Symbicort Turbuhaler, inhalation powder 160/4.5 µg/dose, 120 doses

Composition

1 the delivered dose (the dose coming out of the mouthpiece) contains:

Active ingredients:

budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg.

Auxiliary substances:

lactose monohydrate – 730 mcg.

Pharmacological action

Pharmacodynamics

Symbicort Turbuhaler contains formoterol and budesonide, which have different mechanisms of action and show an additive effect on reducing the frequency of exacerbations of bronchial asthma.

Budesonide. Budesonide, an inhaled glucocorticosteroid, in recommended doses has an anti-inflammatory effect in the bronchi, reducing the severity of symptoms and the frequency of exacerbations of bronchial asthma with a lower frequency of side effects than with the use of systemic glucocorticosteroids. Reduces the severity of edema of the bronchial mucosa, mucus production, sputum formation and hyperreactivity of the respiratory tract.

Formoterol. Formoterol is a selective p2-adrxnrg receptor agonist that induces relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect occurs quickly, within 1-3 minutes after inhalation and persists for 12 hours after taking a single dose.

Budesonide + Formoterol. Bronchial asthma 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 the Turbuhaler Symbicort on bronchial function corresponds to the effect of a combination of monopreparations budesonide and formoterol and exceeds the effect of budesonide alone. The drug is well tolerated.

Symbicort Turbuhaler improves bronchial function and is well tolerated in children aged 6 to 11 years when taking the drug for 12 weeks (two inhalations of 80/4.5 mcg / inhalation twice a day).

Chronic obstructive pulmonary disease (COPD) Patients with severe COPD who received Symbicort Turbuhaler showed a significant reduction in the frequency of exacerbations of the disease compared to patients who received only formoterol or placebo as therapy (the average frequency of exacerbations was 1.4 compared to 1.8 – 1.9 in the placebo/formoterol group). There were no differences between the intake of Symbicort and formoterol on the indicator of forced expiratory volume in the first minute (FEV).

Pharmacokinetics

Suction. Symbicort Turbuhaler is bioequivalent to the corresponding monopreparations with respect to the systemic action of budesonide and formoterol. Despite this, there was a slight increase in cortisol suppression after taking Symbicort Turbuhaler compared to monopreparations. This difference does not imply an impact on clinical safety. There is no evidence of a pharmacokinetic interaction between budesonide and formoterol.

Pharmacokinetic parameters for the corresponding substances are comparable after the appointment of budesonide and formoterol in the form of monopreparations and as part of the Turbuhaler Symbicort. For budesonide, when administered as a combination drug, the area under the concentration-time curve (AUC) is slightly larger, the absorption of the drug is faster, and the maximum concentration in blood plasma is higher.

For formoterol, when administered as part of a combined preparation, the maximum concentration in blood plasma coincides with that for a monopreparation.

Inhaled budesonide is rapidly absorbed and reaches its maximum plasma concentration 30 minutes after inhalation. The average dose of budesonide that enters the lungs after inhalation through a Turbuhaler is 32-44% of the delivered dose. Systemic bioavailability is approximately 49% of the delivered dose. In children aged 6 to 16 years, the average dose of budesonide that entered the lungs after inhalation through a Turbuhaler does not differ from that in adult patients (the final concentration of the drug in blood plasma was not determined).

Inhaled formoterol is rapidly absorbed and reaches its maximum plasma concentration 10 minutes after inhalation. The average dose of formoterol that enters the lungs after inhalation through a Turbuhaler is 28-49% of the delivered dose. Systemic bioavailability is approximately 61% of the delivered dose.

Distribution and metabolism. Approximately 50% of formoterol and 90% of budesonide bind to plasma proteins. The volume of distribution for formoterol is about 4 l/kg and for budesonide 3 l/kg. Formoterol is inactivated by conjugation (active O-demethylated metabolites are formed, mainly in the form of inactivated conjugates). Budesonide undergoes intensive biotransformation (about 90%) at the first passage through the liver with the formation of metabolites with low glucocorticosteroid activity. Glucocorticosteroid activity of the main metabolites of 6-beta-hydroxybudesonide and 16-alpha-hydroxyprednisolone does not exceed 1% of the same activity of budesonide. There is no evidence of a metabolite interaction or substitution reaction between budesonide and formoterol.

The main part of the formoterol dose is metabolized in the liver and then excreted by the kidneys. After inhalation,8-13% of the delivered dose of formoterol is excreted unchanged in the urine. Formoterol has a high systemic clearance (approximately 1.4 l / min); the drug has an average half-life of 17 hours.

Budesonide is primarily metabolized by the enzyme CYP3A4. Budesonide metabolites are excreted in the urine unchanged or in the form of conjugates. Only a small amount of unchanged budesonide is detected in the urine. Budesonide has a high systemic clearance (approximately 1.2 l / min).

The pharmacokinetics of formoterol in children and in patients with renal insufficiency have not been studied. Plasma concentrations of budesonide and formoterol may be elevated in patients with liver disease.

Indications

• Bronchial asthma (insufficiently controlled by inhaled corticosteroids and short-acting beta-2-adrenostimulants or adequately controlled by inhaled corticosteroids and long-acting beta-2-adrenostimulants).
• COPD (Symptomatic treatment in patients with severe chronic obstructive pulmonary disease (FEV

Use during pregnancy and lactation

There are no clinical data on the use of Turbuhaler Symbicort or the combined use of formoterol and budesonide during pregnancy.

During pregnancy, Symbicort Turbuhaler should only be used in cases where the benefits of the drug outweigh the potential risk to the fetus. The lowest effective dose of budesonide needed to maintain adequate control of asthma symptoms should be used. It is not known whether formoterol or budesonide passes into the breast milk of women.

Symbicort Turbuhaler can be prescribed to nursing women only if the expected benefit to the mother is greater than any possible risk to the child.

Contraindications

Hypersensitivity to budesonide, formoterol, or inhaled lactose. Children under 6 years of age.

With caution: Tuberculosis of the lungs (active or inactive form); fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalismia, idiomatic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any localization or other severe cardiovascular diseases (coronary heart disease, tachyarrhythmia or severe heart failure), prolongation of the time interval between the two types of diseases. QT (taking formoterol may cause prolongation of the QTc interval).

Side effects

There was no increase in the frequency of adverse reactions when the two drugs were co-administered. The most common adverse reactions associated with taking the drug are such pharmacologically expected adverse events for (beta-adrenomimetics) as tremor and rapid heartbeat, symptoms usually have a moderate degree of severity and disappear within a few days after the start of treatment. During the course of budesonide treatment in COPD, bruising and pneumonia occurred at rates of 10% and 6%, respectively, compared to 4% and 3% in the placebo group (p >0.001 and p> 0.01, respectively).

The systemic effect of inhaled glucocorticosteroids can occur when taking high doses for a long time.

The use of beta-adrenomimetics can lead to an increase in the blood content of insulin, free fatty acids, glycerol and ketone derivatives.

Interaction

Taking 200 mg of ketoconazole once a day increases the plasma concentration of oral budesonide (a single dose of 3 mg) with their combined use, on average, by 6 times. When ketoconazole was administered 12 hours after budesonide use, the plasma concentration of the latter increased, on average, by 3 times. There is no information about such an interaction with inhaled budesonide, but a noticeable increase in the concentration of the drug in blood plasma should be expected. Since there are no data available for dose recommendations, the combination of drugs described above should be avoided. If this is not possible, the time interval between the use of ketoconazole and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent CYP3A4 inhibitors are also likely to significantly increase the plasma concentration of budesonide.

Beta-adrenergic receptor blockers may weaken the effect of formoterol. Symbicort Turbuhaler should not be administered concomitantly with beta-blockers (including eye drops), except in emergency cases.

Co-use of Symbicort Turbuhaler with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors (MAO), and tricyclic antidepressants may prolong the QT interval and increase the risk of ventricular arrhythmias.

In addition, levodopa. levothyroxine, oxytocin, and alcohol may reduce heart muscle tolerance to p2-adrenomimstics.

Co-use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, can cause an increase in blood pressure. There is an increased risk of arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbons.

When taking Symbicort Turbuhaler and other beta-adrenergic drugs together, the side effect of formoterol may increase.

Hypokalemia may occur as a result of the use of beta-2-adrenomimetics, which may increase with concomitant treatment with xanthine derivatives, mineral derivatives of glucocorticosteroids or diuretics. Hypokalemia may increase the predisposition to arrhythmias in patients taking cardiac glycosides.

There was no interaction of budesonide with other drugs used for the treatment of bronchial asthma.

How to take, course of use and dosage

Symbicort Turbuhaler is not intended for the initial treatment of intermittent and mild persistent bronchial asthma. The dose of drugs included in the Turbuhaler Symbicort is selected individually and depending on the severity of the disease. This should be taken into account not only when starting treatment with combined drugs, but also when changing the dose of the drug. In the event that individual patients require a different dose combination of active components than in the Turbuhaler Symbicort, pV adrenomimetics and/or glucocorticosteroids in separate inhalers should be prescribed.

Bronchial asthma

Adults (18 years and older): Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose: 1-2 inhalations twice a day. If necessary, it is possible to increase the dose to 4 inhalations twice a day. After achieving optimal control of symptoms of bronchial asthma while taking the drug twice a day, it is possible to reduce the dose to the lowest effective dose, up to once a day.

Adolescents (12-17 years): Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose: 1-2 inhalations twice a day.

Children over 2 years of age: Symbicort Turbuhaler 80/4.5 mcg / dose: 1-2 inhalations twice a day.

Patients should visit their doctor regularly to monitor the optimal dose of Symbicort Turbuhaler, the dose should be reduced to the lowest, against which optimal control of symptoms of bronchial asthma is maintained. After achieving optimal control of bronchial asthma when taking the drug twice a day, it is recommended to titrate the dose to the minimum effective dose, up to taking the drug once a day, in cases where, in the opinion of the doctor, the patient needs maintenance therapy in combination with a long-acting bronchodilator.

COPD Adults: 2 inhalations of Symbicort Turbuhaler 160/4.5 mcg / dose twice daily.

Special patient groups: there is no need for special selection of the drug dose for elderly patients. There are no data on the use of Symbicort Turbuhaler in patients with renal or hepatic insufficiency. Since budesonide and formoterol are mainly excreted by the kidneys, with the participation of hepatic metabolism, patients with severe cirrhosis of the liver can expect a slowdown in the rate of elimination of the drug.

Children under 6 years of age:Symbicort Turbuhaler is not recommended for children under 6 years of age.

Instructions for proper use of the Turbuhaler:

Mechanism of action of Turbuhaler: when inhaled by the patient through the mouthpiece, the drug enters the respiratory tract.

It is necessary to instruct the patient:

• carefully read the instructions for use of Turbuhaler
• inhale strongly and deeply through the mouthpiece to ensure that the optimal dose of the drug gets into the lungs,
• never exhale through the mouthpiece.

The patient may not taste or feel the drug after using the Turbuhaler, which is due to the small amount of substance delivered.

Overdose

Symptoms of formoterol overdose: tremor, headache, rapid heartbeat. In some cases, tachycardia, hyperglycemia, hypokalemia, prolongation of the QTc interval, arrhythmia, nausea and vomiting have been reported. If it is necessary to cancel the Turbuhaler Symbicort due to an overdose of formoterol, which is part of the combined drug, the appointment of an appropriate glucocorticosteroid should be considered.

Treatment: supportive and symptomatic. Taking formoterol at a dose of 90 mcg for 3 hours in patients with acute bronchial obstruction is safe. With an acute overdose of budesonide, even in significant doses, no clinically significant effects are expected. If excessive doses are taken chronically, systemic effects of glucocorticosteroids may occur, such as hypercorticism and adrenal suppression.

Special instructions

It is recommended to gradually reduce the dose of the drug before stopping treatment and it is not recommended to abruptly cancel treatment.

Symbicort (80/4.5 micrograms/inhalation) Turbuhaler is not intended for patients with severe bronchial asthma.

Symbicort Turbuhaler is not intended for the initial selection of therapy at the first stages of treatment of bronchial asthma.

Taking formoterol may cause prolongation of the QT interval.

An increase in the frequency of taking bronchodilators as emergency medications indicates a worsening of the course of the underlying disease and serves as a basis for reviewing the tactics of treating bronchial asthma. Unexpected and progressive deterioration in the control of symptoms of asthma or COPD is a potentially life-threatening condition and requires urgent medical intervention. In this situation, the possibility of increasing the dose of glucocorticosteroids or adding systemic anti-inflammatory therapy, such as a course of oral glucocorticosteroids or antibiotic treatment in case of infection, should be considered. Patients are advised to carry emergency medications (short-acting beta-2 adrenomimetics) at all times. It is necessary to pay the patient’s attention to the need for regular intake of Symbicort Turbuhaler in accordance with the selected dose, even in cases where there are no symptoms of the disease.

Treatment with Symbicort Turbuhaler should not be started during the period of exacerbation of bronchial asthma.

As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after taking a dose of the drug. Therefore, it is necessary to stop therapy with Symbicort, review the treatment strategy and, if necessary, prescribe alternative therapy.

Systemic effects can occur when taking any inhaled glucocorticosteroids, especially when taking high doses of drugs for a long period of time.Systemic effects are less likely to occur during inhalation therapy. than when using oral glucocorticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma.

It is recommended to regularly monitor the growth of children receiving long-term corticosteroid therapy in an inhaled form. In case of established growth retardation, therapy should be reviewed in order to reduce the dose of the inhaled glucocorticosteroid. The ratio of the benefits of glucocorticosteroid therapy to the possible risk of growth retardation should be carefully evaluated. When choosing therapy, it is recommended to consult a pediatric pulmonologist.

Based on limited research data on long-term use of glucocorticosteroids, it can be assumed that the majority of children and adolescents receiving inhaled budesonide therapy will eventually reach normal adult growth rates. However, minor (approximately 1 cm), short-term growth retardation was reported, mainly in the first year of treatment.

Due to the potential effect of inhaled glucocorticosteroids on bone mineral density, special attention should be paid to patients taking high doses of the drug for a long period of time 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 micrograms (measured dose) or adults at a daily dose of 800. micrograms (measured dose) showed no noticeable effect on bone mineral density. There are no data on the effect of high doses of Turbuhaler Symbicort on bone mineral density.

If there is reason to believe that the adrenal function was impaired during previous systemic therapy with glucocorticosteroids, precautions should be taken when transferring patients to treatment with Symbicort Turbuhaler. The benefits of budesonide inhalation therapy generally minimize the need for oral steroids, but patients who discontinue oral glucocorticosteroid therapy may experience long-term adrenal insufficiency. Patients who have previously needed urgent high-dose glucocorticosteroids and received long-term treatment with inhaled high-dose glucocorticosteroids may also be at this risk. Additional use of glucocorticosteroids should be considered during periods of stress or surgery. It is recommended to instruct the patient to rinse his mouth with water after inhalation in order to prevent the development of candidiasis of the oral mucosa. Precautions should be taken when treating patients with an extended QTc interval. Taking formoterol may cause prolongation of the QTc interval. Patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system should review the need for and dose of an inhaled glucocorticosteroid. When beta-2-adrenomimetics are co-administered with drugs that may cause or increase the hypokalemic effect, such as xanthine derivatives, steroids, or diuretics, the hypokalemic effect of beta-2-adrenomimetics may be increased. Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve seizures during exacerbation of severe bronchial asthma, since the risk of hypokalemia increases against the background of hypoxia and in other conditions when the probability of developing a hypokalemic effect increases. In such cases, it is recommended to monitor the content of potassium in the serum.

During the treatment period, the blood glucose concentration should be monitored in patients with diabetes mellitus.

Turbuhaler symbicort contains lactose (

AFFECTING THE ABILITY TO DRIVE A CAR OR OTHER MECHANISMS. The Turbuhaler symbicort does not affect the ability to drive a car and operate mechanisms. It may affect the ability to drive a car and operate mechanisms in case of side effects.

Form of production

Powder for inhalation dosed

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Active ingredient

Budesonide, Formoterol

Conditions of release from pharmacies

By prescription

Dosage form

powder for inhalation

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor, Children over 6 years of age, Pregnant women as prescribed by a doctor

Indications

Low Learning Rate, Bronchospasm, Bronchial asthma