Avamys nasal spray 27.5 µg/dose 120 doses fl
Pharmacological group:
Glucocorticosteroid for local use.
Pharmacological properties:
Fluticasone furoate is a synthetic trifluorinated glucocorticosteroid with high affinity for glucocorticosteroid receptors and has a pronounced anti-inflammatory effect.
Pharmacokinetics:
Suction.
Fluticasone furoate is not completely absorbed, undergoing first-pass metabolism in the liver, resulting in negligible systemic exposure. Intranasal administration of 110 mcg once daily does not usually result in measurable plasma concentrations (
Distribution.
Fluticasone furoate is more than 99% bound to plasma proteins. When equilibrium concentration is reached, the volume of distribution of fluticasone furoate averages 608 liters.
Metabolism.
Fluticasone furoate is rapidly eliminated from the systemic circulation (total plasma clearance 58.7 l), mainly through metabolism in the liver with the formation of an inactive 17p-carboxyl metabolite (GW694301X) with the participation of the CYP3A4 enzyme of the cytochrome P450 system. The main route of metabolism is the hydrolysis of the S-fluoromethylcabrothioate group with the formation of a 17P-carboxylic acid metabolite.
In vivo studies have shown that fluticasone furoate is not degraded to fluticasone.
Excretion.
Excretion of fluticasone furoate and its metabolites when administered orally and intravenously is primarily through the intestines, which reflects their excretion in bile. About 1% and 2% are excreted by the kidneys after oral administration and intravenous administration, respectively.
Special groups of patients.
Elderly patients.
Pharmacokinetic data are presented only for a small number of elderly patients (n=23/872; 2.6%). There is no evidence that quantifiable concentrations of fluticasone furoate are higher in elderly patients than in younger patients.
Children.
Fluticasone furoate is not usually found in quantifiable concentrations (
Patients with impaired renal function.
Fluticasone furoate was not detected in the urine of healthy volunteers after intranasal administration. Less than 1% of metabolites are excreted via the kidneys, so renal dysfunction theoretically cannot affect the pharmacokinetics of fluticasone furoate.
Patients with impaired liver function.
A study in patients with moderate hepatic impairment who took 400 mcg of fluticasone furoate as a single inhalation dose showed an increase in maximum concentration (Cmax 42%) and an increase in the area under the concentration-time pharmacokinetic curve compared with healthy volunteers. Based on the study results, on average, the estimated exposure to intranasal fluticasone furoate 110 mcg in this patient population would not result in cortisol suppression. Therefore, mild hepatic impairment is not likely to result in clinically significant effects at the standard adult dose.
Other pharmacokinetic parameters.
Concentrations of fluticasone furoate are usually undetectable (
Fluticasone (Fluticasonum)
Fluticasone propionate is a substance with a strong anti-inflammatory effect. With intranasal administration, no pronounced systemic effect or inhibition of the hypothalamic-pituitary-adrenal system is observed.
Interaction with intracellular glucocorticoid receptors leads to the formation of dimers of the glucocorticoid-glucocorticoid receptor complex. The steroid hormone-receptor complex is transported into the cell nucleus. In the nucleus, this complex interacts with effector elements localized on acceptor sites of chromatin (genes). As a result of the interaction, gene expression is stimulated or inhibited; this leads to changes in the synthesis of messenger RNA and proteins. The anti-inflammatory effect is due to several factors:
1. The drug induces the synthesis of lipocortin, which inhibits the activity of phospholipase A2. Inhibition of phospholipase A2-mediated hydrolysis of membrane phospholipids in damaged tissues prevents the formation of arachidonic acid. Impaired formation of arachidonic acid actually means inhibition of prostaglandin synthesis, since arachidonic acid is a substrate for further metabolism through the cyclooxygenase pathway, as well as through the lipoxygenase pathway with a corresponding inhibition of leukotriene synthesis.
2. The anti-inflammatory effect of glucocorticoids is potentiated by their ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins at the site of inflammation, including pro-inflammatory prostaglandins E2 and I2.
3. Prednisolone inhibits the expression of intercellular adhesion molecules in the endothelium of blood vessels, disrupting the penetration of neutrophils and monocytes into the site of inflammation. After the administration of glucocorticoids, an increase in the concentration of neutrophils in the blood is noted (due to their receipt from the bone marrow and due to the restriction of migration from the blood vessels). This causes a decrease in the number of neutrophils at the site of inflammation.
Glucocorticoids inhibit the transcription of genes for cytokines that stimulate the inflammatory and immune response (IL-1, IL-2, IL-6, IL-8), as well as tumor necrosis factor (and some others).
Suppresses the proliferation of mast cells, eosinophils, lymphocytes, macrophages, neutrophils; reduces the production of inflammatory mediators and other biological active substances (histamine, prostaglandins, leukotrienes, cytokines) during the early and late phases of the allergic reaction. Fluticasone propionate has a rapid anti-inflammatory effect on the nasal mucosa, and its antiallergic effect appears within 2-4 hours after the first application. Reduces sneezing, itchy nose, runny nose, nasal congestion, discomfort in the sinuses and pressure around the nose and eyes. In addition, it relieves eye symptoms associated with allergic rhinitis. A decrease in the severity of symptoms (especially nasal congestion) persists for 24 hours after a single administration of a spray at a dose of 200 mcg. Fluticasone propionate improves the quality of life of patients, including physical and social activity.
Indications for use of the drug Fluticasone
basic anti-inflammatory therapy for asthma; in adults - asthma with mild, moderate and severe course, in children - with insufficient effectiveness of preventive therapy carried out by other means; COPD; prevention and treatment of seasonal allergic rhinitis. Cream and ointment - eczema, nodular prurigo (Hyda), psoriasis, neurodermatoses (including lichen simplex), lichen planus, contact hypersensitivity reactions, discoid lupus erythematosus, generalized erythroderma, insect bites, miliaria erythematosus, seborrheic dermatitis.
Side effects of the drug Fluticasone
Aerosol for inhalation - candidiasis of the oral mucosa and pharynx (to prevent it, it is recommended to rinse your mouth with water after inhalation), hoarseness, paradoxical bronchospasm (requires the use of fast-acting inhaled bronchodilators), hypersensitivity reactions (skin manifestations). Nasal aerosol - very rarely, dryness and irritation of the mucous membrane of the nasopharynx, unpleasant taste and smell, and nosebleeds are possible. In isolated cases, perforation of the nasal septum, especially in patients with a history of surgical intervention in the nasal cavity.
Special instructions for the use of the drug Fluticasone
Treatment of patients with asthma is carried out in stages; The patient's condition is assessed clinically and by examining respiratory function. An increase in the frequency of use of short-acting inhaled β2-agonists to relieve asthma attacks indicates a deterioration in control over the course of the disease and requires a revision of the treatment plan. A sudden and progressive deterioration in the course of asthma poses a potential threat to the patient’s life and requires an increase in the dose of GCS. Patients at risk require daily peak flow measurements. Fluticasone is not intended to relieve an acute attack of asthma; it is used for long-term preventive therapy. To relieve asthma attacks, patients are advised to use fast- and short-acting inhaled bronchodilators. Patients with severe asthma require high doses of inhaled and oral corticosteroids, subject to regular medical supervision. A sudden deterioration in the course of the disease may require an increase in the dose of GCS. A small number of adults may experience a slight decrease in plasma cortisol levels when taking fluticasone in high doses (above 1 mg/day), however, adrenal function and adrenal reserve usually remain within normal limits. Patients who have previously used other inhaled or systemic corticosteroids, after switching to inhaled fluticasone for a long period of time, remain at risk of reducing the functional reserve of the adrenal cortex. This should be taken into account if urgent surgical or other medical procedures are necessary; some patients may require consultation with an endocrinologist to determine the degree of adrenal dysfunction. It is always necessary to take into account the possibility of residual dysfunction of the adrenal cortex in stressful situations (respiratory infections, severe intercurrent illnesses, surgery, trauma, etc.) and decide on the need for additional administration of GCS. In children taking fluticasone at recommended doses, adrenal function and reserve are usually maintained within normal age limits. No systemic side effects in children (especially growth disturbances) were observed with the use of inhaled fluticasone, however, it is necessary to take into account the possible effects of previous treatment with corticosteroids or periodic use of systemic corticosteroids. In general, the therapeutic effect of inhaled fluticasone can significantly reduce the need for oral corticosteroids. Insufficient therapeutic effect or exacerbation of asthma requires an increase in the dose of fluticasone and, if necessary, additional administration of systemic corticosteroids and/or an antibiotic (in the presence of infection). Replacement of systemic steroid treatment with inhaled fluticasone and subsequent therapy require special attention, since it may take considerable time to restore adrenal function after systemic therapy with corticosteroids. In such patients, adrenal function should be regularly monitored and the dose of systemically administered corticosteroids should be gradually reduced. Replacing systemic GCS with its inhaled use may lead to the development of diseases such as allergic rhinitis or eczema, previously controlled by systemic GCS therapy. If these reactions occur, symptomatic therapy with antihistamines is carried out, including the prescription of topical medications; Local administration of GCS is possible. Treatment with fluticasone should not be interrupted suddenly. As with the use of other inhaled corticosteroids, careful monitoring of patients with pulmonary tuberculosis is necessary. Infections of the nasal cavity and paranasal sinuses are not a specific contraindication for the use of nasal aerosol. Although fluticasone is effective in relieving symptoms of seasonal allergic rhinitis, additional therapy may be required to relieve ocular symptoms. When deciding whether to prescribe fluticasone during pregnancy and lactation, the expected benefit to the mother should be weighed against the potential risk to the fetus or child. Avoid getting cream or ointment in your eyes.
