Bronchopulmonary diseases in children are often accompanied by narrowing of the airways and associated difficulty in the passage of air (obstructive syndrome). To eliminate this dangerous symptom, Berodual is used, an inhalation solution that can relax the smooth muscles of the bronchial tree, reduce the production of secretions in the bronchi, and also significantly facilitate breathing. Despite the fact that this drug is a non-hormonal medication, you should read the instructions for use and the features of its use - this will help make the treatment as effective as possible, but not harm the baby.
Pharmacological properties of the drug Berodual n
Berodual N contains two active bronchodilator ingredients: ipratropium bromide, which has an anticholinergic effect, and fenoterol hydrobromide, which is a β-adrenergic agonist. Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. Inhibits vagal reflexes due to antagonistic interaction with acetylcholine, a mediator that ensures the transmission of impulses in the vagus nerve. Anticholinergics prevent the increase in intracellular concentrations of cGMP, which occurs due to the interaction of acetylcholine with muscarinic smooth muscle receptors. Bronchodilation after inhaled administration of ipratropium bromide is mainly due to the local specific effect of the drug. In patients with bronchospasm caused by COPD (chronic bronchitis and emphysema), there was a significant improvement in lung function within 15 minutes after using the drug (increase in forced expiratory volume in 1 second and average forced expiratory volumetric flow rate in the range of 25–75% forced expiratory vital capacity of the lungs (by 15% or more); the maximum effect is observed after 1–2 hours and in most cases lasts up to 6 hours. After using Berodual N for bronchospasm caused by asthma, a significant improvement in lung function (increase in forced expiratory volume1 by 15% and more) noted in 40% of patients. Ipratropium bromide does not have a negative effect on mucus secretion in the respiratory tract, mucociliary clearance and gas exchange in the lungs. Fenoterol hydrobromide is a sympathomimetic, in a therapeutic dose it selectively stimulates β2-adrenergic receptors, but when used in higher doses has a stimulating effect on β1-adrenergic receptors.Binding to β2-adrenergic receptors leads (with the help of the activating Gs protein) to the activation of adenylate cyclase. When the level of cAMP increases, protein kinase A is activated and the corresponding proteins are phosphorylated in smooth muscle cells, which in turn leads to the phosphorylation of myosin light chain kinase, blocking the hydrolysis of phosphoinositide and the opening of calcium-dependent potassium channels. Fenoterol causes relaxation of the smooth muscles of the bronchi and blood vessels and prevents bronchospasm caused by the effects of bronchoconstrictor agents (histamine, methacholine, cold air and allergens). Fenoterol blocks the release of bronchoconstrictor and proinflammatory mediators. When the drug was administered in high doses, an improvement in mucociliary clearance was noted. At higher concentrations of fenoterol in the blood plasma, which is usually achieved by oral administration or intravenous administration, the contractile activity of the myometrium is reduced. When using the drug in high doses, its metabolic effect may occur: lipolysis, glycogenolysis, hyperglycemia and hypokalemia, the latter caused by an increase in the uptake of K+ ions by cells, especially skeletal muscles. The effect of fenoterol on myocardial β2-adrenergic receptors is accompanied by tachycardia and an increase in the force of heart contractions, which is associated with the vascular effect of fenoterol, stimulation of cardiac β2-adrenergic receptors, and in doses exceeding therapeutic doses - stimulation of β1-adrenergic receptors. As with the action of other β-adrenergic substances, a prolongation of the Q-Tc . For fenoterol, these indicators are discrete and are recorded at doses exceeding the recommended ones. The clinical significance of this has not been established. The side effect most often reported with β-sympathomimetics is tremor. In contrast to the effect on bronchial smooth muscle, the systemic effects of β-sympathomimetics are a reason for the development of tolerance. Fenoterol prevents the development of bronchospasm caused by various factors, such as physical activity, cold air, as well as the influence of allergens (immediate reaction). With the simultaneous use of two bronchodilators, bronchial dilation occurs due to the implementation of two different pharmacological mechanisms. The mechanism of action of this combination of drugs allows them to be widely used for diseases of the bronchopulmonary apparatus associated with obstruction of the airways. Thus, the two active substances have a synergistic bronchodilator effect, which allows them to be used in a proportionally reduced dose and, therefore, reduce the risk of side effects. According to clinical studies, in patients with asthma and COPD, Berodual N corresponds in effectiveness to a double dose of fenoterol prescribed without ipratropium bromide, but has better tolerance with long-term use. In case of bronchospasm, the effect of Berodual N develops immediately after administration, so the drug can be used to relieve asthma attacks. Pharmacokinetics. The therapeutic effect of Berodual N manifests itself through a local effect on the respiratory tract. After inhalation, about 16% of the drug settles in the respiratory tract, the rest is swallowed. The active ingredients are absorbed very quickly in the respiratory tract, their maximum concentration in the blood plasma is reached within a few minutes. There is no evidence that the pharmacokinetics of the combination of both ingredients differs from that of each monosubstance. Fenoterol hydrobromide , which enters the digestive tract, is mainly metabolized to sulfate conjugates. Bioavailability after oral administration is low (about 1.5%). Fenoterol and its conjugates are rapidly excreted in the urine (renal clearance - 267 ml/min). About 40–55% of the drug binds to blood plasma proteins. In the unmetabolized state, fenoterol hydrobromide can slowly penetrate the placental barrier and enter breast milk. Ipratropium bromide . Absolute bioavailability after oral administration is about 2%. The half-life in the terminal elimination phase is about 1.6 hours. The total clearance is 2.3 l/min. About 40% of the drug is excreted in the urine (renal clearance - 0.9 l/min), 60% undergoes hepatic clearance. The main metabolites detected in urine bind to muscarinic receptors to a small extent. Renal excretion of unchanged active substance is 4.4–13.1% of the dose after inhalation. The drug minimally (less than 20%) binds to blood plasma proteins. Ipratropium ion does not penetrate the BBB; it is not known whether it penetrates the placental barrier.
I.E. Stepanyan
Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, Moscow
Well known to pulmonologists and therapists, Berodual has been widely used in many countries as an effective bronchodilator for more than a quarter of a century. The idea of creating a combined bronchodilator, the two components of which would act on different mechanisms of bronchospasm, turned out to be successful and ensured the successful use of the drug for many years. Berodual is a combination of the selective β2-adrenergic agonist fenoterol hydrobromide and the M-cholinergic receptor blocker ipratropium bromide. By binding to β2-adrenergic receptors, fenoterol, through the stimulatory Gs protein, activates adenylate cyclase, which leads to an increase in the formation of cAMP, which in turn activates protein kinase A. The latter phosphorylates target proteins in smooth muscle cells, which leads to phosphorylation of myosin light chain kinase, suppression hydrolysis of phosphoinosine and opening of calcium-activated fast potassium channels. Fenoterol relaxes the smooth muscles of the bronchi and blood vessels, it prevents the development of bronchospasm caused by exposure to histamine, methacholine, cold air and allergens. The drug also inhibits the release of inflammatory mediators from mast cells. In addition, high doses of fenoterol enhance mucociliary transport. Fenoterol also exhibits respiratory stimulant properties. The effect of fenoterol on cardiac activity, manifested by an increase in the frequency and strength of heart contractions, is due to stimulation of β-adrenergic receptors of the heart and is insignificantly expressed in therapeutic doses. Ipratropium bromide effectively eliminates bronchospasm associated with the influence of the vagus nerve and reduces the secretion of the bronchial glands. When administered by inhalation, the drug causes bronchodilation, mainly due to local rather than systemic anticholinergic effects. Ipratropium bromide does not have a negative effect on mucus secretion in the respiratory tract, mucociliary clearance and gas exchange. Both components of Berodual are produced separately as independent drugs, which are known in our country under the names Berotec and Atrovent, and are also widely used as effective bronchodilators. When fenoterol hydrobromide and ipratropium bromide are used together, the bronchodilator effect is achieved due to the combined effect on various points of application and pathogenetic mechanisms. Fenoterol provides rapid bronchodilation by stimulating β2-adrenergic receptors located predominantly in the distal airways. The anticholinergic blocker ipratropium bromide acts on M-cholinergic receptors in the proximal parts of the bronchial tree, its effect occurs half an hour after inhalation. The combination of two drugs provides mutual enhancement and a greater breadth of therapeutic action for bronchopulmonary diseases accompanied by obstruction of the airways. The ability to achieve a therapeutic effect using a lower dose of a β-agonist allows one to avoid side effects and the development of tachyphylaxis. Two dosage forms of Berodual are supplied to Russia:
1) metered dose aerosol inhaler (MDI), containing 50 mcg of fenoterol hydrobromide and 20 mcg of ipratropium bromide in 1 dose; 2) solution for inhalation, 1 ml of which contains 500 mcg of fenoterol hydrobromide and 250 mcg of ipratropium bromide.
Tests of the Berodual powder inhaler in patients with reversible bronchial obstruction showed that its effectiveness and safety were not inferior to MDIs [1]. In recent years, Boehringer Ingelheim Pharma GMBH has created an original propellant-free dosing system, Respimat, and Berodual is already produced in this form. The properties of Berodual have been comprehensively studied in numerous studies, most of which were carried out in the early years of its use. It was shown that the combination of fenoterol hydrobromide/ipratropium bromide in patients with bronchial asthma on the first day led to a pronounced bronchodilator effect that persisted for 3 months and did not cause tachyphylaxis [2]. A comparison of the results of both single use and long-term treatment with salbutamol and the combination of fenoterol hydrobromide/ipratropium bromide (Duoventa) in patients with broncho-obstructive diseases revealed the advantage of the combined drug, which demonstrated better effectiveness (reduction of cough, shortness of breath during the day and night, prevention of episodes of bronchospasm, reduction need for additional bronchodilator inhalations) and patient compliance [3-6]. Berodual's ability to reduce the severity of induced cough in both healthy volunteers and asthmatics was more pronounced compared to ipratropium and oxitropium [7]. A comparison of the effectiveness of combination preparations of fenoterol hydrobromide/ipratropium bromide containing different doses of components (Berodual - 50 mcg fenoterol, 20 mcg ipratropium and Duovent - 100 mcg and 40 mcg, respectively) in patients with stable bronchial asthma was carried out in order to determine the optimal dosage regimen. The results of using both drugs, 2 doses 4 times a day for 3 months, showed the identical effect of both drugs on peak flowmetry and spirography indices [8]. A 3-month use of Duovent in patients with COPD over 60 years of age showed a clear reduction in symptoms, improvement in bronchial obstruction, absence of tachyphylaxis and pronounced undesirable effects, including those from the cardiovascular system [9]. In our country, the experience of using Berodual has more than 20 years of history. The drug has established itself as a highly effective bronchodilator, which can be successfully used to treat patients with COPD, bronchial asthma, and broncho-obstructive syndrome in pulmonary tuberculosis [10-12]. At the end of the 20th century, the DAI of Berodual underwent forced changes. Until the end of the 20th century, chlorofluorocarbon (freon) was used as a propellant (carrier gas for drug particles in an aerosol) for Berodual MDIs. The proven effectiveness and safety of freon-containing MDIs for patients at that time led to their widespread use. In the mid-1990s, up to 500 million MDIs were produced annually in Europe alone, the production of which required about 10,000 tons of freon. The problem turned out to be that the freon contained in the MDI entered the atmosphere and destroyed the ozone layer, which protects the earth's surface from harmful ultraviolet radiation. According to the Vienna Convention (1985) and the Montreal Protocol (1987), the international community decided to abandon the production and consumption of substances that destroy the Earth's ozone layer. In 1993, the European Commission issued guidelines for the replacement of chlorofluorocarbon in medicinal products. In accordance with changing requirements, at the end of the 20th century. a new MDI was developed - Berodual N, containing tetrafluoroethane as a propellant that is safe for the ozone layer. Numerous comparative studies of freon and freon-free MDI Berodual have not revealed significant differences in their effectiveness and safety for patients [13-15]. In addition, the new generation of MDIs do not have a cooling effect on the mucous membrane of the respiratory tract, which was characteristic of freon-containing inhalers. Since the beginning of the 21st century. in Russia, instead of the old MDI - Berodual, they began to use a new one - Berodual N. Currently, the indications for prescribing Berodual are clearly defined. Inhalation of a dosed aerosol of Berodual N is used as an “ambulance” to relieve bronchospasm in bronchial asthma and COPD of any severity, as well as for long-term planned bronchodilator therapy in patients with stable COPD stages II-IV [16, 17]. Berodual is also effective for other diseases that involve obstruction of the airways (bronchiectasis, exogenous allergic alveolitis, etc.) and is successfully used to treat bronchial obstruction, which can occur in patients with pneumonia, acute bronchitis, and pulmonary tuberculosis [18]. The undoubted advantage of Berodual is the possibility of using it in the form of a solution for inhalation using a nebulizer. Nebulized inhalations of Berodual solution are widely used in intensive care for patients with exacerbations of bronchial asthma and COPD of any severity, and are also prescribed for routine treatment in cases where patients cannot fully use a metered dose inhaler (young children, elderly patients, etc.) [19, 20]. Indications for the use of Berodual solution through a nebulizer arise in cases of the need to use high doses of bronchodilators, difficulty in coordinating inhalation and injection of medication from a MDI; with FEV1 Berodual is convenient for use in both clinical and outpatient practice. The high level of safety of Berodual makes possible its widespread use in both young children and elderly patients [23]. Berodual can be used for concomitant diseases of the cardiovascular system. After inhalation of the drug, even in high doses, as a rule, there are no cardiotoxic reactions. The results of nebulizer therapy with Berodual in patients with exacerbations of bronchial asthma and concomitant diseases of the cardiovascular system (CHD, hypertension) showed that the drug did not have a noticeable cardiotoxic effect [24]. There is experience of successful use of nebulizer inhalations of Berodual in patients with COPD who were on mechanical ventilation [25]. The safety of Berodual has been proven by the results of many studies; however, it is necessary to remember the peculiarities of drug interactions, the presence of a number of contraindications to the use of the drug and the possibility of undesirable effects. The components of Berodul are highly compatible with each other in MDI and nebulizer solution. The simultaneous use of other β-adrenergic agonists, systemic anticholinergics, xanthine derivatives (for example, theophylline) can enhance not only the bronchodilator effect, but also the side effects of Berodual. A significant weakening of the bronchodilator effect of Berodual is possible with simultaneous use of β-blockers. Hypokalemia associated with the use of β-agonists may be exacerbated by the simultaneous use of xanthine derivatives, steroids and diuretics. This fact should be given special attention when treating patients with severe forms of obstructive airway diseases. Hypokalemia may lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia may enhance the negative effects of hypokalemia on heart rate. In such cases, it is recommended to monitor serum potassium levels. Beta-adrenergic agents should be prescribed with caution to patients receiving MAO inhibitors and tricyclic antidepressants, since these drugs may enhance the effect of beta-adrenergic agents. Inhalation of halogenated hydrocarbon anesthetics, such as halothane, trichlorethylene or enflurane, increases the effects of beta-adrenergic agents on the cardiovascular system. The combined use of Berodual with glucocorticosteroids increases the effectiveness of therapy. It is not advisable to prescribe Berodual to patients with hypertrophic obstructive cardiomyopathy, tachyarrhythmia, hypersensitivity to fenoterol hydrobromide, atropine-like drugs or other components of the drug. The drug should be prescribed with caution for angle-closure glaucoma, coronary insufficiency, arterial hypertension, diabetes mellitus, recent myocardial infarction, severe organic diseases of the heart and blood vessels, hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, cystic fibrosis, in the 1st trimester pregnancy, during breastfeeding. The possibility of an inhibitory effect of Berodual on the contractile activity of the uterus should be taken into account. The most common adverse effects are hand tremors, nervousness, dry mouth, and changes in taste; Headache, dizziness, and tachycardia are less common, especially in patients with aggravating factors. Also possible:
• cough, respiratory tract irritation; rarely – paradoxical bronchospasm; • decreased diastolic blood pressure, increased systolic blood pressure, arrhythmias; • nausea, vomiting, gastrointestinal motility disorders (especially in patients with cystic fibrosis); • if the drug gets into the eyes, reversible disturbances of accommodation, mydriasis develop, symptoms of increased intraocular pressure appear (pain or discomfort in the eyeball, blurred vision, a feeling of a halo or colored spots appearing before the eyes, conjunctival hyperemia); • allergic reactions, which can manifest as skin rash, angioedema of the tongue, lips and face, urticaria; • hypokalemia, increased sweating, feeling of general weakness, myalgia, muscle cramps, mental changes, urinary retention.
Symptoms of Berodual overdose are usually associated with excessive stimulation of β-adrenergic receptors under the influence of fenoterol. The most likely occurrence is rapid heartbeat, slight tremor of skeletal muscles, arterial hypo- or hypertension, an increase in the difference between systolic and diastolic blood pressure, extrasystole, angina pectoris, arrhythmia and a feeling of flushing of the face, increased bronchial obstruction. The use of fenoterol in high doses can lead to stimulation of β1-adrenergic receptors, affect metabolism: cause lipolysis, glycogenolysis, hyperglycemia and hypokalemia (due to increased potassium absorption by skeletal muscles), and inhibit the contractile activity of the uterus. Possible symptoms of overdose caused by 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. Dosage forms of Berodual are constantly being improved taking into account the changing requirements of medical practice. Along with the transition to freon-free forms of MDI, the direction of creating original propellant-free dosing systems, for example, Respimat, is being developed. A study of the effectiveness of inhalation therapy with Berodual in patients with bronchial asthma and COPD using Respimat in comparison with freon MDI showed that the safety profile when using both inhalation devices was the same, and the effect of administering 50 mcg fenoterol/20 mcg ipratropium through Respimat was equivalent to that of twice higher dose administered using a MDI, i.e., the high cost-effectiveness of using the new inhalation device has been proven. [26-28]. Thus, many years of experience in using Berodual in patients with broncho-obstructive diseases gives grounds to assert that, despite the emergence of new effective bronchodilators, this original combination drug has not lost its significance and will remain in clinical and outpatient practice for a long time.
References 1. Rammeloo RH, Luursema PB, Sips AP et al. Therapeutic equivalence of a fenoterol/ipratropium bromide combination (Berodual) inhaled as a dry powder and by metered dose inhaler in chronic obstructive airway disease // Respiration. 1992; 59: 322-326. 2. Carlone S., Angelici E., Palange P. et al. Tolerance to inhaled Duovent. A long-term study // Respiration. 1986; 50: Suppl 2: 218-221. 3. Flint KC, Hockley B., Johnson NM A comparison between a combination of ipratropium bromide plus fenoterol in a single metered dose inhaler (Duovent) and salbutamol in asthma // Postgrad. Med. J. 1983; 59: 724-725. 4. Imhof E., Elsasser S., Karrer W. et al. Comparison of bronchodilator effects of fenoterol/ipratropium bromide and salbutamol in patients with chronic obstructive lung disease // Respiration. 1993; 60: 84-88. 5. Macaluso S., Del Torre L. Efficacy and compliance to prolonged Duovent treatment of bronchospasm. Comparison with salbutamol // Respiration. 1986; 50: Suppl 2: 222-225. 6. Philip-Joet F., Reynaud-Gaubert M., Jirou-Najou JL, Arnaud A. Comparison of Berodual and salbutamol in asthma: a multicenter evaluation // Respiration. 1990; 57: 379-383. 7. Lowry R, Wood A, Johnson T, Higenbottam T. Antitussive properties of inhaled bronchodilators on induced cough // Chest. 1988; 93: 1186-1189. 8. Frølund L., Madsen F., Svendsen UG, Weeke B. Comparison of two aerosols containing both fenoterol and ipratropium in a high (Duovent) and low (Berodual) concentration, respectively // Respiration. 1986; 50: Suppl 2: 270-273. 9. Cecere L., Funaro G., De Cataldis G. et al. Long-term treatment with 'Duovent' in elderly patients affected by chronic obstructive lung disease // Respiration. 1986; 50: Suppl. 2: 245-248. 10. Chuchalin A.G., Kolganova N.A., Pashkova T.L. and others. Berodual in the treatment of bronchial asthma // Sov. Med. 1985; 11: 81. 11. Vizel A.A., Yaushev M.F., Mustafin R.R., Goncharova L.V. Bronchodilator activity of metered aerosols in active respiratory tuberculosis // Probl. tuberk. 1995; 2:7-9. 12. Shmelev E.I., Khmelkova N.G., Nonikov D.V. and others. Experience of long-term use of Berodual in the treatment of patients with chronic obstructive bronchitis // Ter. archive. 1999; 3:22-24. 13. Shmelev E.I. Freon-free liquid inhalers in the treatment of obstructive pulmonary diseases // RMZh. 2002; 23. 14. Maesen FP, Greefhorst LP, Smeets JJ et al. Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual) for the delivery of a fixed combination of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled crossover study in patients with asthma // Respiration. 1997; 64: 273-280. 15. Huchon G., Hofbauer P., Cannizzaro G. et al. Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO // Eur. Respira. J. 2000; 15: 663-669. 16. Goryachkina L.A., Drobik O.S. Pharmacotherapy of obstructive pulmonary diseases: combined bronchodilator Berodual N // Consilium Medicum. Directory of a polyclinic doctor. 2006; 8. 17. Shmelev E.I. The use of a fixed combination of bronchodilators (fenoterol + ipratropium) for exacerbations of chronic obstructive pulmonary disease // Difficult patient. 2007; 15-16. 18. Shmelev E.I., Kuklina G.M. Modern principles of treatment of bronchial obstruction in patients with pulmonary tuberculosis // Probl. tuberk. 2001; 7: 36-40. 19. Tsoi A.N., Arkhipov V.V. Pharmacodynamics of inhaled bronchodilators used in one dose via a nebulizer in patients with severe exacerbations of bronchial asthma // Ter. archive. 2002; 3: 17-21. 20. Shmelev E.I., Khmelkova N.G., Abubikirov A.F. The use of nebulizer therapy with Berodual in patients with exacerbation of chronic obstructive bronchitis // Ter. archive, 2000; 3:26-28. 21. Leshchenko I.V., Ulybin I.B., Bushuev A.V. Clinical and economic effectiveness of nebulizer therapy in emergency care for attacks of bronchial asthma // Ter. Archive. 2000; 8:13-16. 22. Sidorova L.D., German E.Yu., Logvinenko A.S., Korolenko L.P. The use of a nebulizer as a new method of drug administration in the treatment of asthma attacks in patients with bronchial asthma // Ter. archive. 1999; 3: 17-18. 23. Balabolkin I.I. Bronchial asthma in children. M.: Medicine, 2003. 24. Makolkin V.I., Ovcharenko S.I., Peredelskaya O.A., Aksklrod A.S. The effect of high doses of bronchodilators on the state of the cardiovascular system during the treatment of severe exacerbations of bronchial asthma // Cardiology. 2004; 2: 65-69. 25. Guerin C., Chevre A., Dessirier P. et al. Inhaled fenoterol-ipratropium bromide in mechanically ventilated patients with chronic obstructive pulmonary disease // Am. J. Respira. Crit. Care Med. 1999; 159: 1036-1042. 26. Kässner F., Hodder R., Bateman ED A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive pulmonary disease // Drugs. 2004; 64: 1671-1682. 27. Kilfeather SA, Ponitz HH, Beck E. et al. Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD // Respir. Med. 2004; 98: 387-397. 28. Vincken W., Bantje T., Middle MV et al. Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via Respimat Soft Misttrade mark Inhaler versus a Pressurized Metered-Dose Inhaler in Asthma // Clin. Drug Investig. 2004; 24: 17-28.
Use of the drug Berodual n
The dose is set individually. For adults and children over the age of 6 years, the following dosage regimens are recommended: relief of an acute attack of asthma: usually 2 inhalations are sufficient; for severe attacks, if breathing does not improve significantly within 5 minutes, 2 additional inhalations can be performed. If there is no effect after 4 inhalations, it may be necessary to take additional measures. In such cases, the patient should immediately consult a doctor or the nearest medical facility. Intermittent and long-term use: 1-2 inhalations for each procedure, no more than 8 inhalations per day (on average - 1-2 inhalations 3 times a day). In children, dosed aerosol Berodual N should be used only under adult supervision. Aerosol injection. To achieve maximum effect, patients should be instructed regarding the correct use of the metered dose aerosol. Before using the drug in this form for the first time, press the valve twice until a cloud of aerosol appears. Before each use, you must follow the following rules: remove the protective cap, exhale slowly, hold the canister upside down (with the inhalation device facing down), wrap your lips around the tip, inhale as deeply as possible, and simultaneously press the bottom of the canister until one measured dose is released. Hold your breath for a few seconds, then remove the tip from your mouth and exhale slowly. After use, put on the protective cap. If the dosed canister has not been used for more than 3 days, before use, press the valve once until an aerosol appears. The cylinder is designed for 200 doses (inhalations). After using 200 doses, the balloon should be replaced. Although some contents still remain in the balloon, the amount of drug released during inhalation is not sufficient to achieve a therapeutic effect. The tip should be kept clean and, if necessary, can be rinsed with warm water. After using soap or detergent, the handpiece must be rinsed thoroughly with clean water.
Possible analogues, cost of medicine
The average cost of Berodual in domestic pharmacies is 240-290 rubles. If it is impossible to purchase or use it, the doctor may decide to replace it with another product with a similar effect:
- Atrovent;
- Berotek;
- Budesonide;
- Ventolin;
- Ditek;
- Ipravent;
- Ipramol Steri-Neb;
- Combivent;
- Seretide.
It is strictly forbidden to independently select a drug for inhalation for a child, since each of the above analogues has age restrictions and a number of contraindications.
Side effects of the drug Berodual n
The most common symptoms are fine tremor of skeletal muscles and increased excitability, a feeling of dry mouth, and in some cases headache, dizziness, and tachycardia. There are isolated reports of side effects from the organ of vision, including impaired accommodation and glaucoma (see SPECIAL INSTRUCTIONS). Very rarely, allergic reactions are possible: skin rash, angioedema of the tongue, lips and face, urticaria, laryngospasm and anaphylactic reactions. Severe hypokalemia may potentially result from β2-agonist therapy. As with the use of other inhaled drugs, coughing, local irritating effects (for example, pharyngitis, throat irritation), and in some cases bronchospastic reactions were noted. As with the use of other β-adrenergic agonists, Berodual N can cause nausea, vomiting, increased sweating, general weakness, myalgia and spasms. Very rarely, when used in high doses, a decrease in diastolic blood pressure, an increase in systolic blood pressure, arrhythmias, atrial fibrillation and supraventricular tachycardia are observed. In some cases, the development of mental changes under the influence of inhaled therapy with β-adrenergic agonists was reported. Disturbances of accommodation, motility of the digestive tract and urinary retention are rare and are reversible.
Special instructions for use
During pregnancy and breastfeeding. Experimental and clinical studies have not revealed a negative effect of fenoterol and ipratropium bromide on the course of pregnancy and the fetus, however, its use during pregnancy, especially in the first trimester, is not recommended. The effect of fenoterol on uterine contractility during labor should be taken into account. Preclinical studies have shown that fenoterol passes into breast milk. There is no data on the penetration of ipratropium bromide into breast milk. Although fat-insoluble quaternary bases pass into breast milk, it is unlikely, especially when using the aerosol form of the drug, that ipratropium bromide will have a significant effect on the fetus. However, Berodual N should be used with caution during breastfeeding. When using the new dosage form of Berodual N metered aerosol for the first time, patients may note that it tastes slightly different from the previous dosage form of the drug, which contains freon. The patient should be informed that these dosage forms are interchangeable and taste properties are not relevant to the safety and effectiveness of the new dosage form of the drug. In case of acute dyspnea (difficulty breathing), especially if it progresses rapidly, you should immediately consult a doctor. One should remember the need for basic anti-inflammatory therapy in patients with asthma and steroid-dependent forms of COPD. Long-term use:
- in patients with asthma and non-severe forms of COPD, preference is given to using the drug “as needed” (symptomatically oriented depending on the manifestation of symptoms), rather than regular use;
- In patients with severe asthma or steroid-dependent forms of COPD, anti-inflammatory therapy should be administered to control the inflammatory process in the airways and the course of the disease.
Regular use of a drug in high doses containing β2-agonists, such as Berodual N, to eliminate bronchial obstruction can cause uncontrolled worsening of the disease. In the case of increased bronchial obstruction, increasing the dose of β2-agonists above the recommended long-term is not only not justified, but also dangerous. To prevent worsening of the disease, the treatment regimen should be revised towards adequate anti-inflammatory therapy with inhaled corticosteroids. Other sympathomimetic bronchodilators are prescribed simultaneously with Berodual N only under medical supervision. Berodual N can be prescribed only after careful comparison of the expected benefits and possible risks in the following conditions: diabetes mellitus without proper compensation, recent myocardial infarction and other severe organic diseases of the heart and blood vessels, thyrotoxicosis, pheochromocytoma. When using β2-agonists, significant hypokalemia may develop. Berodual N should be prescribed with caution to patients with benign prostatic hyperplasia and urodynamic disorders, as well as to patients with angle-closure glaucoma. There are reports of isolated cases of complications from the organ of vision (mydriasis, increased intraocular pressure, angle-closure glaucoma, eye pain) that occurred as a result of contact with the eyes of an aerosol of ipratropium bromide or its combination with β2-agonists. Signs of an acute attack of angle-closure glaucoma may include pain in the eyes, blurred vision, a sensation of a halo or colored spots in front of the eyes in combination with conjunctival or corneal hyperemia. If these symptoms occur, miotic drugs should be prescribed and specialized medical care should be sought immediately. Patients with cystic fibrosis are prone to developing gastrointestinal motility disorders when using the drug. Very rarely, after taking Berodual N, hypersensitivity reactions such as urticaria, angioedema, skin rash, bronchospasm, oropharyngeal edema and anaphylactic reactions may immediately develop. Warning: the plastic tip is designed specifically for metered-dose aerosol Berodual N and is used for precise dosing of the drug. The tip should not be used with any other metered-dose aerosols. The contents of the can are under pressure. Do not open the can or expose it to temperatures above 50 °C.
Interactions of the drug Berodual n
The simultaneous administration of β-adrenergic agonists for systemic use, anticholinergics and xanthines (theophylline) can increase the bronchodilator effect of Berodual N and lead to an increase in the severity of side effects. A significant reduction in the bronchodilator effect of Berodual N is possible with simultaneous administration of β-adrenergic receptor blockers. The severity of hypokalemia caused by the use of β-adrenergic agonists may increase with the simultaneous administration of xanthines, corticosteroids and diuretics. This fact should be given special attention when treating patients with severe forms of airway obstruction. Hypokalemia may lead to an increased risk of arrhythmias in patients using digoxin. In this case, it is recommended to monitor the level of potassium in the blood serum. Beta-adrenergic agents should be prescribed with caution to patients taking MAO inhibitors and tricyclic antidepressants, since these drugs may increase the severity of the action of beta-adrenergic agents. Inhalation of halogenated carbohydrate anesthetics, such as halothane, trichloroethylene or enflurane, may enhance the cardiovascular effects of beta-adrenergic agents.
Drug interactions
To enhance the therapeutic effect, several drugs are combined in inhalations.
How to dilute with Lazolvan - proportions and doses
Thus, the use of Lazolvan (mucolytic) in one inhalation with Berodual is considered effective. To do this, add 1-2 ml (depending on the indications and age) of Lazolvan to the recommended ratio of saline and Berodual. But much more often, alternating these medications is practiced - first, the child breathes Berodual, which dilates the bronchi, and after 15-20 minutes, inhalation is carried out with a mucolytic, which allows you to effectively remove accumulated sputum.
Inhalations with mucolytic agents should be carried out no later than 2 hours before the child goes to bed - this can lead to an active night cough or stagnation of sputum.
Is it possible to do inhalations with Pulmicort for infants?
In some cases, children are prescribed a combination of Berodual with Pulmicort, a glucocorticosteroid that reduces allergic manifestations and eliminates swelling of the mucous membranes. However, it is strictly not recommended to mix these two drugs, since Pulmicort will increase the effect of Berodual and, accordingly, increase the risk of side effects. The following combination scheme is optimal: inhalation of Pulmicort, and an hour later – inhalation with Berodual.
Price – about 800 rubles
Overdose of the drug Berodual n
It is caused mainly by the action of fenoterol and excessive stimulation of β-adrenergic receptors. The most likely symptoms are tachycardia, palpitations, tremor, hypertension (arterial hypertension) or hypotension, increased pulse pressure, angina attacks, arrhythmia and flushing. Symptoms of an overdose of ipratropium bromide (a feeling of dryness of the oral mucosa, impaired accommodation) are usually mild and transient due to the very low systemic bioavailability of inhaled ipratropium bromide. Treatment: administration of sedatives, tranquilizers, and in severe cases, intensive care. β-adrenergic receptor blockers, preferably β1-selective, are used as specific antidotes; however, the dose should be carefully selected for patients with asthma or COPD, taking into account the possibility of increased bronchial obstruction under their influence, even death.
