Seretide aerosol for inhalation dosed 25+50 mcg/dose 120 doses bottle 1 pc. in Moscow

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.

Description of the dosage form

Aerosol for inhalation metered Seretide®: inhaler - aluminum with a concave bottom, hermetically sealed with a metering valve; the internal surface of the inhaler and valve should not have visible defects.

The contents of the inhaler are a white or almost white suspension.

Powder for inhalation metered Seretide® Multidisc®: inhaler - a round plastic device of 2 shades of purple (dark purple and light purple) with a diameter of about 8.5 cm and a height of about 3 cm, with a dose counter showing 28 or 60 doses.

The contents of the inhaler are white or almost white powder.

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.

Composition and release form

Seretide®

120 doses in an aluminum inhaler (complete with dosing device); in a cardboard box 1 inhaler.

Seretide® Multidisc®

in a round plastic inhaler 1 blister with 28 or 60 cells; There is 1 inhaler in a cardboard pack.

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).

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.

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® and Seretide® Multidisk 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 Css 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 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.

Renal clearance of unchanged fluticasone propionate is negligible (<0.2%), less than 5% of the dose is excreted in the urine as a 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.

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

Drug interactions Seretide™

Non-selective and selective β2-adrenergic blockers should be avoided in patients with reversible bronchial obstruction, unless absolutely necessary. Under normal conditions, after inhaled use of the drug, low plasma concentrations of fluticasone are achieved due to extensive first-pass metabolism and high systemic clearance of the drug mediated by cytochrome P450 3A4 in the liver and intestines. Therefore, clinically significant interactions due to fluticasone propionate are unlikely. Based on drug interaction studies in healthy volunteers, it has been shown that rinatavir (a strong inhibitor of cytochrome P450 3A4) can significantly increase plasma concentrations of fluticasone propionate, which can lead to a significant decrease in plasma cortisol concentrations. According to post-marketing data from the use of the drug, clinically significant drug interactions were reported in patients who were treated with inhaled or intranasal administration of fluticasone propionate and ritanavir, which was the cause of the systemic effects of GCS, including Cuschiig's syndrome and suppression of adrenal function. Therefore, the simultaneous use of fluticasone propionate and ritanavir should be avoided, unless the benefit of use will outweigh the risk of systemic effects of GCS. Based on studies of other cytochrome P450 3A4 inhibitors, it has been proven that other cytochrome P450 3A4 inhibitors have a very minor (erythromycin) or small (ketoconazole) effect on increasing the systemic concentration of fluticasone propionate in the blood plasma, without leading to a significant decrease in cortisol concentrations. However, strong inhibitors of cytochrome P450 3A4 (for example, ketoconazole) should be used with caution, given the possibility of systemic effects of fluticasone propionate. The combined use of ketoconazole and salmeterol causes a significant increase in the concentration of salmeterol in the blood plasma (maximum plasma concentration 1.4 times and 15 times the AUC), which may cause a prolongation of the QT (see SPECIAL INSTRUCTIONS ).

Seretide™ overdose, symptoms and treatment

Symptoms of salmeterol overdose that can be expected are typical of excessive β2-adrenergic receptor stimulation and include tremor, headache, tachycardia, increased systolic blood pressure and hypokalemia. Cardioselective beta-adrenergic blockers are used as optimal antidotes, which should be used with caution when treating patients with a history of bronchospasm. If treatment with Seretide must be discontinued due to an overdose of the β2-agonist included in the drug, the patient should be prescribed appropriate corticosteroid replacement therapy. Inhalation of fluticasone propionate in doses higher than recommended may lead to temporary depression of the hypothalamic-pituitary-adrenal axis. This condition does not require immediate attention as adrenal function returns within a few days. However, when doses higher than recommended are used over a long period of time, significant suppression of adrenal function is possible. Cases of acute adrenal crises have been reported rarely, mainly in children receiving higher than recommended doses of the drug over a long period (several months or years). Hypoglycemia may occur, accompanied by impaired consciousness and/or convulsions. Factors that trigger acute adrenal crisis include trauma, surgery, infection, or a sharp reduction in the dose of inhaled fluticasone propionate. Therefore, Seretide should not be used in doses higher than recommended. The dosage regimen should be regularly reviewed and the dose reduced to the minimum level sufficient to effectively control the disease.

Contraindications

hypersensitivity to the components of the drug;

children under 4 years of age.

With caution: pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, uncontrolled arterial hypertension, arrhythmias, prolongation of the QT interval on the ECG, ischemic heart disease, hypoxia of various origins, cataracts, glaucoma, hypothyroidism, osteoporosis, pregnancy, lactation.