Formoterol

The drug Formoterol is intended for inhalation use in adults and children aged 6 years and older. Formoterol is not intended for oral administration.

The dose of Formoterol is selected individually depending on the needs of the patient. The lowest dose that provides a therapeutic effect should be used. When control of bronchial asthma symptoms is achieved during therapy with Formoterol, it is necessary to 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’s condition.

The drug Formoterol is a capsule with powder for inhalation, which should be used only with the help of a special device that is included in the package.

Adults

Bronchial asthma

The dose of the drug for regular maintenance therapy is 12-24 mcg (contents of 1-2 capsules) 2 times a day.

The drug Formoterol should be used only as additional therapy to inhaled glucocorticosteroids.

The maximum recommended dose of the drug for adults (48 mcg per day) should not be exceeded.

Considering that the maximum daily dose of Foradil is 48 mcg, if necessary, an additional 12-24 mcg per day can be used to relieve the symptoms of bronchial asthma. If the need for additional doses of the drug ceases to be episodic (for example, becomes more often than 2 days a week), the patient should consult a doctor to review therapy, as this may indicate a worsening of bronchial asthma.

Against the background of exacerbation of bronchial asthma, you should not start using or change the dose of Foradil. The drug should not be used to relieve acute attacks of bronchial asthma.

Prevention of asthma attacks caused by an allergen or physical activity

15 minutes before the expected contact with the allergen or before the load, 12 mcg of the drug (contents of 1 capsule) should be used. Patients with a history of severe bronchospasms may require inhalation of the contents of 2 capsules (24 mcg) for prevention.

For COPD, the dose of the drug for regular maintenance therapy is 12-24 mcg (contents of 1-2 capsules) 2 times a day.

COPD

The dose of the drug for regular maintenance therapy is 12-24 mcg (contents of 1-2 capsules) 2 times a day.

Children aged 6 years and older

The maximum recommended dose of formoterol is 24 mcg per day.

Bronchial asthma

The dose of the drug for regular maintenance therapy is 12 mcg 2 times a day. The drug Foradil should be used only as additional therapy to inhaled glucocorticosteroids.

In children from 6 to 12 years of age, it is recommended to use combination drugs containing an inhaled glucocorticosteroid and a long-acting β2-adrenergic receptor agonist, except in cases where their separate use is necessary.

The drug should not be used to relieve acute attacks of bronchial asthma. To stop an acute attack, it is necessary to use short-acting β2-adrenergic receptor agonists.

Prevention of asthma attacks caused by an allergen or physical activity

15 minutes before expected contact with the allergen or before exercise, a dose of 12 mcg of formoterol (contents of 1 capsule) should usually be administered.

Elderly patients (over 65 years old)

There is no data available on the necessary dose adjustment of formoterol in patients over 65 years of age, as well as in patients with impaired renal or hepatic function when prescribing the recommended dosage of the drug.

Instructions for using the inhaler:

1. Remove the protective cap from the inhaler.

2. Grasp the middle of the mouthpiece and the base of the inhaler, rotate the mouthpiece in the direction indicated by the arrow on the body, and open the capsule compartment in the base of the inhaler.

3. With dry hands, take one capsule and place the capsule into the capsule compartment.

Attention! Do not insert capsules directly into the mouthpiece opening. Do not swallow!

4. Close the mouthpiece by rotating it in the opposite direction of the arrow, keeping the inhaler upright.

5. While holding the inhaler upright, press the buttons at the base of the inhaler and puncture the capsule. Release the buttons.

6. Exhale completely, place the inhaler in your mouth, tightly wrapping your lips around the mouthpiece. Take a deep breath.

Attention! Do not press buttons or block air inlets.

7. Remove the mouthpiece from your mouth and hold your breath as long as possible. Then exhale.

Attention! Do not exhale through the mouthpiece!

8. Open the capsule compartment: grab the middle of the mouthpiece and the base of the inhaler, turn the mouthpiece in the direction indicated by the arrow on the body.

9. Remove the capsule shell and visually check for punctures and powder inside the capsule.

If the capsule is not punctured and contains powder, repeat the procedure starting from step 3.

If the capsule is punctured but not empty, reinsert the capsule into the capsule compartment and repeat the procedure from step 6. Do not press the button again!

If the capsule is empty, throw it away.

10. After use, if necessary, wipe the mouthpiece with a dry cloth, close the mouthpiece and put on the protective cap.

Formoterol-native, 12 mcg, capsules with powder for inhalation, 30 pcs.

Anti-inflammatory therapy

In patients with bronchial asthma, native Formoterol should be used only as an additional treatment in cases of insufficient control of symptoms during monotherapy with inhaled corticosteroids or in severe forms of the disease requiring the use of a combination of inhaled corticosteroids and a long-acting β2-adrenergic agonist. Formoterol native should not be used with other long-acting β2-adrenergic receptor agonists.

When prescribing the drug Formoterol-native, it is necessary to assess the condition of patients regarding the adequacy of the anti-inflammatory therapy that they receive. After starting treatment with Formoterol-native, patients should be advised to continue anti-inflammatory therapy without changes, even if improvement is noted.

To relieve an acute attack of bronchial asthma, β2-adrenergic receptor agonists should be used. If the condition suddenly worsens, patients should seek medical help immediately.

Hypokalemia

A consequence of therapy with beta2-agonists, including Formoterol-native, may be the development of potentially serious hypokalemia. Hypokalemia may increase the risk of developing arrhythmias. Because This effect of the drug Formoterol-native can be enhanced by hypoxia and concomitant treatment; special caution should be observed in patients with severe bronchial asthma. In these cases, regular monitoring of serum potassium concentration is recommended.

Paradoxical bronchospasm

Like other inhaled drugs, Formoterol native can cause paradoxical bronchospasm. In this case, the drug should be discontinued immediately and alternative treatment should be prescribed.

The use of formoterol in a dose exceeding 54 mcg/day (more than 4 inhalations) may lead to positive doping tests.

Influence on the ability to drive motor vehicles and other vehicles, to work with moving mechanisms

There are no data on the effect of the drug Formoterol-native on the ability to drive vehicles and operate machinery. In the event of the development of such adverse reactions as dizziness, tremors, convulsions or muscle spasms, it is necessary to refrain from driving vehicles and operating machinery, as well as from engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Contraindications

Allergic reactions to the components of the drug.
Children under 6 years of age.
Lactation.
intolerance , glucose-galactose malabsorption lactase deficiency .

It is recommended to use the drug with caution in case of decompensation of chronic cardiac failure, arrhythmias and tachyarrhythmias, third degree atrioventricular block, coronary heart disease , increased QT interval on the ECG , obstructive hypertrophic cardiomyopathy, arterial hypertension, aneurysm, diabetes mellitus, pheochromocytoma, thyrotoxicosis.

Interaction

It is not recommended to combine formoterol with MAO inhibitors, adrenomimetic agents, tricyclic antidepressants , since the risk of adverse reactions from the circulatory system increases.

When used together, glucocorticosteroids, xanthine derivatives, and diuretics increase the likelihood of a hypokalemic effect from taking the drug.

Beta blockers (including eye drops) can partially or completely stop the effects of formoterol .

When using Quinidine, Procainamide, Disopyramide, phenothiazines, tricyclic antidepressants, and antihistamines together, ventricular arrhythmias increases .

Formoterol: effectiveness and safety in the treatment of chronic obstructive pulmonary diseases

Formoterol is a moderately lipophilic drug. Its action begins within 1–3 minutes. The duration of action reaches 12 hours. It has a dose-dependent effect; the higher bronchoprotective activity of formoterol is not accompanied by an increase in side effects.

Mechanism of action of β2-agonists

The pharmacological effects of β2-agonists are mediated through stimulation of β2-adrenergic receptors. Receptors of this subtype are widely distributed in the smooth muscles of the bronchi, on the surface of mast cells and eosinophils T-lymphocytes, in skeletal muscles, the uterus and the liver. When the β2-agonist molecule interacts with the receptor, a change in the conformation of the receptor occurs, which leads to an increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP), activation of protein kinase A and a decrease in the intracellular concentration of calcium ions, and this promotes relaxation of bronchial smooth muscle. The density of β2-adrenergic receptors on cell membranes increases as the diameter of the bronchi decreases.

Spectrum of action of β2-agonists:

bronchodilator effect (by influencing β-receptors of bronchial smooth muscle);
antiallergic effect (suppress the release of histamine induced by allergen exposure, as they stabilize mast cell membranes to some extent);
influence on the function of the bronchial epithelium and improvement of mucociliary clearance (activate the function of the ciliated epithelium, increasing the movement of cilia, which improves mucociliary transport);
decreased synthesis of leukotrienes;
decreased capillary permeability;
potentiation of long-acting β2-agonists (LABAs), and in particular formoterol, the effects of glucocorticosteroids.

Similarities and differences between long-acting β2-agonists

Currently, the LABA group is represented by two inhaled drugs: salmeterol and formoterol. Despite belonging to the same class, there are certain differences between them that must be taken into account when treating chronic obstructive pulmonary diseases. The onset and duration of action of β2-agonists is related to the size of the molecule and its physicochemical properties. Drugs have different lipophilicities, and this difference determines the characteristics of the drugs' action. According to the microkinetic diffusion theory proposed by GP Anderson, salbutamol, being a short-acting β2-agonist, due to its small molecular size and hydrophilicity, interacts with the receptor through the aqueous phase after 1–5 minutes, which explains the rapid onset of action. But the duration of its action does not exceed 4–6 hours due to rapid leaching from the receptor zone. Salmeterol has a long molecule and is 10,000 times more lipophilic than salbutamol. Salmeterol quickly penetrates into the lipophilic region of the cell membrane and then diffuses through this layer to the receptor, which provides a long-lasting (12 hours) effect of the drug, but its bronchodilator effect occurs much more slowly (on average after 20-30 minutes). Unlike salmeterol, formoterol is a moderately lipophilic drug that can quickly interact with the receptor, so its action begins within 1–3 minutes. At the same time, it penetrates into the lipophilic region of the membrane, from where it is gradually released to re-interact with the active site of the receptor, due to which its duration of action reaches 12 hours.

Salmeterol at a dose of more than 100 mcg does not have a dose-dependent effect; its use is not permitted during exacerbation of asthma, since it can lead to the development of paradoxical bronchoconstriction with increasing doses, as well as in combination with short-acting β2-agonists. Formoterol, having a unique intermediate lipophilicity, also has a dose-dependent effect over the entire range of doses used. Recent studies have shown that formoterol extremely rarely causes reactions of paradoxical bronchoconstriction, is a full β2-agonist, and does not have an antagonistic effect in relation to short-acting β2-agonists and a significant influence on their effects, which is of great clinical importance in situations involving combined taking long- and short-acting adrenergic agonists. In vitro studies have shown that formoterol relaxes smooth muscle by 85%, and salmeterol by only 65%. Also, in an in vitro study, spasmodic muscle relaxes faster with the addition of formoterol than with salmeterol. A number of authors believe that incomplete relaxation of smooth muscles can aggravate the inflammatory process in the bronchial mucosa.

Thus, it should be noted once again that the higher bronchoprotective activity of formoterol is not accompanied by an increase in side effects. This property is important to emphasize, since the pharmacological feature of formoterol is a pronounced and proven dose-dependent effect, i.e. As the dose increases, additional bronchodilation occurs. The combination of rapid effect and the possibility of multiple dosing made it possible to conduct appropriate clinical studies and recommend additional use of this drug if additional bronchodilator effect is needed. Salmeterol should be used in doses no higher than 100 mcg and only as a basic therapy drug, since increasing the dose of salmeterol above 100 mcg does not provide a pronounced bronchodilator effect, but increases the risk of developing side effects characteristic of this class of drugs. These differences in the pharmacological properties of the compared drugs may explain why some patients do not respond sufficiently to salmeterol therapy, but maintain a response to formoterol.

Thus, formoterol is a potent β2-agonist with a 12-hour action. This drug is characterized by a unique combination of pharmacological properties:

high efficiency and β2-selectivity, which provides a unique safety profile of the drug;
rapid onset of action (within 1–3 minutes);
duration of effect for 12 hours;
the absence of an antagonistic effect in relation to short-acting β2-agonists and a significant influence on their effects, which is of great clinical importance in situations involving the combined use of long- and short-acting adrenergic agonists;
lack of accumulation in therapeutic doses.

Combination of inhaled glucocorticosteroid and formoterol (Foradil Combi) in the basic therapy of bronchial asthma

Modern guidelines for the treatment of bronchial asthma (BA) recommend using a combination of inhaled glucocorticosteroid (ICS) and LABA in the treatment of patients with moderate and severe BA. Studies have shown that adding a LABA to low, medium, or high doses of ICS provides greater asthma control than doubling the dose of corticosteroids. This is explained by the sparring effect of LABA and ICS. The data available today allow us to consider these classes of drugs as synergists, since they enhance each other’s effects at the molecular and receptor levels. β2-agonists provide an increase in nuclear translocation of the ICS + receptor complex, while in the presence of LABA, lower doses of ICS are required to activate the receptor. Thus, the anti-inflammatory effect is achieved with half the dose of ICS. In turn, the presence of ICS ensures a high density of β-receptors on the membrane of target cells, preventing the development of the “down” regulation phenomenon. Doctors should remember that the phenomenon of “down” regulation of β-receptors can lead to serious consequences for patients, including the development of asthmatic conditions. Analysis of many clinical trials has shown that the addition of a LABA to various doses of ICS is superior to doubling the dose of ICS in reducing symptoms, improving respiratory function, and reducing the use of medications to relieve symptoms.

S. Mitchell et al. conducted a study to confirm the effectiveness of combination therapy, in particular the combination of ICS and Foradil, in patients who require high doses of ICS. In addition to efficacy indicators, safety indicators were also assessed. Evidence has been obtained that combination therapy not only improves respiratory function and reduces asthma symptoms, but also does not potentiate the suppression of the pituitary-adrenal system, in contrast to the prescription of higher doses of ICS.

In June 2010, the US Food and Drug Administration (FDA), based on safety data, updated recommendations for the use of LABAs in the treatment of asthma. The FDA has confirmed the benefits of LABAs for improving asthma symptoms when used in accordance with current clinical guidelines and prescribing information.

Current FDA recommendations for the use of LABAs include the following:

the use of LABA as monotherapy without combination with a drug that controls the course of asthma (for example, ICS) in the treatment of asthma is contraindicated;
LABAs should not be used in patients whose asthma is controlled by low to moderate doses of ICS;
LABAs should only be used as adjunctive therapy for the treatment of asthma whose symptoms are not adequately controlled by ICS;
When asthma control is achieved with regular medical supervision, the dose of LABA should be gradually reduced (up to complete discontinuation) and, if possible (without loss of control), treatment with drugs that control the course of asthma, such as ICS, should be continued in children and adolescents who require the addition of LABA to ICS , fixed combinations containing both components should be used to ensure compliance with the prescribed treatment.

Currently, a new drug Foradil Combi has appeared in the form of a free combination of formoterol in a dose of 12 mcg and budesonide in doses of 200 mcg and 400 mcg, taken using one inhaler - an Aerolyzer. According to clinical studies, the use of Foradil Combi improves the level of asthma control: the severity of daytime and nighttime symptoms, the need for emergency medications is reduced, the number of unscheduled visits for emergency medical care is reduced, and pulmonary function indicators improve.

The method of using Foradil Combi is physiological. Pre-inhalation of a formoterol capsule (12 mcg) has a bronchodilator effect during the first 3 minutes, during which time the patient replaces the used bronchodilator capsule with a budesonide capsule (200 or 400 mcg). The patient inhales budesonide after the onset of bronchodilation, which improves the intake and distribution of budesonide in the respiratory tract.

Formoterol (Foradil), like other drugs with a prolonged sympathomimetic effect, has found wide use in the treatment of COPD. Formoterol has been shown to provide long-term bronchodilation, combining rapid relief and long-term control, and controls bronchial patency in both reversible and partially reversible obstruction. Having an effect on improving mucociliary transport and an anti-edematous effect, the drug is also used in patients with irreversible obstruction. Patients suffering from COPD note good tolerability and effectiveness of treatment. Patients with COPD are usually middle-aged and elderly, and therefore the high cardiovascular safety of formoterol is of particular importance. In clinical studies, a small percentage of discontinuation of Foradil therapy was noted due to adverse events or low effectiveness of therapy.

Thus, Formoterol improves control over the course of the disease, improves the quality of life in COPD, reduces the number of “unfavorable days”, increases exercise tolerance, increases the interval between exacerbations, and helps alleviate the symptoms of the disease.

Safety profile of β2-agonists

Despite the fact that β2-agonists are highly selective drugs and their activity is mainly associated with stimulation of bronchial β2 receptors, excessive doses may have negative effects on other organs and systems. Since β2 receptors can be found in various tissues, for example, in the left ventricle, in the right atrium, where they make up 26% of all receptors, their increased stimulation can cause tachycardia, myocardial ischemia and even rhythm disturbances up to atrial flutter. Stimulation of β2 receptors in blood vessels also causes tachycardia in response to a decrease in diastolic pressure. Metabolic changes, such as hypokalemia, can lead to prolongation of the QT interval, which in turn predisposes to the development of cardiac arrhythmias. Stimulation of β2 receptors in skeletal muscle causes tremor. In patients with diabetes mellitus, additional glycemic control is recommended. These side effects are common to all β2-agonists, both long-acting and short-acting, but they are quite rare. Since patients with asthma, and especially COPD, have changes not only in the respiratory system, but also in other organs and systems - the heart, skeletal muscle and blood vessels - monitoring the safety of β2-agonists should include analysis of ECG data, primarily the QT interval, as well as serum potassium and glucose levels. This is especially important to consider in patients with COPD who exceed recommended doses and use particularly short-acting β2-agonists uncontrolled.

Drug interactions

Specific side effects may be increased when used together with other sympathomimetics. The effect of formoterol may be reduced by β-blockers. The simultaneous administration of xanthines, corticosteroids, and diuretics may enhance the potential hypokalemic effect of the drug. When prescribing formoterol to patients receiving monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants, the effect of formoterol on the cardiovascular system may be enhanced. The combination of formoterol therapy with quinidine, digitalis, disopyramide, procainamide, phenothiazines, antihistamines and tricyclic antidepressants may be accompanied by a prolongation of the QT interval and an increased risk of developing ventricular arrhythmias.

Features of the Aerolyzer – delivery means of Foradil and Foradil Combi

Budesonide and formoterol capsules in Foradil Combi are administered through a unique Aerolyzer inhaler. It ensures correct inhalation technique for most patients of any age and allows you to control the correctness of inhalation using the “hear-feel-see” principle: the patient hears the capsule rotating, feels the inhalation of the powder and sees the emptying of the capsule.

Additionally, the Aerolyzer has the following advantages:

activated by breathing, does not require coordination of inhalation and activation;
requires less inhalation effort;
provides a high percentage of penetration into the lungs at a “comfortable” inhalation effort;
ensures dosing accuracy with low dose variability;
intuitive ease of use and control (for small children).

More than 90% of patients find the Aerolyzer easy to use.

Side effects

The most common symptoms are nausea, headache , tremor , and dry mouth.

In more rare cases, muscle cramps, tachycardia, myalgia , dizziness, anxiety, agitation, sleep disturbances, increased bronchospasm and nervousness are detected. Even less common are hypersensitivity reactions ( urticaria , severe hypotension , itching, angioedema, exanthema ), changes in the sense of taste, peripheral edema.

Instructions for use Formoterol Easyhaler (Method and dosage)

Formoterol Easyhaler is used for inhalation only.

Bronchial asthma

For continuous maintenance therapy, 1 inhalation of the drug is prescribed twice a day; Some patients may require 2 inhalations twice a day. The highest daily dose for regular use is 4 inhalations. If necessary, the use of additional inhalations, in addition to those prescribed, is allowed to relieve symptoms, but not more than 6 inhalations per day in total. Do not carry out more than 3 inhalations at a time. Frequent (more than 2 times a day or more than 2 days a week) use of the drug or its use in dosages exceeding those recommended for maintenance treatment is a sign of insufficient control of bronchial asthma. In this case, it is necessary to reconsider the treatment regimen.

Prevention of bronchospasm provoked by physical activity

In such cases, take 1 inhalation approximately 15 minutes before the expected physical activity. In severe cases of the disease, the need for 2 inhalations cannot be ruled out, but the maximum daily dose of 6 inhalations should not be exceeded.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

A drug from the group of β-adrenergic agonists . Formoterol acts primarily on β2-adrenergic receptors . It has a bronchodilator effect, relieves and prevents bronchospasm. Suppresses the release of leukotrienes, histamine and prostaglandins from basophils, mast cells and sensitized bronchial cells.

Pharmacokinetics

Ingestion of up to 90% of the active substance during inhalation is acceptable. Rapidly absorbed from the intestines. Absorption reaches 65%. The time for maximum concentration to occur is 30-60 minutes. Plasma protein binding is approximately 62-64%. Half-life is 2.5-3 hours. It is transformed mainly by glucuronidation . It is evacuated from the body by the kidneys and feces.

When used inhalation, it is quickly absorbed, the highest concentration occurs after 15 minutes. Bioavailability is 46%. Reacts with blood by 50%. The half-life is approximately 8 hours.

Analogs

Level 4 ATX code matches:
Onbrez Breezhaler

Fenoterol

Ventolin

Berotek

Foradil

The most well-known analogues of Formoterol Easyhaler: Atimos, Zafiron, Oxis Turbuhaler, Symbicort Turbuhaler, Foradil, Foster.

Overdose

To date, not enough clinical experience has been accumulated in the treatment of overdose, but it is assumed that an overdose of Formoterol Easyhaler is accompanied by nausea, headaches, vomiting, tremor , palpitations, drowsiness , ventricular arrhythmias, tachycardia , changes in pressure, metabolic acidosis, hyperglycemia, hypokalemia , prolongation QT interval.

Supportive and symptomatic treatment and monitoring of potassium in the blood are indicated. If the process is severe, the patient must be hospitalized. Cautious use (since bronchospasm may be provoked) is permitted using cardioselective β-blockers .