

Urinary system disorders: urinary retention.

Interaction

of Beta-adrenomimetics and anticholinergics, xanthine derivatives (including theophylline) may enhance the bronchodilating effect of Berodual.

Concomitant use of other beta-adrenomimetics, systemic anticholinergic agents, xanthine derivatives (for example, theophylline) may increase side effects. It is possible to significantly weaken the bronchodilator effect of Berodual with the simultaneous use of beta-blockers.

Hypokalemia associated with the use of beta-adrenomimetics may be increased by concomitant use of xanthine derivatives, corticosteroids, and diuretics. This fact should be given special attention in the treatment of patients with severe obstructive airway diseases.

Hypokalemia may lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia can increase the negative effect of hypokalemia on the heart rate. In such cases, it is recommended to monitor the level of potassium in the blood serum.

Caution should be exercised when prescribing beta-adrenergic agents to patients treated with MAO inhibitors and tricyclic antidepressants, as these drugs may enhance the effect of beta-adrenergic agents.

The use of inhaled halogenated anesthetics, such as halothane, trichloroethylene, or enflurane, may increase the effect of beta-adrenergic agents on the cardiovascular system.

The combined use of Berodual with cromoglycic acid and / or corticosteroids increases the effectiveness of therapy.

How to take it, course of use and dosage

The dose should be selected individually. During therapy, medical supervision is required (treatment should usually begin with the lowest recommended dose).

The following doses are recommended:

In adults (including the elderly) and adolescents over 12 years of age with acute attacks of bronchial asthma, the drug is prescribed in a dose 1 ml (20 drops). This dose is usually sufficient for rapid relief of mild to moderate bronchospasm attacks. In severe cases, for example, in patients in intensive care units, if the drug is ineffective in the doses indicated above, it may be necessary to use it in higher doses – up to 2.5 ml (50 drops). The maximum dose can reach 4.0 ml (80 drops). The maximum daily dose is 8 ml.

In the case of moderate bronchospasm or as an adjunct to lung ventilation, a dose with a lower level of 0.5 ml (10 drops) is recommended.

In children aged 6-12 years with acute attacks of bronchial asthma for rapid relief of symptoms, it is recommended to prescribe the drug in a dose of 0.5-1 ml (10-20 drops); in severe cases – up to 2 ml (40 drops); in particularly severe cases, the drug can be used (subject to medical supervision) in a maximum dose of 3 ml (60 drops). The maximum daily dose is 4 ml.

In cases of moderate bronchospasm or as an adjunct to lung ventilation, the recommended dose is 0.5 ml (10 drops).

In children under 6 years of age (body weight less than 22 kg) due to the fact that information on the use of the drug in this age group is limited, the following dose is recommended (only under medical supervision): 25 mcg of ipratropium bromide and 50 mcg of fenoterol hydrobromide = 0.1 ml (2 drops) per kg of body weight (per dose), but not more than 0.5 ml (10 drops) (per dose). The maximum daily dose is 1.5 ml.

Rules for using the drug

The solution for inhalation should only be used for inhalation (with a suitable nebulizer) and should not be administered orally.

Treatment should usually start with the lowest recommended dose.

The recommended dose should be diluted with saline solution to a final volume of 3-4 ml, and applied (completely) using a nebulizer. The solution for inhalation should not be diluted with distilled water.

Dilution of the solution should be carried out each time before use; the remains of the diluted solution should be destroyed.

The diluted solution should be used immediately after cooking.

The duration of inhalation can be controlled by the consumption of the diluted volume.

The solution for inhalation can be used using various commercial models of nebulizers. The dose reaching the lungs and the systemic dose depend on the type of nebulizer used and may be higher than the corresponding doses when using the metered-dose aerosol of Berodual HFA and CFC (which depends on the type of inhaler). In cases where wall-mounted oxygen is available, the solution is best applied at a flow rate of 6-8 l/min.

Follow the instructions for use, maintenance, and cleaning of the nebulizer.

Overdose

Symptoms: symptoms of overdose are usually associated primarily with the action of fenoterol (the appearance of symptoms associated with excessive stimulation of beta-adrenergic receptors). The most likely occurrence is tachycardia, palpitation, tremor, increased or decreased blood pressure, increased differences between systolic and diastolic blood pressure, angina, arrhythmia, a feeling of hot flashes to the face, a feeling of heaviness behind the sternum, increased bronchial obstruction, metabolic acidosis.

Possible symptoms of overdose due to the action of ipratropium bromide (such as dry mouth, impaired eye accommodation) are mild and transient, which is explained by the wide therapeutic range of doses of this drug and its local use.

Treatment: sedatives and tranquilizers are recommended; in severe cases, intensive care is recommended. As a specific antidote, it is possible to use beta-blockers, preferably selective beta-1-blockers. However, in patients with bronchial asthma or chronic obstructive pulmonary disease, the possibility of increasing bronchial obstruction under the influence of beta-blockers should be considered and their dose should be carefully selected.

Special instructions

The patient should be informed that if there is an unexpected rapid increase in shortness of breath (difficulty breathing), they should immediately consult a doctor.

It should be noted that in patients with bronchial asthma, Berodual® should be used only as needed. In patients with mild chronic obstructive pulmonary disease, symptomatic treatment may be preferable to regular use.

In patients with bronchial asthma, one should be aware of the need to conduct or strengthen anti-inflammatory therapy to control the inflammatory process of the respiratory tract and the course of the disease.

Regular use of increasing doses of drugs containing beta-2-adrenomimetics, such as Berodual®, to relieve bronchial obstruction may cause uncontrolled worsening of the course of the disease. In the case of increased bronchial obstruction, simply increasing the dose of beta-2-adrenomimetics (including Berodual) more than the recommended dose for a long time is not only not justified, but also dangerous. To prevent a life-threatening worsening of the disease, consideration should be given to reviewing the patient’s treatment plan and adequate anti-inflammatory therapy with inhaled corticosteroids.

Patients with a history of cystic fibrosis may have gastrointestinal motility disorders.

Other sympathomimetic bronchodilators should be administered simultaneously with Berodual only under medical supervision.

Patients should be instructed on the correct use of Berodual inhalation solution. To prevent the solution from getting into the eyes, it is recommended that the solution used with the nebulizer be inhaled through the mouthpiece. In the absence of a mouthpiece, a face mask that fits snugly should be used. Patients predisposed to developing glaucoma should take special care to protect their eyes.

Berodual® should be used with caution in patients predisposed to acute-angle glaucoma, or in patients with concomitant urinary tract obstruction (for example, prostatic hyperplasia or bladder neck obstruction).

In athletes, the use of Berodual due to the presence of fenoterol in its composition can lead to positive results of doping tests.

The preparation contains a preservative-benzalkonium chloride and a stabilizer-disodium edetate dihydrate. During inhalation, these components can cause bronchospasm in sensitive patients with hyperreactivity of the respiratory tract.

Influence on the ability to drive motor vehicles and manage mechanisms

Studies of the effects of the drug on the ability to drive vehicles and use mechanisms have not been conducted. However, patients should be warned that during Berodual treatment they may experience undesirable sensations such as dizziness, tremor, eye accommodation disorders, mydriasis and blurred vision. Therefore, caution should be recommended when driving vehicles or using machinery. If patients experience the above-mentioned undesirable sensations, they should refrain from such potentially dangerous activities as driving a car or operating mechanisms.

Form of production

Solution for inhalation.

Storage conditions

Keep out of reach of children at a temperature not exceeding 30°C; do not freeze.

Shelf

life is 5 years.

Active ingredient

Ipratropium bromide, Fenoterol

Conditions of release from pharmacies

By prescription

Dosage form

solution for inhalation

Purpose

For adults, Pregnant women only in the second trimester as prescribed by a doctor, For children from birth

Indications

Bronchospasm, Bronchial asthma, Bronchitis, Chronic Obstructive pulmonary Disease