SERETIDE MULTIDISK POWDER FOR INHALATION 50MKG/100MKG/DOSE

Dosage form

Powder for inhalation of white or almost white color; the inhaler is round, plastic, deep purple and light purple with a dose counter.

Composition

1 dose contains: salmeterol (in the form of xinafoate) 50 mcg, fluticasone propionate 100 mcg
Excipients: lactose monohydrate.

Packing

60 doses - foil strips (1) - Multidisk plastic inhalers (1).

Mechanism of action

Seretide Multidisk is a combination drug containing salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbations. Seretide may be an alternative for patients who simultaneously receive a β2-adrenoreceptor agonist and inhaled corticosteroids (from different inhalers).
Salmeterol is a selective long-acting β2-adrenoreceptor agonist (up to 12 hours), which has a long side chain that binds to the outer domain of the receptor.
The pharmacological properties of salmeterol provide protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours),than short-acting β2-adrenoreceptor agonists. The beginning of the development of the bronchodilator effect is observed within 10-20 minutes.
Salmeterol is a potent and long-acting inhibitor of mast cell mediators, such as histamine, leukotrienes and prostaglandin D2, from human lung tissue. Salmeterol inhibits the early and late phases of the response to inhaled allergens; the latter lasts more than 30 hours after the administration of a single dose, i.e. at the time when the bronchodilating effect is already absent. A single injection of salmeterol weakens the hyperreactivity of the bronchial tree. This suggests that in addition to the bronchodilator effect, salmeterol has an additional effect, the clinical significance of which has not been fully established. This mechanism of action differs from the anti-inflammatory effect of GCS.
In therapeutic doses, salmeterol does not affect the cardiovascular system.
Fluticasone propionate - GCS for local use, when administered by inhalation in recommended doses, has a pronounced anti-inflammatory and antiallergic effect in the lungs, which leads to a decrease in clinical symptoms and a decrease in the frequency of exacerbations of diseases accompanied by airway obstruction. Restores the patient's response to bronchodilators, allowing to reduce the frequency of their use. The action of fluticasone propionate, prescribed in recommended doses, is not accompanied by adverse reactions characteristic of systemic corticosteroids.
With prolonged use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal cortex hormones remains within the normal range in both adults and children. After the transfer of patients receiving other inhaled corticosteroids, the admission of fluticasone propionate daily secretion of adrenal cortex hormones gradually normalized, despite the previous and current periodic use of oral corticosteroids. This indicates restoration of adrenal function in the background of inhaled fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within the normal range, as evidenced by the normal increase in cortisol production in response to appropriate stimulation (it must be taken into account that the residual decrease in adrenal reserve caused by previous therapy may persist for a long time).
A study conducted among 318 adult patients with persistent bronchial asthma showed that when using a double dose of Seretide for 14 days (regardless of the dose of the components in the preparation), there is a slight increase in the frequency of adverse events associated with the action of beta-adrenomimetic (tremor - 1 patient [1%], 0 patients at the usual dose; rapid heartbeat - 6 patients [3%], 1 patient [<1%] at the usual dose; convulsions: 6 patients [3%],1 patient [<1%] with a normal dose), while the incidence of adverse events associated with the action of an inhaled corticosteroid remains at the same level (for example, oral candidiasis - 6 patients [6%], 16 patients [8%] at the usual dose; hoarseness - 2 patients [2%], 4 patients [2%] at the usual dose) compared with the usual treatment regimen (1 inhalation 2 times / day). Thus, a double dose of the drug can be used in cases where patients require an additional short (up to 14 days) course of corticosteroid therapy.

Indications and usage

The drug is intended for the treatment of bronchial asthma in patients who have been shown combination therapy with long-acting beta2-adrenomimetic and inhaled GCS
- In patients with insufficient disease control against the background of continuous monotherapy with inhaled GCS with occasional use of short-acting beta2-adrenergic mimic.
- In patients with adequate disease control during therapy with inhaled GCS and long-acting beta2-adrenergic mimic.
- As a starting maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms, daily use of funds for rapid relief of symptoms), if there are indications for GCS to achieve disease control.
- Maintenance therapy for COPD and a FEV1 value of <60% of the proper values ​​(before inhalation of a bronchodilator) and repeated exacerbations in history, in which the pronounced symptoms of the disease persist despite regular therapy with bronchodilators.

Contraindications

- Children's age up to 4 years.
- Hypersensitivity to the drug.
Precautions should be prescribed with: pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, uncontrolled hypertension, arrhythmia, lengthening QT interval on the ECG, ischemic heart disease, hypoxia various Genesis, cataract, glaucoma, hypothyroidism, osteoporosis, pregnancy, in the period of lactation.

Pregnancy and Breastfeeding

During pregnancy and lactation (breastfeeding) Seretide can be prescribed only if the intended benefit to the mother outweighs any possible risk to the fetus or child.

Dosage and administration

Seretide Multidisk is for inhalation only. To obtain the optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. The doctor sets the course of treatment and dose change individually. The patient should be prescribed Seretide Multidisk in the dosage form, which contains a dose of fluticasone propionate, corresponding to the severity of the disease. If a patient cannot achieve adequate disease control with inhaled corticosteroid monotherapy,switching to a combination therapy with salmeterol and fluticasone propionate in an equivalent dose of a corticosteroid can lead to improved control of asthma. Those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhalation therapy with a combination of salmeterol with fluticasone propionate may reduce the dose of corticosteroid without losing control of asthma.

Recommended doses for adults and children aged 12 and over - 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times / day, or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times / day, or 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times / day
In adults over 18 years old with a doubling of the dose against the background of the use of any form of release of Seretide Multidisk for 14 days, the same safety and tolerability is maintained as with the regular use of this combination in 1 inhalation 2 times / day. The dose can be doubled in cases where patients need additional short-term (up to 14 days) inhalation therapy of GCS, as described in some guidelines for the treatment of bronchial asthma.
Children aged 4 and over - 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times / day.
For adult COPD The maximum recommended dose is 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times / day.
Mode of application: Multidisk inhaler has an indicator that, after inhalation, shows the number of remaining doses.The numbers are in descending order from 60 to 0. The numbers from 5 to 0 are red in color, warning that there are only a few doses left in the inhaler. The appearance in the window of the figure 0 means that the inhaler is empty and is not suitable for further use.
Inhalation:
1. Open the inhaler: hold the case with one hand, placing the thumb of the other hand in a special recess; To open the inhaler, press your thumb all the way down until you hear a click.
2. Press the lever: hold the inhaler (with your right or left hand) with the mouthpiece towards your face; push the lever all the way away until you hear a click. Now the inhaler is ready to go. By pressing the lever the next cell with a powder for inhalation is opened; while the number of remaining doses decreases, which is indicated in the indicator window. Press the lever just before the inhalation, otherwise it will lead to a waste of the drug.
3. Inhale the dose of the drug: keep the inhaler at a distance from the mouth and take a deep breath without effort. Never exhale into the inhaler. Close the mouthpiece with your lips. Take a slow and deep breath through your mouth (not through your nose). Take the inhaler out of your mouth. Hold your breath for about 10 seconds or more as you can. Exhale slowly. Do not exhale into the inhaler.
4. Close the inhaler: place your thumb in a special groove and push it towards you, until it stops, until you hear a click. The lever automatically returns to its original position.
Cleaning the nebulizer: After applying the nebulizer, the mouthpiece is wiped with a dry cloth.

Sometimes hypersensitivity reactions have been reported, incl. manifested as skin reactions, angioedema (mainly edema of the face and oropharynx), respiratory disorders (shortness of breath and / or bronchospasm), and in very rare cases - Anaphylactic reactions . Anxiety, behavioral disorders (including hyperactivity and irritability, mainly in children), sleep disorders, and hyperglycemia were also very rarely observed.

Salmeterol
Since the cardiovascular system: palpitations, headache (as a rule, transient, decrease with the continuation of therapy salmeterol); in predisposed patients, cardiac arrhythmias are possible (including atrial fibrillation, supraventricular tachycardia, extrasystole).
From the digestive system: rarely - abdominal pain, nausea, vomiting; in some cases - a violation of taste, irritation of the mucous membranes of the oropharynx.
Allergic reactions: rarely - rash, angioedema, local edema.
Other: tremor, hypokalemia (as a rule, transient, decrease with the continuation of therapy salmeterol); rarely - arthralgia, nervousness; in some cases, painful muscle spasms; There are also very rare reports of hyperglycemia.

Fluticasone Propionate
On the part of the respiratory system: due to local exposure, hoarseness of the voice, candidiasis of the oral cavity and pharynx are possible.
Allergic reactions: skin manifestations, angioedema (mainly of the face and oropharynx), respiratory symptoms (shortness of breath and / or bronchospasm), anaphylactic reactions.
Systemic reactions: possible development of systemic reactions, including Cushing's syndrome, cushing-like symptoms, suppression of adrenal function, growth retardation in children and adolescents, decrease in bone mineral density, cataracts and glaucoma.
Anxiety, sleep disorders and behavioral disorders, including hyperactivity and irritability (mainly in children), hyperglycemia have been reported very rarely.

The combination of salmeterol and fluticasone propionate: with prolonged use in doses exceeding the recommended, possible significant inhibition of the function of the adrenal cortex; very rarely (mainly in children who received this combination in doses exceeding those recommended, for several months or years) - acute adrenal crisis (hypoglycemia, accompanied by impaired consciousness and / or seizures).

Seretide Multidisk is intended for long-term treatment of the disease, and not for the relief of seizures. To relieve seizures, patients should be prescribed inhaled short-acting bronchodilators (for example, salbutamol), which patients are advised to always carry with them.With the development of paradoxical bronchospasm, you should immediately apply a short-acting inhaled bronchodilator, cancel Seretid® Multidisk and begin, if indicated, alternative therapy. Treatment of bronchial asthma is recommended in stages, monitoring the patient's clinical response to treatment and lung function. The patient must be taught to use the inhaler correctly. The severity and frequency of coarsening of the voice and candidiasis can be reduced by rinsing the mouth with water after inhalation of Seretide Multidisk. When candidiasis is prescribed antifungal drugs for local use, continuing therapy with Seretide Multidisk.
In the elderly and patients with renal insufficiency or impaired liver function, dose reduction is not required. The drug can be used for initial maintenance therapy in patients with persistent bronchial asthma (the onset of symptoms or the daily use of remedies for the relief of seizures) when there are indications for GCS and in determining their approximate dosage. More frequent use of short-acting bronchodilators to relieve symptoms indicates a worsening of disease control, and in such situations the patient should consult a doctor. A sudden and progressive deterioration in the control of the bronchospastic syndrome represents a potential threat to life. In such situations, the need to control the doctor.If the applied dose of Seretide Multidisk does not provide adequate control of the disease, then an additional administration of GCS may be required, and if the exacerbation is caused by an infection, antibiotics are prescribed. Because of the danger of developing an exacerbation, the sudden discontinuation of Seretide Multidisk should be avoided, and the dose should be reduced gradually under the supervision of a physician. When using any inhaled corticosteroids, it is possible to develop systemic effects (suppression of adrenal function, growth retardation in children and adolescents, decrease in bone mineral density, cataracts and glaucoma), especially with long-term use in high doses, but the likelihood of such effects is much lower than with treatment of oral forms of corticosteroids. Given this, the dose of inhaled corticosteroids should be titrated to the minimum, which ensures the maintenance of effective control. In emergency and planned stressful situations, it is always necessary to remember about the possibility of suppressing the function of the adrenal glands and the emergence of the need to use GCS.
When resuscitation or surgical interventions are performed, determination of the degree of adrenal insufficiency is required. In some patients, individual sensitivity to GCS for inhalation may be noted. In connection with possible adrenal insufficiency, special care should be taken and the indicators of the function of the adrenal cortex should be regularly monitored when transferring patients taking GCS orally for fluticone propionate for inhalation.When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions can occur (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and / or topical preparations (including GCS for local use). The abolition of systemic corticosteroids against the background of inhaled fluticasone propionate should be carried out gradually. Patients should carry with them a card indicating that they may need additional intake of GCS in various stressful situations.
Use in pediatrics: It is recommended to control the growth dynamics of children who receive long-term therapy with inhaled GCS. Currently there are no data on the use of Seretide Multidisc in children under 4 years of age.
Control of laboratory parameters: in patients with exacerbation of asthma, hypoxia, it is necessary to control the concentration of potassium in the blood plasma. There are very rare reports of increased blood glucose levels, this should be remembered when prescribing a combination of salmeterol with fluticasone propionate for diabetic patients.

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided unless it is really necessary and justified.In diseases involving reversible airway obstruction, the use of both non-selective and cardio-selective beta-blockers should be avoided, unless it is really necessary and justified. When fluticasone propionate is used in the form of inhalations, its plasma concentration is low due to intensive metabolism during the "first pass" through the liver under the influence of the CYP3A4 isoenzyme and high systemic clearance. Because of this, a clinically significant interaction with fluticasone propionate is unlikely. Care must be taken with the simultaneous use of known inhibitors of CYP3A4 and fluticasone propionate, since in such situations it is possible to increase the content of the latter in plasma. Ritonavir (a highly active inhibitor of the isoenzyme CYP3A4) can cause a significant increase in the concentration of fluticasone propionate in the blood plasma, as a result of which serum cortisol concentrations are significantly reduced. There are reports of clinically significant drug interactions in patients who simultaneously received fluticasone propionate and ritonavir, which was manifested by the development of Itsenko-Cushing syndrome and adrenal suppression. With this in mind, the simultaneous use of fluticasone propionate and ritonavir should be avoided, except in cases where the potential benefit of combination therapy for a patient exceeds the risk of developing systemic side effects of GCS.Other inhibitors of the isoenzyme CYP3A4 cause a negligible (erythromycin) and a slight (ketoconazole) increase in the content of fluticasone propionate in the plasma, at which the concentration of serum cortisol remains practically unchanged. Despite this, caution is advised when using fluticasone propionate and strong CYP3A4 inhibitors (for example, ketoconazole) at the same time, since such combinations do not exclude the likelihood of increasing plasma concentration of fluticasone propionate. With simultaneous use of the drug Seretid® Multidisk, xanthine derivatives, GCS and diuretics increase the risk of hypokalemia (especially in patients with exacerbation of bronchial asthma, with hypoxia); MAO inhibitors and tricyclic antidepressants increase the risk of cardiovascular side effects. Seretide Multidisk is compatible with cromoglicic acid.

Symptoms: tremor, headache and tachycardia caused by the action of salmeterol; temporary suppression of the hypothalamic-pituitary-adrenal system, due to the action of fluticasone. With prolonged inhalation of the drug Seretide Multidisk in excessively high doses, a marked inhibition of adrenal function is possible. There are rare reports of an acute adrenal crisis that occurs predominantly in children who receive Seretide Multidisk in excessively high doses for a long time (several months or years). Acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and / or convulsions.The situations that can serve as trigger factors for acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate, which is part of Seretide Multidisk.
Treatment: symptoms caused by the action of salmeterol, should be stopped by the introduction of an antidote - a cardioselective beta-blocker. In those cases when it is necessary to discontinue Seretide Multidisk due to an overdose of salmeterol which is part of it, the patient should be given an appropriate replacement GCS. Symptoms caused by the action of fluticasone propionate, usually do not require emergency treatment, since in most cases the normal function of the adrenal glands is restored within a few days. In chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex. In order to avoid overdose, patients should not use Seretide Multidisk in doses higher than recommended. It is important to regularly evaluate the effectiveness of therapy and reduce the dose of Seretide Multidisk to the minimum level that provides effective control of the symptoms of the disease.

The drug should be stored out of reach of children at a temperature not exceeding 30 ° C.

2 years.

Seretide Multidisk