Foradil Combi, 200 mcg+12 mcg, capsules with powder for inhalation, set, 120 pcs.

Compound

The drug Foradil Combi is available in the form of a set of capsules of formoterol and budesonide .
1 capsule of formoterol contains 12 mcg of the active substance formoterol fumarate, and lactose acts as an excipient (up to 25 mg). The capsule shell contains 100% gelatin (79 mg).

1 capsule of budesonide contains 200 mcg or 400 mcg of the active substance budesonide, and lactose acts as an excipient (up to 25 mg). The capsule shell contains red iron oxide (E172), as well as titanium dioxide (E171), water and gelatin.

Foradil Combi 12mcg+400mcg por d/ing caps No. 60+60

Dosage

400 mcg+12 mcg

Active substance

Budesonide + Formoterol

Manufacturer

Pharmachemi BV./Novartis Pharma Stein AG (Netherlands/Switzerland)

Shelf life

2 years

Storage conditions

(protect from moisture)

Registration certificate number

LSR-003336/09 dated 04/23/2014

Compound

Characteristic

Directions for use and doses

Inhalation,

only with the help of a special device - an Aerolyzer, which is included in the package. Formoterol and budesonide are intended for inhalation use - the drugs are capsules with powder for inhalation.

Formoterol and budesonide should be prescribed individually, at the minimum effective dose.

When control of bronchial asthma symptoms is achieved during formoterol therapy, 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.

In the event of exacerbation of bronchial asthma, do not treat with formoterol or change the dose of the drug. Formoterol should not be used to relieve acute attacks of bronchial asthma.

When conducting therapy using an inhalation device, it is necessary to gradually adjust the dose of the drug to doses sufficient to maintain the therapeutic effect.

Budesonide + formoterol

Pre-inhalation of a β-adrenergic agonist dilates the bronchi, improves the entry of budesonide into the respiratory tract and enhances its therapeutic effect, therefore maintenance therapy for bronchial asthma and COPD is carried out in the following sequence:

- inhalation of formoterol;

- budesonide inhalation.

Adults

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

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

Considering that the maximum daily dose of formoterol is 48 mcg, if necessary, an additional 12–24 mcg/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 consider changing therapy, because this may indicate a worsening of the disease.

2. The minimum dose of budesonide in one capsule is 200 mcg. The drug should not be prescribed if a single dose of less than 200 mcg is required. In adult patients with mild bronchial asthma, treatment begins with the minimum effective dose of 200 mcg/day. The maintenance dose of budesonide for adult patients is 400–800 mcg/day in 2 divided doses (200–400 mcg 2 times a day).

In case of exacerbation of bronchial asthma during the transfer of a patient from the use of dosage forms of GCS for oral administration to inhalation or when reducing the dose of dosage forms of GCS for oral administration, budesonide can be prescribed at a dose of 1600 mcg/day in 2–4 doses.

Children ≥6 years old

1. The dose of formoterol for regular maintenance therapy is 12 mcg 2 times a day. The maximum recommended dose of the drug is 24 mcg/day.

2. Due to the lack of clinical experience in children under 6 years of age, budesonide should not be prescribed to patients in this age group.

Treatment of children with mild bronchial asthma should begin with a dose of 200 mcg/day.

The dose of budesonide for regular maintenance therapy is 100–200 mcg 2 times a day. If necessary, the dose of budesonide can be increased to a maximum of 800 mcg/day.

Special patient groups

Renal dysfunction.

There is no data on the need to adjust the dose of the drug in patients with impaired renal function. Based on the pharmacokinetics of oral budesonide, it is unlikely that the systemic exposure of the drug would change in a clinically significant manner in these patients.

Liver dysfunction.

There is no data on the need to adjust the dose of the drug in patients with impaired liver function, however, budesonide is eliminated mainly by the liver. In this regard, the drug should be used with caution in patients with severe liver dysfunction. In patients with mild or moderate hepatic impairment, exposure to the drug is unlikely to be significantly altered based on the pharmacokinetic parameters of oral budesonide.

Elderly patients (over 65 years old).

There is no data on the need to adjust the dose of the drug in patients over 65 years of age.

Instructions for inhalation

To ensure correct use of the drug, the nurse or doctor should teach the patient the correct technique for using the inhaler; explain that capsules with powder for inhalation should only be used using an Aerolyzer; Warn the patient that the capsules are for inhalation use only and are not intended to be swallowed. In children and adolescents, inhalation of budesonide and formoterol should be carried out under adult supervision. It is necessary to ensure that the child performs the inhalation technique correctly.

It is important to warn the patient that if the gelatin capsule ruptures, small pieces of gelatin may enter the mouth or throat as a result of inhalation. In order to minimize this phenomenon, you should not pierce the capsule more than once.

The capsule should be removed from the blister pack immediately before use (see also Instructions for use of the Aerolyzer

).

Rinsing the mouth with water after inhaling budesonide can prevent irritation of the oral and pharyngeal mucosa and also reduce the risk of systemic adverse events.

There are isolated reports of accidental swallowing of drug capsules whole. Most of these cases are not associated with the development of adverse events. The nurse or doctor should teach the patient the correct technique for using the drug, especially if the patient's breathing does not improve after inhalation.

Instructions for use of the Aerolyzer

1. It is necessary to remove the cap from the Aerolyzer.

2. Hold the Aerolizer firmly by the base and turn the mouthpiece in the direction of the arrow.

3. Place the capsule in the cell located at the base of the Aerolyzer (it has the shape of a capsule). It must be remembered that you need to remove the capsule from the blister pack immediately before inhalation.

4. Turn the mouthpiece to close the Aerolizer.

5. Holding the Aerolizer strictly in a vertical position, press all the way down on the blue buttons located on the sides once. Then release them.

Note.

At this stage, if the capsule is pierced, it may break, causing small pieces of gelatin to enter the mouth or throat. Since gelatin is edible, it will not cause any harm. To ensure that the capsule does not collapse completely, the following requirements must be met: do not pierce the capsule more than once; follow storage rules; remove the capsule from the blister only immediately before inhalation.

6. It is necessary to exhale completely.

7. You should take the mouthpiece into your mouth and tilt your head back slightly. Holding the mouthpiece tightly with your lips, take a quick, even, as deep breath as possible. There should be a characteristic rattling sound created by the rotation of the capsule and spraying of the powder. If there is no characteristic sound, then you should open the Aerolizer and see what happened to the capsule. It may be stuck in the cell. In this case, you need to carefully remove the capsule. Under no circumstances should you try to release the capsule by repeatedly pressing the buttons on the sides of the Aerolyzer.

8. If a characteristic sound occurs when inhaling, you must hold your breath as long as possible. At the same time, remove the mouthpiece from your mouth. Then exhale. Open the Aerolyzer and see if there is any powder left in the capsule. If there is powder left in the capsule, repeat the steps described in steps 6–8.

9. After completing the inhalation procedure, you must open the Aerolizer, remove the empty capsule, close the mouthpiece and the Aerolizer with the cap.

Arolizer care:

To remove any remaining powder, wipe the mouthpiece and cell with a dry cloth. You can also use a soft brush.

Conditions for dispensing from pharmacies

On prescription.

Pharmaceutical actions

glucocorticoid, β2-adrenomimetic, bronchodilator

Release form

The drug Foradil Combi is available in the form of a set of capsules with powder for inhalation. Capsules are packed in 10 pcs. in 1 blister. One cardboard pack can contain from 4 to 18 blisters, i.e. 40 capsules (30 pieces with formoterol and 10 pieces with budesonide), 60 capsules (30 pieces with formoterol and 30 pieces with budesonide), 70 capsules (60 pieces with formoterol and 10 pieces with budesonide), 90 capsules (30 pieces with formoterol and 60 pieces with budesonide), 120 capsules (60 pieces with formoterol and 60 pieces with budesonide), and 150 capsules (30 pieces with formoterol and 120 pieces with budesonide), or 180 capsules (60 pieces with formoterol and 120 pieces with budesonide).

The drug Foradil Combi goes on sale complete with an aerolyzer (device for inhalation).

Foradil Combi capsules with powder d/ing set 12mcg+200mcg No. 120

Directions for use and doses

Inhalation, only using a special Aerolyzer device, which is included in the package.
Formoterol and budesonide are intended for inhalation use; the drugs are capsules with powder for inhalation. Formoterol and budesonide should be prescribed individually, at the minimum effective dose.

When control of bronchial asthma symptoms is achieved during formoterol therapy, 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. Against the background of exacerbation of bronchial asthma, you should not start treatment with formoterol or change the dosage of the drug. Formoterol should not be used to relieve acute attacks of bronchial asthma.

When prescribing therapy with an inhalation device to a patient, the dose of the drug should be gradually adjusted (titrated) to doses sufficient to maintain the therapeutic effect.

Budesonide + Formoterol

Adults: preliminary inhalation of β-adrenergic stimulants dilates the bronchi, improves the entry of Budesonide into the respiratory tract and enhances its therapeutic effect. Therefore, maintenance therapy for bronchial asthma and COPD is carried out as follows:

- first, formoterol is inhaled,

- then inhalation of budesonide.

1. The dose of formoterol for regular maintenance therapy is 1224 mcg (contents of 12 capsules) 2 times a day.

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

Considering that the maximum daily dose of formoterol is 48 mcg, if necessary, an additional dose of 1224 mcg/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, it becomes more often than 2 days a week), the patient should be advised to consult a doctor about reviewing therapy, because this may indicate a worsening of the disease.

2. The minimum dose of the drug in one capsule is 200 mcg. The drug cannot be used if a single dose of less than 200 mcg is required. Adult patients with mild asthma can begin treatment at the minimum effective dose of 200 mcg/day. The maintenance dose of budesonide for adult patients is 400,800 mcg/day in 2 divided doses (200,400 mcg 2 times a day).

In case of exacerbation of bronchial asthma during the transfer from oral corticosteroids to inhaled ones or when reducing the dose of oral corticosteroids, budesonide can be prescribed at a dose of 1600 mcg/day in 24 doses.

Children &ge,6 years

Pre-inhalation of β-adrenergic stimulants dilates the bronchi, improves the entry of budesonide into the respiratory tract and enhances its therapeutic effect. Therefore, maintenance therapy for bronchial asthma is carried out as follows:

- first, formoterol is inhaled,

- then inhalation of budesonide.

1. The dose of formoterol for regular maintenance therapy is 12 mcg 2 times a day. The maximum recommended dose of the drug is 24 mcg/day.

2. Due to the lack of clinical experience in children under 6 years of age, budesonide should not be used in this age group.

Treatment of children with mild forms of bronchial asthma can begin with a dose of 200 mcg/day.

The dose of budesonide for regular maintenance therapy is 100-200 mcg 2 times a day. If necessary, the dose of budesonide can be increased to a maximum of 800 mcg/day.

Special patient groups

Renal dysfunction. There are no data to support dose adjustment in patients with impaired renal function. Based on pharmacokinetic data for oral budesonide, it is unlikely that the systemic exposure of the drug would be altered in a clinically significant manner in these patients.

Liver dysfunction. There are no data to support dose adjustment in patients with impaired liver function. But budesonide is eliminated mainly by the liver. In this regard, the drug should be used with caution in patients with severe liver dysfunction. In patients with mild or moderate hepatic impairment, drug exposure is unlikely to be significantly altered based on the pharmacokinetic parameters of oral budesonide.

Elderly patients (over 65 years old). There is no evidence to support the need to use the drug at a different dose in patients over 65 years of age compared to younger patients.

Instructions for inhalation

To ensure proper use of medications, the physician or other health care professional should show the patient how to use the inhaler, explain to the patient that inhalation powder capsules should only be used with an Aerolyzer, and warn the patient that the capsules are for inhalation use only and are not intended to be swallowed. In children and adolescents, inhalation of budesonide and formoterol should be carried out under adult supervision. It is necessary to ensure that the child performs the inhalation technique correctly. It is important that the patient understands that due to the breakdown of the gelatin capsule, small pieces of gelatin may enter the mouth or throat as a result of inhalation. In order to minimize this phenomenon, you should not pierce the capsule more than once. The capsule should be removed from the blister pack immediately before use (see also Instructions for use of the Aerolyzer).

Rinsing the mouth with water after inhaling budesonide can prevent irritation of the oral and pharyngeal mucosa and also reduce the risk of systemic adverse events.

There are isolated reports of patients accidentally swallowing capsules of the drug whole. Most of these cases are not associated with the development of adverse events. The healthcare professional should explain to the patient how to use the drug correctly, especially if the patient does not experience improvement in breathing after inhalation.

Instructions for use of the Aerolyzer

1. It is necessary to remove the cap from the Aerolyzer.

2. Hold the Aerolizer firmly by the base and turn the mouthpiece in the direction of the arrow.

3. Place the capsule in the cell located at the base of the Aerolyzer (it has the shape of a capsule). It must be remembered that you need to remove the capsule from the blister pack immediately before inhalation.

4. Turn the mouthpiece to close the Aerolizer.

5. Holding the Aerolyzer in a strictly vertical position, press all the way down on the blue buttons located on the sides of the Aerolyzer once. Then release them.

Note. At this stage, if the capsule is pierced, it may break, causing small pieces of gelatin to enter the mouth or throat. Since gelatin is edible, it will not cause any harm. To ensure that the capsule does not completely collapse, the following requirements must be met: do not pierce the capsule more than once, follow storage rules, remove the capsule from the blister only immediately before inhalation.

6. It is necessary to exhale completely.

7. You should take the mouthpiece into your mouth and tilt your head back slightly. Holding the mouthpiece tightly with your lips, take a quick, even, as deep breath as possible. There should be a characteristic rattling sound created by the rotation of the capsule and spraying of the powder. If there is no characteristic sound, then you should open the Aerolizer and see what happened to the capsule. It may be stuck in the cell. In this case, you need to carefully remove the capsule. Under no circumstances should you try to release the capsule by repeatedly pressing the buttons on the sides of the Aerolyzer.

8. If a characteristic sound occurs when inhaling, you must hold your breath as long as possible. At the same time, remove the mouthpiece from your mouth. Then exhale. Open the Aerolyzer and see if there is any powder left in the capsule. If there is powder left in the capsule, repeat the steps described in paragraph 68.

9. After completing the inhalation procedure, you must open the Aerolizer, remove the empty capsule, close the mouthpiece and the Aerolizer with the cap.

Caring for the Arolizer: to remove any remaining powder, wipe the mouthpiece and cell with a dry cloth. You can also use a soft brush.

Pharmacodynamics and pharmacokinetics

Formoterol

Suction

With a single dose of 120 mcg, it was determined that formoterol is rapidly absorbed into plasma and its Cmax is 266 pmol/l and is achieved within 5 minutes after the inhalation procedure.

When taking formoterol at a dose of 12 mcg and 24 mcg 2 times a day for 12 weeks in patients with COPD, the plasma concentration of formoterol is in the range of 11.5-25.7 pmol/l.

Please note that the amount of active substance in the systemic circulation increases in proportion to the amount of the inhaled dose.

Distribution

Formoterol has a fairly strong binding to plasma proteins, which is about 60-64%.

Metabolism

The main route of metabolism of the active substance is direct conjugation (with the participation of glucuronic acid). A secondary metabolic pathway is O-demethylation (followed by glucuronidation).

Removal

In patients suffering from bronchial asthma and COPD , approximately 7 - 10% of unchanged formoterol is determined in the urine.

Please note that the active substance and its metabolites are completely eliminated from the body through the kidneys (70%) and intestines (30%). T1/2 of the drug is about 3 hours. The renal clearance of formoterol reaches 150 ml/min.

Budesonide

Suction

This substance is completely and quickly absorbed after administration. Its absolute bioavailability reaches 73%.

Distribution

The Vd of budesonide is 3 l/kg, and the binding to plasma proteins reaches about 88%. Systemic clearance of the drug was determined at 0.5 l/min. Places of accumulation of budesonide can be the spleen, lymph nodes, thymus gland, adrenal cortex, reproductive organs and bronchi, as well as in some cases the placental barrier.

Metabolism

The metabolism of budesonide does not occur in the lungs. After administration, almost all of the drug (more than 90%) is metabolized in the liver and at the same time forms several inactive metabolites . Budesonide has a fairly high systemic clearance - 84 l/h and a fairly short T1/2 - 2 hours.

Removal

T1/2 is 2 or 2.5 hours. The active substance is excreted both through the intestines in the form of inactive metabolites (10%) and by the kidneys (70%).

Foradil Combi

Formoterol

The use of formoterol has been shown to improve the quality of life of patients with COPD.

Formoterol belongs to the class of long-acting beta2-agonists. Another long-acting beta2-agonist, salmeterol, was associated with an increased incidence of asthma-related deaths (13 of 13,176 patients) compared with placebo (3 of 13,179 patients). Clinical studies have not been conducted to assess the incidence of deaths associated with bronchial asthma during the use of formoterol.

Anti-inflammatory therapy

In patients with bronchial asthma, 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 beta2-agonist. Formoterol should not be used concomitantly with other long-acting beta2-agonists. When using formoterol, it is necessary to assess the patient's condition regarding the adequacy of the anti-inflammatory therapy used. After starting treatment with formoterol, the patient should be advised to continue anti-inflammatory therapy without changes, even if improvement is noted.

To relieve an acute attack of bronchial asthma, short-acting beta2-agonists should be used. If the condition suddenly worsens, the patient should immediately seek medical help.

Severe exacerbations of bronchial asthma

In clinical studies in patients receiving formoterol for 4 weeks, there was an increase in the incidence of severe exacerbations of bronchial asthma (0.9% with a dosage regimen of 10-12 mcg 2 times a day, 1.9% with 24 mcg 2 times a day per day) compared to the placebo group (0.3%), especially in children 5-12 years old.

In two large controlled clinical trials involving 1095 adults and children 12 years of age and older, severe asthma exacerbations (requiring hospitalization) were more common in patients receiving formoterol 24 mcg twice daily (9/271, 3.3 %), compared with the formoterol 12 mcg twice daily (1/275, 0.4%), placebo (2/277, 0.7%) and albuterol (2/272, 0.7%) groups. .

When formoterol was used for 16 weeks, another large clinical trial including 2085 adults and adolescents did not find an increase in the incidence of severe exacerbations of bronchial asthma depending on the increasing dose of formoterol. However, in this study, the incidence of severe exacerbations was higher in the formoterol group (with a dosage regimen of 24 mcg 2 times a day - 2/527, 0.4%, with a dosage regimen of 12 mcg 2 times a day - 3/527, 0.6%) compared with placebo (1/517, 0.2%). In the open-label phase of this study, when using formoterol at a dose of 12 mcg 2 times a day (patients could use up to two additional doses of the drug if necessary), the incidence of severe exacerbations of bronchial asthma was 1/517, 0.2%.

In a 52-week, multicenter, randomized, double-blind clinical trial of 518 children aged 6 to 12 years, the incidence of severe asthma exacerbations was higher with formoterol 24 mcg twice daily (11/171, 6.4 %), 12 mcg twice daily (8/171, 4.7%) compared with placebo (0/176, 0.0%).

However, the results of the above clinical studies do not allow us to quantify the incidence of severe exacerbations of bronchial asthma in different groups.

Hypokalemia

Therapy with beta2-agonists, including formoterol, may result in potentially serious hypokalemia. Hypokalemia may increase the risk of developing arrhythmias.

Since this effect of the drug 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 levels is recommended.

Paradoxical bronchospasm

As with other inhalation therapy, the possibility of developing paradoxical bronchospasm should be taken into account. If this condition develops, the drug should be discontinued immediately and alternative treatment should be initiated.

Budesonide

To ensure that budesonide reaches the lungs, it is important to instruct patients to correctly inhale the drug in accordance with the instructions for use.

The patient should be informed that the drug is not intended to relieve attacks, but for regular daily preventive use even in the absence of symptoms of bronchial asthma.

If paradoxical bronchospasm develops, you should immediately stop using budesonide, assess the patient's condition and, if necessary, begin therapy with other drugs. Paradoxical bronchospasm must be immediately relieved with a short-acting beta2-agonist. The patient should always have at his disposal a short-acting beta2-agonist inhaler to relieve exacerbations of bronchial asthma.

The patient should be informed about the need to consult a doctor if the condition worsens (increased need for short-acting bronchodilators, increased attacks of shortness of breath). In such cases, it is necessary to conduct an examination and consider the possibility of increasing the dose of inhaled GCS or GCS for oral administration.

To reduce the risk of developing candidal infections of the oral cavity and pharynx, it is recommended to thoroughly rinse your mouth with water after each inhalation of the drug. With the development of candidal infection of the oral cavity and pharynx, local antifungal therapy can be performed without stopping treatment with budesonide.

Dysphonia may develop, but this phenomenon is temporary and goes away after discontinuation of therapy, dose reduction and/or voice rest.

In case of exacerbation of bronchial asthma, the dose of budesonide should be increased or, if necessary, treated with a short course of systemic corticosteroids and/or antibiotic therapy should be used if infection develops.

It is necessary to regularly monitor the growth dynamics of children and adolescents receiving long-term therapy with inhaled corticosteroids. If growth is delayed, the need to reduce the dose of inhaled corticosteroids (use of the minimum effective dose) and refer the child for consultation to an allergist should be considered.

The long-term consequences of growth retardation (impact on final adult height) in children receiving therapy with inhaled corticosteroids have not been studied. There has been no adequate study of the possibility of compensating for growth retardation in children after discontinuation of therapy with oral corticosteroids.

Budesonide generally has no effect on adrenal function. However, in some patients, with long-term use at the recommended daily dose, systemic effects of budesonide may be observed.

When using inhaled GCS in high doses or for a long period of time, systemic adverse events may develop (however less often than when using GCS for oral administration), such as suppression of adrenal function, hyperadrenocorticism/Cushing's syndrome, growth retardation in children and adolescents, decreased bone mineral density, hypersensitivity reactions, cataracts, glaucoma and, less commonly, a number of behavioral disorders including psychomotor hyperactivity, sleep disturbances, agitation, depression or aggression (especially in children). In this regard, the smallest dose of inhaled corticosteroids that provides a therapeutic effect should be used.

Risk of developing pneumonia in patients with COPD

In patients with COPD receiving inhaled corticosteroids, an increase in the incidence of pneumonia, including that requiring hospitalization, was noted. The risk of developing pneumonia increases with increasing doses of GCS, but this effect has not been confirmed in all studies.

Differences in the risk of developing pneumonia between different drugs containing inhaled corticosteroids have not been clinically proven.

Physicians should be alert to the early detection of pneumonia in patients with COPD, since the clinical signs of such an infection coincide with those of an exacerbation of COPD.

Risk factors for pneumonia in patients with COPD include smoking, older age, low body mass index, and severe COPD.

Patients with hormone-independent bronchial asthma

In patients with hormone-independent bronchial asthma, the therapeutic effect of budesonide develops on average within 10 days after the start of treatment. At the beginning of budesonide therapy in patients with increased bronchial secretion of the drug by inhalation, it is possible to add GCS to therapy for oral administration in a short course (lasting about 2 weeks).

Patients with hormone-dependent bronchial asthma

To transfer the patient from oral corticosteroids to inhaled budesonide, stabilization of the condition is necessary.

During the first 10 days, high doses of budesonide are used in combination with previously used corticosteroids for oral administration at the same dose. Then the daily dose of GCS for oral administration is gradually reduced (2.5 mg every month in terms of prednisolone) to the minimum possible level. Treatment with corticosteroids, including budesonide, should not be abruptly interrupted.

In the first months after transition, the patient's condition should be carefully monitored until the function of the hypothalamic-pituitary-adrenal axis is restored sufficient to ensure an adequate response to stressful situations (for example, trauma, surgery, or severe infection). The function of the hypothalamic-pituitary-adrenal system should be regularly monitored.

In some cases, a patient with dysfunction of the adrenal cortex may need additional use of GCS for oral administration during stressful situations. Patients in this category are recommended to always have a warning card with them, indicating that in stressful situations they need additional systemic use of GCS.

When transferring patients from systemic corticosteroids to inhaled budesonide therapy, reactions such as allergic rhinitis, eczema, lethargy, muscle and joint pain, and sometimes nausea and vomiting, which were previously relieved by taking systemic corticosteroids, may occur. Treatment of these reactions should be carried out with antihistamines or corticosteroids for local use.

Contraindications

It is not recommended to use Foradil Combi:

• during lactation (when breastfeeding);
• with active pulmonary tuberculosis ;
• with hereditary galactose intolerance, severe lactase deficiency and syndrome of impaired glucose-galactose absorption;
• in children under 6 years of age;
• with hypersensitivity to budesonide , formoterol , as well as any other components of the drug.

You should use the drug Foradil with extreme caution:

• for coronary heart disease ;
• for heart rhythm disturbances ;
• for severe heart failure ;
• for idiopathic subvalvular aortic stenosis ;
• with hypertrophic obstructive cardiomyopathy ;
• with thyrotoxicosis ;
• with known or suspected QT prolongation;
• for diabetes mellitus .

Side effects

Formoterol

During treatment with Foradil, patients may experience quite severe discomfort from the following side effects:

• From the immune system: from hypersensitivity reactions ( hypotension, urticaria, angioedema, itching, exanthema ).
• Mental disorders: agitation , anxiety, increased excitability, insomnia
• From the nervous system: headache, tremor, dizziness, taste disturbances .
• From the cardiovascular system: palpitations, tachycardia, peripheral edema .
• From the respiratory system: from bronchospasms , including paradoxical ones.
• Local reactions: from irritation of the mucous membrane of the larynx and pharynx .
• From the digestive system: for nausea .
• From the musculoskeletal system: from muscle cramps, myalgia .
• Other: from distortion of taste sensations .

Please note that significant changes in laboratory tests such as hyperglycemia and hypokalemia, as well as prolongation of the QT interval, have been observed with the use of this drug in clinical practice.

During clinical trials, when using the drug Foradil Combi in treatment regimens, a slight increase in the incidence of exacerbation of bronchial asthma was revealed in comparison with placebo.

Budesonide

Since Foradil Combi is a combination drug and contains budesonide , patients may also experience discomfort from the following side effects:

• From the endocrine system: from suppression of the functions of the adrenal cortex, Cushing's syndrome, hypercortisolism, growth retardation in childhood .
• From the organs of vision: from cataracts, glaucoma .
• From the immune system: from hypersensitivity reactions, rash, urticaria, angioedema, itching, contact dermatitis .
• Mental disorders: from psychomotor hyperactivity, sleep disorders, anxiety, depression, aggressive behavior, behavioral disorders .
• Musculoskeletal and connective tissue disorders: decreased bone (mineral) density .
• From the respiratory system, chest and mediastinal organs: cough, paradoxical bronchospasm, candidiasis of the laryngeal and oral mucosa, pharyngeal irritation, dysphonia .

Foradil combi Capsules, 120 pcs., 12/400 mcg/mcg

special instructions

Formoterol It has been shown that the use of formoterol improves the quality of life of patients with COPD. Formoterol belongs to the class of long-acting beta2-agonists. Another long-acting beta2-agonist, salmeterol, was associated with an increased incidence of asthma-related deaths (13 of 13,176 patients) compared with placebo (3 of 13,179 patients). Clinical studies have not been conducted to assess the incidence of deaths associated with bronchial asthma during the use of formoterol. Anti-inflammatory therapy In patients with asthma, formoterol should be used only as an adjunctive treatment when symptoms are insufficiently controlled on inhaled corticosteroid monotherapy or when the disease is severe and requires the use of an inhaled corticosteroid and a long-acting β2-adrenergic agonist. Formoterol should not be co-administered with other long-acting β2-adrenergic agonists. When prescribing formoterol, it is necessary to assess the condition of patients regarding the adequacy of the anti-inflammatory therapy they receive. After starting treatment with formoterol, patients should be advised to continue anti-inflammatory therapy without changes, even if improvement is noted. To relieve an acute attack of bronchial asthma, short-acting beta2-adrenergic receptor agonists should be used. If the condition suddenly worsens, patients should seek medical help immediately. Severe exacerbations of bronchial asthma In clinical studies with the use of formoterol, there was a slight increase in the incidence of severe exacerbations of bronchial asthma compared to placebo, especially in children 6-12 years of age. In placebo-controlled clinical studies in patients receiving formoterol for 4 weeks, there was an increase in the incidence of severe exacerbations of bronchial asthma (0.9% with a dosage regimen of 10-12 mcg 2 times a day, 1.9% with a dosage regimen of 10-12 mcg 2 times a day, 1.9% with a dosage regimen of 24 mcg 2 times a day days) compared to the placebo group (0.3%), especially in children 6-12 years old. In two large controlled clinical trials involving 1095 adults and children 12 years of age and older, severe asthma exacerbations (requiring hospitalization) were more common in patients receiving formoterol 24 mcg twice daily (9/271, 3.3%) , compared with the groups of formoterol at a dose of 12 mcg 2 times / day (1/275, 0.4%), placebo (2/277, 0.7%) and albuterol (2/272, 0.7%). When formoterol was used for 16 weeks, another large clinical trial of 2085 adults and adolescents did not find an increase in the incidence of severe asthma exacerbations with increasing formoterol dosage. However, in this study, the incidence of severe exacerbations was higher in the formoterol group (with a dosage 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 the open-label phase of this study, when using formoterol at a dose of 12 mcg 2 times a day (if necessary, patients could use up to two additional doses of the drug), the incidence of severe exacerbations of bronchial asthma was 1/517, 0.2%. In a 52-week, multicenter, randomized, double-blind clinical trial that included 518 children aged 6 to 12 years, the incidence of severe asthma exacerbations was higher with formoterol 24 mcg twice daily (11/171, 6.4 %), 12 mcg 2 times / day (8/171, 4.7%) compared with placebo (0/176, 0.0%). However, the results of the above clinical studies do not allow us to quantify the incidence of severe exacerbations of bronchial asthma in different groups. Hypokalemia Potentially serious hypokalemia may occur as a consequence of therapy with beta2-agonists, including formoterol. Hypokalemia may increase susceptibility to the development of arrhythmias. Because this effect of the drug 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 As with other inhalation therapy, the possibility of developing paradoxical bronchospasm should be taken into account. If it occurs, the drug should be discontinued immediately and alternative treatment should be prescribed. Impact on the ability to drive vehicles and operate machinery Patients who experience dizziness or other central nervous system disorders while using the drug formoterol should refrain from driving vehicles or operating machinery during the period of use of the drug. Budesonide To ensure that budesonide reaches the lungs, it is important to instruct patients to correctly inhale the drug in accordance with the instructions for use. Patients should be informed that the drug is not intended to relieve attacks, but for regular daily preventive use even in the absence of symptoms of bronchial asthma. If paradoxical bronchospasm develops, you should immediately stop using budesonide, assess the patient's condition and, if necessary, prescribe therapy with other drugs. Paradoxical bronchospasm must be immediately relieved with a short-acting beta2-agonist. Patients should always have a short-acting beta2-agonist inhaler available to relieve acute exacerbations of bronchial asthma. Patients should be informed about the need to consult a doctor if their condition worsens (increased need for short-acting bronchodilators, increased attacks of shortness of breath). In such cases, it is necessary to examine the patient and consider the possibility of increasing the dose of inhaled or oral GCS. To reduce the risk of developing candidal infections of the oral cavity and pharynx, the patient should thoroughly rinse his mouth with water after each inhalation of the drug. With the development of candidal infection of the oral cavity and pharynx, local antifungal therapy can be performed without stopping treatment with budesonide. In case of exacerbation of bronchial asthma, the dose of budesonide should be increased or, if necessary, a short course of systemic corticosteroids should be administered and/or antibiotic therapy should be prescribed if infection develops. It is necessary to regularly monitor the growth dynamics of children and adolescents receiving long-term therapy with inhaled corticosteroids. If growth is delayed, the need to reduce the dose of inhaled corticosteroids (prescribed in the minimum effective dose) and refer the child for consultation to an allergist should be considered. The long-term consequences of growth retardation (impact on final adult height) in children receiving therapy with inhaled corticosteroids have not been studied. There has been no adequate study of the possibility of compensating for growth retardation in children after discontinuation of therapy with oral corticosteroids. Budesonide usually has no effect on adrenal function. However, in some patients, with long-term use at recommended daily doses, systemic effects of budesonide may be observed. When prescribing inhaled corticosteroids in high doses or over a long period of time, systemic adverse reactions may develop (however less frequently than when using oral corticosteroids), such as suppression of adrenal function, hypercortisolism/Cushing's syndrome, growth retardation in children and adolescents, decreased mineral bone density, hypersensitivity reactions, cataracts, glaucoma and, less commonly, a number of behavioral disorders, including psychomotor hyperactivity, sleep disturbances, agitation, depression or aggression (especially in children). Patients with hormone-independent bronchial asthma In patients with hormone-independent bronchial asthma, the therapeutic effect of budesonide develops on average within 10 days after the start of treatment. At the beginning of budesonide therapy in patients with increased bronchial secretion, oral corticosteroids can be added to the drug inhalations in a short course (lasting about 2 weeks). Patients with hormone-dependent bronchial asthma When switching from oral administration of corticosteroids to inhaled use of budesonide, patients should be in a relatively stable condition. During the first 10 days, high doses of budesonide are prescribed in combination with previously used oral corticosteroids at the same dose. Then the daily dose of oral corticosteroids begins to be gradually reduced (2.5 mg every month in terms of prednisolone) to the minimum possible level. Treatment with corticosteroids, including budesonide, should not be abruptly interrupted. The patient's condition should be carefully monitored in the first months after transition until the hypothalamic-pituitary-adrenal axis has recovered sufficiently to provide an adequate response to stressful situations (for example, trauma, surgery, or severe infection). The function of the hypothalamic-pituitary-adrenal system should be regularly monitored. In some cases, patients with reduced adrenal cortex function may need additional administration of GCS for oral administration during stressful situations. This category of patients is recommended to always carry a warning card with them, which should indicate that in stressful situations they need additional systemic administration of GCS. When transferring patients from systemic corticosteroids to inhaled budesonide therapy, reactions such as allergic rhinitis, eczema, lethargy, pain in muscles and joints, and sometimes nausea and vomiting, which were previously suppressed by taking systemic corticosteroids, may occur. Treatment of these reactions should be carried out with antihistamines or local corticosteroids. Effect on the ability to drive vehicles and operate machinery There is no data on the effect of budesonide on the ability to drive vehicles and operate machinery. A negative effect of the drug on the ability to drive vehicles and operate machinery is unlikely.

Foradil Combi, instructions for use (Method and dosage)

Formoterol and budesonide are available in the form of capsules with a special powder for inhalation, which must be used exclusively with the help of a special inhaler device that comes with the package.

Instructions for Foradil Combi 12 mcg + 400 mcg

When taking Foradil Combi, the following recommendations should be taken into account:

With regular maintenance therapy, the dose of formoterol varies between 12 and 24 mcg (contents of 1 or 2 capsules) 2 times a day. Taking into account the fact that the maximum daily dose of the active substance should not exceed 48 mcg, in case of urgent need, it is allowed to take an additional 12-24 mcg per day in order to relieve the symptoms of bronchial asthma .

The minimum dose of the drug in 1 capsule is 200 mcg. Foradil Combi is not prescribed if the treatment regimen requires doses less than 200 mcg.

The maintenance dose of budesonide for adults can vary from 400 to 800 mcg per day in 2 divided doses.

In case of severe exacerbation of bronchial asthma, budesonide can be prescribed at a dose of 1600 mcg per day in 2-4 doses.

Directions for use and doses

Inhalation, only with the help of a special device - Aerolyzer, which is included in the package. Formoterol and budesonide are intended for inhalation use - the drugs are capsules with powder for inhalation.

Formoterol and budesonide should be prescribed individually, at the minimum effective dose.

When control of bronchial asthma symptoms is achieved during formoterol therapy, 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.

In the event of exacerbation of bronchial asthma, do not treat with formoterol or change the dose of the drug. Formoterol should not be used to relieve acute attacks of bronchial asthma.

When conducting therapy using an inhalation device, it is necessary to gradually adjust the dose of the drug to doses sufficient to maintain the therapeutic effect.

Budesonide + formoterol

Pre-inhalation of a β-adrenergic agonist dilates the bronchi, improves the entry of budesonide into the respiratory tract and enhances its therapeutic effect, therefore maintenance therapy for bronchial asthma and COPD is carried out in the following sequence:

- inhalation of formoterol;

- budesonide inhalation.

Adults

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

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

Considering that the maximum daily dose of formoterol is 48 mcg, if necessary, an additional 12–24 mcg/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 consider changing therapy, because this may indicate a worsening of the disease.

2. The minimum dose of budesonide in one capsule is 200 mcg. The drug should not be prescribed if a single dose of less than 200 mcg is required. In adult patients with mild bronchial asthma, treatment begins with the minimum effective dose of 200 mcg/day. The maintenance dose of budesonide for adult patients is 400–800 mcg/day in 2 divided doses (200–400 mcg 2 times a day).

In case of exacerbation of bronchial asthma during the transfer of a patient from the use of dosage forms of GCS for oral administration to inhalation or when reducing the dose of dosage forms of GCS for oral administration, budesonide can be prescribed at a dose of 1600 mcg/day in 2–4 doses.

Children ≥6 years old

1. The dose of formoterol for regular maintenance therapy is 12 mcg 2 times a day. The maximum recommended dose of the drug is 24 mcg/day.

2. Due to the lack of clinical experience in children under 6 years of age, budesonide should not be prescribed to patients in this age group.

Treatment of children with mild bronchial asthma should begin with a dose of 200 mcg/day.

The dose of budesonide for regular maintenance therapy is 100–200 mcg 2 times a day. If necessary, the dose of budesonide can be increased to a maximum of 800 mcg/day.

Special patient groups

Renal dysfunction. There is no data on the need to adjust the dose of the drug in patients with impaired renal function. Based on the pharmacokinetics of oral budesonide, it is unlikely that the systemic exposure of the drug would change in a clinically significant manner in these patients.

Liver dysfunction. There is no data on the need to adjust the dose of the drug in patients with impaired liver function, however, budesonide is eliminated mainly by the liver. In this regard, the drug should be used with caution in patients with severe liver dysfunction. In patients with mild or moderate hepatic impairment, exposure to the drug is unlikely to be significantly altered based on the pharmacokinetic parameters of oral budesonide.

Elderly patients (over 65 years old). There is no data on the need to adjust the dose of the drug in patients over 65 years of age.

Instructions for inhalation

To ensure correct use of the drug, the nurse or doctor should teach the patient the correct technique for using the inhaler; explain that capsules with powder for inhalation should only be used using an Aerolyzer; Warn the patient that the capsules are for inhalation use only and are not intended to be swallowed. In children and adolescents, inhalation of budesonide and formoterol should be carried out under adult supervision. It is necessary to ensure that the child performs the inhalation technique correctly.

It is important to warn the patient that if the gelatin capsule ruptures, small pieces of gelatin may enter the mouth or throat as a result of inhalation. In order to minimize this phenomenon, you should not pierce the capsule more than once.

The capsule should be removed from the blister pack immediately before use (see also Instructions for use of the Aerolyzer).

Rinsing the mouth with water after inhaling budesonide can prevent irritation of the oral and pharyngeal mucosa and also reduce the risk of systemic adverse events.

There are isolated reports of accidental swallowing of drug capsules whole. Most of these cases are not associated with the development of adverse events. The nurse or doctor should teach the patient the correct technique for using the drug, especially if the patient's breathing does not improve after inhalation.

Instructions for use of the Aerolyzer

1. It is necessary to remove the cap from the Aerolyzer.

2. Hold the Aerolizer firmly by the base and turn the mouthpiece in the direction of the arrow.

3. Place the capsule in the cell located at the base of the Aerolyzer (it has the shape of a capsule). It must be remembered that you need to remove the capsule from the blister pack immediately before inhalation.

4. Turn the mouthpiece to close the Aerolizer.

5. Holding the Aerolizer strictly in a vertical position, press all the way down on the blue buttons located on the sides once. Then release them.

Note. At this stage, if the capsule is pierced, it may break, causing small pieces of gelatin to enter the mouth or throat. Since gelatin is edible, it will not cause any harm. To ensure that the capsule does not collapse completely, the following requirements must be met: do not pierce the capsule more than once; follow storage rules; remove the capsule from the blister only immediately before inhalation.

6. It is necessary to exhale completely.

7. You should take the mouthpiece into your mouth and tilt your head back slightly. Holding the mouthpiece tightly with your lips, take a quick, even, as deep breath as possible. There should be a characteristic rattling sound created by the rotation of the capsule and spraying of the powder. If there is no characteristic sound, then you should open the Aerolizer and see what happened to the capsule. It may be stuck in the cell. In this case, you need to carefully remove the capsule. Under no circumstances should you try to release the capsule by repeatedly pressing the buttons on the sides of the Aerolyzer.

8. If a characteristic sound occurs when inhaling, you must hold your breath as long as possible. At the same time, remove the mouthpiece from your mouth. Then exhale. Open the Aerolyzer and see if there is any powder left in the capsule. If there is powder left in the capsule, repeat the steps described in steps 6–8.

9. After completing the inhalation procedure, you must open the Aerolizer, remove the empty capsule, close the mouthpiece and the Aerolizer with the cap.

Caring for the Arolizer: to remove any remaining powder, wipe the mouthpiece and cell with a dry cloth. You can also use a soft brush.

Overdose

Formoterol

Symptoms of formoterol can be expressed as: nausea, severe vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias , as well as metabolic acidosis, hypokalemia, hyperglycemia and arterial hypertension .

In order to relieve symptoms, it is necessary to carry out supportive and symptomatic therapy. In cases of severe overdose, hospitalization is necessary.

Budesonide

Budesonide has low acute toxicity. With a single inhalation of a large amount of the drug, it can cause temporary suppression of the function of the hypothalamic-pituitary-adrenal system and this does not require emergency assistance.

Interaction

Formoterol

Since Foradil is a beta2-agonist, it should be taken with extreme caution by patients who are already using drugs such as procainamide, disopyramide, quinidine and phenothiazines .

It is also not recommended to take Foradil together with antihistamines, MAO inhibitors, tricyclic antidepressants, as well as other drugs that prolong the QT interval, as this can not only adversely affect the cardiovascular system, but also increase the risk of serious ventricular arrhythmias .

Please also note that simultaneous use of Foradil with other sympathomimetic drugs may cause side effects of the drug.

The potential hypokalemic effect of beta2-adrenomimetics can also be affected by simultaneous use of diuretics, xanthine and corticosteroids with Foradil. Hypokalemia increases the patient's susceptibility to the occurrence and development of severe cardiac arrhythmias if digitalis preparations are present in their treatment regimen.

Beta-blockers can significantly weaken the effect of Foradil.

Budesonide

In order to avoid a decrease in the metabolism of budesonide and an increase in its systemic concentration, you should not take Foradil Combi and CYP3A4 inhibitors ( itraconazole, ketoconazole, ritonavir, nelfinavir, amiodarone, clarithromycin) . If it is not possible to refuse to take these active ingredients and budesonide together rifampicin, phenobarbital, phenytoin can also cause an increase in the metabolism of budesonide and a decrease in its systemic concentration .

Methandrostenolone and estrogens can significantly enhance the effect of budesonide .

Pharmacological action of Foradil Combi

Foradil Combi is a drug with anti-inflammatory and bronchodilator effects. Formoterol is a selective β 2 -adrenergic receptor agonist. It has a bronchodilator effect in patients with both reversible and irreversible airway obstruction. The effect of the drug occurs quickly (within 1-3 minutes) and persists for 12 hours after inhalation. When using the drug in therapeutic doses, the effect on the cardiovascular system is minimal and is observed only in rare cases.

Inhibits the release of histamine and leukotrienes from mast cells. Animal experiments have shown some anti-inflammatory properties of formoterol, such as the ability to inhibit the development of edema and the accumulation of inflammatory cells. In human studies, Foradil Combi has been shown to be effective in preventing bronchospasm caused by inhaled allergens, exercise, cold air, histamine or methacholine.

Since the bronchodilator effect of Foradil Combi remains pronounced for 12 hours after inhalation, maintenance therapy, in which Foradil Combi is prescribed 2 times a day, 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 chronic obstructive pulmonary disease (COPD), formoterol causes a rapid onset of a bronchodilator effect and an improvement in quality of life parameters.

Budesonide is a glucocorticosteroid (GCS) for inhalation use with virtually no systemic effect. 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 arachidonic acid metabolic products - cyclic endoperoxides and prostaglandins.

Prevents the marginal accumulation of neutrophils, reduces inflammatory exudation and the production of cytokines, inhibits the migration of macrophages, reduces the severity of infiltration and granulation processes, the formation of a 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-adrenergic receptors, 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 with GCS develops on average within 10 days after the start of therapy. When used regularly 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.

Analogs

Level 4 ATX code matches:
Tevacomb

Foster

Symbicort Turbuhaler

Seretide

Today, Foradil Combi has about 10 analogues in terms of pharmacological action among domestic and foreign medicines.

The main analogues of the drug Foradil Combi on the market are: Atmadisk Forte , Biasten , Seretide and Seretide Multidisk . Tevacomb and Foster are also popular .

Reviews of Foradil Combi

The rating of Foradil Combi on the forums is 4.9 on a 5-point scale. Forum visitors include the following advantages of the drug:

• high efficiency;
• easy-to-use inhaler;
• affordable price.

After analyzing reviews of Foradil Combi on the forums, it was revealed that for some discussion participants the drug caused side effects in the form of severe nausea and headache , but during the course of treatment these symptoms completely disappeared.

One of the most frequently asked questions to specialists is the question: “Hormonal or not?” Doctors honestly answer that this drug is hormonal and advise everyone to consult with their doctor before starting to use this drug.

There is no information about the drug Foradil on Wikipedia.