Seretide Multidisc, inhalation powder 50 µg/100 µg, 60 doses

Composition

Active ingredients:

salmeterol (in the form of xynafoate) 50 mcg,

fluticasone propionate 100 mcg;

Auxiliary substances:

lactose monohydrate.

Pharmacological action

Seretide Multidisk has an anti-asthmatic, bronchodilating, anti-inflammatory effect.

Pharmacodynamics

Seretide Multidisk is a combination drug containing salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the occurrence of bronchospasm, fluticasone propionate improves lung function and prevents exacerbations. The drugs may be an alternative for patients who are simultaneously receiving a beta_-2-adrenergic agonist and inhaled corticosteroids.

Salmeterol is a selective long-acting (up to 12 hours) beta_-2-adrenergic agonist with 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 beta_-2-adrenergic agonists. The beginning of the bronchodilator effect — within 10-20 minutes. Salmeterol is a strong and long-acting inhibitor of the release of mast cell mediators from human lung tissue, such as histamine, LT and PG_D2.

Salmeterol inhibits the early and late phases of the response to inhaled allergens; the latter lasts more than 30 hours after the first dose, i. e. at a time when the bronchodilating effect is no longer present. A single injection 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 definitively established. This mechanism of action differs from the anti-inflammatory effect of corticosteroids. In therapeutic doses, salmeterol has no effect on CCC.

Fluticasone propionate belongs to the group of corticosteroids for topical use and, when inhaled at the recommended doses, has a pronounced anti-inflammatory and anti-allergic 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 prolonged use of inhaled fluticasone propionate in the maximum recommended doses, the daily secretion of adrenal cortex hormones remains within the normal range in both adults and children. After transferring patients receiving other inhaled corticosteroids to fluticasone propionate, the daily secretion of adrenal cortex hormones gradually improves, despite the previous and current periodic use of oral steroids. This indicates the restoration of adrenal function against the background of inhaled fluticasone propionate. With prolonged use of fluticasone propionate, the reserve function of the adrenal cortex also remains within the normal range, as indicated by a normal increase in cortisol production in response to appropriate stimulation (it should be borne in mind that the residual decrease in adrenal reserve caused by previous therapy may persist for a long time).

A study of 318 adult patients with persistent asthma showed that when doubling the dose of the drugs and seretide seretide Multidisk within 14 days (regardless of dose components in the product) is a small increase in the frequency of adverse events associated with the action of β-agonists (tremor — 1 patient (1%), and 0 patients in normal dose; rapid heartbeat — 6 patients (6%),1 patient (

Pharmacokinetics

When co-administered by inhalation, salmeterol and fluticasone propionate do not affect each other’s pharmacokinetics, so the pharmacokinetic characteristics of each component of Seretide Multidisk can be considered separately.

Even though the plasma concentrations of salmeterol and fluticasone propionate are very low, interactions with other substrates and inhibitors of the SURZA 4 isoenzyme cannot be excluded.

Salmeterol:  it acts locally in the lung tissue, so its content in plasma does not correlate with the therapeutic effect. Data on its pharmacokinetics are very limited due to technical problems: when inhaled at therapeutic doses, its_cmax in plasma is extremely low (about 200 pg / ml or lower). After repeated inhalations of salmeterol xynafoate, hydroxynaphthoic acid can be detected in the blood, the C_ss of which is about 10 pg/ml. These concentrations are 1000 times lower than the equilibrium levels observed in toxicity studies.

Fluticasone Propionate:  the absolute bioavailability of inhaled fluticasone propionate in healthy people varies depending on the inhaler used (when using salmeterol/fluticasone propionate with a metered-dose aerosol for inhalation, it is 5.3% of the nominal dose). Patients with asthma and COPD have lower plasma concentrations of fluticasone propionate. Systemic absorption occurs mainly through the lungs, and at first it is faster, but then slows down.

Part of the inhaled dose can 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 presystemic metabolism. Bioavailability from the gastrointestinal tract is less than 1%. As the inhaled dose increases, a linear increase in the plasma concentration of fluticasone propionate is observed. Fluticasone propionate distribution is characterized by rapid plasma clearance (1150 ml / min), high_vss (about 300 l) and a final T_1/2of about 8 h. Fluticasone propionate has a relatively high degree of binding to plasma proteins (91%). It is rapidly eliminated from the blood, mainly as a result of metabolism by the CYP3A4 isoenzyme to an inactive carboxyl metabolite.

Renal clearance of unchanged fluticasone propionate is negligible (

It is excreted through the gastrointestinal tract, mainly in the form of a hydroxylated metabolite.

Indications

Treatment of bronchial asthma in patients who are indicated for combination therapy with a long-acting beta_-2-adrenomimetic and an inhaled corticosteroid:

• in patients with insufficient control of the disease by the constant background of monotherapy with inhaled corticosteroids for occasional use of β₂-agonists of short-acting;
• in patients with adequate control of the disease during therapy with inhaled corticosteroid and β₂-agonists with long-acting;
• as a starting maintenance therapy in patients with persistent bronchial asthma (daily symptoms, daily use of tools for the rapid relief of symptoms) if there are indications for the appointment of corticosteroids to achieve control of the disease;

Maintenance therapy for COPD in patients with forced inspiratory volume (FEV 1)

Use during pregnancy and lactation

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

Contraindications

Hypersensitivity to the components of the drug Seretide Multidisk; children under 4 years of age.

With caution:  tuberculosis of the lungs, 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, coronary heart disease, hypoxia of various origins, cataracts, glaucoma, hypothyroidism, osteoporosis, pregnancy, lactation.

Interaction

Due to the risk of developing bronchospasm, the use of selective and non-selective beta-blockers should be avoided, except when it is really necessary and justified.

In diseases associated with reversible airway obstruction, the use of both non-selective and cardioselective beta-blockers should be avoided, except in cases where this is really necessary and justified. When using fluticasone propionate as an inhalation, its plasma concentration is low due to intensive metabolism during the “first pass” through the liver under the influence of the CYP3A4 isoenzyme and high systemic clearance.

Therefore, a clinically significant interaction involving fluticasone propionate is unlikely. Caution should be exercised when concomitantly using known inhibitors of CYP3A4 and fluticasone propionate, since in such situations, an increase in the content of the latter in plasma is possible. Ritonavir (a highly active inhibitor of the CYP3A4 isoenzyme) can cause a significant increase in the concentration of fluticasone propionate in blood plasma, as a result of which serum cortisol concentrations significantly decrease.

There are reports of clinically significant drug interactions in patients who received fluticasone propionate and ritonavir concomitantly, which was manifested by the development of Itsenko-Cushing syndrome and adrenal suppression.Given this, the concomitant 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 corticosteroids.

Other inhibitors of the CYP3A4 isoenzyme cause negligible (erythromycin) and insignificant (ketoconazole) increases in the content of fluticasone propionate in plasma, which practically do not decrease the concentration of serum cortisol. Despite this, caution is recommended when using fluticasone propionate concomitantly with strong CYP3A4 inhibitors (for example, ketoconazole), since such combinations do not exclude the possibility of increasing the concentration of fluticasone propionate in plasma.

When used concomitantly with Seretide® Multi-disc xanthine derivatives, corticosteroids, and diuretics increase the risk of hypokalemia (especially in patients with acute asthma, hypoxia); MAO inhibitors and tricyclic antidepressants increase the risk of cardiovascular side effects. Multidisk seretide is compatible with Cromoglicic acid.

How to take, course of use and dosage

Seretide Multidisk is intended for inhalation only. For optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD.

The doctor sets the course of treatment and dose changes individually. The patient should be prescribed Seretide Multidisk in a dosage form that contains a dose of fluticasone propionate that corresponds to the severity of the disease. If the patient is unable to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent dose of corticosteroid may lead to 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 reducing the dose of corticosteroid without losing control of bronchial asthma.

The recommended dose for adults and children aged 12 years and older is 1 inhalation (50 mcg of salmeterol and 100 micrograms fluticasone propionate) 2 times/day, or 1 inhalation (50 mcg of salmeterol and 250 µg fluticasone propionate) 2 times/day, or 1 inhalation (50 mcg of salmeterol and 500 micrograms fluticasone propionate) 2 times/day.

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

Children aged 4 years and older – 1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times / day. For adults with COPD, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times / day. Method of application: The Multidisk inhaler has an indicator that shows the number of remaining doses after inhalation. The numbers are in descending order from 60 to 0. The numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. When the number 0 appears in the window, it means that the inhaler is empty and unsuitable for further use.

Overdose

Symptoms: tremor, headache and tachycardia caused by the action of salmeterol; temporary suppression of the hypothalamic-pituitary-adrenal system, due to the action of fluticasone. Prolonged inhalation of Seretide Multidisk in excessively high doses may cause significant suppression of adrenal function.

There are rare reports of acute adrenal crisis, which occurs mainly in children receiving Seretide Multidisk in excessively high doses for a long time (several months or years). Acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and / or convulsions. Situations that can trigger an acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate, which is part of Seretide Multidisk.

Treatment: symptoms caused by the action of salmeterol should be stopped by the introduction of an antidote – a cardioselective beta-blocker. In cases where the withdrawal of Seretide Multidisk is required due to an overdose of salmeterol, the patient should be prescribed an appropriate replacement corticosteroid.

Symptoms caused by 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. In order to avoid overdose, patients should not use Seretide Multidisk in doses exceeding the recommended ones. It is important to regularly evaluate the effectiveness of therapy and reduce the dose of Seretide Multidisk to a minimum level that provides effective control of symptoms of the disease.

Special instructions

Seretide Multidisk is intended for long-term treatment of the disease, and not for the relief of seizures. Short-acting inhaled bronchodilators (such as salbutamol) should be prescribed to patients to stop seizures, and patients are advised to carry them at all times.

If paradoxical bronchospasm develops, a short-acting inhaled bronchodilator should be used immediately, and Seretide®should be discontinued. Multi-disc and start, 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 voice coarsening and candidiasis can be reduced by rinsing the mouth with water after inhalation of Seretide Multidisk. When candidiasis is prescribed antifungal drugs for topical use, continuing therapy with Seretide Multidisk.

In the elderly and patients with renal insufficiency 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 means to stop attacks) if there are indications for the appointment of corticosteroids and when determining their approximate dosage. More frequent use of short-acting bronchodilators to relieve symptoms indicates a deterioration in disease control, and in such situations, the patient should consult a doctor. Sudden and progressive deterioration of bronchospastic syndrome control is potentially life-threatening. In such situations, a doctor’s supervision is necessary. If the applied dose of Seretide Multidisk does not provide adequate disease control, then additional use of corticosteroids may be required, and if the exacerbation is caused by infection, then antibiotics are prescribed. Because of the risk of exacerbation, sudden withdrawal of Seretide Multidisk should be avoided, and the dose of the drug should be reduced gradually under the supervision of a doctor. When using any inhaled corticosteroids, systemic effects may develop (adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma), especially with prolonged use in high doses, but the likelihood of such effects is much lower than with oral forms of corticosteroids. Taking this into account, the dose of inhaled corticosteroids should be titrated to the minimum, which ensures the maintenance of effective control. In emergency and planned stressful situations, it is always necessary to remember about the possibility of suppressing the function of the adrenal glands and the need for the use of corticosteroids.

When performing resuscitation measures or surgical interventions, it is necessary to determine the degree of adrenal insufficiency. Some patients may have an individual high sensitivity to corticosteroids for inhalation. Due to possible adrenal insufficiency, special care should be taken and the function of the adrenal cortex should be regularly monitored when transferring patients who have taken corticosteroids orally to treatment with fluticasone propionate for inhalation. When patients are transferred from taking systemic corticosteroids to inhaled therapy, allergic reactions may occur (for example, allergic rhinitis, eczema), which were previously suppressed by systemic corticosteroids. In such situations, it is recommended to conduct symptomatic treatment with antihistamines and / or topical medications (including topical corticosteroids). Discontinuation of systemic corticosteroids during fluticasone propionate inhalation should be carried out gradually. Patients should carry a card indicating that they may need to take additional corticosteroids for various stressful situations. Use in pediatrics: It is recommended to monitor the growth dynamics of children who receive long-term therapy with inhaled corticosteroids. Currently, there are no data on the use of Seretide Multidisk in children under 4 years of age.

Monitoring of laboratory parameters: in patients with acute bronchial asthma, hypoxia, it is necessary to monitor the concentration of potassium in the blood plasma. There are very rare reports of an increase in blood glucose levels, this should be borne in mind when prescribing a combination of salmeterol with fluticasone propionate to patients with diabetes mellitus.

Form of production

Powder for inhalation.

Storage conditions

At temperatures below 30 °C

Shelf life

18 months

Active ingredient

Salmeterol, Fluticasone

Conditions of release from pharmacies

By prescription

Dosage form

powder for inhalation

Purpose

Children prescribed by a doctor, Nursing mothers, Adults prescribed by a doctor, Pregnant women prescribed by a doctor, Children over 4 years of age

Indications

Bronchial Asthma, Low learning rate