Foradil combi capsules with powder for ing 12 200mkg N120
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Active ingredients
Budesonide + Formoterol
Release form
Capsules
Composition
Capsules with powder for inhalation transparent colorless, size No3, marked CG on the lid and FXF on the case or CG on the case and FXF on the lid in black ink; capsule contents - easily flowing white powder. 1 caps. formoterol fumarate dihydrate 12 mcg Auxiliary substances: lactose monohydrate - up to 25 mg. Composition of capsule shell: gelatin 100% - 49 mg. Capsules with powder for inhalation are hard gelatin, size No3, with a lid light pink color and colorless transparent body, with a printed image and the inscription BUDE 200, the contents of the capsules are white powder. 1 capsule capsules 200 mcg Auxiliary substances: lactose monohydrate - up to 24.77 mg. The composition of the capsule (cap): iron red oxide ( E172) - 0.086% m / m, titanium dioxide (E171) - 2% m / m, water - 15% m / m, gelatin - 83% m / m. The composition of the capsule shell (body): water - 14.5% m / m, gelatin - 85.5% m / m.
Pharmacological effect
A drug with anti-inflammatory and bronchodilatory effects. Formoterol Selective β2-adrenoreceptor agonist. It has a bronchodilator effect in patients with both reversible and irreversible airway obstruction. The action of the drug occurs quickly (within 1-3 minutes) and lasts for 12 hours after inhalation. With the use of the drug in therapeutic doses, the effect on the cardiovascular system is minimal and is noted only in rare cases. It inhibits the release of histamine and leukotrienes from mast cells. In animal experiments, some anti-inflammatory properties of formoterol were shown, such as the ability to inhibit the development of edema and the accumulation of inflammatory cells. Clinical studies have shown that the drug effectively prevents bronchospasm caused by inhaled allergens, exercise, cold air, histamine or methacholine. Since the bronchodilator effect of formoterol remains pronounced for 12 hours after inhalation, the administration of the drug 2 times / day for long-term maintenance therapy allows in most cases to provide the necessary control of bronchospasm in chronic lung diseases both during the day and at night. In patients with stable COPD Formoterol causes a rapid onset of a bronchodilator effect and an improvement in the quality of life parameters. BudesonideBudesonide is a GCS for inhalation use; adayuschim systemic action.Like other inhaled corticosteroids, budesonide has pharmacological effects by interacting with intracellular glucocorticoid receptors. Budesonide has anti-inflammatory, antiallergic and immunosuppressive effects. Increases the production of lipocortin, which is an inhibitor of phospholipase A2, inhibits the release of arachidonic acid, inhibits the synthesis of metabolites of arachidonic acid metabolism - cyclic endoperexia and prostaglandins. Warns neutrophil marginal accumulation, reduces inflammatory exudation and cytokine production, inhibits macrophage migration, reduces the severity of infiltration and granulation processes, the formation of chemotaxis substance (which explains the effectiveness in late allergy reactions); inhibits the release of inflammatory mediators from mast cells (immediate allergic reaction). Increases the number of active β-adrenoreceptors, restores the patient's response to bronchodilators, allowing them to reduce the frequency of their use, reduces swelling of the bronchial mucosa, mucus production, sputum formation and reduces airway hyperreactivity. Increases mucociliary transport. The therapeutic effect of the drug in patients requiring treatment of GCS develops on average within 10 days after the start of therapy. With regular use in patients with bronchial asthma, budesonide reduces the severity of chronic inflammation in the lungs, and thus improves pulmonary function, the course of bronchial asthma, reduces bronchial hyperreactivity and prevents exacerbations of the disease.
Pharmacokinetics
Formoterol Absorption After a single inhalation of formoterol fumarate at a dose of 120 mcg to healthy volunteers, formoterol was rapidly absorbed into the plasma, Cmax of formoterol in the plasma was 266 pmol / L and was achieved within 5 min after inhalation. In patients with COPD who received formoterol at a dose of 12 μg or 24 μg 2 times / day for 12 weeks, plasma formoterol concentrations, measured 10 minutes, 2 hours and 6 hours after inhalation, were in the ranges of 11.5–25.7 pmol / L and 23.3-50.3 pmol, respectively. In studies that examined the total excretion of formoterol and its (R, R) - and (S, S) -enantiomers with urine, it was shownthat the amount of formoterol in the systemic circulation increases in proportion to the inhalation dose (12-96 mcg). After inhalation use of formoterol at a dose of 12 mcg or 24 mcg 2 times / day for 12 weeks, the excretion of unchanged formoterol in the urine in patients with bronchial asthma increased by 63 -73%, and in patients with COPD - by 19-38%. This indicates some cumulation of formoterol in the plasma after repeated inhalations. It did not show a greater cumulation of one of the enantiomers of formoterol compared to others after repeated inhalations. Just as it was reported for other medicines used as inhalations, most of the formoterol used with the inhaler will be swallowed and then absorbed from Gastrointestinal tract. With the appointment of 80 μg of 3H-labeled formoterol, at least 65% of formoterol was absorbed by two healthy volunteers orally. The distribution of formoterol binding to plasma proteins is 61-64% (with albumin - 34%). In the range of concentrations observed after using the drug in therapeutic doses, saturation of binding sites is not achieved. Metabolism The main route of metabolism of formoterol is direct conjugation with glucuronic acid. Another metabolic pathway is O-demethylation followed by glucuronization. Secondary metabolic pathways include conjugation of formoterol with sulfate followed by deformation. Many isoenzymes are involved in the process of glucuronization (UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7 and 2B15) and O-demethylation (CYP2D6, CYP2C19, CYP2C9, CYP2A6) of formoterol, which is supposed to be in the same line, it is in the way to put the line, it is a line, it is a line that it is in the face of the line, and it is in the process of formathromol, but it is in the process of going into the line, or an isoenzyme involved in the metabolism of formoterol. At therapeutic concentrations, formoterol does not inhibit cytochrome P450 isoenzymes. Excretion In patients with bronchial asthma and COPD who received formoterol fumarate at a dose of 12 μg or 24 μg 2 times / day for 12 weeks, approximately 10% or 7% were respectively determined in the urine as unchanged formoterol. The calculated proportions of (R, R) - and (S, S) -enantiomers of unchanged formoterol in urine are 40% and 60%, respectively, after a single dose of formoterol (12-120 mcg) in healthy volunteers and after single and repeated doses of formoterol in patients with bronchial asthma. The active substance and its metabolites are completely excreted from the body: by the kidneys - 70%, through the intestines - 30%. Renal clearance of formoterol is 150 ml / min.T1 / 2 is 2-3 hours. In healthy volunteers, the final T1 / 2 of formoterol from plasma after a single inhalation at a dose of 120 mcg is 10 hours; the final T1 / 2 (R, R) - and (S, S) -enantiomers, calculated by excretion with urine, were 13.9 h and 12.3 h, respectively. Pharmacokinetics in special clinical situationsAfter weight correction, the pharmacokinetic parameters of formoterol in men and women There are no significant differences. The pharmacokinetics of formoterol in elderly patients aged 65 years and older has not been studied. In a clinical study in children aged 5-12 years with bronchial asthma, who received formoterol fumarate at a dose of 12 mcg or 24 mcg 2 times / day for 12 weeks, excretion unchanged In urine formoterol increased by 18-84% compared with the corresponding figure measured after the first dose. In clinical studies in children, about 6% of unchanged formoterol was determined in the urine. The pharmacokinetics of formoterol in patients with impaired liver and / or kidney function was not studied. Budesonide Absorption Budesonide is rapidly and completely absorbed after inhalation, while Cmax in the blood plasma is reached immediately after administration. After inhalation of budesonide, taking into account the sedimentation of the drug on the mucous membrane of the oropharynx, the absolute bioavailability is 73%. Absolute bioavailability when taking the drug inside is ± 10%. The distribution of Vd is 3 l / kg. Plasma protein binding - 88%. Systemic clearance of inhalation drug - 0.5 l / min. In experimental studies, budesonide accumulated in the spleen, lymph nodes, thymus, adrenal cortex, reproductive organs, and bronchi, and also penetrated the placental barrier. MetabolismBudesonide is not metabolized in the lungs. After absorption, the drug is almost completely (about 90%) metabolized in the liver with the formation of several inactive metabolites (biological activity is 100 times less compared to budesonide), including 6β-hydroxybudesonide and 16α-hydroxyprednisolone (systemic clearance - 1.4 l / min). Budesonide has a high systemic clearance - 84 l / h and a short T1 / 2 - 2.8 h. The main metabolic pathway of budesonide in the liver using the CYP3A4 isoenzyme of the P450 system can be altered by the effect of inhibitors or inducers of CYP3A4.Excreted through the intestine in the form of metabolites - 10%, kidneys - 70%. Pharmacokinetics in special clinical situations. The concentration of budesonide in the blood plasma increases in patients with liver disease. The pharmacokinetics of budesonide in children and adolescents has not been studied. However, data on other inhalants containing budesonide suggest that the clearance of budesonide in children over 3 years old is approximately 50% higher than in adult patients.
Indications
Bronchial asthma: - inadequately controlled by inhaled GCS and short-acting beta2-agonists as an on-demand therapy; - adequately controlled by inhaled GCS and long-acting beta2-agonists. Chronic obstructive pulmonary disease (COPD) (with proven effectiveness of GCS).
Contraindications
- lactation period (breastfeeding); - active pulmonary tuberculosis; - hereditary galactose intolerance, severe lactase deficiency and glucose-galactose absorption disorder; - children under 6 years old; - hypersensitivity to formoterol, budesonide, or any other component of the drug. extreme caution when using formoterol (especially in terms of dose reduction) and careful monitoring of patients is required in the presence of the following comorbidities: coronary artery disease; heart rhythm and conduction disturbances, especially AV degree III blockade; severe chronic heart failure; idiopathic subvalvular aortic stenosis; hypertrophic obstructive cardiomyopathy, aortic aneurysm; thyrotoxicosis; known or suspected lengthening of the QT interval (QT corrected more than 0.44 sec), hypokalemia, hypocalcemia and pheochromocytoma. Considering the hyperglycemic effect characteristic of beta-adrenomimetics, including formoterol, in patients with diabetes mellitus it is recommended that additional regular monitoring of glucose concentration in blood be recommended. relieving acute bronchospasm, the drug should not be prescribed as the main therapy for asthmatic status or other acute asthmatic conditions caution should be exercised when using budesonide in patients with inactive pulmonary tuberculosis, with fungal, bacterial and viral infections of the respiratory tract, cirrhosis of the liver, glaucoma.Also, given the possibility of the development of fungal infections, it is necessary to prescribe the drug with caution in bronchiectasis and pneumoconiosis. Capsules formoterol and budesonide contain lactose.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
Formoterol The safety of using Foradil Kombi during pregnancy and lactation has not yet been established. Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. Formoterol, as well as other beta2-adrenomimetics, can slow down the process of childbirth due to tocolytic action (relaxing action on the smooth muscles of the uterus). It is not known whether formoterol is excreted in human breast milk. While taking Foradil Kombi, breastfeeding should be discontinued. Budesonid In experimental animal studies, the possible teratogenic effect of GCS on the fetus was revealed. There is no data on the teratogenic effect of budesonide or whether the drug has reproductive toxicity when used in humans. Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. If necessary, the treatment of GCS during pregnancy, they are preferably prescribed in the form of inhalation, because GCS for inhalation use have a less systemic effect compared with oral GCS. It is not known whether budesonide is excreted in human breast milk. Perfume There are no data on the effect of the drug on fertility.In experimental animal studies, no effect on fertility was found when orally using formoterol and subcutaneous injection of budesonide.
Dosage and administration
Formoterol and budesonide are intended for inhalation use. Drugs are capsules with powder for inhalation, which should be used only with a special device - an aerolizer, which is included in the package. Formoterol and budesonide should be prescribed individually, in the minimum effective dose. consider the possibility of gradually reducing the dose of the drug. Reducing the dose of formoterol is carried out under regular medical supervision of the patient. Against the background of exacerbation of asthma should not begin treatment with formoterol or change the dosage of the drug. Formoterol should not be used to relieve acute attacks of bronchial asthma. When a patient is prescribed therapy with an inhalation device, the dose should be gradually adjusted (titrated) to doses sufficient to maintain a therapeutic effect. Budesonide + formoterol respiratory tract and enhances its therapeutic effect. Therefore, for maintenance therapy of bronchial asthma and COPD, inhalation of formoterol is first carried out, then inhalation of budesonide. The dose of formoterol for regular maintenance therapy is 12-24 μg (contents of 1-2 capsules) 2 times / day. Do not exceed the maximum recommended dose of the drug for adults (48 mcg / day). Considering that the maximum daily dose of formoterol is 48 mcg, if necessary, you can additionally use 12-24 mcg / day to relieve symptoms of bronchial asthma. If the need to use additional doses of the drug ceases to be episodic (for example, it becomes more often than 2 days a week), the patient should be advised to consult with a physician regarding the revision of therapy, since this may indicate a worsening of the course of the disease. The minimum dose of the drug in a single capsule is 200 micrograms. The drug is not prescribed, if you want to use a single dose of less than 200 mg.In adult patients with mild asthma, treatment can be started at the minimum effective dose of 200 mcg / day. The maintenance dose of budesonide for adult patients is 400-800 mcg / day in 2 doses (200-400 mcg 2 times / day). With exacerbation of asthma during the transfer from oral GCS to inhalation or with a decrease in the dose of oral GCS, budesonide can be administered in a dose of 1600 mcg / day in 2-4 doses. Children aged 6 years and older. budesonide in the airways and enhances its therapeutic effect. Therefore, for the maintenance treatment of bronchial asthma, first inhalation of formoterol is carried out, then inhalation of budesonide. The dose of formoterol for regular maintenance therapy is 12 mcg 2 times / day. The maximum recommended dose of the drug is 24 mg / day.2. Treatment of children with mild asthma begins with a dose of 200 mg / day. The dose of budesonide for regular maintenance therapy is 100-200 mcg 2 times / day. If necessary, the dose of budesonide can be increased to a maximum of 800 μg / day. Due to the lack of clinical experience in children under 6 years of age, budesonide should not be used in this age group. Patients with impaired renal functionData on the need for dose adjustment in patients with impaired renal function not received. Based on the pharmacokinetics of budesonide for oral administration, it is unlikely that these patients may have clinically significant systemic effects of the drug. Patients with impaired liver function There is no evidence of the need for dose adjustment in patients with impaired liver function. But budesonide is metabolized mainly in the liver. Therefore, the drug should be used with caution in patients with severely impaired liver function. Patients with mild or moderate hepatic impairment are unlikely to significantly change the effects of the drug, taking into account the pharmacokinetic parameters for budesonide for oral administration. Elderly patients (over 65 years) Data on the need for dose adjustment in patients over 65 years of age, compared with younger patients , not received. Rules of inhalation In order to ensure the correct use of drugs,the doctor or other medical professional must show the patient how to use the inhaler; explain to the patient that it is necessary to use capsules with powder for inhalation only with the help of an airliser; warn the patient that the capsules are intended for inhalation use only and are not intended for ingestion. In children and adolescents inhalation of budesonide and formoterol should be carried out under the supervision of adults. It is necessary to make sure that the child correctly performs the inhalation technique. It is important for the patient to understand that due to the destruction of the gelatin capsule, small pieces of gelatin can be inhaled through the mouth by mouth or throat. In order to minimize this phenomenon, you should not pierce the capsule more than 1 time. Remove the capsule from the blister pack immediately before use. . There are separate reports of patients accidentally swallowing capsules of the preparation as a whole. Most of these cases are not associated with the development of adverse events. The health care provider should explain to the patient how to use the drug correctly, especially if the patient does not improve breathing after inhalation. Instructions for the use of an aerolizer1. Remove cap from airliner.2. Hold the aerolizer firmly by the base and turn the mouthpiece in the direction of the arrow. Place the capsule in the cell located at the base of the aerolizer (it has the shape of a capsule). It should be remembered that the capsule should be removed from the blister pack immediately before the inhalation. Turning the mouthpiece, close the airliner.5. Holding the aerolizer in a strictly upright position, push the blue buttons on the sides of the aerolizer once to the end. Then let them go. At this stage, when the capsule is punctured, it can collapse, as a result of which small pieces of gelatin can get into the mouth or throat. Since gelatin is edible, it causes no harm. In order for the capsule not to collapse completely, the following requirements should be fulfilled: do not pierce the capsule more than once; follow the rules of storage; remove the capsule from the blister only immediately prior to inhalation.Make a full exhalation. Take the mouthpiece in your mouth and slightly tilt your head back. Grip the mouthpiece tightly with your lips and take a quick, even, deep breath. In this case, the patient should hear the characteristic rattling sound created by rotating the capsule and spraying the powder. If there was no characteristic sound, then you need to open the airliner and see what happened to the capsule. Perhaps she was stuck in a cell. In this case, you need to carefully remove the capsule. In no case do not try to free the capsule by repeated pressing the buttons on the sides of the aerolizer. If a characteristic sound is heard when inhaled, you should hold your breath as long as possible. At the same time, remove the mouthpiece from the mouth. Then exhale. Open the aeroliser and see if there is any powder remaining in the capsule. If powder remains in the capsule, repeat the steps described in paragraphs 6-8.9. After the end of the inhalation procedure, open the aerolizer, remove the empty capsule, close the mouthpiece and close the aerolizer with a cap. To remove any remaining powder, wipe the mouthpiece and cell with a dry cloth. You can also use a soft brush.
Side effects
The adverse reactions reported in clinical trials are distributed according to the frequency of occurrence. The following criteria were used to estimate the frequency: very often (≥1 / 10); often (from ≥1 / 100, less than 1/10); infrequently (≥1 / 1000, less than 1/100); rarely (≥1 / 10,000, less than 1/1000); very rarely (less than 1/10 000), including individual messages. Within each group, undesirable reactions are distributed in order of decreasing significance. Formoterol Allergic reactions: very rarely - hypersensitivity reactions, such as arterial hypotension, urticaria, angioedema, pruritus, rash. insomnia. From the nervous system: often - headache, tremor; infrequently - dizziness; very rarely - taste disorders. From the cardiovascular system: often - a feeling of heartbeat; infrequently - tachycardia; very rarely - peripheral edema. From the respiratory system: infrequently - bronchospasm, including paradoxical, irritation of the pharyngeal mucosa and larynx. From the digestive system: rarely - dryness of the oral mucosa; very rarely - nausea. From the musculoskeletal system: infrequently - muscle spasm, myalgia. Adverse reactions according to post-marketing observations in the appointment of formoterol (Foradil) Laboratory and instrumental data: hypokalemia,hyperglycemia, prolongation of the QT interval (during ECG), increased blood pressure (including hypertension). On the respiratory system: cough. On the skin and subcutaneous tissues: rash. On the cardiovascular system: angina, arrhythmias, in t . h. atrial fibrillation, ventricular extrasystoles, tachyarrhythmia. Budesonides Endocrine system: rarely - suppression of the adrenal cortex, Cushing's syndrome, hypercorticism, growth retardation in children and adolescents. From the organ of vision: rarely - cataract, glaucoma. Allergic reactions: rarely, it is rarely; , rash, urticaria, angioedema, pruritus, contact dermatitis (delayed-type hypersensitivity reaction IV). On the psyche: postmarketing observations - psychomotor hyperactivity, n sleep disturbances, anxiety, depression, aggressive behavior, behavioral disorders (especially in children). From the musculoskeletal system: rarely - a decrease in bone mineral density. From the respiratory system: often - cough; rarely, paradoxical bronchospasm, candidiasis of the mucous membranes of the oral cavity and larynx, pharyngeal irritation, dysphonia, disappearing after cessation of budesonide therapy or dose reduction. In a three-year clinical study, the use of budesonide in patients with COPD showed an increase in the incidence of subcutaneous hematomas (10%) and pneumonia (6%) compared with the placebo group (4% and 3%, for patients less than 0.001 and others less than 0.01, respectively).
Overdose
FormoterolSimptomy: overdose of formoterol can be expected to lead to a phenomenon characteristic of superfluous actions of other beta2-agonists, such as nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia, hypertension. Treatment: shown to support and symptomatic therapy. In serious cases, hospitalization is necessary. The use of beta-blockers can be considered, but only under the condition of extreme caution and under close medical supervision, since the use of such agents may cause bronchospasm. BudesonidesBudesonide has low acute toxicity.A single inhalation of a large amount of the drug can lead to a temporary suppression of the function of the hypothalamic-pituitary-adrenal system, which does not require emergency therapy. With an overdose of budesonide, treatment can be continued in doses sufficient to maintain a therapeutic effect.
Interaction with other drugs
Formoterol Formoterol (as well as other beta2-adrenostimulyatory) should be used with caution in patients receiving drugs such as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, macrolides, MAO inhibitors, tricyclic antidepressants, as well as other drugs known about they lengthen the QT interval, because in these cases, the effect of adrenostimulyatorov on the cardiovascular system may increase. When using drugs that can lengthen the QT interval, the risk of ventricular arrhythmias increases. Simultaneous use of other sympathomimetic drugs may aggravate the side effects of formoterol. Simultaneous use of xanthine derivatives, GCS or diuretics may increase the potential hypokalemic effect of beta2-adrenostimuly. with the use of halogenated hydrocarbons, the risk of arrhythmias increases. Beta-blockers can weaken s effect of formoterol. In this regard, it is not necessary to prescribe formoterol together with beta-blockers (including eye drops), unless the use of this combination of drugs is not forced by any extraordinary causes. Budesonide Use of the drug with CYP3A4 inhibitors (for example, itraconazole, ketoconazole, ritonavir, non-finamin , amiodarone, clarithromycin) can lead to a decrease in the metabolism of budesonide and an increase in its systemic concentration. When prescribing budesonide together with CYP3A4 inhibitors, it is necessary to regularly monitor the function of the adrenal cortex and, if necessary, change the dose of budesonide. , estrogens enhance the effect of budesonide.
special instructions
FormoterolIt is shown that the use of formoterol improves the quality of life of patients with COPD. Formoterol belongs to the class of long-acting beta2-adrenomimetics. Against the background of the use of another beta2-adrenergic long-acting, salmeterol, there was an increase in the frequency of deaths associated with bronchial asthma (13 of 13,176 patients) compared with placebo (3 of 13,179 patients). No clinical studies have been conducted to assess the incidence of deaths associated with bronchial asthma against the use of formoterol. Anti-inflammatory therapy Formoterol should be used only as an additional treatment in patients with bronchial asthma with insufficient control of symptoms against inhaled corticosteroids monotherapy or in case of severe disease requiring the use of an inhaled corticosteroid and a long-acting β2-adrenoreceptor agonist. Formoterol should not be administered in conjunction with other long-acting β2-adrenoreceptor agonists. When prescribing formoterol, it is necessary to assess the condition of the patients regarding the adequacy of the anti-inflammatory therapy they receive. After initiation of treatment with formoterol, patients should be advised to continue the anti-inflammatory therapy unchanged, even if there will be an improvement. For the relief of an acute attack of bronchial asthma, short-acting beta2-adrenoreceptor agonists should be used. With a sudden deterioration, patients should immediately seek medical help. Severe exacerbations of bronchial asthma In clinical studies with formoterol, there was a slight increase in the incidence of severe exacerbations of bronchial asthma compared with placebo, especially in children 6-12 years of age. In placebo-controlled clinical studies in patients who received formoterol for 4 weeks, there was an increase in the incidence of severe exacerbations of bronchial asthma (0.9% with a dosing regimen of 10-12 mcg 2 times / day, 1.9% - at 24 mcg 2 times / day) compared with the placebo group (0.3%), especially in children 6-12 years old. In two large controlled clinical trials that included 1095 adult patients and children from 12 years and older, severe exacerbations of asthma (requiring hospitalization) were more often observed in patientsreceiving formoterol in a dose of 24 mg 2 times / day (9/271, 3.3%), compared with the formoterol groups in a dose of 12 mg 2 times / day (1/275, 0.4%), placebo (2/277, 0.7%) and albuterol (2/272, 0.7%). When using formoterol for 16 weeks in another large clinical study, which included 2085 adult patients and adolescents, there was no increase in the incidence of severe exacerbations of bronchial asthma, depending on the dose of formoterol. However, in this study, the incidence of severe exacerbations was higher in the formoterol group (with a dosing regimen of 24 mcg 2 times / day - 2/527, 0.4%, with 12 mcg 2 times / day - 3/527, 0.6%) compared with placebo (1/517, 0.2%). In from