Seretide Multidisk, 1 piece, 50 mcg+250 mcg/dose, dosed powder for inhalation

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.

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.

Pharmacodynamics

The drugs Seretide® and Seretide® Multidisc are combination drugs 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. The drugs may be an alternative for patients who simultaneously receive a β2-adrenergic agonist and inhaled corticosteroids.

Salmeterol is a selective, long-acting (up to 12 hours) β2-adrenergic receptor agonist that 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-lasting bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists. The onset of the bronchodilator effect is within 10–20 minutes. Salmeterol is a strong and long-acting inhibitor of the release of mast cell mediators such as histamine, LT and PG 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 administration of 1 dose, i.e. at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to its bronchodilator activity, 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. At therapeutic doses, salmeterol has no effect on CCC.

Fluticasone propionate belongs to the group of corticosteroids for topical use and, when inhaled 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 effect of fluticasone propionate is not accompanied by adverse reactions characteristic of systemic corticosteroids.

With long-term use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal hormones remains within normal limits in both adults and children. After switching patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually improves, despite previous and current intermittent use of oral steroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, 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® and Seretide® Multidisc for 14 days (regardless of the dose of the components in the drug), there was a slight increase in the incidence of adverse events associated with the action of β- adrenergic agonists (tremor - 1 patient (1%), 0 patients - at the usual dose; rapid heartbeat - 6 patients (6%), 1 patient (<1%) - at the usual dose; convulsions - 6 patients (6%), 1 patient (<1%) - at the usual dose), while the frequency of adverse events associated with the action of the 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 to the usual treatment regimen. 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.

Seretide Multidisc powder for inhalation dosage 50 µg + 250 µg/dose 60 doses

Registration Certificate Holder

GlaxoSmithKline Trading (Russia)

Dosage form

Medicine - Seretide® Multidisk

Description

Dosed powder for inhalation

white or almost white.

1 dose*

salmeterol xinafoate micronized 72.5 mcg, which corresponds to the content of salmeterol 50 mcg fluticasone propionate micronized** 250 mcg

Excipients

: lactose monohydrate - up to 12.5 mg.

28 doses - aluminum blisters (1) - plastic inhalers with dose counter (1) - cardboard packs. 60 doses - aluminum blisters (1) - plastic inhalers with dose counter (1) - cardboard packs.

* to compensate for production losses, a mixture of all substances can be placed in a blister with an excess of up to 6%. ** the indicated amounts for micronized fluticasone propionate imply 100% m/m activity (purity). The actual amount of micronized fluticasone propionate substance may be adjusted depending on the purity of the substance batch.

Indications

The drug is intended for the regular treatment of bronchial asthma if combination therapy with a long-acting beta2-agonist and an inhaled corticosteroid is indicated:

• patients with insufficient disease control on the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting beta2-adrenergic agonist;
• patients with adequate disease control during therapy with an inhaled corticosteroid and a long-acting beta2-agonist;
• as initial maintenance therapy in patients with persistent bronchial asthma if there are indications for prescribing GCS to achieve disease control.

The drug is intended for maintenance therapy in patients with COPD with an FEV1 value <60% of the normal value (before inhalation of a bronchodilator) and a history of repeated exacerbations, in whom severe symptoms of the disease persist despite regular bronchodilator therapy.

Contraindications for use

• hypersensitivity to the components of the drug;
• children under 4 years of age.

Carefully _

Like all other inhaled drugs containing corticosteroids, Seretide® Multidisc should be used with caution in patients with acute or latent pulmonary tuberculosis.

The drug Seretide® Multidisk should be prescribed with caution in case of thyrotoxicosis.

The drug Seretide® Multidisk should be used with caution in case of fungal, viral or bacterial infections of the respiratory system.

When taking any drugs from the sympathomimetic group, especially when therapeutic doses are exceeded, the development of cardiovascular phenomena such as an increase in systolic blood pressure and heart rate is possible. For this reason, the drug Seretide® Multidisk should be prescribed with caution to patients with cardiovascular diseases, incl. arrhythmias, such as supraventricular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation.

All sympathomimetic drugs in dosages exceeding therapeutic doses can cause a transient decrease in serum potassium levels. Therefore, Seretide® Multidisc should be administered with caution to patients with hypokalemia.

The drug Seretide® Multidisc should be used with caution in persons with a history of an allergic reaction to lactose and milk protein, because residual amounts of protein may be part of lactose.

Any inhaled GCS can cause systemic effects, especially with long-term use in high doses. Therefore, the drug should be used with caution in case of glaucoma, cataracts, osteoporosis (see section “Special instructions”).

There are very rare reports of increased blood glucose levels, so patients with diabetes should use Seretide® Multidisk with caution (see section "Side effects").

pharmachologic effect

The drug Seretide® Multidisc is a combination drug that contains salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of symptoms of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbation of the disease. Due to its more convenient dosing regimen, Seretide® Multidisk may be an alternative for patients who simultaneously receive a β2-adrenergic receptor agonist and inhaled corticosteroids from different inhalers.

Salmeterol

is a selective long-acting (up to 12 hours) β2-adrenergic receptor agonist, which has a long side chain that binds to the outer domain of the receptor.

The pharmacological properties of salmeterol provide more effective protection against histamine-induced bronchoconstriction and longer-lasting bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists.

In vitro studies have shown that salmeterol is a potent inhibitor of the release of mast cell mediators such as histamine, leukotrienes and prostaglandin D2 from the human lung, and has a long period of action.

Salmeterol inhibits the early and late phases of the response to inhaled allergens.
Inhibition of the late phase response persists for more than 30 hours after taking a single dose, at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to bronchodilator activity, has an additional effect not associated with bronchial dilation, the clinical significance of which has not been fully established. This mechanism of action differs from the anti-inflammatory effect of GCS. Fluticasone propionate
belongs to the group of corticosteroids for topical use and, 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 bronchial asthma. Fluticasone propionate does not cause the adverse effects that are observed with systemic administration of corticosteroids.

With long-term use of inhaled fluticasone propionate, the daily secretion of adrenal hormones remains within normal limits in both adults and children, even when using the maximum recommended doses. After switching patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually improves, despite previous and current intermittent use of oral steroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, 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).

Drug interactions

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, unless they are absolutely necessary for the patient.

In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive first-pass metabolism and high systemic clearance under the influence of the CYP3A4 isoenzyme of the cytochrome P450 system in the intestine and liver. This makes a clinically significant interaction involving fluticasone propionate unlikely.

A drug interaction study showed that ritonavir, a highly active inhibitor of the CYP3A4 isoenzyme, can cause a sharp increase in plasma fluticasone propionate concentrations, resulting in a significant decrease in serum cortisol concentrations.

During post-marketing surveillance, there were reports of clinically significant drug interactions in patients who simultaneously received fluticasone propionate (intranasal or inhaled) and ritonavir. This interaction has caused side effects such as Cushing's syndrome and adrenal suppression. Considering the above, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS.

Studies have shown that other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in plasma fluticasone propionate, with virtually no decrease in serum cortisol concentrations. Despite this, caution is recommended during concomitant use of fluticasone propionate and strong CYP3A4 inhibitors (e.g., ketoconazole), as such combinations may increase plasma concentrations of fluticasone propionate, which could potentially increase the systemic effects of fluticasone propionate.

When studying drug interactions, it was found that the use of ketoconazole as concomitant systemic therapy significantly increases the concentration of salmeterol in the blood plasma (increase in Cmax by 1.4 times and AUC by 15 times). This may lead to prolongation of the QTc interval. Caution should be exercised when co-administering strong CYP3A4 inhibitors (eg, ketoconazole) and salmeterol.

Xanthine derivatives, corticosteroids and diuretics increase the risk of developing hypokalemia (especially in patients with exacerbation of bronchial asthma, during hypoxia). MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the cardiovascular system.

The drug Seretide® Multidisk is compatible with cromoglycic acid.

Dosage regimen

Seretide® Multidisc is intended for inhalation only.

The patient should be informed that to obtain optimal effect the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD.

The physician 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.

Bronchial asthma

The dose of Seretide® Multidisk should be reduced to the lowest dose that provides effective control of symptoms.

If taking Seretide® Multidisk 2 times a day provides control over symptoms, as part of reducing the dose to the minimum effective, it is possible to reduce the frequency of taking the drug to 1 time a day.

The patient should be prescribed a form of Seretide® Multidisk that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If therapy with inhaled corticosteroids does not provide adequate control of the disease, then replacing them with Seretide® Multidisk at a dose therapeutically equivalent to the dose of administered corticosteroids may improve control of bronchial asthma. In patients in whom the course of bronchial asthma can be controlled exclusively with the help of inhaled corticosteroids, replacing them with the drug Seretide® Multidisc may allow reducing the dose of corticosteroids required to control the course of asthma.

Recommended Doses

Adults and children 12 years and older:

one inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times/day, or one inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times/day, or one inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times /day

Children 4 years and older:

one inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® Multidisc in children under 4 years of age

.

Chronic obstructive pulmonary disease (COPD)

For adult patients

the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day. A reduction in all-cause mortality has been demonstrated for this dosage of Seretide® Multidisc.

Special patient groups

There is no need to reduce the dose of Seretide® Multidisk in elderly patients, as well as in patients with impaired renal or hepatic function.

Instructions for use of the Multidisk inhaler

When you remove Seretide® Multidisc from the box, it is in the closed position.

Seretide® Multidisk contains 28 or 60 doses in powder form. Each dose is measured and protected hygienically. Neither maintenance of the dose level nor additional filling is required.

The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0 or 28 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

To carry out inhalation, follow five sequential steps:

1. open the inhaler;

2. press the lever;

3. inhale the dose of the drug;

4. close the inhaler;

5. Rinse your mouth.

How does the inhaler work?

When you turn the inhaler lever, a small hole in the mouthpiece opens, one dose is already ready for inhalation. When closing the inhaler, the lever automatically returns to its original position, thus remaining ready for the next required dose. The packaging protects the inhaler when not in use.

1. Open the inhaler. Hold the body with one hand, placing the thumb of the other hand in the special recess. To open the inhaler, push your thumb all the way down until you hear a click.

2. Press the lever. Hold the inhaler with the mouthpiece towards your face. The inhaler can be held with your right or left hand. Push the lever away from you until it stops until you hear a click. The inhaler is now ready for use. When you press the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. Press the lever only before inhalation, otherwise it will lead to wastage of the drug.

3. Inhale the dose of the drug. Before inhaling the drug, read this section carefully.

• Hold the inhaler at some distance from your mouth and exhale deeply without force. Remember: never exhale into an inhaler!
• Cover the mouthpiece tightly with your lips. Take a steady, deep breath through your mouth (not your nose).
• Remove the inhaler from your mouth.
• Hold your breath for about 10 seconds or as long as you can.
• Exhale slowly.

4. Close the inhaler. To close the inhaler, place your thumb in the special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position. The inhaler is again ready for use.

5. Rinse your mouth. After using the inhaler, rinse your mouth with water and then spit it out.

Remember:

keep the inhaler dry. Keep it closed when not in use. You should never exhale into an inhaler. Turn the lever only when you are ready to take a dose. Do not exceed the prescribed dose. Keep the inhaler out of the reach of children.

Overdose

It is not recommended to prescribe the drug in doses exceeding those specified in the “Dosage regimen” section. It is important to regularly review the patient's dosage regimen and reduce the dose to the lowest recommended dose that provides effective symptom control.

Symptoms

Expected symptoms and signs of salmeterol overdose are typical of excessive beta2-adrenergic stimulation and include tremor, headache, tachycardia, increased systolic blood pressure and hypokalemia.

Acute overdose of fluticasone propionate by inhalation can provoke temporary suppression of the hypothalamic-pituitary-adrenal axis. This usually does not require any emergency measures, since normal adrenal function is restored within a few days.

When taking the drug at a dose 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 have been described, which occurred mainly in children who received doses of the drug higher than recommended for a long time (several months or years). Acute adrenal crisis is characterized by hypoglycemia, accompanied by confusion and/or convulsions. Situations that may trigger an acute adrenal crisis include trauma, surgery, infection, or any rapid reduction in the dose of fluticasone propionate contained in Seretide® Multidisc. Treatment
There is no specific treatment for overdose of salmeterol and fluticasone propionate. In case of overdose, maintenance therapy should be carried out and the patient's condition should be monitored. In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

Side effect

All undesirable reactions presented below are characteristic of the active ingredients - salmeterol and fluticasone propionate separately. The profile of adverse reactions of the drug Seretide® Multidisc does not differ from the profile of adverse reactions of its active substances.

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and < 1/1000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on data from clinical trials of the drug and post-registration surveillance.

Clinical trial data

Frequency of occurrence of adverse reactions

Infectious and parasitic diseases:

often - candidiasis of the oral cavity and pharynx, pneumonia (in patients with COPD); rarely - esophageal candidiasis.

From the immune system:

hypersensitivity reactions: infrequently - skin hypersensitivity reactions, shortness of breath, rarely - anaphylactic reactions.

From the endocrine system:

possible systemic effects (see section "Special Instructions"): infrequently - cataracts, rarely - glaucoma.

Metabolism and nutrition:

uncommon - hyperglycemia; very rarely - hypokalemia.

Mental disorders:

infrequently - anxiety, sleep disturbances; rarely - changes in behavior, incl. hyperactivity and irritability (especially in children).

From the nervous system:

very often - headache (see section "Special instructions"); infrequently - tremor (see section "Special instructions").

From the heart:

infrequently - rapid heartbeat (see sections “With caution” and “Special instructions”), tachycardia, atrial fibrillation; rarely - arrhythmia, including ventricular extrasystole, supraventricular tachycardia and extrasystole.

From the respiratory system, chest and mediastinal organs:

often - hoarseness and/or dysphonia; infrequently - pharyngeal irritation.

For the skin and subcutaneous tissues:

infrequently - bruising.

From the musculoskeletal system and connective tissue:

often - muscle spasms, arthralgia.

Post-registration observation data

Frequency of occurrence of adverse reactions

From the immune system:

hypersensitivity reactions: rarely - angioedema (mainly swelling of the face and oropharynx), bronchospasm.
From the endocrine system:
possible systemic effects (see section "Special Instructions") rarely - Cushing's syndrome, Cushingoid symptoms, suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density.

From the respiratory system, chest and mediastinal organs:

rarely - paradoxical bronchospasm (see section "Special instructions").

special instructions

Seretide® Multidisk is not intended for the relief of acute symptoms, since in such cases a rapid and short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be advised to always have 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 drugs to relieve attacks) if there are indications for the use of corticosteroids and their approximate dosage has been determined.

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

A sudden and increasing deterioration in asthma control is potentially life-threatening, and in such situations the patient should also consult a doctor. The physician should consider prescribing a higher dose of GCS. If the dose of Seretide® Multidisk used does not provide adequate control of the disease, the patient should also consult a doctor.

Patients with asthma should not abruptly stop treatment with Seretide® Multidisk due to the risk of exacerbation; the dose of the drug should be reduced gradually under the supervision of a physician.

In patients with COPD, drug withdrawal may be accompanied by symptoms of decompensation and requires medical supervision.

Clinical studies have provided evidence of an increased incidence of pneumonia in patients with COPD receiving Seretide® Multidisk (see section “Side Effects”). Clinicians should be aware of the possibility of developing pneumonia in COPD, since the clinical presentation of pneumonia and exacerbation of COPD are often similar.

Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; it should be noted, however, that the likelihood of such symptoms occurring is much lower than during treatment with oral corticosteroids (see section “Overdose”). Possible systemic effects include Cushing's syndrome, Cushingoid 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 control of symptoms.

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

When carrying out 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 possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function regularly monitored. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids, may occur. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs, incl. GCS for local use.

After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special patient card containing an indication of the possible need for additional administration of corticosteroids in stressful situations.

In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to control the concentration of K+ ions in the plasma.

There are very rare reports of increased blood glucose levels, and this should be kept in mind when prescribing a combination of salmeterol and fluticasone propionate to patients with diabetes mellitus (see section "Side effects").

During the post-marketing period, there have been reports of clinically significant drug interactions between fluticasone propionate and ritonavir, leading to systemic effects of GCS, including Cushing's syndrome and adrenal suppression. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, unless the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS (see section “Drug Interactions”).

Data from a clinical study of the safety of salmeterol added to the treatment of bronchial asthma compared with placebo showed that the incidence of deaths due to bronchial asthma was higher in the salmeterol group. When taking salmeterol compared with placebo, the risk of serious respiratory adverse reactions or death in African-American patients appears to be greater than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effects associated with the use of GCS were not studied in this study.

Like other inhaled drugs, Seretide® Multidisk can cause paradoxical bronchospasm, manifested by an increase in shortness of breath immediately after use. In this case, you should immediately use a short-acting inhaled bronchodilator, discontinue Seretide® Multidisk and, if necessary, begin alternative therapy.

There are reports of side effects associated with the pharmacological action of beta2-antagonists, such as tremor, subjective palpitations and headache.
However, these phenomena are short-term in nature, and their severity decreases with regular therapy. Effect on the ability to drive vehicles and operate machinery.
Clinical studies have not provided data on the effect of the drug on the ability to drive vehicles and operate machinery; however, side effects that the drug may cause should be taken into account.

Storage conditions

The drug should be stored out of the reach of children at a temperature below 30°C.

Best before date

Shelf life: 2 years.

Do not use after the expiration date stated on the package.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Fertility

There are no data on the effect on fertility in humans. In animal studies, there was no effect of fluticasone propionate or salmeterol xinafoate on male or female fertility.

Pregnancy

Data on the use of the drug in pregnant women are limited. Use during pregnancy is permissible only if the potential benefit to the mother outweighs the possible risk to the fetus.

A retrospective study found no increased risk of major congenital malformations (SCDCs) following exposure to fluticasone propionate during the first trimester of pregnancy compared with other inhaled corticosteroids.

When conducting reproductive toxicity studies in animals with the administration of each component of the drug separately or in combination, the effect on the fetus of excessive systemic concentrations of the active beta2-adrenergic agonist and GCS was revealed.

Extensive experience in the clinical use of drugs of this class indicates that when using therapeutic doses, the described effects are not clinically significant.

Breastfeeding period

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 equally low. This is confirmed by studies on animals, in whose milk low concentrations of the drug were determined. There are no related data regarding women's breast milk.

The use of the drug during breastfeeding is permissible only if the potential benefit to the mother outweighs the possible risk to the child.

Use for renal impairment

Restrictions for impaired renal function - No restrictions.

In patients with impaired renal function

no dose reduction is required.

Use for liver dysfunction

Restrictions for liver dysfunction - No restrictions. In patients with liver dysfunction

no dose reduction is required.

Use in elderly patients

Restrictions for elderly patients - No restrictions.

There is no need to reduce the dose of the drug in elderly patients.

Use in children

Restrictions for children - With caution.

It is recommended to monitor the growth dynamics of children who receive long-term therapy with inhaled GCS.

The use of the drug is contraindicated in children under 4 years of age.

Terms of sale

The drug is available with a prescription.

RU/SFC/0039/16 12/23/2016

Contacts for inquiries

GlaxoSmithKline Trading JSC (Russia)

125167 Moscow Leningradsky Prospekt, 37a, bldg. 4 BC "Arcus III" Tel. Fax

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.

Seretide Multidisc por d/inhal 50mcg+500mcg 60 doses (Glaxo)

Seretide Multidisk has anti-asthmatic, bronchodilating, anti-inflammatory effects. Pharmacodynamics The drug Seretide Multidisc 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. The drugs may be an alternative for patients who simultaneously receive a β2-adrenergic receptor agonist and inhaled corticosteroids. Salmeterol is a selective long-acting (up to 12 hours) β2-adrenergic receptor agonist, 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-adrenergic agonists. The onset of the bronchodilator effect is within 10–20 minutes. Salmeterol is a strong and long-acting inhibitor of the release of mast cell mediators such as histamine, LT and PG 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 administration of 1 dose, i.e. at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to its bronchodilator activity, 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 has no effect on CCC. Fluticasone propionate belongs to the group of corticosteroids for topical use and, when inhaled 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 respiratory obstruction ways. Restores the patient's response to bronchodilators, allowing to reduce the frequency of their use. The effect of fluticasone propionate is not accompanied by adverse reactions characteristic of systemic corticosteroids. With long-term use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal hormones remains within normal limits in both adults and children. After switching patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually improves, despite previous and current intermittent use of oral steroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, 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). Study , conducted among 318 adult patients with persistent bronchial asthma, showed that when using a double dose of Seretide and Seretide Multidisk for 14 days (regardless of the dose of the components in the drug), there is a slight increase in the frequency of adverse events associated with the action of β-adrenomimetic (tremor - 1 patient (1%), 0 patients - at the usual dose; palpitations - 6 patients (6%), 1 patient (Pharmacokinetics When administered together by inhalation, salmeterol and fluticasone propionate do not affect the pharmacokinetics of each other, therefore the pharmacokinetic characteristics of each component of the drugs Seretide Multidisk can be considered separately. Even despite the very low concentrations of salmeterol and fluticasone propionate in plasma, interactions with other substrates and inhibitors of the CYPZA4 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 steady-state 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 by metered dose inhalation aerosol, it is 5.3% from the nominal dose). In patients with bronchial asthma and COPD, lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs predominantly through the lungs, and is initially more rapid, 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. The renal clearance of unchanged fluticasone propionate is negligible (Excreted through the gastrointestinal tract, mainly in the form of a hydroxylated metabolite.

Indications of the drug Seretide® Multidisc

treatment of bronchial asthma in patients who are indicated for combination therapy with a long-acting β2-adrenergic agonist and an inhaled corticosteroid:

- in patients with insufficient disease control on the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting β2-adrenergic agonist;

- in patients with adequate disease control during therapy with an inhaled corticosteroid and a long-acting β2-adrenergic agonist;

- as initial maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms, daily use of drugs for rapid relief of symptoms) if there are indications for prescribing GCS to achieve disease control;

maintenance therapy for COPD in patients with a forced inspiratory volume (FEV1) value <60% of the normal value (before bronchodilator inhalation) and a history of repeated exacerbations, in whom severe symptoms of the disease persist despite regular bronchodilator therapy.

Seretide Multidisc por d/ingal 50 mcg+250 mcg/dose 60 doses x1

SERETIDE® MULTIDISK Representative office: GlaxoSmithKline group of companies ATX code: R03AK06 Marketing authorization holder: GLAXO WELLCOME UK Limited, manufactured by GLAXO OPERATIONS UK, Limited salmeterol + fluticasone propionate

Release form, composition and packaging

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

1 dose salmeterol (as xinafoate) 50 mcg fluticasone propionate 100 mcg

Excipients: lactose monohydrate.

28 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs. 60 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs.

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

1 dose salmeterol (as xinafoate) 50 mcg fluticasone propionate 250 mcg

Excipients: lactose monohydrate.

28 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs. 60 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs.

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

1 dose salmeterol (as xinafoate) 50 mcg fluticasone propionate 500 mcg

Excipients: lactose monohydrate.

28 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs. 60 doses - foil strips (1) - plastic "Multidisk" inhalers (1) - cardboard packs.

Clinical and pharmacological group: Drug with anti-inflammatory and bronchodilator effects

Registration No.: •powder for inhalation. dosed 50 mcg+100 mcg/1 dose: inhalers 28 or 60 doses - P N011630/01, 06/10/10. Validity period of reg. beat is not limited. VED. •powder for inhalation. dosed 50 mcg+250 mcg/1 dose: inhalers 28 or 60 doses - P N011630/01, 06/10/10. Validity period of reg. beat is not limited. VED. •powder for inhalation. dosed 50 mcg+500 mcg/1 dose: inhalers 28 or 60 doses - P N011630/01, 06/10/10. Validity period of reg. beat is not limited. VED.

———————————————————————————

Pharmacological action | Pharmacokinetics | Indications | Dosage regimen | Side effect | Contraindications | Pregnancy and lactation | Special instructions | Overdose | Drug interactions | Terms of release from pharmacies | Storage conditions and expiration dates

--------------------------- Pharmachologic effect

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® Multidisk may be an alternative for patients who are simultaneously receiving a β2-adrenergic agonist and inhaled corticosteroids.

Salmeterol is a selective long-acting β2-adrenergic receptor agonist (up to 12 hours), having 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-lasting bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists. The onset of development of the bronchodilator effect is observed within 10-20 minutes.

Salmeterol is a strong and long-acting inhibitor of the release 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 lasting more than 30 hours after administration of one dose, i.e. at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates 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.

In therapeutic doses, salmeterol has no effect on the cardiovascular system.

Fluticasone propionate, a corticosteroid for topical use, when inhaled 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 effect of fluticasone propionate, prescribed in recommended doses, is not accompanied by adverse reactions characteristic of systemic corticosteroids.

With long-term use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal hormones remains within normal limits in both adults and children. After transferring patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually normalizes, despite previous and current periodic use of oral corticosteroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, 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 the drug for 14 days (regardless of the dose of the components in the drug), there was a slight increase in the frequency of adverse events associated with the action of beta-agonists (tremor - 1 patient [1%], 0 patients at usual dose, palpitations - 6 patients [3%], 1 patient [ Pharmacokinetics

Simultaneous inhalation administration of salmeterol and fluticasone propionate does not affect the pharmacokinetics of each of these substances.

Salmeterol

Salmeterol acts locally in the lung tissue, and therefore its plasma levels do not correlate with the therapeutic effect.

Data on the pharmacokinetics of salmeterol are limited, because It is technically difficult to determine very low plasma concentrations of the drug (Cmax 200 pg/ml or less) after inhalation administration in therapeutic doses. With regular use of inhaled salmeterol xinafoate, hydroxynaphthoic acid is determined in the blood, the Css value of which is about 10 pg/ml. These concentrations are 1000 times lower than equilibrium levels observed in toxicity studies.

Fluticasone propionate

Suction and distribution

After inhalation administration, the absolute bioavailability of fluticasone propionate in healthy people is 10-30%. In patients with bronchial asthma and chronic obstructive pulmonary disease (COPD), lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs primarily in the lungs, and is initially faster but then slows down.

Part of the inhaled dose may be swallowed, but the systemic effect is minimal due to the poor solubility of fluticasone propionate in water and intensive metabolism during the “first pass” through the liver. The bioavailability of fluticasone propionate when absorbed 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 Vd of fluticasone propionate at steady state is about 300 l.

Fluticasone propionate has a relatively high degree of binding to plasma proteins (91%).

Metabolism and excretion

Fluticasone propionate is rapidly eliminated from the blood, mainly as a result of metabolism with the participation of the CYP3A4 isoenzyme with the formation of an inactive carboxyl metabolite.

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

The final T1/2 is approximately 8 hours.

The renal clearance of unchanged fluticasone propionate is negligible (Excreted through the intestines primarily as a hydroxylated metabolite.

Indications for use of the drug SERETID® MULTIDISK

The drug is intended for the treatment of bronchial asthma in patients who are indicated for combination therapy with a long-acting beta2-adrenergic agonist and inhaled corticosteroids:

- in patients with insufficient control of the disease against the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting beta2-adrenergic agonist,

- in patients with adequate disease control during therapy with inhaled GCS and a long-acting beta2-adrenergic agonist,

- as initial maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms, daily use of drugs for rapid relief of symptoms) if there are indications for prescribing GCS to achieve disease control.

Maintenance therapy for COPD and FEV1 value

Dosage regimen

Seretide® Multidisc is intended 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 determines the course of treatment and dose changes individually.

The patient should be prescribed Seretide® Multidisk in a dosage form that contains a dose of fluticasone propionate appropriate to the severity of the disease.

If a patient fails to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent corticosteroid dose may result in improved asthma control. For those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhaled therapy with a combination of salmeterol and fluticasone propionate may allow a reduction in the dose of the corticosteroid without loss of control of bronchial asthma.

Recommended doses for adults and children aged 12 years and older - 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 or 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2

In adults over 18 years of age, doubling the dose while using any form of release of Seretide Multidisk for 14 days maintains the same safety and tolerability as with regular use of this combination of 1 inhalation 2. The dose can be doubled in cases where patients need additional short-term (up to 14 days) inhaled GCS therapy, as described in some guidelines for the treatment of bronchial asthma.

Children aged 4 years and older - 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2

For COPD in adults, the maximum recommended dose is 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2

Mode of application

The Multidisc inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

Carrying out inhalation

1. Open the inhaler: hold the body with one hand, placing the thumb of the other hand in the special recess, to open the inhaler, press the thumb away from you until you hear a click.

2. Press the lever: hold the inhaler (with your right or left hand) with the mouthpiece towards your face, press the lever away from you until it stops until you hear a click. The inhaler is now ready for use. When you press the lever, the next cell with powder for inhalation is opened, and the number of remaining doses decreases, which is indicated in the indicator window. Press the lever only before inhalation, otherwise it will lead to wastage of the drug.

3. Inhale the dose of the drug: hold the inhaler at some distance from your mouth and exhale deeply without force. You should never exhale into an inhaler. Cover the mouthpiece tightly with your lips. Take a slow, deep breath through your mouth (not your nose). Remove the inhaler from your mouth. Hold your breath for about 10 seconds or as long as you can. Exhale slowly. Do not exhale into the inhaler.

4. Close the inhaler: place your thumb in the special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position.

Cleaning the inhaler After using the inhaler, wipe the mouthpiece with a dry cloth.

Side effect

Since Seretide® Multidisk contains salmeterol and fluticasone propionate, it should be expected that it may cause side effects characteristic of these components. Their simultaneous use does not cause additional side effects.

Seretide® Multidisc may cause paradoxical bronchospasm.

In clinical studies of Seretide Multidisk, there were occasional reports of bruising, as well as increased incidence of pneumonia (in patients with COPD).

As part of post-marketing surveillance, the following data on adverse events were obtained.

Seretide® Multidisc

Sometimes hypersensitivity reactions have been reported, incl. manifested in the form of skin reactions, angioedema (mainly swelling of the face and oropharynx), respiratory disorders (shortness of breath and/or bronchospasm), and in very rare cases, anaphylactic reactions.

Also very rarely observed were anxiety, behavioral disorders (including hyperactivity and irritability, mainly in children), sleep disorders, and hyperglycemia.

Salmeterol

From the cardiovascular system: palpitations, headache (usually transient, decrease as therapy with salmeterol continues), 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 - disturbance of taste, irritation of the mucous membranes of the oropharynx.

Allergic reactions: rarely - rash, angioedema, local edema.

Other: tremor, hypokalemia (usually transient, decreasing as salmeterol therapy is continued), rarely - arthralgia, nervousness, in some cases - painful muscle spasms, there are also very rare reports of hyperglycemia.

Fluticasone propionate

From the respiratory system: due to local effects, 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: Systemic reactions may develop, including Cushing's syndrome, Cushingoid symptoms, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma.

Very rarely, anxiety, sleep disturbances and behavioral disorders, including hyperactivity and irritability (mainly in children), and hyperglycemia have been reported.

Combination of salmeterol and fluticasone propionate

With long-term use in doses exceeding the recommended ones, significant suppression of the function of the adrenal cortex is possible; very rarely (mainly in children who received this combination in doses exceeding the recommended ones for several months or years) - acute adrenal crisis (hypoglycemia, accompanied by impaired consciousness and /or convulsions).

Contraindications to the use of the drug SERETID® MULTIDISK

- children under 4 years of age,

- hypersensitivity to the components of the drug.

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.

Use of the drug SERETID® MULTIDISK during pregnancy and breastfeeding

During pregnancy and lactation (breastfeeding), Seretide® Multidisc can be prescribed only if the expected benefit of therapy for the mother outweighs any potential risk to the fetus or child.

Use for liver dysfunction

In patients with impaired liver function, no dose reduction is required.

Use for renal impairment

In patients with impaired renal function, no dose reduction is required

Use in children under 12 years of age

It is recommended to monitor the growth dynamics of children who receive long-term therapy with inhaled GCS.

There are currently no data on the use of Seretide Multidisc in children under 4 years of age.

special instructions

Seretide® Multidisk is intended for long-term treatment of the disease, and not for the relief of attacks. To relieve attacks, patients should be prescribed short-acting inhaled bronchodilators (for example, salbutamol), which patients are advised to always have with them.

If paradoxical bronchospasm develops, you should immediately use a short-acting inhaled bronchodilator, discontinue Seretide® Multidisk and begin, if indicated, alternative therapy.

Treatment of bronchial asthma is recommended to be carried out in stages, monitoring the patient's clinical response to treatment and lung function. The patient must be taught how to use the inhaler correctly.

The severity and frequency of deepening of the voice and candidiasis can be reduced by rinsing the mouth with water after inhalation of Seretide Multidisc. For candidiasis, antifungal drugs are prescribed for topical use, while therapy with Seretide Multidisk is continued.

In elderly people and patients with renal failure or impaired liver function, no dose reduction is required.

The drug can be used for initial maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms or daily use of drugs to relieve attacks) if there are indications for the use of corticosteroids and their approximate dosage has been determined.

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

Sudden and progressive deterioration in control of bronchospastic syndrome is potentially life-threatening. In such situations, medical supervision is necessary. If the dose of Seretide Multidisk used does not provide adequate control of the disease, then additional administration of GCS may be required, and if an exacerbation is caused by an infection, then antibiotics are prescribed.

Due to the risk of exacerbation, sudden discontinuation of Seretide Multidisk should be avoided; the dose of the drug should be reduced gradually under the supervision of a physician.

When using any inhaled corticosteroids, systemic effects may develop (suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma), especially with long-term use in high doses, but the likelihood of such effects occurring is much lower than with treatment with oral forms of GCS. Given this, the dose of inhaled corticosteroids should be titrated to the minimum that ensures the maintenance of effective control.

In emergency and planned stressful situations, it is always necessary to remember the possibility of suppression of adrenal function and the need to use GCS.

When carrying out resuscitation measures or surgical interventions, it is necessary to determine the degree of adrenal insufficiency.

Some patients may experience individual high sensitivity to inhaled corticosteroids.

Due to possible adrenal insufficiency, special caution should be exercised and regular monitoring of adrenal function indicators when transferring patients who have taken oral corticosteroids to treatment with inhaled fluticasone propionate. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids, may occur. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs (including corticosteroids for topical use).

Cancellation of systemic corticosteroids against the background of inhaled fluticasone propionate should be carried out gradually. Patients should carry a card with them indicating that they may need to take additional corticosteroids in various stressful situations.

Use in pediatrics

It is recommended to monitor the growth dynamics of children who receive long-term therapy with inhaled GCS.

There are currently no data on the use of Seretide Multidisc in children under 4 years of age.

Control of laboratory parameters

In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to monitor the concentration of potassium in the blood plasma.

There are very rare reports of increased blood glucose levels; this should be kept in mind when prescribing a combination of salmeterol with fluticasone propionate to patients with diabetes mellitus.

Overdose

Symptoms: tremor, headache and tachycardia caused by the action of salmeterol, temporary inhibition of the hypothalamic-pituitary-adrenal system, which is caused by the action of fluticasone.

With prolonged inhalation of the drug Seretide® Multidisk in excessively high doses, noticeable suppression of adrenal function is possible. There are rare reports of acute adrenal crisis, which occurs predominantly in children receiving Seretide® Multidisk in excessively high doses for a long time (several months or years). Acute adrenal crisis is characterized by hypoglycemia, accompanied by confusion and/or convulsions. Situations that may trigger an acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate contained in Seretide Multidisc.

Treatment: symptoms caused by the action of salmeterol should be relieved by administering an antidote - a cardioselective beta-blocker. In cases where it is necessary to discontinue Seretide Multidisk due to an overdose of salmeterol in its composition, the patient should be prescribed an appropriate replacement GCS.

Symptoms caused by the action of fluticasone propionate usually do not require emergency treatment, since in most cases normal adrenal function is restored within a few days.

In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

To avoid overdose, patients should not use Seretide® Multidisk in doses higher than recommended. It is important to regularly assess the effectiveness of therapy and reduce the dose of Seretide Multidisk to the minimum level that ensures effective control of the symptoms of the disease.

Drug interactions

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 accompanied by reversible airway obstruction, the use of both non-selective and cardioselective beta-blockers should be avoided, unless it is really necessary and justified.

When fluticasone propionate is used in the form of inhalations, its concentration in the blood plasma is low due to intensive metabolism during the “first pass” through the liver under the influence of the CYP3A4 isoenzyme and high systemic clearance. This makes a clinically significant interaction involving fluticasone propionate unlikely.

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.

Ritonavir (a highly active inhibitor of the CYP3A4 isoenzyme) 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 Cushing's syndrome and suppression of adrenal function. Given this, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit of combination therapy for the patient outweighs the risk of developing systemic side effects of GCS.

Other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in plasma fluticasone propionate levels, with virtually no decrease in serum cortisol concentrations. Despite this, caution is recommended when using fluticasone propionate concomitantly with strong CYP3A4 inhibitors (eg, ketoconazole), since such combinations may increase the plasma concentrations of fluticasone propionate.

When used simultaneously with the drug Seretide® Multidisk, xanthine derivatives, corticosteroids and diuretics increase the risk of developing hypokalemia (especially in patients with exacerbation of bronchial asthma, during hypoxia), MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the cardiovascular system.

Seretide® Multidisk is compatible with cromoglycic acid.

Conditions for dispensing from pharmacies The drug is dispensed with a prescription.

Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life: 18 months.

Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life: 18 months. Manufacturer: Glaxo Wellcome Operations UK Ltd, Great Britain Registration certificate holder: Glaxo Wellcome UK Limited, Great Britain Forms of release: powder for inhalation dosed 50 mcg + 0500 mcg / dose, Multidisk metering inhalers, powder for inhalation dosed 50 mcg + 100 mcg / dose dose, metering inhalers "Multidisk", powder for inhalation dosed 50 mcg+250 mcg/dose, metering inhalers "Multidisk", powder for inhalation dosed 50 mcg+500 mcg/dose, metering inhalers "Multidisk" Registration data: P N011630/ 01 from 06/10/2010 Registration certificate status: valid Pharmaceutical article number: ND 42-10479-05, ND 42-10479-99

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.

Side effects

Seretide® and Seretide® Multidisc contain salmeterol and fluticasone propionate, and therefore it is expected that the drugs may cause side effects characteristic of these components. There is no evidence that the simultaneous use of salmeterol and fluticasone propionate causes additional side effects.

May cause paradoxical bronchospasm. In this case, you should immediately use a short-acting inhaled bronchodilator, discontinue the drug, and begin alternative therapy if indicated.

Salmeterol: pharmacological side effects of the beta2-adrenergic agonist have been described, such as tremor, palpitations and headache, hypokalemia, which, as a rule, are transient and weaken as salmeterol therapy is continued.

In sensitive patients, arrhythmias (including atrial fibrillation, supraventricular tachycardia and premature beats) may occur.

Arthralgia, nervousness, abdominal pain, nausea, vomiting and hypersensitivity reactions including skin rash, peripheral edema and angioedema have been reported.

Cases of irritation of the mucous membranes of the oropharynx and changes in taste sensations (dysgeusia) have been described.

Case reports of painful muscle spasms and very rare cases of hyperglycemia have been published.

Fluticasone propionate: Some patients may experience a deepening or hoarseness of the voice and candidiasis (thrush) of the mouth and throat.

Skin hypersensitivity reactions have been described. Hypersensitivity reactions have also been reported, manifested as angioedema (mainly swelling of the face and oropharynx), respiratory disorders (mainly shortness of breath and/or bronchospasm) and anaphylactic reactions.

The severity and frequency of deepening of the voice and candidiasis can be reduced by rinsing the mouth with water after inhalation. Symptomatic candidiasis can be treated with topical antifungals while continuing therapy with Seretide® or Seretide® Multidisc.

Very rarely, anxiety, sleep disturbances and behavioral disorders, including hyperactivity and irritability, have been reported (mainly in children); hyperglycemia.

Systemic reactions are theoretically possible, including Cushing's syndrome or Cushingoid symptoms, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma.

With long-term use of doses of the combination of salmeterol with fluticasone propionate that exceed the permitted doses, significant depression of the function of the adrenal cortex is possible. There are very rare reports of acute adrenal crisis, which occurred primarily in children receiving higher than approved doses of this combination for a long time (several months or years); Symptoms of adrenal crisis included hypoglycemia accompanied by decreased level of consciousness and/or seizures.

Seretide Multidisc Powder, 60 d, 50+100 mcg+mcg, for inhalation

special instructions

Seretide Multidisk is not intended for the relief of acute symptoms, since in such cases a rapid and short-acting inhaled bronchodilator (eg salbutamol) should be used. Patients should be advised to always have 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 drugs to relieve attacks) if there are indications for the use of corticosteroids and their approximate dosage has been determined. More frequent use of short-acting bronchodilators to relieve symptoms indicates worsening disease control, and in such situations the patient should consult a doctor. A sudden and increasing deterioration in asthma control is potentially life-threatening, and in such situations the patient should also consult a doctor. The physician should consider prescribing a higher dose of GCS. If the dose of Seretide Multidisc used does not provide adequate control of the disease, the patient should also consult a doctor. Patients with asthma should not abruptly stop treatment with Seretide Multidisc due to the risk of exacerbation; the dose of the drug should be reduced gradually under the supervision of a physician. In patients with COPD, drug withdrawal may be accompanied by symptoms of decompensation and requires medical supervision. Clinical studies have provided evidence of an increase in the incidence of pneumonia in patients with COPD receiving Seretide Multidisk (see section Side effects). Clinicians should be aware of the possibility of developing pneumonia in COPD, since the clinical presentation of pneumonia and exacerbation of COPD are often similar. Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; it should be noted, however, that the likelihood of such symptoms occurring is much lower than with treatment with oral corticosteroids (see Overdose section). Possible systemic effects include Cushing's syndrome, Cushingoid 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 control of symptoms. In emergency and planned situations that can cause stress, it is always necessary to remember the possibility of adrenal suppression and be prepared to use GCS (see section Overdose). When carrying out 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 possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function regularly monitored. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids, may occur. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs, incl. GCS for local use. After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special patient card containing an indication of the possible need for additional administration of corticosteroids in stressful situations. In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to control the concentration of K+ ions in the plasma. There are very rare reports of increased blood glucose levels, and this should be kept in mind when prescribing a combination of salmeterol and fluticasone propionate to patients with diabetes mellitus (see section Side effects). During the post-marketing period, there have been reports of clinically significant drug interactions between fluticasone propionate and ritonavir, leading to systemic effects of GCS, including Cushing's syndrome and adrenal suppression. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, except in cases where the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS (see section Drug Interactions). Data from a clinical study of the safety of salmeterol added to the treatment of bronchial asthma compared with placebo showed that the incidence of deaths due to bronchial asthma was higher in the salmeterol group. When taking salmeterol compared with placebo, the risk of serious respiratory adverse reactions or death in African-American patients appears to be greater than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effects associated with the use of GCS were not studied in this study. Like other inhaled drugs, Seretide Multidisk can cause paradoxical bronchospasm, manifested by an increase in shortness of breath immediately after use. In this case, you should immediately use a short-acting inhaled bronchodilator, discontinue Seretide Multidisk and, if necessary, begin alternative therapy. There are reports of side effects associated with the pharmacological action of beta2-antagonists, such as tremor, subjective palpitations and headache. However, these phenomena are short-term in nature, and their severity decreases with regular therapy. Effect on the ability to drive vehicles and operate machinery In clinical studies, no data were obtained on the effect of the drug on the ability to drive vehicles and other mechanisms, however, side effects that the drug may cause should be taken into account.

Interaction

Due to the risk of developing bronchospasm, the simultaneous use of selective and non-selective beta-blockers should be avoided unless they are absolutely necessary for the patient.

In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive first-pass metabolism and high systemic clearance under the influence of the CYP3A4 isoenzyme of the cytochrome P450 system in the intestine and liver. This makes clinically significant interactions involving fluticasone propionate unlikely.

Drug interaction studies have shown that ritonavir (a highly active inhibitor of the CYP3A4 isoenzyme) can cause a sharp increase in plasma concentrations of fluticasone propionate, resulting in a significant decrease in serum cortisol concentrations.

There are reports of clinically significant drug interactions in patients who received fluticasone propionate and ritonavir concomitantly. These interactions have caused side effects such as Cushing's syndrome and adrenal suppression. Given the above, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS.

Other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in plasma fluticasone propionate levels, with virtually no decrease in serum cortisol concentrations. Despite this, caution is recommended when using fluticasone propionate concomitantly with strong CYP3A4 inhibitors (e.g. ketoconazole), since such combinations may increase the plasma concentrations of fluticasone propionate.

Xanthine derivatives, corticosteroids and diuretics increase the risk of developing hypokalemia (especially in patients with exacerbation of bronchial asthma, during hypoxia).

MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the cardiovascular system.

Compatible with cromoglycic acid.

Seretide multidisc (vial 50mcg+250mcg 60doses)

A country

France
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.

Active substance

Salmeterol + Fluticasone

Compound

Bottle 60 doses Salmeterol xinafoate micronized 72.5 mcg, fluticasone propionate micronized** 250 mcg per 1 dose*.* to compensate for production losses, a mixture of all substances can be placed in a blister with an excess of up to 6%.** the indicated quantities for micronized fluticasone propionate imply activity 100% m/m (purity). The actual amount of micronized fluticasone propionate substance can be adjusted depending on the purity of the batch of the substance. Excipients: lactose monohydrate - up to 12.5 mg. Dosed powder for inhalation, white or almost white.

pharmachologic effect

The drug Seretide® Multidisc is a combination drug that contains salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of symptoms of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbation of the disease. Due to its more convenient dosage regimen, Seretide® Multidisc may be an alternative for patients who simultaneously receive an β2-adrenergic receptor agonist and inhaled corticosteroids from different inhalers. Salmeterol is a selective long-acting (up to 12 hours) β2-adrenergic receptor agonist, which has a long side chain that binds to the outer domain of the receptor. The pharmacological properties of salmeterol provide more effective protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours) than short-acting β2-adrenergic receptor agonists. In vitro studies have shown that salmeterol is a potent inhibitor of the release of mast cell mediators from the human lung, such as histamine, leukotrienes and prostaglandin D2, and has a long period of action. Salmeterol inhibits the early and late phases of the response to inhalant allergens. Inhibition of the late phase response persists for more than 30 hours after taking a single dose, at a time when the bronchodilator effect is no longer present. A single administration of salmeterol weakens the hyperreactivity of the bronchial tree. This indicates that salmeterol, in addition to bronchodilator activity, has an additional effect not associated with bronchial dilation, the clinical significance of which has not been fully established. This mechanism of action differs from the anti-inflammatory effect of GCS. Fluticasone propionate belongs to the group of GCS for topical use and, when administered in 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 bronchial asthma. Fluticasone propionate does not cause the adverse effects that are observed with systemic administration of corticosteroids. With long-term use of inhaled fluticasone propionate, the daily secretion of adrenal hormones remains within normal limits in both adults and children, even when using the maximum recommended doses. After switching patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal hormones gradually improves, despite previous and current intermittent use of oral steroids. This indicates restoration of adrenal function with inhaled use of fluticasone propionate. With long-term use of fluticasone propionate, the reserve function of the adrenal cortex also remains within normal limits, 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).

Indications for use

The drug is intended for the regular treatment of bronchial asthma if combination therapy with a long-acting beta2-adrenergic agonist and an inhaled corticosteroid is indicated: - patients with insufficient disease control on the background of constant monotherapy with inhaled corticosteroids with periodic use of a short-acting beta2-adrenergic agonist; - patients with adequate disease control on the background therapy with an inhaled corticosteroid and a long-acting beta2-adrenergic agonist; - as initial maintenance therapy in patients with persistent bronchial asthma if there are indications for prescribing GCS to achieve disease control. The drug is intended for maintenance therapy in patients with COPD with an FEV1 value. Method of administration Seretide® Multidisk intended for inhalation only. The patient should be informed that to obtain an 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. Bronchial asthma The dose of Seretide® Multidisc should be reduced to the lowest dose that provides effective control of symptoms. If taking Seretide® Multidisk 2 times a day provides control of symptoms, as part of reducing the dose to the minimum effective, it is possible to reduce the frequency of taking the drug to 1 time/day. The patient should be prescribed a form of the drug Seretide® Multidisk, which contains a dose of fluticasone propionate corresponding to the severity of his disease. If therapy with inhaled corticosteroids does not provide adequate control of the disease, then replacing them with Seretide® Multidisk at a dose therapeutically equivalent to the dose of administered corticosteroids may improve control of bronchial asthma. In patients in whom the course of bronchial asthma can be controlled exclusively with the help of inhaled corticosteroids, their replacement with the drug Seretide® Multidisc may reduce the dose of corticosteroids required to control the course of asthma. Recommended doses Adults and children 12 years of age and older: one inhalation (50 mcg salmeterol and 100 mcg of fluticasone propionate) 2 times/day, or one inhalation (50 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times/day, or one inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times/day. Children 4 years old and older: one inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times a day. Currently there is no data on the use of Seretide® Multidisc in children under 4 years of age. Chronic obstructive pulmonary disease (COPD) For adult patients, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day. This dosage of Seretide® Multidisk has demonstrated a reduction in mortality from all causes. Special groups of patients There is no need to reduce the dose of Seretide® Multidisk in elderly patients, as well as in patients with impaired renal or hepatic function. Instructions for use of the Multidisk inhaler When you remove Seretide® Multidisk from the box, it is in the closed position. The drug Seretide® Multidisc contains 28 or 60 doses in powder form. Each dose is measured and protected hygienically. There is no need to maintain the dose level or fill it additionally. The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0 or 28 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use. To carry out inhalation, follow five sequential steps: 1. open the inhaler;2. press the lever;3. inhale the dose of the drug;4. close the inhaler;5. rinse your mouth. How the inhaler works When you turn the inhaler lever, a small hole in the mouthpiece opens, one dose is ready for inhalation. When closing the inhaler, the lever automatically returns to its original position, thus remaining ready for the next required dose. The packaging protects the inhaler when not in use.1. Open the inhaler. Hold the body with one hand, placing the thumb of the other hand in the special recess. To open the inhaler, push your thumb all the way down until you hear a click.2. Click on the lever. Hold the inhaler with the mouthpiece facing your face. The inhaler can be held with your right or left hand. Push the lever away from you until it stops until you hear a click. The inhaler is now ready for use. When you press the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. Press the lever only before inhalation, otherwise it will lead to wastage of the drug.3. Inhale the dose of the drug. Before inhaling the drug, read this section carefully. — Hold the inhaler at some distance from your mouth and exhale deeply without force. Remember: you should never exhale into the inhaler!—Place your lips tightly around the mouthpiece. Inhale evenly and deeply through your mouth (not your nose).- Remove the inhaler from your mouth.- Hold your breath for about 10 seconds or as long as you can.- Exhale slowly.4. Close the inhaler. To close the inhaler, place your thumb in the special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position. The inhaler is again ready for use. 5. Rinse your mouth. After using the inhaler, rinse your mouth with water and then spit it out. Remember: keep the inhaler dry. Keep it closed when not in use. You should never exhale into an inhaler. Turn the lever only when you are ready to take a dose. Do not exceed the prescribed dose. Keep the inhaler out of the reach of children.

Interaction

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, unless they are absolutely necessary for the patient. In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive first-pass metabolism and high systemic clearance under the influence of the CYP3A4 isoenzyme of the cytochrome P450 system in the intestines and liver. This makes a clinically significant interaction involving fluticasone propionate unlikely. A drug interaction study showed that ritonavir, a highly active inhibitor of the CYP3A4 isoenzyme, can cause a sharp increase in plasma fluticasone propionate concentrations, resulting in a significant decrease in serum cortisol concentrations. During post-marketing surveillance, there were reports of clinically significant drug interactions in patients who simultaneously received fluticasone propionate (intranasal or inhaled) and ritonavir. This interaction has caused side effects such as Cushing's syndrome and adrenal suppression. Given the above, the simultaneous use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic side effects of GCS. Studies have shown that other inhibitors of the CYP3A4 isoenzyme cause a negligible (erythromycin) and insignificant (ketoconazole) increase in fluticasone levels propionate in plasma, at which the concentration of serum cortisol practically does not decrease. Despite this, caution is recommended during concomitant use of fluticasone propionate and strong CYP3A4 inhibitors (for example, ketoconazole), since such combinations may increase the plasma concentrations of fluticasone propionate, which could potentially increase the systemic effects of fluticasone propionate. When studying drug interactions It was found that the use of ketoconazole as concomitant systemic therapy significantly increases the concentration of salmeterol in the blood plasma (increase in Cmax by 1.4 times and AUC by 15 times). This may lead to prolongation of the QTc interval. Caution should be exercised when co-prescribing strong CYP3A4 inhibitors (for example, ketoconazole) and salmeterol. Xanthine derivatives, corticosteroids 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 side effects from the cardiovascular system. The drug Seretide® Multidisk is compatible with cromoglycic acid.

Side effect

All undesirable reactions presented below are characteristic of the active ingredients - salmeterol and fluticasone propionate separately. The profile of adverse reactions of the drug Seretide® Multidisc does not differ from the profile of adverse reactions of its active substances. The adverse reactions presented below are listed in accordance with the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is determined as follows: very often (? 1/10), often (? 1/100 and Contraindications - hypersensitivity to the components of the drug; - children under 4 years of age. With caution, like all other inhaled drugs containing corticosteroids, the drug Seretide ® Multidisc should be used with caution in patients with acute or latent pulmonary tuberculosis. The drug Seretide® Multidisk should be prescribed with caution in case of thyrotoxicosis. The drug Seretide® Multidisc should be used with caution in case of fungal, viral or bacterial infections of the respiratory system. When taking any drugs of the sympathomimetic group , especially when therapeutic doses are exceeded, the development of such cardiovascular phenomena as an increase in systolic blood pressure and heart rate is possible. For this reason, the drug Seretide® Multidisk should be prescribed with caution to patients with cardiovascular diseases, including arrhythmias, such as supraventricular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation. All sympathomimetic drugs in dosages exceeding therapeutic ones can cause a transient decrease in the level of potassium in the blood serum. Therefore, the drug Seretide® Multidisk should be prescribed with caution to patients with hypokalemia. The drug Seretide® Multidisk should be used with caution in persons with a history of an allergic reaction to lactose and milk protein, because residual amounts of protein may be part of lactose. Any inhaled GCS can cause systemic effects, especially with long-term use in high doses. Therefore, the drug should be used with caution in case of glaucoma, cataracts, osteoporosis (see section “Special instructions”). There are very rare reports of increased blood glucose levels, so patients with diabetes should use the drug Seretide® Multidisc with caution (see section “ Side effects. Use during pregnancy and lactation Fertility There are no data on the effect on fertility in humans. In animal studies, there was no effect of fluticasone propionate or salmeterol xinafoate on male or female fertility. Pregnancy Data on the use of the drug in pregnant women are limited. Use during pregnancy is permissible only if the potential benefit to the mother outweighs the possible risk to the fetus. According to the results of a retrospective study, there was no increased risk of serious congenital malformations (SCDM) after exposure to fluticasone propionate during the first trimester of pregnancy compared to other trimesters inhaled corticosteroids. When conducting reproductive toxicity studies in animals with the administration of each component of the drug individually or in combination, the effect on the fetus of excessive systemic concentrations of the active beta2-adrenergic agonist and corticosteroids was revealed. Extensive experience in the clinical use of drugs of this class indicates that when Using therapeutic doses, the described effects are not clinically significant. Breastfeeding period 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 equally low. This is confirmed by studies on animals, in whose milk low concentrations of the drug were determined. There are no related data regarding women's breast milk. The use of the drug during breastfeeding is permissible only if the potential benefit to the mother outweighs the possible risk to the child.

Overdose

It is not recommended to prescribe the drug in doses exceeding those specified in the “Dosage regimen” section. It is important to regularly review the patient's dosing regimen and reduce the dose to the lowest recommended dose that provides effective symptom control. Symptoms Expected symptoms and signs of salmeterol overdose are typical of excessive beta2-adrenergic stimulation and include tremor, headache, tachycardia, increased systolic blood pressure, and hypokalemia. Acute overdose of fluticasone propionate by inhalation can provoke temporary suppression of the hypothalamic-pituitary-adrenal axis. This usually does not require any emergency measures, since normal adrenal function is restored within a few days. When taking the drug at a dose higher than recommended for a long period of time, significant suppression of adrenal function is possible. Rare cases of acute adrenal crisis have been described, which occurred mainly in children who received doses of the drug higher than recommended for a long time (several months or years). Acute adrenal crisis is characterized by hypoglycemia, accompanied by confusion and/or convulsions. Situations that can serve as triggers for acute adrenal crisis include trauma, surgery, infection, or any rapid reduction in the dose of fluticasone propionate contained in Seretide® Multidisc. Treatment There is no specific treatment for overdose of salmeterol and fluticasone propionate. In case of overdose, maintenance therapy should be carried out and the patient's condition should be monitored. In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

special instructions

Seretide® Multidisk is not intended for the relief of acute symptoms, since in such cases a rapid and short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be informed to always have a drug on hand to relieve acute symptoms. The combination of salmeterol and fluticasone propionate can be used for initial maintenance therapy in patients with persistent asthma (daily onset of symptoms or daily use of asthma control agents) when indicated to the prescription of GCS 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. A sudden and increasing deterioration in control of bronchial asthma poses a potential threat to life, and in such situations situations, the patient should also consult a doctor. The physician should consider prescribing a higher dose of GCS. If the dose of Seretide® Multidisc used does not provide adequate control of the disease, the patient should also consult a doctor. Patients with asthma should not abruptly stop treatment with Seretide® Multidisk due to the risk of exacerbation; the dose of the drug should be reduced gradually under the supervision of a physician. In patients with COPD, discontinuation of the drug may be accompanied by symptoms of decompensation and requires medical supervision. Clinical studies have provided evidence of an increase in the incidence of pneumonia in patients with COPD receiving Seretide® Multidisk (see section “Side Effects”). Clinicians should be aware of the possibility of developing pneumonia in COPD, since the clinical presentation of pneumonia and exacerbation of COPD are often similar. Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; it should be noted, however, that the likelihood of such symptoms occurring is much lower than during treatment with oral corticosteroids (see section “Overdose”). Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, when treating bronchial asthma, it is important to reduce the dose to the lowest dose that provides effective control of symptoms. In emergency and planned situations that can cause stress, you must always remember the possibility of adrenal suppression and be prepared to use GCS (see section “Overdose”) . When carrying out resuscitation 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 possibility of adrenal suppression, patients transferred from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and regularly control the function of their adrenal cortex. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids, may occur. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs, incl. GCS for local use. After starting treatment with inhaled fluticasone propionate, systemic GCS should be withdrawn gradually, and such patients should have a special patient card containing an indication of the possible need for additional administration of GCS in stressful situations. In patients with exacerbation of bronchial asthma, hypoxia is necessary monitor the concentration of K+ ions in the plasma. There are very rare reports of increased blood glucose levels, and this should be remembered when prescribing a combination of salmeterol and fluticasone propionate to patients with diabetes mellitus (see section “Side effects”). Reports have been received in the post-registration period about a clinically significant drug interaction between fluticasone propionate and ritonavir, leading to systemic effects of GCS, including Cushing's syndrome and suppression of adrenal function. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, except in cases where the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS (see section “Drug Interactions”). Data from a clinical study of the safety of salmeterol added to ongoing therapy for bronchial asthma, compared with placebo showed that the incidence of deaths due to bronchial asthma was higher in the salmeterol group. When taking salmeterol compared with placebo, the risk of serious respiratory adverse reactions or death in African-American patients appears to be greater than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effects associated with the use of GCS were not studied in this study. Like other inhaled drugs, Seretide® Multidisk can cause paradoxical bronchospasm, manifested by an increase in shortness of breath immediately after use. In this case, you should immediately use a short-acting inhaled bronchodilator, discontinue Seretide® Multidisk and begin, if necessary, alternative therapy. There are reports of side effects associated with the pharmacological action of beta2-antagonists, such as tremor, subjective palpitations and headache. However, these phenomena are short-term in nature, and their severity decreases with regular therapy. Effect on the ability to drive vehicles and operate machinery In clinical studies, no data were obtained on the effect of the drug on the ability to drive vehicles and other mechanisms, however, side effects that may cause should be taken into account a drug.

Dispensing conditions in pharmacies

On prescription

Directions for use and doses

To obtain the optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. 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 patient should be prescribed a dosage form of Seretide® or Seretide® Multidisk that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If a patient is unable to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent corticosteroid dose may result in improved asthma control. For those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhaled therapy with a combination of salmeterol and fluticasone propionate may allow a reduction in the dose of the corticosteroid without loss of control of bronchial asthma.

Seretide®

Inhalation, intended for inhalation only.

Recommended Doses

Adults and children 12 years of age and older: 2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day or 2 inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times a day, or 2 inhalations (25 mcg salmeterol and 250 mcg of fluticasone propionate) 2 times a day.

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

Currently, there is no data on the use of Seretide® in children under 4 years of age.

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms. If control of symptoms is ensured by taking Seretide® 2 times a day, reducing the dose to the minimum effective may include a single dose of the drug per day.

COPD

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 in elderly patients or in patients with impaired renal or hepatic function.

Seretide® Multidisc

Inhalation, intended for inhalation only.

Recommended Doses

Adults and children 12 years of age and older: 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times a day or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day, or 1 inhalation (50 mcg salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

In adults over 18 years of age, doubling the dose while using any form of Seretide® Multidisk for up to 14 days maintains the same safety and tolerability as with regular use of this combination, 1 inhalation 2 times a day. The dose may be doubled in cases where patients require additional short-term (up to 14 days) inhaled corticosteroid therapy, as described in some asthma treatment guidelines.

Children 4 years of age and older: 1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® Multidisk in children under 4 years of age.

COPD

For adult patients, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose in elderly patients or in patients with impaired renal or hepatic function.

Seretide®

Instructions for use of the inhaler

Checking the inhaler: before using the inhaler for the first time or if the inhaler has not been used for a week or longer, you must remove the cap from the mouthpiece by lightly squeezing the cap on the sides, shake the inhaler well and release 1 stream into the air to make sure it is working.

Using an inhaler

1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides.

2. Inspect the inhaler inside and out, including the mouthpiece, for loose parts.

3. Shake the inhaler well to ensure that any loose parts are removed and that the contents of the inhaler are evenly mixed.

4. Hold the inhaler between your thumb and the other four fingers in a vertical position, bottom up, with your thumb resting on the base under the mouthpiece.

5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it without biting.

6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray Seretide® while continuing to inhale deeply and slowly.

7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue holding your breath for as long as possible.

8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 3–7.

9. After using the inhaler, rinse your mouth with water and then spit it out.

10. Close the mouthpiece cap by pressing and snapping into position.

The drug can also be used through a spacer (for example Volumatic).

Attention! When following steps 4, 5 and 6, you should not rush. You should begin inhaling as slowly as possible, just before pressing the inhaler valve. It is recommended to practice in front of a mirror the first few times. If you see a "fog" coming from the top of the inhaler or from the corners of your mouth, then you should start over from step 2.

If your doctor has given other instructions for using your inhaler, you should strictly follow them. You should contact your doctor if you have difficulty using your inhaler.

Using an inhaler in children

Young children cannot use the inhaler themselves and must be assisted by an adult. It is necessary to wait until the child exhales and activate the inhaler at the moment the child begins to inhale. You should practice using the inhaler with your child. Older children and adults with weak hands should hold the inhaler with both hands. In this case, both index fingers should be located on the top of the inhaler, and both thumbs should be on the base below the mouthpiece. For children, the drug is administered using an inhaler through a spacer with a face mask (for example, Babyhaler).

Cleaning the inhaler: the inhaler must be cleaned at least once a week. Remove the protective cap from the mouthpiece. Do not remove the metal can from the plastic casing. Use a dry cloth or cotton swab to wipe the mouthpiece inside and out and the plastic casing outside. Close the mouthpiece with the protective cap.

Do not immerse the metal can in water.

Seretide® Multidisc

Instructions for use of the inhaler

Inhaler device

Multidisk is closed (Fig. 1)

Multidisk is open (Fig. 2)

The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

Using an inhaler

To carry out inhalation, follow 4 sequential steps:

1) open the inhaler;

2) press the lever,

3) inhale a dose of the drug;

4) close the inhaler;

5) rinse your mouth with water.

1. Open the inhaler (Fig. 3).

You should hold the body with one hand, placing the thumb of the other hand in a special recess. To open the inhaler, you need to press your thumb away from you until it clicks.

2. Press the lever (Fig. 4).

You must hold the inhaler with the mouthpiece towards your face. The inhaler can be held with your right or left hand. Press the lever away from you until it stops until you hear a click. The inhaler is now ready for use. After pressing the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. You should press the lever only before inhalation, otherwise this will lead to wastage of the drug.

3. Inhale a dose of medicine (Fig. 5).

You should hold the inhaler at some distance from your mouth and exhale deeply without force.

Remember: never exhale into an inhaler!

You need to wrap your lips tightly around the mouthpiece. Take a slow, deep breath through your mouth (not your nose).

Remove the inhaler from your mouth.

Hold your breath for about 10 seconds or longer as possible.

Exhale slowly. Do not exhale into the inhaler.

4. Close the inhaler (Fig. 6)

In order to close the inhaler, you need to place your thumb in a special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position.

5. After using the drug, rinse your mouth with water and spit it out.

Cleaning the inhaler: After using the inhaler, the mouthpiece should be wiped with a dry cloth.

Seretide Multidisk, 1 piece, 50 mcg+250 mcg/dose, dosed powder for inhalation

To obtain the optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. 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 patient should be prescribed a dosage form of Seretide® or Seretide® Multidisk that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If a patient is unable to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent corticosteroid dose may result in improved asthma control. For those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhaled therapy with a combination of salmeterol and fluticasone propionate may allow a reduction in the dose of the corticosteroid without loss of control of bronchial asthma.

Seretide®

Inhalation,

intended for inhalation only.

Recommended Doses

Adults and children 12 years and older:

2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day or 2 inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times a day, or 2 inhalations (25 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day day.

Children 4 years and older:

2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day.

Currently, there is no data on the use of Seretide® in children under 4 years of age.

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms. If control of symptoms is ensured by taking Seretide® 2 times a day, reducing the dose to the minimum effective may include a single dose of the drug per day.

COPD

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 in elderly patients or in patients with impaired renal or hepatic function.

Seretide® Multidisc

Inhalation,

intended for inhalation only.

Recommended Doses

Adults and children 12 years and older:

1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times a day or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day, or 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times a day day.

In adults over 18 years of age, doubling the dose while using any form of Seretide® Multidisk for up to 14 days maintains the same safety and tolerability as with regular use of this combination, 1 inhalation 2 times a day. The dose may be doubled in cases where patients require additional short-term (up to 14 days) inhaled corticosteroid therapy, as described in some asthma treatment guidelines.

Children 4 years and older:

1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® Multidisk in children under 4 years of age.

COPD

For adult patients, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose in elderly patients or in patients with impaired renal or hepatic function.

Seretide®

Instructions for use of the inhaler

Checking the inhaler:

Before using the inhaler for the first time or if the inhaler has not been used for a week or longer, you must remove the cap from the mouthpiece by lightly squeezing the cap on the sides, shake the inhaler well and release 1 stream into the air to make sure that it is working.

Using an inhaler

1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides.

2. Inspect the inhaler inside and out, including the mouthpiece, for loose parts.

3. Shake the inhaler well to ensure that any loose parts are removed and that the contents of the inhaler are evenly mixed.

4. Hold the inhaler between your thumb and the other four fingers in a vertical position, bottom up, with your thumb resting on the base under the mouthpiece.

5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it without biting.

6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray Seretide® while continuing to inhale deeply and slowly.

7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue holding your breath for as long as possible.

8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 3–7.

9. After using the inhaler, rinse your mouth with water and then spit it out.

10. Close the mouthpiece cap by pressing and snapping into position.

The drug can also be used through a spacer (for example Volumatic).

Attention! When following steps 4, 5 and 6, you should not rush. You should begin inhaling as slowly as possible, just before pressing the inhaler valve. It is recommended to practice in front of a mirror the first few times. If you see a "fog" coming from the top of the inhaler or from the corners of your mouth, then you should start over from step 2.

If your doctor has given other instructions for using your inhaler, you should strictly follow them. You should contact your doctor if you have difficulty using your inhaler.

Using an inhaler in children

Young children cannot use the inhaler themselves and must be assisted by an adult. It is necessary to wait until the child exhales and activate the inhaler at the moment the child begins to inhale. You should practice using the inhaler with your child. Older children and adults with weak hands should hold the inhaler with both hands. In this case, both index fingers should be located on the top of the inhaler, and both thumbs should be on the base below the mouthpiece. For children, the drug is administered using an inhaler through a spacer with a face mask (for example, Babyhaler).

Cleaning the inhaler:

The inhaler must be cleaned at least once a week. Remove the protective cap from the mouthpiece. Do not remove the metal can from the plastic casing. Use a dry cloth or cotton swab to wipe the mouthpiece inside and out and the plastic casing outside. Close the mouthpiece with the protective cap.

Do not immerse the metal can in water.

Seretide® Multidisc

Instructions for use of the inhaler

Inhaler device

Multidisk is closed (Fig. 1)

Multidisk is open (Fig. 2)

The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

Using an inhaler

To carry out inhalation, follow 4 sequential steps:

1) open the inhaler;

2) press the lever,

3) inhale a dose of the drug;

4) close the inhaler;

5) rinse your mouth with water.

1. Open the inhaler (Fig. 3).

You should hold the body with one hand, placing the thumb of the other hand in a special recess. To open the inhaler, you must press your thumb all the way away

until a click is heard.

2. Press the lever (Fig. 4).

You must hold the inhaler with the mouthpiece towards your face. The inhaler can be held with your right or left hand. Press the lever away from you until it stops

until a click is heard.
The inhaler is now ready for use. After pressing the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. You should press the lever only before inhalation
, otherwise this will lead to a waste of the drug.

3. Inhale a dose of medicine (Fig. 5).

You should hold the inhaler at some distance from your mouth and exhale deeply without force.

Remember: never exhale into an inhaler!

You need to wrap your lips tightly around the mouthpiece. Take a slow, deep breath through your mouth (not your nose).

Remove the inhaler from your mouth.

Hold your breath for about 10 seconds or longer as possible.

Exhale slowly. Do not exhale into the inhaler.

4. Close the inhaler (Fig. 6)

In order to close the inhaler, you need to place your thumb in a special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position.

5. After using the drug, rinse your mouth with water and spit it out.

Cleaning the inhaler:

After using the inhaler, the mouthpiece should be wiped with a dry cloth.

Overdose

Symptoms: objective and subjective symptoms of salmeterol overdose include tremor, headache and tachycardia. Inhalation of doses of fluticasone propionate higher than recommended may cause temporary depression of the hypothalamic-pituitary-adrenal axis. This usually does not require any emergency measures, since in most cases normal adrenal function is restored within a few days.

With prolonged inhalation of excessively large doses of Seretide® and Seretide® Multidisc, significant adrenal suppression may occur. There are rare reports in the literature of acute adrenal crisis, which occurs predominantly in children receiving excessively high doses over a long period of time (several months or years); acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and/or convulsions. Situations that may trigger an acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate.

Treatment: antidotes are cardioselective β-blockers. In cases where it is necessary to discontinue the drugs Seretide® and Seretide® Multidisk due to an overdose of salmeterol included in its composition, the patient should be prescribed an appropriate replacement GCS.

Patients should be aware that they should not take Seretide® and Seretide® Multidisk in doses higher than recommended. It is important to regularly assess the effectiveness of therapy and reduce the dose to the minimum effective, i.e. to one that provides effective control of disease symptoms.

In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

Seretide Multidisc powder for inhalation 50+500 mcg/dose 60 doses in Moscow

To obtain the optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. 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 patient should be prescribed a dosage form of Seretide® or Seretide® Multidisk that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If a patient is unable to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent corticosteroid dose may result in improved asthma control. For those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhaled therapy with a combination of salmeterol and fluticasone propionate may allow a reduction in the dose of the corticosteroid without loss of control of bronchial asthma.

Seretide®

Inhalation,

intended for inhalation only.

Recommended Doses

Adults and children 12 years and older:

2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day or 2 inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times a day, or 2 inhalations (25 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day day.

Children 4 years and older:

2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day.

Currently, there is no data on the use of Seretide® in children under 4 years of age.

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms. If control of symptoms is ensured by taking Seretide® 2 times a day, reducing the dose to the minimum effective may include a single dose of the drug per day.

COPD

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 in elderly patients or in patients with impaired renal or hepatic function.

Seretide® Multidisc

Inhalation,

intended for inhalation only.

Recommended Doses

Adults and children 12 years and older:

1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times a day or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day, or 1 inhalation (50 mcg salmeterol and 500 mcg fluticasone propionate) 2 times a day day.

In adults over 18 years of age, doubling the dose while using any form of Seretide® Multidisk for up to 14 days maintains the same safety and tolerability as with regular use of this combination, 1 inhalation 2 times a day. The dose may be doubled in cases where patients require additional short-term (up to 14 days) inhaled corticosteroid therapy, as described in some asthma treatment guidelines.

Children 4 years and older:

1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® Multidisk in children under 4 years of age.

COPD

For adult patients, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose in elderly patients or in patients with impaired renal or hepatic function.

Seretide®

Instructions for use of the inhaler

Checking the inhaler:

Before using the inhaler for the first time or if the inhaler has not been used for a week or longer, you must remove the cap from the mouthpiece by lightly squeezing the cap on the sides, shake the inhaler well and release 1 stream into the air to make sure that it is working.

Using an inhaler

1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides.

2. Inspect the inhaler inside and out, including the mouthpiece, for loose parts.

3. Shake the inhaler well to ensure that any loose parts are removed and that the contents of the inhaler are evenly mixed.

4. Hold the inhaler between your thumb and the other four fingers in a vertical position, bottom up, with your thumb resting on the base under the mouthpiece.

5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it without biting.

6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray Seretide® while continuing to inhale deeply and slowly.

7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue holding your breath for as long as possible.

8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 3–7.

9. After using the inhaler, rinse your mouth with water and then spit it out.

10. Close the mouthpiece cap by pressing and snapping into position.

The drug can also be used through a spacer (for example Volumatic).

Attention! When following steps 4, 5 and 6, you should not rush. You should begin inhaling as slowly as possible, just before pressing the inhaler valve. It is recommended to practice in front of a mirror the first few times. If you see a "fog" coming from the top of the inhaler or from the corners of your mouth, then you should start over from step 2.

If your doctor has given other instructions for using your inhaler, you should strictly follow them. You should contact your doctor if you have difficulty using your inhaler.

Using an inhaler in children

Young children cannot use the inhaler themselves and must be assisted by an adult. It is necessary to wait until the child exhales and activate the inhaler at the moment the child begins to inhale. You should practice using the inhaler with your child. Older children and adults with weak hands should hold the inhaler with both hands. In this case, both index fingers should be located on the top of the inhaler, and both thumbs should be on the base below the mouthpiece. For children, the drug is administered using an inhaler through a spacer with a face mask (for example, Babyhaler).

Cleaning the inhaler:

The inhaler must be cleaned at least once a week. Remove the protective cap from the mouthpiece. Do not remove the metal can from the plastic casing. Use a dry cloth or cotton swab to wipe the mouthpiece inside and out and the plastic casing outside. Close the mouthpiece with the protective cap.

Do not immerse the metal can in water.

Seretide® Multidisc

Instructions for use of the inhaler

Inhaler device

Multidisk is closed (Fig. 1)

Multidisk is open (Fig. 2)

The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

Using an inhaler

To carry out inhalation, follow 4 sequential steps:

1) open the inhaler;

2) press the lever,

3) inhale a dose of the drug;

4) close the inhaler;

5) rinse your mouth with water.

1. Open the inhaler (Fig. 3).

You should hold the body with one hand, placing the thumb of the other hand in a special recess. To open the inhaler, you must press your thumb all the way away

until a click is heard.

2. Press the lever (Fig. 4).

You must hold the inhaler with the mouthpiece towards your face. The inhaler can be held with your right or left hand. Press the lever away from you until it stops

until a click is heard.
The inhaler is now ready for use. After pressing the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. You should press the lever only before inhalation
, otherwise this will lead to a waste of the drug.

3. Inhale a dose of medicine (Fig. 5).

You should hold the inhaler at some distance from your mouth and exhale deeply without force.

Remember: never exhale into an inhaler!

You need to wrap your lips tightly around the mouthpiece. Take a slow, deep breath through your mouth (not your nose).

Remove the inhaler from your mouth.

Hold your breath for about 10 seconds or longer as possible.

Exhale slowly. Do not exhale into the inhaler.

4. Close the inhaler (Fig. 6)

In order to close the inhaler, you need to place your thumb in a special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position.

5. After using the drug, rinse your mouth with water and spit it out.

Cleaning the inhaler:

After using the inhaler, the mouthpiece should be wiped with a dry cloth.

special instructions

Treatment of bronchial asthma is recommended to be carried out in stages, monitoring the patient's clinical response to treatment and lung function. The patient must be taught how to use the inhaler correctly.

Seretide® and Seretide® Multidisc are not intended for the relief of acute symptoms, since in such cases a rapid and short-acting inhaled bronchodilator (for example salbutamol) should be used. Patients should be advised to always have medication available to relieve acute symptoms.

Salmeterol/fluticasone propionate can be used for initial maintenance therapy in patients with persistent asthma (daily onset of symptoms or daily use of anti-attack medications) if there are indications for corticosteroids and their approximate dosage has been determined.

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

Sudden and increasing deterioration in control of bronchospastic syndrome poses a potential threat to life, and in such situations the patient should also consult a doctor. It is possible that the doctor will prescribe a higher dose of GCS. If the dose of Seretide® and Seretide® Multidisk used does not provide adequate control of the disease, then the patient should also consult a doctor who may prescribe additional corticosteroids, and if an exacerbation is caused by an infection, then antibiotics.

Due to the risk of exacerbation, treatment with Seretide® and Seretide® Multidisc should not be stopped abruptly; the dose of the drug should be reduced gradually under the supervision of a physician.

Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; It should be noted, however, that the likelihood of such symptoms occurring is much lower than with treatment with oral corticosteroids. Possible systemic effects include suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density, and the development of cataracts and glaucoma. Considering the above, the dose of inhaled GCS should be titrated to the minimum that ensures the maintenance of effective control.

In emergency and planned situations that can cause stress, it is always necessary to remember the possibility of adrenal suppression and be prepared to use GCS.

When carrying out 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.

Some patients may be more sensitive to the effects of inhaled corticosteroids than most patients.

Due to the possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function should be regularly monitored. When transferring patients from taking systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids, may occur. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs, incl. GCS for local use.

After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special card with them indicating the possible need for additional administration of corticosteroids in stressful situations.

In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to monitor the concentration of K+ in plasma.

There are very rare reports of increased blood glucose levels, and this should be kept in mind when prescribing the combination of salmeterol with fluticasone propionate to patients with diabetes mellitus.

Instructions for use SERETIDE MULTIDISK

Seretide® Multidisc™ is not intended for the relief of acute symptoms, as in such cases a rapid and short-acting inhaled bronchodilator should be used. Patients should be advised to always have medication available to relieve an acute asthma attack.

Treatment with Seretide should not be started in patients during an exacerbation or when there is significant or rapid worsening of the disease.

During treatment with Seretide®, serious adverse reactions associated with asthma, as well as exacerbations of the disease, may occur. Patients should be informed of the need to continue treatment and contact their doctor if asthma symptoms are uncontrollable or worsen after starting treatment with Seretide.

The need for more frequent use of drugs to relieve acute asthma attacks (short-acting bronchodilators) or a decrease in their therapeutic effect indicates a deterioration in disease control, and in such situations the patient should consult a doctor.

Sudden and progressive deterioration of asthma control is potentially life-threatening, and in such situations the patient should undergo urgent medical evaluation. The need to increase the dose of corticosteroids should be considered.

Once asthma control is achieved, a gradual reduction in the dose of Seretide may be considered. When reducing the dose, it is important to regularly monitor patients. The minimum effective dose of Seretide should be used.

Patients with exacerbation of COPD are typically prescribed systemic corticosteroids, so in these situations patients should be aware that they should seek medical attention if symptoms worsen while using Seretide.

Treatment with Seretide should not be stopped abruptly in patients with asthma due to the risk of exacerbation. The dose should be reduced under medical supervision. In patients with COPD, discontinuation of therapy may lead to symptomatic decompensation and should be carried out under medical supervision.

As with all inhaled corticosteroids, Seretide should be used with caution in patients with active or latent pulmonary tuberculosis and fungal, viral or other respiratory tract infections. If necessary, appropriate treatment should be started immediately.

In rare cases, Seretide may cause cardiac arrhythmias, such as supraventricular tachycardia, extrasystole and atrial fibrillation, as well as a slight temporary decrease in serum potassium when taking high therapeutic doses. Therefore, Seretide should be administered with caution to patients with severe cardiovascular disorders, including cardiac arrhythmias, diabetes mellitus, thyrotoxicosis, untreated hypokalemia and patients predisposed to low serum potassium levels.

There are very rare reports of increased blood glucose levels, and this should be taken into account when prescribing the drug to patients with diabetes.

Inhaled drugs can cause paradoxical bronchospasm, which is manifested by increased wheezing and shortness of breath immediately after inhalation of the drug. Paradoxical bronchospasm must be treated immediately with a fast-acting inhaled bronchodilator. If paradoxical bronchospasm occurs, it is necessary to immediately stop using the drug Seretide, assess the patient's condition and, if necessary, prescribe therapy with other drugs.

There have been reports of pharmacological side effects of β2-adrenergic agonist treatment, such as tremor, palpitations and headache, which are usually transient and decrease with continued therapy.

Seretide® contains lactose up to 12.5 mg/dose, which generally does not cause problems in patients with lactose intolerance.

Any inhaled corticosteroid can cause systemic effects, especially with long-term use at high doses; however, such effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid appearance, adrenal suppression, decreased bone mineral density, cataracts and glaucoma, and in rarer cases a range of psychological and behavioral disorders including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression (eg , in children). Therefore, it is important to regularly evaluate patient management, with the dose of inhaled corticosteroid reduced to the minimum dose that maintains effective asthma control.

Long-term therapy with inhaled corticosteroids in high doses can lead to suppression of adrenal function and the development of acute adrenal crisis. Very rare cases of suppression of adrenal function and acute adrenal crisis have also been described with the use of fluticasone propionate in the dose range from 500 to 1000 mcg. Situations that potentially trigger acute adrenal crisis include trauma, surgery, infection, or any rapid reduction in drug dosage. Symptoms present are usually vague and may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased blood pressure, decreased mental capacity, hypoglycemia, and seizures. Additional systemic corticosteroids may be required during periods of stress or elective surgery.

The benefits of inhaled fluticasone propionate therapy minimize the need for oral steroids, but patients transitioning from oral corticosteroid therapy may be at risk for adrenal suppression for a significant period of time. Therefore, treatment of such patients should be carried out with extreme caution with constant monitoring of adrenal function. Patients who have received high doses of corticosteroid drugs for emergency conditions in the past may also be at risk. In emergency and routine stressful clinical situations, the possibility of residual adrenal dysfunction should always be kept in mind and the need for appropriate corticosteroid therapy should be considered. Consultation with a specialist may be required to assess the degree of adrenal dysfunction before elective surgery.

Ritonavir may significantly increase plasma concentrations of fluticasone propionate. Therefore, the combined use of these drugs should be avoided unless the potential benefit outweighs the risk of systemic corticosteroid side effects. A similar risk of developing systemic side effects exists when fluticasone propionate is co-administered with other strong CYP3A inhibitors.

In the TORCH study, patients with COPD receiving Seretide 50+500 mcg twice daily had an increased number of reports of lower respiratory tract infections (particularly pneumonia and bronchitis) compared with the placebo group. Similar increases were also observed in studies SCO40043 and SCO1000250, which compared the lower dose of Seretide 50+250 mcg twice daily, which is not approved for the treatment of COPD, with salmeterol 50 mcg twice daily as monotherapy. A similar incidence of pneumonia in the Seretide group was observed in all studies. In the TORCH study, older patients, patients with a low BMI (<25 kg/m2), and patients with very severe disease (FEV1 <30% predicted) were at increased risk of developing pneumonia, regardless of treatment. Physicians should be vigilant about the possible development of pneumonia and other lower respiratory tract infections in patients with COPD, because The clinical manifestations of these infections and COPD are often similar. If pneumonia develops in a patient with severe COPD, treatment with Seretide should be reconsidered.

Data from the large clinical trial SMART (the Salmeterol Multi-Center Asthma Research Trial) showed that in African-American patients, the risk of serious respiratory adverse events or death was higher with salmeterol compared with placebo. It is unknown whether this is due to pharmacogenetic or other factors. Patients of black African or Afro-Caribbean descent should be advised that in cases where asthma symptoms are not controlled or worsen while taking Seretide, it is necessary to consult a doctor while continuing treatment. Concomitant use with systemic ketoconazole significantly increases the systemic exposure of salmeterol, which may lead to an increased incidence of systemic side effects (e.g., QTc prolongation and heart palpitations). In this regard, concomitant use of Seretide with ketoconazole or other strong CYP3A4 inhibitors should be avoided, unless the benefit outweighs the potential increased risk of systemic side effects during treatment with salmeterol.

Use in pediatrics

Children and adolescents under 16 years of age taking high doses of fluticasone (usually 1000 mcg/day or more) are at particular risk of developing systemic side effects. Systemic effects, in particular, can be observed with prolonged use of the drug in high doses. Possible systemic effects include Cushing's syndrome, Cushingoid appearance, adrenal suppression, acute adrenal crisis, growth retardation in children and adolescents, and, in rarer cases, a range of psychological and behavioral disturbances including psychomotor hyperactivity, sleep disturbance, anxiety, depression, or aggression. Consideration should be given to having the child or adolescent examined by a pediatrician who specializes in the treatment of respiratory diseases.

It is recommended that the height of children receiving long-term inhaled corticosteroid therapy be regularly measured.

The dose of inhaled corticosteroid should be reduced to the minimum dose that maintains effective asthma control.

Impact on the ability to drive vehicles and operate machinery

Seretide® Multidisk™ has no or very little effect on the ability to drive a car or drive machinery.