Advair is a combined bronchodilatory medication (contains salmeterol and fluticasone).
Advair: instructions for Use
Salmeterol is a long-term action (12 hours) 2-β selective adrenoreceptor agonists. Salmeterol molecule has a long side chain, which binds to external receptor area. Due to these pharmacological properties, salmeterol is more effective for histamininduced bronchospasm prevention and causes longer bronchodilation in comparison with ordinary short-term action 2-β receptors agonists. Effectively inhibits release of lung tissue mast cell neuromediators, such as histamine, leukotrienes and PgD2. It suppresses early and late allergic reaction stages; after administration of a single dose it decreases bronchial hyperreactivity, late stage inhibition lasts 30 hours, when bronchodilatory effect is no longer present.
Fluticasone is a local glucocorticosteroid. At pulmonary administration has expressed anti-inflammatory effect, which leads to symptoms severity decrease and reduces exacerbations frequency, accompanied with respiratory obstruction. At long-term inhaled fluticasone administration in maximal dose daily and reserve adrenal cortex hormones secretion remains within normal range at adults and children. Residual reserve adrenal function decrease may persist long after therapy.
Simultaneous pulmonary salmeterol and fluticasone administration doesn’t affect pharmacokinetics of each of these substances.
Salmeterol: pulmonary administration in therapeutic doses causes very low drug concentrations in plasma (200 pg/ml or less). At regular inhaled salmeterol administration hydroxynaphthoic acid is determined in systemic circulation in concentrations up to 100 ng/ml.
Fluticasone: after inhalation relative bioaccessibility is observed – 10-30% depending on drug delivery system. Systemic absorption occurs primarily in lungs. Part of inhaled dose may be swallowed, but its systemic effect is minimal due to low drug solubility in water and intensive metabolism during «first passage» through liver. Fluticasone ingestion bioaccessibility is less than 1%. There is a direct correlation between inhaled dosage and fluticasone systemic effect, volume of distribution – about 300 l. It is metabolized in liver to inactive metabolites accompanied with CYP3A4 cytochrome P450 system. Less than 5% of metabolites are excreted with urine. Plasma clearance – 1,15 l/min. T1/2 – 8 h.
- children’s age (up to 4 years).
- pulmonary tuberculosis;
- fungal, viral or bacterial respiratory infection;
- uncontrolled hypokalemia;
- idiopathic hypertrophic subaortic stenosis (IHSS);
- uncontrolled arterial hypertension;
- prolongation of Q-T interval at ECG;
- hypoxia of different genesis;
- lactation period.
- Advair is intended for long-term treatment and disease exacerbations prevention rather than for rapid symptoms relief (short-term action inhaled bronchodilators should be used).
- The drug should be taken regularly, even if symptoms are absence.
- Increase demand for short-term action bronchodilator indicates disease exacerbations.
- Do not abruptly stop the drug therapy.
- Long-term administration of any inhaled glucocorticosteroids, especially in high doses, may cause systemic impact. It is important to reduce inhaled glucocorticosteroids dosage to minimal efficient after achieving therapeutic benefit for controlling disease in order to prevent systemic side effects development.
- It is recommended to regularly monitor children’s growth dynamics, receiving inhaled glucocorticosteroids for a long time.
- Due to possible adrenal insufficiency patients should be careful and regular monitor adrenal cortex function indications when transferring patients from oral glucocorticosteroids to inhaled fluticasone. Systemic glucocorticosteroids cancellation should be gradual. During stress period additional glucocorticosteroids intake may be necessary.
- If Advair is withdrawn because of salmeterol overdose, patient should be prescribed appropriate glucocorticosteroid substitutional therapy.
- In rare cases when transferring patients from systemic glucocorticosteroids to inhalation therapy hypereosinophilia may occur (including Churg-Strauss disease). This usually happens during dosage reduction or systemic glucocorticosteroids withdrawal, but the cause still has not been established.
- When transferring patients from systemic glucocorticosteroids to inhalation therapy allergic reactions may also manifest (including allergic rhinitis, eczema), which previously were suppressed by systemic drugs.