Symbicort Turbuhaler, inhalation powder 80/4.5 µg/dose, 120 doses

Composition

Active ingredients:

budesonide,

formoterol fumarate dihydrate Auxiliary substances:

lactose monohydrate.

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

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

From the central nervous system:  headache; psychomotor agitation, restlessness, nausea, dizziness, sleep disorders; depression, behavioral disorders (mainly in children), taste disorders.

From the cardiovascular system:  palpitations; tachycardia; atrial fibrillation, supraventricular tachycardia, extrasystole; angina pectoris, blood pressure fluctuations.

Musculoskeletal disorders:  tremor; muscle cramps.

Respiratory system disorders:  candidiasis of the oral and pharyngeal mucosa, mild irritation in the throat, cough, hoarseness; bronchospasm.

Dermatological reactions:   bruising; exanthema, pruritus, dermatitis.

Allergic reactions:  urticaria, angioedema, anaphylactic reactions.

Metabolic disorders: hypokalemia; hyperglycemia, symptoms of systemic corticosteroid action (including adrenal hypofunction).

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 administration, on average, by 6 times. When ketoconazole was administered 12 hours after budesonide administration, 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 described above should be avoided. If this is not possible, the time interval between the administration 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 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), MAO inhibitors, and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.

In addition, levodopa, levothyroxine, oxytocin, and alcohol may reduce the tolerance of the heart muscle to beta-2-adrenomimetics. 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 corticosteroids 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

should be taken into account not only at the beginning of treatment with combined drugs, but also when changing the dose of the drug. In the event that individual patients require a different combination of Active ingredient doses than in Symbicort Turbuhaler, beta-2-adrenomimetics and/or corticosteroids in separate inhalers should be prescribed separately. The dose should be reduced to the lowest level, against which optimal control of asthma symptoms is maintained. Patients should be constantly monitored by a doctor for adequate dose selection of Symbicort Turbuhaler. If you achieve complete control over the symptoms of bronchial asthma against the background of the minimum recommended dose of the drug, at the next stage you can try the appointment of monotherapy with inhaled corticosteroids. There are two approaches to prescribing Symbicortturbuhaler therapy. A. Symbicort Turbuhaler as maintenance therapy: the drug is prescribed as maintenance therapy in combination with a separate short-acting beta-2-adrenostimulant to stop seizures. The patient should always have a separate inhaler with a short-acting beta-2-adrenostimulator to stop seizures. Adults (18 years and older) are prescribed Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose 1-2 inhalations 2 times / day. If necessary, it is possible to increase the dose to 4 inhalations 2 times / day. Adolescents (12-17 years old) are prescribed Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose 1-2 inhalations 2 times / day. Children over the age of 6 years are prescribed Symbicort Turbuhaler 80/4.5 mcg / dose of 1-2 inhalations 2 times a day. After achieving optimal control of symptoms of bronchial asthma while taking the drug 2 times/day, it is recommended to titrate the dose to the lowest effective dose, up to 1 time/day, in cases where, in the opinion of the doctor, the patient requires maintenance therapy in combination with long-acting bronchodilators. An increase in the frequency of use of short-acting beta-2-adrenostimulants is an indicator of deterioration in overall disease control and requires a review of anti-asthmatic therapy.

Overdose

Symptoms: acute overdose of budesonide, even in significant doses, is not expected to cause clinically significant symptoms. Chronic use of budesonide in excessive doses may cause systemic effects of corticosteroids, such as hypercorticism and suppression of adrenal function.

In case of overdose of formoterol – tremor, headache, rapid heartbeat; in some cases, the development of tachycardia, hyperglycemia, hypokalemia, prolongation of the QTc interval, arrhythmia, nausea, vomiting has been reported.

In acute bronchial obstruction, taking formoterol at a dose of 90 mcg for 3 hours was safe.

Treatment: supportive and symptomatic treatment is indicated.

If it is necessary to cancel the Turbuhaler Symbicort due to an overdose of formoterol, which is also part of the combined drug, the appointment of appropriate corticosteroids should be considered.

Special instructions

Powder for inhalation containing budesonide and formoterol in a ratio of 80/4.5 mcg / dose is not indicated for patients with severe bronchial asthma. It is not intended for initial selection of therapy at the first stages of treatment of bronchial asthma. It is recommended to gradually reduce the dose of the drug before discontinuing treatment. An increase in the frequency of taking bronchodilators for emergency care indicates a worsening of the course of the underlying disease and serves as a basis for reviewing the tactics of treatment of bronchial asthma. To minimize the possibility of developing a fungal lesion of the oropharynx, it is necessary to rinse your mouth with water after each inhalation. There are no data on the use of the drug for the relief of acute attacks of bronchial asthma. Patients should be strictly advised to carry emergency medications at all times.

Treatment should not be started during the period of acute bronchial asthma. As with any other inhaled therapy, paradoxical bronchospasm may occur (in this case, the treatment strategy should be reviewed and, if necessary, alternative therapy should be prescribed). The manifestation of systemic action during inhalation therapy is less likely than when using oral corticosteroids. However, it can occur when taking any inhaled corticosteroids, especially when using high doses over a long period of time (it is very important to use the lowest effective dose of inhaled corticosteroids, which provides optimal control of asthma symptoms). Doctors should carefully monitor the growth of children and adolescents who take corticosteroids in any dosage form for a long time, and evaluate the ratio of the benefits of corticosteroid therapy and the possible risk of growth retardation. If the adrenal function has been impaired during previous systemic corticosteroid therapy, precautions should be taken when transferring patients to inhaled drug treatment (patients who stop therapy with oral corticosteroids may have insufficient adrenal function for a long time). In stressful situations, it is always necessary to keep in mind the possibility of residual adrenal dysfunction in such patients.

There are no clinical data on the use of the drug or the combined use of formoterol and budesonide during pregnancy. In pregnant women, the drug should only be used if the intended benefit to the mother exceeds the potential risk to the fetus, and the lowest effective dose of budesonide should be used, which is necessary to maintain adequate control of asthma symptoms. It is not known whether formoterol or budesonide passes into the breast milk of women (the drug can be prescribed to nursing women only if the expected benefit to the mother is greater than any possible risk to the child). During treatment, it is recommended to monitor the concentration of K+ in the blood serum, as well as glucose in patients with diabetes mellitus. Contains lactose (less than 1 mg / dose). Usually, this amount does not cause problems in patients with lactose intolerance.

Form of production

Powder for inhalation.

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

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

Indications

Bronchial Asthma, Bronchospasm, Low Learning Rate