Berodual®
If shortness of breath (difficulty breathing) suddenly increases rapidly, you should consult a doctor immediately.
Hypersensitivity
After using BERODUAL®, immediate hypersensitivity reactions may occur, signs of which, in rare cases, may be: urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, anaphylactic shock.
Paradoxical bronchospasm
BERODUAL®, like other inhaled drugs, can cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm develops, the use of BERODUAL® should be stopped immediately and switched to alternative therapy
Long-term use
— in patients suffering from bronchial asthma, BERODUAL® should be used only as needed;
- in patients with mild forms of chronic obstructive pulmonary disease, symptomatic treatment may be preferable to regular use;
- in patients with bronchial asthma, one should remember the need to carry out or intensify 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 β2-adrenergic agonists, such as BERODUAL®, to relieve bronchial obstruction can cause uncontrolled worsening of the disease. In case of increased bronchial obstruction, increasing the dose of β2-agonists, including BERODUAL®, more than recommended for a long time is not only not justified, but also dangerous. To prevent 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.
Other sympathomimetic bronchodilators should be prescribed simultaneously with BERODUAL® only under medical supervision.
Gastrointestinal disorders
In patients with a history of cystic fibrosis, gastrointestinal motility disorders are possible.
BERODUAL® should be used with caution in patients predisposed to acute-angle glaucoma. There are isolated reports of complications from the organ of vision (for example, increased intraocular pressure, mydriasis, angle-closure glaucoma, eye pain) that developed when inhaled ipratropium bromide (or ipratropium bromide in combination with β2-adrenergic receptor agonists) entered the eyes. Symptoms of acute angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo on objects and colored spots in front of the eyes in combination with corneal edema and redness of the eyes due to conjunctival vascular injection.
If any combination of these symptoms develops, the use of eye drops that reduce intraocular pressure and immediate consultation with a specialist are indicated.
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 a nebulizer be inhaled through the mouthpiece. If there is no mouthpiece, a mask that fits tightly to the face should be used. Patients predisposed to developing glaucoma should take special care to protect their eyes.
Systemic effects
For the following diseases: recent myocardial infarction, diabetes mellitus with inadequate glycemic control, severe organic diseases of the heart and blood vessels, hyperthyroidism, pheochromocytoma or urinary tract obstruction (for example, prostatic hyperplasia or bladder neck obstruction), BERODUAL® should be used only after careful risk/benefit assessments, especially when using doses higher than recommended.
Effect on the cardiovascular system
In post-marketing studies, rare cases of myocardial ischemia have been reported when taking beta-agonists. Patients with concomitant serious heart disease (for example, coronary heart disease, arrhythmias or severe heart failure) receiving BERODUAL® should be warned to consult a doctor if they develop heart pain or other symptoms indicating worsening of heart disease. It is necessary to pay attention to symptoms such as shortness of breath and chest pain, as they can be of both cardiac and pulmonary etiology.
Hypokalemia
When using β2-agonists, hypokalemia may occur (see section "Overdose").
In athletes, the use of BERODUAL® due to the presence of fenoterol in its composition can lead to positive results of doping tests.
The drug contains a preservative, benzalkonium chloride, and a stabilizer, disodium edetate dihydrate. During inhalation, these components may cause bronchospasm in sensitive patients with airway hyperresponsiveness.
Berodual n 20mcg+50mcg/dose 200doses 10ml aerosol for inhalation dosed
Release form:
Aerosol for inhalation dosed.
Composition 1 dose contains:
Active ingredients: fenoterol hydrobromide 50 mcg; ipratropium bromide monohydrate 21 mcg, which corresponds to the content of ipratropium bromide 20 mcg.
Excipients: absolute ethanol, purified water, citric acid, tetrafluoroethane (HFA 134a, propellant).
Packaging: Bottle 10 ml.
Pharmachologic effect:
Combined bronchodilator drug. Contains two components with bronchodilator activity: ipratropium bromide - an m-anticholinergic blocker, and fenoterol hydrobromide - a beta2-adrenergic agonist. With inhaled ipratropium bromide, bronchodilation is due primarily to local rather than systemic anticholinergic effects.
Berodual N, indications for use:
Prevention and symptomatic treatment of obstructive airway diseases with reversible bronchospasm: COPD. Bronchial asthma. Chronic bronchitis, complicated or not complicated by emphysema.
Contraindications: Hypertrophic obstructive cardiomyopathy. Tachyarrhythmia. I trimester of pregnancy. Children's age up to 6 years. Hypersensitivity to the components of the drug. Hypersensitivity to atropine-like substances.
With caution: use the drug for angle-closure glaucoma, coronary insufficiency, arterial hypertension, poorly controlled diabetes mellitus, recent myocardial infarction, severe organic diseases of the cardiovascular system, hyperthyroidism, pheochromocytoma, prostatic hypertrophy, bladder neck obstruction, cystic fibrosis, children over 6 years old.
Method of administration and dosage: The dose is set individually. To relieve attacks of bronchial asthma, adults and children over 6 years of age are prescribed 2 inhalation doses. If breathing relief does not occur within 5 minutes, 2 more inhalation doses can be prescribed. The patient should be informed that if there is no effect after 4 inhalation doses and additional inhalations are necessary, consult a doctor immediately.
Rules for using the drug: The patient must be instructed on the correct use of the metered-dose aerosol.
Before using the metered-dose aerosol for the first time, press the bottom of the can twice.
Storage conditions:
Store out of the reach of children at a temperature not exceeding 25°C. The contents of the cylinder are under pressure. The container must not be opened or heated above 50°C.
Shelf life: 3 years.
The feasibility of including the drug Berodual N in the treatment of exacerbations of bronchial asthma
O.A. TSVETKOVA
, Doctor of Medical Sciences, Professor,
First Moscow State Medical University named after. THEM. Sechenov The purpose of the article is to determine the place of the combined bronchodilator Berodual N in the treatment of exacerbations of bronchial asthma and recommendations for various delivery methods for varying degrees of severity of exacerbations of bronchial asthma.
The treatment of bronchial asthma is of interest to the general practitioner, since asthma is a fairly common disease, and providing assistance during its exacerbation (an attack of suffocation) does not always bring quick and tangible results. Severe exacerbations occur in 3-5% of patients with bronchial asthma, and their mortality rate ranges from 1 to 10% [9]. Today, most patients, and doctors, consider bronchial asthma to be a chronic, steadily progressing serious disease, which not only leads to loss of ability to work, but can lead to death during an exacerbation. And although this idea has lost most of its gloomy colors in the last decade thanks to the new concept of diagnosing and treating patients, the problem of providing qualified, timely assistance at the time of exacerbation remains acute and not always solvable. It is also alarming that, despite the low mortality rates from asthma (0.4–0.6 per 100,000), a number of countries are experiencing a steady increase in mortality [3, 8].
The reasons for this are seen in the increasing proportion of severe asthma, inadequate basic treatment, as well as drug complications during the provision of care.
Treatment tactics for bronchial asthma should be based on an assessment of the severity of its exacerbation. The basis of treatment for exacerbation of bronchial asthma is repeated administration of a fast-acting short-acting inhaled β2-agonist or anticholinergic drug, as well as their combinations, early administration of systemic corticosteroids and inhaled oxygen. Therapy for bronchial asthma should be as safe as possible for patients. Following the recommendations for the treatment of exacerbations of bronchial asthma both at the prehospital stage and in the hospital can significantly reduce the frequency of severe exacerbations of bronchial asthma.
Exacerbations of bronchial asthma (asthma attacks) are episodes of progressive increase in shortness of breath, cough, wheezing, chest tightness, or a combination of these symptoms. During exacerbations, a narrowing of the lumen of the bronchi occurs, which is accompanied by a decrease in speed indicators of the external respiratory function (ERF) - peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC). Moreover, these measurements can serve as a more reliable indicator of the severity of bronchospasm. The causes of exacerbation are usually:
• poorly selected basic treatment; • poor adherence to it; • contact with a provoking trigger factor, which can be: - allergens, - pollutants, - respiratory infections, - physical activity and hyperventilation, - weather changes, - medications, food additives, - emotional stress, - smoking.
The severity of an exacerbation can range from mild to life-threatening (deadly).
As a rule, deterioration increases over several hours or days (type 1) - due to the formation of mucus plugs in the respiratory tract due to respiratory tract infections and insufficient anti-inflammatory therapy. Clinically, this is expressed by prolonged increasing obstruction with episodes of acute bronchospasms. This option is more common. However, sometimes the development of an attack occurs rapidly, literally in a few minutes (type 2), due to spasm of the smooth muscles of the bronchial wall. This option can occur in young patients due to contact with an allergen, psycho-emotional stress, and also due to taking pyrosolone-type drugs if they are intolerant (aspirin asthma). The prognosis for type 2 exacerbations is worse.
Careful monitoring of the patient's condition and the effect of the therapy is mandatory for successful treatment.
The severity of the exacerbation determines the amount of treatment. The degree of assistance that a patient can receive at home depends on the experience of the doctor and the patient, as well as on the availability of medications and instruments. Ideally, the level of PEF should be a measure of control over one’s well-being both in remission and in exacerbation.
Every asthma patient should have a plan that includes:
- clinical signs of deterioration, - measures of medication assistance.
Bronchodilators
To relieve mild and moderate exacerbations, short-acting β2-agonists are used (2-4 puffs every 20 minutes for an hour or through a nebulizer 5 mg of salbutamol, or 1 mg of fenoterol, or 20-40 drops of Berodual solution). Anticholinergics can be used as an alternative, since their effect is slower and weaker. According to research, in patients with bronchial asthma, the combined use of anticholinergics with β2-agonists provides a mutually reinforcing effect of these drugs and has a pronounced bronchodilator effect, especially in moderate and severe asthma, as well as in patients with asthma and concomitant chronic obstructive bronchitis. Such a combination drug containing ipratropium bromide and a short-acting β2-agonist is Berodual (ipratropium bromide + fenoterol). The mechanism of action of the β2-adrenergic agonist fenoterol is associated with the activation of adenylate cyclase coupled to the adrenergic receptor, which leads to an increase in the formation of cyclic adenosine monophosphate, which stimulates the calcium pump, and, as a consequence, to a decrease in the concentration of calcium in myofibrils and bronchodilation. Ipratropium bromide is a blocker of M-cholinergic receptors, eliminates bronchospasm associated with the influence of the vagus nerve, and when administered by inhalation causes bronchodilation, mainly due to local rather than systemic anticholinergic effects [7, 11, 13]. Does not have a negative effect on mucus secretion in the respiratory tract, mucociliary clearance and gas exchange. The addition of ACP to β2-agonists enhances their bronchodilation effect. Both active components of Berodual N (fenoterol and ipratropium bromide) relax the smooth muscles of the bronchi, acting on different targets, as a result of which their bronchodilator effect is enhanced. The combination of complementary components makes it possible to obtain a pronounced bronchodilator effect using half the dose of fenoterol (50 mcg) than in Berotek N, which minimizes the likelihood of undesirable effects (as a rule, they occur only with an overdose). Thanks to this, Berodual N can also be prescribed to patients with concomitant diseases of the cardiovascular system. The prescription of the drug Berodual for the relief of exacerbation of bronchial asthma is justified if patients have an altered β2 receptor (genetic abnormality of the β2 receptor, consisting in the replacement of Gly in the 16th position with Arg with the formation of the genotype b2-APB16 Arg/Arg receptor, insensitive to any β2-agonists); with a decrease in receptor β2 activity; with the phenomena of “night asthma” (a variant of asthma in which attacks of suffocation occur in the second half of the night against the background of bronchial obstruction caused by vagal activity).
Many patients with bronchial asthma prefer to use Berodual N to relieve symptoms. Of no small importance is the effect of the drug on the course of bronchial asthma with a predominant influence of the tone of the parasympathetic nervous system, the so-called. cholinergic asthma. Its features are the elderly age of patients (usually, but not always), increased sweating, hyperhidrosis of the palms, frequent combination with peptic ulcer disease, the predominance of attacks at night and in the morning, often a productive cough with mucous foamy sputum, a pronounced reaction to nonspecific provoking factors ( physical activity, cold air, strong odors), symptoms from the cardiovascular system - a tendency to bradycardia, hypotension and rhythm disturbances. For signs of “cholinergic asthma,” it seems optimal to use Berodual N, which affects the tone of the parasympathetic system and contains small doses of a short-acting β2-agonist. Berodual N is an effective drug in the treatment of bronchial asthma in combination with COPD [1, 2, 4, 7]. With exacerbation of bronchial asthma against the background of viral respiratory infections, a violation of the parasympathetic regulation of bronchial tone occurs, associated with receptor dysfunction, which makes the use of Berodual N justified when symptoms of obstruction appear. For bronchial asthma, Berodual N inhalations should not be recommended for continuous use as basic therapy. During the period of exacerbation, it is used as one of the first-choice drugs in combination with basic ICS therapy, and during the period of remission it can be used as needed to prevent bronchospasm caused by physical activity or contact with an allergen. 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. 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, which persisted for 3 months, and did not cause tachyphylaxis. Comparison of the results of both single use and long-term treatment with salbutamol and the combination of fenoterol hydrobromide/ipratropium bromide 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 in the need for additional inhaled bronchodilator) and higher patient compliance [13, 15—17].
Berodual N is available in the form of a metered-dose freon-free inhaler and a solution for nebulizer therapy. The Berodual N metered dose inhaler contains ipratropium bromide (20 mcg) and fenoterol hydrobromide (50 mcg) in one dose. When using it, side effects are less common because the dose of β2-agonist in this drug is half that of standard inhalers; in this case, the combination of two drugs potentiates the effect of each other. Fenoterol begins to act after 4 minutes, the maximum effect is observed after 45 minutes, the duration of action is 5–6 hours. The creators of Berodual regularly modify its release forms taking into account the requirements of the time. In accordance with modern environmental safety standards at the end of the 20th century. A new metered dose aerosol inhaler (MDI) Berodual N was developed, containing tetrafluoroethane as a propellant that is safe for the ozone layer. Numerous comparative studies of freon and freon-free MDI Berodual N have not revealed significant differences in their effectiveness and safety for patients [12]. It should also be noted that compliance is affected by the following features of the inhaler:
• the inhaler is compact, convenient to take with you (always at hand); • the device has been in use for a long time and does not cause difficulties in use by patients; • the inhaler is universal, used in the same device as most drugs for basic asthma therapy, which does not cause additional problems.
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. Berodual can also be used as a nebulizer solution [7]. The absolute indication for nebulizer therapy is the inability to deliver the drug into the respiratory tract with any other inhalation device. The recommended dose of Berodual immediately before use is diluted with isotonic sodium chloride solution to a volume of 3–4 ml and inhaled through a nebulizer for several minutes until the solution is completely consumed. 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 or are contraindicated with a metered dose inhaler (young children, elderly patients, etc.) [6, 10, 13, 15, 16]. Indications for the use of Berodual H 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 < 1 l or with a subjective preference for the nebulizer. 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 [18].
Long-term use of Berodual has shown its high effectiveness and safety, including in patients with concomitant diseases of the cardiovascular system. Side effects are extremely minor and occur mainly in case of overdose, and even in excessively high doses there are no cardiotoxic reactions. MDI Berodual H can be prescribed to children from 6 years of age, and Berodual H solution - from the first days of life, which indicates a high safety profile of the drug. Despite the emergence of new combinations of long-acting bronchodilators, this original combination drug has not lost its significance and firmly holds its place in the treatment of bronchial asthma.
Conclusion
The combination of pharmacological components provides Berodual N with:
• more pronounced and long-lasting bronchodilator effect than each of the components; • a wide range of indications, including bronchial asthma, chronic obstructive bronchitis and a combination of these diseases in one patient; • greater safety in concomitant cardiovascular pathology than monotherapy with β2-agonists; • convenience for patients and cost-effectiveness of treatment compared to the use of two separate aerosols; • the possibility of using the drug using both a metered aerosol and a nebulizer; • absence of tachyphylaxis with long-term use.
Literature
1. Avdeev S.N., Chuchalin A.G. Sympathomimetics for severe exacerbation of bronchial asthma. RMJ, 2000, 8 (4): 166–173. 2. Avdeev S.N. New freon-free technology of inhalation therapy. Consilium Medicum, 2005, 7: 1. Pulmonology: 27–30. 3. Global strategy for the treatment and prevention of bronchial asthma. M., 2011. 4. Petrov V.I. Drug therapy for bronchial asthma and chronic obstructive pulmonary disease: data from evidence-based medicine and real clinical practice. Clinical Medicine, 2012, 90, 3: 59-62. 5. Samoilenko V.A. The influence of different types of inhalation devices on the effectiveness of treatment of bronchial asthma. Atmosphere. Pulmonology and Allergology, 2012, 1: 6-10. 6. Tsoi A.N., Arkhipov V.V. Pharmacodynamics of inhaled bronchodilators used in a single dose via a nebulizer in patients with severe exacerbations of bronchial asthma. Ter. archive, 2002, 3: 17–21. 7. Shmelev E.I. Freon-free liquid inhalers in the treatment of obstructive pulmonary diseases. RMJ, 2002, 23: 1063–1065. 8. Federal clinical guidelines for the diagnosis and treatment of bronchial asthma. Russian Respiratory Society. M., 2013. https://www.pulmonology.ru/download/clinasthma22013.docx. 9. Asthma. Edited by F. Chung, L. M. Fabbri. Eur. Resp. Monograph., 8, monograph 23, 2003, 457. 10. High-dose inhaled versus intravenous salbutamol combined with theophylline in severe acute asthma. Swedish Society of Chest Medicine. Eur. Respira. J. 1990; 3: 163–70. 11. 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. 12. 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. 13. 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. 14. Miravitlles M. The overlap syndrome between asthma and COPD: implications for management. Hot Topics Respira. Med., 2011, 16: 15–20. 15. Rodrigo C, Rodrigo G. How often should beta-agonists be administered? Chest., 1998, 113: 1427–1428. 16. Shrewsbury S et al. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ, 2000, 320: 1368–1373. 17. Sorkness R, Bleecker E, Busse W et al. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. J. Appl. Physiol. 2008, 104: 94–03. 18. 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.
Source:
Medical Council, No. 16, 2014
Berodual® N
If shortness of breath (difficulty breathing) suddenly increases rapidly, you should consult a doctor immediately.
Hypersensitivity
After using BERODUAL®, immediate hypersensitivity reactions may occur, signs of which in rare cases may include: urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, anaphylactic shock.
Paradoxical bronchospasm
BERODUAL®, like other inhaled drugs, can cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm develops, the use of BERODUAL® should be stopped immediately and switched to alternative therapy
Long-term use:
— in patients suffering from bronchial asthma, BERODUAL® should be used only as needed;
- in patients with mild forms of chronic obstructive pulmonary disease, symptomatic treatment may be preferable to regular use;
- in patients with bronchial asthma, one should remember the need to carry out or intensify 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 β2-adrenergic agonists. such as BERODUAL®, to relieve bronchial obstruction can cause uncontrolled worsening of the disease. In case of increased bronchial obstruction, increasing the dose of β2-agonists, including BERODUAL®, more than recommended for a long time is not only not justified, but also dangerous. To prevent 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.
Other sympathomimetic bronchodilators should be co-administered with BERODUAL only under medical supervision.
Gastrointestinal disorders
In patients with a history of cystic fibrosis, gastrointestinal motility disorders are possible.
BERODUAL® should be used with caution in patients predisposed to acute-angle glaucoma. There are isolated reports of complications from the organ of vision (for example, increased intraocular pressure, mydriasis, angle-closure glaucoma, eye pain) that developed when inhaled ipratropium bromide (or ipratropium bromide in combination with β2-adrenergic receptor agonists) entered the eyes. Symptoms of acute angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo on objects and colored spots in front of the eyes in combination with corneal edema and redness of the eyes due to conjunctival vascular injection. If any combination of these symptoms develops, the use of eye drops that reduce intraocular pressure and immediate consultation with a specialist are indicated.
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 a nebulizer be inhaled through the mouthpiece. If there is no mouthpiece, a mask that fits tightly to the face should be used. Patients predisposed to developing glaucoma should take special care to protect their eyes.
Systemic effects
For the following diseases: recent myocardial infarction, diabetes mellitus with inadequate glycemic control, severe organic diseases of the heart and blood vessels, hyperthyroidism, pheochromocytoma or urinary tract obstruction (for example, prostatic hyperplasia or bladder neck obstruction).
BERODUAL® should be used only after a careful risk/benefit assessment, especially when using doses higher than recommended.
Effect on the cardiovascular system
In post-marketing studies, rare cases of myocardial ischemia have been reported when taking beta-agonists. Patients with concomitant serious heart disease (for example, coronary heart disease, arrhythmias or severe heart failure) receiving BERODUAL® should be warned to consult a doctor if they develop heart pain or other symptoms indicating worsening of heart disease. It is necessary to pay attention to symptoms such as shortness of breath and chest pain, as they can be of both cardiac and pulmonary etiology.
Hypokalemia
When using β2-agonists, hypokalemia may occur (see section "Overdose").
In athletes, the use of BERODUAL® due to the presence of fenoterol in its composition can lead to positive results of doping tests.
The drug contains a preservative, benzalkonium chloride, and a stabilizer, disodium edetate dihydrate. During inhalation, these components may cause bronchospasm in sensitive patients with airway hyperresponsiveness.
