Symbicort turbuhaler
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Symbicort Turbuhaler (Symbicort®Turbuhaler®)
Composition:
Active substances: 1 inhalation (1 dose) contains: 160 mcg micronized budesonide;
4.5 mcg formoterol fumarate dihydrate;
Excipient: lactose monohydrate.
Pharmaceutical form. Powder for inhalation, metered.
Main physico-chemical properties:
Inhaler (60 doses): red rotating dose counter. The rotating dose counter has embossed Braille code. White-colored cap. Inside the cap there are five ribs.
The number 60 is visible in the dose indicator window. The mouthpiece has four rods and is rotatable.
Contents: white to almost white in color, mainly in the form of rounded granules.
Inhaler (120 doses): red rotating dose counter. The rotating dose counter has embossed Braille code. White-colored cap. Inside the cap there are five ribs.
The number 120 is visible in the dose indicator window. The mouthpiece has four rods and is rotatable.
Contents: white to almost white in color, mainly in the form of rounded granules.
Pharmacotherapeutic group.
Adrenergic agents in combination with corticosteroids or other agents, excluding anticholinergic agents. Formoterol and budesonide. ATC code R03AK07.
Pharmacological properties.
Pharmacodynamics.
Mechanisms of action and pharmacodynamic effects
The medicinal product Symbicort Turbuhaler contains formoterol and budesonide, which have different mechanisms of action and exhibit an additive effect in reducing the frequency of asthma exacerbations. The specific properties of budesonide and formoterol allow the combination to be used for maintenance therapy and symptom relief or for maintenance therapy of bronchial asthma.
Budesonide
Budesonide is a glucocorticosteroid that, when inhaled, exerts a dose-dependent anti-inflammatory action in the airways, resulting in a reduction of symptoms and decreased frequency of asthma exacerbations. Inhaled budesonide causes fewer adverse reactions than systemic corticosteroids. The precise mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.
Formoterol
Formoterol is a selective β2-adrenergic agonist that, when administered by inhalation, induces rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilating effect is dose-dependent; the medicinal product begins to act within 1–3 minutes. The duration of action lasts at least 12 hours after a single dose.
Clinical efficacy and safety
Bronchial asthma
Clinical efficacy of maintenance therapy with budesonide/formoterol
Clinical studies in adult patients have shown that adding formoterol to budesonide alleviates asthma symptoms, improves lung function, and reduces the frequency of exacerbations. In two 12-week studies, the effect of budesonide/formoterol on lung function was equivalent to that of budesonide and formoterol used in a free combination and superior to budesonide used as monotherapy. All treatment groups used short-acting β2-adrenergic agonists as needed. Over time, no signs of attenuation of the anti-asthmatic effect were observed.
Two 12-week studies were conducted in pediatric patients, in which 265 individuals aged 6–11 years received maintenance doses of budesonide/formoterol (2 inhalations of 80 mcg/4.5 mcg/inhalation twice daily) and short-acting β2-adrenergic agonists as needed. In both studies, improvements in lung function were observed, and treatment was well tolerated compared to the use of an equivalent dose of budesonide as monotherapy.
Clinical efficacy of maintenance therapy and use of budesonide/formoterol for symptom relief
Overall, 12,076 patients with bronchial asthma were included in 5 double-blind efficacy and safety studies of the medicinal product (4,447 patients were randomized to the group receiving maintenance therapy and budesonide/formoterol for symptom relief), which lasted 6 or 12 months. To be eligible for the study, patients had to have asthma symptoms despite the use of inhaled glucocorticosteroids.
The use of budesonide/formoterol for maintenance therapy and symptom relief provided a statistically significant and clinically meaningful reduction in the rate of severe asthma exacerbations compared to all other treatment groups.
Comparable efficacy and safety of the medicinal product in adolescents and adults were demonstrated in 6 double-blind studies, including the 5 aforementioned studies and one additional study using a higher maintenance dose – two inhalations of 160/4.5 mcg twice daily. Assessments were based on data from a total of 14,385 asthma patients, of whom 1,847 were adolescents. The number of adolescent patients who used more than 8 inhalations of the medicinal product on any day during treatment with budesonide/formoterol for maintenance and symptom relief was limited, and such use was infrequent.
In studies involving patients who sought medical attention due to acute asthma symptoms, the use of budesonide/formoterol provided rapid and effective relief of bronchospasm symptoms, similar to that of salbutamol and formoterol.
COPD
In two 12-month studies, the effect of the medicinal product on lung function and the frequency of exacerbations (defined by the number of courses of oral steroids and/or antibiotics and/or hospitalizations) was evaluated in patients with moderate or severe COPD. The inclusion criterion for both studies was a pre-bronchodilator FEV1 value of < 50% of predicted normal. The median post-bronchodilator FEV1 at study entry was 42% of predicted normal.
The mean number of exacerbations per year (as defined above) was significantly reduced in the budesonide/formoterol group compared to formoterol monotherapy or placebo (mean rate 1.4 vs. 1.8–1.9 in the placebo/formoterol groups). The mean number of days of oral corticosteroid use per patient over 12 months was slightly reduced in the budesonide/formoterol group (7–8 days/patient/year compared to 11–12 and 9–12 days in the placebo and formoterol groups, respectively). Regarding changes in lung function parameters such as FEV1, treatment with budesonide/formoterol was not more effective than treatment with formoterol alone.
Pharmacokinetics.
Absorption
The fixed-dose combination of budesonide and formoterol and the corresponding monoproducts were found to be bioequivalent with regard to systemic exposure to budesonide and formoterol. Despite this, after administration of the fixed-dose combination, a slight increase in cortisol suppression was observed compared to administration of the drugs separately. This difference was considered clinically insignificant regarding safety.
No signs of pharmacokinetic interaction between budesonide and formoterol were observed.
Pharmacokinetic parameters of the respective substances were similar after administration of budesonide and formoterol as monoproducts or in the fixed-dose combination. After administration of the fixed combination, the AUC of budesonide was slightly higher, and the rate of absorption and maximum plasma concentration were slightly greater than when the active substances were administered separately. The maximum plasma concentration of formoterol after administration of the fixed combination was similar to that after administration of the monoproduct. Inhaled budesonide is rapidly absorbed; plasma concentration reaches maximum within 30 minutes after inhalation. The mean pulmonary deposition of budesonide after inhalation via a dry powder inhaler ranged from 32% to 44% of the delivered dose. Systemic bioavailability is approximately 49% of the delivered dose. In children aged 6–16 years, pulmonary deposition is within the same range as in adults at the same doses. Corresponding plasma concentrations were not detectable.
Inhaled formoterol is rapidly absorbed; plasma concentration reaches maximum within 10 minutes after inhalation. In studies, the mean pulmonary deposition of formoterol after inhalation via a dry powder inhaler ranged from 28% to 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 are bound to plasma proteins. The volume of distribution of formoterol is approximately 4 L/kg, and that of budesonide is 3 L/kg. Formoterol is inactivated via conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are predominantly present as inactivated conjugates). Budesonide undergoes extensive (approximately 90%) biotransformation during first-pass metabolism through the liver, forming metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites, 6-β-hydroxy-budesonide and 16-α-hydroxy-prednisolone, does not exceed 1% of the activity of budesonide. There are no signs of metabolic interaction or displacement reactions between formoterol and budesonide.
Elimination
The majority of the formoterol dose undergoes hepatic metabolism and is subsequently excreted by the kidneys. After inhalation, 8–13% of the delivered dose of formoterol is excreted unchanged in urine. Formoterol has a high systemic clearance (approximately 1.4 L/min), and its terminal half-life is on average 17 hours.
Budesonide is metabolized primarily by the CYP3A4 enzyme. Budesonide metabolites are excreted in urine in unchanged or conjugated form. Only a small amount of unchanged budesonide is detected in urine. Budesonide has a high systemic clearance (approximately 1.2 L/min), and its plasma half-life after intravenous administration is approximately 4 hours.
The pharmacokinetics of budesonide or formoterol in patients with renal impairment is unknown. In patients with liver disease, exposure to budesonide and formoterol in blood may be increased.
Linearity/non-linearity
Systemic exposure to budesonide and formoterol is linearly correlated with the administered dose.
Clinical characteristics.
Indications.
Bronchial asthma
Symbicort Turbuhaler 160 mcg/4.5 mcg is indicated in adults and children aged 12 years and older for regular treatment of bronchial asthma when combined therapy (inhaled corticosteroid and long-acting β2-adrenoceptor agonist) is appropriate:
- if their condition is not adequately controlled by inhaled corticosteroids and short-acting β2-adrenoceptor agonists used as needed, or
- if their condition is well controlled by inhaled corticosteroids and long-acting β2-adrenoceptor agonists.
Chronic obstructive pulmonary disease (COPD)
Symbicort Turbuhaler is indicated for symptomatic treatment in adult patients aged 18 years and older with COPD, with forced expiratory volume in one second (FEV1) < 70% of predicted normal (post-bronchodilator) and a history of exacerbations despite regular bronchodilator therapy.
Contraindications.
Hypersensitivity to the active substances or to any of the excipients listed in the section "Composition" (lactose, which contains a small amount of milk proteins).
Interaction with other medicinal products and other forms of interaction.
Pharmacokinetic interactions
Plasma levels of budesonide may markedly increase when the medicinal product is co-administered with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, and HIV protease inhibitors); therefore, concomitant use of these medicinal products should be avoided. If this is not possible, the interval between administration of the inhibitor and budesonide should be as long as possible (see section "Special precautions for use"). Patients taking potent CYP3A4 inhibitors should not use Symbicort Turbuhaler simultaneously for both maintenance therapy and symptom relief.
The potent CYP3A4 inhibitor ketoconazole, administered at a dose of 200 mg once daily, increased the plasma concentration of oral budesonide (3 mg as a single dose) on average by 6-fold when administered concurrently. When ketoconazole was administered 12 hours after budesonide, the budesonide concentration increased on average by 3-fold, indicating that staggered administration of the drugs with a time interval may reduce the increase in plasma budesonide concentration. Limited data on this interaction with high doses of inhaled budesonide show that when itraconazole 200 mg once daily was co-administered with inhaled budesonide (1000 mcg as a single dose), plasma levels of budesonide may markedly increase (on average by four-fold).
Pharmacodynamic interactions
β-adrenergic blockers may attenuate or antagonize the effect of formoterol. Therefore, Symbicort Turbuhaler should not be used concomitantly with β-adrenergic blockers (including eye drops), unless there are compelling reasons.
Concomitant use of quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.
In addition, L-dopa, L-thyroxine, oxytocin, and alcohol may impair cardiac tolerance to β2-sympathomimetics.
Concomitant use of monoamine oxidase inhibitors, including medicinal products with similar properties such as furazolidone and procarbazine, may provoke hypertensive reactions.
Patients undergoing concomitant anaesthesia with halogenated hydrocarbons are at increased risk of developing arrhythmias.
Concomitant use of other β-adrenergic or anticholinergic medicinal products may have a potentially additive bronchodilator effect.
Hypokalaemia may increase susceptibility to arrhythmias in patients taking cardiac glycosides.
Hypokalaemia may occur as a result of β2-agonist therapy and may be potentiated by concomitant use of xanthine derivatives, corticosteroids, and diuretics (see section "Special precautions for use").
No interactions between budesonide and formoterol with any other medicinal products used for the treatment of bronchial asthma have been observed.
Children.
Interaction studies have been conducted only in adult patients.
Special precautions for use.
If discontinuation of treatment is necessary, it is recommended to gradually reduce the dose rather than abruptly stop therapy. Inhaled corticosteroids should not be completely withdrawn except when temporarily necessary to confirm the diagnosis of asthma.
The patient should consult a physician if they consider the treatment ineffective or if the maximum recommended daily dose of Symbicort Turbuhaler has been exceeded (see section "Dosage and administration"). Sudden and progressive worsening of control over bronchial asthma or COPD is potentially life-threatening, and the patient should seek urgent medical evaluation. In such cases, the need for intensified corticosteroid therapy should be considered, for example, initiating a course of oral corticosteroids or antibiotic treatment if a bacterial infection is present.
Patients should be advised to always carry a "rescue" inhaler: either Symbicort Turbuhaler (for patients with bronchial asthma using Symbicort Turbuhaler as maintenance and reliever therapy), or a separate short-acting bronchodilator (for all patients using Symbicort Turbuhaler only as maintenance therapy).
Patients must be reminded of the necessity to use Symbicort Turbuhaler at the prescribed maintenance doses regularly, even in the absence of disease symptoms. After achieving control of bronchial asthma symptoms, gradual dose reduction of Symbicort Turbuhaler may be considered. During dose reduction, it is important that patients undergo regular monitoring. The lowest effective dose of Symbicort Turbuhaler should be used (see section "Dosage and administration").
Patients should not initiate treatment with Symbicort Turbuhaler during an exacerbation, acute episode, or significant worsening of bronchial asthma. Serious adverse reactions related to bronchial asthma and disease exacerbations may occur during treatment with Symbicort Turbuhaler. Patients should continue treatment and consult a physician if symptoms of bronchial asthma do not resolve or worsen after starting therapy with Symbicort Turbuhaler.
There are no clinical trial data on the use of Symbicort Turbuhaler in COPD patients with pre-bronchodilator FEV1 > 50% of predicted and post-bronchodilator FEV1 < 70% of predicted (see section "Pharmacodynamics").
As with any other inhaled therapy, paradoxical bronchospasm with immediate wheezing and shortness of breath after drug administration may occur. If a patient develops paradoxical bronchospasm, Symbicort Turbuhaler should be discontinued immediately, the patient's condition assessed, and alternative therapy initiated if necessary. Paradoxical bronchospasm, which requires immediate treatment, is reversed by short-acting inhaled bronchodilators (see section "Adverse reactions").
Systemic effects may occur with inhaled administration of all inhaled corticosteroids, especially at high doses and during prolonged treatment. The likelihood of such effects is much lower with inhaled corticosteroids compared to oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataract and glaucoma, and less frequently, psychiatric disturbances or behavioral changes, including psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggression (especially in children) (see section "Adverse reactions").
The potential impact on bone mineral density should be considered, particularly in patients receiving high doses over a prolonged period, which is an additional risk factor for osteoporosis. In long-term studies of inhaled budesonide at average daily doses of 400 mcg (delivered dose) in children or 800 mcg (delivered dose) in adults, no significant effect on bone mineral density was observed. Information regarding the effect of Symbicort Turbuhaler at higher doses is lacking.
If there is reason to suspect that previous systemic steroid therapy has impaired adrenal function, caution should be exercised when switching patients to treatment with Symbicort Turbuhaler.
The advantages of inhaled budesonide therapy generally minimize the need for oral steroids; however, patients previously treated with long-term oral steroids may still be at risk of adrenal dysfunction.
Recovery after discontinuation of oral steroids may take a long time, so patients previously on oral corticosteroids and switched to inhaled budesonide may remain at risk of adrenal dysfunction for a prolonged period. In such cases, regular monitoring of hypothalamic-pituitary-adrenal (HPA) axis function is required.
Long-term treatment with high doses of inhaled corticosteroids, especially when doses higher than recommended are used, may also lead to clinically significant adrenal suppression. Therefore, additional systemic corticosteroid therapy should be considered during periods of stress, such as severe infections or planned surgical procedures. Rapid dose reduction of steroids may lead to acute adrenal crisis. Symptoms and signs observed during acute adrenal crisis are not always clear but may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension, and hypoglycemia.
Treatment with additional systemic steroids or inhaled budesonide must not be abruptly discontinued.
When switching from oral steroid therapy to Symbicort Turbuhaler, a lower systemic steroid effect is generally observed, which may lead to the emergence of allergy symptoms or arthritis symptoms such as rhinitis, eczema, and muscle and joint pain. If these conditions develop, specific treatment should be initiated. Insufficient glucocorticoid effect may be suspected if symptoms such as fatigue, headache, nausea, and vomiting occur, although this is rare. In such cases, a temporary increase in the dose of oral glucocorticoids may sometimes be necessary.
To minimize the risk of oropharyngeal candidiasis (see section "Adverse reactions"), patients should be instructed to rinse their mouth with water after inhaling the maintenance dose of the drug. If oropharyngeal candidiasis is present, the oral cavity should be rinsed with water after inhalation of the drug as needed.
Concomitant use of itraconazole, ritonavir, or other potent CYP3A4 inhibitors should be avoided (see section "Interaction with other medicinal products and other forms of interaction"). If this is unavoidable, the time interval between administration of interacting drugs should be as long as possible. Concomitant use of Symbicort Turbuhaler for both maintenance and reliever therapy is not recommended in patients taking potent CYP3A4 inhibitors.
Symbicort Turbuhaler should be used with caution in patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, untreated hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe arterial hypertension, aneurysm, or other serious cardiovascular diseases such as ischemic heart disease, tachyarrhythmia, or severe heart failure.
The drug should be used with caution in patients with QTc interval prolongation. Formoterol may cause QTc interval prolongation.
The need for inhaled corticosteroids and their dosage should be reassessed in patients with active or inactive pulmonary tuberculosis, fungal or viral respiratory tract infections.
With high-dose use of β2-adrenergic agonists, potentially serious hypokalemia may occur. Concomitant treatment with β2-adrenergic agonists and medicinal products that may cause hypokalemia or enhance the hypokalemic effect (e.g., xanthine derivatives, steroids, and diuretics) may potentiate the hypokalemic effect of β2-adrenergic agonists. Particular caution is required in patients with unstable bronchial asthma requiring frequent use of bronchodilators for symptom relief, as well as in acute severe asthma, since the risk of hypokalemia is increased under conditions of hypoxia and other states that increase the likelihood of this complication. In such cases, serum potassium levels should be monitored.
As with other β2-adrenergic agonists, patients with diabetes mellitus should monitor blood glucose levels more closely.
Visual disturbances may occur with systemic and local corticosteroid use. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should consult an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which has been reported after systemic or local corticosteroid use.
Symbicort Turbuhaler contains lactose monohydrate (< 1 mg/inhalation). This amount usually does not cause problems in patients who are lactose intolerant. This excipient contains small amounts of milk proteins that may cause allergic reactions.
Pneumonia in COPD patients
An increased incidence of pneumonia, including cases requiring hospitalization, has been observed in COPD patients receiving inhaled corticosteroids. Some data suggest an increased risk of pneumonia with higher steroid doses, although this has not been consistently demonstrated in all studies.
There is no convincing clinical evidence of differences in pneumonia risk among various inhaled corticosteroid products.
Physicians should be vigilant regarding the possible development of pneumonia in COPD patients, as clinical signs of such infections overlap with symptoms of COPD exacerbation.
Risk factors for pneumonia in COPD patients include smoking, advanced age, low body mass index (BMI), and severe COPD.
Children. Regular measurement of height is recommended in children receiving long-term inhaled corticosteroid therapy. If growth retardation occurs, therapy should be re-evaluated with the aim of reducing the inhaled corticosteroid dose to the lowest dose at which effective control of bronchial asthma symptoms is maintained, if possible.
The benefit of corticosteroid use must be carefully weighed against the potential risk of growth retardation. Additionally, referral to a pediatric respiratory specialist may be appropriate.
Limited long-term study data indicate that most children and adolescents receiving inhaled budesonide therapy eventually achieve normal adult height. However, an initial slight and transient reduction in growth velocity (approximately 1 cm) has been observed, typically during the first year of treatment.
Use during pregnancy or breastfeeding.
Pregnancy
There are no clinical data on the use of Symbicort Turbuhaler or concomitant therapy with formoterol and budesonide during pregnancy. Data from animal studies on the effect of the drug on embryofetal development did not reveal any additional adverse effects with this combination.
Sufficient data on the use of formoterol in pregnant women are lacking. In reproductive toxicity studies in animals, formoterol caused adverse effects at very high systemic doses.
Data from approximately 2000 pregnancies did not show any increased teratogenic risk associated with inhaled budesonide use. Animal studies have demonstrated that glucocorticoids may cause developmental abnormalities; however, these findings are likely not relevant to humans when the drug is used at recommended doses.
Animal studies have also shown that high-dose glucocorticoid use during pregnancy increases the risk of intrauterine growth retardation, development of cardiovascular disease in adult animals, and permanent changes in glucocorticoid receptor density, metabolism, and neurotransmitter profiles at dose ranges below teratogenic doses.
Symbicort Turbuhaler may be used during pregnancy only if the benefit of treatment outweighs the potential risks. The lowest effective dose of budesonide that provides adequate control of bronchial asthma symptoms should be used.
Breastfeeding
Budesonide passes into breast milk. However, no effect on the breastfed infant is expected when the drug is used at therapeutic doses. It is unknown whether formoterol passes into human breast milk.
In rats, small amounts of formoterol were detected in maternal milk. The use of Symbicort Turbuhaler in breastfeeding women should be considered only if the expected benefit to the mother outweighs any potential risk to the infant.
Fertility
There are no data on the potential effect of budesonide on fertility. In animal studies on the effect of formoterol on reproductive function, a slightly reduced fertility level was observed in male rats at high systemic exposure.
Ability to affect reaction speed when driving or operating machinery.
Symbicort Turbuhaler has no effect or a negligible effect on the ability to drive or operate machinery.
Administration and Dosage
Route of administration: Inhalation.
Dosing
Asthma
Symbicort Turbuhaler is not intended for initial treatment of asthma. The doses of the components in Symbicort Turbuhaler should be individually adjusted and modified according to the severity of the disease. This should be taken into account not only at the beginning of treatment with combination medications but also during adjustments of the maintenance dose. If a patient requires a combination of doses different from those available in the combined inhaler, appropriate doses of β₂-adrenoceptor agonists and/or corticosteroids should be prescribed using separate inhalers.
The dose should be gradually reduced to the lowest dose that effectively controls symptoms. Patients should undergo regular follow-up examinations by the physician who prescribed the medication to ensure that the dose of Symbicort Turbuhaler remains optimal. After achieving long-term symptom control with the lowest recommended dose, an attempt should be made to control symptoms using only an inhaled corticosteroid.
There are two regimens for using Symbicort Turbuhaler:
A. Use of Symbicort Turbuhaler for maintenance therapy: Symbicort Turbuhaler is used for regular maintenance treatment in combination with a separate short-acting bronchodilator used as needed for symptom relief.
B. Use of Symbicort Turbuhaler for maintenance therapy and symptom relief: Symbicort Turbuhaler is used for regular maintenance treatment and also as needed for symptom relief.
A. Use of Symbicort Turbuhaler for maintenance therapy
Patients should be advised to always carry a separate short-acting bronchodilator for immediate symptom relief at any time.
Recommended doses
Adults (aged 18 years and older): 1–2 inhalations twice daily. Some patients may require up to 4 inhalations twice daily.
Children (aged 12–17 years): 1–2 inhalations twice daily.
After achieving symptom control with twice-daily administration, the dose is usually titrated down to the lowest effective dose, including reducing to once-daily use of Symbicort Turbuhaler, when, in the physician’s opinion, the patient requires maintenance therapy with a long-acting bronchodilator in combination with an inhaled corticosteroid.
An increased use of a separate short-acting bronchodilator indicates worsening of the underlying disease and requires reassessment of asthma management.
Children (aged 6 years and older): For children aged 6–11 years, a lower-dose formulation is available (80 mcg/4.5 mcg per dose).
Children under 6 years of age: Due to limited available data, Symbicort Turbuhaler is not recommended for children under 6 years of age.
B. Use of Symbicort Turbuhaler for maintenance therapy and symptom relief
Patients should take their daily maintenance dose of Symbicort Turbuhaler and also use this medication as needed for symptom relief. Patients should be advised to always carry Symbicort Turbuhaler for immediate symptom relief in emergency situations. Patients using Symbicort Turbuhaler for symptom relief should discuss with their physician the possibility of using this medication for prevention of bronchoconstriction triggered by allergens or physical exertion; in such cases, the frequency of as-needed use should be considered. If frequent use of bronchodilators is required without a corresponding need to increase the dose of inhaled corticosteroids, alternative medications for symptom relief should be considered.
The use of Symbicort Turbuhaler for maintenance therapy and symptom relief should be considered, in particular, for patients:
- with poorly controlled asthma who frequently require symptom-relief medications;
- with a history of asthma exacerbations requiring medical intervention.
Patients who frequently and in large amounts use Symbicort Turbuhaler as needed should be closely monitored for the development of dose-dependent adverse reactions.
Recommended doses
Adults and children (aged 12 years and older): The recommended maintenance dose is 2 inhalations per day—1 inhalation in the morning and 1 in the evening, or 2 inhalations either in the morning or in the evening. Some patients may require a maintenance dose of 2 inhalations twice daily. As needed, when symptoms occur, 1 additional inhalation should be taken. If symptoms persist after several minutes, an additional inhalation may be taken. In any single episode, no more than 6 inhalations should be used.
A total daily dose exceeding 8 inhalations is generally not required; however, during a limited period, the total daily dose may be increased up to 12 inhalations. Patients using more than 8 inhalations per day are strongly advised to consult their physician. They should undergo reassessment and review of their maintenance therapy regimen.
Children under 12 years of age: Symbicort Turbuhaler is not recommended for use in children under 12 years of age for maintenance therapy and symptom relief.
Chronic Obstructive Pulmonary Disease (COPD)
Recommended doses
Adults: 2 inhalations twice daily.
General information
Special patient groups
No special dosage requirements are needed for elderly patients. Data on the use of Symbicort Turbuhaler in patients with impaired renal or hepatic function are lacking. Since both budesonide and formoterol are primarily eliminated via hepatic metabolism, increased plasma concentrations of the drug may be expected in patients with severe hepatic cirrhosis.
Method of administration
Instructions for correct use of Symbicort Turbuhaler
Preparing a new Symbicort Turbuhaler inhaler for use
Before the first use, a new Symbicort Turbuhaler inhaler must be prepared for use as follows:
- Unscrew and remove the cap. A rattling sound may be heard.
- Hold the Symbicort Turbuhaler inhaler vertically with the red dose indicator at the bottom.
- Turn the red dose indicator fully to one side, then fully to the other side (the order does not matter). A click should be heard.
- Turn the dose indicator again fully in both directions.
- The Symbicort Turbuhaler inhaler is now ready for use.
How to inhale
Each dose must be taken by following the instructions below every time.
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The amount of medicine inhaled is very small. This means you may not taste the medicine after inhalation. Provided you follow the instructions correctly, you can be confident that you have received the dose and the medicine has reached your lungs.
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- After daily morning and/or evening inhalations, rinse the mouth with water, without swallowing it.
Do not attempt to remove or unscrew the mouthpiece. It is fixed on the Symbicort Turbuhaler inhaler and must not be removed. Do not use the inhaler if it is damaged or if the mouthpiece has become detached.
As with other inhalers, caregivers should ensure that children prescribed Symbicort Turbuhaler inhale according to the instructions above.
Cleaning the Symbicort Turbuhaler inhaler
The outer surface of the mouthpiece should be wiped once a week with a dry cloth. Do not use water or other liquids.
When to use a new inhaler
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- The appearance of red color in the indicator window means that approximately 20 doses remain in the inhaler. When 10 doses remain, the dose indicator window turns completely red. When the "0" mark on the red window reaches the center of the indicator window, the inhaler should be replaced with a new one (Fig. 5).
Note
- The dose counter will continue to rotate and click even after the Symbicort Turbuhaler inhaler is empty.
- The sound heard when shaking the Symbicort Turbuhaler inhaler is caused by the desiccant, not the medication. Therefore, this sound cannot be used to determine how much Symbicort Turbuhaler medication remains in the inhaler.
- If more than one dose is accidentally loaded into the Symbicort Turbuhaler inhaler, only one dose will still be inhaled into the lungs. However, the dose indicator will register the total number of doses dispensed.
In case of overdose
The medication should be taken as directed in the instructions or by a physician. Do not exceed the prescribed dose without consulting your doctor.
The most common symptoms that may occur in case of an overdose of Symbicort Turbuhaler are tremor, headache, or rapid heartbeat.
In case of a missed inhalation
- If an inhalation is missed, it should be taken as soon as remembered. However, if the next scheduled dose is due soon, the missed dose should not be taken.
- Do not take a double dose to make up for a missed dose.
For further questions regarding the use of this medication, consult your doctor or pharmacist.
The inhaler is activated by inspiratory flow, meaning that when the patient inhales through the mouthpiece, the active substances are delivered into the airways along with the inhaled air.
Note
It is important to instruct the patient:
- to follow the instructions for medical use of Symbicort Turbuhaler;
- to inhale strongly and deeply through the mouthpiece to ensure optimal delivery of the dose to the lungs;
- never to exhale through the mouthpiece;
- to close the Symbicort Turbuhaler inhaler with the cap after use;
- to rinse the mouth with water after each maintenance dose to minimize the risk of developing oral candidiasis. In case of oral candidiasis, rinse the mouth with water after using the medication as needed.
The patient may not taste or feel the Symbicort Turbuhaler medication during inhalation due to the small dose inhaled.
Other information
On the lower part of the rotating dose counter, there is an embossed Braille code identifying Symbicort Turbuhaler (the code for Symbicort Turbuhaler is the number 6, distinguishing it from other AstraZeneca medications).
Children. Symbicort is not recommended for children under 6 years of age. For children aged 6–11 years, a lower-dose formulation is available (80 mcg/4.5 mcg per dose).
Overdose.
Overdose of formoterol is likely to cause effects typical of β2-adrenergic agonists: tremor, headache, palpitations. In isolated cases, tachycardia, hyperglycemia, hypokalemia, QTc interval prolongation, arrhythmia, nausea, and vomiting have been reported. Supportive and symptomatic therapy may be indicated. Administration of 90 mcg over 3 hours in patients with acute bronchial obstruction has been shown to be safe.
Acute overdose of budesonide, even in excessive doses, is not expected to cause clinical problems. However, prolonged use of excessive doses may lead to manifestations of systemic glucocorticosteroid effects such as hypercorticism and adrenal suppression.
If treatment with Symbicort Turbuhaler needs to be discontinued due to formoterol overdose, consider using an appropriate inhaled corticosteroid.
Adverse reactions
Since Symbicort Turbuhaler contains budesonide and formoterol, the same adverse reactions associated with the use of each of the active substances alone may occur. Concomitant use of the two substances did not increase the frequency of adverse reactions. The most commonly observed adverse reactions associated with the use of the medicinal product are pharmacologically predictable side effects of β2-adrenoceptor agonists, such as tremor and palpitations. These adverse reactions were usually mild and disappeared within a few days of treatment.
The adverse reactions listed below, caused by the use of budesonide or formoterol, are presented by system organ classes and by frequency of occurrence. Adverse reactions by frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), and very rare (< 1/10000).
| System organ class (SOC) |
Frequency |
Adverse reaction to drug use |
| Infections and parasitic disorders |
Common |
Oral and pharyngeal candidiasis |
| Immune system disorders |
Uncommon |
Immediate or delayed hypersensitivity reactions, such as exanthema, urticaria, pruritus, dermatitis, angioneurotic edema, and anaphylactic reaction |
| Endocrine disorders |
Very rare |
Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density |
| Metabolism and nutrition disorders |
Uncommon |
Hypokalemia |
| Very rare |
Hyperglycemia |
|
| Psychiatric disorders |
Uncommon |
Aggression, psychomotor hyperactivity, anxiety, sleep disorders |
| Very rare |
Depression, behavioral disturbances (mainly in children) |
|
| Nervous system disorders |
Common |
Headache, tremor |
| Uncommon |
Dizziness |
|
| Very rare |
Taste disturbance |
|
| Eye disorders |
Uncommon |
Blurred vision (see also section "Special precautions for use") |
| Very rare |
Cataract, glaucoma |
|
| Cardiac disorders |
Common |
Palpitations |
| Uncommon |
Tachycardia |
|
| Uncommon |
Cardiac arrhythmias, e.g., atrial fibrillation, supraventricular tachycardia, extrasystoles |
|
| Very rare |
Angina pectoris, QTc interval prolongation |
|
| Vascular disorders |
Very rare |
Changes in blood pressure |
| Respiratory, thoracic and mediastinal disorders |
Common |
Mild throat irritation, cough, hoarseness |
| Uncommon |
Bronchospasm |
|
| Gastrointestinal disorders |
Uncommon |
Nausea |
| Skin and subcutaneous tissue disorders |
Uncommon |
Increased tendency to bruising |
| Musculoskeletal and connective tissue disorders |
Uncommon |
Muscle cramps |
Candidiasis of the oropharynx results from deposition of the medicinal product in the oral cavity. Patients should be instructed to rinse their mouth with water after each inhalation of the maintenance dose to minimize the risk of oral candidiasis. Oropharyngeal candidiasis usually responds to local antifungal treatment without the need to discontinue inhaled corticosteroid therapy. If oropharyngeal candidiasis develops, patients should also rinse their mouth with water after using the medicinal product as needed.
As with any other inhaled therapy, paradoxical bronchospasm, characterized by immediate wheezing and shortness of breath following drug administration, may very rarely occur (less than 1 case per 10,000 patients). Paradoxical bronchospasm should be treated immediately and responds to administration of a fast-acting inhaled bronchodilator. In such cases, treatment with Symbicort Turbuhaler should be discontinued immediately, the patient's condition should be assessed, and alternative therapy initiated if necessary (see section "Special instructions for use").
Systemic effects may occur with inhaled corticosteroids, particularly at high doses and with prolonged use. The likelihood of such effects is lower with inhaled corticosteroids compared to oral formulations. Potential systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataract, and glaucoma. Increased susceptibility to infections and impaired ability to adapt to stress may also occur. These effects are likely dose-dependent and influenced by duration of treatment, concomitant or prior use of steroid medicinal products, and individual patient sensitivity.
Treatment with β2-adrenergic agonists may lead to increased blood levels of insulin, free fatty acids, glycerol, and ketone bodies.
Children. Regular monitoring of growth is recommended in children receiving long-term inhaled corticosteroid therapy (see section "Special instructions for use").
Reporting of suspected adverse reactions
It is important to report suspected adverse reactions during the post-marketing phase of the medicinal product. This allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are obliged to report any suspected adverse reactions through the national reporting system.
Shelf life.
2 years.
Storage conditions.
Keep out of the reach of children. Store at temperatures not exceeding 30°C. Keep the container tightly closed to protect from moisture.
Packaging.
60 doses or 120 doses in a plastic inhaler; 1 inhaler per cardboard box.
Prescription status.
Prescription only.
Manufacturer.
AstraZeneca AB/AstraZeneca AB.
Manufacturer's address and place of business.
Forskaragatan 18, Sodertalje, 151 36, Sweden/Forskaragatan 18, Sodertalje, 151 36, Sweden.