Seretide, inhalation aerosol 25+250mcg/dose, 120 doses

Composition

1 dose contains salmeterol xynafoate (equivalent to salmeterol 25 mcg) 36.3 mcg,

fluticasone propionate 250 mcg.

Auxiliary substances:

1,1,1,2-tetrafluoroethane (up to 75 mg).

Pharmacological action

Seretide 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 h) 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 conducted among 318 adult patients with persistent bronchial asthma showed that when using a double dose of Seretide drugs 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 beta-adrenomimetics (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 ( 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.

Indications

Basic therapy of diseases accompanied by reversible airway obstruction (including bronchial asthma in children and adults), when it is advisable to prescribe a combination therapy-a bronchodilator and a drug from the group of inhaled corticosteroids:  – in patients receiving effective maintenance doses of long-acting b-adrenergic agonists and inhaled corticosteroids – – in patients who persist in symptoms of the disease against the background of inhaled corticosteroid therapy; – in patients receiving regular treatment with bronchodilators and requiring inhaled corticosteroids.

Maintenance therapy for COPD.

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

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

With caution, the drug should be prescribed for 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, coronary heart disease, hypoxia of various origins, cataracts, glaucoma, hypothyroidism, osteoporosis, during pregnancy and lactation.

Side effects

Since Seretide contains salmeterol and fluticasone propionate, its side effects are typical for each of these drugs. Their simultaneous use does not cause additional side effects. Seretide can cause paradoxical bronchospasm.

Salmeterol

From the cardiovascular system:  palpitations, headache (usually transient, decreasing with continued salmeterol therapy); usually in predisposed patients-cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystole).

From the digestive system:  rarely-abdominal pain, nausea, vomiting; in some cases-a violation of taste sensations.

Allergic reactions:  rash, angioedema.

Other services:  tremor, hypokalemia (usually transient, decrease as salmeterol therapy continues); rarely-arthralgia, nervousness, peripheral edema; in some cases-irritation of the oropharyngeal mucosa, painful muscle spasms. Fluticasone Propionate

Respiratory system disorders:  hoarseness of voice, candidiasis of the oral cavity and pharynx.

Allergic reactions:  skin manifestations, angioedema (mainly of the face and oropharynx), bronchospasm, anaphylactic reactions.

Systemic reactions:  theoretically, it is possible to inhibit the function of the adrenal glands, stunted growth in children and adolescents, reduced bone mineral density, cataracts and glaucoma.

Interaction

The use of selective and non-selective beta-blockers should be avoided, except when it is really necessary and justified.

Even though salmeterol has a very low plasma concentration, its interaction with other substrates and inhibitors of the CYP3A4 isoenzyme cannot be excluded.

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, 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 side effects from the cardiovascular system.

Seretide is compatible with Cromoglicic acid.

How to take, course of use and dosage

Seretide 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 the drug in a dosage form that contains a dose of fluticasone propionate that corresponds to the severity of the disease.

The recommended dose for adults and children aged 12 years and older is 2 inhalations (25 µg salmeterol and 50 µg fluticasone propionate) 2 times/day, or 2 inhalations (25 µg salmeterol and 125 µg fluticasone propionate) 2 times/day, or 2 inhalations (25 µg salmeterol and 250 µg fluticasone propionate) 2 times/day.

For children aged 4 years and above recommended 2 inhalations (25 µg salmeterol and 50 µg fluticasone propionate) 2 times/day. The dose of Seretide should be reduced to the minimum effective dose.

For adults with COPD, the maximum recommended dose is 2 inhalations (25 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times / day.

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

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 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 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.

Treatment: symptoms caused by the action of salmeterol should be stopped by the introduction of an antidote – a cardioselective beta-blocker. In cases where withdrawal of Seretide 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 in doses exceeding the recommended ones. It is important to regularly evaluate the effectiveness of therapy and reduce the dose of Seretide to the minimum level that provides effective control of symptoms of the disease.

Special instructions

Seretide 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, Seretide should be discontinued, and alternative therapy should be initiated if indicated.

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 your mouth with water after inhaling Seretide. When candidiasis is prescribed antifungal drugs for topical use, continuing therapy with Seretide.

More frequent use of short-acting bronchodilators to relieve symptoms indicates a deterioration in disease control, 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 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 should be avoided, 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.

Form of production

Metered-dose inhalation aerosol.

Storage conditions

At temperatures below 30 °C

Shelf life

2 years

Active ingredient

Salmeterol, Fluticasone

Conditions of release from pharmacies

By prescription

Dosage form

aerosol for inhalation

Purpose

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

Indications

Low learning rate, Bronchial asthma