SYMBICORT TURBUHALER POWDER FOR INHALATION 160MKG/4.5MKG/DOSE

Mechanism of action

Combined medication for the treatment of bronchial asthma. Contains formoterol and Budesonide, which have different mechanisms of action and exhibit an additive effect in reducing the frequency of exacerbations of asthma.
Budesonide - GCS for inhalation use. When used in recommended doses, it has an anti-inflammatory effect in the lungs, reducing the severity of symptoms and the frequency of exacerbations of asthma with a lower incidence of side effects than when using systemic corticosteroids. The exact mechanism responsible for the anti-inflammatory effect of the drug is unknown.
Formoterol is a selective agonist b2-adrenoreceptors. It causes relaxation of the smooth muscles of the bronchi in patients with reversible airway obstruction. Bronchodilatory effect occurs quickly, within 1-3 minutes after inhalation, and lasts for 12 hours after taking a single dose.
In clinical studies, it was found that with the combined use of formoterol and budesonide, the severity of asthma symptoms decreases, lung function improves and the frequency of exacerbations of the disease decreases.
The effect of Symbicort Turbuhaler on lung function corresponds to the effect of a combination of monodrugs budesonide and formoterol and exceeds the effect of budesonide. The drug is well tolerated.
While receiving Symbicort Turbuchaler for 12 weeks (two inhalations of 80 / 4.5 mcg / inhalation twice a day), lung function was improved in children aged 6 to 11 years and good tolerability was noted.
Patients with severe COPD while receiving Symbicort Turbuhaler showed a significant decrease in the frequency of exacerbations of the disease compared with patients who received only formoterol or placebo as a therapy (average frequency of exacerbations 1.4 compared with 1.8-1.9 in the placebo / formoterol group). There were no differences between Symbicort and formoterol intake on expiratory forced exponent (FEV1).

Suction
Symbicort Turbuhaler is bioequivalent with the corresponding monopreparations (budesonide and formoterol) in relation to their systemic action. Despite this, there was a slight increase in suppression of cortisol after taking Symbicort Turbuhaler compared with monopreparations. This difference does not affect the clinical safety of Symbicort Turbuhaler. There is no evidence for the pharmacokinetic interaction of budesonide and formoterol. The pharmacokinetic parameters of budesonide and formoterol were comparable after their administration as monopreparations and as part of Symbicort Turbuhaler.
When using the combined drug AUC, budesonide was slightly larger, the drug was absorbed faster and the C valuemax was higher; Cmax formoterol coincided with that for a single product. Inhaled budesonide is rapidly absorbed and reaches Cmax in 30 minutes. The average dose of budesonide in 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, which entered the lungs after inhalation through the turbuhaler, does not differ from that in adult patients (the final concentration of the drug in the blood plasma was not determined).
Inhalable formoterol is rapidly absorbed and reaches Cmax 10 minutes after inhalation. Studies have shown that the average dose of formoterol, which entered the lungs after inhalation through a turbuhaler, is 28-49% of the delivered dose. Systemic bioavailability is about 61% of the delivered dose.
Distribution and metabolism
About 50% of formoterol and 90% of budesonide bind to plasma proteins. Vd formoterol is about 4 l / kg, budesonide - 3 l / kg. Formoterol is metabolized in the liver by conjugation to form active O-demethylated and deformed metabolites, but mostly inactivated conjugates. Budesonide undergoes intensive biotransformation (about 90%) during the "first pass" through the liver to form metabolites with low glucocorticoid activity.Glucocorticoid activity of the main metabolites - 6-b-hydroxybudesonide and 16-a-hydroxyprednisolone - does not exceed 1% of the similar activity of budesonide. There is no evidence of interaction of metabolites or substitution reactions between budesonide and formoterol.
Formoterol is metabolized in the liver. Budesonide is metabolized primarily with the participation of the CYP3A4 enzyme.
Removal
After inhalation, 8–13% of the delivered dose of formoterol is excreted unchanged in the urine. Formoterol has high system clearance (approximately 1.4 l / min.), T1/2 averages 17 hours
Budesonide is excreted in the urine as metabolites (conjugates) and only in small quantities in unchanged form. Budesonide has a high system clearance (approximately 1.2 l / min); T1/2 after the on / in the introduction of an average of 4 hours
Pharmacokinetics in special clinical situations
The pharmacokinetics of formoterol in children and in patients with renal insufficiency has not been studied.
Plasma concentrations of budesonide and formoterol may increase in patients with liver disease.

Indications and usage

- supportive therapy of bronchial asthma in cases where the use of a combination of inhaled GCS and b is clinically justified2long-acting agonists: in patients whose condition is not sufficiently controlled by inhaled GCS and inhalation beta2short-acting adrenomimetics used as emergency medications "as needed" or in patients whose condition is already adequately controlled by inhaled GCS and beta2long-acting agonists.
Symbicort turbuhaler with a content in 1 dose of budesonide 80 mcg and formoterol 4.5 mcg is not indicated for patients with severe bronchial asthma.
- symptomatic therapy in patients with severe chronic obstructive pulmonary disease (COPD) (FEV1 <50% of the estimated normal level) and with recurring exacerbations in history, which have pronounced symptoms of the disease, despite the treatment with long-acting bronchodilators.

Symbicort Turbuhaler is not intended for the initial selection of therapy in the early stages of treatment of bronchial asthma.
Selection of the dose of drugs that are part of Symbicort Turbuhaler, is carried out individually and depending on the severity of the disease. This must be taken into account when starting treatment with combination drugs. In the event that individual patients require a dosage that goes beyond the recommended treatment regimen, it should be administered separately b2-adrenomimetics and / or glucocorticoids in the appropriate dosage.
At bronchial asthma adults and adolescents (12 years and older) designate Symbicort Turbuhaler 80 / 4.5 mcg / dose 1-2 inhalations 2 times / day, Symbicort Turbuhaler 160 / 4.5 mcg / dose - 1-2 inhalations 2 times / day.
After achieving optimal control of the symptoms of bronchial asthma while taking the drug 2 times / day, the dose may be reduced to the lowest effective level, up to and including 1 time / day.
Children aged 6 to 12 years designate Symbicort Turbuhaler 80 / 4.5 mcg / dose 1-2 inhalations 2 times / day.
At COPD for adults they prescribe Symbicort Turbuhaler 160 / 4.5 mcg / dose, 2 inhalations, 2 times / day.
There is no need for a special selection of the drug dose for elderly patients.
There is no data on the admission of Symbicort Turbuhaler patients with renal or hepatic failure. Since budesonide and formoterol are excreted mainly by the kidneys, with the participation of hepatic metabolism, in patients with severe cirrhosis of the liver, we can expect a slower rate of excretion of the drug.
Instructions for proper use of the turbuhaler
The mechanism of action of the turbuhaler is such that when the patient inhales through the mouthpiece, the air flows carry the medicinal substance into the respiratory tract.
The following instructions should be given to the patient: carefully read the “Instructions for use”, which is in the package with each turbuhaler; breathe heavily and deeply through the mouthpiece to ensure that the optimal dose of the drug is released into the lungs; never exhale through the mouthpiece; In order to minimize the possibility of developing a fungal infection of the oropharynx, the patient should rinse his mouth with water after each inhalation. The patient may not feel the taste or feel the drug after using the turbuhaler, due to the small amount of the substance delivered.

Since Symbicort Turbuhaler contains budesonide and formoterol, we can expect the development of the same side effects, which are noted in the case of the use of these drugs separately. Against the background of co-administration of two drugs, there was no increase in the incidence of adverse reactions.
The most frequent adverse reactions associated with taking the drug are those pharmacologically expected for beta.2-adrenomimetikov undesirable side effects, like tremor and tachycardia, which usually have a moderate degree of severity and disappear in a few days after the start of treatment.
Side effects that are associated with budesonide or formoterol are listed below.
From the side of the central nervous system: often (1/100) - headache; possible - agitation, anxiety, nausea, dizziness, sleep disturbances.
Since the cardiovascular system: often (1/100) - tachycardia; more pronounced tachycardia is possible.
From the musculoskeletal system: often (1/100) - tremor; possible muscle cramps.
On the part of the respiratory system: often (1/100) - candidiasis of the oral mucosa, mild throat irritation, cough, hoarseness, pneumonia; rarely (1/1000) - bronchospasm; in rare cases, paradoxical bronchospasm.
Dermatological reactions: often (1/100) - hemorrhages in the subcutaneous fat; rarely (1/1000) - rash, urticaria, pruritus.
Symptoms of systemic action of budesonide: in rare cases - depression, behavioral disturbance (mainly in children), adrenal hypofunction, allergic reactions of immediate or delayed types (includingdermatitis, angioedema and bronchospasm).
Symptoms associated with the action of formoterol: in isolated cases - angina, hyperglycemia, change in taste, fluctuations in blood pressure.
For other b2-adrenomimetic cardiac arrhythmias such as atrial fibrillation, supraventricular tachycardia and extrasystole were noted.

- children's age up to 6 years;
- hypersensitivity to budesonide, formoterol or inhaled lactose.

There are no clinical data on the use of Symbicort Turbuhaler or the combined use of formoterol and budesonide during pregnancy.
During pregnancy, Symbicort Turbuhaler should be prescribed only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus. Budesonide should be used in the smallest effective dose necessary to maintain adequate control of the symptoms of bronchial asthma.
It is not known whether formoterol and budesonide penetrate into breast milk. Symbicort turbuhaler can be assigned to nursing women, if the expected benefit of therapy for the mother outweighs the potential risk to the child.

AT experimental studies study of the toxic effects of a combination of drugs on reproductive function in animals was not conducted. When studying the effect of formoterol on reproductive function in animals, it was found that side effects were observed at very high concentrations of the drug in the body.

Care should be taken when using Symbicort Turbuchaler in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial respiratory infections.
Turbuchaler should be prescribed with caution.
Care should be taken when treating patients with a long QTc interval. Acceptance of formoterol may cause prolongation of the QTc interval.
With extreme caution should use the drug for acute exacerbation of severe bronchial asthma, since the risk of hypokalemia increases against the background of hypoxia. During the treatment of exacerbation of severe bronchial asthma, it is recommended to monitor the content of potassium in serum.
When using the drug in patients with diabetes, it is necessary to additionally monitor the concentration of glucose in the blood.
It is recommended to gradually reduce the dose of the drug before discontinuing treatment.
The increase in the frequency of taking bronchodilators, as an emergency medicine, indicates a worsening of the course of the underlying disease and serves as a basis for reviewing the tactics of treating bronchial asthma. An unexpected and progressive deterioration in the control of symptoms of bronchial asthma or COPD is a potentially life-threatening condition and requires urgent medical intervention. In this situation, the possibility of increasing the dose of GCS or adding systemic anti-inflammatory therapy, for example, a course of oral GCS or treatment with antibiotics, should be considered in case of an infection.
Patients are advised to keep emergency medications with them at all times (b2 - short-acting adrenomimetics).
Treatment Symbicort turbuhaler should not begin in 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. When a severe reaction develops, the treatment tactics should be reviewed and, if necessary, alternative therapy should be prescribed.
Systemic effects can occur when taking any inhaled GCS, especially when taking high doses of drugs over a long period of time. The manifestation of systemic action is less likely with inhalation therapy than with the use of oral corticosteroids. Possible systemic effects include suppression of adrenal function, growth retardation in children and adolescents, a decrease in bone mineral density, cataracts, and glaucoma. Particular attention should be paid to patients with advanced COPD with low bone mineral density due to the possible effects on bone tissue.Therefore, it is very important to use the lowest effective dose of inhaled GCS, which provides optimal control of the symptoms of bronchial asthma.
It is necessary to carefully monitor the growth of children and adolescents who take GCS for a long time in any dosage form, and evaluate the ratio of the benefits of GCS therapy to the possible risk of growth retardation.
If there is reason to believe that, against the background of previous systemic treatment of GCS, the adrenal function was impaired, precautions should be taken when transferring patients to Symbicort Turbuhaler.
Advantages of inhaled budesonide therapy, as a rule, minimize the need to take oral GCS, however, patients who discontinue therapy with oral GCS for a long time may have insufficient adrenal function. Patients who in the past needed emergency high-dose corticosteroids may also be in this risk group. In extreme cases and any situations that can cause stress, it is always necessary to remember about the possibility of residual adrenal dysfunction in such patients. In such situations it is necessary to provide adequate treatment of corticosteroids. Depending on the degree of adrenal dysfunction, it may be necessary to consult a specialist before carrying out the recommended procedures.
Symbicort turbuhaler contains lactose (less than 1 mg / dose).Usually this amount does not cause problems in patients with lactose intolerance.
Pediatric use
In children under 6 years old efficacy and safety of the drug has not been fully studied. Symbicort Turbuhaler is not recommended for use in this category of patients.
Influence on ability to drive motor transport and control mechanisms
Symbicort Turbuhaler does not affect the ability to drive vehicles and control mechanisms.

It is recommended to gradually reduce the dose of the drug before discontinuing treatment.
The increase in the frequency of taking bronchodilators, as an emergency medicine, indicates a deterioration in the course of the underlying disease and serves as a basis for revising the tactics of treating bronchial asthma. An unexpected and progressive deterioration in the control of symptoms of bronchial asthma or COPD is a potentially life-threatening condition and requires urgent medical intervention. In this situation, consider the possibility of increasing the dose of glucocorticosteroids or adding systemic anti-inflammatory therapy, for example, a course of oral glucocorticosteroids or treatment with antibiotics, in the event of infection.
Patients are advised to always carry with them emergency medications (? 2-adrenergic short-acting).
Treatment Symbicort turbuhaler should not begin in 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. When a severe reaction develops, the treatment tactics should be reviewed and, if necessary, alternative therapy should be prescribed.
Systemic effects can occur when taking any inhaled glucocorticosteroids, especially when taking high doses of drugs over a long period of time. The manifestation of systemic action is less likely with inhalation therapy than with oral glucocorticosteroids. Possible systemic effects include suppression of adrenal function, growth retardation in children and adolescents, a decrease in bone mineral density, cataracts, and glaucoma. Particular attention should be paid to patients with advanced COPD with low bone mineral density due to the possible effects on bone tissue. Therefore, it is very important to use the lowest effective dose of inhaled glucocorticosteroids, which provides optimal control of the symptoms of bronchial asthma.
Doctors need to carefully monitor the growth of children and adolescents who take glucocorticosteroids for a long time in any dosage form, and evaluate the ratio of the benefits of glucocorticosteroid therapy to the possible risk of stunting.
If there is reason to believe that, against the background of previous systemic steroid therapy, the adrenal function was impaired, precautions should be taken when transferring patients to Symbicort Turbuhaler.
The benefits of budesonide inhalation therapy usually minimize the need to take oral steroids, however, in patients who discontinue therapy with oral steroids, insufficient adrenal function may persist for long periods. Patients who in the past needed emergency high-dose glucocorticosteroids may also be in this risk group. In extreme cases and any situations that can cause stress, it is always necessary to remember about the possibility of residual adrenal dysfunction in such patients. In such situations, it is necessary to provide adequate treatment with glucocorticosteroids. Depending on the degree of adrenal dysfunction, it may be necessary to consult a specialist before carrying out the recommended procedures.

Symptoms: in case of overdose of formoterol, reactions typical of agonists are most likely to occur b2-adrenergic receptors: tremor, headache, tachycardia. Arterial hypotension, metabolic acidosis, hypokalemia and hyperglycemia may also occur.
In acute overdose of budesonide, even in large doses, clinically significant symptoms are not expected. Chronic administration of budesonide in excessive doses may result in systemic action of corticosteroids.
For acute bronchial obstruction, formoterol administration at a dose of 90 mcg for 3 hours was safe.
Treatment: shown supportive and symptomatic treatment.

With simultaneous ingestion of Ketoconazole at a dose of 200 mg 1 time / day and budesonide at a dose of 3 mg, the concentration of budesonide in plasma increases on average 6 times. When taking ketoconazole 12 hours after taking budesonide, the concentration of the latter in plasma increases by an average of 3 times. There is no information about such interaction with budesonide during inhalation, but a noticeable increase in the plasma concentration of the drug should be expected. Since no data are currently available for advice on dose selection, this combination of drugs should be avoided. If this is not possible, the intervals between taking ketoconazole and budesonide should be maximized. The possibility of reducing the dose of budesonide should also be considered. Other potent inhibitors of CYP3A4 may also significantly increase the content of budesonide in plasma.
Β-adrenoreceptor blockers can weaken or inhibit the action of formoterol. Symbicort turbuhaler should not be administered simultaneously with beta-blockers (including eye drops), unless absolutely necessary.
With simultaneous use of Symbicort Turbuhaler and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors and tricyclic antidepressants, the QT interval may be prolonged and the risk of ventricular arrhythmias may increase.
L-Dopa, L-thyroxin, oxytocin and alcohol can reduce the tolerance of the heart muscle to beta2-sympathomimetics.
With the simultaneous appointment of MAO inhibitors, as well as drugs with similar properties (furazolidone, procarbazine), hypertensive reactions may develop.
When conducting anesthesia with halogenated hydrocarbon preparations during the use of Symbicort Turbuhaler, there is an increased risk of arrhythmias in patients.
With the simultaneous use of other b-adrenoreceptor agonists, additive action is possible.
Hypokalemic effect can be enhanced with the simultaneous appointment of xanthine derivatives, steroids and diuretics. Hypokalemia increases the susceptibility to the development of arrhythmias in patients taking digitalis glycosides.
No interaction of budesonide with other drugs used to treat bronchial asthma.

Store at temperatures below 30 ° C out of the reach of children.