Symbicort Rapichaler inhalation aerosol metered dose 80 µg+4.5 µg/dose 8ml, 120 doses

Composition

Each delivered dose contains: Active ingredients: budesonide micronized 160 mcg, formoterol fumarate dihydrate micronized 4.5 mcg; Excipients: povidone K 25 0.75 mcg, macrogol 1000 223.8 mcg, apaflurane 227 to 74.6 mcg.

Pharmacological action

Symbicort ® Rapihaler contains budesonide and formoterol, which have different mechanisms of action and exhibit an additive effect in obstructive airway diseases. The inhaler contains a suspension for inhalation. Pressing the top of the inhaler releases a certain amount of suspension at a high rate. If the patient inhales at the same time as the drug is released, it enters directly into the respiratory tract. Mechanism of Action Budesonide Budesonide is a glucocorticosteroid that has a local anti-inflammatory effect. The exact mechanism of anti-inflammatory action of glucocorticosteroids in obstructive pulmonary diseases is not fully understood. The specific activity of budesonide, estimated by its affinity for glucocorticosteroid receptors, is 15 times higher than that of prednisone. An obvious effect of budesonide (a decrease in cortisol concentration to 80% of normal levels) was established for a dose of 800 mcg; in some patients, a significant decrease in cortisol concentration was noted. The results of a long-term study indicate that children and adolescents receiving budesonide inhaled at a low or medium dose achieve normal growth in adulthood. However, it is necessary to consider the possibility of a temporary growth retardation of about 1 cm during the first year of treatment. Formoterol Formoterol, presented as a racemic mixture, is a selective beta-2-adrenergic stimulator that has a relaxing effect on the smooth muscles of the bronchi in patients with reversible airway obstruction. The effect of formoterol begins quickly (within 1-3 minutes after inhalation) and continues for 12 hours after one inhalation. Clinical efficacy The bronchial asthma therapeutic equivalence of Symbicort® Rapihaler and Symbicort® Turbuhaler® was established in two studies of the efficacy and safety of these drugs in medium and high doses in patients with bronchial asthma aged 6 to 79 years. This equivalence was confirmed by the results of a long-term study, which indicate that the safety profile and tolerability of the drugs Symbicort® Rapihaler and Symbicort® Turbuhaler® are comparable. The results of clinical studies showed that the addition of formoterol to budesonide reduced the severity of asthma symptoms, improved lung function and reduced the frequency of exacerbations. When Simbicort Rapihaler was prescribed as maintenance therapy to adult patients, its effect on lung function was similar to that of budesonide and formoterol, used as separate preparations in the form of powder for inhalation, and exceeded the effect of budesonide used as monotherapy in adults and children. In all these types of therapy, a short-acting beta-2-adrenergic agonist was additionally used as needed. No decrease in the anti-asthmatic effect was observed over time. Chronic obstructive pulmonary disease (COPD)Efficacy and safety of Symbicort ® Rapihaler in patients with moderate to severe COPD (pre-bronchodilatory forced expiratory volume in the first second (FEV 1))Both studies examined the efficacy of Symbicort Rapihaler 160 mcg + 4.5 mcg / dose compared with placebo and formoterol Turbuhaler 4.5 mcg; Study 002 also compared the efficacy of Symbicort Rapihaler 160 mcg + 4.5 mcg / dose with budesonide 160 mcg in the form of a metered-dose aerosol. The drugs were used for 2 inhalations 2 times a day. Of the 1964 and 1704 mostly severe COPD patients randomized in these trials,494 and 277 patients received Symbicort Rapihaler 160 mcg + 4.5 mcg / dose. The mean age of patients in these studies was 63 years; prior to treatment, the FEV-1 value averaged 1.04-1.05 liters, or 34% of the proper value. Study 001 In this study, the efficacy of the drug for 12 months was evaluated using the primary efficacy variable, defined as the change in the average FEV 1 value, which was evaluated before inhalation and 1 hour after use of the drug during the treatment period relative to baseline values. When treated with Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose, there was a significant increase in FEV 1 measured 1 hour before inhalation, by 0.04 liters (p = 0.008) compared to formoterol therapy, and by 0.09 liters (p During the entire treatment period, the Symbicort® Rapihaler 160 mcg + 4.5 mcg/dose group showed a significant increase in FEV 1, measured 1 hour after inhalation, by 0.03 liters (p = 0.023) compared to formoterol and by 0.18 liters (pIn a subgroup of patients (n = 491), serial FEV 1 measurements were performed for 12 hours. At the end of the treatment period, the onset of bronchodilation (an increase in FEV 1 by more than 15%) in patients receiving Symbicort® Rapihaler 160 mcg + 4.5 mcg/dose (n = 121) was observed, on average,5 minutes after inhalation. The maximum increase in FEV1 was observed approximately 2 hours after inhalation, and clinically significant improvement in this indicator persisted for 12 hours. The use of Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose significantly reduced the number of severe exacerbations: by 37% (p Compared with placebo, the time to onset of the first severe COPD exacerbation was significantly increased with Symbicort® Rapihaler 160 mcg + 4.5 mcg/dose, while the immediate risk of severe COPD exacerbation was reduced by 26% (p = 0.009). During treatment with Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose, there was a statistically significant improvement in the quality of life of patients compared to placebo (assessment according to the Respiratory Questionnaire of St. George Hospital; -2.39 units; p = 0.006). Study 002 In this study, the effectiveness of the drug for 6 months was evaluated using the primary efficacy variable, defined as the change in the average FEV 1 value, which was evaluated before inhalation and 1 hour after use of the drug during the treatment period relative to baseline values. When treated with Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose, there was a significant increase in FEV 1 measured 1 hour before inhalation, by 0.04 liters (p = 0.026) compared to formoterol therapy, and by 0.08 liters (p In the group treated with Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose, there was a significant increase in FEV 1, measured 1 hour after inhalation, by 0.04 liters (p = 0.039) compared with formoterol and by 0.17 liters (pThe power of study 002 was insufficient to assess the impact on the frequency of severe COPD exacerbations. The values obtained in the treatment groups are consistent with the results of Study 001, although the differences did not reach statistical significance. Thus, the number of exacerbations when taking Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose was reduced by 20% compared to placebo and formoterol. In a subgroup of patients (n = 618), serial FEV 1 measurements were performed for 12 hours. At the end of the treatment period, the onset of bronchodilation (an increase in FEV 1 by more than 15%) in patients receiving Symbicort® Rapihaler 160 mcg + 4.5 mcg/dose (n = 101) was observed, on average,5 minutes after inhalation. The maximum increase in FEV1 was observed approximately 2 hours after inhalation, and clinically significant improvement in this indicator persisted for 12 hours. During treatment with Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose, there was a statistically significant improvement in the quality of life of patients compared to placebo, budesonide and formoterol (assessment according to the St. George’s Hospital Respiratory Questionnaire). : placebo -3.12 units (p = 0.003), budesonide -2.42 units (p = 0.024), formoterol -2.56 units (p = 0.017).

Indications

-Bronchial asthma, insufficiently controlled by taking inhaled glucocorticosteroids in small doses and-2-adrenostimulants of short action, with the expediency of combined therapy with inhaled glucocorticosteroids and-2-adrenostimulants of long action. – Symptomatic therapy in patients with COPD with post-bronchodilator FEV 1

Contraindications

* Hypersensitivity to budesonide, formoterol or excipients included in the preparation. * Grade 3 atrioventricular block. * Initial treatment for asthmatic status or acute attacks of asthma and COPD that require intensive care. * Children under 6 years of age.* Children under 12 years of age (for a dosage of 160 mcg + 4.5 mcg/dose). With caution: pulmonary tuberculosis (active or inactive), fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, decreased adrenal cortex function, uncontrolled hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any localization or other severe cardiovascular diseases (ischemic disease heart disease, tachyarrhythmia or severe heart failure), prolongation of the QT interval (taking formoterol may cause prolongation of the QTc interval).

Side effects

When budesonide and formoterol were co-administered, there was no increase in the incidence of adverse reactions. The most common adverse reactions associated with taking the drug are pharmacologically expected adverse events for beta-₂-adrenomimetics, such as tremor and rapid heartbeat; symptoms are usually moderate and disappear within a few days after the start of treatment.

Bruising and pneumonia occurred in 10% and 6% of patients treated with budesonide in COPD, respectively, compared to 4% and 3% in the placebo group (p <0.001 and p < 0.001). Since Symbicort® Rapihaler contains two active ingredients, budesonide and formoterol, undesirable effects may occur when it is used, similar in nature and intensity to the effects described for these two drugs when used separately.

In clinical studies, respiratory diseases, mainly bronchitis, nasopharyngitis, sinusitis, and upper respiratory tract viral infection, were observed in at least 3% of patients treated with Symbicort® 160 mcg + 4.5 mcg/dose and more often than in the placebo group.

Adverse reactions associated with the use of budesonide or formoterol are presented below, using preferred terms for classes of systems and organs and indicating the absolute frequency. The frequency of reactions is presented in the following gradation: very common (≥1/10); common (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (

It is possible to develop systemic effects of inhaled corticosteroids(adrenal insufficiency, hypercorticism, decreased growth rate in children and adolescents, cataracts, glaucoma, increased blood pressure). IOP in rare cases), especially with prolonged use of the drug in high doses.

The use of beta_-2-adrenomimetics can lead to an increase in the blood content of insulin, free fatty acids, glycerol and ketone bodies.

Interaction

Taking 200 mg of ketoconazole once a day increased the plasma concentration of budesonide (a single oral dose of 3 mg) with their combined use, on average by 6 times. When ketoconazole was administered 12 hours after budesonide use, the plasma concentration of the latter increased by an average of 3 times. There is no information about such an interaction with inhaled budesonide in high doses, but a significant increase in the concentration of the drug in blood plasma is possible.

There are no recommendations for dose adjustment, and the combination of drugs described above should be avoided. If this is not possible, the time interval between the use of a CYP3A4 inhibitor and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent CYP3A4 inhibitors are also likely to significantly increase the plasma concentration of budesonide. Maintenance therapy with Symbicort Rapihaler is not recommended in patients receiving potent CYP3A4 inhibitors.

Beta-adrenergic receptor blockers may weaken or inhibit the action of formoterol. Simbicort Rapihaler should not be administered concomitantly with beta-blockers (including eye drops), except in emergency cases.

Co-use of Symbicort Rapihaler with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors, and tricyclic antidepressants may prolong the QTc interval and increase the risk of ventricular arrhythmias.

In addition, levodopa, levothyroxine, oxytocin, and alcohol may reduce the tolerance of the heart muscle to beta_-2-adrenomimetics.

The combined use 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 arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbons.

When Simbicort ® Rapihaler is co-administered with other beta-adrenomimetics or anticholinergic drugs, the side effects of formoterol may increase.

Hypokalemia may occur as a result of the use of beta_-2-adrenomimetics, which may increase with concomitant treatment with xanthine derivatives, mineralocorticoids and corticosteroids, or diuretics. Hypokalemia may increase the risk of cardiac arrhythmias in patients taking cardiac glycosides.

There was no interaction of budesonide and formoterol with other drugs used for the treatment of bronchial asthma.

How to take it, course of use and dosage

By inhalation. The drug Symbicort ® Rapihaler enters directly into the lungs after inhalation, so the patient should be trained in the correct use of the inhaler (see Instructions for use of the drug Symbicort® Rapihaler).

The patient should be informed about the need to regularly use the drug Symbicort® Rapihaler, i. e. continue taking it even in the absence of symptoms of the disease in order to achieve the greatest therapeutic effect.

Bronchial asthma

Dosage of Symbicort®Rapihaler should be regularly monitored by the attending physician, who adjusts it individually, depending on the severity of the disease, in accordance with current recommendations. The initial dose is selected to achieve effective symptom control. After achieving the desired clinical effect, the dose should be gradually reduced to the minimum, allowing optimal control of the symptoms of bronchial asthma. Thus, later it is possible to switch to therapy only with inhaled corticosteroids. When stopping treatment with Simbicort® Rapihaler, it is recommended to gradually reduce the dose.

In the case of severe bronchial asthma, regular medical monitoring is necessary, as life-threatening situations may occur.Patients with severe bronchial asthma have persistent symptoms of the disease, frequent exacerbations, and the values of the maximum expiratory velocity are less than 60% of the normal value, vary within more than 30%, and do not normalize, despite taking bronchodilators. Such patients are prescribed high-dose inhaled corticosteroids or oral corticosteroids.

If symptoms suddenly worsen, it is possible to increase the dose of corticosteroids under the supervision of a doctor. At the same time, an increase in the dose of inhaled corticosteroids should not be achieved due to more frequent use of the combined drug. With an unstable course of bronchial asthma, it is possible to switch to monopreparation therapy.

Recommendations for the use of Symbicort ® Rapihaler in patients receiving oral corticosteroids are given in the section “Special instructions”.

Doses

Bronchial asthma

Patients receive a daily maintenance dose of Symbicort ® Rapihaler and, if necessary, a fast — acting bronchodilator to relieve symptoms.

Children aged 6-11 years. Symbicort ® Rapihaler 80 mcg + 4.5 mcg / dose: 2 inhalations 2 times a day. The maximum daily dose is 4 inhalations of 80 mcg + 4.5 mcg / dose.

Children aged 12 to 17 years. Symbicort ® Rapihaler 80 mcg + 4.5 mcg / dose: 2 inhalations 1-2 times a day. If symptoms worsen, you can temporarily increase the dose (no more than 1 week) to 4 inhalations 2 times a day.

Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose: 2 inhalations 1-2 times a day. If symptoms worsen, you can temporarily increase the dose (no more than 1 week) to 4 inhalations 2 times a day.

Adults over the age of 18. Symbicort ® Rapihaler 80 mcg + 4.5 mcg / dose: 2 inhalations 1-2 times a day. If symptoms worsen, you can increase the dose to 4 inhalations 2 times a day temporarily or as a maintenance dose.

Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose: 2 inhalations 1-2 times a day. If symptoms worsen, you can temporarily increase the dose to 4 inhalations 2 times a day temporarily or as a maintenance dose.

Statistically, the equivalence of the drugs Symbicort ® Turbuhaler® and Symbicort® Rapihaler was established when using 2 inhalations of 80 mcg + 4.5 mcg / dose or 160 mcg + 4.5 mcg / dose 2 times a day. However, this equivalence has not been confirmed for all dosages.

Patients should be informed about the need to always have a fast-acting bronchodilator with them to stop seizures. Frequent use of the drug to stop seizures indicates a worsening of bronchial asthma and requires correction of therapy.

COPD

Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose: 2 inhalations 2 times a day. The maximum daily dose is 4 inhalations.

Symbicort ® Rapihaler 160 mcg + 4.5 mcg / dose is not used (not registered) for the treatment of COPD.

Special patient groups

There are no data on the use of Symbicort ® Rapihaler in patients with impaired liver and kidney function. The elimination of budesonide and formoterol occurs mainly through liver metabolism, so it is possible to increase exposure in patients with severe liver disease. Such patients should be closely monitored. No dose adjustment is required in elderly patients.

Overdose

Symptoms

Budesonide. Inhaled use in doses higher than recommended may lead to short-term or prolonged suppression of the hypothalamic-pituitary-adrenal system. With an acute overdose of budesonide, even if excessive doses are used, no clinically significant effects are expected. With chronic use of the drug in excessive doses, a systemic effect of corticosteroids may occur.

An overdose of formoterol is likely to develop effects typical of beta_-2-adrenergic agonists: tremor, headache, nausea, vomiting, rapid heartbeat, tachycardia, tachyarrhythmia, angina, as well as an increase or decrease Blood pressure, nervousness, muscle cramps, dizziness, metabolic acidosis, hypokalemia and hyperglycemia. In case of overdose of formoterol, symptomatic maintenance treatment is recommended.

Treatment

Severe overdose. If less than an hour has passed since oral use of the drug in a high dose and severe intoxication is not excluded, the following measures are recommended: gastric lavage and subsequent use of activated carbon (if necessary — repeatedly), monitoring and correction of electrolyte disturbances and acid-base balance, use of cardioselective beta-blockers with caution, due to the possible development of an attack of bronchial asthma.

Special instructions

It is recommended to gradually reduce the dose of the drug before stopping treatment and it is not recommended to abruptly cancel treatment.

Symbicort ® Rapihaler is not intended for the initial selection of therapy for bronchial asthma.

If the therapy is not effective enough, you should consult a doctor. Unexpected and progressive deterioration in COPD symptom control is a potentially life-threatening condition and requires urgent medical intervention. In this situation, you should consider increasing the dose of corticosteroids, for example, the appointment of a course of oral corticosteroids, or treatment with antibiotics in case of infection.

A large-scale American study evaluated the safety of using salmeterol, another beta_-2-adrenergic receptor agonist, compared with placebo in addition to conventional therapy. There was an increase in the incidence of asthma-related deaths in patients treated with salmeterol compared to patients treated with placebo (13/13176 (0.1%) vs. 3/13179 (0.02%).

However, to date, there are no results of studies evaluating the incidence of fatal outcomes due to bronchial asthma in patients receiving formoterol, the Active ingredient of the drug Symbicort ® Rapihaler. It is possible that the increased risk of death due to bronchial asthma during treatment with salmeterol is associated with the class-specific effect of beta_-2-adrenergic receptor agonists, which include formoterol.

Patients are advised to always carry an inhalation medication to stop seizures.

The patient’s attention should be drawn to the need to regularly take a maintenance dose of Simbicort® Rapihaler in accordance with the doctor’s prescription, even in cases where there are no symptoms of the disease.

If symptoms of asthma can be controlled, the dose of Symbicort® Rapihaler can be gradually reduced, and it is important to constantly monitor the patient’s condition. The lowest effective dose of Symbicort®should be prescribed Rapihaler (see “Dosage and use”).

Treatment with Simbicort ® Rapihaler should not be initiated during the period of exacerbation or significant deterioration of the course of bronchial asthma.

During treatment with Symbicort® Rapihaler, exacerbations of bronchial asthma may occur and serious adverse events associated with bronchial asthma may develop. Patients should continue treatment but seek medical attention if their asthma symptoms are not under control or if their condition worsens after starting therapy.

Data from clinical trials of Symbicort® in patients with COPD with prebronchodilatation FEV₁ <50% of normal and with postbronchodilatation FEV₁

As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after taking a dose of the drug. In this case, you should discontinue therapy with Symbicort®, review the treatment strategy and, if necessary, prescribe an alternative therapy. With paradoxical bronchospasm, it is necessary to immediately apply a fast-acting inhaled bronchodilator.

Systemic effects can occur when taking any inhaled corticosteroids, especially when using drugs in high doses for a long period of time. Systemic effects are less likely to occur with inhaled therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decreased BMD, cataracts, and glaucoma.

It is recommended to regularly monitor the growth of children receiving inhaled corticosteroids for a long time. In the case of established growth retardation, therapy should be reviewed in order to reduce the dose of inhaled corticosteroids. The relationship between the benefits of corticosteroid therapy and the possible risk of growth retardation should be carefully evaluated.

Based on limited research data on long-term use of corticosteroids, it can be assumed that the majority of children and adolescents receiving inhaled budesonide therapy will eventually reach normal adult growth rates. However, slight short-term growth retardation was reported, mainly in the first year of treatment.

Children taking immunosuppressants, including corticosteroids, are more susceptible to infectious diseases than healthy children. For example, chickenpox and measles can be very severe and sometimes fatal. Special care should be taken not to expose children and adults with weakened immune systems to the risk of infection with viruses.

If there is a risk of chickenpox infection, Ig treatment is prescribed topically or with a mixture of Ig IV.If there are signs and symptoms of chickenpox, antiviral treatment should be prescribed. It is necessary to continue anti-asthmatic therapy in case of viral infection of the upper respiratory tract. Those patients who have severe exacerbations of bronchial asthma due to viral infection of the respiratory tract should be prescribed short-term oral corticosteroid treatment.

Due to the potential effect of inhaled corticosteroids on BMD, special attention should be paid to patients with risk factors for osteoporosis who take high doses of the drug for a long period of time. Studies of long-term use of inhaled budesonide in children at an average daily dose of 400 mcg (measured dose) or adults at a daily dose of 800 mcg (measured dose) did not show a significant effect on BMD. There are no data on the effect of higher doses of Symbicort® on BMD.

If there is reason to believe that adrenal function has been impaired during previous systemic corticosteroid therapy, precautions should be taken when transferring patients to treatment with Symbicort®.

The benefits of budesonide inhalation therapy generally minimize the need for oral corticosteroids, but patients who discontinue oral corticosteroid therapy may experience long-term adrenal insufficiency. Patients who have previously needed urgent high-dose corticosteroids or received long-term treatment with inhaled corticosteroids in high doses may also be at this risk group. Additional use of corticosteroids should be considered during periods of stress or surgery.

It is recommended to instruct the patient to rinse his mouth with water after inhalation to reduce the risk of candidiasis of the oral mucosa and pharynx. It is also necessary to rinse your mouth with water after inhalation in case of candidiasis of the oral mucosa and pharynx.

Precautions should be taken when treating patients with an extended QT interval. Taking formoterol may cause prolongation of the QT interval.

The need for and dose of inhaled corticosteroids should be reviewed in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.

Co-use of beta_-2-adrenomimetics with drugs that may cause or enhance the hypokalemic effect, such as xanthine derivatives, steroids, or diuretics, may increase the hypokalemic effect of beta_-2-adrenomimetics. Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators, as the risk of hypokalemia increases with hypoxia. In such cases, it is recommended to monitor the concentration of potassium in the serum.

The use of formoterol at a dose of 90 mcg for 3 hours in patients with acute bronchial obstruction was safe. During the treatment period, the blood glucose concentration should be monitored in patients with diabetes mellitus.

Clinical studies and meta-analyses have shown that the use of inhaled corticosteroids in COPD can lead to an increased risk of developing pneumonia. However, the absolute risk of using budesonide is small. A meta-analysis of 11 double-blind studies involving 10,570 patients with COPD did not show a statistically significant increase in the risk of developing pneumonia in patients treated with budesonide (including in combination with formoterol), compared with patients treated without budesonide (placebo or formoterol). The incidence of such a serious adverse event as pneumonia was 1.9% per year with therapy including budesonide, and 1.5% per year with therapy without budesonide.

The combined risk ratio when comparing budesonide-only therapy with budesonide-free therapy was 1.15 (95% CI: 0.83,1.57). The combined risk ratio when comparing budesonide / formoterol with formoterol or placebo was 1 (95% CI: 0.69,1.44). A causal relationship between the development of pneumonia and the use of drugs containing budesonide has not been established.

Influence on the ability to drive vehicles and mechanisms. It is expected that the drug Symbicort ® Rapihaler does not affect the ability to drive vehicles and mechanisms.

Storage conditions

At a temperature not exceeding 30 °C.

Keep out of reach of children.

Shelf

life is 2 years. After the first opening of the package — 3 months.

Do not use after the expiration date indicated on the package.

Active ingredient

Budesonide, Formoterol

Conditions of release from pharmacies

By prescription

Dosage form

aerosol for inhalation