Seretide, 25 mcg+125 mcg/dose, 120 doses, metered-dose inhalation aerosol, 1 pc., GlaxoSmithKline Trading buy in Moscow at a low price

Pharmacological properties of the drug Seretide™

Pharmacodynamics. Seretide is a combination drug containing salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol is a selective, long-acting (12 hour) β2-agonist that has a side chain that binds to the outer domain of the receptor. Provides effective protection against histamine-induced bronchoconstriction and longer-lasting bronchodilation (at least 12 hours) than recommended doses of traditional short-acting β2-agonists. Salmeterol is a strong, long-acting inhibitor of the release of mast cell mediators such as histamine, leukotrienes and prostaglandin D2 from human lung tissue. Inhibits the early and late phases of the response to inhaled allergens; the latter lasts more than 30 hours after administration of one dose, that is, at a time when the bronchodilator effect is no longer present. The administration of a single dose of salmeterol weakens the hyperreactivity of the bronchial tree. This is evidence that salmeterol, in addition to the bronchodilator effect, has an additional effect, the clinical significance of which has not been fully established. This mechanism of action differs from the anti-inflammatory effect of GCS. Fluticasone propionate is a corticosteroid for topical use; when administered by inhalation, it has a pronounced anti-inflammatory and antiallergic effect on the lungs. This is manifested by a decrease in the severity of symptoms and a decrease in the frequency of asthma attacks without the side effects characteristic of systemic corticosteroids. With long-term use of inhaled fluticasone propionate at the maximum recommended doses, daily excretion of adrenal hormones remains within normal limits in both adults and children. After patients receiving other inhaled corticosteroids switch to fluticasone propionate, the daily excretion of adrenal hormones gradually normalizes, despite the previous and concomitant periodic use of oral corticosteroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With prolonged use of fluticasone propionate, adrenal reserve function remains within normal limits, as evidenced by a normal increase in cortisol production in response to appropriate stimulation. However, it should be taken into account that the residual decrease in adrenal reserve caused by previous therapy may persist for a long time. Research has found:

71% of patients treated with salmeterol/fluticasone achieved a “good level of control”* of asthma symptoms compared to 59% of patients treated only with GCS;
41% of patients treated with salmeterol/fluticasone achieved “complete control”** of asthma symptoms compared to 28% of patients treated only with GCS;
the incidence of exacerbations was 29% lower in patients treated with salmeterol/fluticasone compared with inhaled corticosteroids without salmeterol;
when “good” or “complete control” of asthma symptoms is achieved, quality of life indicators improve, according to a specially developed questionnaire regarding indicators of the quality of life of patients with asthma.

*“Complete control” of asthma symptoms means the absence of disease symptoms and the absence of the need to use short-acting β2-adrenergic receptor agonists; the level of pulmonary function is ≥80% of predicted, there are no night awakenings, there are no exacerbations and side effects requiring a change in treatment; **“Good control” of asthma symptoms means the presence of occasional symptoms or an intermittent need for the use of short-acting β2-adrenergic agonists or a level of pulmonary function ≤80% predicted plus no night awakenings, no exacerbations and no side effects requiring a change in treatment.

According to the following 2 studies, an improvement in pulmonary function and an increase in the number of days without asthma symptoms were demonstrated; the use of emergency medications was reduced by 60% when taking a dose of inhaled GCS as part of Seretide than when taking only inhaled GCS, provided that adequate control of the inflammatory process in the airways was maintained (according to bronchial biopsy and bronchoalveolar lavage). This improvement lasts for at least 12 months. Pharmacokinetics. Simultaneous inhalation administration of salmeterol and fluticasone does not affect the pharmacokinetics of each of these substances. Salmeterol Salmeterol acts locally in the bronchi, so its therapeutic effect does not depend on the concentration in the blood plasma. The plasma concentration of salmeterol when administered in inhalation at therapeutic doses is very low (approximately 200 pg/ml or less). With regular use of inhaled salmeterol xinafoate, hydroxynaphthoic acid is detected in the systemic circulation at a concentration of up to 100 ng/ml. This concentration is approximately 1000 times lower than the steady-state concentrations determined during toxicological studies. No side effects were identified with regular long-term use (for more than 12 months) of the drug in patients with airway obstruction. According to a study of drug interactions between salmeterol and ketoconazole, when used in combination, the concentration of salmeterol in the blood plasma significantly increases. Fluticasone propionate The absolute bioavailability of fluticasone propionate for each of the available inhalation devices was assessed from comparative pharmacokinetic studies using the inhalation and intravenous routes of administration. In healthy adults, the absolute bioavailability for fluticasone propionate Discus was 7.8%, for fluticasone propionate Evohaler - 10.9%; for Seretide Evohaler - 5.3%, for Seretide Discus - 5.5%, respectively. In patients with asthma and COPD, the degree of systemic influence of inhaled fluticasone propionate is less. Systemic absorption occurs mainly through the lungs, quickly at first, then over a longer period of time. The remainder of the inhalation dose is swallowed, producing minimal systemic effects due to the low solubility of fluticasone propionate in water and first-pass metabolism of the drug. Thus, its oral bioavailability is ≤1%. There is a linear dose dependence of the systemic effect with increasing inhalation dose of the drug. Fluticasone propionate is characterized by high plasma clearance (1150 ml/min), a large volume of distribution (approximately 300 l) and an elimination half-life of about 8 hours. The degree of binding to plasma proteins is moderately high - about 91%. Fluticasone propionate is rapidly eliminated from the systemic circulation, mainly by metabolism to inactive compounds with the participation of the cytochrome CYP 3A4 enzymatic system. The renal clearance of fluticasone propionate is very low (≤0.2%), of which ≤5% is excreted as metabolites. CYP3A4 inhibitors should be co-administered with caution due to the possibility of increased systemic exposure to fluticasone propionate.

Seretide 250mcg 120dose aer

Seretide 250mcg 120dose aer

Trade name Seretide™ Evohaler™ International nonproprietary name No Dosage form Inhalation aerosol, dosage 25/50 mcg, 25/125 mcg, 25/250 mcg, 120 doses Composition One dose of the drug contains active substances: salmeterol xinafoate 36.3 mcg (equivalent to 25 mcg salmeterol) and fluticasone propionate 50 mcg or 125 mcg or 250 mcg, excipient - 1,1,1,2-tetrafluoroethane (propellant HFA-134a), ozone-safe. Description Aluminum cylinder placed in a plastic sprayer, equipped with a metering valve and a protective cap. The balloon contains a white or almost white suspension. Pharmacotherapeutic group: Sympathomimetics in combination with other drugs for the treatment of obstructive airway diseases. Salmeterol in combination with other drugs for the treatment of obstructive diseases of the respiratory tract ATC code R03AK06 Pharmacological properties Pharmacokinetics Simultaneous inhalation administration of salmeterol and fluticasone propionate does not affect the pharmacokinetics of each of these substances. Salmeterol Salmeterol acts locally at the level of the lungs, so its plasma level does not determine the therapeutic effect. Data on the pharmacokinetics of salmeterol are limited because it is technically difficult to determine very low plasma concentrations of the drug (200 mg/mL or less) after inhalation administration at therapeutic doses. With regular inhalation use of salmeterol xinafoate, hydroxynaphthoic acid is detected in the systemic circulation in concentrations of up to 100 ng/ml. These concentrations are approximately 1000 times lower than the steady-state concentrations detected during toxicological studies. No undesirable effects of the drug were detected during its long-term use on a regular basis (more than 12 months) in patients with airway obstruction. In vitro studies have shown that salmeterol is metabolized primarily through the cytochrome P450 3A4 (CYP3A4) system to β-hydroxysalmeterol. Fluticasone propionate After inhalation administration, the absolute bioavailability of fluticasone propionate is approximately 10.9%, depending on the drug delivery system. Patients with asthma and chronic obstructive pulmonary disease (COPD) experience lower systemic exposure to inhaled fluticasone propionate. Systemic absorption occurs primarily in the lungs. Part of the inhaled dose may be swallowed, but its systemic effect is minimal due to intensive metabolism during the first passage through the liver. The bioavailability of fluticasone propionate when taken orally is less than 1%. There is a direct relationship between the inhaled dose and the systemic effect of fluticasone propionate. Fluticasone propionate has a high plasma clearance (1150 ml/min). Fluticasone propionate is rapidly cleared from the systemic circulation, mainly due to biotransformation to an inactive derivative by the CPY3A4 enzyme of the cytochrome P450 system. Caution should be exercised when prescribing fluticasone propionate and CPY3A4 enzyme inhibitors simultaneously, as the systemic effect of fluticasone propionate may be increased. The half-life is approximately 8 hours. The renal clearance of fluticasone propionate is negligible (less than 0.2%), and less than 5% of the metabolite is excreted in the urine.

Pharmacodynamics Combined drug for inhalation use. Seretide™ Evohaler™ contains two active components: salmeterol and fluticasone propionate, which have different mechanisms of action. Seretide™ Evohaler™ provides a more convenient treatment regimen for patients who simultaneously receive drugs from the b-adrenergic agonists and inhaled glucocorticosteroids (GCS). Salmeterol Salmeterol is a selective b2-adrenergic receptor agonist with a long-lasting effect (12 hours). The salmeterol molecule has a long side chain that binds to the external site of the receptor. Salmeterol is effective in preventing histamine-induced bronchospasm, causes bronchodilation, and reduces bronchial hyperreactivity. Long-term inhibition of the release of mast cell mediators, such as histamine, leukotrienes and prostaglandin D2, in the lung tissues. Suppresses early and late stage reactions to inhaled allergens. After one dose, suppression of the late stage lasts up to 30 hours. Fluticasone propionate Fluticasone propionate belongs to the group of topical corticosteroids and, when administered in inhalation in recommended doses, has an anti-inflammatory effect in the lungs, which leads to a decrease in the severity of symptoms and a decrease in the frequency of asthma exacerbations. The effect of fluticasone propionate is not accompanied by adverse reactions characteristic of systemic corticosteroids. With long-term use of fluticasone propionate in maximum doses in the form of inhalations, the daily secretion of adrenal hormones remains within normal limits in adults and children. After transferring patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones is gradually restored to normal, despite the previous oral administration of corticosteroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, as confirmed by the results of the stimulation test. However, it must be taken into account that a residual decrease in adrenal reserve function may persist for a long time after therapy. Indications for use : Asthma (reversible airway obstruction), when it is advisable to prescribe combination therapy of bronchodilators and drugs from the group of inhaled corticosteroids: - in patients receiving maintenance doses of long-acting beta-adrenergic agonists and inhaled corticosteroids - in patients who continue to have symptoms of the disease during therapy with inhaled GCS - in patients receiving regular treatment with bronchodilators and requiring inhaled GCS. Maintenance therapy for COPD (chronic obstructive pulmonary disease) in adults, including chronic bronchitis and emphysema. Directions for use and dosage Seretide™ Evohaler™ is intended for inhalation only. Patients should be advised that to obtain optimal effects, Seretide™ Evohaler™ should be used regularly, even in the absence of symptoms. Patients should undergo regular medical examination to maintain the optimal dose of Seretide™ Evohaler™ and dose changes should only be made on the recommendation of a physician. Asthma (reversible airway obstruction) Dosage should be titrated to achieve the minimum effective dose that maintains optimal control of asthma symptoms. Once control is achieved when taking the drug twice a day, further titration of the dose is necessary to switch to taking the drug once a day. The starting dose of Seretide™ Evohaler™ should be based on the dose of fluticasone propionate that is recommended for the treatment of the disease severity. If disease control is inadequate when using exclusively inhaled forms of GCS, switching to Seretide™ Evohaler™ at a dose equivalent to the dose of GCS may lead to improved control of asthma symptoms. In patients with adequate control of asthma symptoms with inhaled corticosteroids, switching to Seretide™ Evohaler™ may reduce the required dose of corticosteroids.

Adults and adolescents 12 years of age and older: two inhalations of 25 mcg salmeterol and 50 mcg fluticasone propionate twice daily or two inhalations of 25 mcg salmeterol and 125 mcg fluticasone propionate twice daily or two inhalations of 25 mcg salmeterol and 250 mcg fluticasone propionate twice a day. Children 4 years and older: two inhalations of 25 mcg salmeterol and 50 mcg fluticasone propionate twice daily. There are no data on the use of Seretide™ Evohaler™ in children under 4 years of age. Chronic obstructive pulmonary disease (COPD) For adult patients, the maximum recommended dose is 2 inhalations (25 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times a day. Selected patient groups: There is no need to adjust the dose in elderly patients or with impaired renal or hepatic function.

Instructions for using the inhaler Checking the inhaler: Before first use or after a long (week or more) break in the use of the inhaler, remove the mouthpiece cap by lightly pressing on the sides of the cap, shake the inhaler thoroughly and spray one spray into the air to ensure adequate operation.

How to use the inhaler: 1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides. 2. Inspect the inhaler inside and out, including the mouthpiece, for loose parts. 3. Shake the inhaler thoroughly to remove any loose parts from the surface of the device and mix the contents of the inhaler evenly. 4. Hold the inhaler vertically between your thumb and fingers, placing your thumb on the base, below the mouthpiece. 5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it without biting. 6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray, while continuing to inhale deeply and slowly. 7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue to hold your breath as deeply as possible. 8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 2 - 6. 9. After using the drug, rinse your mouth and spit out the water 10. Close the mouthpiece cap by pressing and snapping into the desired position. It is important to take your time when performing steps 4, 5 and 6. It is very important to begin inhaling as slowly as possible immediately before spraying. The first few times you can practice in front of a mirror. If a cloud appears on the top of the inhaler or near the mouth, repeat steps from step 2. If your doctor has given other instructions for using the inhaler, follow those instructions. If you experience any difficulties, tell your doctor about them. Children Young children may need adult assistance when using the inhaler. You should ask the child to exhale and spray immediately after the child begins to inhale. You can practice the technique together. Older children or people with weak hands should use both hands to hold the inhaler. Place both index fingers on the top of the inhaler and both thumbs on the base below the mouthpiece.

Cleaning: The inhaler should be cleaned at least once a week. 1. Remove the mouthpiece cap. 2. Do not remove the can from the plastic case. 3. Wipe the inner and outer surfaces of the mouthpiece and plastic body with a dry cloth or napkin. 4. Replace the mouthpiece cap. DO NOT PLACE THE METAL CAN IN THE WATER. Side effects Very often ≥ 1 in 10, often ≥ 1 in 100 and < 1 in 10, sometimes ≥ 1 in 1000 and < 1 in 100, rarely ≥ 1 in 10,000 and < 1 in 1,000, very rarely < 1 in 10,000. Very often - headache Often - candidiasis of the oral cavity and pharynx, hoarseness of voice - pneumonia (in patients with COPD) - muscle cramps, arthralgia Uncommon - irritation of the mucous membrane of the oropharynx - skin allergic reactions - shortness of breath - cataracts - hyperglycemia - feeling of fear, sleep disturbance - tremor - palpitations, atrial fibrillation - hematomas Rarely - anaphylactic reactions - glaucoma - behavioral changes, including increased activity and irritability (especially in children) - cardiac arrhythmia (including atrial fibrillation, supraventricular tachycardia, extrasystole) - angioedema (especially swelling of the face and oropharynx), paradoxical bronchospasm - Cushing's syndrome, suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density. Contraindications - history of hypersensitivity to any component of the drug Drug interactions The use of non-selective and selective beta-blockers should be avoided, unless they are absolutely necessary for the patient. In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive first-pass metabolism and high systemic clearance under the influence of cytochrome P450 3A4 in the intestine and liver. This makes clinically significant interactions involving fluticasone propionate unlikely. Drug interaction studies have shown that ritonavir (a highly active cytochrome P450 3A4 inhibitor) can significantly increase plasma concentrations of fluticasone propionate, resulting in a significant decrease in serum cortisol concentrations. There are reports of clinically significant drug interactions in patients who received fluticasone propionate and ritonavir concomitantly. These interactions have caused side effects such as Cushing's syndrome and adrenal suppression. Considering the above, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS. Other cytochrome P450 3A4 inhibitors cause a negligible small (erythromycin) and insignificant (ketoconazole) increase in plasma fluticasone propionate, with virtually no decrease in serum cortisol concentrations. Despite this, caution is recommended during concomitant use of fluticasone propionate and strong cytochrome P450 3A4 inhibitors (eg, ketoconazole), as this combination may potentially increase the systemic effects of fluticasone propionate. Concomitant use of salmeterol and ketoconazole results in a significant increase in plasma salmeterol levels and may lead to prolongation of the QT interval. Special instructions Seretide™ Evohaler™ is not intended for the relief of acute symptoms when a rapid- or short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be advised to always have medication available to relieve acute symptoms. More frequent use of short-acting bronchodilators to relieve symptoms indicates worsening disease control, and in such situations the patient should consult a doctor. Sudden and progressive deterioration in control of bronchospastic syndrome is potentially life-threatening, and in such situations the patient should immediately consult a doctor. It is possible that the doctor will prescribe a higher dose of GCS. In cases where the prescribed dose of Seretide™ Evohaler™ does not provide adequate control of the disease, the patient should consult a doctor who may prescribe additional corticosteroids and antibiotics if the infection develops. Due to the risk of exacerbation, treatment with Seretide™ Evohaler™ should not be abruptly stopped in patients with asthma; the dose of the drug should be reduced gradually under the supervision of a physician. In patients with COPD, drug withdrawal may be accompanied by symptoms of decompensation and requires medical supervision. An increase in the incidence of pneumonia has been identified while taking Seretide™ Evohaler™ in patients with COPD, and therefore the attending physician should be attentive to possible clinical symptoms of pneumonia in such patients. As with other inhaled corticosteroid products, Seretide™ Evohaler™ should be administered with caution to patients with active or latent pulmonary tuberculosis. Seretide™ Evohaler™ should be administered with caution to patients with thyrotoxicosis. When using sympathomimetic drugs, especially in doses higher than recommended, an increase in systolic pressure is possible, and therefore caution should be exercised when prescribing Seretide™ Evohaler™ to patients with cardiovascular diseases. Seretide™ Evohaler™ should be used with caution in patients with a predisposition to low serum potassium levels. Any inhaled corticosteroids can cause systemic effects, especially with long-term use of high doses; It should be noted, however, that the likelihood of such symptoms occurring is much lower than with treatment with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, it is especially important that when a therapeutic effect is achieved, the dose of inhaled corticosteroids is reduced to the minimum effective dose that controls the course of the disease. In emergency and planned situations that can cause stress, it is always necessary to remember the possibility of adrenal suppression and be prepared to use GCS. It is recommended to regularly monitor the growth of children receiving long-term treatment with inhaled corticosteroids. After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special card with them indicating the possible need for additional administration of corticosteroids in stressful situations. Due to the possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function should be regularly monitored. There are very rare reports of increased blood glucose levels and therefore Seretide™ Evohaler™ should be administered with caution to patients with diabetes mellitus. Inhaled drugs can cause paradoxical bronchospasm, which must be treated immediately with a rapid-acting inhaled bronchodilator. Seretide™ Evohaler™ should be discontinued immediately, the patient examined and alternative therapy prescribed. Ritonavir (a cytochrome P450 3A4 inhibitor) may significantly increase plasma concentrations of fluticasone propionate, which may lead to systemic effects, including Cushing's syndrome and adrenal suppression. Therefore, the simultaneous use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS. Data from a clinical study of the safety of salmeterol added to the treatment of bronchial asthma compared with placebo showed that the incidence of deaths due to bronchial asthma was higher in the salmeterol group. African American patients are thought to be at higher risk for serious respiratory adverse events/death than other patients. The significance of pharmacokinetic factors or other causes is unknown. Concomitant use of GCS was not studied in this study. In a drug interaction study, it was found that the use of ketoconazole as concomitant systemic therapy enhances the effect of salmeterol. This may lead to prolongation of the QT interval. Caution should be exercised when co-administering strong CYP3A4 inhibitors (eg, ketoconazole) and salmeterol. The development of palpitations while taking β2-blockers was noted, but the attacks were transient and disappeared with regular use of these drugs. If hoarseness and candidiasis of the oral cavity and pharynx occurs or to prevent hoarseness, it is recommended to rinse your mouth and throat with water after inhalation. Pregnancy and lactation The use of the drug during pregnancy and lactation is justified only if the expected benefit to the mother outweighs any possible risk to the fetus or child. Since the plasma concentration of Seretide™ Evohaler™ is extremely low when Seretide™ Evohaler™ is inhaled at recommended doses, it is assumed that the level of salmeterol and fluticasone in breast milk is also insignificant, but there is no clinical evidence to support these data. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms. Care should be taken when driving a car or working with moving mechanisms. Overdose There is no information on overdose with Seretide™ Evohaler™. Data on overdose of individual drugs salmeterol and fluticasone propionate are presented. Symptoms: an overdose of salmeterol is manifested by tremor, headache, tachycardia, decreased systolic pressure and hyperkalemia. Inhalation of fluticasone propionate in doses higher than recommended may lead to temporary depression of the hypothalamic-pituitary-adrenal axis. This phenomenon does not require immediate intervention, since adrenal function is restored within a few days. Exceeding recommended doses over a long period may result in significant suppression of adrenal function. There are rare reports in the literature of acute adrenal crisis, which occurs primarily in children receiving excessively high doses of the drug over a long period of time (several months or years); acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and/or convulsions. Situations that may trigger an acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate contained in Seretide™ Evohaler™. Treatment: There is no specific antidote. The optimal antidotes are cardioselective beta1-blockers, but they should be used with caution in patients with a history of bronchospasm. If Seretide™ Evohaler™ has to be discontinued due to salmeterol overdose, the patient should be given appropriate steroid replacement therapy. In case of an overdose of fluticasone propionate, treatment with Seretide™ Evohaler™ can be continued in doses sufficient to maintain the therapeutic effect. Release form and packaging Aerosol for inhalation, dosed 25/50 mcg, 25/125 mcg, 25/250 mcg. 120 doses of the drug in an aluminum cylinder placed in a plastic sprayer equipped with a dosing valve and a protective cap. 1 plastic spray, along with instructions for use in the state and Russian languages, is placed in a cardboard pack. Storage conditions Store at a temperature not exceeding 30 °C. Protect from hypothermia and direct sunlight. The therapeutic effect of the drug may decrease when the can is cooled. The canister should not be punctured, broken or burned, even after complete use. Keep out of the reach of children! Shelf life: 2 years Do not use after the expiration date indicated on the package. Conditions for dispensing from pharmacies By prescription

Indications for use of the drug Seretide™

Reversible obstructive diseases of the respiratory tract Systematic treatment of reversible broncho-obstructive diseases of the respiratory tract, including asthma in children and adults if it is necessary to prescribe a bronchodilator in combination with inhaled corticosteroids. The drug is intended for the treatment of:

patients receiving effective maintenance doses of selective long-acting β2-adrenergic receptor agonists and inhaled corticosteroids;
patients who experience symptoms of the disease during treatment with inhaled corticosteroids;
patients regularly receiving bronchodilators and requiring the use of inhaled corticosteroids.

COPD Basic therapy for COPD, including chronic bronchitis and emphysema.

Use of the drug Seretide™

The drug is intended for inhalation use only. Patients should understand that the drug should be used regularly, even in the absence of attacks of bronchial obstruction, since it is prescribed to prevent the disease. Patients should be under regular medical supervision, they need to select the optimal dose of Seretide, which can only be changed as directed by a doctor. Reversible obstructive airway diseases. Seretide is prescribed in the minimum effective dose to ensure control of the symptoms of the disease. When control is achieved by using the drug 2 times a day, you can try to reduce the dose to the minimum effective, the frequency of use is 1 time a day. The amount of fluticasone propionate in the chosen form should correspond to the severity of the disease. If asthma symptoms are not sufficiently controlled using inhaled corticosteroids alone, such control can be improved by replacing inhaled corticosteroid therapy with Seretide at a therapeutically equivalent dose of corticosteroids. For patients whose asthma symptoms are sufficiently controlled by the use of corticosteroids alone, replacing them with Seretide may allow a reduction in the dose of corticosteroids while maintaining control of asthma symptoms. Seretide Discus is for inhalation use only. Recommended doses Adults and adolescents over 12 years of age: 1 inhalation (50 mcg salmeterol/100 mcg fluticasone propionate) 2 times a day; or 1 inhalation (50 mcg salmeterol/250 mcg fluticasone propionate) 2 times a day; or 1 inhalation (50 mcg salmeterol/500 mcg fluticasone propionate) 2 times a day. Adults aged 18 years and older: If an adult patient aged 18 years or older requires short-term (up to 14 days) additional therapy with inhaled corticosteroids, he can be prescribed a double dose of any form of Seretide, comparable in safety and tolerability profile to the usual dose of Seretide 2 times. per day. Children aged 4 to 12 years : 1 inhalation (50 mcg salmeterol/100 mcg fluticasone propionate) 2 times a day. There are no data on the use of the drug in children under 4 years of age, so use is not recommended. COPD . For adult patients, the maximum recommended dose is 1 inhalation (50 mcg salmeterol/500 mcg fluticasone propionate) 2 times a day. Selected groups of patients: There is no need for dose adjustment in elderly patients and in patients with liver or kidney pathology. Discus is a device designed to release powder and then inhale it. Before use, open and charge the device by sliding the lever. Then place the mouthpiece in your mouth and wrap your lips around it, then inhale the dose and close the device. The indicator shows the number of doses remaining in the Discus. Rules for using the Discus inhaler The new Discus inhaler must be closed. Contains 60 doses of the drug in powder form. The dose indicator at the top shows how many doses are left. In this way, every dose is precisely measured and hygienically protected. There is no need for special care of the inhaler and refilling doses. Numbers 5 to 0 appear in red to indicate remaining doses. Usage:

open the inhaler;
move the lever;
inhale;
close the inhaler.

How the Discus inhaler works: when you press the lever in the inhaler, a small hole in the mouthpiece opens slightly and a dose is unpacked for inhalation. When closing the inhaler, the lever automatically rotates to its original position and the inhaler is ready to prepare the next dose if necessary. The case protects the inhaler when not in use. Caring for your Discus inhaler: wipe the mouthpiece of the inhaler with a dry cloth. Need to remember:

the inhaler is stored in a dry place;
the inhaler must be closed when not in use;
never exhale into a Discus inhaler;
press the lever only when you are ready to take a dose;
never exceed the recommended dose.

Seretide Evohaler is for inhalation use only. Recommended doses Adults and adolescents 12 years of age and older: 2 inhalations of 25 mcg salmeterol/50 mcg fluticasone propionate 2 times daily; or 2 inhalations of 25 mcg salmeterol/125 mcg fluticasone propionate 2 times a day; or 2 inhalations of 25 mcg salmeterol/250 mcg fluticasone propionate 2 times a day. Adults 18 years of age and older: If an adult requires short-term (up to 14 days) adjunctive therapy with an inhaled corticosteroid, a double dose of any form of Seretide Evohaler can be administered, which will have a safety and tolerability profile comparable to the usual dose of Seretide Evohaler twice daily. day. Children aged 4 years and older : 2 inhalations of 25 mcg salmeterol/50 mcg fluticasone propionate 2 times a day. There are no data regarding the use of Seretide Evohaler in children under 4 years of age. COPD For adult patients, the maximum recommended dose is 2 inhalations (25 mcg salmeterol/250 mcg fluticasone propionate) 2 times a day. Selected patient groups: There is no need to adjust the dose in elderly patients or in patients with insufficient renal or hepatic function. For patients who find it difficult to coordinate inhalation with nebulization of the inhaler, it is recommended to use a spacer (a device for facilitating the administration of inhaled drugs AeroChamber Plus - see below). Use of a device for administering metered inhalation aerosols AeroChamber Plus To avoid deterioration of disease control due to improper use of metered inhalation aerosols, it is recommended to use an additional device - a Spencer with an AeroChamber Plus mask. This is a volumetric chamber through which the aerosol from the inhaler enters the patient's respiratory tract. The AeroChamber Plus spacer can be used in children under the age of 4 years, and the spacer with a face mask can be used from the first days of life (0-18 months - orange mask, 1 year-5 years - yellow mask). The use of AeroChamber Plus allows you to reduce the oropharyngeal disposition of the drug: fewer aerosol particles are retained in the oropharynx, larynx and trachea, and more reach the lower respiratory tract (due to the presence of a valve and diaphragm in this spacer). In addition, it slows down the speed of the aerosol jet, due to which its large non-respirable particles (4.7 microns) are eliminated. AeroChamber Plus has a universal adapter. Rules for using the AeroChamber Plus spacer :

carefully check the spacer for damage or foreign objects;
remove the cap from the inhaler mouthpiece;
shake the inhaler;
insert the inhaler mouthpiece into the adapter;
carefully and tightly press the mask to your face;
press the inhaler once and inhale slowly;
keep the mask pressed to your face for 6 breaths after pressing the inhaler;
Carefully remove the mask from your face.

Rules for caring for the AeroChamber Plus spacer:

it is necessary to wash the spacer before the first use, after which the spacer is washed once a week;
disconnect the adapter for the inhaler, do not disconnect the mask and valves;
immerse the spacer with the disconnected adapter in warm water with detergent for 15 minutes;
rinse the spacer thoroughly with warm water;
shake off any remaining water from the spacer, do not wipe it dry;
leave the spacer at room temperature in a vertical position until completely dry, then reattach the adapter;
After 24 months with constant use, the spacer should be replaced.

Seretide Multidisk powder for inhalation dosed 50 µg + 250 µg/dose 60 doses

Release form, composition and packaging

Aerosol for inhalation dosed in the form of a suspension of white or almost white color.
1 dose of salmeterol xinafoate* 36.3 mcg, which corresponds to the content of salmeterol 25 mcg of fluticasone propionate* 50 mcg

Excipients: 1,1,1,2-tetrafluoroethane - up to 75 mg.

120 doses - aluminum inhalers (1) with a plastic spray - cardboard packs.

* the composition includes an excess of up to 10% salmeterol xinafoate and up to 15% fluticasone propionate to compensate for losses during production and in the dosing device inside the inhaler (excess is not taken into account in the given composition).

pharmachologic effect

Mechanism of action

The drug Seretide® is a combination drug that contains salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of symptoms of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbation of the disease. Due to its more convenient dosing regimen, Seretide® may be an alternative for patients who simultaneously receive a β2-adrenergic receptor agonist and inhaled corticosteroids from different inhalers.

Salmeterol is a selective, long-acting (up to 12 hours) β2-adrenergic receptor agonist that has a long side chain that binds to the outer domain of the receptor.

The pharmacological properties of salmeterol provide more effective protection against histamine-induced bronchoconstriction and longer-lasting bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists.

In vitro studies have shown that salmeterol is a potent inhibitor of the release of mast cell mediators such as histamine, leukotrienes and prostaglandin D2 from the human lung, and has a long period of action.

Salmeterol inhibits the early and late phases of the response to inhaled allergens. Inhibition of the late phase response persists for more than 30 hours after taking a single dose, at a time when the bronchodilator effect is no longer present.

Fluticasone propionate belongs to the group of corticosteroids for topical use and, when administered by inhalation in recommended doses, has a pronounced anti-inflammatory and antiallergic effect in the lungs, which leads to a decrease in clinical symptoms and a decrease in the frequency of exacerbations of bronchial asthma. Fluticasone propionate does not cause the adverse effects that are observed with systemic administration of corticosteroids.

With long-term use of inhaled fluticasone propionate, the daily secretion of adrenal hormones remains within normal limits in both adults and children, even when used in the maximum recommended doses. After switching patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually improves, despite previous and current intermittent use of oral steroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, as evidenced by the normal increase in cortisol production in response to appropriate stimulation (it must be taken into account that the residual decrease in adrenal reserve caused by previous therapy may persist for a long time).

Pharmacokinetics

There is no data indicating that when administered together by inhalation, salmeterol and fluticasone propionate affect each other's pharmacokinetics, and therefore the pharmacokinetic characteristics of each component of Seretide® can be considered separately.

A study conducted in 15 healthy volunteers who simultaneously received salmeterol (inhaled 50 mcg twice daily) and the CYP3A4 inhibitor ketoconazole (oral 400 mg once daily) for 7 days showed a significant increase in salmeterol concentrations in blood plasma (increase in Cmax by 1.4 times and AUC by 15 times). There was no increase in salmeterol accumulation with repeated doses. In three patients, treatment was discontinued due to QTc prolongation or palpitations with sinus tachycardia. In the remaining 12 patients, the simultaneous use of salmeterol and ketoconazole did not have a clinically significant effect on heart rate, blood potassium levels, or the duration of the QTc interval (see sections "With caution", "Special instructions and precautions for use", "Interaction with other drugs" ").

Suction

Salmeterol acts locally in the lung tissues, so its content in the blood plasma is not an indicator of therapeutic effects. Data on its pharmacokinetics are very limited due to technical problems: when inhaled in therapeutic doses, its Cmax in plasma is extremely low (about 200 pg/ml and below). After regular inhalations of salmeterol, hydroxynaphthoic acid can be detected in the blood, the Css of which is about 100 ng/ml. These concentrations are 1000 times lower than the Css observed in toxicity studies. No adverse effects were observed with long-term regular use of the drug (for more than 12 months) in patients with airway obstruction.

Fluticasone propionate: The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies depending on the inhaler used, but is 5.3% when the combination of salmeterol and fluticasone propionate is administered by metered dose inhalation aerosol. In patients with bronchial asthma and COPD, lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs primarily through the lungs. At first she is faster, but then her speed slows down.

Part of the inhalation dose may be swallowed, but this part makes a minimal contribution to systemic absorption due to the low solubility of fluticasone propionate in water and due to its first-pass metabolism; bioavailability from the gastrointestinal tract is less than 1%. As the inhalation dose increases, a linear increase in the concentration of fluticasone propionate in the blood plasma is observed.

Distribution

There are no data on the distribution of salmeterol.

Fluticasone propionate has a large Vd at steady state (about 300 L) and has a relatively high degree of binding to plasma proteins (91%).

Metabolism

The results of an in vitro study showed that salmeterol is extensively metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system to α-hydroxysalmeterol by aliphatic oxidation. In a repeated-dose study of salmeterol and erythromycin in healthy volunteers, there were no clinically significant changes in the pharmacodynamic effects when taking 500 mg of erythromycin 3 times a day. However, a study of the interaction of salmeterol and ketoconazole showed a significant increase in the concentration of salmeterol in the blood plasma (see sections “Special instructions and precautions for use”, “Interaction with other drugs”).

Fluticasone propionate is rapidly eliminated from the blood, mainly as a result of metabolism under the action of the CYP3A4 isoenzyme of the cytochrome P450 system to an inactive carboxyl metabolite. Caution must be exercised when using known CYP3A4 inhibitors and fluticasone propionate simultaneously, since in such situations the plasma levels of the latter may increase.

Removal

There are no data regarding the elimination of salmeterol.

The distribution of fluticasone propionate is characterized by rapid plasma clearance (1150 ml/min) and a final T1/2 of approximately 8 hours. The renal clearance of unchanged fluticasone propionate is negligible (<0.2%), less than 5% of the dose is excreted in the form of a metabolite in the urine.

Indications

The drug Seretide® is intended for the regular treatment of bronchial asthma if combination therapy with a long-acting beta2-adrenergic agonist and inhaled corticosteroids is indicated:

- patients with insufficient disease control on the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting beta2-adrenergic agonist;

— patients with adequate disease control during therapy with inhaled GCS and a long-acting beta2-adrenergic agonist;

— as initial maintenance therapy in patients with persistent bronchial asthma if there are indications for prescribing GCS to achieve disease control.

The drug Seretide® is intended for maintenance therapy in patients with COPD with an FEV1 value <60% of the predicted value (before inhalation of a bronchodilator) and a history of repeated exacerbations, in whom severe symptoms of the disease persist despite regular bronchodilator therapy.

Dosage regimen

Seretide® is intended for inhalation only.

The patient should be informed that to obtain optimal effect the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD.

The physician should regularly evaluate the effectiveness of the patient's treatment.

Determining the duration of the course of therapy and changing the dose of the drug is possible only on the recommendation of a doctor.

Bronchial asthma

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms.

If taking Seretide® 2 times a day provides control over symptoms, as part of reducing the dose to the minimum effective, it is possible to reduce the frequency of taking the drug to 1 time a day.

The patient should be prescribed a form of Seretide that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If therapy with inhaled corticosteroids does not provide adequate control of the disease, then replacing them with the drug Seretide® at a dose therapeutically equivalent to the dose of administered corticosteroids may improve control of bronchial asthma. In patients in whom the course of bronchial asthma can be controlled exclusively with the help of inhaled corticosteroids, replacing them with the drug Seretide® may reduce the dose of corticosteroids required to control the course of asthma.

Recommended Doses

Adults and children 12 years of age and older: two inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times / day, or two inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times / day, or two inhalations (25 mcg salmeterol and 250 mcg of fluticasone propionate) 2 times a day.

Children 4 years of age and older: two inhalations (25 mcg of salmeterol and 50 mcg of fluticasone propionate) 2 times a day.

Currently, there is no data on the use of Seretide® in children under 4 years of age.

Chronic obstructive pulmonary disease (COPD)

For adult patients, the maximum recommended dose is two inhalations (25 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose of Seretide in elderly patients, or in patients with impaired renal or hepatic function.

Instructions for use of the inhaler (for patients)

Checking the inhaler

Before using the inhaler for the first time, or if the inhaler has not been used for a week or more, remove the cap from the mouthpiece by slightly squeezing the cap on the sides, hold the inhaler between the thumb and fingers of one hand, so that the thumb is on the base under the mouthpiece, Shake the inhaler well and release two streams into the air to make sure that the inhaler is working.

Using an inhaler

1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides.

2. Inspect the inhaler from the outside and inside, including the mouthpiece, for foreign objects.

3. Shake the inhaler well to ensure that any foreign objects are removed and that the contents of the inhaler are evenly mixed.

4. Hold the inhaler between the thumb and fingers of one hand in a vertical position, bottom up, with the thumb resting on the base under the mouthpiece.

5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it, but without biting down on the mouthpiece.

6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray Seretide® while continuing to inhale deeply and slowly.

7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue holding your breath for as long as possible.

8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 3-7.

9. After using the inhaler, rinse your mouth with water and then spit it out.

10. Immediately close the mouthpiece cap by pressing and clicking into position. If latching does not occur, turn the mouthpiece cap and try closing the mouthpiece again. Do not press the cap with force.

The drug can also be used through a spacer. Attention! When following steps 5, 6 and 7, you should not rush.

You should begin inhaling as slowly as possible, just before pressing the inhaler valve.

It is recommended to practice in front of a mirror the first few times.

If you see "fog" coming from the top of the inhaler or from the corners of your mouth, then you should start all over again, starting from step 2.

If your doctor gives you other instructions for using your inhaler, follow them strictly. Contact your doctor if you have difficulty using your inhaler.

Children

Young children may need help using the inhaler and should be assisted by an adult. Wait for the child to exhale and activate the inhaler as the child begins to inhale. Practice using the inhaler with your child. Older children and adults with weak hands should hold the inhaler with both hands. In this case, both index fingers should be located on the top of the inhaler, and both thumbs should be on the base below the mouthpiece.

Cleaning the inhaler

The inhaler must be cleaned at least once a week.

1. Remove the protective cap from the mouthpiece.

2. Do not remove the metal can from the plastic casing.

3. Use a dry cloth or cotton swab to wipe the inside and outside of the mouthpiece and plastic housing.

4. Close the mouthpiece with the protective cap.

Do not immerse the metal can in water.

Side effect

All undesirable reactions presented below are characteristic of the active ingredients - salmeterol and fluticasone propionate separately. The profile of adverse reactions of the drug Seretide® does not differ from the profile of adverse reactions of its active substances.

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and < 1/1000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on data from clinical trials of the drug and post-registration surveillance.

Clinical trial data

Frequency of occurrence of adverse reactions

Infectious and parasitic diseases: often - candidiasis of the oral cavity and pharynx, pneumonia (in patients with COPD); rarely - esophageal candidiasis.

From the immune system: hypersensitivity reactions: infrequently - skin hypersensitivity reactions, shortness of breath; rarely - anaphylactic reactions.

From the endocrine system: possible systemic effects (see section “Special Instructions”): infrequently - cataracts; rarely - glaucoma.

From the side of metabolism and nutrition: infrequently - hyperglycemia; very rarely - hypokalemia.

Mental disorders: infrequently - anxiety, sleep disorders; rarely - changes in behavior, incl. hyperactivity and irritability (especially in children).

From the nervous system: very often - headache (see section "Special instructions"); infrequently - tremor (see section "Special instructions").

From the heart: infrequently - rapid heartbeat (see sections “With caution” and “Special instructions”), tachycardia, atrial fibrillation; rarely - arrhythmia, including ventricular extrasystole, supraventricular tachycardia and extrasystole.

From the respiratory system, chest and mediastinal organs: often - hoarseness and/or dysphonia; infrequently - pharyngeal irritation.

From the skin and subcutaneous tissues: infrequently - bruising.

From the musculoskeletal system and connective tissue: often - muscle spasms, arthralgia.

Post-registration observation data

Frequency of occurrence of adverse reactions

From the immune system: hypersensitivity reactions: rarely - angioedema (mainly swelling of the face and oropharynx), bronchospasm.

From the endocrine system: possible systemic effects (see section "Special Instructions") rarely - Cushing's syndrome, Cushingoid symptoms, suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density.

From the respiratory system, chest and mediastinal organs: rarely - paradoxical bronchospasm (see section "Special instructions").

Contraindications for use

- hypersensitivity to the components of the drug;

- children under 4 years of age.

Carefully

Like all other inhaled drugs containing corticosteroids, Seretide® should be used with caution in patients with acute or latent pulmonary tuberculosis.

The drug Seretide® should be prescribed with caution in case of thyrotoxicosis.

Seretide® should be used with caution in case of fungal, viral or bacterial infections of the respiratory system.

When taking any drugs from the sympathomimetic group, especially when therapeutic doses are exceeded, the development of cardiovascular phenomena such as an increase in systolic blood pressure and heart rate is possible. For this reason, Seretide® should be prescribed with caution to patients with cardiovascular diseases, incl. arrhythmias, such as supraventricular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation.

All sympathomimetic drugs in dosages exceeding therapeutic doses can cause a transient decrease in serum potassium levels. Therefore, Seretide® should be administered with caution to patients with hypokalemia.

Any inhaled GCS can cause systemic effects, especially with long-term use in high doses. Therefore, the drug should be used with caution in case of glaucoma, cataracts, osteoporosis (see section “Special instructions and precautions for use”).

There are very rare reports of increased blood glucose levels, so patients with diabetes should use Seretide® with caution (see section "Side effects").

Use during pregnancy and breastfeeding

Fertility

There are no data on the effect on fertility in humans. In animal studies, there was no effect of fluticasone propionate or salmeterol xinafoate on male or female fertility.

Pregnancy

Data on the use of the drug in pregnant women are limited. Use during pregnancy is permissible only if the potential benefit to the mother outweighs the possible risk to the fetus.

A retrospective study found no increased risk of major congenital malformations (SCDCs) following exposure to fluticasone propionate during the first trimester of pregnancy compared with other inhaled corticosteroids.

When conducting reproductive toxicity studies in animals with the administration of each component of the drug separately or in combination, the effect on the fetus of excessive systemic concentrations of the active beta2-adrenergic agonist and GCS was revealed.

Extensive experience in the clinical use of drugs of this class indicates that when using therapeutic doses, the described effects are not clinically significant.

Breastfeeding period

The concentration of salmeterol and fluticasone propionate in the blood plasma after inhalation of the drug in therapeutic doses is extremely low, so their concentration in breast milk should be equally low. This is confirmed by studies on animals, in whose milk low concentrations of the drug were determined. There are no related data regarding women's breast milk.

The use of the drug during breastfeeding is permissible only if the potential benefit to the mother outweighs the possible risk to the child.

Use for liver dysfunction

In patients with impaired liver function, no dose reduction is required.

Use for renal impairment

In patients with impaired renal function, no dose reduction is required.

Use in children

The use of the drug is contraindicated in children under 4 years of age.

Use in elderly patients

In elderly patients, no dose reduction is required.

special instructions

Seretide® is not intended for the relief of acute symptoms, since in such cases a rapid and short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be advised to always have medication available to relieve acute symptoms.

The combination of salmeterol and fluticasone propionate can be used for initial maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms or daily use of drugs to relieve attacks) if there are indications for the use of corticosteroids and their approximate dosage has been determined.

More frequent use of short-acting bronchodilators to relieve symptoms indicates worsening disease control, and in such situations the patient should consult a doctor.

Sudden and increasing deterioration in control of bronchospastic syndrome poses a potential threat to life, and in such situations the patient should also consult a doctor. The physician should consider prescribing a higher dose of GCS. If the dose of Seretide® used does not provide adequate control of the disease, the patient should also consult a doctor.

Patients with asthma should not abruptly stop treatment with Seretide due to the risk of exacerbation; the dose of the drug should be reduced gradually under the supervision of a physician. In patients with COPD, drug withdrawal may be accompanied by symptoms of decompensation and requires medical supervision.

Clinical studies have provided evidence of an increased incidence of pneumonia in patients with COPD receiving Seretide® (see section “Side Effects”). Clinicians should be aware of the possibility of developing pneumonia in COPD, since the clinical presentation of pneumonia and exacerbation of COPD are often similar.

Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; however, the likelihood of such symptoms occurring is much lower than with treatment with oral corticosteroids (see section “Overdose”). Possible systemic reactions include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, when treating asthma, it is important to reduce the dose to the lowest dose that provides effective control of the disease.

In emergency and planned situations that can cause stress, it is always necessary to remember the possibility of adrenal suppression and be prepared to use GCS (see section “Overdose”).

When carrying out resuscitation measures or surgical interventions, it is necessary to determine the degree of adrenal insufficiency.

It is recommended to regularly measure the height of children who receive long-term therapy with inhaled corticosteroids.

Due to the possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function regularly monitored.

After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special patient card containing an indication of the possible need for additional administration of corticosteroids in stressful situations.

In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to control the concentration of K+ ions in the plasma.

There are very rare reports of increased blood glucose levels, and this should be kept in mind when prescribing a combination of salmeterol and fluticasone propionate to patients with diabetes mellitus (see section "Side effects").

During the post-marketing period, there have been reports of clinically significant drug interactions between fluticasone propionate and ritonavir, leading to systemic effects of GCS, including Cushing's syndrome and adrenal suppression. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, unless the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS (see section “Drug Interactions”).

Data from a clinical study of the safety of salmeterol added to the treatment of bronchial asthma compared with placebo showed that the incidence of deaths due to bronchial asthma was significantly higher in the salmeterol group. When taking salmeterol compared with placebo, the risk of serious respiratory adverse reactions or death in African-American patients appears to be greater than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effect associated with the use of GCS on the risk of death in patients with asthma was not studied in this study.

Like other inhaled drugs, Seretide® can cause paradoxical bronchospasm, manifested by an increase in shortness of breath immediately after use. In this case, you should immediately use a fast- and short-acting inhaled bronchodilator, discontinue Seretide®, examine the patient and, if necessary, begin alternative therapy (see section “Side Effects”).

Impact on the ability to drive vehicles and operate machinery

In clinical studies, no data were obtained on the effect of the drug on the ability to drive vehicles and other mechanisms, however, the side effects that the drug may cause should be taken into account.

Overdose

It is not recommended to prescribe the drug in doses exceeding those specified in the “Dosage regimen” section. It is important to regularly review the patient's dosage regimen and reduce the dose to the lowest recommended dose that provides effective disease control.

Symptoms

Expected symptoms and signs of salmeterol overdose are typical of excessive beta2-adrenergic stimulation and include tremor, headache, tachycardia, increased systolic blood pressure and hypokalemia.

Acute overdose of fluticasone propionate by inhalation can provoke temporary suppression of the hypothalamic-pituitary-adrenal axis. This usually does not require any emergency measures, since normal adrenal function is restored within a few days.

Treatment

There is no specific treatment for overdose of salmeterol and fluticasone propionate. In case of overdose, maintenance therapy should be carried out and the patient's condition should be monitored. In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

Drug interactions

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, unless they are absolutely necessary for the patient.

In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive first-pass metabolism and high systemic clearance under the influence of the CYP3A4 isoenzyme of the cytochrome P450 system in the intestine and liver. This makes a clinically significant interaction involving fluticasone propionate unlikely.

A drug interaction study showed that ritonavir, a highly active inhibitor of the CYP3A4 isoenzyme, can cause a sharp increase in plasma fluticasone propionate concentrations, resulting in a significant decrease in serum cortisol concentrations. During post-marketing surveillance, there were reports of clinically significant drug interactions in patients who simultaneously received fluticasone propionate (intranasal or inhaled) and ritonavir. These interactions caused systemic side effects characteristic of GCS, such as Cushing's syndrome and adrenal suppression. Considering the above, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS.

Studies have shown that other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in fluticasone propionate levels in

Side effects of Seretide™

Since Seretide contains salmeterol and fluticasone propionate, adverse reactions of the type and severity that are characteristic of each component can be expected. No additional side effects were noted with the simultaneous use of 2 components of the drug. As with other inhaled drugs, paradoxical bronchospasm may occur with an immediate increase in the severity of shortness of breath after inhalation. If such a condition develops, a rapid and short-acting inhaled bronchodilator should be immediately used. Seretide should be discontinued immediately, the patient examined and, if necessary, alternative therapy prescribed. Data from clinical studies Salmeterol-fluticasone propionate Isolated cases of hematomas have been reported. Commonly reported side effects included hoarseness/dysphonia, throat irritation, headache, oral and throat candidiasis, and palpitations. Patients with COPD may develop pneumonia. Post-licensing data Salmeterol-fluticasone propionate Infrequent skin hypersensitivity reactions have been described. There are isolated reports of hypersensitivity reactions that manifest as angioedema (mainly swelling of the face and oropharynx), respiratory symptoms (shortness of breath and/or bronchospasm) and very rarely anaphylactic reactions. There have been isolated cases of anxiety, sleep disturbances and behavioral changes, including hyperactivity and agitation (mainly in children), as well as isolated cases of hyperglycemia. Salmeterol There are reports of pharmacological side effects of treatment with β2-agonists, such as tremor, palpitations, headache (usually transient, the severity of which decreases with regular use of the drug). In patients with higher sensitivity, cardiac arrhythmia (including atrial fibrillation, supraventricular tachycardia and extrasystole) is noted. Rarely - arthralgia and very rarely - hypersensitivity reactions and anaphylaxis, including edema and angioedema, bronchospasm and anaphylactic shock. There are reports of irritation of the mucous membranes of the mouth and throat. Uncommon: rash; common: muscle spasm. There are isolated reports of the development of hyperglycemia. Fluticasone propionate Some patients experienced hoarseness and candidiasis of the mucous membrane of the mouth and throat. Skin hypersensitivity reactions have been described, in isolated cases - angioedema of the face and oropharynx, the development of respiratory symptoms - shortness of breath and bronchospasm, and extremely rarely - anaphylactic reactions. Rinsing the mouth and throat with water after inhaling the drug can help reduce the incidence of dysphonia and candidiasis. Symptomatic candidiasis can be treated with topical antifungals while continuing to take Seretide. Possible systemic effects include adrenal suppression, Cushing's syndrome, Cushingoid signs, growth retardation in children and adolescents, decreased bone mineralization, cataracts and glaucoma. There are isolated reports of the development of hyperglycemia. There are anecdotal reports of anxiety, sleep disturbances and behavioral disturbances, including hyperactivity and agitation (mainly in children).

Seretide air d/ingal 25+250 mcg/dose 120 doses bal/pack cards x1

Trade name: Seretide International name: Salmeterol+Fluticasone

Release forms: dosed aerosol for inhalation 25 mcg+50 mcg/dose, 25 mcg+125 mcg/dose, 25 mcg+250 mcg/dose (aluminum inhalers with metering valve) 120 doses

Composition: salmeterol xinafoate 36.3 mcg [equiv. 25 mcg of salmeterol], fluticasone propionate 50/125/250 mcg - 1 dose

Pharmacological group: combined bronchodilator (selective beta2-adrenergic agonist + local glucocorticosteroid)

Pharmacological group according to ATK: R03AK06 (Salmeterol in combination with other drugs for the treatment of obstructive airway diseases)

Pharmacological action: selective beta-adrenergic blocking, bronchodilator, local glucocorticosteroid, local anti-inflammatory,

Indications: Broncho-obstructive diseases (patients receiving maintenance therapy with long-acting beta2-adrenergic receptor agonists and inhaled corticosteroids, with persistent symptoms of the disease during therapy with inhaled corticosteroids, regularly using bronchodilators, for whom corticosteroid therapy is indicated).

Dosage regimen: Inhalation. The initial dose of the drug is determined based on the dose of fluticasone that is recommended for the treatment of the disease of this severity. The initial dose should then be gradually reduced to the minimum effective dose. Adults and adolescents aged 12 years and older: 2 inhalations (25 mcg salmeterol and 50 mcg fluticasone) 2 times a day or 2 inhalations (25 mcg salmeterol and 125 mcg fluticasone) 2 times a day or 2 inhalations (25 mcg salmeterol and 250 mcg of fluticasone) 2 times a day. Children from 4 to 12 years: 2 inhalations (25 mcg salmeterol and 50 mcg fluticasone) 2 times a day.

Contraindications: Hypersensitivity, children's age (up to 4 years).

Side effects: Salmeterol: tremor, palpitations, headache, arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystole), arthralgia, allergic reactions (skin rash, angioedema), skeletal muscle spasms. Fluticasone: hoarseness, dysphonia, irritation of the pharyngeal mucosa, candidiasis of the oral cavity and pharynx, paradoxical bronchospasm, allergic skin reactions. With long-term use in high doses, systemic effects of fluticasone may be observed: decreased function of the adrenal cortex, osteoporosis, growth retardation in children, cataracts, glaucoma. Overdose. Symptoms: tremor, headache, tachycardia, suppression of adrenal function. Treatment: selective beta-blockers, discontinuation of the drug (after a few days, adrenal function is restored on its own).

Pharmacodynamics: Combined bronchodilator (contains salmeterol and fluticasone). Salmeterol is a selective long-acting beta2-adrenergic receptor agonist (12 hours). The salmeterol molecule has a long side chain that binds to the external site of the receptor. Due to these pharmacological properties, salmeterol is more effective in preventing histamine-induced bronchospasm and causes longer-lasting bronchodilation compared to conventional short-acting beta2-agonists. Effectively and for a long time inhibits the release of mast cell mediators such as histamine, leukotrienes and PgD2 in lung tissues. Suppresses the early and late stages of an allergic reaction; after administration of a single dose, bronchial hyperreactivity decreases; suppression of the late stage lasts 30 hours, when the bronchodilator effect is no longer present. Fluticasone is a local GCS. When administered by inhalation, it has a pronounced anti-inflammatory effect, which leads to a decrease in the severity of symptoms and a decrease in the frequency of exacerbations of diseases accompanied by airway obstruction. With long-term use of inhaled fluticasone in maximum doses, the daily and reserve secretion of adrenal hormones remains within normal limits in adults and children. Residual decrease in adrenal reserve function may persist for a long time after therapy.

Pharmacokinetics: Simultaneous inhalation administration of salmeterol and fluticasone does not affect the pharmacokinetics of either substance. Salmeterol: after inhalation administration in therapeutic doses, very low concentrations of the drug in plasma are created (200 pg/ml or less). With regular use of inhaled salmeterol, hydroxynaphthoic acid is detected in the systemic circulation in concentrations of up to 100 ng/ml. Fluticasone: after inhalation administration, the relative bioavailability is 10-30% depending on the drug delivery system. Systemic absorption occurs primarily in the lungs. Part of the inhaled dose can be swallowed, but its systemic effect is minimal due to the drug’s poor solubility in water and intensive metabolism during the “first pass” through the liver. The bioavailability of fluticasone when swallowed is less than 1%. There is a direct relationship between the size of the inhaled dose and the systemic effect of fluticasone; the volume of distribution is about 300 liters. Metabolized in the liver to an inactive metabolite with the participation of CYP3A4 of the cytochrome P450 system. Less than 5% of the metabolite is excreted in the urine. Plasma clearance - 1.15 l/min. T1/2 - 8 hours.

Special instructions: The drug is intended for long-term treatment and prevention of exacerbations of the disease, and not for stopping attacks (short-acting inhaled bronchodilators should be used). The drug should be taken regularly, even in the absence of symptoms of the disease. An increased need for the use of short-acting bronchodilators indicates a worsening of the disease. It is not recommended to abruptly stop treatment with the drug. With long-term use of any inhaled corticosteroids, especially in high doses, systemic effects may be observed. It is important that when a therapeutic effect is achieved, the dose of inhaled corticosteroids is reduced to the minimum effective dose that controls the course of the disease in order to avoid the development of systemic side effects. It is recommended to regularly monitor the growth dynamics of children receiving inhaled corticosteroids for a long time. Due to possible adrenal insufficiency, caution should be exercised and regular monitoring of adrenal cortex function indicators when transferring patients who have taken oral corticosteroids to treatment with inhaled fluticasone. Cancellation of systemic corticosteroids against the background of inhaled fluticasone should be carried out gradually. During periods of stress, you may need to take additional corticosteroids. If the drug has to be discontinued due to an overdose of salmeterol, the patient must be prescribed appropriate corticosteroid replacement therapy. In rare cases, when transferring patients from taking systemic corticosteroids to inhaled therapy, conditions accompanied by hypereosinophilia (including Charge-Strauss syndrome) may occur. As a rule, this occurs during dose reduction or withdrawal of systemic corticosteroids, but a cause-and-effect relationship has not been established. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (including allergic rhinitis, eczema), which were previously suppressed by systemic drugs, may also occur. Carefully. Pulmonary tuberculosis, thyrotoxicosis.

Interaction: Beta-blockers reduce effectiveness. Inhibitors of the CYP3A4 enzyme (including ketoconazole, ritonavir) increase the concentration of fluticasone in the blood plasma.

Drug registration number: P No. 015937/01

Date of registration (re-registration) of the drug: October 26, 2004

Special instructions for the use of Seretide™

Treatment of reversible obstructive airway diseases should be carried out according to a sequential program, the patient's condition must be regularly monitored both clinically and by determining indicators of pulmonary function. Seretide is not a drug for the relief of acute symptoms when the use of fast- and short-acting bronchodilators (for example, salbutamol) is necessary. The patient should be advised to always carry an appropriate medication to relieve symptoms. An increase in the frequency of use of short-acting bronchodilators to relieve asthma attacks indicates a deterioration in disease control, in which case the patient should consult a doctor. The rapid and progressive deterioration of asthma control poses a potential threat to life, which requires a revision of treatment tactics, and it may be necessary to increase the dose of GCS. The patient should also be examined if the prescribed dose of Seretide does not provide adequate control of asthma symptoms. The need for additional administration of GCS, as well as antibiotic therapy in case of infection, should be assessed. Given the risk of exacerbation of asthma or COPD, treatment with Seretide should not be abruptly stopped; the dose should be reduced gradually under medical supervision. Like other inhaled drugs containing corticosteroids, Seretide should be prescribed with caution to patients with active or latent pulmonary tuberculosis or thyrotoxicosis. In clinical studies of patients with COPD who received Seretide, an increased incidence of pneumonia was demonstrated. Doctors should be careful about the possible development of pneumonia in this category of patients, since the clinical symptoms of pneumonia and exacerbation of COPD often coincide. Cardiovascular effects, such as increases in systolic blood pressure and heart rate, can sometimes occur with all symatomimetics, especially in doses that exceed therapeutic doses. Therefore, Seretide should be used with caution in the treatment of patients with existing cardiovascular disease. The use of all sympathomimetics in doses that exceed therapeutic doses may lead to a transient increase in plasma potassium levels. Therefore, Seretide should be used with caution in patients predisposed to hypokalemia. Systemic effects can occur when using any inhaled GCS, especially in high doses over a long period of time; these effects are much less likely than with oral administration of corticosteroids (see OVERDOSE ). Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children, decreased bone mineralization, cataracts, and glaucoma. Therefore, it is important to titrate the dose of inhaled corticosteroids to the minimum effective, ensuring the ability to control asthma symptoms. You should always keep in mind the possibility of adrenal dysfunction in extreme situations, which may require the use of corticosteroids. It is recommended to regularly monitor growth dynamics in children receiving inhaled GCS for a long period. Some patients may be more sensitive to the effects of inhaled corticosteroids than most patients. Given the possibility of dysfunction of the adrenal cortex, it is necessary to transfer patients from oral corticosteroid therapy to inhaled fluticasone propionate with extreme caution, while regularly monitoring the function of the adrenal cortex. After administration of inhaled fluticasone propionate, systemic therapy should be discontinued gradually. Patients should have a special card with them indicating the need for additional administration of GCS in stressful situations. There are isolated reports of the development of hyperglycemia, which should be taken into account when prescribing Seretide to patients with diabetes mellitus. According to post-marketing data from the use of the drug, clinically significant drug interactions were reported in patients using fluticasone propionate and ritanavir, which was the cause of the systemic effects of GCS, including Cushing's syndrome and adrenal suppression. Therefore, the combined use of fluticasone propionate and ritanavir should be avoided, unless the benefit of this use is greater than the risk of systemic effects of GCS. A large clinical trial conducted in the United States ( SMART ), which compared the safety of Serevent (a component of Seretide Evohaler) or placebo as an addition to conventional therapy, showed an increase in asthma-related deaths in patients treated with Serevent. These studies suggest that African-American patients are at higher risk of severe respiratory complications or death when treated with Serevent compared to placebo. It is not known whether this is due to pharmacogenetic or other factors. SMART study did not determine whether concomitant use of inhaled corticosteroids would alter the risk of asthma-related deaths. According to a drug interaction study, combined use with systemic ketoconazole increases the effect of salmeterol. This may lead to prolongation of the QT . Therefore, caution should be exercised when concomitantly using salmeterol and strong CYP3A4 inhibitors (for example, ketoconazole). During pregnancy and breastfeeding. Prescribing medications during pregnancy and lactation is permissible only if the expected benefit to the mother outweighs the potential risk to the fetus or child. There is insufficient experience with the use of salmeterol xinafoate and fluticasone propionate during pregnancy and lactation. Reproductive toxicity studies in animals, conducted both with individual components of the drug and with their combination, revealed the effects on the fetus that can be expected when using a strong β2-agonist and corticosteroids in high doses. Experience in the clinical use of drugs of these classes indicates the absence of such effects in therapeutic doses. Salmeterol xinafoate and fluticasone propionate do not have genotoxic potential. The plasma concentrations of salmeterol xinafoate and fluticasone propionate after inhalation at therapeutic doses are very low, and therefore their concentrations in breast milk can be expected to be correspondingly low. There are no data on the concentration of drugs in human breast milk. Children. There are no data regarding the use of Seretide in children under 4 years of age, therefore the use of the drug is not recommended. Impact on the ability to drive vehicles and operate other machinery. No specific studies were carried out; Based on the pharmacology of both drugs, it can be assumed that there is no effect.

Seretide aerosol for inhalation 25 mcg+125 mcg/dose 120 doses

Registration Certificate Holder

GlaxoSmithKline Trading (Russia)

Dosage form

Medicine - Seretide®

Description

Aerosol for inhalation dosed

in the form of a white or almost white suspension.

1 dose

salmeterol xinafoate* 36.3 mcg, which corresponds to the content of salmeterol 25 mcg fluticasone propionate* 125 mcg

Excipients

: 1,1,1,2-tetrafluoroethane - up to 75 mg.

120 doses - aluminum inhalers (1) with a plastic spray - cardboard packs.

Indications

The drug Seretide® is intended for the regular treatment of bronchial asthma if combination therapy with a long-acting beta2-adrenergic agonist and inhaled corticosteroids is indicated:

patients with insufficient disease control on the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting beta2-adrenergic agonist;
patients with adequate disease control during therapy with inhaled GCS and a long-acting beta2-adrenergic agonist;
as initial maintenance therapy in patients with persistent bronchial asthma if there are indications for prescribing GCS to achieve disease control.

Contraindications for use

hypersensitivity to the components of the drug;
children under 4 years of age.

Carefully _

Like all other inhaled drugs containing corticosteroids, Seretide® should be used with caution in patients with acute or latent pulmonary tuberculosis.

The drug Seretide® should be prescribed with caution in case of thyrotoxicosis.

Seretide® should be used with caution in case of fungal, viral or bacterial infections of the respiratory system.

There are very rare reports of increased blood glucose levels, so patients with diabetes should use Seretide® with caution (see section "Side effects").

pharmachologic effect

Mechanism of action

Salmeterol

is a selective long-acting (up to 12 hours) β2-adrenergic receptor agonist, which has a long side chain that binds to the outer domain of the receptor.

A single administration of salmeterol weakens the hyperreactivity of the bronchial tree.
This indicates that salmeterol, in addition to bronchodilator activity, has an additional effect not associated with bronchial dilation, the clinical significance of which has not been fully established. This mechanism of action differs from the anti-inflammatory effect of GCS. Fluticasone propionate
belongs to the group of corticosteroids for topical use and, when administered by inhalation in recommended doses, has a pronounced anti-inflammatory and antiallergic effect in the lungs, which leads to a decrease in clinical symptoms and a decrease in the frequency of exacerbations of bronchial asthma. Fluticasone propionate does not cause the adverse effects that are observed with systemic administration of corticosteroids.

Drug interactions

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, unless they are absolutely necessary for the patient.

Studies have shown that other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in plasma fluticasone propionate, with virtually no decrease in serum cortisol concentrations. Despite this, caution is recommended during concomitant use of fluticasone propionate and strong CYP3A4 inhibitors (e.g., ketoconazole), as such combinations may increase plasma concentrations of fluticasone propionate, which could potentially increase the systemic effects of fluticasone propionate.

When studying drug interactions, it was found that the use of ketoconazole as concomitant systemic therapy significantly increases the concentration of salmeterol in the blood plasma (increase in Cmax by 1.4 times and AUC by 15 times). This may lead to prolongation of the QTc interval. Caution should be exercised when co-administering strong CYP3A4 inhibitors (eg, ketoconazole) and salmeterol.

Xanthine derivatives, corticosteroids and diuretics increase the risk of developing hypokalemia (especially in patients with exacerbation of bronchial asthma, during hypoxia).

MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the cardiovascular system.

Seretide® is compatible with cromoglycic acid.

Dosage regimen

Seretide® is intended for inhalation only.

The patient should be informed that to obtain optimal effect the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD.

The physician should regularly evaluate the effectiveness of the patient's treatment.

Determining the duration of the course of therapy and changing the dose of the drug is possible only on the recommendation of a doctor.

Bronchial asthma

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms.

If taking Seretide® 2 times a day provides control over symptoms, as part of reducing the dose to the minimum effective, it is possible to reduce the frequency of taking the drug to 1 time a day.

The patient should be prescribed a form of Seretide that contains a dose of fluticasone propionate appropriate to the severity of his disease.

Recommended Doses

Adults and children 12 years and older:

two inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times/day, or two inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times/day, or two inhalations (25 mcg salmeterol and 250 mcg fluticasone propionate) 2 times /day

Children 4 years and older:

two inhalations (25 mcg of salmeterol and 50 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® in children under 4 years of age

Chronic obstructive pulmonary disease (COPD)

For adult patients

the maximum recommended dose is two inhalations (25 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose of Seretide in elderly patients, or in patients with impaired renal or hepatic function.

Instructions for use of the inhaler (for patients)

Checking the inhaler

Using an inhaler