Salticasone, 50 mcg+100 mcg 60 pcs

Clinical and pharmacological group: Anti-inflammatory and bronchodilator

Pharmacological action

Combination drug that contains salmeterol and fluticasone propionate with different mechanisms of action. Salmeterol prevents symptoms of bronchospasm; fluticasone propionate improves pulmonary function and prevents exacerbation of the disease.

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 h) 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 h after a single dose, at which time the bronchodilator effect is no longer present. A single dose of salmeterol attenuates bronchial hyperresponsiveness. This indicates that salmeterol, in addition to its bronchodilator activity, 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 – GCS for topical use and when administered by inhalation in recommended doses 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.

Pharmacokinetics

Salmeterol

Acts locally in the lung tissues, so its plasma content does not correlate with therapeutic effects. Data on its pharmacokinetics are very limited because when inhaled at therapeutic doses, its C_max in plasma is extremely low (about 200 pg/mL and below). After regular inhalation with salmeterol, hydroxynaphthic acid, C_ss of which is about 100 ng/mL, can be detected in the blood. These concentrations are 1000 times lower than the C_ss observed in toxicity studies. Results of in vitro studies have shown that salmeterol is extensively metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system to α-hydroxysalmeterol by aliphatic oxidation.

The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies depending on the inhaler used; it is 5.3% when the combination of salmeterol and fluticasone propionate is administered with a metered dose inhalation aerosol. Patients with bronchial asthma and COPD have lower plasma concentrations of fluticasone propionate. Systemic absorption occurs primarily through the lungs. At first it is more rapid, but then its rate 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 GI tract is less than 1%. As the inhaled dose increases, there is a linear increase in plasma concentrations of fluticasone propionate. Fluticasone has a large V_d in equilibrium (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 by the CYP3A4 isoenzyme of the cytochrome P450 system to an inactive carboxyl metabolite. Fluticasone distribution is characterized by rapid plasma clearance (1150 ml/min) and a final T_1/2 of approximately 8 h. Renal clearance of unchanged fluticasone propionate is negligible (< 0.2%), with less than 5% of the dose excreted in the urine as a metabolite.

Indications

For the regular treatment of bronchial asthma if combined therapy with a long-acting beta2-adrenomimetic and an inhaled GCS is indicated.

For maintenance therapy in patients with COPD with an ORP1< 60% of normal before inhaled bronchodilator and a history of recurrent exacerbations in whom severe symptoms persist despite regular bronchodilator therapy.

Active ingredient

Composition

How to take, the dosage

It is used only in the form of inhalation.

The dose and route of administration are determined individually, depending on the indication, age of the patient, the dosage form used, and the inhaler used.

Interaction

Because of the risk of bronchospasm, the use of selective and nonselective beta-adrenoblockers should be avoided unless they are urgently needed by the patient.

A drug interaction study has shown that ritonavir, a highly active CYP3A4 isoenzyme inhibitor, can cause a dramatic increase in plasma concentrations of fluticasone propionate, resulting in significantly lower serum cortisol concentrations. There are reports of clinically significant drug interactions between fluticasone and ritonavir, which led to systemic effects of GCS, including Cushing’s syndrome and suppression of adrenal function. Therefore, it is recommended that fluticasone propionate and ritonavir be avoided together unless the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS.

Studies have shown that other CYP3A4 isoenzyme inhibitors cause negligible (erythromycin) and minor (ketoconazole) increases in plasma fluticasone 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, which may potentially increase its systemic effects.

In a drug interaction study, it was found that the use of ketoconazole as concomitant systemic therapy significantly increased plasma concentrations of salmeterol (1.4-fold increase in Cmax and 15-fold increase in AUC). This may lead to prolongation of the QTc interval. Caution should be exercised when co-administering strong CYP3A4 inhibitors (e.g., ketoconazole) and salmeterol.

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.

Special Instructions

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

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

The sudden and worsening worsening of bronchospastic syndrome control is potentially life-threatening, and in these situations, the patient should also see a physician.

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

Any inhaled GKS can cause systemic effects, especially with long-term use at high doses; however, these symptoms are much less likely to occur than with oral GKS. Possible systemic reactions include Cushing’s syndrome, Cushing’s traits, depressed adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, when treating bronchial asthma, it is important to reduce the dose to the lowest dose that provides effective control of the disease.

In emergency and routine situations with the potential for stress, the possibility of inhibition of adrenal cortical function and the need for GCS should always be considered.

In resuscitation or surgical procedures, a determination of the degree of adrenal insufficiency is required.

It is recommended that the height of children who receive prolonged therapy with inhaled GCS be measured regularly.

In view of the potential for adrenal depression, patients transferred from oral GKS to inhaled therapy with fluticasone propionate should be treated with extreme caution and their adrenal function monitored regularly.

After initiation of inhaled fluticasone treatment, systemic GCS should be withdrawn gradually, and these patients should have a special patient record indicating the possible need for additional GCS administration in stressful situations.

In patients with exacerbations of bronchial asthma, hypoxia, plasma potassium concentrations should be monitored.

There are very rare reports of elevated blood glucose levels; this should be considered if this combination should be used in patients with diabetes mellitus.

Contraindications

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

With caution: Patients with acute or latent pulmonary tuberculosis; thyrotoxicosis; fungal, viral or bacterial respiratory infections; cardiovascular disease, supraventricular tachycardia and extrasystole, ventricular extrasystole, atrial fibrillation; hypokalemia; glaucoma, cataracts, osteoporosis; diabetes.

Side effects

Infectious and parasitic diseases: often – oral and pharyngeal candidiasis, pneumonia (in patients with COPD); rarely – oesophageal candidiasis.

The immune system: hypersensitivity reactions: infrequent – skin hypersensitivity reactions, dyspnea; rarely – anaphylactic reactions.

Endocrine system disorders: infrequent cataracts; rarely – glaucoma, Cushing’s syndrome, cushingoid symptoms, depressed adrenal function, growth retardation in children and adolescents, decreased bone mineral density.

Metabolism and nutrition: infrequent – hyperglycemia; very rare – hypokalemia.

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

Nervous system disorders: very common – headache; infrequent – tremor.

Heart: infrequent – palpitations, tachycardia, atrial fibrillation; rarely – arrhythmia, including ventricular extrasystole, supraventricular tachycardia and extrasystole.

Respiratory system: frequently – hoarseness of voice and/or dysphonia; infrequently – irritation of the throat; rarely – paradoxical bronchospasm.

Skin and subcutaneous tissue: infrequent – bruising.

Muscular system disorders: often – muscle cramps, arthralgia.

Pregnancy use

Similarities