Instruction for use: Salticasone-nativ

Active substance Salmeterol + Fluticasone

ATX Code R03AK06 Salmeterol + Fluticasone

Pharmacotherapeutic group:

Bronchodilator combination means (beta2-agonists selective glucocorticosteroid + local) [beta-adrenergic agonist in combination]

The nosological classification (ICD-10)

J44 Other chronic obstructive pulmonary disease

Allergic bronchitis, Bronchitis asthma, Asthmatic bronchitis, wheeze bronchitis, Bronchitis is an obstructive, bronchi disease, Shortness of sputum in acute and chronic respiratory diseases, Cough in inflammatory diseases of the lung and bronchus, Reversible airflow obstruction, Reversible obstructive airway disease, Obstructive bronchitis disease, Obstructive lung disease, Obstructive bronchitis, Spastic bronchitis, Chronic lung disease, Chronic nonspecific lung diseases, Chronic obstructive pulmonary disease, Chronic obstructive bronchitis, Chronic obstructive airway disease, Chronic obstructive pulmonary disease, Restrictive lung pathology

J45 Asthma

Asthma physical effort, status asthmaticus, Bronchial asthma, Asthma lung flow, Bronchial asthma with obstruction of sputum discharge, Bronchial asthma heavy currents, Bronchial asthma physical effort, hypersecretory asthma, Hormone-dependent form of bronchial asthma, Relief of asthma attacks in bronchial asthma, Non-allergic asthma, nocturnal asthma, Exacerbation of asthma, Asthma attacks, Endogenous forms of asthma, Night asthma, Cough with bronchial asthma

Structure and Composition

The powder for inhalation dose 1 capsule.

active substance:

salmeterol xinafoate 72.5 / 72.5 / 72.5 mg

(In terms of salmeterol - 50/50/50 g)

fluticasone propionate 100/250/500 mg

Excipients: Sodium benzoate - 2/2/2 mg; lactose monohydrate - until 12/12/12 mg

gelatin capsules

Capsule body: indigotine - - / 0.3 / -%; iron oxide yellow - - / 1.7143 / -%; azorubin - - / - / 0.0016%; Black Diamond - - / - / 0.0958%; patent blue - - / - / 0.1643%; quinoline yellow - - / - / 1.1496%; titanium dioxide - 2/2 / 1.3333%; Gelatin - 100/100/100%

cap capsule: azorubin - - / - / 0.0016%; Black Diamond - - / - / 0.0958%; patent blue - - / - 0.1642%; quinoline yellow - - / - / 1.1496%; titanium dioxide - 2/1 / 1.3333%; Gelatin - 100/100/100%

The drug forms

Dosage 50 g + 100 g: hard gelatin capsules ¹ 3, body - white cap - white.

Dosage 50 .mu.g + 250 mg: Hard gelatin capsules ¹ 3, body - white cap - green.

Dosage 50 mg + 500 mg: hard gelatine capsules number 3, the case - green cap - green.

The contents of capsules - powder white or nearly white.

pharmachologic effect

bronchodilatory, glucocorticoid, beta-agonists.

pharmacodynamics

Saltikazon®-native - combined preparation containing salmeterol and fluticasone propionate which have different mechanisms of action. Salmeterol prevents bronchospasm, fluticasone propionate improves lung function and prevents aggravation. The drug Saltikazon®-native can be an alternative for patients who are at the same time receive a .beta.2-agonist and inhaled corticosteroids adrenergic receptors of different inhalers. Salmeterol - is a selective long-acting (12 h) β2-adrenoceptor agonist having a long side chain which binds to the outer domain of the receptor.

The pharmacological properties of salmeterol offer protection against histamine-induced bronchoconstriction and longer lasting bronchodilation (lasting at least 12 hours) than the β2-adrenergic receptor agonists, short-acting. Home bronchodilator effect - for 10-20 minutes.

Salmeterol is a potent and long-acting inhibitor release from human pulmonary mast cells of tissue mediators such as histamine, PGD2 and radiotherapy. Salmeterol inhibits the early and late phase response to inhaled allergen; the effect lasts more than 30 hours after a single dose when the bronchodilatory effect is no longer present.

A single administration of salmeterol attenuates bronchial hyper-responsiveness of the tree. This indicates that the effect of bronchodilator salmeterol in addition has an additional effect, the clinical significance is not completely established.

Fluticasone propionate - a synthetic corticosteroids for topical application, improves lung function and prevents exacerbations.

Fluticasone propionate inhibits the influx of mast cells, eosinophils, lymphocytes, macrophages, neutrophils, reduces the production and release of mediators of inflammation and other biologically active agents (including histamine, PG, LT, and cytokines) involved in the formation of allergen-specific sensitization. This reduces the permeability of capillaries, exudation disappears, decreases mucus secretion by mucous glands restored patency of the bronchial tree.

With inhalational administration at the recommended doses of fluticasone propionate exhibits pronounced anti-inflammatory and antiallergic action in the lungs, which reduces the clinical symptoms and reducing exacerbations diseases accompanied by airway obstruction. Restores the patient's response to bronchodilators by reducing the frequency of their use.

With prolonged use of inhaled fluticasone propionate at recommended doses, the maximum daily secretion of adrenal hormones remained in the normal range. After the transfer of patients treated with other inhaled corticosteroids, to receive fluticasone propionate daily secretion of adrenal hormones gradually returning to normal, despite the previous and current periodic use of oral corticosteroids. This indicates a recovery of adrenal function on the background of the use of inhaled fluticasone propionate. With prolonged use of fluticasone propionate backup function of the adrenal cortex also remained within normal limits, as evidenced by an increase in the normal production of cortisol in response to appropriate stimulation (please note that the reduction in residual adrenal reserve, caused by previous therapy can be maintained for a long time).

Pharmacokinetics

Simultaneous inhalational administration of salmeterol and fluticasone propionate did not affect the pharmacokinetics of each of these substances. Even at a very low concentration of drug Saltikazon®-native plasma, we can not exclude its interaction with other substrates and inhibitors of isoenzyme SYR3A4.

salmeterol

Salmeterol acts locally in the lung tissue and therefore its content in the plasma is not correlated with the therapeutic effect. Data on the pharmacokinetics of its very limited due to technical problems: inhalation therapeutic doses its Cmax in plasma is extremely low (200 pg / ml and below). Salmeterol plasma concentration correlates with the dose of inhaled drug. With regular use of inhaled salmeterol in the blood is determined gidroksinaftoevaya acid, Css values which make up about 10 pg / ml. These concentration 1000 times lower than the equilibrium levels observed in toxicity studies.

fluticasone propionate

Absorption and distribution. After the introduction of the absolute bioavailability of inhaled fluticasone propionate in healthy subjects is 10-30% of the nominal dose. Patients with COPD and asthma have lower concentrations of fluticasone propionate in plasma. Systemic absorption occurs primarily in the lungs, and it is more intense at the beginning, but then slows down.

Part of the inhaled dose may be swallowed, but due to poor solubility of fluticasone propionate in water metabolism and intensive first-pass liver minimum systemic effect. The bioavailability of fluticasone propionate in its absorption from the gastrointestinal tract is less than 1%.

Inhalation between increasing dose and concentration of fluticasone propionate is a direct correlation is observed in the plasma.

Vss fluticasone propionate is around 300 liters.

The degree of binding to plasma proteins is approximately 91%.

Metabolism and excretion. With the participation of CYP3A4 fluticasone propionate is rapidly eliminated from the blood to form an inactive carboxyl metabolite.

Fluticasone propionate has a high plasma clearance (1150 ml / min).

The final T1 / 2 of about 8 hours.

Renal clearance of fluticasone propionate unmodified negligible (<0.2%) as a metabolite in the urine output of less than 5% of the dose. Care must be taken while the application of known inhibitors SYR3A4 and fluticasone propionate, because these situations may increase the content of the latter in plasma. Displayed through the gastrointestinal tract mainly in the form of a hydroxylated metabolite.

Indications

treatment of asthma in patients, which shows the combination therapy β2-adrenoceptor agonists and long-acting inhaled corticosteroids:

- Patients with inadequate control of the disease against a background of continuing monotherapy with inhaled corticosteroids with occasional use of β2-adrenomimetic short-acting;

- Patients with adequate control of the disease during therapy with inhaled corticosteroids and β2-adrenoceptor agonists of long action;

- As a starting maintenance therapy in patients with persistent asthma (daily occurrence of symptoms, daily use of tools for the rapid relief of symptoms) in the presence of indications for corticosteroids to achieve control of the disease.

maintenance therapy in COPD patients with a value of forced expiratory volume (FEV1) <60% of predicted values (up to inhaled bronchodilator) and a history of repeated exacerbations in whose disease severe symptoms persist despite regular bronchodilator therapy.

Contraindications

Hypersensitivity to the drug;

age 18 years.

Precautions: pulmonary tuberculosis (acute and delayed), fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, hypokalemia, cardiovascular disease (including idiopathic hypertrophic subaortic stenosis, uncontrolled hypertension, QT prolongation on an electrocardiogram, coronary artery disease), arrhythmias (supraventricular tachycardia and arrhythmia, ventricular arrhythmia, atrial fibrillation), cataract, glaucoma, hypothyroidism, osteoporosis, pregnancy, lactation, allergic reactions to lactose and milk protein in history.

Pregnancy and breast-feeding

During pregnancy and Saltikasone®-native lactation (breastfeeding) may be given only if the expected benefit to the mother outweighs any possible risk to the fetus or child.

Side effects

Since drug- Saltikasone®-native contains salmeterol and fluticasone propionate, it is expected the development of adverse reactions specific to each component separately. Additional side effects associated with simultaneous use of the two components of the drug are not marked.

Determination of frequency: very common (≥1 / 10); often (1/100 to 1/10); infrequently (from 1/1000 to 1/100); rarely (from 1/1000 to 1/10000); very rare (<1/10000).

Infectious and parasitic diseases: often - candidiasis of the mucous membranes of the mouth and throat, pneumonia (patients with COPD).

Immune system: rarely - hypersensitivity reactions, such as rash, urticaria, pruritus, rash, dermatitis, angioedema, anaphylactic reaction, bronchospasm.

On the part of metabolism: rarely - hyperglycemia; very rarely - hypokalemia.

From endocrine system: rarely - hypercortisolism; very rarely - the symptoms of systemic effects of GCS (including hypofunction of the adrenal glands, Cushing's syndrome), decreased bone mineral density.

On the part of the central nervous system: very often - headache; infrequently - nausea, dizziness, agitation, anxiety, sleep disorders; rarely - behavioral disorders; very rarely - depression, taste disturbances.

From the CCC: rarely - palpitations, tachycardia, atrial fibrillation; rarely - arrhythmias, including ventricular arrhythmia, supraventricular tachycardia and extrasystoles; very rarely - angina, fluctuations in blood pressure, peripheral edema.

With the respiratory system: often - cough, hoarseness and / or dysphonia, which disappears after discontinuation of therapy or dose reduction; rare - irritation of the throat; rarely - bronchospasm, including paradoxical.

For the skin: rarely - bruising.

From the musculoskeletal system: often - tremor, muscle cramps, arthralgia; rarely - myalgia; rarely - a decrease in bone mineral density.

Other: rarely - cataracts; rarely - glaucoma.

To reduce the risk of candidiasis after inhalation Saltikasone®-native is recommended to rinse the mouth and throat with water.

Systemic action of inhaled corticosteroids can be observed while taking the drug at high doses for a prolonged time.

Interaction

Avoid the use of selective and nonselective .beta.-blockers except when it is really necessary and justified, because of the risk of bronchospasm.

Fluticasone propionate is extensively metabolized during the first passage through the liver under the influence of CYP3A4 isoenzyme. Because of this factor, as well as high systemic clearance, in applying fluticasone propionate by inhalation in the concentration in plasma - is low. This clinically significant interactions involving fluticasone propionate are unlikely.

With simultaneous application of known inhibitors of CYP3A4 and fluticasone propionate should be careful, because in these situations may increase the content of the latter in plasma.

Ritonavir (highly active inhibitor of isozyme CYP3A4) can cause a significant increase in the concentration of fluticasone propionate in the plasma, thereby substantially decreasing the concentration of serum cortisol. There have been reports of clinically significant drug interactions in patients who are concurrently receiving fluticasone propionate and ritonavir, which manifested the development of Cushing's syndrome and adrenal suppression. With this in mind, avoid simultaneous use of fluticasone propionate and ritonavir, unless the potential benefit of combination therapy to the patient outweighs the risk of systemic side effects of corticosteroids.

Other inhibitors of CYP3A4 produce negligible (erythromycin) and minor (ketoconazole) increased content of fluticasone propionate in plasma, in which almost no decrease in serum cortisol concentrations. Despite this, it is advisable to be careful while applying fluticasone propionate and potent inhibitors of CYP3A4 (e.g. ketoconazole), since under such combinations do not exclude the probability of increasing the concentration of fluticasone propionate in plasma, which could potentially increase the systemic effects of fluticasone propionate.

When studying drug interactions was found that the use as a concomitant systemic therapy enhances the effect of ketoconazole salmeterol. This can lead to a lengthening of QT interval.

Caution must be exercised with concomitant use of strong inhibitors SYR3A4 (such as ketoconazole) and salmeterol.

Xanthine derivatives, corticosteroids and diuretics increase the risk of hypokalemia (especially in patients with acute exacerbation of bronchial asthma, during hypoxia) while their application to drug Saltikazon®-native.

MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the CAS while the use of drug- Saltikasone®-native

Saltikasone®-native compatible with kromoglitsievoy acid.

Dosing and Administration

Inhalation.

For optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of asthma and COPD.

The course of treatment and the dose change is appointed the doctor individually.

Should be prescribed to the patient in a dosage form that contains a dose of fluticasone propionate corresponding disease severity.

Bronchial asthma. If the patient does not receive appropriate therapy, taking only the inhaled corticosteroids, their replacement by drug Saltikasone®-native dose of a therapeutically equivalent dose administered corticosteroids may improve the control of asthma. In patients who have asthma can be controlled for exclusively using inhaled corticosteroids and their replacement by drug Saltikasone®-native can afford to reduce the dose of corticosteroids needed to control of asthma.

Adults (18 years and older). 1 inhalation (50 micrograms salmeterol and 100 micrograms fluticasone propionate), 2 times a day, or 1 inhalation (50 micrograms salmeterol and 250 micrograms fluticasone propionate), 2 times a day, or 1 inhalation (50 micrograms salmeterol and 500 micrograms fluticasone propionate), 2 times a day .

In adults over 18 years by doubling the dose-native Saltikazon® retained the same safety and tolerability as with regular use of this combination 2 times a day. The dose may be doubled in cases where patients need additional short-term (up to 14 days) inhaled corticosteroid therapy, as described in the guidelines for the treatment of bronchial asthma.

There is currently no data on the use Saltikasone®-native drug in patients under the age of 18 years.

Dose Saltikasone®-native should be reduced to the lowest dose that provides effective control of symptoms.

If symptoms control provides the drug Saltikasone®-native -2 times a day, a dose reduction to the minimum effective may include a single dose of the drug per day.

COPD. The maximum recommended dose for adults is: one inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose Saltikasone®-native in elderly patients and in patients with impaired renal or hepatic function.

Instructions for inhalation

Powder Inhaler "Inhaler CDM®» -. White plastic device with a movable upper part and with a retractable compartment for capsules, a height of about 6 cm in order to ensure a correct use of the drug, it should be used only with the "Inhalera CDM®».

The capsules are intended for inhalation use and are not intended to be swallowed. Acheikova removed from the capsule packaging should immediately before use.

Instructions for use of the inhaler "Inhaler CDM®»

"Inhaler CDM®» - is a single-dose inhaler that allows to dose and inhale the drug in very small doses. Saltikasone®-native enters the respiratory tract of the patient, together with the air flow when the active inhalation through the mouthpiece.

"Inhaler CDM®» is very easy to use. Follow step by step instructions below:

Step 2. Firmly hold the device with one hand, index finger and thumb of the other hand to open the capsule compartment, as shown in Fig. 2. To do this, press the index finger on PUSH in the mobile part of the "Inhalera CDM®», shifting it to the opposite side.

Step 3: Hold the device with one hand, insert the capsule in preparation to cover the socket. Ensure that the capsule is properly inserted into the slot.

Step 4: Hold down the "Inhaler CDM®» in an upright position, close the compartment by pressing the thumb in the opposite direction until it stops, until a click is heard.

Step 5: Hold the device "Inhaler CDM®» vertically, to bring it into working condition. To do this, press firmly on the mouthpiece so that the arrow stamped on the body disappeared behind the bottom of the device to the upper border line. Then let go of the mouthpiece to return it to its original position. This will punctured the capsule, opening access to the drug in the lumen of the mouthpiece.

Step 6. Note: prior to inhalation should exhale. Do not breathe out through the mouthpiece!

Step 7. Gently squeeze the mouthpiece "Inhalera CDM®» teeth, pursed lips and inhale deeply and strongly through the mouth. vibrating sound inside the capsule compartment is heard, published by the capsule in rotation and dispersion of the drug. The mouthpiece should not be chewed and heavily compress your teeth!

Step 8. After opening of the inhalation chamber for a capsule to remove a capsule blank, and then close it.

Warning: during inhalation should not close the holes located on the sides of the mouthpiece. This may hinder the free movement of air within the inhaler, thereby reducing dispersion of the capsule contents.

Do not press on the mouthpiece inhalation. It can block the movement of the capsule. Hold your breath for about 10 seconds or longer, as much as possible. Remove the inhaler from the mouth. Make a slow exhalation. Then breathe normally. Repeat steps 5-7 again to guarantee the inhalation dose.

Always close the container tightly after use "Inhaler CDM®» cap, it will keep the mouthpiece clean.

Regularly (once a week) Clean the outside of the mouthpiece with a dry cloth.

Overdose

symptoms

Salmeterol. The objective and subjective symptoms of salmeterol overdose are tremor, headache, tachycardia, increased Sad and hypokalemia.

Treatment: antidotes are cardioselective β-blockers. In cases where it is necessary to stop the drug Saltikazon®-native due to an overdose of being a part of salmeterol, the patient should be assigned to the appropriate replacement adrenoagonists.

Fluticasone propionate. Inhalation of fluticasone propionate doses exceeding recommended may cause temporary suppression of the hypothalamic-pituitary-adrenal system. it does not usually require the adoption of any emergency measures, since in most cases normal adrenal function is recovered in a few days.

Saltikasone®-native. Prolonged inhalation of excessive doses of the drug Saltikazon®-native may be significant adrenal suppression.

Patients should know that should not be used Saltikasone®-native drug in doses exceeding recommended.

Important is regular evaluation of the effectiveness of therapy and dose reduction Saltikasone®-native to the minimum effective drug, ie, so, which provides effective control of symptoms. In chronic overdose recommended control reserve of adrenocortical function.

special instructions

Saltikazon®-native is not suitable for cupping. In the case of seizures, patients should use an inhaled short-acting bronchodilator (eg salbutamol), which patients are advised to always have with you.

In the case of paradoxical bronchospasm should immediately apply inhaled short-acting bronchodilator, cancel Saltikasone®-native and start, if indicated, alternative therapy.

Treatment of asthma is recommended gradually, controlling the patient's clinical response to treatment and lung function. The patient must be taught how to use the inhaler.

Saltikasone®-native can be used for the initial maintenance therapy in patients with persistent asthma (daily occurrence of symptoms or daily use of cupping) in the presence of indications for corticosteroids and determining their approximate dosage.

It is necessary to rinse your mouth with water after inhalation drug Saltikazon®-native, to reduce the severity and frequency of the deepening of the voice, and candidiasis. When candidiasis prescribe antifungal drugs for local use, continuing therapy with Saltikazon®-native.

More frequent use of short-acting bronchodilators to relieve symptoms indicates deterioration of disease control in such situations, the patient should seek medical advice.

Sudden and progressive deterioration in control of bronchospastic syndrome is a potentially life-threatening. In such situations, the physician control required. If applied dose Saltikazon®-native does not provide adequate control of the disease, you may need additional appointment of GCS. In the event that the aggravation caused by infection, the prescribed antibiotics.

If resuscitation or surgical procedures require a degree of adrenal insufficiency.

Some patients may have individual high sensitivity to inhaled corticosteroids. Any inhaled corticosteroids may cause systemic effects, especially with prolonged use at high doses; It should be noted, however, that the probability of occurrence of such symptoms are much lower than in the treatment of oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, cataract and glaucoma.

It should be particularly careful and regular monitoring of indicators of adrenocortical function when transferring patients taking corticosteroids by mouth, for the treatment of fluticasone propionate for inhalation, due to possible adrenal insufficiency. When transferring patients receiving systemic corticosteroids allergic reactions may occur on inhalation therapy (eg allergic rhinitis, eczema), which previously suppressed by systemic GCS. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and / or topical drugs (including corticosteroids for topical application).

Patients should carry a card indicating that they may need additional intake of corticosteroids at different stressful situations.

There are very rare reports of increased blood glucose levels. This should be remembered by assigning a combination of salmeterol and fluticasone propionate in patients with diabetes mellitus.

In the treatment of drug Saltikasone®-native patients with COPD should be aware of the increased incidence of pneumonia. Clinical signs develop pneumonia often resemble an exacerbation of the underlying disease.

release Form

The powder for inhalation dose, 50 micrograms + 100 micrograms, 50 micrograms + 250 micrograms, 50 micrograms + 500 micrograms. On 10 caps. in the polymer foil and strip cellular pack of film printed aluminum foil or aluminum laminate and aluminum foil printing.

3 or 6, the contour of cellular packages with the device is placed in a cardboard box for inhalation or without it.

Conditions of supply of pharmacies

On prescription.

Storage conditions

In a dry, dark place at a temperature no higher than 25 ° C.

Keep out of the reach of children.

The shelf life

2 years.

Do not use beyond the expiration date printed on the package.