SERETIDE

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 GROUP (Great Britain)

Pharmaceutical form, composition and packaging

Aerosol for inhalation dose in the form of a suspension of white or almost white.

Excipients: 1,1,1,2-tetrafluoroethane (to 75 mg).

120 doses – inhalers aluminum (1) the metering valve acts – packs cardboard.

Aerosol for inhalation dose in the form of a suspension of white or almost white.

Excipients: 1,1,1,2-tetrafluoroethane (to 75 mg).

120 doses – inhalers aluminum (1) the metering valve acts – packs cardboard.

Aerosol for inhalation dose in the form of a suspension of white or almost white.

Excipients: 1,1,1,2-tetrafluoroethane (to 75 mg).

120 doses – inhalers aluminum (1) the metering valve acts – 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^® It may be an alternative for patients, are obtained simultaneously agonist β₂-adrenoceptor agonist and inhaled corticosteroids (from different inhalers).

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 by using double dose of Seretide^® 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%, Depending on the inhaler. 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_ss fluticasone propionate sostavlyaet 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^® It 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 in a dosage form, which contains a dose of fluticasone propionate, proper severity of the disease.

The recommended dose for Adults and children 12 and older – 2 inhalation (25 mcg salmeterol and 50 micrograms fluticasone propionate) 2 times / day, or 2 inhalation (25 mcg salmeterol and 125 micrograms fluticasone propionate) 2 times / day, or 2 inhalation (25 mcg salmeterol and 250 micrograms fluticasone propionate) 2 times / day.

To children 4 and older recommended 2 inhalation (25 mcg salmeterol and 50 micrograms fluticasone propionate) 2 times / day.

The dose of Seretide^® should be reduced to the minimum effective dose. If symptom control offer 2 Seretide inhalation per day, Minimal effective dose can be 1 inhalations per day.

At COPD to Adult The maximum recommended dose is 2 inhalation (25 mcg salmeterol and 250 micrograms fluticasone propionate) 2 times / day.

In Elderly patients and patients c impaired hepatic or renal function a dose reduction is not required.

Mode of application

Before the first use of an inhaler or an inhaler if you have not used a week or longer, remove the cap from the mouthpiece, gently squeezing the sides of the cap, shake the inhaler well and release one jet in the air, To make sure, it works.

Using the inhaler

1. Remove the cap from the mouthpiece, gently squeezing the sides of the cap, and inspect the mouthpiece inside and outside, To make sure, it was clean.

2. Well shake the inhaler.

3. Hold the inhaler between your thumb and forefinger vertically upside down, while the thumb should be positioned on the basis of a mouthpiece.

4. Make maximum exhalation, put mouthpiece in your mouth between your teeth and grasping his lips, no clenching teeth.

5. At the start of the breath through your mouth, press the top of the inhaler to release a dose of Seretide^®, while continuing to take a deep breath.

6. Holding his breath, removed the mouthpiece from the mouth and remove your finger from the top of the inhaler. Continue to hold your breath as long as possible.

7. For the second dose, holding the inhaler in a vertical position, wait around 30 seconds and then repeat step 2-6.

8. Tight-fitting mouthpiece protective cap.

The drug can also be applied via a spacer (eg, “Volyumatyk”).

It will be appreciated, that step 4, 5 and 6 should be carried out slowly, all requirements. It should begin to breathe in as slowly as possible, immediately before pressing the inhaler valve. In the first few times it is recommended to practice before the mirror. If you notice “fog”, leaving the top of the inhaler or the mouth corners, you should start again from stage 2.

The patient should follow the recommendations of a physician on the use of the inhaler, when difficulties arise, consult your doctor.

Adults should assist young children to use an inhaler. It wait, when the child exhale and bring the inhaler at the onset of inhalation.

It is recommended to practice using an inhaler with the child. Older children and adults with weak hands should hold the inhaler with both hands. Thus both index fingers should be placed at the top of the inhaler, and both thumbs – based on the lower die. Children drug is administered via an inhaler through a spacer with face mask (eg “Bebikhalyer”).

Cleaning the inhaler

The inhaler should be cleaned at least 1 times a week.

You should remove the protective cap from the mouthpiece. Do not remove the metal canister from the plastic casing. A dry cloth or cotton swab to wipe the inside and outside of the mouthpiece and the plastic casing – outside. Close the mouthpiece protective cap. Do not immerse the metal canister into water.

Side effect

As Seretide^® soderzhit salmeterol and fluticasone propionate, its side effects characteristic of each of these drugs. The simultaneous use of them causes additional side effects.

Seretide^® may cause paradoxical bronchospasm.

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

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

Seretide^®

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: rash, angioedema, Local swelling.

Other: tremor, kaliopenia (usually, transient, decrease with continued therapy salmeterol); rarely – artralgii, nervousness; rarely – giperglikemiâ; in some cases – painful muscle spasms.

Fluticasone propionate

The respiratory system: 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: theoretically 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.

Contraindications

- Children up to age 4 years;

- Hypersensitivity to the drug.

FROM caution It should be prescribed the drug for pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes, uncontrollable gipokaliemii, idiopathic hypertrophic subaortic stenosis, uncontrolled hypertension, aritmijax, QT prolongation on the ECG, CHD, hypoxia of different genesis, Cataracts, glaucoma, gipotireoze, osteoporosis, pregnancy, in the period of lactation.

Pregnancy and lactation

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

Cautions

Seretide^® 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^® 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^®. Candidiasis prescribe antifungal drugs for local use, continuing therapy Seretide^®.

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, In such situations, 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^® does 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^®, 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.

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

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^® 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.

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 of Seretide^® excessively high doses probably significant adrenal suppression. There are rare reports of acute adrenal Stroke, which occurs mainly in children, receiving Seretide^® in extremely 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^® 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^® as a result of 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^® doses, exceeding recommended. Important is regular evaluation of the effectiveness of therapy and dose reduction of Seretide^® 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.

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, which manifested the development of Cushing's syndrome 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.

In an application with Seretide^® xanthine derivatives, SCS and diuretics increase the risk of hypokalemia (especially in patients with acute exacerbation of bronchial asthma, during hypoxia).

In an application with Seretide^® MAO inhibitors and tricyclic antidepressants increase the risk of side effects from the cardiovascular system.

Seretide^® compatible with kromoglitsievoy acid.

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; Do not freeze, Do not expose to direct sunlight. Shelf life – 2 year.