Seretide Multidisc, inhalation powder 50mcg/500mcg, 60 doses

Composition

1 dose of powder for inhalation contains:

Active ingredients:

salmeterol xynafoate 72.5 mcg (based on salmeterol 50 mcg),

fluticasone propionate (micronized) 500 mcg;

Auxiliary substances:

lactose monohydrate-up to 12.5 mg

Pharmacological action

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

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 (

of Pharmacokinetical combines the introduction of inhaled salmeterol and fluticasone propionate did not affect the pharmacokinetics of each other therefore, the pharmacokinetic characteristics of each of the component drugs 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: acts topically in the lung tissue, so its plasma content 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 individuals 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.

The distribution of fluticasone propionate is characterized by a rapid plasma clearance (1150 ml / min), a large V_ss (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

Pregnant and lactating women should only be prescribed the drug if the expected 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.

Side effects

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

They can cause paradoxical bronchospasm. In this case, you should immediately apply a short-acting inhaled bronchodilator, cancel the drug, and start alternative therapy if indicated.

Salmeterol: pharmacological side effects of a beta_-2-adrenergic agonist are described, such as tremor, palpitation and headache, hypokalemia, which, as a rule, are transient and weaken with continued therapy with salmeterol.

Sensitive patients may experience arrhythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystole).

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, changes in taste sensations (dysgeusia) are described.

Cases of painful muscle spasms and very rare cases of hyperglycemia have been reported.

Fluticasone propionate: some patients may experience roughness or hoarseness of the voice and candidiasis (thrush) of the mouth and pharynx.

Hypersensitivity skin reactions are described. Hypersensitivity reactions have also been reported in the form of angioedema (mainly facial and oropharyngeal edema), respiratory disorders (mainly dyspnea and/or bronchospasm) and anaphylactic reactions.

The severity and frequency of voice coarsening and candidiasis can be reduced by rinsing your mouth with water after inhalation. Symptomatic candidiasis can be treated with topical antifungal medications, while continuing therapy with Seretid or Seretidmultidisk.

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

It is theoretically possible to develop systemic reactions, including Cushing’s syndrome or Cushing’s symptoms, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma.

Long-term use of salmeterol and fluticasone propionate combination doses that exceed the permitted doses may cause significant suppression of the adrenal cortex. There are very rare reports of an acute adrenal crisis, which occurred mainly in children who received higher than permitted doses of this combination for a long time (several months or years); symptoms of an adrenal crisis included hypoglycemia, accompanied by a decrease in consciousness and/or convulsions.

Interaction

Due to the risk of developing bronchospasm, the simultaneous use of selective and non-selective beta-blockers should be avoided, except in cases where they are extremely necessary for the patient.

In normal situations, inhalation of fluticasone propionate is accompanied by low plasma concentrations due to intensive metabolism during the “first” passage and high systemic clearance under the influence of the cytochrome P450 isoenzyme CYP3A4 in the intestine and liver. Because of this, clinically significant interactions involving fluticasone propionate are 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 caused side effects such as Cushing’s syndrome and adrenal suppression. With this in mind, the concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risk of 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.

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

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

Compatible with Cromoglicic acid.

How to take, course of use and dosage

For 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 Seretide Multidisk Form of production that contains a dose of fluticasone propionate that corresponds to the severity of his 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.

Inhaled, intended for inhalation only.

Recommended doses

Adults and children 12 years and older: 1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day or 1 inhalation (50 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times a day, or 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a 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 up to 14 days, the same safety and tolerability is maintained as with regular use of this combination of 1 inhalation 2 times a 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 4 years and older: 1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

Currently, there are 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, as well as in patients with impaired renal or hepatic function.

Overdose

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

Prolonged inhalation of excessively high doses of Seretidi Seretide Multidisk may cause significant adrenal suppression. In the literature, there are rare reports of acute adrenal crisis, which occurs mainly in children who receive 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 the drug.

Treatment: Antidotes are cardioselective beta-blockers. In cases where it is necessary to cancel the drugs Seretide and Seretide Multidisk due to an overdose of salmeterol, the patient should be prescribed an appropriate replacement corticosteroid.

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

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

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®preparations Multidisks are not intended to relieve acute symptoms, since in such cases a fast – and short-acting inhaled bronchodilator (for example, salbutamol) should be used. Patients should be informed that they should always have a medication available to relieve acute symptoms.

Salmeterol / fluticasone propionate 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 increasing deterioration of bronchospastic syndrome control is potentially life-threatening, and in such situations, the patient should also consult a doctor. It is possible that the doctor will prescribe a higher dose of corticosteroids. If the dose used is Seretide® and Seretide®If the multi-disc does not provide adequate disease control, the patient should also consult a doctor who can prescribe additional corticosteroids, and if the exacerbation is caused by an infection, then antibiotics.

Due to the risk of exacerbation, treatment with Seretide® and Seretide®is recommended. Multi-disc should not be abruptly stopped, the dose of the drug should be reduced gradually under the supervision of a doctor.

Any inhaled corticosteroid may cause systemic effects, especially when used for a long time in high doses; it should be noted, however, that the likelihood of such symptoms is much lower than when treated with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, and the development of cataracts and glaucoma. Given the above, the dose of inhaled corticosteroids should be titrated to the minimum, ensuring the maintenance of effective control.

In emergency and planned situations that can cause stress, you should always be aware of the possibility of adrenal suppression and be prepared for the use of corticosteroids.

When performing 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.

In view of the potential for adrenal suppression, patients transferred from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal cortex function should be monitored regularly. When transferring patients 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.

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

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

There are very rare reports of elevated blood glucose levels, and 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 dosed

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 as prescribed by a doctor, Adults as prescribed by a doctor, Children over 12 years of age, Nursing mothers, Pregnant women as prescribed by a doctor

Indications

Low learning rate, Bronchial asthma