Simbikort Turbukhaler of 320 mkg

General characteristics. Structure:

Each delivered dose (the dose leaving a mouthpiece) contains in quality of active agents: the budesonid micronized 320 mkg and a formoterol of a fumarat of a dihydrate of 9 mkg.
Excipients: lactoses monohydrate of 491 mkg / dose.
DESCRIPTION
Inhaler: the rotating doser of red color on which Braille's code is squeezed out. Cover of white color. In a window of the indicator of dosing figure "60" is visible. The mouthpiece can rotate.
Contents: granules from white till almost white color, preferential rounded shape.

Pharmacological properties:

Pharmacodynamics. Simbikort Turbukhaler contains формотерол and будесонид which have different mechanisms of action and show the additive effect concerning decrease in frequency of exacerbations of bronchial asthma.

Budesonid. Budesonid, an inhalation glucocorticosteroid, in the recommended doses has antiinflammatory effect in bronchial tubes, reducing expressiveness of symptoms and frequency of exacerbations of bronchial asthma with a smaller frequency of side effects, than when using system glucocorticosteroids. Reduces expressiveness of hypostasis mucous bronchial tubes, products of slime, formation of a phlegm and hyperreactivity of respiratory tracts.

Formoterol. Formoterol - the selection agonist of r2-adrsnsrgichesky receptors which causes relaxation of smooth muscles of bronchial tubes in patients with reversible obstruction of respiratory tracts. Broncholitic action comes quickly, within 1-3 minutes after inhalation and remains within 12 hours after reception of a single dose.

Budesonid + Formoterol. Bronchial asthma Addition of a formoterol to a budesonid reduces expressiveness of symptoms of bronchial asthma, improves function of bronchial tubes and reduces the frequency of exacerbations of a disease.

Simbikort Turbukhaler's action on function of bronchial tubes corresponds to action of a combination of monodrugs of a budesonid and formoterol and exceeds action of one budesonid. Drug has good tolerance.

Simbikort Turbukhaler improves function of bronchial tubes and has good tolerance at children aged from 6 up to 11 years against the background of administration of drug within 12 weeks (two inhalations on 80/4.5 mkg / inhalation twice a day).

The Chronic Obstructive Pulmonary Diseases (COPD) At patients from heavy HOBL against the background of Simbikort Turbukhaler's reception considerable decrease in frequency of exacerbations of a disease in comparison with the patients receiving as therapy only формотерол or placebo was observed (average frequency of aggravations 1.4 but to comparison with 1.8 - 1.9 in group of placebo / формотерол). Distinctions between Simbikort's reception and a formoterola on an indicator of volume of the forced exhalation in the first minute are noted (OFV).

Pharmacokinetics. Absorption. Simbikort Turbukhaler биоэквивалентен to the corresponding monodrugs concerning systemic action of a budesonid and a formoterol. Despite it, small strengthening of suppression of cortisol after Simbikort Turbukhaler's reception in comparison with monodrugs was noted. This distinction does not dig round influence on clinical safety. There are no proofs of pharmacokinetic interaction of a budesonid and a formoterol.

Pharmacokinetic indicators for the corresponding substances are comparable after purpose of a budesonid and a formoterol in the form of monodrugs and as a part of Simbikort Turbukhaler. For a budesonid, at introduction as a part of the combined drug, the area under a curve "concentration time" (AUC) is slightly more, absorption of drug happens quicker and the size of the maximum concentration in a blood plasma is higher.

For a formoterol at introduction as a part of the combined drug the maximum concentration in a blood plasma matches that for monodrug.

Iigaliruyemy будесонид is quickly absorbed and reaches the maximum concentration in plasma in 30 minutes after performing inhalation. The average dose of the budesonid which got into lungs after performing inhalation through Turbukhaler makes 32-44% of the delivered dose. System bioavailability makes about 49% of the delivered dose. At children aged from 6 up to 16 years the average dose of the budesonid which got into lungs after performing inhalation through Turbukhaler does not differ from indicators at adult patients (final concentration of drug in a blood plasma was not defined).

Inhalated формотерол quickly it is absorbed and reaches the maximum concentration in a blood plasma in 10 minutes after performing inhalation. The average dose of the formoterol which got into lungs after performing inhalation through Turbukhaler makes 28-49% of the delivered dose. System bioavailability makes about 61% of the delivered dose.

Distribution and metabolism. About 50% of a formoterol and 90% of a budesonid contact proteins of plasma. Distribution volume for a formoterol makes about 4 l/kg and for a budesonid of 3 l/kg. Formoterol is inactivated by conjugation (are formed active O-demetilirovannye metabolites, generally in the form of the inactivated conjugates). Budesonid is exposed to intensive biotransformation (about 90%) at the first passing through a liver with formation of the metabolites having low glucocorticosteroid activity. Glkyukortikosteroidny activity of the main metabolites 6 - beta гидроксибудесонида and 16-alpha hydroxyprednisolonum - does not exceed 1% of similar activity of a budesonid. There are no proofs of interaction of metabolites or substitution reaction between budesonidy and formoteroly.

The main part of a dose of a formoterol is exposed to metabolism in a liver and then is removed by kidneys. After inhalation of 8-13% of the delivered dose of a formoterol it is removed in not changed view with urine. Formoterol has high system clearance (about 1.4 l/min.); the elimination half-life of drug averages 17 hours.

Budesonid is metabolized preferential with CYP3A4 enzyme participation. Metabolites of a budesonid are removed with urine in not changed look or in the form of conjugates. In urine only the insignificant quantity of not changed budesonid is found. Budesonid has high system clearance (about 1.2 l/min).

The pharmacokinetics of a formoterol at children and at patients with a renal failure is not studied. Concentration of a budesonid and formoterol in a blood plasma can increase at patients with liver diseases.

Indications to use:

The bronchial asthma (which is insufficiently controlled by reception of inhalation GKS and a beta of 2-adrenostimulyator of short action or adequately controlled by inhalation GKS and beta2-adrenostimulyator of long action).
HOBL (symptomatic therapy at patients with heavy chronic obstructive pulmonary diseases (OFV <50% of estimated settlement level) and with the repeating aggravations in the anamnesis which have the expressed disease symptoms, despite therapy by bronkhodilyatator of long action).

Route of administration and doses:

Simbikort Turbukhaler is not intended for initial treatment of bronchial asthma of an intermittent and easy persistent current. Selection of a dose of the drugs which are Simbikort Turbukhaler's part happens individually and depending on severity of a disease. It needs to be considered not only at an initiation of treatment the combined drugs, but also at change of a dose of drug.
If certain patients need other combination of doses of active components, than in Simbikort Turbukhaler, it is necessary to appoint beta2-adrenomimetik and/or glucocorticosteroids in separate inhalers.
Bronchial asthma
Adults (18 years are also more senior): Simbikort Turbukhaler of 320/9 mkg / dose: 1 inhalation twice a day. If necessary increase in a dose up to 2 inhalations twice a day is possible. After achievement of optimum control of symptoms of bronchial asthma against the background of administration of drug twice a day, the dose decline to the smallest effective is possible, up to reception once a day.
Teenagers (12-17 years): Simbikort Turbukhaler of 320/9 mkg / dose: 1 inhalation twice a day.
Children up to 12 years: Simbikort Turbukhaler of 320/9 mkg / a dose is not recommended to children up to 12 years in a type of lack of clinical data.
Patients should visit regularly the doctor for control of an optimum dose Simbikort Turbukhaler. The dose should be lowered to the smallest against the background of which optimum control of symptoms of bronchial asthma remains. After achievement of optimum control of bronchial asthma at administration of drug twice a day, it is recommended to titrate a dose to minimum effective, up to administration of drug once a day when, according to the doctor, the patient needs a maintenance therapy in a combination with a bronkhodilyatator of long action.
HOBL
Adults: 1 inhalation Simbikort Turbukhaler of 320/9 mkg / dose twice a day.
Special groups of patients: there is no need for special selection of a dose of drug for patients of advanced age. There are no data on Simbikort Turbukhaler's reception of 320/9 mkg / a dose patients with a renal or liver failure. As будесонид and формотерол are removed mainly by kidneys, with the participation of hepatic metabolism, at patients with heavy cirrhosis it is possible to expect delay of speed of removal of drug.
Instructions for the correct use of Turbukhaler:
Mechanism of action of Turbukhaler: at inhalation by the patient through a mouthpiece drug comes to respiratory tracts.
It is necessary to instruct the patient:
it is attentive to study the application instruction of Turbukhaler,
to inhale strongly and deeply through a mouthpiece to guarantee hit of an optimum dose of drug in lungs,
never to exhale through a mouthpiece.
The patient can not feel taste or not feel drug after Turbukhaler's use that is caused by a small amount of the delivered substance.

Features of use:

It is recommended to reduce gradually a drug dose before the termination of treatment and it is not recommended to cancel treatment sharply.
Simbikort (320/9 mikrogramm/ingalyation) Turbukhaler is not intended for patients with heavy bronchial asthma.
Simbikort Turbukhaler does not intend for initial selection of therapy at the first stages of treatment of bronchial asthma.
Reception of a formoterol can cause lengthening of an interval of QT.
Increase in frequency of reception of bronchodilators, as drugs of acute management, indicates deterioration in a current of a basic disease and forms the basis for review of tactics of treatment of bronchial asthma. The unexpected and progressing deterioration in control of symptoms of bronchial asthma or HOBL is the state which is potentially menacing for life and demands urgent medical intervention. In this situation it is necessary to consider the possibility of increase in a dose of glucocorticosteroids or addition of system antiinflammatory therapy, for example, of a course of peroral glucocorticosteroids or treatment by antibiotics in case of accession of an infection. Patients are recommended to have constantly at themselves drugs of acute management (beta2-adrenomimetik of short action).
It is necessary to draw the attention of the patient to need of regular reception Simbikort Turbukhaler according to the picked-up dose even in cases of lack of symptoms of a disease.
Treatment by Simbikort Turbukhaler should not be begun in the period of an exacerbation of bronchial asthma.
As well as at any other inhalation therapy, emergence of a paradoxical bronchospasm with immediate strengthening of rattles after reception of a dose of drug is possible. In this connection it is necessary to stop therapy by Simbikort, to reconsider tactics of treatment and, if necessary, to appoint alternative therapy.
Systemic action can be shown at reception of any inhalation glucocorticosteroids, especially at reception of high doses of drugs during a long span. Manifestation of systemic action is less probable when performing inhalation therapy, than when using peroral glucocorticosteroids. Suppression of function of adrenal glands, a growth inhibition at children and teenagers, decrease in mineral density of a bone tissue, a cataract and glaucoma belong to possible system effects.
It is regularly recommended to monitorirovat growth of children, it is long receiving glucocorticosteroid therapy in the inhalated form. In case of the established growth inhibition it is necessary to reconsider therapy for the purpose of a dose decline of the inhalated glucocorticosteroid. It is necessary to estimate carefully a ratio of advantage of glucocorticosteroid therapy to possible risk of a growth inhibition. At the choice of therapy it is recommended to address the children's pulmonologist.
Based on limited these researches about long reception of glucocorticosteroids, it is possible to assume that most of the children and teenagers receiving therapy by an inhalation budesonid will be reached finally normal for adult indicators of growth. At the same time it was reported about insignificant (approximately on 1 cm), a short-term growth inhibition generally in the first year of treatment.
Because of potentially possible action of inhalation glucocorticosteroids on the mineral density of a bone tissue it is necessary to pay special attention to the patients accepting high doses of drug during the long period with existence of risk factors of osteoporosis. Researches of prolonged use of the inhalated budesonid at children in an average daily dose of 400 micrograms (the measured dose) or adults in a daily dose of 800 micrograms (the measured dose) did not show noticeable action on the mineral density of a bone tissue. There are no data on action of high doses of Simbikort Turbukhaler on the mineral density of a bone tissue.
If there are bases to believe that against the background of the previous system therapy glucocorticosteroids broke function of adrenal glands, it is necessary to take precautionary measures at transfer of patients into treatment by Simbikort Turbukhaler.
Advantages of inhalation therapy budesonidy, as a rule, minimize need of reception of peroral steroids, however at patients,
stopping therapy by peroral glucocorticosteroids, insufficient function of adrenal glands can remain for a long time. Patients who in the past needed urgent reception of high doses of glucocorticosteroids received prolonged treatment by inhalation glucocorticosteroids in a high dose, can also be in this risk group. It is necessary to provide additional purpose of glucocorticosteroids in the period of a stress or surgical intervention.
It is recommended to instruct the patient about need to rinse a mouth water after inhalation for the purpose of prevention of development of candidiasis of a mucous membrane of an oral cavity.
It is necessary to observe precautionary measures at treatment of patients with the extended QTS-interval. Reception of a formoterol can cause lengthening of a QTS-interval.
It is necessary to reconsider need of use and a dose of the inhalated glucocorticosteroid at patients with active or inactive forms of a pulmonary tuberculosis, fungal, viral or bacterial infections of a respiratory organs.
At joint purpose of beta2-adrenomimetik with drugs which can cause or strengthen gipokaliyemichesky effect, for example, xanthine derivatives, steroids or diuretics, strengthening of gipokaliyemichesky effect of beta2-adrenomimetik is possible. It is necessary to observe special precautionary measures at the patients with unstable bronchial asthma applying bronkhodilyatator of short action for removal of attacks at an exacerbation of heavy bronchial asthma as the risk of development of a hypopotassemia increases against the background of a hypoxia and at other states when the probability of manifestation of development of gipokaliyemichesky effect increases. In such cases it is recommended to control the content of potassium in serum.
During treatment it is necessary to control concentration of glucose in blood at the patients suffering from a diabetes mellitus.
Simbikort Turbukhaler contains lactose (<1 mg / inhalation). Usually such quantity does not cause problems in patients with a lactose intolerance.
INFLUENCE ON ABILITY TO DRIVE THE CAR OR OTHER MECHANISMS
Simbikort Turbukhaler does not exert impact on ability to drive the car and to manage mechanisms. Can exert insignificant impact at manifestation of side effect.

Side effects:

Against the background of joint purpose of two drugs increase in frequency of emergence of side reactions was not noted. The most frequent side reactions connected with administration of drug are such pharmacological expected by-effects, undesirable to 2-adrenomimetik, as a tremor and a cardiopalmus, symptoms usually have moderate degree of manifestation and pass in several days after an initiation of treatment. During use of a budesonid at HOBL, bruises and pneumonia met frequency of 10% and 6%, respectively, in comparison with 4% and 3% in group with placebo (р> 0,001 and p> 0,01, respectively).
Frequent                        Central nervous system:            Headache
(> 1/100, <1/10)      Cardiovascular system:        Heartbeat
                                  Musculoskeletal system:             Tremor
                                  Respiratory tracts:                          Candidiases of a mucous membrane 
                                                                                         oral cavities and drinks, cough, 
                                                                                          hoarseness, slight irritation in a throat
Less frequent             Cardiovascular system:         Tachycardia
(> 1/1,000, <1/100)    Musculoskeletal system:              Muscular spasms
                                  Central nervous system:        Psychomotor excitement, 
                                                                                            concern, nausea, dizziness, 
                                                                                            sleep disorders
                                   Skin:                                              Bruises
Rare                        Skin:                                               Dieback, urticaria, itch, dermatitis,
(> 1/10,000,                                                                       angioedema
<1/1,000)                   Respiratory tracts:                           Bronchospasm
                                   Metabolic disturbances:            Hypopotassemia
                                   Cardiovascular system:         Fibrillation of auricles, 
                                                                                           supraventricular tachycardia, 
                                                                                           premature ventricular contraction
Very rare              Metabolic disturbances:           Hyperglycemia, signs or symptoms
(<1/10,000)                                                                    system glucocorticosteroid effects 
                                                                                           (including a hypoadrenalism)

                                   Psychiatric symptoms:           Depression, behavior disorders 
                                                                                          (mainly at children)
                                   Central nervous system:        Taste disturbances
                                  Cardiovascular system:         Stenocardia, fluctuations arterial 
                                                                                           pressure
Systemic action of inhalation glucocorticosteroids can meet at reception of high doses for an appreciable length of time.
Use of 2-adrenomimetik can lead to increase in content in blood of insulin, free fatty acids, a glitserol and ketonic derivatives.

Interaction with other medicines:

Reception of 200 mg of a ketokonazol increases concentration in plasma of a peroral budesonid (a single dose of 3 mg) at their joint appointment, on average, by 6 times once a day. At purpose of a ketokonazol in 12 hours after reception of a budesonid, concentration in plasma of the last increased, on average, by 3 times. Information on similar interaction with an inhalation budesonid is absent, however it is necessary to expect noticeable increase in concentration of drug in a blood plasma. As the doses given for recommendations about selection are absent, it is necessary to avoid the above described combination of drugs. If it is impossible, time intervals between purpose of a ketokonazol and budesonid should be increased as much as possible. Also it is necessary to consider the possibility of a dose decline of a budesonid. Other powerful CYP3A4 inhibitors probably can also increase considerably concentration of a budesonid in plasma.
Blockers of beta and adrenergic receptors can weaken action of a formoterol. Simbikort Turbukhaler it is not necessary to appoint along with beta adrenoblockers (including eye drops), except for forced cases.
Joint appointment of Simbikort Turbukhaler and quinidine, Disopyramidum, procaineamide, fenotiazin, antihistaminic drugs (terfenadin), monoamine oxidase inhibitors (MAO) and tricyclic antidepressants can extend an interval of QT and increase risk of developing of ventricular arrhythmias.
Besides, the levodopa, left thyroxine, oxytocin and alcohol can reduce tolerance of a cardiac muscle to beta2-adrenomimetika.
Joint purpose of MAO inhibitors, and also the drugs having similar properties such as furasolidone and Procarbazinum, can cause increase in the ABP. There is an increased risk of development of arrhythmias in patients when carrying out the general anesthesia drugs of halogenated hydrocarbons.
At joint reception of Simbikort Turbukhaler and other beta and adrenergic medicines strengthening of side effect of a formoterol is possible.
The hypopotassemia which can amplify at the accompanying treatment by xanthine derivatives, mineral derivatives of glucocorticosteroids or diuretics can result from use of beta2-adrenomimetik.
The hypopotassemia can increase predisposition to development of arrhythmias in the patients accepting cardiac glycosides.
Interaction of a budesonid with other medicines used for treatment of bronchial asthma was not noted.

Contraindications:

Hypersensitivity to a budesonid, a formoterol or the inhalated lactose.
Children's age up to 12 years.

With care: pulmonary tuberculosis (active or inactive form); fungal, viral or bacterial infections of a respiratory organs, a thyrotoxicosis, a pheochromocytoma, a diabetes mellitus, an uncontrollable hypopotassemia, an idiopathic hypertrophic subaortal stenosis, heavy arterial hypertension, aneurism of any localization or other serious cardiovascular illness (coronary heart disease, a tachyarrhythmia or heart failure of heavy degree), lengthening of an interval of QT (reception of a formoterol can cause lengthening of a QTS-interval).

USE DURING PREGNANCY AND FEEDING BY THE BREAST
There are no clinical data on Simbikort Turbukhaler's use or sharing of a formoterol and a budesonid during pregnancy.
During pregnancy Simbikort Turbukhaler it is necessary to use only when the advantage of use of drug outweighs potential risk for a fruit. It is necessary to use the smallest effective dose of a budesonid necessary for maintenance of adequate control of symptoms of bronchial asthma. It is not known whether gets формотерол or будесонид into breast milk of women. Simbikort Turbukhaler can be appointed to the feeding women, only if the expected advantage for mother is more, than any possible risk for the child.

Overdose:

Symptoms of overdose of a formoterol: tremor, headache, tachycardia. It was in some cases reported about development of tachycardia, a hyperglycemia, hypopotassemia, lengthening of a QTS-interval, arrhythmia, nausea and vomiting.
In case of need Simbikort Turbukhaler's cancellations owing to overdose of the formoterol which is a part of the combined drug it is necessary to consider a question of purpose of the corresponding glucocorticosteroid.
Treatment: supporting and symptomatic. Reception by patients with acute bronchial obstruction of a formoterol in a dose of 90 mkg within 3 hours is safe.
At acute overdose of a budesonid, even in considerable doses, clinically significant effects are not expected. At chronic reception of overdoses systemic action of glucocorticosteroids, such as hypercorticoidism and suppression of function of adrenal glands can be shown.

Storage conditions:

At a temperature below 30 °C, in places unavailable to children. Period of validity 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Powder for inhalations dosed 320 + 9 micrograms / a dose. The plastic inhaler with control of the first opening (a protective film with the indication of the place of opening) containing 60 doses of drug, consisting of the portioning device, a tank for storage of powder, a tank for a desiccant, a mouthpiece and the screw-on cover. Each inhaler is located in a cardboard pack with the application instruction.