Seretide, aerosol 25 mcg+50 mcg/dose 120 doses

The drug Seretide® is a combined preparation that contains salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents symptoms of bronchospasm, fluticasone propionate improves pulmonary function and prevents exacerbation of the disease. Due to its more convenient dosing regimen, Seretide® may be an alternative for patients who simultaneously receive a β₂-adrenoreceptor agonist and an inhaled GCS from different inhalers.

Salmeterol is a selective long-acting (up to 12 h) β₂ adrenoreceptor agonist that has a long side chain that binds to the outer domain of the receptor.

The pharmacological properties of salmeterol provide more effective protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours) than short-acting β₂-adrenoreceptor agonists.

In vitro studies have shown that salmeterol is a potent inhibitor of the release from the human lung of mast cell mediators such as histamine, leukotrienes and prostaglandin D₂ and has a long duration of action.

Salmeterol inhibits the early and late phases of response to inhaled allergens. Inhibition of the late phase response persists for more than 30 hours after a single dose, at which time the bronchodilator effect is no longer present.

Single administration of salmeterol attenuates bronchial hyperresponsiveness. This indicates that in addition to bronchodilator activity, salmeterol has an additional action unrelated to bronchial dilation, the clinical significance of which has not been definitively established. This mechanism of action is different from the anti-inflammatory effect of GCS.

Fluticasone propionate belongs to a group of GCS for local use and when administered by inhalation in the recommended doses it has a pronounced anti-inflammatory and anti-allergic effect in the lungs, which leads to a reduction of clinical symptoms, reducing the frequency of exacerbations of bronchial asthma. Fluticasone propionate does not cause adverse effects observed with systemic corticosteroids.

In long-term use of inhaled fluticasone propionate, daily secretion of adrenal cortical hormones remains within normal limits in both adults and children, even when used at the maximum recommended doses. After switching patients receiving other inhaled GCSs to fluticasone propionate, daily adrenal hormone secretion gradually improves despite prior and current intermittent use of oral steroids. This indicates recovery of adrenal function against the background of inhaled use of fluticasone propionate. With prolonged use of fluticasone propionate, reserve function of the adrenal cortex also remains within normal limits, as evidenced by a normal increase in cortisol production in response to appropriate stimulation (it should be considered that the residual decrease in adrenal reserve caused by previous therapy may persist for a long time).

Indications

Baseline therapy of diseases accompanied by reversible airway obstruction (including bronchial asthma in children and adults) when the prescription of combined therapy – bronchodilator and a drug from the group of inhaled GCS is advisable:

– in patients receiving effective maintenance doses of long-acting b-adrenoceptor agonists and inhaled GCS;
– in patients with persistent symptoms of the disease against the background of inhaled GCS therapy;
– in patients receiving regular bronchodilator treatment and in need of inhaled GCS.

Maintenance therapy for COPD.

Active ingredient

Composition

1 dose of aerosol for inhalation contains:

acting substances:

salmeterol xinaphoate (equivalent to salmeterol 25 µg) 36.3 µg,

fluticasone propionate 50 µg.,

auxiliary substances:

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

How to take, the 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 course of treatment and dose changes are determined individually by the doctor.

The patient should be prescribed the drug in a dosage form that contains a dose of fluticasone propionate appropriate for the severity of the disease.

. Recommended doses for adults and children aged 12 years and older are 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 older, 2 inhalations (25 µg salmeterol and 50 µg fluticasone propionate) 2 times/day are recommended.

The dose of Seretide should be reduced to the lowest effective dose.

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

In elderly patients and patients with hepatic or renal impairment no dose reduction is required.

Interaction

The use of selective and nonselective beta-adrenoblockers should be avoided unless it is really necessary and justified.

Even despite very low plasma concentrations of salmeterol, its interaction with other substrates and inhibitors of CYP3A4 isoenzyme cannot be excluded.

When fluticasone propionate is used as inhaled, its plasma concentrations are low due to intensive metabolism during “first passage” through the liver under the influence of CYP3A4 isoenzyme and high systemic clearance. Because of this clinically significant interaction involving fluticasone propionate is unlikely.

Caution should be exercised when concomitant use of known CYP3A4 inhibitors and fluticasone propionate, because in these situations the plasma levels of the latter may increase.

Ritonavir (a highly active inhibitor of CYP3A4 isoenzyme) can cause a significant increase in plasma concentrations of fluticasone propionate, resulting in a significant decrease in serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients who simultaneously received fluticasone propionate and ritonavir, which was manifested by the development of Icenko-Cushing’s syndrome and depression of adrenal function.

Bearing this in mind, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient from the combined therapy exceeds the risk of systemic side effects of GCS.

Other CYP3A4 isoenzyme inhibitors cause negligible (erythromycin) and minor (ketoconazole) increases in plasma fluticasone propionate with virtually no reduction in serum cortisol concentrations. Despite this, caution is recommended when concomitant use of fluticasone propionate and strong CYP3A4 inhibitors (e.g., ketoconazole), since such combinations do not exclude the possibility of increasing plasma concentrations of fluticasone propionate.

When used concomitantly with Seretide, xanthine derivatives, GCS and diuretics increase the risk of hypokalemia (especially in patients with exacerbation of bronchial asthma, with hypoxia); MAO inhibitors and tricyclic antidepressants increase the risk of cardiovascular side effects.

Seretide is compatible with cromoglycic acid.

Special Instructions

Seretide is intended for long-term treatment of the disease, not for seizure management. Patients should be prescribed short-acting inhaled bronchodilators (e.g., salbutamol) to control the attacks and patients are recommended to have them with them at all times.
If paradoxical bronchospasm develops, a short-acting inhaled bronchodilator should be used immediately, Seretide should be stopped and an alternative therapy should be started, if indicated.

The treatment of bronchial asthma is recommended 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. If candidiasis occurs, antifungal medications for topical use are prescribed while continuing therapy with Seretide.

The more frequent use of short-acting bronchodilators to relieve symptoms indicates worsening disease control; in these situations, the patient should consult a physician.

The sudden and progressive worsening of bronchospastic syndrome control is potentially life threatening. In such situations, a physician’s supervision is necessary. If the dose of Seretide used does not adequately control the disease, an additional prescription of GCS may be required, and if the exacerbation is caused by an infection, antibiotics are prescribed.

Because of the risk of exacerbations, abrupt withdrawal of Seretide should be avoided and the dose of the drug should be reduced gradually under medical supervision.

When using any inhaled GCS it is possible to develop systemic effects (inhibition of adrenal function, growth retardation in children and adolescents, reduced bone mineral density, cataracts and glaucoma), especially with long-term use at high doses, but the possibility of these effects is much lower than with treatment with oral forms of GCS. With this in mind, the dose of inhaled GCS should be titrated to the lowest dose that maintains effective control.

In emergency and routine stress situations, the possibility of adrenal function depression and the need for GCS should always be kept in mind.

In case of resuscitation or surgery, the degree of adrenal insufficiency needs to be determined.
Some patients may have an individual high sensitivity to inhaled GCS.

Due to possible adrenal insufficiency, special care should be taken and adrenal function parameters should be regularly monitored when transferring patients who were on oral GCS to fluticasone propionate for inhalation. Allergic reactions (e.g., allergic rhinitis, eczema) that were previously suppressed by systemic GCS may occur when transferring patients from systemic GCS to inhaled therapy. In these situations it is recommended to conduct symptomatic treatment with antihistamines and/or topical agents (including GCS for topical use).

Cancellation of systemic GCS against the background of inhalation of fluticasone propionate should be carried out gradually. Patients should carry a card indicating that they may need to take additional GCS for various stressful situations.

Contraindications

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

. The drug should be used with caution in case of pulmonary tuberculosis, fungal, viral or bacterial respiratory infections, thyrotoxicosis, pheochromocytoma, diabetes, uncontrolled hypokalemia, Idiopathic hypertrophic subaortic stenosis, uncontrolled arterial hypertension, arrhythmias, prolonged QT interval in ECG, CHD, hypoxia of different genesis, cataracts, glaucoma, hypothyroidism, osteoporosis, pregnancy, 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 may cause paradoxical bronchospasm.

Salmeterol
Cardiovascular system: palpitations, headache (usually transient, decreases as therapy with salmeterol continues); usually in predisposed patients – cardiac rhythm disturbances (including atrial fibrillation, supraventricular tachycardia, extrasystole).

Digestive system: rarely – abdominal pain, nausea, vomiting; in some cases – taste disorders.
Allergic reactions: rash, angioedema.

Other: tremor, hypokalemia (usually transient, decreases with continuation of therapy with salmeterol); rarely – arthralgia, nervousness, peripheral edema; in some cases – irritation of oropharyngeal mucosa, painful muscle spasms.

Fluticasone propionate

Respiratory system: hoarseness of voice, candidiasis of the mouth and pharynx.

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

Systemic reactions: theoretically possible inhibition of adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma.

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.

In prolonged inhalation of Seretide at excessively high doses, marked suppression of adrenal function is possible. 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 seizures. Situations that may serve as triggers for acute adrenal crisis include trauma, surgery, infection, or a rapid decrease in the dose of fluticasone propionate in Seretide.

Treatment: Salmeterol-induced symptoms should be managed by administration of an antidote, a cardioselective beta-adrenoblocker. In cases where Seretide needs to be withdrawn due to an overdose of its constituent salmeterol, an appropriate replacement GCS should be administered to the patient.

Symptoms caused by fluticasone propionate usually do not require emergency therapy because in most cases normal adrenal function is restored within a few days. In chronic overdose, monitoring of adrenal cortical reserve function is recommended.

To avoid overdose, patients should not use Seretide in doses greater than recommended. Regular evaluation of the effectiveness of therapy and reduction of the Seretide dose to the minimum level that provides effective control of disease symptoms is important.

Pregnancy use

In pregnancy and during lactation (breastfeeding), Seretide may be administered only if the anticipated benefit to the mother outweighs any possible risk to the fetus or child.

Similarities