Pharmacy No. 84. Delivery of medicines to your home and office.

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Seretide, 1 piece, 25 mcg+125 mcg/dose, dosed aerosol for inhalation

Seretide has anti-asthmatic, bronchodilator, anti-inflammatory effects.

Pharmacodynamics The drug Seretide is a combination drug containing salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbations. The drugs may be an alternative for patients who simultaneously receive a β 2 -adrenergic receptor agonist and inhaled corticosteroids.

Salmeterol is a selective, long-acting (up to 12 hours) β 2 -adrenergic receptor agonist, which has a long side chain that binds to the outer domain of the receptor.

The pharmacological properties of salmeterol provide protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists. The onset of the bronchodilator effect is within 10–20 minutes. Salmeterol is a strong and long-acting inhibitor of the release of mast cell mediators such as histamine, LT and PG D2 from human lung tissue.

Salmeterol inhibits the early and late phases of the response to inhaled allergens; the latter lasts more than 30 hours after administration of 1 dose, i.e. at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to its bronchodilator activity, 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. At therapeutic doses, salmeterol has no effect on CCC.

Fluticasone propionate belongs to the group of corticosteroids for topical use and, when inhaled 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 diseases accompanied by airway obstruction. Restores the patient's response to bronchodilators, allowing to reduce the frequency of their use. The effect of fluticasone propionate is not accompanied by adverse reactions characteristic of systemic corticosteroids.

With long-term use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal hormones remains within normal limits in both adults and children. 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).

A study conducted among 318 adult patients with persistent bronchial asthma showed that when using a double dose of Seretide and Seretide Multidisc for 14 days (regardless of the dose of the components in the drug), there was a slight increase in the incidence of adverse events associated with the action of β-adrenergic agonists ( tremor - 1 patient (1%), 0 patients - at the usual dose; rapid heartbeat - 6 patients (6%), 1 patient (

Pharmacokinetics When administered together by inhalation, salmeterol and fluticasone propionate do not affect each other's pharmacokinetics, therefore the pharmacokinetic characteristics of each component of Seretide preparations can be considered separately.

Even despite the very low plasma concentrations of salmeterol and fluticasone propionate, interactions with other substrates and inhibitors of the CYP3A4 isoenzyme cannot be excluded.

Salmeterol: acts locally in the lung tissue, so its plasma levels do not correlate with the therapeutic effect. 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 repeated inhalations of salmeterol xinafoate, hydroxynaphthoic acid can be detected in the blood, the C ss of which is about 10 pg/ml. These concentrations are 1000 times lower than equilibrium levels observed in toxicity studies.

Fluticasone propionate: The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies depending on the inhaler used (when using salmeterol/fluticasone propionate using a metered dose inhalation aerosol, it is 5.3% of the nominal dose). In patients with bronchial asthma and COPD, lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs primarily through the lungs, and is initially faster but then 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 the drug 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 plasma concentration of fluticasone propionate is observed. The distribution of fluticasone propionate is characterized by rapid clearance from plasma (1150 ml/min), a large V ss (about 300 l) and a final half-life of approximately 8 hours. Fluticasone propionate has a relatively high degree of binding to plasma proteins (91%). It is rapidly eliminated from the blood, mainly as a result of metabolism under the action of the CYP3A4 isoenzyme to an inactive carboxyl metabolite.

The renal clearance of unchanged fluticasone propionate is negligible (

It is excreted through the gastrointestinal tract, mainly in the form of a hydroxylated metabolite.

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

Instructions for use SERETIDE®

Seretide® is not intended for the relief of acute asthma symptoms that require the use of a rapid- or short-acting bronchodilator. Patients should be advised to always have an inhaler available for relief during an acute asthma attack.

Seretide should not be started during an exacerbation, significant worsening or acute progression of asthma.

During treatment with Seretide®, serious adverse reactions associated with asthma, as well as exacerbations of the disease, may occur. Patients should be informed of the need to continue treatment and contact their doctor if asthma symptoms are uncontrollable or worsen after starting Seretide®.

Both an increase in the frequency of use of drugs that facilitate breathing (short-acting bronchodilators) and a decrease in the therapeutic response to the use of relief drugs indicate a deterioration in asthma control and require the patient to consult a doctor.

Sudden and progressive deterioration in asthma control can be potentially life-threatening, so the patient should consult a doctor immediately. Increasing the corticosteroid dose should be considered.

The dose of Seretide can be gradually reduced once asthma symptoms are under control. It is important to reduce the dose under the systematic supervision of a physician. The minimum effective dose of Seretide® should be used (see section “Dosage regimen”).

Treatment with Seretide should not be stopped abruptly in patients with asthma due to the risk of exacerbation. The dose of the drug should be reduced gradually under the supervision of a physician.

As with other inhaled drugs containing corticosteroids, Seretide should be used with caution in patients with active or latent pulmonary tuberculosis, fungal, viral and other respiratory tract infections. If necessary, appropriate treatment should be started immediately.

In rare cases, Seretide may cause cardiac arrhythmias such as supraventricular tachycardia, extrasystoles and atrial fibrillation, as well as a slight transient decrease in serum potassium levels when using high therapeutic doses. Seretide should be used with caution in patients with severe cardiovascular disease or cardiac arrhythmias, as well as in patients with diabetes mellitus, thyrotoxicosis, in patients with uncorrected hypokalemia or in patients predisposed to low serum potassium levels.

In very rare cases, an increase in the concentration of glucose in the blood was observed (see section “Side Effects”), this should be taken into account when prescribing the drug to patients with diabetes mellitus.

Inhaled drugs can cause paradoxical bronchospasm, which is manifested by increased wheezing and shortness of breath immediately after inhalation of the drug. Paradoxical bronchospasm must be treated immediately with a fast-acting inhaled bronchodilator. Seretide should be immediately discontinued, the patient's condition assessed and, if necessary, alternative therapy prescribed.

There have been reports of pharmacological side effects of β2-adrenergic agonist treatment, such as tremor, palpitations and headache, which are usually transient and decrease with continued therapy.

Any inhaled corticosteroids can cause systemic effects, especially with long-term use of high doses. These symptoms are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, decreased bone mineral density, cataracts, and glaucoma, and, more rarely, psychological and behavioral effects such as psychomotor hyperactivity, sleep disturbance, anxiety, depressive syndrome, and aggressiveness (especially in children) (for information on the systemic effects of inhaled corticosteroids in children and adolescents, see below). Therefore, it is important to regularly assess the patient's condition and reduce the dose of inhaled corticosteroid to the minimum effective dose that maintains optimal asthma control.

Long-term therapy with high doses of inhaled corticosteroids can lead to suppression of adrenal function and the development of acute adrenal crisis. Very rare cases of suppression of adrenal function and acute adrenal crisis have also been described with the use of fluticasone propionate in the dose range from 500 to <1000 mcg. Situations that potentially trigger acute adrenal crisis include trauma, surgery, infection, or any sudden dose reduction. Presenting symptoms are usually vague and may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, hypotension, depression of consciousness, hypoglycemia and seizures. In situations that can cause stress, or during planned surgery, you must be prepared for additional use of corticosteroids.

Systemic absorption of salmeterol and fluticasone propionate occurs primarily in the lungs. Because the use of a spacer with a metered dose inhaler may increase delivery of the drug to the lungs, the potential for an increased risk of adverse systemic effects should be considered. The results of a single dose pharmacokinetics study indicate that the systemic exposure of salmeterol and fluticasone propionate when using the AeroChamber Plus spacer with the Seretide® inhaler may be almost 2 times higher than when using the Volumatic spacer.

The benefits of therapy with inhaled fluticasone propionate should minimize the need for oral steroids, but patients transitioning from oral steroids may remain at risk of impaired adrenal reserve for a significant period of time. Therefore, patients switched from oral therapy should be treated with extreme caution, subject to regular monitoring of adrenal cortical function. Patients who have received high-dose acute corticosteroid therapy in the past may also be at risk. In emergency and routine stressful clinical situations, the possibility of residual adrenal dysfunction should always be kept in mind and the need for appropriate corticosteroid therapy should be considered. Consultation with a specialist may be required to assess the degree of adrenal dysfunction before elective surgery.

The use of ritonavir can lead to a significant increase in the concentration of fluticasone propionate in the blood plasma. Therefore, concurrent use should be avoided unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. An increased risk of systemic side effects also occurs with simultaneous use of fluticasone propionate and other strong CYP3A inhibitors (see section "Drug Interactions").

Results from a 3-year clinical trial in patients with chronic obstructive pulmonary disease (COPD) receiving salmeterol and fluticasone propionate in a fixed-dose combination via the Multidisc/Accuhaler device compared with placebo showed an increased incidence of lower respiratory tract infections (in features of pneumonia and bronchitis) (see section “Side effects”). In this study, older patients, patients with a low BMI (<25 kg/m2), and patients with very severe disease (FEV1 <30% predicted) were at increased risk of developing pneumonia, regardless of treatment. Prescribers should constantly consider the possibility of pneumonia and other lower respiratory tract infections in patients with COPD, since the clinical manifestations of these infections and exacerbations are often similar. If pneumonia develops in a patient with severe COPD, therapy with Seretide should be reconsidered. The safety and effectiveness of Seretide®, a metered dose inhalation aerosol, have not been studied in patients with COPD, therefore this dosage form of Seretide® is not intended for the treatment of patients with COPD.

Results from a large clinical trial (SMART, the Salmeterol Multicenter Research Trial for the Treatment of Asthma) showed that in African-American patients, the risk of serious respiratory adverse events or death was higher with salmeterol compared with placebo. It is unknown whether this is due to pharmacogenetic or other factors. Therefore, black patients of African or Afro-Caribbean origin should be advised to continue treatment and seek medical attention if asthma symptoms are not controlled or worsened while using Seretide.

Concomitant use of systemic ketoconazole significantly increases the systemic exposure of salmeterol. This may result in an increased incidence of systemic effects (eg, prolongation of the QTc interval and increased heart rate). Therefore, concomitant use with ketoconazole or other strong CYP3A4 inhibitors should be avoided unless the potential benefit to the patient outweighs the risk of systemic side effects of salmeterol (see Drug Interactions section).

Use in pediatrics

Children and adolescents <16 years of age receiving high doses of fluticasone propionate (usually ≥1000 mcg/day) may be at particular risk. Systemic effects may develop, especially with prolonged use in high doses. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, acute adrenal crisis and growth retardation in children and adolescents, and, more rarely, psychological and behavioral effects such as psychomotor hyperactivity, sleep disturbance, anxiety, depressive syndrome and aggressiveness. You should consider having your child or adolescent examined by a pediatrician who specializes in treating respiratory diseases.

It is recommended to regularly monitor the growth of children receiving long-term therapy with inhaled corticosteroids. The dose of inhaled corticosteroid should be reduced to the minimum effective dose that maintains optimal asthma control.

Impact on the ability to drive vehicles and operate machinery

The effect of Seretide® on the ability to drive vehicles and operate complex machinery is absent or negligible.

Seretide Multidisc por d/inhal 50mcg+500mcg 60 doses (Glaxo)

Seretide Multidisk has anti-asthmatic, bronchodilating, anti-inflammatory effects. Pharmacodynamics The drug Seretide Multidisc is a combination drug containing salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbations. The drugs may be an alternative for patients who simultaneously receive a β2-adrenergic receptor agonist and inhaled corticosteroids. 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. The pharmacological properties of salmeterol provide protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic agonists. The onset of the bronchodilator effect is within 10–20 minutes. Salmeterol is a strong and long-acting inhibitor of the release of mast cell mediators such as histamine, LT and PG D2 from human lung tissue. Salmeterol inhibits the early and late phases of the response to inhaled allergens; the latter lasts more than 30 hours after administration of 1 dose, i.e. at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to its bronchodilator activity, 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. In therapeutic doses, salmeterol has no effect on CCC. Fluticasone propionate belongs to the group of corticosteroids for topical use and, when inhaled 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 diseases accompanied by respiratory obstruction ways. Restores the patient's response to bronchodilators, allowing to reduce the frequency of their use. The effect of fluticasone propionate is not accompanied by adverse reactions characteristic of systemic corticosteroids. With long-term use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal hormones remains within normal limits in both adults and children. 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). Study , conducted among 318 adult patients with persistent bronchial asthma, showed that when using a double dose of Seretide and Seretide Multidisk for 14 days (regardless of the dose of the components in the drug), there is a slight increase in the frequency of adverse events associated with the action of β-adrenomimetic (tremor - 1 patient (1%), 0 patients - at the usual dose; palpitations - 6 patients (6%), 1 patient (Pharmacokinetics When administered together by inhalation, salmeterol and fluticasone propionate do not affect the pharmacokinetics of each other, therefore the pharmacokinetic characteristics of each component of the drugs Seretide Multidisk can be considered separately. Even despite the very low concentrations of salmeterol and fluticasone propionate in plasma, interactions with other substrates and inhibitors of the CYPZA4 isoenzyme cannot be excluded. Salmeterol: acts locally in the lung tissue, so its plasma levels do not correlate with the therapeutic effect. 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 repeated inhalations of salmeterol xinafoate, hydroxynaphthoic acid can be detected in the blood, the Css of which is about 10 pg/ml. These concentrations are 1000 times lower than steady-state levels observed in toxicity studies. Fluticasone propionate: The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies depending on the inhaler used (when using salmeterol/fluticasone propionate by metered dose inhalation aerosol, it is 5.3% from the nominal dose). In patients with bronchial asthma and COPD, lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs predominantly through the lungs, and is initially more rapid, but then 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 the drug 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 plasma concentration of fluticasone propionate is observed. The distribution of fluticasone propionate is characterized by rapid plasma clearance (1150 ml/min), a large Vss (about 300 l) and a final half-life of approximately 8 hours. Fluticasone propionate has a relatively high degree of plasma protein binding (91%). It is rapidly eliminated from the blood, mainly as a result of metabolism under the action of the CYP3A4 isoenzyme to an inactive carboxyl metabolite. The renal clearance of unchanged fluticasone propionate is negligible (Excreted through the gastrointestinal tract, mainly in the form of a hydroxylated metabolite.