Symbicort® Turbuhaler® (Symbicort® Turbuhaler®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceBudesonide + FormoterolBudesonide + Formoterol
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  • 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
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    powder d / inhal. 
    NATIVA, LLC     Russia
    • Dosage form: & nbsppowder for inhalation dosed
    Composition:Each delivered dose (dose exiting from the mouthpiece) contains as active substances: budesonide micronized 320 μg and formoterol fumarate dihydrate 9 μg.
    Excipients: lactose monohydrate 491 μg / dose.
    Description:Inhaler: Rotating batcher of red color, on which the braille code is squeezed out. The cover is white. On the inside of the lid there are 5 ribbed thickenings in the form of longitudinal strips. In the dosing indicator window, the figure "60" is visible. The mouthpiece has four longitudinal ribs and can rotate.
    Content: granules from white to almost white, mostly round in shape.
    Pharmacotherapeutic group:Bronchodilator combined (beta2-adrenomimetic selective + glucocorticosteroid local)
    ATX: & nbsp

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

    Pharmacodynamics:Symbicort Turbuhaler contains formoterol and budesonide, which have different mechanisms of action and show an additive effect in reducing the frequency of exacerbations of bronchial asthma.
    The special properties of budesonide and formoterol make it possible to use their combination at the same time as maintenance therapy and for relief of seizures, or as a supporting therapy for bronchial asthma.
    Budesonide. Budesonide is a glucocorticosteroid that, after inhalation, has a rapid (within a few hours) and dose-dependent anti-inflammatory effect on the respiratory tract, reducing the severity of symptoms and the frequency of exacerbations of bronchial asthma. With the appointment of inhaled budesonide, there is a lower incidence of serious adverse effects than with systemic glucocorticosteroids. Reduces the severity of the bronchial mucosa edema, mucus production, sputum formation and airway hyperreactivity.
    The exact mechanism of the anti-inflammatory effect of glucocorticosteroids is unknown.
    Formoterol. Formoterol is a selective agonist β2-adrenergic receptors, after inhalation of which there is a rapid and prolonged relaxation of the smooth muscles of the bronchi in patients with reversible airway obstruction. The dose-dependent bronchodilator effect occurs within 1 to 3 minutes after inhalation and persists for at least 12 hours after taking a single dose.
    Symbicort Turbuhaler: Budesonide + Formoterol
    Bronchial asthma
    Addition of formoterol to budesonide reduces the severity of symptoms of bronchial asthma, improves lung function and reduces the frequency of exacerbations of the disease.
    The action of Symbicort Turbuhaler on lung function corresponds to the action of a combination of mono preparations of budesonide and formoterol and exceeds the action of one budesonide. In all cases, beta2-adrenostimulator of short action was used to stop seizures. There was no decrease in the anti-asthmatic effect over time. The drug is well tolerated.

    Chronic obstructive pulmonary disease (COPD)
    In patients with severe COPD against the background of receiving Symbicort Turbuhaler there was a significant decrease in the frequency of exacerbations of the disease compared with patients receiving as therapy only formoterol or placebo (mean frequency of exacerbations 1.4 compared with 1.8 to 1.9 in the placebo / formoterol group). There was no difference between the intake of Symbicort and formoterol in the index of forced expiratory volume in the first second (FEV1).
    Pharmacokinetics:

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

    Pharmacokinetic parameters for the relevant substances are comparable after the appointment of budesonide and formoterol in the form of monopreparations and as part of Symbicort Turbuhaler. For budesonide, when administered in a combination preparation, the area under the concentration-time curve (AUC) is somewhat larger, the absorption of the drug is faster and the maximum concentration in the blood plasma is higher. For formoterol, when administered as a combination, the maximum concentration in the blood plasma coincides with that for a mono drug.
    Inhalable budesonide quickly absorbed and reaches the maximum concentration in the plasma 30 minutes after the inhalation. The average dose of budesonide, which fell into the lung after inhalation through 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 fell into the lung after inhalation through Turbuhaler, does not differ from those in adult patients (the final concentration of the drug in the blood plasma was not determined). Inhalable formoterol quickly absorbed and reaches the maximum concentration in the blood plasma 10 minutes after the inhalation. The average dose of formoterol, which fell into the lung after inhalation through 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. The distribution volume for formoterol is about 4 l / kg and for budesonide is 3 l / kg. Formoterol is inactivated by conjugation (active O-demethylated metabolites are formed mainly in the form of inactivated conjugates). Budesonide is subjected to intensive biotransformation (about 90%) during the first passage through the liver with the formation of metabolites with low glucocorticosteroid activity. Glucocorticosteroid activity of the main metabolites - 6-β-hydroxybudesonide and - 16α-hydroxy-prednisolone - does not exceed 1% of the analogous activity of budesonide. There is no evidence for the interaction of metabolites or substitution reactions between budesonide and formoterol.

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

    Budesonide is metabolized predominantly with the participation of the enzyme CYP3A4. Metabolites of budesonide are excreted by the kidneys in unmodified form or in the form of conjugates. In urine, only a small amount of unmodified budesonide is found. Budesonide has a high system clearance (approximately 1.2 l / min).

    The pharmacokinetics of formoterol and budesonide in patients with renal insufficiency have not been studied. The concentration of budesonide and formoterol in blood plasma can be increased in patients with liver disease.

    Indications:

    Bronchial asthma (insufficiently controlled by the intake of inhaled glucocorticosteroids and beta2-adrenergic stimulants of short action as therapy on demand, or adequately controlled by inhaled GCS and long-acting beta2-adrenostimulants).

    COPD (symptomatic therapy in patients with severe chronic obstructive pulmonary disease (FEV)1 <50% of the estimated calculated level) and with repeated exacerbations in the anamnesis, which have severe symptoms of the disease, despite long-acting bronchodilator therapy).

    Contraindications:- Hypersensitivity to budesonide, formoterol or inhaled lactose.
    - Children under 12 years old.
    Carefully:Tuberculosis of the lungs (active or inactive form); fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, any aneurysm of any localization or other severe cardiovascular diseases (coronary heart disease,tachyarrhythmia or severe heart failure), prolongation of the QT interval (taking formoterol may cause an extension of the QTc interval).
    Pregnancy and lactation:There are no clinical data on the use of Symbicort Turbuhaler or sharing of formoterol and budesonide during pregnancy. During pregnancy, Symbicort Turbuhaler should be used only in those cases when the benefit of using the drug exceeds the potential risk to the fetus. The lowest effective dose of budesonide needed to maintain adequate control of asthma symptoms should be used. Inhalable budesonide is excreted in breast milk, however, when applied in therapeutic doses, no effect on the child was noted. It is not known whether the formoterol in the breast milk of women. Symbicort Turbuhaler may be prescribed to lactating women only if the expected benefit to the mother is greater than any possible risk to the child.
    Dosing and Administration:

    Bronchial asthma

    Symbicort Turbuhaler is not intended for the initial treatment of bronchial asthma of intermittent and easy persistent flow.Selection of the dose of drugs that make up Symbicort occurs individually and depending on the severity of the disease. This need to be taken into account not only at the beginning of treatment with combined preparations, but also with a change in the maintenance dose of the drug. In the event that individual patients require a different combination of doses of active components than in Symbicort Turbuhaler, β2adrenomimetics and / or glucocorticosteroids in separate inhalers.

    Patients should visit the doctor regularly to monitor the optimal dose of Symbicort Turbuhaler. The dose should be reduced to the lowest, against which the optimal control of symptoms of bronchial asthma remains. After achieving optimal control of asthma while taking the drug twice a day is recommended to titrate the dose to the minimum effective until the drug once a day, in cases where, in the judgment of the physician, the patient requires supportive therapy in combination with a bronchodilator long-acting .
    Adults (18 years and over): Symbicort Turbuhaler 320/9 mcg / dose: 1 inhalation twice a day.If necessary, it is possible to increase the dose to 2 inhalations twice a day. Once the optimal
    control of symptoms of bronchial asthma on the background of taking the drug twice a day, it is possible to reduce the dose to the lowest effective, up to a dose once a day.
    Adolescents (12-17 years): Symbicort Turbuhaler 320/9 mcg / dose: 1 inhalation twice a day.
    Children under 12 years of age: Symbicort Turbuhaler 320/9 mcg / dose is not recommended for children under 12 due to the lack of clinical data. Symbicort Turbuhaler 320/9 mcg / dose is intended only for maintenance therapy.
    COPD
    Adults: 1 inhalation Symbicort Turbuhaler 320/9 mcg / dose twice a day.
    Special patient groups: there is no need for a special dose selection for elderly patients. There is no data on the reception of Symbicort Turbuhaler 320/9 μg / dose in patients with renal or hepatic insufficiency. As budesonide and formoterol are excreted mainly by the kidneys, with the participation of hepatic metabolism, then in patients with severe cirrhosis of the liver, a slowing down of the drug release rate can be expected.


    Instructions for proper use of Turbuhaler:

    The mechanism of action of the turbuhaler: when inhaled by the patient through the mouthpiece, the drug enters the respiratory tract. It is necessary to instruct the patient:

    -read carefully the instructions for using Turbuhaler

    - inhale deeply and deeply through the mouthpiece to ensure that the optimal dose of the drug reaches the lungs

    never exhale through the mouthpiece

    - Rinse your mouth with water after inhalation of maintenance doses to reduce the risk of developing candidiasis of the mucous membrane of the mouth and throat. It is also necessary to rinse the mouth with water after the inhalation for relief of symptoms in the case of candidiasis of the mucous membrane of the oral cavity and pharynx.

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

    INSTRUCTION FOR USE OF TURBUCHALER

    Turbuhaler - multi-dose inhaler, which allows you to dose and inhale the drug in very small doses (Figure 1).

    When you inhale, the powder from Turbuhaler is delivered to the lungs. It is therefore important that you breathed deeply and deeply through the mouthpiece.

    Preparing the Turbuhaler for first use:

    Before first Using Turbuhaler it must be prepared for work.

    Unscrew and remove the lid.

    Hold the inhaler vertically with the red dispenser down (Fig. 2). Do not hold the inhaler for mouthpiece when you turn the dispenser.

    Turn the dispenser all the way in one direction (no matter, clockwise or counterclockwise), and then also against the stop in the opposite direction. During the rotation of the dispenser, you will hear a click. Follow the procedure twice.

    The inhaler is now ready for use, and You must not repeat this procedure training of Turbuhaler to work before each use. In order to take the drug, follow the instructions below.

    How to use SIMBIKORT® TURBUCHALER®

    To take one dose, follow the procedure described below.

    1. Unscrew and remove the cover.

    2. Hold the inhaler vertically with the red dispenser downward (Figure 2). Do not hold the inhaler for the mouthpiece when you turn the dispenser. To measure the dose, turn the dispenser all the way in one direction (no matter clockwise or counterclockwise), and then as far as it will go in the opposite direction.During the rotation of the dispenser, you will hear a click.

    3. Exhale. Do not exhale through the mouthpiece.

    4. Carefully place the mouthpiece between the teeth, compress the lips and inhale deeply and deeply through the mouth (Figure 3). The mouthpiece should not be chewed or compressed with teeth.

    5. Before exhaling, remove the inhaler from the mouth.

    6. If more than one dose is required, repeat steps 2-5.

    7. Close the inhaler cover, check that the cover of the inhaler has been carefully screwed.

    8. Rinse your mouth with water without swallowing.

    IMPORTANT!

    Do not attempt to remove the mouthpiece, since it is attached to the inhaler and is not removed.

    The Turbuhaler's mouthpiece rotates, but do not turn it unnecessarily.

    Since the amount of inhaled powder is very small, you may not feel the taste of the powder after inhalation. However, if you followed the instructions, you can be sure that you inhaled (inhaled) the necessary dose of the drug.

    If you mistakenly repeated the procedure for loading the inhaler more than once before taking the drug, with inhalation, you still get one dose of the drug. While the dose indicator will show the total number of measured doses.

    The sound that you hear when you shake the inhaler is produced by a dehumidifying agent, not a medicine.

    How do I know when the inhaler needs to be replaced?

    The dose indicator (Figure 4) shows the approximate number of doses remaining in the inhaler, the count of doses filled Turbuhaler starts with the 60th or 120th dose (depending on the total number of doses purchased by you Turbuhaler).

    The indicator shows an interval of 10 doses, so it does not show every metered (loaded) dose. You can be sure that Turbuhaler delivers the necessary dose of the drug, even if you do not notice the changes in the dose indicator window.

    The appearance of a red background in the dose indicator window means that there are 10 doses remaining in the Turbuhaler. When the figure 0 appears on a red background in the middle of the dose indicator window (Figure 5), the inhaler should be replaced with a new one.


    Note that even when the dose indicator window shows a number of 0, the dispenser continues to rotate. However, the dose indicator stops fixing the number of doses (stops moving) and the number of doses in the inhaler window remains 0.

    Cleaning

    Regularly (once a week), clean the mouthpiece from the outside with a dry cloth.

    Do not use water or other liquids to clean the mouthpiece.

    Recycling

    Be careful with the inhaler used, remember that some amount of the drug may remain inside the inhaler.
    Side effects:Against the background of the joint appointment of two drugs, there was no increase in the incidence of adverse reactions.
    The most common adverse reactions associated with taking the drug are pharmacologically expected adverse effects for p2-adrenomimetics, such as tremor and heart palpitations; symptoms usually have a moderate degree of severity and go through a few days after the start of treatment. AT
    the use of budesonide in COPD, bruising and pneumonia occurred at a frequency of 10% and 6%, respectively, compared with 4% and 3% in the placebo group (p <0.001 and p <0.01, respectively).
    Frequent (> 1/100, <1/10)
    Central Nervous System: Headache
    Cardiovascular system: Palpitation
    Musculoskeletal system: Tremor
    Respiratory tract: Candidiasis of the oral and pharyngeal mucosa, cough, hoarseness, slight irritation in the throat
    Infrequent (> 1/1000, <1/100)
    Cardiovascular system: Tachycardia
    Musculoskeletal system: Muscle cramps
    Central nervous system: Psychomotor agitation, anxiety, nausea, dizziness, sleep disturbances
    Skin: Bleeding
    Rare (> 1/10000, <1/1000)
    Skin: Immediate and delayed hypersensitivity reactions (eg, dermatitis, exanthema, urticaria, pruritus, angioedema, anaphylactic reaction
    Respiratory tract: Bronchospasm
    Metabolic disorders: hypokalemia
    Cardiovascular system: Arrhythmia (eg, atrial fibrillation, supraventricular tachycardia, extrasystole)
    Very rare (<1/10000)
    Metabolic disorders: Hyperglycemia, signs or symptoms of systemic glucocorticosteroid effects (including adrenal hypofunction)
    Psychiatric symptoms: Depression, behavioral disorders (mainly in children)
    Central Nervous System: Taste Disorders
    Cardiovascular system: Angina pectoris, fluctuations in blood pressure
    The systemic effect of inhaled glucocorticosteroids can occur when taking high doses for a long time.
    The use of β2-adrenomimetikov can lead to an increase in the blood levels of insulin, free fatty acids, glycerol and ketone derivatives.
    Overdose:Symptoms of an overdose of formoterol: tremor, headache, heart palpitations. In some cases, the development of tachycardia, hyperglycaemia, hypokalemia, lengthening of the QTc interval, arrhythmia, nausea and vomiting has been reported. Supportive and symptomatic treatment may be prescribed.
    If it is necessary to cancel Symbicort Turbuhaler due to an overdose of formoterol, which is part of the combined preparation, consideration should be given to the appointment of an appropriate glucocorticosteroid.
    In acute overdose of budesonide, even in significant doses, no clinically significant effects are expected. When chronic intake of excessive doses, the systemic action of glucocorticosteroids, such as hypercorticism and suppression of adrenal function, may manifest itself.
    Interaction:The administration of 200 mg of ketoconazole once a day raises the concentration in the plasma of oral budesonide (a single dose of 3 mg) when administered jointly, on average, 6-fold.With the appointment of ketoconazole 12 hours after the administration of budesonide, the concentration in the plasma of the latter increased, on average, 3-fold.
    There is no information about such interaction with inhaled budesonide, however, we should expect a significant increase in the concentration of the drug in the blood plasma. Since there is no data for recommendations for dose selection, the above combination of drugs should be avoided. If this is not possible, the time interval between administration of ketoconazole and budesonide should be maximized. You should also consider the possibility of reducing the dose of budesonide. Other potent inhibitors of CYP3A4 are also likely to significantly increase the concentration of budesonide in plasma. It is not recommended to use Symbicort as maintenance therapy and to relieve seizures for patients receiving potent CYP3A4 inhibitors.
    Blockers (beta-adrenergic receptors can weaken the action of formoterol.) Symbicort should not be given concomitantly with beta-blockers (including eye drops), except for forced cases.
    The joint appointment of Symbicort Turbuhaler and quinidine, disopyramide,procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase (MAO) inhibitors and tricyclic antidepressants can prolong the QTc interval and increase the risk of ventricular arrhythmias. Besides, levodopa, levothyroxine, oxytocin and alcohol can reduce heart muscle tolerance to β2-adrenomimetics.
    Co-administration 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 arrhythmia in patients with general anesthesia with preparations of halogenated hydrocarbons.
    With the joint administration of Symbicort turbuhaler and other β-adrenergic drugs, the side effect of formoterol may be increased. As a result of the application of β2-adrenomimetics hypokalemia may occur, which can be intensified by concomitant treatment with xanthine derivatives, mineral derivatives of glucocorticosteroids or diuretics. Hypokalemia may increase predisposition to the development of arrhythmias in patients taking cardiac glycosides.
    No interaction of budesonide and formoterol with other medications used to treat bronchial asthma was noted.
    Special instructions:It is recommended to gradually reduce the dose of the drug before discontinuing treatment and it is not recommended to abruptly cancel treatment.
    Symbicort Turbuhaler is not intended for initial selection of therapy at the first stages of treatment of bronchial asthma.
    Reception of formoterol may cause prolongation of the QT interval.
    An increase in the frequency of 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 management of symptoms of bronchial asthma or COPD is potentially life threatening and requires urgent medical intervention. In this
    should consider increasing the dose of glucocorticosteroids or adding a systemic
    anti-inflammatory therapy, for example, the course of oral glucocorticosteroids or treatment with antibiotics in case of infection.Patients are advised to have
    first-aid preparations (    β2short-acting adrenomimetics). It is necessary to draw the patient's attention to the necessity of regular intake of Symbicort Turbuhaler according to the chosen dose even in cases of absence of symptoms of the disease.
    Treatment with Symbicort Turbuhaler should not be started during an exacerbation or a significant deterioration in the course of bronchial asthma. As with any other inhaled therapy, it is possible that
    paradoxical bronchospasm with an immediate increase in wheezing after taking a dose of the drug. In this connection, it is necessary to stop the therapy with Symbicort, to reconsider the tactics of treatment and, if necessary, to prescribe alternative therapy.
    Systemic action may occur when taking any inhaled glucocorticosteroids, especially when taking high doses of drugs for a long period of time. The manifestation of systemic action is less likely in inhalation therapy than with oral glucocorticosteroids. Possible systemic effects include suppression of adrenal function, 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 glucocorticosteroid therapy in an inhaled form. In the case of established growth retardation, therapy should be reviewed to reduce the dose of an inhaled glucocorticosteroid. It is necessary to carefully evaluate the ratio of the benefits of glucocorticosteroid therapy to the possible risk of growth retardation. When choosing a therapy, it is recommended to consult a pediatric pulmonologist. Based on limited data on long-term glucocorticosteroid intake, it can be assumed that most children and
    adolescents receiving inhaled budesonide therapy will eventually achieve normal adult growth rates. At the same time, a slight (about 1 cm) short-term growth retardation was reported, mainly in the first year of treatment. Because of the potential action
    inhalation glucocorticosteroids on the mineral density of bone tissue should be given special attention to patients taking high doses of the drug for a long period with the presence of risk factors for osteoporosis.
    Studies of prolonged use of inhaled budesonide in children at an average daily dose of 400 micrograms (metered dose) or adults at a daily dose of 800 micrograms (metered dose) did not show a significant effect on bone mineral density. There is no data on the effect of high doses
    Symbicort Turbuhaler on the mineral density of bone tissue.
    If there is reason to believe that against the background of previous systemic therapy of glucocorticosteroids, adrenal function has been disrupted, precaution should be taken when transferring patients to Symbicort by Turbuchaler.
    The advantages of inhaled budesonide therapy, as a rule, minimize the need for oral steroids, but in patients who stop oral glucocorticosteroid therapy, adrenal insufficiency may persist for a long time. Patients who in the past needed an urgent intake of high doses of glucocorticosteroids or received long-term treatment with high-dose inhaled glucocorticosteroids may also be at this risk group.It is necessary to provide additional appointment of glucocorticosteroids during the period of stress or surgical intervention.
    It is recommended to instruct the patient about the need to rinse the mouth with water after inhalation in order to prevent the development of candidiasis of the oral mucosa. Precautions should be observed in the treatment of patients with an extended QTc-interval. Taking formoterol can cause an extension of the QTc interval. The need and dose of an inhaled glucocorticosteroid in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system should be reviewed. When co-appointed     β2-adrenomimetics with drugs that can cause or exacerbate the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, possibly increasing hypokalemic effect β2-adrenomimetics. Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve attacks with exacerbation of severe bronchial asthma,as the risk of hypokalemia increases with hypoxia and other conditions, when the likelihood of developing hypokalemic effects increases. In such cases it is recommended to monitor the potassium content in the serum.
    During the treatment period it is necessary to control the concentration of glucose in the blood in patients with diabetes mellitus.
    Symbicort Turbuhaler contains lactose (<1 mg / inhalation). Usually this amount does not cause problems in patients with lactose intolerance.

    Effect on the ability to drive transp. cf. and fur:Symbicort Turbuhaler does not affect the ability to drive a car and operate machinery. It can influence the ability to drive a car and operate machinery in the event of a side effect.
    Form release / dosage:Powder for inhalation dosed 320 + 9 microgram / dose.
    Packaging:A plastic inhaler with a first opening control (protective film indicating the location of the opening) containing 60 doses of the preparation, consisting of a dispensing device, a powder storage tank, a desiccant tank, a mouthpiece and a screw cap. Each inhaler is placed in a cardboard box with instructions for use.
    Storage conditions:At temperatures below 30 ° C, in places inaccessible to children.
    Shelf life:2 years. Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-002623/07
    Date of registration:07.09.2007
    The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden
    Manufacturer: & nbsp
    Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.
    Information update date: & nbsp2015-11-28
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