Foradyl Combi - instructions for use, dose, side effects, contraindications

Active substanceBudesonide + FormoterolBudesonide + Formoterol

Similar drugsTo uncover

Symbicort® Turbuhaler®

powder d / inhal.

AstraZeneca AB Sweden

Symbicort® Turbuhaler®

powder d / inhal.

AstraZeneca AB Sweden

Foradil Combi

capsules d / inhal.

Novartis Pharma AG Switzerland

Formisonide®-native

powder d / inhal.

NATIVA, LLC Russia

Dosage form: & nbsp

capsules with powder for inhalation set

Composition:

1 capsule Formoterol contains: active ingredient: formoterol fumarate dihydrate 0.012 mg; auxiliary substances: lactose monohydrate up to 25 mg; capsule shell: gelatin 100% (49.0 mg).

1 capsule Budesonide contains: active ingredient: budesonide 200 μg or 400 μg; auxiliary substances: lactose monohydrate up to 24.77 mg / 24.54 mg; shell capsule (lid): iron oxide red (E172) 0.086 / 0.12%, m / m, titanium dioxide (E171) 2.0 / 2.46%, m / m, water 15.0 / 14.5% , m / m, gelatin 83,0 / 82,8%, m / m. Capsule 400 μg contains also iron oxide black (EI72) 0.075%, m / m, dye crimson (Ponso 4R) 0.04%, m / m; shell capsule (body): water 14.5 / 14.5%, m / m, gelatin 85.5 / 85.5%, m / m.

Description:

Formoterol:

Transparent colorless capsules, marked CG on the lid and FXF on the body or CG on the body and FXF on the lid with black ink. The size of capsule number 3.

The contents of the capsule are white, easily flowing powder.

Budesonide Capsules 200 mcg:

Hard gelatin capsules №3 with a lid of light pink color and colorless

transparent body. The capsule contains "BUDE 200". The contents of the capsules are white powder.

Capsules 400 mcg:

Hard gelatin capsules №3 with a pink lid and colorless transparent

housing. The capsule contains "BUDE 400". The contents of the capsules are white powder.

Pharmacotherapeutic group:bronchodilating agent combined (β2-adrenomimetic selective + glucocorticosteroid local)

ATX: & nbsp

R.03.A.K.07 Formoterol and budesonide

Pharmacodynamics:

Formoterol

Formoterol is a selective β agonist₂adrenoreceptors. It has a bronchodilator effect in patients with reversible airway obstruction. The effect of the drug occurs quickly (within 1-3 minutes) and persists for 12 hours after inhalation. With the use of therapeutic doses, the effect on the cardiovascular system is minimal and is noted only in rare cases.

Formoterol inhibits the release of histamine and leukotrienes from mast cells. In animal experiments, some of the anti-inflammatory properties of the preparation have been shown, such as the ability to inhibit the development of edema and the accumulation of inflammatory cells.

Clinical studies have shown that the drug effectively prevents bronchospasm caused by inhaled allergens, physical activity, cold air, histamine or methacholine. Since the bronchodilator effect of formoterol remains pronounced within 12 hours after inhalation, the use of the drug 2 times a day for prolonged maintenance therapy allows in most cases to provide the necessary control of bronchospasm in chronic lung diseases during day and night.

In patients with chronic obstructive pulmonary disease (COPD) of stable course formoterol also causes a rapid onset of bronchodilator effect and an improvement in the quality of life.

Budesonide

Budesonide is a glucocorticosteroid (GCS) for inhalation, with little or no systemic effect. Like other inhaled glucocorticosteroids, budesonide has pharmacological effects through interaction with intracellular glucocorticoid receptors. Budesonide has anti-inflammatory, anti-allergic and immunosuppressive effects, increases lipocortial production,which inhibits the phospholipase A2, inhibits the release of arachidonic acid, inhibits the synthesis of metabolic products of arachidonic acid-cyclic edroperoxides and prostaglandins; prevents cluster accumulation of neutrophils, reduces inflammatory exudation and production of cytokines, inhibits migration of macrophages, reduces the intensity of infiltration and granulation processes, the formation of a chemotaxis substance (which explains the effectiveness of delayed-type allergic reactions); inhibits the release of inflammatory mediators from mast cells (an allergic reaction of an immediate type). Increases the number of "active" beta-adrenergic receptors, restores the patient's response to bronchodilators, reducing the frequency of their use, reduces edema of the bronchial mucosa, mucus production, sputum formation and reduces airway hyperreactivity; mucociliary clearance. Therapeutic effect of the drug in patients who need treatment with GCS. develops on average within 10 days after initiation of therapy. With regular use in patients with bronchial asthma budesonide reduces the severity of chronic inflammation in the lungs and thus improves their function, facilitates the symptoms of bronchial asthma, reduces the hyperreactivity of the bronchi and prevents the development of exacerbation of the disease.

Pharmacokinetics:

Formoterol

Suction

After a single inhalation, 120 μg of healthy volunteers formoterol quickly absorbed; the maximum concentration in the blood plasma (C_max) was 266 pmol / L and reached within 5 minutes after inhalation. When ingested quickly absorbed from the digestive tract. Absorption - 65%, TS_max 0.5-1 hour. In patients with COPD who received the drug at a dose of 12 or 24 μg twice a day for 12 weeks, its concentration in the blood plasma, measured after 10 minutes, 2 hours and 6 hours after inhalation, was in the ranges 11.5-25.7 pmol / l and 23.3-50.3 pmol / l, respectively.

When studying the total excretion of formoterol and its (R.R) and (S, S) enantiomers in urine, it was shown that the concentration in the systemic blood flow increases in proportion to the amount of inhaled dose (12-96 μg).

After inhalation of the drug at a dose of 12 or 24 μg twice a day for 12 weeks, excretion of the drug unchanged in urine in patients with bronchial asthma increased by 63-73%, and in patients with COPD - by 19-38%.The ego indicates some cumulation of the drug in the blood plasma after repeated inhalations. At the same time, there was no greater cumulation of one of the enantiomers of formoterol compared to another after repeated inhalations.

Just as it was reported for other drugs used in the form of inhalations, most of the drug used with the inhaler is swallowed (about 90%) and then absorbed from the gastrointestinal tract (GIT). When 80 μg of the 3H-labeled preparation was administered orally, at least 65% of the drug was absorbed in two healthy volunteers.

Binding to blood plasma proteins and distribution

Binding of the drug to plasma proteins is 61-64%, binding to albumin of serum - 34%.

In the range of concentrations noted after the application of therapeutic doses of the preparation, saturation of binding sites is not achieved.

Metabolism

The main route of metabolism is formoterol direct conjugation with glucuronic acid. Another way of metabolism is O-demethylation followed by conjugation with glucuronic acid (glucuronidation).

Low-value metabolic pathways include conjugation of the drug with sulfate, followed by deforming. A lot of isoenzymes participate in the processes of glucuronidation (UGTIA1, 1 AZ, 1A6, IA7, IA8 .1A9.IA10, 2B7 and 2B15) and O-demethylation (CYP2D6.2C19.2C9 and 2A6) of the drug, which implies a low probability of drug interaction by inhibiting any isoenzyme. taking part in the metabolism of formoterol. In therapeutic concentrations, the drug does not inhibit the isozymes of the cytochrome 1450 system.

Excretion

In patients with bronchial asthma and COPD who received the drug at a dose of 12 or 24 μg twice a day for 12 weeks, approximately 10% and 7% of the dose, respectively, was determined in the urine unchanged. The calculated fractions of (RR) and (SS) enantiomers of the unchanged drug in urine are 40% and 60%, respectively, after a dose of formoterol (12-120 μg) once in healthy volunteers and after a single and repeated dose of formoterol in patients with bronchial asthma .

The active substance and its metabolites are completely eliminated from the body: 70% by the kidneys, 30% through the intestine. Kidney clearance of the drug is 150 ml / min. T1 / 2 - 2-3 hours.

In healthy volunteers, the final half-life of the drug from the blood plasma after a single inhalation of formoterol at a dose of 120 μg is 10 hours: the final half-life (RR) and (S, S) enantiomers calculated from urinary excretion were 13.9 and 12.3 hours, respectively.

Pharmacokinetics in selected patient groups

Floor

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

Patients ≥65 years of age

The pharmacokinetics of formoterol in patients ≥65 years of age have not been studied.

Patients aged ≤ 18 years

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

In clinical studies in children in urine was determined about 6% of unchanged drug.

Patients with impaired hepatic and / or renal function

Pharmacokinetics of the drug in patients with impaired liver and / or kidney function has not been studied.

Budesond

Absorption

Budesond quickly and completely absorbed after inhalation, the maximum concentration of the drug in the blood plasma is achieved immediately after use. After inhalation budesonide taking into account the sedimentation of the drug on the mucous membrane of the oropharynx absolute bioavailability is 73%. Absolute bioavailability when taking the drug inside is ± 10%.Distribution

The volume of distribution of the drug is 3 l / kg. In studies budesond accumulated in the spleen, lymph nodes, thymus gland, adrenal cortex, reproductive organs and bronchi, and also penetrated the placental barrier.

Metabolism

Budesond is not metabolized in the lungs. The systemic clearance of the inhaled drug is 0.5 l / min. The connection with plasma proteins is 88%. 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 than budesonide), including 6β-hydroxybuddesonide and 16α-hydroxyprednisolone (systemic clearance 1.4 l / min) . Budesond has a high system clearance of 84 l / h and a short half-life of 2.8 h.

The main pathway of metabolism of budesonide in the liver with the CYP3A4 isoenzyme of the P450 system can be altered by inhibitors or inductors of the CYP3A4 isoenzyme.

Excretion

T_1/2- 2-2.8 hours. It is excreted through the intestines in the form of metabolites - 10%, kidneys - 70%. Concentration of budesonide in blood plasma is increased in patients with liver disease.Pharmacokinetics in selected patient groups Patients <18 years of age

The pharmacokinetics of budesonide in children has not been studied. However, data on other inhalation preparations containing budesonide, suggest that the clearance of the drug in children over 3 years old is approximately 50% higher than in adults.

Indications:

Bronchial asthma:

- Insufficiently controlled intake of inhaled glucocorticosteroids (GCS) and short-acting Br-agonists as therapy on demand;

- adequately controlled by inhaled GCS and β₂agonists of long-lasting action. Chronic obstructive pulmonary disease (COPD) (with proven efficacy of GCS).

Contraindications:

-Increased sensitivity to formoterol or any other component of the drug.

-Increased sensitivity to budesonide or any other component of the drug.

-Child up to 6 years.

-The period of breastfeeding.

Active pulmonary tuberculosis.

It is not recommended for patients with rare hereditary diseases, such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption, since the dosage form contains lactose.

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

Formoterol

Exercise caution when using formoterol (especially when decreasing the dose) and careful monitoring of patients is required in the presence of the following concomitant diseases: coronary heart disease; disturbance of rhythm and conduction of the heart, especially atrioventricular blockade of the third degree: heart disease in the stage of decompensation (including chronic heart failure of severe degree); idiopathic subvalvular aortic stenosis; severe arterial hypertension, aortic aneurysm; hypertrophic obstructive cardiomyopathy, thyrotoxicosis; known or suspected prolongation of the QT interval (QT corrected> 0.44 sec), hypokalemia, hypocalcemia and pheochromocytoma.

Considering the hyperglycemic effect characteristic of β₂-adrenomimetics, including formoterol, in patients with diabetes, additional regular monitoring of blood glucose concentration is recommended.

Budesonide

Because the budesonide is not effective for relief of acute bronchospasm, the drug should not be used as the main therapy for asthmatic status or other acute asthmatic conditions.

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

Pregnancy and lactation:

Formoterol

The safety of formoterol during pregnancy and lactation has not been established to date.

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. Formoterol, as well as other β₂-adrenomimetiki, can inhibit the ancestral activity due to tocolytic action (a relaxing effect on the smooth musculature of the uterus). It is not known whether the formoterol in breast milk. Patients receiving treatment with formoterol should stop breastfeeding.

Budesonide

In experimental studies in animals, a possible teratogenic effect of glucocorticosteroids (GCS) was revealed. There is no evidence of a teratogenic effect of budesonide or the presence of reproductive toxicity in human use. The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to carry out GCS therapy during pregnancy, they are preferably used in the form of inhalations, since glucocorticosteroids for inhalation use have a lower systemic effect compared to oral dosage forms.

Budesonide is secreted into breast milk. The use of the drug in the period of breastfeeding is contraindicated.

Fertility

There are no data on the effect of the drug on fertility. Studies have shown no effect on fertility in animals with oral administration of formotrol and subcutaneous administration of budesonide.

Dosing and Administration:

Formoterol and budesonide are intended for inhalation use.

Preparations are capsules with powder for inhalation,which should be used only with the help of a special device - the Air-conditioner, which is included in the package.

Formoterol and budesonide should be applied individually, in the minimum effective dose.

When you reach the control of symptoms of bronchial asthma on the background of therapy with formoterol, you should consider the possibility of a gradual decrease in the dose of the drug.

Reduction of the dose of formoterol is carried out under regular medical supervision.

Against the background of exacerbation of bronchial asthma should not be treated with formoterol or change the dose of the drug. Formoterol It should not be used to stop acute attacks of bronchial asthma.

When performing therapy with an inhalation device, the dose of the drug should be gradually adjusted to doses sufficient to maintain a therapeutic effect.

Budesopid + Formoterol

Adults

Preliminary inhalation of beta-adrenomimetics expands the bronchi, improves the flow of budesonide in the respiratory tract and enhances its therapeutic effect, therefore maintenance therapy for bronchial asthma and COPD is carried out in the following sequence:

1- inhalation of formoterol,

2-inhaled budesonide.

1. The dose of formoterol for regular maintenance therapy is 12-24 μg (1-2 capsules content) 2 times a day.

Do not exceed the maximum recommended dose of the drug for adults (48 mcg per day).

Given that the maximum daily dose of formoterol is 48 μg, if necessary, you can additionally apply 12-24 μg per day to alleviate the symptoms of bronchial asthma. If the need for additional doses of the drug ceases to be episodic (for example, more often than 2 days per week), the patient should consult a physician to consider the issue of changing therapy, as this may indicate a worsening of the course of the disease.

2. The minimum dose of budesonide in one capsule is 200 μg. Do not use the drug if a single dose of less than 200 micrograms is required. In adult patients with mild asthma, treatment is started with a minimum effective dose of 200 μg / bp. The maintenance dose of budesonide for adult patients is 400-800 μg per day in 2 divided doses (200-400 μg twice a day).

With exacerbation of bronchial asthma during translationpatient with the use of medicinal forms of GCS for oral administration to inhalation forms or with a decrease in the dosage of dosage forms of GCS for oral administration budesonide should be used at a dose of 1600 mcg / day in 2-4 doses.

Children aged ≥6 years

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 μg per day.

2. Due to the lack of clinical experience in children younger than 6 years, budesond should not be used in patients of this age group.

Treatment in children with bronchial asthma of mild severity should start with a dose of 200 mcg / day. The dose of budesonide for regular maintenance therapy is 100-200 μg 2 times a day. If necessary, the dose of budesonide can be increased to a maximum of 800 μg / day.

Individual patient groups

Patients with impaired renal function

There is no data on the need for dose adjustment in patients with impaired renal function. Based on the pharmacokinetics of budesonide when administered internally, it is unlikely that the systemic effect of the drug in these patients may change clinically.

Impaired liver function

There is no data on the need for dose adjustment in patients with impaired liver function, however, budsonide is excreted mainly by the liver. In this regard, the drug should be used with caution in patients with impaired hepatic function. In patients with impaired liver function of mild or moderate severity, a significant change in the effect of the drug is unlikely given the pharmacokinetic indices of budesonide when ingested.

Elderly patients (over 65 years of age)

There is no data on the need for dose adjustment in patients older than 65 years.

Instructions for inhalation

To ensure proper use of the drug by a nurse or doctor, the patient should be trained in the correct technique for using the inhaler; clarify that the use of capsules with powder for inhalation should be done only with the help of Aerolazsra; warn the patient that the capsules are for inhalation use only and are not intended for ingestion. In children and adolescents inhalation budesonide and formoterol should be carried out under the supervision of adults.It is necessary to make sure that the child correctly performs the technique of inhalation.

It is important to warn the patient that when a gelatin capsule is destroyed, small pieces of gelatin, as a result of inhalation, can enter the mouth or throat. In order to reduce this phenomenon to a minimum, do not pierce the capsule more than 1 time.

Remove the capsule from the blister pack immediately before use (see also the Instruction for the use of the Airlighter.).

Rinsing the mouth with water after inhalation budesonide can prevent the development of irritation of the oral and pharyngeal mucosa, as well as reduce the risk of developing systemic adverse events.

There are separate reports of accidental ingestion of the capsules of the preparation as a 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 of the drug, especially if, after inhalation, the patient does not experience improvement in breathing.

INSTRUCTION FOR THE USE OF AEROLYSER

1. Remove the cap from the air conditioner.

2. Hold the air conditioner firmly at the base, turn the mouthpiece in the direction of the arrow.

3.Place the capsule in the cell located at the base of the Airlighter (it has the shape of a capsule). Remember that remove the capsule from the blister pack immediately before inhalation.

4. Turn the mouthpiece and close the air conditioner.

5. Holding the air-conditioner in a strictly vertical position, press down one time to the blue buttons located on the sides of the air-conditioner. Then release them.

Note. At this stage, when piercing the capsule, it can collapse, resulting in small pieces of gelatin can get into your mouth or throat. Because the gelatin it will not do you any harm. To ensure that the capsule does not completely break down, the following requirements should be met: do not puncture the capsule more than once; observe the rules of storage; Remove the capsule from the blister just before the inhalation.

6. Take a full exhalation.

7. Take the mouthpiece into your mouth and slightly tilt your head back. Tightly grasp the mouthpiece with your lips and make a quick, uniform, maximum deep breath.

You should hear a characteristic rattling sound produced by rotating the capsule and spraying the powder.

If you do not hear the characteristic sound, you need to open the air conditioner and see what happened to the capsule. Perhaps she was stuck in the cell. In this case, you need to carefully remove the capsule. Do not try to release the capsule by repeatedly pressing the buttons on the sides of the air conditioner.

8. If by inhalation you have heard a characteristic sound, hold your breath for as long as possible. At the same time, take the mouthpiece out of your mouth. Then exhale. Open Aerolizsr and see if the powder remained in the capsule. If powder remains in the capsule, repeat the actions described in paragraphs 6-8.

After the end of the inhalation procedure, open the air conditioner, remove the empty capsule, close the mouthpiece and close the air cap with the cap.

How to care for the Arolizer

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

Side effects:

The adverse events (AEs) identified in clinical trials are grouped according to the classification of organs and systems of MedDRA organs. are listed in order of decreasing frequency of occurrence.

The following criteria were used to estimate the frequency: very often (> 1/10); often (> 1/100. <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages. Within each group, unwanted events are distributed in order of decreasing importance. Since in the postmarketing period reports of AEs are received voluntarily from a population of undetermined size, it is not possible to reliably estimate the incidence of their occurrence, and therefore "frequency is unknown" for these AEs.

Formoterol

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

Disorders of the psyche: infrequently - agitation, a sense of anxiety, increased excitability, insomnia.

Disturbances from the nervous system: often - headache, tremor; infrequently - dizziness; very rarely - a violation of taste.

Heart disorders: often - palpitations; infrequently, tachycardia; very rarely - peripheral edema; frequency unknown - angina, heart rhythm disturbance, incl. Atrial fibrillation, ventricular extrasystoles, tachyarrhythmia.

Disturbances from the respiratory system, the thoracic and mediastinal organs: infrequently - bronchospasm, including paradoxical, irritation of the mucous membrane of the pharynx and larynx; frequency is unknown - cough.

Disturbances from the gastrointestinal tract: infrequent - dryness of the oral mucosa; very rarely - nausea.

Disorders from the musculoskeletal and connective tissue: infrequently - muscle spasm, myalgia.

Laboratory and instrumental data: the frequency is unknown - the decrease in serum potassium, the increase in serum glucose concentration, the prolongation of the QT interval on the electrocardiogram, the increase in blood pressure (including arterial hypertension).

Disturbances from the skin and subcutaneous tissues: frequency is unknown - rash.

Budesonide

Disorders from the endocrine system: rarely - suppression of adrenal cortex function, Itenko-Cushing syndrome, hypercorticism, hypokorticism, growth retardation in children and adolescents.

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

Impaired immune system: rarely - hypersensitivity reactions, rash, urticaria, angioedema, itching; frequency unknown - contact dermatitis (hypersensitivity reaction of delayed type (IV).

Disorders of the psyche: the frequency is unknown - psychomotor hyperactivity, sleep disorders, anxiety, depression, aggressive behavior, behavioral disorders (especially in children).

Disturbances from the gastrointestinal tract: often - difficulty swallowing; frequency is unknown - a violation of taste.

Disorders from the musculoskeletal and connective tissue: rarely - a decrease in bone mineral density.

Disturbances from the respiratory system, chest and mediastinum: often - cough; rarely - paradoxical bronchospasm, candidiasis of the mucous membrane of the mouth and larynx, irritation of the pharynx, dysphonia, resolved after discontinuing therapy with budesonide or after a dose reduction.

In a 3-year clinical trial using budesonide in patients with COPD, there was an increase in the incidence of subcutaneous hematoma (10%) and pneumonia (6%) compared with the placebo group (4% and 3%, with p <0.001 and p <0 , 01, respectively).

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Formoterol

Symptoms

An overdose of formoterol can probably lead to the development of phenomena characteristic of beta2-adrenomimetics: nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmia, metabolic acidosis, hypokalemia, hyperglycemia, hypertension.

Treatment

Supportive and symptomatic therapy is indicated. Serious cases require hospitalization.

Cardioselective beta-blockers can be considered, under careful medical supervision, provided extreme caution is observed, since the use of such drugs can cause bronchospasm.

Budesonide

Budesonide has a low acute toxicity. A single inhalation of a large amount of the drug may lead to a temporary suppression of the function of the hypothalamic-pituitary-adrenal system, which does not require emergency therapy.

In case of an overdose with budesonide, treatment can be continued at doses sufficient to maintain a therapeutic effect.

Interaction:

Formoterol

Formotherol, as well as other β₂-adrenomimetics, should be used with caution in patients receiving such medications as quinidine, disopyramide, procainamide, phenothiazines. antihistamines, macrolide antibiotics, inhibitors of monoamine oxidase (MAO), tricyclic antidepressants, as well as other drugs that can prolong QT interval, since in these cases adrenomimietikov action on the cardiovascular system can be enhanced. When using drugs that can extend the QT interval, the risk of ventricular arrhythmias increases.

Simultaneous use of other sympathomimetic drugs can lead to aggravation of side effects of formoterol.

The simultaneous use of xanthine derivatives, glucocorticosteroids or diuretics can potentiate the potential hypokalemic effect of β₂-adrenomimetics.

In patients receiving anesthesia using halogenated hydrocarbons, the risk of arrhythmia increases.

Beta-adrenoblockers can weaken the action of formoterol. And communication with this should not be applied formoterol simultaneously with beta-blockers (including eye drops),If only to the use of such a combination of drugs do not force any extraordinary reasons.

Budesonide

The use of the drug together with inhibitors of the isoenzyme CYP3A4 (for example, itraconazole, ketoconazole, ritonavir, nelfinavir, amiodarone, clarithromycin) can lead to a decrease in the metabolism of budesonide and increase its systemic concentration. When budesonide is used together with inhibitors of the CYP3A4 isoenzyme, the function of the adrenal cortex should be monitored regularly and, if necessary, the dose of budesonide should be changed.

When budesonide is used together with preparations inducing the isoenzyme CYP3A4 (for example, rifampicin, phenobarbital, phenytoin), it is possible to accelerate the metabolism of budesonide and reduce its systemic concentration. Methandrostenolone, estrogens strengthen the action of budesonide.

Special instructions:

Formoterol

It is shown that when using formoterol, the quality of life of patients with COPD is improved. Formoterol belongs to the class β₂-adrenomimetics of long-acting. Against the background of the application of another β₂long-acting adrenomimetic, salmeterol, there was an increase in the frequency of legal outcomes associated with bronchial asthma (13 of 13,176 patients) compared with placebo (3 of 13,179 patients).Clinical studies to assess the frequency of development of legal outcomes associated with bronchial asthma, against the background of the use of formoterol was not conducted.

Anti-inflammatory therapy

In patients with bronchial asthma formoterol should be used only as an additional treatment with insufficient control of symptoms against the background of monotherapy with inhaled glucocorticosteroids or in a severe form of the disease requiring the use of a combination of inhaled corticosteroid and 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 the anti-inflammatory therapy without changes, even if improvement is noted.

To stop an acute attack of bronchial asthma, beta2-adrenomimetics of short action should be used. In case of sudden deterioration of the condition, patients should immediately seek medical help.

Severe exacerbations of bronchial asthma

13 placebo-controlled clinical trials in patients who received formoterol for 4 weeks, there was an increase in the incidence of severe exacerbations of bronchial asthma (0.9% with a dosing regimen of 10-12 mcg 2 times a day, 1.9% at 24 mcg 2 times a day) compared with the placebo group (0.3 %), especially in children 6-12 years old.

In two large controlled clinical trials involving 1,095 adult patients and children 12 years of age and older, severe exacerbations of bronchial asthma (requiring hospitalization) were more frequent in patients who received formoterol in a dose of 24 mcg 2 times a day (9/271, 3.3%), compared with formoterol groups at a dose of 12 mcg 2 times a day (1/275 0.4%), placebo (2/277, 0.7%) and albuterol (2/272 0.7%).

When using formoterol for 16 weeks in another large clinical trial involving 2085 adult patients and adolescents, there was no increase in the frequency of severe exacerbations of bronchial asthma, depending on the increase in the dose of formoterol. However, in this study, the frequency of severe exacerbation was higher in the formoterol group (with a dosage regimen of 24 μg 2 times a day - 2/527, 0.4%, 12 μg 2 times a day - 3/527, 0.6%). compared with placebo (1/517, 0.2%).In the open phase of this study, when using formoterol at a dose of 12 μg 2 times a day (if necessary, patients could use up to two additional doses of the drug), the frequency of severe exacerbations of bronchial asthma was 1/517, 0.2%.

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

However, the results of the above clinical studies do not allow quantitative assessment of the incidence of severe exacerbations of bronchial asthma in various groups.

Hypokalemia

The consequence of therapy is β₂-adrenomimetics, including formoterol, there may be a development of potentially serious hypokalemia. Hypokalemia may increase predisposition to the development of arrhythmias.

Since this action of the drug can be intensified by hypoxia and concomitant treatment, special care should be taken in patients with severe bronchial asthma.In these cases, regular monitoring of the potassium content in serum is recommended.

Paradoxical bronchospasm

As with other inhalation therapies, the possibility of developing a paradoxical bronchospasm should be considered. With the development of this condition, you should immediately cancel the drug and prescribe an alternative treatment.

Budesonide

To ensure that budesonide enters the lungs, it is important to instruct patients to properly administer the inhalation of the drug in accordance with the instructions for use. It should be informed to the patient that the drug is not intended to stop attacks, but for regular daily prophylactic use even in the absence of symptoms of bronchial asthma.

With the development of paradoxical bronchospasm should immediately stop using budesonide, assess the patient's condition and, if necessary, start therapy with other medications. Paradoxical bronchospasm should be immediately stopped with the help of β₂-adrenomimetics of short action. The patient should always have an inhaler with β₂-adrenomimetikom short-acting for relief of exacerbations of bronchial asthma.

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

To reduce the risk of candidal infection of the oral cavity and pharynx, it is recommended to thoroughly rinse the 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 discontinuing treatment with budesonide.

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

It is necessary to regularly monitor the growth dynamics of children and adolescents receiving long-term inhaled glucocorticosteroids. If growth is delayed, consider the need to reduce the dose of inhaled glucocorticosteroids (the minimum effective dose) and refer the child to a consultation with an allergist.

Long-term effects of the growth delay (effect on final adult height) in children receiving therapy with inhaled glucocorticosteroids, ns studied. Adequate study of the ability to compensate for the delayed growth in children after the abolition of oral GCS therapy was not carried out.

Budesonide usually does not affect the function of the adrenal glands. However, in some patients with prolonged use at recommended daily doses, a systemic effect of budesonide may be noted.

In the application of inhaled corticosteroids at high doses and for a long period of time may develop systemic adverse events (but less frequently than when using SCS for oral administration), such as suppression of adrenocortical function, hyperadrenocorticism / Cushing's syndrome, growth retardation in children and adolescents, decrease in bone mineral density, hypersensitivity reactions, cataracts, glaucoma, and, rarely, a number of behavioral disorders including psychomotor hyperactivity, insomnia, 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 initiation of treatment. At the beginning of budesonide therapy in patients with increased bronchial secretion to inhalation of the drug, it is possible to add to the GKS therapy for oral administration with a short course (duration about 2 weeks).

Patients with hormone-dependent bronchial asthma

It is necessary to stabilize the patient's state when going from taking GCS inward to the inhalation use of budesonide.

During the first 10 days, high doses of budesonide are used in combination with previous SCS for oral administration at the previous dose. Then the daily dose of GCS for oral administration is gradually reduced (but 2.5 mg every month in terms of prednisolone) to the lowest possible level. Do not abruptly discontinue treatment with GCS, including budesonide.

In the first months after the transition, the patient's condition should be carefully monitored until the function of the hypothalamic-hygiene-adrenal system is restored, sufficient to provide adequate response to stressful situations (for example, trauma, surgery or severe infection).It is necessary to regularly monitor the performance of the gynothalamo-gynophysial-paternoster system.

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

When transferring patients from systemic GCS to inhaled therapy with budesonide, such reactions as allergic rhinitis, eczema, blocking, pain in muscles and joints, sometimes nausea and vomiting, which were previously stopped by the reception of systemic GCS, may appear. Treatment of these reactions should be carried out with antihistamines or GCS for topical use.

Effect on the ability to drive transp. cf. and fur:

Patients who, with the use of formoterol, experience dizziness or other disturbances from the central nervous system, one should refrain from managing motor vehicles or working with mechanisms during the period of application of the drug.

In connection with the possibility of developing neuropsychiatric symptoms when using budesonide, care should be taken when managing vehicles and mechanisms.

Form release / dosage:

Capsule with powder for inhalation set.

Packaging:

10 capsules with formoterol in the blister. 10 capsules with budesonide per blister. For 3 or 6 blisters with capsules with formoterol 12 μg and 1,3,6 or 12 blisters with capsules with budesonide 200 μg or 400 μg complete with device for inhalation (aerolaser) and instructions for use in cardboard pack.

Storage conditions:

In a dry place, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003336/09

Date of registration:30.04.2009

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS PHARMA, AG Switzerland