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).

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%).

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.

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 .

Foradil Combi set of capsules with por d/ing 400 mcg/12 mcg pack cont cell/pack card x120

Foradil Combi set of capsules with por d/ing 400 mcg/12 mcg x120, ATX code: R03AK07 (Formoterol and budesonide)

Active substances

budesonide Rec.INN registered by WHO formoterol Rec.INN registered by WHO

Dosage forms

FORADIL COMBI

set of capsules with powder for inhalation: 40, 60, 70, 90, 120, 150 or 180 pcs. in a pack, including: caps. 12 mcg formoterol: 30 or 60 pcs., caps. 200 mcg budesonide: 10, 30, 60 or 120 pcs. included with inhalation device (aerolyzer) reg. No.: LSR-003336/09 from 04/30/09 - Indefinitely

set of capsules with powder for inhalation: 40, 60, 70, 90, 120, 150 or 180 pcs. in a pack, including: caps. 12 mcg formoterol: 30 or 60 pcs., caps. 400 mcg budesonide: 10, 30, 60 or 120 pcs. included with inhalation device (aerolyzer) reg. No.: LSR-003336/09 from 04/30/09 - Indefinitely

set of capsules with powder for inhalation: 120 pcs. in a pack, including: caps. 12 mcg formoterol: 60 pcs., caps. 200 mcg budesonide: 60 pcs. included with inhalation device (aerolyzer) reg. No.: LSR-003336/09 from 04/30/09 - Indefinitely

set of capsules with powder for inhalation: 120 pcs. in a pack, including: caps. 12 mcg formoterol: 60 pcs., caps. 400 mcg budesonide: 60 pcs. included with inhalation device (aerolyzer) reg. No.: LSR-003336/09 from 04/30/09 - Indefinitely Clinical-pharmacological group: Drug with anti-inflammatory and bronchodilator action Pharmaco-therapeutic group: Bronchodilator (selective beta2-adrenergic agonist + local glucocorticosteroid)

pharmachologic effect

A drug with anti-inflammatory and bronchodilator effects.

Formoterol

Selective β2-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.

Clinical studies have shown that the drug effectively prevents bronchospasm caused by inhaled allergens, exercise, cold air, histamine or methacholine. Since the bronchodilatory effect of formoterol remains pronounced for 12 hours after inhalation, prescribing the drug 2 times a 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 bronchodilator effect and improvement in quality of life parameters.

Budesonide

Budesonide is a GCS for inhalation use with virtually no systemic effects. Like other inhaled corticosteroids, budesonide exerts its pharmacological effects through interaction 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 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.

Pharmacokinetics

Formoterol

Suction

After a single inhalation of formoterol fumarate at a dose of 120 mcg to healthy volunteers, formoterol was rapidly absorbed into the plasma, the Cmax of formoterol in plasma was 266 pmol/l and was achieved within 5 minutes after inhalation. In patients with COPD who received formoterol at a dose of 12 mcg or 24 mcg 2 times a 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 urinary excretion of formoterol and its (R,R)- and (S,S)-enantiomers, it was shown that the amount of formoterol in the systemic circulation increases in proportion to the size of the inhaled dose (12-96 mcg).

After inhaled use of formoterol at a dose of 12 mcg or 24 mcg 2 times a day for 12 weeks, the urinary excretion of unchanged formoterol in patients with bronchial asthma increased by 63-73%, and in patients with COPD - by 19-38%. This indicates some accumulation of formoterol in plasma after repeated inhalations. However, there was no greater accumulation of one of the enantiomers of formoterol compared to the others after repeated inhalations.

As has been reported for other inhaled medicinal products, the majority of formoterol administered by inhalation will be swallowed and subsequently absorbed from the gastrointestinal tract. When 80 mcg of 3H-labeled formoterol was administered orally to two healthy volunteers, at least 65% of the formoterol was absorbed.

Distribution

The binding of formoterol to plasma proteins is 61-64% (with albumin - 34%).

In the concentration range observed after administration of 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 glucuronidation.

Minor metabolic pathways include conjugation of formoterol with sulfate followed by deformylation. Multiple isoenzymes are involved in the process of glucuronidation (UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7 and 2B15) and O-demethylation (CYP2D6, CYP2C19, CYP2C9, CYP2A6) of formoterol, which suggests a low likelihood of drug interactions through inhibition of any or an isoenzyme involved in the metabolism of formoterol. At therapeutic concentrations, formoterol does not inhibit isoenzymes of the cytochrome P450 system.

Removal

In patients with bronchial asthma and COPD who received formoterol fumarate at a dose of 12 mcg or 24 mcg 2 times a day for 12 weeks, approximately 10% or 7%, respectively, was 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 μg) in healthy volunteers and after single and repeated doses of formoterol in patients with bronchial asthma. asthma.

The active substance and its metabolites are completely excreted from the body: by the kidneys - 70%, through the intestines - 30%. The 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 of (R,R)- and (S,S)-enantiomers, calculated from urinary excretion, was 13.9 hours and 12.3 hours respectively.

Pharmacokinetics in special clinical situations

After correction for body weight, the pharmacokinetic parameters of formoterol in men and women do not differ significantly.

The pharmacokinetics of formoterol in elderly patients aged 65 years and older have not been studied.

In a clinical study in children aged 5-12 years with asthma who received formoterol fumarate at a dose of 12 mcg or 24 mcg 2 times a day for 12 weeks, excretion of unchanged formoterol in urine increased by 18-84% compared with the corresponding indicator , measured after the first dose.

In clinical studies in children, about 6% unchanged formoterol was detected in the urine.

The pharmacokinetics of formoterol in patients with impaired liver and/or renal function have not been studied.

Budesonide

Suction

Budesonide is rapidly and completely absorbed after inhalation, with Cmax in blood plasma achieved immediately after administration. After inhalation of budesonide, taking into account the deposition of the drug on the mucous membrane of the oropharynx, the absolute bioavailability is 73%. The absolute bioavailability when taking the drug orally is ±10%.

Distribution

Vd is 3 l/kg. Plasma protein binding - 88%. Systemic clearance of the drug administered by inhalation is 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.

Metabolism

Budesonide 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 of 84 l/h and a short T1/2 of 2.8 hours. The main pathway of budesonide metabolism in the liver via the CYP3A4 isoenzyme of the P450 system can be altered by inhibitors or inducers of CYP3A4.

Removal

T1/2 - 2-2.8 hours. Excreted through the intestines in the form of metabolites - 10%, by the kidneys - 70%.

Pharmacokinetics in special clinical situations

Plasma concentrations of budesonide are increased in patients with liver disease.

The pharmacokinetics of budesonide in children and adolescents have not been studied. However, data on other inhaled products containing budesonide suggest that the clearance of budesonide in children over 3 years of age is approximately 50% higher compared to adult patients.

Indications

Bronchial asthma:

- insufficiently controlled by taking inhaled corticosteroids and short-acting beta2-agonists as on-demand therapy,

- adequately controlled by inhaled corticosteroids and long-acting beta2-agonists.

Chronic obstructive pulmonary disease (COPD) (with proven effectiveness of the use of GCS).

ICD-10 codes

Dosage regimen

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

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

Pre-inhalation of beta-agonists dilates the bronchi, improves the entry of budesonide into the respiratory tract and enhances its therapeutic effect. Therefore, for maintenance therapy of bronchial asthma and COPD, formoterol is first inhaled, then budesonide is inhaled.

1. The dose of formoterol for regular maintenance therapy is 12-24 mcg (contents of 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, 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 is not prescribed if a single dose of less than 200 mcg is required. 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 divided doses (200-400 mcg 2 times/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 2-4 doses.

Children aged 6 years and older

Pre-inhalation of beta-agonists dilates the bronchi, improves the entry of budesonide into the respiratory tract and enhances its therapeutic effect. Therefore, for maintenance therapy of bronchial asthma, formoterol is first inhaled, then budesonide is inhaled.

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. Treatment of children with mild forms of bronchial asthma begins 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.

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 function

There are no data available on the need for dose adjustment in patients with impaired renal function. Based on the pharmacokinetics of oral budesonide, it is unlikely that clinically significant systemic exposure to the drug is possible in these patients.

Patients with liver dysfunction

There are no data on 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 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 data available on the need to adjust the dose of the drug in patients over 65 years of age, compared with younger patients.

Rules 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 aerosolizer, and warn the patient that the capsules are for inhalation use only and are not intended for inhalation use. for swallowing. 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.

Remove the capsule from the blister pack immediately before use.

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 medical professional must explain to the patient how to use the drug correctly, especially if the patient’s breathing does not improve after inhalation.

Instructions for using the aerolizer

1. Remove the cap from the aerolizer.

2. Hold the aeralizer 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 aerolizer (it has the shape of a capsule). It should be remembered that you need to remove the capsule from the blister pack immediately before inhalation.

4. Turn the mouthpiece and close the aerolyzer.

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

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 does 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. Exhale completely.

7. Place the mouthpiece in your mouth and tilt your head back slightly. Cover the mouthpiece tightly with your lips and take a quick, even, as deep breath as possible. In this case, the patient should hear a characteristic rattling sound created by the rotation of the capsule and spraying of the powder. If there was no characteristic sound, then you need to 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 aerolizer.

8. If a characteristic sound is heard when inhaling, you should hold your breath as long as possible. At the same time, remove the mouthpiece from your mouth. Then exhale. Open the aerolizer 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, open the aerolizer, remove the empty capsule, close the mouthpiece and close the aerolizer with the cap.

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

Side effect

Adverse reactions observed in clinical studies are distributed according to frequency of occurrence. The following criteria were used to assess the frequency: very often (≥1/10), often (from ≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/100) 10,000, <.1/1000), very rare (<.1/10,000), including isolated reports. Within each group, adverse reactions are distributed in order of decreasing importance.

Formoterol

Allergic reactions: very rarely - hypersensitivity reactions, such as arterial hypotension, urticaria, angioedema, itching, rash.

From the mental side: infrequently - agitation, anxiety, increased excitability, insomnia.

From the nervous system: often - headache, tremor, infrequently - dizziness, very rarely - taste disturbances.

From the cardiovascular system: often - palpitations, infrequently - tachycardia, very rarely - peripheral edema.

From the respiratory system: infrequently - bronchospasm, including paradoxical, irritation of the mucous membrane of the pharynx and larynx.

From the digestive system: infrequently - dryness of the oral mucosa, very rarely - nausea.

From the musculoskeletal system: infrequently - muscle spasm, myalgia.

Adverse reactions according to post-marketing observations when prescribing formoterol (Foradil)

Laboratory and instrumental data: hypokalemia, hyperglycemia, prolongation of the QT interval (during ECG), increased blood pressure (including arterial hypertension).

From the respiratory system: cough.

From the skin and subcutaneous tissues: rash.

From the cardiovascular system: angina pectoris, heart rhythm disturbances, incl. atrial fibrillation, ventricular extrasystoles, tachyarrhythmia.

Budesonide

From the endocrine system: rarely - suppression of adrenal cortex function, Cushing's syndrome, hypercortisolism, growth retardation in children and adolescents.

From the side of the organ of vision: rarely - cataracts, glaucoma.

Allergic reactions: rarely - hypersensitivity reactions, rash, urticaria, angioedema, itching, contact dermatitis (delayed hypersensitivity reaction type IV).

From the psyche: post-marketing observations - psychomotor hyperactivity, sleep disturbances, anxiety, depression, aggressive behavior, behavioral disorders (especially in children).

From the musculoskeletal system: rarely - decrease in bone mineral density.

From the respiratory system: often - cough, rarely - paradoxical bronchospasm, candidiasis of the oral mucosa and larynx, pharyngeal irritation, dysphonia, which disappears after stopping budesonide therapy or reducing the dose of the drug.

In a three-year clinical study, when using budesonide in patients with COPD, there was an increase in the incidence of subcutaneous hematomas (10%) and pneumonia (6%) compared with the placebo group (4% and 3%, with p <.001 and p <.0.01, respectively ).

Contraindications for use

- lactation period (breastfeeding),

- active pulmonary tuberculosis,

- hereditary galactose intolerance, severe lactase deficiency and glucose-galactose malabsorption syndrome,

- children under 6 years of age,

- hypersensitivity to formoterol, budesonide or any other component of the drug.

Formoterol

Particular caution when using formoterol (especially in terms of dose reduction) and careful monitoring of patients is required in the presence of the following concomitant diseases: coronary artery disease, cardiac arrhythmia and conduction disorders, especially third-degree AV block, severe chronic heart failure, idiopathic subvalvular aortic stenosis , hypertrophic obstructive cardiomyopathy, aortic aneurysm, thyrotoxicosis, known or suspected prolongation of the QT interval (QT corrected > 0.44 sec), hypokalemia, hypocalcemia and pheochromocytoma.

Given the hyperglycemic effect characteristic of beta-agonists, including formoterol, additional regular monitoring of blood glucose concentrations is recommended in patients with diabetes.

Budesonide

Because budesonide is not effective in relieving acute bronchospasm, the drug should not be prescribed as primary therapy for status asthmaticus or other acute asthmatic conditions.

Caution should be exercised when using budesonide in patients with inactive pulmonary tuberculosis, fungal, bacterial and viral respiratory tract infections, liver cirrhosis, and glaucoma. Also, given the possibility of developing fungal infections, the drug should be prescribed with caution for bronchiectasis and pneumoconiosis.

Formoterol and budesonide capsules contain lactose.

Use during pregnancy and breastfeeding

Formoterol

The safety of using Foradil Combi during pregnancy and lactation has not yet been established.

Use during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Formoterol, as well as other beta2-agonists, can slow down the process of labor due to its tocolytic effect (relaxing effect on the smooth muscles of the uterus).

It is not known whether formoterol is excreted into breast milk in humans. Breastfeeding should be stopped while taking Foradil Combi.

Budesonide

Experimental studies on animals revealed a possible teratogenic effect of GCS on the fetus. There is no data on the teratogenic effect of budesonide or on the presence of reproductive toxicity in the drug when used in humans.

Use during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. If it is necessary to carry out GCS therapy during pregnancy, it is preferable to prescribe them in the form of inhalations, because GCS for inhalation have less systemic effect compared to oral GCS.

It is not known whether budesonide is excreted into breast milk in humans.

Fertility

There is no data on the effect of the drug on fertility. Experimental studies on animals did not reveal any effect on fertility with oral formoterol and subcutaneous administration of budesonide.

Use for liver dysfunction

There are no data on 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 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.

Use for renal impairment

There are no data available on the need for dose adjustment in patients with impaired renal function. Based on the pharmacokinetics of oral budesonide, it is unlikely that clinically significant systemic exposure to the drug is possible in these patients.

Use in children Contraindication: children under 6 years of age.

Use in elderly patients No data have been obtained on the need to adjust the dose of the drug in patients over 65 years of age, compared with younger patients.

special instructions

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.

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.

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 .

Foradil Combi 12 mcg/400 mcg No. 60+No. 60 capsules with powder for inhalation

Content

Pharmacological action Indications Dosage regimen Side effects Contraindications for use With caution Method of administration and doses Special groups of patients Instructions for inhalation Instructions for use of the Aerolyzer Special instructions Drug interactions Storage conditions Expiration date

pharmachologic effect

Combined bronchodilator. Budesonide and formoterol have different mechanisms of action and exhibit an additive effect in reducing the frequency of exacerbations of bronchial asthma and COPD.

The special properties of budesonide and formoterol make it possible to use their combination simultaneously as maintenance therapy and for the relief of attacks, or as maintenance therapy for bronchial asthma.

Budesonide is a corticosteroid that, after inhalation, has a rapid (within several hours) and dose-dependent anti-inflammatory effect on the respiratory tract, reducing the severity of symptoms and the frequency of exacerbations of bronchial asthma. When prescribing inhaled budesonide, there is a lower incidence of serious adverse effects than when using systemic corticosteroids. Reduces the severity of edema of the bronchial mucosa, mucus production, sputum formation and airway hyperreactivity. The exact mechanism of the anti-inflammatory effect of GCS is unknown.

Formoterol is a selective β2-adrenergic agonist that, following inhalation, causes rapid and long-lasting relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator dose-dependent effect occurs quickly, within 1-3 minutes after inhalation and persists for at least 12 hours after taking a single dose.

The addition of formoterol to budesonide reduces the severity of symptoms of bronchial asthma, improves bronchial function and reduces the frequency of exacerbations of the disease. The effect of this fixed combination on bronchial function corresponds to the effect of the combination of budesonide and formoterol monotherapy and exceeds the effect of budesonide alone. In all cases, a short-acting beta2-agonist agonist was used to relieve attacks. There was no decrease in anti-asthmatic effect over time. The combination is well tolerated.

Indications

Bronchial asthma, insufficiently controlled by taking inhaled corticosteroids and short-acting beta2-agonists or adequately controlled by inhaled corticosteroids and long-acting beta2-agonists.

Symptomatic treatment of patients with severe COPD (FEV1 <50% predicted level) and with a history of recurrent exacerbations who have severe symptoms of the disease despite therapy with long-acting bronchodilators.

Dosage regimen

The method of administration and dosage regimen of a particular drug depend on its release form and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular drug with the indications for use and dosage regimen should be strictly observed.

The dose and frequency of use are set individually, depending on the indications, clinical situation, age of the patient, and dosage form used.

Side effect

• From the nervous system: often (>1/100, <1/10) - headache; less often (>1/1000, <1/100) - psychomotor agitation, anxiety, nausea, dizziness, sleep disturbances; very rarely (<1/10,000) - depression, behavioral disorders (mainly in children), taste disturbances.
• From the cardiovascular system: often (>1/100, <1/10) - palpitations; less often (>1/1000, <1/100) - tachycardia; rarely (>1/10,000, <1/1000) - atrial fibrillation, supraventricular tachycardia, extrasystole; very rarely (<1/10,000) - angina pectoris, blood pressure fluctuations.
• From the musculoskeletal system: often (>1/100, <1/10) - tremor; less often (>1/1000, <1/100) - muscle cramps.
• From the respiratory system: often (>1/100, <1/10) - candidiasis of the oral mucosa and pharynx, mild irritation in the throat, cough, hoarseness; rarely (>1/10,000, <1/1000) - bronchospasm.
• Dermatological reactions: less often (>1/1000, <1/100) - bruising; rarely (>1/10,000, <1/1000) - exanthema, itching, dermatitis.
• Allergic reactions: rarely (>1/10,000, <1/1000) - urticaria, angioedema, anaphylactic reactions.
• Metabolic disorders: rarely (>1/10,000, <1/1000) - hypokalemia; very rarely (<1/10,000) - hyperglycemia, symptoms of systemic action of GCS (including adrenal hypofunction).

The systemic effect of inhaled corticosteroids can be observed when taking the drug in high doses for a long time.

The use of beta2-adrenergic agonists can lead to an increase in the blood levels of insulin, free fatty acids, glycerol, and ketone derivatives.

Contraindications for use

Hypersensitivity to budesonide, formoterol or inhaled lactose; children's age (depending on the dosage form used).

Carefully

Pulmonary tuberculosis (active or inactive form), fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any location or other severe cardiovascular diseases (CHD, tachyarrhythmia or severe heart failure), prolongation of the QT interval.

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 the blue buttons located on the sides completely 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. You need 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.

special instructions

It is recommended to gradually reduce the dose before stopping treatment. It is not recommended to abruptly cancel treatment.

The combination of budesonide/formoterol is not used for the initial selection of therapy in the first stages of treatment of bronchial asthma.

Taking formoterol may cause QT prolongation.

An increase in the frequency of taking bronchodilators as emergency medications indicates a worsening of the underlying disease and serves as a basis for revising the treatment tactics for bronchial asthma. Sudden and progressive deterioration in control of symptoms of asthma or COPD is a potentially life-threatening condition and requires urgent medical attention. In this situation, you should consider increasing the dose of GCS or adding systemic anti-inflammatory therapy, for example, a course of oral GCS or antibiotic treatment in case of infection. Patients are advised to carry emergency medications (short-acting beta2-agonists) with them at all times.

The patient's attention should be drawn to the need to regularly take the drug containing the combination of budesonide/formoterol in accordance with the selected dose, even in cases where there are no symptoms of the disease.

Treatment should not be started during periods of exacerbation or significant worsening of bronchial asthma.

As with any other inhaled therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after taking a dose of the combination drug. In this regard, therapy should be discontinued, treatment tactics should be reconsidered and, if necessary, alternative therapy should be prescribed.

Systemic effects may occur when taking any inhaled corticosteroids, especially when taking drugs in high doses over a long period of time. Systemic effects are less likely to occur with inhalation therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, decreased bone mineral density, cataracts, and glaucoma.

Due to the potential effect of inhaled corticosteroids on bone mineral density, special attention should be paid to patients taking high doses of the drug for a long period with the presence of risk factors for osteoporosis. Studies of long-term use of inhaled budesonide in children at an average daily dose of 400 mcg (metered dose) or adults at a daily dose of 800 mcg (metered dose) did not show a significant effect on bone mineral density.

If there is reason to believe that adrenal function has been impaired due to previous systemic GCS therapy, precautions should be taken when transferring patients to treatment with the budesonide/formoterol combination.

The benefits of inhaled budesonide therapy generally minimize the need for oral steroids, but patients who discontinue oral corticosteroid therapy may experience long-term adrenal insufficiency. Patients who in the past required acute use of high doses of corticosteroids or received long-term treatment with high-dose inhaled corticosteroids may also be at this risk. It is necessary to provide additional administration of GCS during periods of stress or surgery.

The need for the use and dose of inhaled GCS should be reconsidered in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.

When beta2-agonists are co-administered with drugs that can cause or enhance the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, the hypokalemic effect of beta2-agonists may be enhanced.

Special precautions should be taken in patients with unstable bronchial asthma using short-acting bronchodilators to relieve attacks during exacerbation of severe bronchial asthma, because the risk of developing hypokalemia increases against the background of hypoxia and in other conditions when the likelihood of developing a hypokalemic effect increases. In such cases, it is recommended to monitor serum potassium levels.

During treatment, blood glucose concentrations should be monitored in patients with diabetes mellitus.

Impact on the ability to drive vehicles and machinery

The budesonide/formoterol combination may have minor effects if side effects occur. Care must be taken when driving vehicles and machinery during the treatment period.

Drug interactions

Taking ketoconazole at a dose of 200 mg 1 time/day increases the plasma concentration of budesonide when administered orally (single dose 3 mg) when administered together by an average of 6 times. When ketoconazole was prescribed 12 hours after taking budesonide, the plasma concentration of the latter increased, on average, 3 times. There is no information about such an interaction with budesonide when administered inhaled, but a noticeable increase in the concentration of the drug in the blood plasma should be expected. Because There are no data for dose selection recommendations; the above combination of drugs should be avoided. If possible, the time interval between the administration of ketoconazole and budesonide should be increased as much as possible. A dose reduction of budesonide should also be considered. Other strong CYP3A4 inhibitors are also likely to significantly increase budesonide plasma concentrations.

β2-adrenergic receptor blockers can reduce the intensity of the action of formoterol. The combination of formoterol + budesonide should not be prescribed simultaneously with beta-blockers (including eye drops), except in cases of emergency.

Co-administration of a combination of formoterol + budesonide and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors, tricyclic antidepressants may prolong the QT interval and increase the risk of ventricular arrhythmias.

In addition, levodopa, levothyroxine, oxytocin and alcohol can reduce the tolerance of the heart muscle to beta2-agonists.

The simultaneous use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, may cause an increase in blood pressure. There is an increased risk of developing arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbon preparations.

With the simultaneous use of a combination of budesonide/formoterol and other beta-adrenergic drugs, the side effects of formoterol may be increased. As a result of the use of beta2-adrenergic agonists, hypokalemia may develop, which may be exacerbated by concomitant treatment with xanthine derivatives, corticosteroids or diuretics. Hypokalemia may increase the susceptibility to the development of arrhythmias in patients taking cardiac glycosides.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging. (protect from moisture)

Keep out of the reach of children.

Best before date

2 years.

Do not use after the expiration date stated on the package.

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.