Salmecort inhalation aerosol 25 µg+50 µg/dose, 120 doses

Composition

Aerosol for inhalation dosed 1 dose (based on salmetsrol 25 mcg): Salmeterol xynafoate 36.3 mcg, Fluticasone propionate 50 mcg,125 mcg 250 mcg. Auxiliary substances:  1,1,1,2-tetrafluoroethane (HFA-134 a) 73,099 mg (for a dosage of 25 +50 mcg),73,024 mg (for a dosage of 25 + 125 mcg),72,900 mg (for a dosage of 25 + 250 mcg), Polyethylene Glycol 1000 0.01464 mg

Pharmacological action

Salmecort is a combined bronchodilator (contains salmeterol and fluticasone propionate). Salmeterol is a long-acting selective beta-2-adrenergic receptor agonist (at least 12 hours). The salmeterol molecule has a long side chain that binds to the outer domain of the receptor. Due to these pharmacological properties, salmeterol is more effective in preventing histamine-induced bronchospasm and causes longer bronchodilation compared to conventional short-acting beta-2 receptor agonists. Effectively and permanently inhibits the release of mast cell mediators in lung tissues, such as histamine, leukotrienes, and PgD2. Suppresses the early and late stages of an allergic reaction; after a single dose, bronchial hyperreactivity decreases, late-stage inhibition persists for more than 30 hours after a single dose, when the bronchodilating effect is no longer present. Fluticasone propionate is a local glucocorticosteroid (GCS). When inhaled at the recommended doses, it has a pronounced anti-inflammatory and anti-allergic 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 prolonged use of inhaled fluticasone propionate in maximum doses, the daily and reserve secretion of adrenal cortex hormones remains within the normal range in adults and children. A residual decrease in the reserve function of the adrenal glands may persist for a long time after therapy. Pharmacokinetics: There is no evidence that co-use of salmeterol and fluticasone propionate by inhalation affects the pharmacokinetics of each of these substances. Salmeterol: after inhaled use in therapeutic doses, very low concentrations of the drug are created in the blood plasma (200 pg / ml or less). With regular use of inhaled salmeterol in the systemic circulation, hydroxynaphthoic acid is detected in concentrations up to 100 ng / ml. Fluticasone propionate: after inhaled use, the relative bioavailability is 10 to 30%, depending on the drug delivery system. Systemic absorption occurs mainly in the lungs. Part of the inhaled dose can be swallowed, but its systemic effect is minimal due to the weak solubility of the drug in water and intensive metabolism during the” first pass ” through the liver. The bioavailability of fluticasone by ingestion is less than 1%. There is a direct relationship between the inhaled dose and the systemic effect of fluticasone, the volume of distribution is about 300 liters. It is 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. The plasma clearance is 1.15 l/min. The half-life of T 1/2 is about 8 hours.

Indications

The drug Salmecort is intended for the regular treatment of bronchial asthma in patients who are indicated for combination therapy with a long-acting beta-2-adrenomimetic and an inhaled glucocorticosteroid:

• in patients with insufficient control of the disease by the constant background of monotherapy with inhaled corticosteroids in the periodic use of beta 2-agonists short-acting;
• in patients with adequate control of the disease during therapy with inhaled glucocorticosteroid and beta 2-agonists long-acting;
• as a starting maintenance therapy in patients with persistent bronchial asthma (daily symptoms, daily use of tools for the rapid relief of symptoms) in the presence of indications for the appointment of corticosteroids to achieve control of the disease;
• maintenance therapy in patients with COPD, where the value of the forced expiratory volume (FEV 1) < 60% of the expected values (up to inhalation of a bronchodilator) with re-exacerbation history, and who have symptoms of the disease persist despite regular therapy with bronchodilators.

Use during pregnancy and lactation

Pregnant women and women during lactation should be prescribed the drug only if the expected benefit to the mother exceeds any possible risk to the fetus or child. There are insufficient data on the use of salmeterol and fluticasone propionate during pregnancy and lactation. Pregnancy Excessive systemic concentrations of active beta-2-adrenomimetics and corticosteroids affect the fetus. Extensive clinical experience with the use of drugs of this class indicates that when using therapeutic doses, the described effects are not clinically significant. Salmeterol and fluticasone propionate are not genotoxic. Lactation 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 as low. There are no data on the concentrations of salmeterol and fluticasone propionate in breast milk of women during lactation.

Contraindications

• Hypersensitivity to one or more components of the drug,
• children (up to 4 years).

With caution: Like all other inhaled medications containing corticosteroids, Salmecort should be used with caution in patients with acute or latent pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, and thyrotoxicosis. When taking any drugs of the sympathomimetic group, especially if the therapeutic doses are exceeded, cardiovascular events such as an increase in systolic blood pressure and heart rate may develop. For this reason, Salmecort should be used with caution in patients suffering from cardiovascular diseases, including arrhythmias such as supraventicular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation. All sympathomimetic drugs in dosages exceeding therapeutic ones can cause a transient decrease in serum potassium levels, so Salmecort should be prescribed with caution in patients with hypokalemia. Any inhaled corticosteroid may cause systemic effects, especially with prolonged use in high doses, so the drug should be used with caution in glaucoma, cataracts, osteoporosis (see the section “Special instructions and precautions for use”). There are very rare reports of increased blood glucose levels, so patients with diabetes should use the drug Salmecort with caution (see the section “Side effects”).

Side effects

All the adverse reactions listed below are characteristic of the active ingredients-salmeterol and fluticasone propionate separately. The safety profile of Salmecort does not differ from the profile of adverse reactions of its active ingredients. The adverse reactions listed below are listed according to the lesion of organs and organ systems and frequency of occurrence. The frequency of occurrence is determined as follows:

• very common (>1/10), >
• common (>1/100 and ><1/10),
• infrequent (>1/1000 and ><1/100),
• rare (>1/10000 and ><1/1000),
• very rare (

Infections and infestations: Common: oral and pharyngeal candidiasis, pneumonia (in patients with COPD). Immune system disorders: Infrequently: hypersensitivity skin reactions; Rarely: anaphylactic reactions, angioedema (mainly swelling of the face and oropharynx), bronchospasm. Endocrine system disorders: Possible systemic effects include (see sections “With caution” and “Special instructions”)Rare: Cushing’s syndrome, Cushing’s symptoms, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density. Visual disturbances: Infrequently: cataract; rarely: glaucoma. Metabolic and nutritional disorders: Infrequently: hyperglycemia; Very rarely: hypokalemia. Mental disorders: Infrequently: anxiety, sleep disorders; Rarely: changes in behavior, including increased activity and irritability (especially in children). Nervous system disorders: Very common: headache (see section “Special instructions”); Infrequently: tremor (see section “Special instructions”). Violation of the heart: Infrequently: rapid heartbeat (see the section “With caution” and “Special instructions”), tachycardia, atrial fibrillation; Rarely: arrhythmia, including ventricular extrasystole, supraventricular tachycardia extrasystole. Respiratory, thoracic and mediastinal disorders: Common: hoarseness and / or dysphonia; uncommon: pharyngeal irritation; Rare: paradoxical bronchospasm (see section “Special instructions”). Skin and subcutaneous tissue disorders: Infrequently: bruising. Musculoskeletal and connective tissue disorders: Common: muscle spasms, arthralgia. Disorders of the gastrointestinal tract: Very rare: dyspepsia, nausea. Children and adolescents It is theoretically possible to develop systemic reactions, including Cushing’s syndrome, Cushing’s symptoms, adrenal suppression, and growth retardation in children and adolescents. Very rarely, you may experience anxiety, sleep disorders, and behavioral disorders, including hyperactivity and irritability.

Interaction

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, except in cases where they are extremely necessary for the patient. Concomitant use of salmeterol with ketoconazole should be avoided if the benefit of use does not exceed the potential risk of systemic adverse reactions during treatment with salmeterol. There is a similar risk of interaction with other strong CYP3A4 inhibitors (itraconazole, telithromycin, ritonavir). Fluticasone Propionate In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive metabolism during the “first” passage and high systemic clearance under the influence of the cytochrome P-450 isoenzyme CYP3A4 in the intestine and liver. Because of this, clinically significant interactions involving fluticasone propionate are unlikely. Ritonavir, as a highly active inhibitor of the CYP3A4 enzyme, can cause a sharp increase in the concentration of fluticasone propionate in plasma, resulting in a significant decrease in serum cortisol concentrations. Concomitant use with ritanovir causes side effects such as Cushing’s syndrome and adrenal suppression. With this in mind, the concomitant use of fluticasone propionate and ritanovir should be avoided unless the potential benefit to the patient outweighs the risk of systemic side effects of corticosteroids. Other inhibitors of the CYP3A4 isoenzyme cause negligible (erythromycin) and insignificant (ketoconazole) increases in the content of fluticasone propionate in plasma, which practically do not decrease the concentration of serum cortisol. Despite this, caution is recommended when concomitantly using strong CYP3A4 inhibitors (for example, ketoconazole), since such combinations do not exclude an increase in the concentration of fluticasone propionate in plasma. Xanthine derivatives, corticosteroids (glucocorticosteroids) and diuretics increase the risk of hypokalemia (especially in patients with acute asthma, hypoxia). Monoamine oxidase inhibitors and tricyclic antidepressants increase the risk of cardiovascular side effects. Compatible with Cromoglicic acid.

How to take, course of use and dosage

By inhalation. For inhalation use only. The patient should be informed about. that for optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. The doctor 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. The initial dose of the drug is determined based on the dose of fluticasone, which is recommended for the treatment of the disease of this severity. The initial dose should then be gradually reduced to the minimum effective dose. During treatment, you should regularly see a doctor in order to select the optimal dose. The patient should not independently change the dosage of the drug prescribed by the doctor. Bronchial asthmaif taking Salmecort 2 times a day provides control over symptoms, as part of reducing the dose to the minimum effective dose, it is possible to reduce the frequency of taking the drug up to 1 time a day. The patient should be prescribed a form of Salmecort that contains a dose of fluticasone propionate appropriate to the severity of the disease. If inhaled corticosteroid therapy does not provide adequate disease control, replacing it with Salmecort at a dose that is therapeutically equivalent to the dose of corticosteroids administered may improve asthma control. In patients who can control the course of asthma exclusively with inhaled corticosteroids. replacing them with Salmecort may reduce the dose of corticosteroids needed to control the course of asthma. Recommended doses:Adults and children aged 12 years and older:two inhalations (25 mcg of salmeterol and 50 mcg of fluticasone propionate) 2 times a day, or two inhalations (25 mcg of salmeterol and 125 mcg of fluticasone propionate) 2 times a day, or two inhalations (25 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times a day. Children aged 4 years and older:two inhalations (25 mcg of salmeterol and 50 mcg of fluticasone propionate) 2 times a day. All patients taking the drug as maintenance therapy should consult a doctor 6-12 weeks after the initial intake. Chronic obstructive pulmonary disease For adult patients, the maximum recommended dose is 2 inhalations (25 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times a day. Special patient groups There is no need to reduce the dose of Salmecort in elderly patients, as well as in patients with impaired renal or hepatic function.

Overdose

It is not recommended to prescribe the drug in doses exceeding those indicated in the section “Dosage and use”. It is very important to regularly review the patient’s dosage regimen and reduce the dose to the lowest recommended dose that provides effective disease control (“Dosage and use”). Symptoms The expected symptoms and signs of salmeterol overdose are typical of excessive beta-2-adrenergic stimulation, and include tremor, headache, tachycardia, increased systolic blood pressure, and hypokalemia. Acute overdose of fluticasone propionate by inhalation may cause temporary suppression of the hypothalamic-pituitary-adrenal system. This usually does not require any emergency measures, as normal adrenal function is restored within a few days. When taking the drug in doses higher than recommended for a long period of time, significant suppression of the function of the adrenal cortex is possible. Rare cases of acute adrenal crisis are described, which occurred mainly in children who received doses of the drug higher than recommended for a long time (several months or years). Acute adrenaline crisis is manifested by hypoglycemia, accompanied by confusion and / or convulsions. Situations that can trigger an acute adrenal crisis include trauma, surgery, infection, or any rapid reduction in the dose of inhaled fluticasone propionate, which is part of the Salmecort preparation. Treatment There is no specific treatment for overdose of salmeterol and fluticasone propionate. In case of overdose, maintenance therapy should be performed and the patient’s condition monitored. When using the drug in doses exceeding those indicated in the instructions for a long time, suppression of the function of the adrenal cortex may occur.

Special instructions

Salmecort is not intended for the relief of acute symptoms, since in such cases a fast – and short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be informed that they should always have a 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 seizure medications) if there are indications for the appointment of corticosteroids and when determining their approximate dosage. More frequent use of short-acting bronchodilators to relieve symptoms indicates a deterioration in disease control, and in such situations, the patient should consult a doctor. Sudden and increasing deterioration in asthma control is potentially life-threatening, and in such situations, the patient should also consult a doctor. Your doctor should consider taking a higher dose of corticosteroids. If the dose of Salmecort used does not provide adequate disease control, the patient should also consult a doctor. Patients with asthma should not drastically reduce treatment with Salmecort due to the risk of exacerbation, the dose of the drug should be reduced gradually under the supervision of a doctor. In patients with COPD, discontinuation of the drug may be accompanied by symptoms of decompensation and requires medical supervision. Patients with COPD receiving Salmecort may have an increased incidence of pneumonia (see section “Side effects”). Doctors should be aware of the possibility of developing pneumonia in patients with COPD, as the clinical picture of COPD exacerbation and pneumonia are often similar. Any inhaled corticosteroid may cause systemic reactions, especially when used for a long time in high doses; however, the likelihood of such symptoms is much lower than when treated with oral corticosteroids (see section “Overdose”). Possible systemic reactions include Cushing’s syndrome, Cushing’s 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 disease control. In emergency and planned situations that can cause stress, you should always be aware of the possibility of adrenal suppression and be prepared for the use of CORTICOSTEROIDS (see the section “Overdose”). When performing 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 potential for adrenal suppression, patients transferred from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal cortex function should be monitored regularly.When patients are transferred from taking systemic corticosteroids to inhaled therapy, allergic reactions may occur (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids. In such situations, it is recommended to conduct symptomatic treatment with antihistamines and / or topical medications, including topical corticosteroids. After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be discontinued gradually, and such patients should carry a special patient card indicating the possible need for additional corticosteroid use in stressful situations. In patients with acute bronchial asthma, hypoxia, it is necessary to monitor the concentration of potassium K+ ions in plasma. There are very rare reports of increased blood glucose levels, and this should be borne in mind when prescribing a combination of salmeterol with fluticasone propionate to patients with diabetes mellitus (see the section “Side effects”). Due to the potential for systemic effects of corticosteroids, including Cushing’s syndrome and adrenal suppression, co-use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risk associated with systemic effects of corticosteroids (see section “Interactions with other medications”). When taking salmeterol, the risk of serious adverse reactions from the respiratory system or death in patients of African-American origin is presumably higher than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effect of concomitant use of inhaled corticosteroids on the risk of death in patients with asthma has not been studied. Like other inhaled medications, Salmecort can cause paradoxical bronchospasm, which is manifested by an increase in shortness of breath immediately after use. In this case, you should immediately apply a fast-and short-acting inhaled bronchodilator, cancel Salmecort and start alternative therapy, if necessary (see the section “Side effects”). Adverse reactions associated with the pharmacological action of beta-2 antagonists may occur, such as tremor, a subjective sense of palpitation, and headache. However, these reactions are short-term in nature, and their severity decreases with regular therapy (see the section “Side effects”). Influence on the ability to drive vehicles and mechanisms:In clinical studies, no data have been obtained on the effect of the drug on the ability to drive vehicles and other mechanisms, but it is necessary to take into account the side effects that the drug can cause.

Storage conditions

At a temperature not exceeding 25 °C, do not freeze. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Salmeterol, Fluticasone

Conditions of release from pharmacies

By prescription

Dosage form

aerosol for inhalation