Seretide MULTYDYSK

Active material: Fluticasone, Salmeterol
When ATH: R03AK06
CCF: The drug is a bronchodilator and anti-inflammatory action
ICD-10 codes (testimony): J44, J45
When CSF: 04.03
Manufacturer: GLAXO WELLCOME UK LIMITED (Great Britain)

Pharmaceutical form, composition and packaging

The powder for inhalation white or nearly white; Inhaler round, plastic, dark purple and light purple with a dose counter.

Excipients: lactose monohydrate.

28 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.
60 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.

The powder for inhalation white or nearly white; Inhaler round, plastic, dark purple and light purple with a dose counter.

Excipients: lactose monohydrate.

28 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.
60 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.

The powder for inhalation white or nearly white; Inhaler round, plastic, dark purple and light purple with a dose counter.

Excipients: lactose monohydrate.

28 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.
60 doses – strips of foil (1) – plastic inhalers “Multidisk” (1) – packs cardboard.

Pharmacological action

Combined preparation, soderzhit salmeterol and fluticasone propionate, that have different mechanisms of action. Salmeterol prevents bronchospasm, fluticasone propionate improves lung function and prevents exacerbations. Seretide^® Multidisk can be an alternative for patients, are obtained simultaneously agonist β₂-adrenoceptor agonist and inhaled corticosteroids.

Salmeterol – selective agonist β₂-adrenoceptor long-acting (to 12 no), having a long side chain, which binds to the outer domain of the receptor.

Pharmacological properties salmeterol protect against histamine-induced bronchoconstriction and longer bronchodilation (not less than 12 no), чем агонисты b₂-adrenergic short-acting. The onset of bronchodilator effect occurs within 10-20 m.

Salmeterol is a strong and long-acting inhibitor of the release of the lung tissue of human mast cell mediators, such, kak histamine, leykotrienы and prostaglandin D₂.

Salmeterol inhibits the early and late phase response to inhaled allergens; the latter takes over 30 hours after administration of a single dose of, t. it is. while, when the bronchodilator effect is no longer present. A single administration of salmeterol attenuates bronchial hyper-responsiveness tree. This indicates that, bronchodilator salmeterol in addition to that effect has the additional effect, the clinical significance of which is not fully established. This mechanism of action differs from the anti-inflammatory effect of GCS.

At therapeutic doses, salmeterol no effect on the cardiovascular system.

Fluticasone propionate – SCS for local use, When inhaled at recommended doses has a pronounced anti-inflammatory and anti-allergic effect in the lungs, which reduces the clinical symptoms and decrease the frequency of exacerbations, accompanied by airway obstruction. It restores the patient's response to bronchodilators, allowing to reduce the frequency of their use. Action fluticasone propionate, assigned at the recommended doses, It is not accompanied by side effects, typical of systemic corticosteroids.

With prolonged use of inhaled fluticasone propionate at recommended doses, the maximum daily secretion of adrenal hormones remained in the normal range in both adults, and children. After the transfer of patients, receiving other inhaled corticosteroids, appointment Valium daily secretion of adrenal hormones gradually returning to normal, Notwithstanding the foregoing and ongoing periodic use of oral corticosteroids. This indicates that the recovery of adrenal function on the background of the use of inhaled fluticasone propionate. With prolonged use of fluticasone propionate backup function of the adrenal cortex also remained within normal limits, as evidenced by the normal increase of cortisol in response to appropriate stimulation (must be considered, reduction of the residual adrenal reserve, caused by previous therapy, It can be maintained for a long time).

Research, conducted among 318 adult patients with persistent asthma, found, that when using a double dose during 14 days (Irrespective of the dose of the preparation of components) there is a slight increase in the frequency of adverse events, associated with the effect of beta-agonists (tremor – 1 patient [1%], 0 patients with normal dose; cardiopalmus – 6 patients [3%], 1 patient [<1%] at the usual dose; convulsions: 6 patients [3%], 1 patient [<1%] at the usual dose), The frequency of adverse events, associated with the effect of inhaled corticosteroid is stagnant (eg, oral candidiasis – 6 patients [6%], 16 patients [8%] at the usual dose; hoarseness – 2 patient [2%], 4 patient [2%] at the usual dose) compared to the conventional treatment regimen (1 ingalyatsiya 2 times / day). Thus, double the dose of the drug can be used in cases, when patients need additional short (to 14 days) course of corticosteroid therapy.

Pharmacokinetics

Simultaneous inhalational administration of salmeterol and fluticasone propionate did not affect the pharmacokinetics of each substance.

Salmeterol

Salmeterol acts locally in the lung tissue, and therefore its content in the plasma is not correlated with the therapeutic effect.

The data on the pharmacokinetics of salmeterol limited, It has been technically difficult to determine very low concentrations in plasma (C_max 200 pg / ml or less) after inhalation administration of therapeutic doses. With regular use of inhaled salmeterol xinafoate in the blood is determined by the acid gidroksinaftoevaya, C values_ss which is about 10 pg / ml. These concentration 1000 times lower than the equilibrium levels, observed in toxicity studies.

Fluticasone propionate

Absorption and distribution

After the introduction of the absolute bioavailability of inhaled fluticasone propionate in healthy people is 10-30%. In patients with asthma and chronic obstructive pulmonary disease (COPD) have lower concentrations of fluticasone propionate in plasma. Systemic absorption occurs primarily in the lungs, and at first it faster, but then slows down.

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

As the inhalation dose observed linear increase in the concentration of fluticasone propionate in plasma.

V_d fluticasone propionate at steady state is about 300 l.

Valium 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 involving CYP3A4 isoenzyme to inactive carboxyl metabolite.

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

The final T_1/2 approximately 8 no.

Pochechnыy clearance neizmenennogo fluticasone propionate insignificant (<0.2%), as a metabolite in the urine output of less than 5% dose.

Displayed through the intestine mainly in the form of a hydroxylated metabolite.

Testimony

The drug is intended for the treatment of asthma patients, which shows a combination therapy of beta₂-adrenoceptor agonists and long-acting inhaled corticosteroids:

- In patients with poor control of the disease against a background of continuing monotherapy with inhaled corticosteroids for occasional use beta₂-adrenomimetic short-acting;

- In patients with adequate control of the disease during therapy with inhaled corticosteroids and beta₂-adrenoceptor agonists long-acting;

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

Supportive therapy in patients with COPD and FEV1< 60% by proper values (to inhaled bronchodilator) and repeated exacerbations history, which expressed symptoms persist, despite regular bronchodilator therapy.

Dosage regimen

Seretide^® Multidisk is intended only for inhalation.

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

The course of treatment and changing doses doctor sets individually.

The patient should be prescribed Seretide^® Multidisk in the dosage form, which contains a dose of fluticasone propionate, proper severity of the disease.

If the patient fails to achieve adequate control of the disease using inhaled corticosteroids alone, switch to a combination therapy of fluticasone propionate and salmeterol in an equivalent dose of corticosteroid may improve asthma control. Those patients, who inhaled corticosteroid monotherapy provides adequate control of asthma, the transition to a combination of inhalation therapy with salmeterol fluticasone propionate can afford to reduce the dose of corticosteroid without loss of asthma control.

The recommended dose for Adults and children 12 and older – 1 ingalyatsiya (50 mcg salmeterol and 100 micrograms fluticasone propionate) 2 times / day, or 1 ingalyatsiya (50 mcg salmeterol and 250 micrograms fluticasone propionate) 2 times / day, or 1 ingalyatsiya (50 mcg salmeterol and 500 micrograms fluticasone propionate) 2 times / day.

In adults over 18 years by doubling the dose during treatment of any form of release Seretide^® Multidiska for 14 days retained the same safety and tolerability, both with regular use of this combination in 1 inhalation 2 times / day. The dose can be double in cases, when patients need additional short (to 14 days) inhalation therapy GCS, as described in some treatment guidelines for asthma.

For children 4 and older – 1 ingalyatsiya (50 mcg salmeterol and 100 micrograms fluticasone propionate) 2 times / day.

At COPD to Adult the maximum recommended dose – 1 ingalyatsiya (50 mcg salmeterol and 500 micrograms fluticasone propionate) 2 times / day.

Mode of application

Inhaler “Multidisk” It has an indicator, which after inhalation shows the number of remaining doses. Numbers are in descending order from 60 to 0. The numbers 5 to 0 are red, warning about, inhaler that there are only a few doses. The appearance of the numbers in the box 0 means, that the inhaler is empty and is not suitable for further use.

Inhalation

1. Open inhaler: Hold the body with one hand, placing the thumb of the other hand in an indentation; to open the inhaler, Press your thumb away from you until it stops, until you hear a click.

2. Press the lever: keep the inhaler (right or left hand) mouthpiece-to-face; Press the lever away from you until it stops, until you hear a click. Now, the inhaler is ready for use. When you press the lever opened another cell with the powder for inhalation; wherein the number of remaining doses is reduced, as indicated in the window display. Press the lever just prior to inhalation, otherwise it will lead to a waste of the drug.

3. Inject the dose: keep the inhaler at a certain distance away from your mouth and take a deep breath without effort. You can never do exhale into the inhaler. Desktop ranges mouthpiece gubami. Take a slow, deep breath through your mouth (not through the nose). Remove the inhaler from the mouth. Hold your breath for about 10 sec or longer, as you can. Take a slow breath. You can not breathe out into the inhaler.

4. Close the inhaler: Place your thumb in a special groove and push toward you, against the stop, until you hear a click. The lever automatically returns to its original position.

Cleaning the inhaler

After using the inhaler mouthpiece wipe with a dry cloth.

Side effect

As Seretide^® Multidisk contains salmeterol and fluticasone propionate is expected, that it can cause side effects, typical of these components. The simultaneous use of them causes additional side effects.

Seretide^® Multidisk may cause paradoxical bronchospasm.

In clinical studies the use of Seretide^® Multidisk sometimes reports of bruises, and frequent cases of pneumonia (COPD patients).

As part of post-marketing surveillance following data were obtained about adverse events.

Seretide^® Multidisk

Sometimes the reported hypersensitivity reactions, incl. manifested in the form of skin reactions, angioedema (mainly, swelling of the face and oropharyngeal), respiratory disorders (dyspnoea and / or bronchospasm), and in very rare cases – anaphylactic reactions.

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

Salmeterol

Cardio-vascular system: heartbeat, headache (usually, transient, decrease with continued therapy salmeterol); in predisposed patients may be heart rhythm disturbances (incl. atrial fibrillation, supraventricular tachycardia, arrythmia).

From the digestive system: rarely – stomach ache, nausea, vomiting; in some cases – dysgeusia, irritation of the oropharynx.

Allergic reactions: rarely – rash, angioedema, Local swelling.

Other: tremor, kaliopenia (usually, transient, decrease with continued therapy salmeterol); rarely – artralgii, nervousness; in some cases – painful muscle spasms; There are also very rare reports of hyperglycaemia.

Fluticasone propionate

The respiratory system: due to local effects are possible hoarseness, candidiasis of the oral cavity and pharynx.

Allergic reactions: cutaneous manifestations, angioedema (mainly facial and oropharyngeal), respiratory symptoms (dyspnoea and / or bronchospasm), anaphylactic reactions.

Systemic reactions: may develop systemic reactions, including Cushing's syndrome, Cushingoid symptoms, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.

Very rarely it reported an alarm, sleep disorders and behavioral disorders, including hyperactivity and irritability (predominantly, children), giperglikemii.

Combination salmeterol and fluticasone propionate

With prolonged use at dosages, exceeding recommended, perhaps a significant inhibition of the function of the adrenal cortex; rarely (mainly in children, receiving this combination at doses, exceeding recommended, within a few months or years) – acute adrenal crisis (gipoglikemiâ, accompanied by disturbances of consciousness and / or convulsions).

Contraindications

- Children up to age 4 years;

- Hypersensitivity to the drug.

FROM caution: pulmonary tuberculosis, Fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes, nekontroliruemaя gipokaliemiя, idiopathic hypertrophic stenosis subaortalnыy, uncontrolled hypertension, Arrhythmia, QT prolongation on the ECG, CHD, hypoxia of different genesis, Cataract, glaucoma, gipotireoz, osteoporosis, pregnancy, lactation.

Pregnancy and lactation

During pregnancy and lactation (breast-feeding) Seretide^® Multidisk can assign only, if the expected benefit of therapy to the mother outweighs any potential risk to the fetus or child.

Cautions

Seretide^® Multidisk is intended for long-term treatment of the disease, instead of cupping. For cupping patients should be prescribed a short-acting inhaled bronchodilators (eg, salbutamol), that patients are advised to always carry.

With the development of paradoxical bronchospasm should immediately apply a short-acting inhaled bronchodilator, Seretide cancel^® Multidisk and start, when indicated, alternative therapy.

Treatment of asthma is recommended in stages, controlling the clinical response of the patient to be treated and lung function. The patient must be taught how to use the inhaler.

The severity and frequency of the deepening of the voice, and candidiasis can be reduced by rinsing the mouth with water after inhalation of Seretide^® Multidiska. Candidiasis prescribe antifungal drugs for local use, continuing therapy Seretide^® Multidiskom.

In the elderly and patients with renal or hepatic impairment dose reduction is not required.

The preparation may be used for the initial maintenance therapy in patients with persistent asthma (daily occurrence of symptoms or the daily use of cupping) in the presence of indications for corticosteroids and determining their approximate dosage.

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

Sudden and progressive deterioration in control of bronchospastic syndrome is a potentially life-threatening. In these situations, a physician is necessary to monitor. If you use a dose of Seretide^® Multidiska not provide adequate control of the disease, you may need supplementation GCS, and if the aggravation caused by an infection, then prescribe antibiotics.

Because of the risk of exacerbation should avoid sudden cancellation of Seretide^® Multidiska, the dose should be reduced gradually under medical supervision.

When using any of inhaled corticosteroids may develop systemic effects (adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma), especially during prolonged use at high doses, However, the likelihood of such effects is significantly lower, than treatment with oral corticosteroids forms. Considering this, the dose of inhaled corticosteroids should be titrated to the lowest, who maintains effective control.

In emergency situations, stress and planning must always be mindful of the possibility of adrenal suppression and the emergence of the need for corticosteroids.

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

In some patients, there may be individual high sensitivity to inhaled corticosteroids for.

Due to possible adrenal insufficiency should be treated very carefully and regularly monitor the performance of the functions of the adrenal cortex when transferring patients, taking into GCS, treatment flutikazonom propionatom dlya ingalyatsiy. When transferring patients receiving systemic corticosteroids to inhalation therapy may manifest allergic reactions (eg, nasal allergy, eczema), which previously suppressed systemic corticosteroids. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and / or topical preparations (incl. SCS for local use).

Abolition of systemic corticosteroids to inhaled fluticasone propionate background should be gradual. Patients should carry a card, indicating, they may require additional GCS under different stressful situations.

Use in Pediatrics

It is recommended to monitor the dynamics of the growth of children, receiving prolonged treatment with inhaled corticosteroids.

There is currently no data on the use of Seretide^® Multydyska in children aged 4 years.

Monitoring of laboratory parameters

In patients with acute exacerbation of bronchial asthma, Hypoxia is necessary to control the concentration of potassium in the blood plasma.

There are very rare reports of increased blood glucose levels, it should be remembered, assigning a combination of salmeterol with fluticasone propionate diabetics.

Overdose

Symptoms: tremor, headache, and tachycardia, caused by the action of salmeterol; temporary suppression of the hypothalamic-pituitary-adrenal axis, due to the action of fluticasone.

During prolonged inhalation drug Seretide^® Multidisk excessively high doses probably significant adrenal suppression. There are rare reports of acute adrenal Stroke, which occurs mainly in children, receiving Seretide^® Multidisk excessively high doses for long periods (months or years). Acute adrenal crisis manifested hypoglycemia, accompanied by confusion and / or convulsions. Situations, which can serve as a triggering factor of acute adrenal crisis, include injury, surgical intervention, infection or rapid dose reduction is part of the Seretide^® Mulytidiska fluticasone propionate.

Treatment: symptoms, due to the action of salmeterol, should be to stop the introduction of an antidote – cardioselective beta-blockers. Where, when you want to cancel Seretide^® Multidiska due to an overdose of being a part of salmeterol, the patient should designate an appropriate replacement GCS.

Symptoms, caused by the action of fluticasone propionate, usually do not require emergency care, because in most cases the normal adrenal function recovers in a few days.

In chronic overdose recommended to control the backup function of the adrenal cortex.

To avoid overdose, patients should not use Seretide^® Multidisk doses, exceeding recommended. Important is regular evaluation of the effectiveness of therapy and dose reduction of Seretide^® Multidiska to its lowest level, which provides effective control of symptoms.

Drug Interactions

Because of the risk of bronchospasm should avoid applying selective and nonselective beta-blockers except, when it is really necessary and justified.

In diseases, accompanied by reversible airway obstruction, should be avoided as a non-selective, and cardioselective beta-blockers, except, when it is really necessary and justified.

When applying fluticasone propionate by inhalation of its plasma concentration is low due to an intensive metabolism in “first pass” through the liver under the influence of CYP3A4 and high systemic clearance. Because of this clinically significant interactions involving fluticasone propionate are unlikely.

Care must be taken while the application of known inhibitors of CYP3A4 and Valium, because in these situations may increase the content of the last plasma.

Ritonavir (highly potent inhibitor of CYP3A4) It can cause a significant increase in the concentration of fluticasone propionate in plasma, thereby significantly reduced serum cortisol concentrations. There are reports of clinically significant drug interactions in patients, kotorыe odnovremenno received fluticasone propionate and ritonavir, that the development of the syndrome manifested Cushing and adrenal suppression. Considering this, Avoid simultaneous use of fluticasone propionate and ritonavir, except, where the potential benefits of combination therapy to the patient outweighs the risk of systemic side effects of corticosteroids.

Other inhibitors of CYP3A4 causing negligible (Erythromycin) and minor (ketoconazole) increase of fluticasone propionate in plasma, in which virtually reduced concentration of serum cortisol. Despite this, caution is recommended at concomitant use of fluticasone propionate and potent inhibitors of CYP3A4 (eg, ketoconazole), since under such combinations do not exclude the probability of increasing the concentration of fluticasone propionate in plasma.

While the use of the drug Seretide^® Multidisk xanthine derivatives, SCS and diuretics increase the risk of hypokalemia (especially in patients with acute 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 acid kromoglitsievoy.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 18 months.