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: 320 mcg micronized budesonide;
9.0 mcg formoterol fumarate dihydrate;
Excipient: lactose monohydrate.
Pharmaceutical form. Powder for inhalation, metered.
Main physicochemical characteristics:
Inhaler: a rotating red-colored dosing device. The rotating dosing device has embossed Braille code. The cap is white-colored. Inside the cap there are five ribs.
In the dose indicator window, the number 60 is visible. 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 mechanisms of action of both components are described below.
Budesonide
Budesonide is a glucocorticosteroid that, when inhaled, exerts a dose-dependent anti-inflammatory effect in the airways, leading to a reduction in symptoms and decreased frequency of asthma exacerbations. Inhaled budesonide is associated with fewer adverse reactions compared to systemic corticosteroids. The precise mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.
Formoterol
Formoterol is a selective β2-adrenergic agonist that, upon 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 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 the fixed combination budesonide/formoterol on lung function was equivalent to that of the free combination of budesonide and formoterol and was superior to budesonide monotherapy. All treatment groups used short-acting β2-adrenergic agonists as needed. There was no evidence of diminished anti-asthmatic effect over time.
Two 12-week studies were conducted in pediatric patients, in which 265 individuals aged 6–11 years received maintenance therapy with budesonide/formoterol (2 inhalations of 80 mcg/4.5 mcg/inhalation twice daily) and as-needed short-acting β2-adrenergic agonists. In both studies, improvements in lung function and appropriate tolerability were observed compared to treatment with the corresponding dose of budesonide as monotherapy.
COPD
Two 12-month studies evaluated 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) in patients with moderate to 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 versus 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
Fixed-dose combinations of budesonide and formoterol were found to be bioequivalent to the corresponding monoproducts with respect to systemic exposure to budesonide and formoterol. Despite this, after administration of the fixed-dose combination, a slight increase in cortisol secretion suppression was observed compared to administration of the individual drugs. This difference was considered clinically insignificant.
There was no evidence of pharmacokinetic interaction between budesonide and formoterol.
Pharmacokinetic parameters of the respective active substances were similar after administration of budesonide and formoterol as monoproducts and in the fixed-dose combination. After administration of the combined medicinal product, the AUC of budesonide, rate of absorption, and maximum plasma concentration were slightly higher. 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. In studies, the average lung 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, lung deposition is within the same range as in adults at the same doses. Corresponding plasma concentrations were not determined.
Inhaled formoterol is rapidly absorbed; plasma concentration reaches maximum within 10 minutes after inhalation. In studies, the average lung 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 is approximately 4 L/kg for formoterol and 3 L/kg for budesonide. Formoterol is inactivated via conjugation reactions (producing active O-demethylated and deformylated metabolites, but these are predominantly present as inactivated conjugates). Budesonide undergoes extensive (approximately up to 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 that of budesonide. There is no evidence 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 administered formoterol dose is excreted unchanged in urine.
Formoterol has a high systemic clearance (approximately 1.4 L/min), and its terminal half-life averages 17 hours.
Budesonide is metabolized primarily by the CYP3A4 enzyme. Budesonide metabolites are excreted in urine in unchanged or conjugated forms. Only a negligible amount of unchanged budesonide is detected in urine. Budesonide has 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 children and patients with renal impairment are unknown. In patients with liver disease, systemic exposure to budesonide and formoterol 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 320 mcg/9.0 mcg is indicated in adults and children aged 12 years and older for regular treatment of bronchial asthma when combination therapy (inhaled corticosteroid and long-acting β2-adrenoceptor agonist) is appropriate:
- if their condition is not adequately controlled with inhaled corticosteroids and as-needed short-acting β2-adrenoceptor agonists, or
- if their condition is well controlled with 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 who have a forced expiratory volume in 1 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 used concomitantly 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").
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 times when administered concomitantly. When ketoconazole was administered 12 hours after budesonide, budesonide concentration increased on average by 3 times, indicating that staggered administration of the medicinal products with an 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 times).
Pharmacodynamic interactions
Beta-blockers may attenuate or antagonize the effect of formoterol. Therefore, Symbicort Turbuhaler should not be used concomitantly with beta-blockers (including ophthalmic 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 receiving 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 arrhythmia in patients taking cardiac glycosides.
No interactions between budesonide and formoterol with any other medicinal products used for the treatment of bronchial asthma have been observed.
Children. Drug interaction studies have been conducted only in adults.
Special precautions for use.
If discontinuation of treatment is necessary, it is recommended to gradually reduce the dose rather than abruptly stop therapy.
The patient should consult a physician if treatment appears ineffective or if the maximum recommended daily dose of Symbicort Turbuhaler has been exceeded (see section "Dosage and administration"). Increased use of short-acting bronchodilators indicates worsening of the patient's condition and the need to reassess bronchial asthma management. Sudden and progressive deterioration in control of bronchial asthma or COPD is potentially life-threatening; therefore, urgent medical evaluation is required. In such cases, intensification of corticosteroid therapy should be considered, for example, initiating a course of oral corticosteroids or antibiotic treatment if bacterial infection is present.
Patients should be advised to always carry a "rescue" inhaler.
Patients should be reminded of the necessity to continue maintenance therapy with Symbicort Turbuhaler as prescribed, even in the absence of symptoms.
After achieving control of bronchial asthma symptoms, gradual dose reduction of Symbicort Turbuhaler may be considered. Regular patient monitoring is essential during this process. 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 or acute or severe worsening of bronchial asthma.
Serious adverse reactions related to bronchial asthma or exacerbations of the disease may occur during treatment with Symbicort Turbuhaler. Patients should continue treatment and consult a physician if asthma symptoms do not resolve or worsen after starting therapy with Symbicort Turbuhaler.
There are no clinical 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 increase in wheezing and onset of dyspnea after inhalation may occur. If paradoxical bronchospasm develops, Symbicort Turbuhaler should be discontinued immediately, the patient's condition assessed, and alternative therapy initiated if necessary. Paradoxical bronchospasm, which requires immediate treatment, responds to a fast-acting inhaled bronchodilator (see section "Adverse reactions").
Systemic effects may occur with inhaled corticosteroids, particularly 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, glaucoma, and less frequently, psychiatric disturbances or behavioral changes, including psychomotor hyperactivity, sleep disturbances, 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 on the effect of Symbicort Turbuhaler at higher doses is lacking.
Precautions should be taken when switching patients from prior systemic steroid therapy with impaired adrenal function to treatment with Symbicort Turbuhaler.
The benefits of inhaled budesonide therapy generally minimize the need for oral corticosteroids, but patients previously treated with oral corticosteroids for a prolonged period may still be at risk of adrenal insufficiency. Recovery after discontinuation of oral corticosteroids may take considerable time; thus, patients previously on oral corticosteroids and switched to inhaled budesonide may remain at risk for adrenal insufficiency for a prolonged period. In such cases, hypothalamic-pituitary-adrenal (HPA) axis function should be monitored regularly.
Prolonged treatment with high doses of inhaled corticosteroids, especially when higher than recommended doses are used, may also lead to clinically significant adrenal suppression. Therefore, additional systemic corticosteroid therapy should be considered during periods of stress (e.g., severe infections) or planned surgical procedures. Rapid dose reduction of corticosteroids may precipitate acute adrenal crisis. Symptoms and signs that may occur during acute adrenal crisis can be nonspecific but may include anorexia, abdominal pain, weight loss, increased fatigue, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension, and hypoglycemia.
Treatment with additional systemic corticosteroids or inhaled budesonide must not be abruptly discontinued.
When switching from oral corticosteroid 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 or joint pain. If these conditions develop, specific treatment should be initiated. Glucocorticoid insufficiency should be suspected if, rarely, symptoms such as increased fatigue, headache, nausea, and vomiting occur. In such cases, temporary increase in the dose of oral glucocorticoids may sometimes be necessary.
To reduce the risk of oropharyngeal candidiasis (see section "Adverse reactions"), patients should be instructed to rinse the mouth with water after each maintenance dose.
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 unavoidable, the time interval between administration of interacting medicinal products should be as long as possible.
Symbicort Turbuhaler should be used with caution in patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, untreated hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm, or other severe 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 and dosage of inhaled corticosteroids should be reassessed in patients with active or inactive pulmonary tuberculosis, or fungal or viral respiratory tract infections.
With high-dose use of β2-adrenoceptor agonists, potentially serious hypokalemia may develop. When β2-adrenoceptor agonists are used concomitantly with medicinal products that may cause hypokalemia or enhance its effect (e.g., xanthine derivatives, steroids, diuretics), the hypokalemic effect of β2-adrenoceptor agonists may be potentiated. Particular caution is required in patients with unstable bronchial asthma receiving various short-acting bronchodilators, or in acute severe asthma, as the risk of hypokalemia is increased in the presence of hypoxia and other conditions that increase the likelihood of this complication. In such cases, serum potassium levels should be monitored.
As with other β2-adrenoceptor agonists, blood glucose levels should be monitored more closely in patients with diabetes mellitus.
Visual disturbances, including blurred vision, may occur with systemic or local corticosteroid use. If a patient develops such symptoms, ophthalmological consultation is recommended 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 with lactose intolerance. This excipient contains small amounts of milk proteins, which 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 corticosteroid doses, although this has not been consistently demonstrated in all studies.
There are no conclusive clinical data showing differences in pneumonia risk among inhaled corticosteroid products.
Physicians should remain vigilant for possible pneumonia in COPD patients, as clinical signs of infection may resemble 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 monitoring of growth in children receiving long-term inhaled corticosteroid therapy is recommended. If growth retardation occurs, therapy should be reassessed with the aim of reducing the inhaled corticosteroid dose to the lowest dose that maintains effective control of bronchial asthma symptoms, if possible. The benefits of corticosteroid therapy and the potential risk of growth suppression should be carefully weighed. Referral to a pediatric respiratory specialist may also be appropriate.
Due to limited long-term data on glucocorticoid treatment, it is expected that most children and adolescents receiving inhaled budesonide will eventually achieve normal adult height. However, an initial slight and transient reduction in growth velocity (approximately 1 cm) has been observed. This delay is typically seen during the first year of treatment.
Use during pregnancy or breastfeeding
Pregnancy
There are no clinical data on the use of Symbicort Turbuhaler or combined therapy with formoterol and budesonide during pregnancy. Data from animal studies on the effects of this combination on embryofetal development did not reveal any additional adverse effects when used in combination.
Adequate data on the use of formoterol in pregnant women are lacking. Reproductive toxicity studies in animals showed adverse effects with very high systemic doses of formoterol.
Data from approximately 2000 pregnancies did not show any increased teratogenic risk associated with inhaled budesonide. Animal studies have shown that glucocorticoids can cause congenital malformations. However, these findings are likely not clinically relevant to humans when the drug is used at recommended doses.
Animal studies also demonstrated that high-dose glucocorticoid use during pregnancy increased risks of intrauterine growth retardation, development of cardiovascular disease in adult offspring, and permanent changes in glucocorticoid receptor density, metabolism, and neurotransmitter profiles at doses below teratogenic levels.
Symbicort Turbuhaler may be used during pregnancy only if the benefit to the mother outweighs the potential risks to the fetus. 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 effects on the infant are 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 effects of formoterol on reproductive function, a slightly reduced fertility 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 vehicles or operate machinery.
Method of administration and dosage.
Route of administration – inhalation.
Dosing
Bronchial asthma
Symbicort Turbuhaler is not indicated for initial treatment of bronchial asthma. The doses of 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 drugs, but also during adjustment of maintenance dose. If a patient requires a dose combination different from those available in the combined inhaler, appropriate doses of β2-adrenergic agonists and/or corticosteroids should be prescribed using separate inhalers.
Recommended doses
Adults (aged 18 years and older): 1 inhalation twice daily. Some patients may require up to 2 inhalations twice daily.
Adolescents (aged 12–17 years): 1 inhalation twice daily.
Patients must undergo regular follow-up examinations by the physician who prescribed the medication to ensure that the dose of Symbicort Turbuhaler remains optimal. The dose should be gradually reduced to the lowest dose that effectively controls symptoms. After achieving long-term control with the lowest recommended dose, consideration should be given to controlling symptoms using an inhaled corticosteroid alone.
Typically, after achieving symptom control with twice-daily administration, the dose should be titrated down to the lowest effective dose, including reducing to once-daily use of Symbicort Turbuhaler, if the physician considers that the patient requires maintenance therapy with a long-acting bronchodilator.
More frequent use of a short-acting bronchodilator indicates worsening of the patient's condition and the need to review bronchial asthma treatment.
Children aged 6 years and older: a lower-dose formulation (80 mcg/4.5 mcg/dose) is available for children aged 6–11 years.
Children under 6 years of age: due to limited data available, Symbicort Turbuhaler is not recommended for children under 6 years of age.
Symbicort Turbuhaler 320 mcg/9.0 mcg should only be used for maintenance therapy. For maintenance therapy and symptom relief, lower-strength formulations of Symbicort Turbuhaler are available (160 mcg/4.5 mcg/dose and 80 mcg/4.5 mcg/dose).
COPD
Recommended doses
Adults: 1 inhalation twice daily.
General information
Special patient groups
No special dosage adjustments are required for elderly patients. Data on the use of Symbicort Turbuhaler in patients with renal or hepatic impairment are lacking. Since budesonide and formoterol are primarily eliminated via hepatic metabolism, increased drug exposure 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 as follows:
- Unscrew and remove the cap. A rattling sound may be heard.
- Hold the Symbicort Turbuhaler inhaler vertically with the red dose indicator pointing downwards.
- Rotate the red dose indicator fully to one side, then fully to the other side (the order does not matter). A click should be heard.
- Rotate the red dose indicator again in both directions.
- The Symbicort Turbuhaler inhaler is now ready for use.
How to perform inhalation
To take a dose, follow the instructions below.
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Fig. 4 |
The amount of medication inhaled is very small. This means you may not taste the medicine after inhalation. Provided you follow the instructions, you can be confident that you have received the dose and that the medication 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 securely attached to 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 use the inhaler according to the above instructions.
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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Fig. 5 |
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- The appearance of red color in the indicator window means that approximately 20 doses remain in the inhaler. When the inhaler contains 10 doses, the dose indicator window becomes completely red. When the "0" mark in the red window reaches the center of the dose indicator window, the inhaler should be replaced with a new one.
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 help determine how much medication remains in the inhaler.
- If more than one dose is accidentally loaded into the Symbicort Turbuhaler inhaler, only one dose will still be delivered to the lungs during inhalation. However, the dose indicator will register the total number of doses dispensed.
In case of overdose
The medication should be used exactly as directed in the instructions or as prescribed 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 include tremor, headache, or rapid heartbeat.
In case of a missed inhalation
- If a dose is missed, it should be taken as soon as remembered. However, if it is almost time for the next dose, the missed dose should be skipped.
- 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;
- to inhale deeply and forcefully 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 oral candidiasis. In case of oral candidiasis, rinse the mouth with water after each use as needed.
The patient may not taste or feel the Symbicort Turbuhaler medication during inhalation due to the small dose inhaled.
Children. Symbicort Turbuhaler 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 result in 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 systemic effects of glucocorticosteroids, 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 instead.
Adverse Reactions
Since Symbicort Turbuhaler contains budesonide and formoterol, adverse reactions associated with the use of each active substance separately may occur. Concomitant use of the two substances did not increase the frequency of adverse reactions. The most commonly reported 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 in intensity and disappeared within a few days of treatment.
The adverse reactions caused by budesonide or formoterol listed below are presented by system organ class and frequency of occurrence. Adverse reactions are categorized by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), and very rare (< 1/10,000).
| System organ class (SOC) |
Frequency |
Adverse reaction to the use of the medicinal product |
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| Infections and infestations |
Common |
Oral and pharyngeal candidiasis |
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| Immune system disorders |
Uncommon |
Hypersensitivity reactions of immediate or delayed type, e.g. exanthema, urticaria, pruritus, dermatitis, angioedema and anaphylactic reactions |
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| Endocrine disorders |
Very rare |
Cushing's syndrome, adrenal suppression, growth retardation, decreased bone mineral density |
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| Metabolism and nutrition disorders |
Uncommon |
Hypokalaemia |
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| Very rare |
Hypoglycaemia |
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| Psychiatric disorders |
Uncommon |
Aggression, psychomotor hyperactivity, anxiety, sleep disturbances |
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| Very rare |
Depression, behavioural disturbances (mainly in children) |
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| Nervous system disorders |
Common |
Headache, tremor |
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| Uncommon |
Dizziness |
|||
| Very rare |
Taste disturbance |
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| Eye disorders |
Uncommon |
Blurred vision (see section "Special warnings and precautions for use") |
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| Very rare |
Cataract and glaucoma |
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| Cardiac disorders |
Common |
Palpitations |
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| Uncommon |
Tachycardia |
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| Uncommon |
Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles |
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| Very rare |
Angina pectoris, QTc interval prolongation |
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| Vascular disorders |
Very rare |
Changes in blood pressure |
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| Respiratory, thoracic and mediastinal disorders |
Common |
Mild irritation in the throat, cough, hoarseness |
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| Uncommon |
Bronchospasm |
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| Gastrointestinal disorders |
Uncommon |
Nausea |
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| Skin and subcutaneous tissue disorders |
Uncommon |
Increased tendency to bruising |
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| Musculoskeletal and connective tissue disorders |
Uncommon |
Muscle cramps |
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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 topical antifungal treatment without the need to discontinue inhaled corticosteroid therapy. In the event of oropharyngeal candidiasis, patients should also rinse their mouth with water after administration of the medicinal product as needed.
As with any other inhaled therapy, paradoxical bronchospasm, characterized by immediate wheezing and dyspnea following drug administration, may very rarely occur (less than 1 case per 10,000 patients). Paradoxical bronchospasm, which requires immediate treatment, responds to administration of a rapid-acting inhaled bronchodilator. In such cases, treatment with Symbicort Turbuhaler should be discontinued immediately, the patient's condition should be evaluated, and alternative therapy initiated if necessary (see section "Special precautions 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 stress response may also be observed. These effects are likely dependent on dose, duration of exposure, influence of concomitant and previously administered steroids, and individual sensitivity.
Treatment with β2-adrenoceptor 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 corticosteroids (see section "Special precautions for use").
Reporting of suspected adverse reactions
It is important to report suspected adverse reactions during the post-marketing period of the medicinal product. This allows for 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 reach and sight of children. Store below 30°C. Keep the container tightly closed to protect from moisture.
Packaging.
60 doses in a plastic inhaler; 1 inhaler per cardboard box.
Prescription status.
Prescription only.
Manufacturer.
AstraZeneca AB/AstraZeneca AB.
Manufacturer's address.
Forskargatan 18, Sodertalje, 151 36, Sweden.