Salticasone inhalation powder, 50mcg + 100mcg capsules 60pcs

Composition

Composition for one dose: Active ingredients: Salmeterol xynafoate 72.5 mcg (based on salmeterol) 50 mcg Fluticasone propionate 250 mcgmomedical substances: Sodium benzoate 2.0 mg Lactose monohydrate up to 12.0 mg gelatin capsules * capsule body: titanium dioxide 2%, gelatin up to 100% capsule cap: titanium dioxide 1%, gelatin up to 100%* applicable for the preparation intended for use with the Inhaler CDM®

single-dose inhaler Pharmacological action

Clinical and pharmacological group: A drug with anti-inflammatory and bronchodilator actionpharmacological action

A combination drug that contains salmeterol and fluticasone propionate, which have different mechanisms of action. Salmeterol prevents the onset of symptoms of bronchospasm, fluticasone propionate improves lung function and prevents exacerbation of the disease.

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 more effective protection against histamine-induced bronchoconstriction and longer bronchodilation (lasting at least 12 hours) than short-acting beta_-2-adrenergic agonists.

In vitro studies have shown that salmeterol is a potent inhibitor of the release of mast cell mediators from the human lungs, such as histamine, leukotrienes and prostaglandin_D2, and has a long period of action.

Salmeterol inhibits the early and late phases of the response to inhaled allergens. Inhibition of the late-phase response persists for more than 30 hours after a single dose, while 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 that is not associated with bronchial dilation, the clinical significance of which has not been definitively established. This mechanism of action differs from the anti-inflammatory effect of corticosteroids.

Fluticasone-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, a decrease in the frequency of exacerbations of bronchial asthma.

Pharmacokinetics

Salmeterol

It acts locally in lung tissues, so its content in blood plasma does not correlate with therapeutic effects. Data on its pharmacokinetics are very limited, because when inhaled at therapeutic doses, its_cmax in plasma is extremely low (about 200 pg / ml or lower). After regular inhalation with salmeterol, hydroxynaphthoic acid can be detected in the blood, the C_ss of which is about 100 ng / ml. These concentrations are 1000 times lower than the_csssobserved in toxicity studies. The results of an in vitro study showed that salmeterol is extensively metabolized by the cytochrome P450 isoenzyme CYP3A4 to α-hydroxysalmeterol by aliphatic oxidation.

Fluticasone

The absolute bioavailability of inhaled fluticasone propionate in healthy people varies depending on the inhaler used; when a combination of salmeterol and fluticasone propionate is administered using a metered-dose aerosol for inhalation, it is 5.3%. Patients with bronchial asthma and COPD have lower plasma concentrations of fluticasone propionate. Systemic absorption occurs primarily through the lungs. It’s faster at first, but then it 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 fluticasone propionate in water and due to its presystemic metabolism; bioavailability from the gastrointestinal tract is less than 1%. As the inhaled dose increases, there is a linear increase in the concentration of fluticasone propionate in the blood plasma. Fluticasone has a largeVd at steady state (about 300 L) and has a relatively high degree of binding to plasma proteins (91%). It is rapidly eliminated from the blood, mainly as a result of metabolism under the action of the cytochrome P450 isoenzyme CYP3A4 to an inactive carboxyl metabolite. Fluticasone distribution is characterized by rapid plasma clearance (1150 ml / min) and a final T_1/2of approximately 8 h. The renal clearance of unchanged fluticasone propionate is negligible (

Indications

For regular treatment of bronchial asthma, if combination therapy with a long-acting beta_-2-adrenomimetic and inhaled corticosteroids is indicated.

For maintenance therapy in patients with COPD with an FEV value of 1

Use during pregnancy and lactation

Use during pregnancy and lactation is permitted only if the potential benefit to the mother exceeds the possible risk to the fetus or infant.

Contraindications

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

With caution:  patients with acute or latent pulmonary tuberculosis; thyrotoxicosis; fungal, viral or bacterial infections of the respiratory system; cardiovascular diseases, supraventricular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation; hypokalemia; glaucoma, cataracts, osteoporosis; diabetes mellitus.

Side effects

Infectious and parasitic diseases:  often-candidiasis of the oral cavity and pharynx, pneumonia (in patients with COPD); rarely-candidiasis of the esophagus.

From the immune system:  hypersensitivity reactions: infrequently-skin hypersensitivity reactions, shortness of breath; rarely-anaphylactic reactions.

From the endocrine system:  infrequently-cataracts; rarely-glaucoma, Cushing’s syndrome, Cushing’s symptoms, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density.

From the side of metabolism and nutrition:  infrequently-hyperglycemia; very rarely-hypokalemia.

Mental disorders:  infrequently-anxiety, sleep disorders; rarely – changes in behavior, including hyperactivity and irritability (especially in children).

Nervous system disorders:  very often – headache; infrequently-tremor.

From the side of the heart:  infrequently-rapid heartbeat, tachycardia, atrial fibrillation; rarely-arrhythmia, including ventricular extrasystole, supraventricular tachycardia and extrasystole.

Respiratory system disorders:  often – hoarseness of voice and / or dysphonia; infrequently-pharyngeal irritation; rarely-paradoxical bronchospasm.

Skin and subcutaneous tissue disorders:  infrequently – bruising.

Musculoskeletal disorders:  often-muscle spasms, arthralgia.

Interaction

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

A drug interaction study has shown that ritonavir, a highly active inhibitor of the CYP3A4 isoenzyme, can cause a sharp increase in the concentration of fluticasone propionate in plasma, resulting in a significant decrease in serum cortisol concentrations. There are reports of clinically significant drug interactions between fluticasone and ritonavir that have resulted in systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, except in cases where the potential benefit to the patient exceeds the risk associated with the systemic effects of corticosteroids.

Studies have shown that other inhibitors of the CYP3A4 isoenzyme cause negligible (erythromycin) and insignificant (ketoconazole) increases in the content of fluticasone 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 in plasma, which can potentially increase its systemic effects.

In the study of drug interactions, it was found that the use of ketoconazole as concomitant systemic therapy significantly increases the concentration of salmeterol in blood plasma (an increase in_Cmax by 1.4 times and AUC by 15 times). This can lead to a longer QT interval_c. Caution should be exercised when co-prescribing strong CYP3A4 inhibitors (for example, ketoconazole) and salmeterol.

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.

How to take it, course of administration and dosage

It is used only in the form of inhalations.

The dose and dosage regimen are determined individually, depending on the indications, the patient’s age, the dosage form used and the inhaler used.

Special instructions

This combination is not intended to relieve acute symptoms, since in such cases a fast – and short-acting inhaled bronchodilator (for example, salbutamol) should be used.

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.

Patients with asthma should not abruptly stop treatment with this combination, the dose of the drug should be reduced gradually under the supervision of a doctor. In patients with COPD, discontinuation of the drug may be accompanied by symptoms of decompensation and requires medical supervision.

Any inhaled corticosteroid can cause systemic effects, especially when used for a long time in high doses; however, the likelihood of such symptoms is much lower than when treated with oral corticosteroids. Possible systemic reactions include Cushing’s syndrome, Cushing’s features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, in the treatment of bronchial asthma, it is important to reduce the dose to the lowest dose that provides effective control of the disease.

In emergency and planned situations with the possibility of stress, you should always take into account the possibility of suppression of the adrenal cortex and the need for 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.

Due to 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.

After starting treatment with inhaled fluticasone, systemic corticosteroids should be discontinued gradually, and such patients should carry a special patient card indicating 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 potassium in plasma.

There are very rare reports of an increase in blood glucose levels, this should be taken into account when using this combination in patients with diabetes mellitus.

Active ingredient

Salmeterol, Fluticasone

Conditions of release from pharmacies

By prescription

Dosage form

Capsules