Salmecort, aerosol 25 mcg+125 mcg/dose 120 doses

Salmecort is a combined bronchodilator (contains salmeterol and fluticasone propionate). Salmeterol is a selective agonist of beta2-adrenoreceptors with prolonged action (at least 12 hours). 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 to prevent histamine-induced bronchospasm and causes more prolonged bronchodilation compared to conventional short acting beta2-receptor agonists. Effectively and long-lasting inhibits the release of mast cell mediators such as histamine, leukotrienes and PgD2 in the lung tissue.

Suppresses early and late stage of allergic reaction; after administration of a single dose bronchial hyperresponsiveness decreases, inhibition of the late stage persists for over 30 h after a single dose, when the bronchodilator effect is no longer.

Fluticasone propionate is a glucocorticosteroid (GCS) of local action. When administered by inhalation in recommended doses it produces evident anti-inflammatory and anti-allergic effect leading to reduction of symptoms and frequency of exacerbations of diseases accompanied by airway obstruction.

During long-term use of inhaled fluticasone propionate at maximum doses, daily and reserve secretion of adrenal cortex hormones remains within normal limits in adults and children. A residual decrease in reserve adrenal function may persist long after therapy.

Pharmacokinetics
There is no evidence that co-administration of salmeterol and fluticasone propionate by inhalation affects the pharmacokinetics of either substance.

Salmeterol: After inhalation administration at therapeutic doses, very low plasma concentrations of the drug are produced (200 pg/ml or less). With regular use of inhaled salmeterol, hydroxynaphthoic acid is detected in the systemic bloodstream in concentrations up to 100 ng/ml.

Fluticasone propionate: after inhalation relative bioavailability is 10 to 30%, depending on the drug delivery system. Systemic absorption occurs primarily in the lungs. Part of the inhaled dose may be swallowed, but its systemic effect is minimal due to the weak water solubility of the drug and intense metabolism during “first passage” through the liver.

The bioavailability of fluticasone when swallowed is less than 1%. There is a direct correlation between the magnitude of the inhaled dose and the systemic effect of fluticasone; the volume of distribution is about 300L. It is metabolized in the liver to an inactive metabolite involving CYP3A4 of the cytochrome P450 system. Less than 5% of the metabolite is excreted in the urine. Plasma clearance is 1.15 l/min. The elimination half-life T1/2 is about 8 hours.

Indications

Bronchial asthma, Low learning capacityThe drug Salmecort is intended for regular treatment of bronchial asthma in patients who are indicated for combined therapy with a long-acting beta2-adrenomimetic and an inhaled glucocorticosteroid:

• in patients with insufficient disease control on continuous monotherapy with inhaled glucocorticosteroids with intermittent use of a short-acting beta2-adrenomimetic;
• in patients with adequate disease control against a background of therapy with inhaled glucocorticosteroid and long-acting beta2-adrenomimetic;
supportive therapy in patients with COPD who have a history of recurrent exacerbations and whose symptoms persist despite regular bronchodilator therapy.

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Active ingredient

Salmeterol, Fluticasone

Composition

Aerosol for metered inhalation

How to take, the dosage

Inhaled. For inhaled use only. The patient should be informed 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 therapy and changing the dose of the drug is possible only on the doctor’s recommendation. The initial dose of the drug is determined based on the dose of fluticasone recommended for the treatment of the disease of this severity. Then the initial dose should be gradually reduced to the minimum effective dose.

During treatment, a physician should be seen regularly to adjust the optimal dose. The patient should not independently change the doses of the drug prescribed by the physician.

Bronchial asthma
If taking Salmecort 2 times a day provides control of symptoms, as part of reducing the dose to the minimum effective, a reduction to once a day is possible.

A patient should be prescribed a form of Salmecort that contains a dose of fluticasone propionate appropriate for the severity of his disease. If therapy with inhaled GCS does not adequately control the disease, their replacement with Salmecort in a dose therapeutically equivalent to the dose of injected GCS may improve asthma control.

In patients whose asthma can be controlled by inhaled GCS alone, their replacement with Salmecort may allow a reduction in the dose of GCS needed to control the course of asthma.

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

Children 4 years and older:
two inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times daily.

All patients taking the drug as maintenance therapy should have a medical consultation 6-12 weeks after initial administration.

Chronic obstructive pulmonary disease
For adult patients, the maximum recommended dose is 2 inhalations (25 µg salmeterol and 250 µg fluticasone propionate) 2 times daily.

Special patient groups
There is no need to reduce the dose of Salmecort in elderly patients and in patients with renal or hepatic impairment.

Interaction

Because of the risk of bronchospasm, the use of selective and non-selective beta-adrenoblockers should be avoided unless they are urgently needed by the patient.

Salmeterol
Concomitant use with ketoconazole should be avoided unless the benefit of use exceeds 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 “first” passage and high systemic clearance under the influence of cytochrome P-450 system CYP3A4 isoenzyme in the gut and liver. Because of this clinically significant interactions involving fluticasone propionate are unlikely.

Ritonavir, as a highly active CYP3A4 enzyme inhibitor, can cause a sharp increase in plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations.

Concomitant use with ritanovir causes such side effects as Cushing’s syndrome and suppression of adrenal function. In view of the above, concomitant use of fluticasone propionate and ritanovir should be avoided unless the potential benefit to the patient exceeds the risk of systemic side effects of GCS.

Other CYP3A4 isoenzyme inhibitors cause negligible (erythromycin) and minor (ketoconazole) increase in plasma fluticasone propionate with almost no reduction in serum cortisol concentrations.

Despite this, caution is recommended with concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole) because such combinations do not exclude an increase in plasma concentrations of fluticasone propionate.

Xanthine derivatives, GCS (glucocorticosteroids) and diuretics increase the risk of hypokalemia (especially in patients with exacerbation of bronchial asthma, with hypoxia). Monoamine oxidase inhibitors and tricyclic antidepressants increase the risk of cardiovascular side effects. It is compatible with cromoglycic acid.

Special Instructions

Salmecort is not intended to relieve acute symptoms, as in such cases a fast-acting and short-acting inhaled bronchodilator (e.g. salbutamol) should be used. Patients should be informed that they should always have a drug on hand to relieve acute symptoms.

The combination of salmeterol and fluticasone propionate may be used for initial maintenance therapy in patients with persistent bronchial asthma (daily onset of symptoms or daily use of an attack control agent) if there are indications for prescribing GCS and in determining the approximate dosage of these.

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

Sudden and increasing worsening of bronchial asthma control is potentially life threatening, and in such situations the patient should also consult a physician. The physician should consider a higher dose of GCS. If the dose of Salmecort used does not adequately control the disease, the patient should also consult a physician.

Patients with asthma should not reduce treatment with Salmecort abruptly because of the danger of an exacerbation, the dose should be reduced gradually under the supervision of a physician. In patients with COPD, discontinuation of the drug may be accompanied by decompensation symptoms and requires physician monitoring.

In patients with COPD receiving Salmecort, the frequency of pneumonia may increase (see section “Side effects”). Physicians should be aware of the possibility of pneumonia in patients with COPD, since the clinical picture of exacerbation of COPD and pneumonia are often similar.
Any inhaled GCS may cause systemic reactions, especially when used in high doses for a long time; however, the probability of these symptoms is much lower than when treated with oral GCS (see section “Overdose”). Possible systemic reactions include Cushing’s syndrome, cushingoid traits, depressed adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma.
Therefore, when treating asthma, it is important to reduce the dose to the lowest dose that provides effective control of the disease.

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

In resuscitation or surgical interventions, the degree of adrenal insufficiency must be determined. It is recommended to regularly measure the height of children who receive prolonged therapy with inhaled GCS.

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

Allergic reactions (e.g., allergic rhinitis, eczema) that were previously suppressed by systemic GCS may occur when transferring patients from systemic GCS to inhalation therapy. In such situations it is recommended to conduct symptomatic treatment with antihistamines and/or drugs of local action, including GCS for topical use.

After treatment with inhaled fluticasone propionate systemic GCS should be withdrawn gradually, and such patients should have a special patient card with an indication of the possible need for additional GCS administration in stress situations.
In patients with exacerbation of bronchial asthma, hypoxia it is necessary to monitor the concentration of plasma potassium ions K+.

There are very rare reports of increased blood glucose levels, and this should be remembered when prescribing the combination salmeterol with fluticasone propionate to diabetic patients (see.

Because of the potential for systemic GCS effects, including Cushing’s syndrome and inhibition of adrenal function, coadministration of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient exceeds the risk associated with systemic GCS effects (see “Interaction with other drugs”).

When taking salmeterol, the risk of serious adverse reactions from the respiratory system or mortality is presumed to be higher in African-American patients than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effect of concomitant use of inhaled GCS on the risk of death in patients with asthma has not been studied.
Like other inhaled drugs, Salmecort can cause paradoxical bronchospasm, manifested by an increase in dyspnea immediately after use.

In this case a fast-acting and short-acting inhaled bronchodilator should be used immediately, Salmecort should be discontinued and alternative therapy should be started, if necessary (see section “Side effects”).

There may be adverse reactions associated with the pharmacological effects of beta2-antagonists such as tremor, subjective palpitations and headache. However, these reactions are transient and their severity decreases with regular therapy (see section “Side effects”).

Impact on the ability to drive.
No data on the effect of the drug on the ability to drive vehicles and other mechanisms have been obtained in clinical trials, but side effects that may be caused by the drug should be taken into account.

Contraindications

Side effects

All adverse reactions presented below are characteristic of the active ingredients – salmeterol and fluticasone propionate separately. The safety profile of the drug Salmecort does not differ from the profile of adverse reactions of its active ingredients.

The adverse reactions presented below are listed according to the affected organs and organ systems and the frequency of occurrence. The frequency is defined as follows: very frequently (>1/10), frequently (>1/100 and <1/10), infrequently (>1/1000 and <1/100), rarely (>1/10000 and <1/1000), very rarely (<1/10000, including individual cases).

Infections and invasions:
Frequently: oral and pharyngeal candidiasis, pneumonia (in patients with COPD).

Immune system disorders:
Infrequent: skin hypersensitivity reactions;
Rarely: anaphylactic reactions, angioedema (mainly facial and oropharyngeal edema), bronchospasm;

Endocrine system disorders:
Possible systemic effects include (see “Caution” and “Special Directions” sections)
Rarely: Cushing’s syndrome, cushingoid symptoms, depressed adrenal function, growth retardation in children and adolescents, reduced bone mineral density;

Visual organ disorders:
Infrequent: cataract; rare: glaucoma;

Metabolic and nutritional disorders:
Infrequent: hyperglycemia;
Very rare: hypokalemia:

Mental disorders:
Infrequent: anxiety, sleep disturbances;
Rarely: Behavioral changes, including increased activity and irritability (especially in children);

Nervous system disorders:
Very common: headache (see Heart disorders:
Infrequent: palpitations (see section “Special Precautions”); infrequent: tremor (see section “Special Precautions”);

Chronic disorders:
Infrequent: palpitations (see section “Caution”). Caution and Special Indications), tachycardia, atrial fibrillation;
Rarely: arrhythmias, including ventricular extrasystole, supraventricular tachycardia extrasystole;

Respiratory, thoracic and mediastinal disorders:
Frequently: hoarseness of voice and/or dysphonia; infrequently: pharyngeal irritation;
Rarely: paradoxical bronchospasm (see Skin and subcutaneous tissue disorders:
Infrequent: Bleeding;

Skeletal and muscular system and connective tissue disorders:
Frequently: muscle spasms, arthralgia;

Gastrointestinal tract disorders:
Very rare: dyspepsia, nausea.