Avamys nasal spray 27.5 mcg/dose 120 doses buy in Moscow at a price of 801 rubles

Pharmacological properties of the drug Fluticasone

GCS for inhalation and intranasal use. It has an anti-inflammatory effect, as a result of which it reduces the severity and frequency of asthma attacks, improves lung function and reduces the severity of COPD symptoms. The use of fluticasone is not accompanied by the development of side effects characteristic of systemic therapy with GCS. The level of secretion of endogenous corticosteroids during long-term treatment with inhaled fluticasone remains within normal limits even when used at the maximum dose. When replacing other inhaled corticosteroids with fluticasone, the function of the adrenal cortex is normalized, including in patients who continue to periodically use oral corticosteroids. However, any residual decrease in adrenal functional reserve after previous treatment with systemic corticosteroids may persist for a long time, which should be taken into account when determining the dose.

Avamis

AVAMYS Representative office: GlaxoSmithKline group of companies ATX code: R01AD12 Registration certificate holder: GlaxoSmithKline Trading, JSC produced by GLAXO OPERATIONS UK, Limited fluticasone furoate Release form, composition and packaging Dosed nasal spray in the form of a homogeneous white suspension. 1 dose of fluticasone furoate (micronized) 27.5 mcg Excipients: dextrose, dispersible cellulose (contains 11% carmellose sodium), polysorbate 80, benzalkonium chloride (50% solution), disodium edetate, purified water.

30 doses - orange glass bottles equipped with a spray device (1) - a plastic case with an indicator window, a push valve and a cap with an elastomer stop. 60 doses - orange glass bottles equipped with a spray device (1) - a plastic case with an indicator window, a push valve and a cap with an elastomer stop. 120 doses - orange glass bottles equipped with a spray device (1) - a plastic case with an indicator window, a push valve and a cap with an elastomer stop.

Clinical and pharmacological group: GCS for intranasal use Registration No.: •nasal dosage spray. 27.5 mcg/1 dose: vial. 30, 60 or 120 doses per dosage. spraying device - LSR-000477/10, 01/28/10. Validity period of reg. beat is not limited. DLO. ——————————————————————————— The description of the drug AVAMIS is based on the officially approved instructions for use of the drug AVAMIS for specialists and approved by the manufacturer for the 2013 edition of the year. ——————————————————————————— Pharmacological action | Pharmacokinetics | Indications | Dosage regimen | Side effect | Contraindications | Pregnancy and lactation | Special instructions | Overdose | Drug interactions | Terms of release from pharmacies | Storage conditions and expiration dates ——————————————————————————— Pharmacological action of GCS for topical use. Fluticasone furoate is a synthetic trifluorinated glucocorticosteroid with high affinity for glucocorticoid receptors and has a pronounced anti-inflammatory effect. Pharmacokinetics Absorption Fluticasone furoate is not completely absorbed, undergoing primary metabolism in the liver, resulting in negligible systemic exposure. Intranasal administration at a dose of 110 mcg 1 time / usually does not lead to the achievement of detectable concentrations in plasma (Distribution of Fluticasone furoate is bound to plasma proteins by more than 99%. When the equilibrium concentration is reached, Vd of fluticasone furoate is, on average, 608 l. Metabolism of 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 17β-carboxyl metabolite (GW694301X) with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system. The main route of metabolism is hydrolysis of the S-fluoromethylcabrothioate group with the formation 17β-carboxyl metabolite. In vivo studies have shown that fluticasone furoate is not broken down to fluticasone. Excretion: Excretion of fluticasone furoate and its metabolites when administered orally and intravenously occurs primarily through the intestines, reflecting their excretion in the bile. When taken orally and IV administration is excreted by the kidneys: 1% and 2%, respectively. Pharmacokinetics in special clinical situations 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. In children, when administered intranasally at a dose of 110 mcg 1 time / fluticasone furoate is usually not detected in concentrations that can be quantified (Fluticasone furoate was not detected in the urine of healthy volunteers when administered intranasally. Less than 1% of the metabolites are excreted by the kidneys, thus causing dysfunction kidneys theoretically cannot affect the pharmacokinetics of fluticasone furoate. In a study in patients with moderate hepatic impairment, inhaled use of fluticasone furoate at a dose of 400 mcg as a single inhalation showed an increase in Cmax by 42% and an increase in AUC0-∞ by 172%, compared with healthy volunteers. Based on the study results, on average, the estimated exposure to fluticasone furoate 110 mcg administered intranasally in this patient population would not result in cortisol suppression. Therefore, mild liver dysfunction would likely not result in clinically significant effects at the standard dose for adults. Concentrations of fluticasone furoate are usually not determined (Indications for use of the drug AVAMIS - symptomatic treatment of seasonal and year-round allergic rhinitis in adults and children over 2 years of age.

Dosage regimen The drug is used intranasally. To achieve maximum therapeutic effect, it is necessary to adhere to a regular regimen of use. The onset of action can be observed within 8 hours after the first administration. It may take several days to achieve maximum effect. The reason for the lack of immediate effect should be carefully explained to the patient. For the symptomatic treatment of seasonal and year-round allergic rhinitis in adults and adolescents aged 12 years and older, the recommended initial dose is 55 mcg (2 sprays) in each nostril 1 time / (110 mcg /). Once adequate symptom control is achieved, dose reduction to 27.5 mcg (1 spray) in each nostril 1 time per nostril (55 mcg/) may be effective for maintenance treatment. For children aged 2 to 11 years, the recommended starting dose is 27.5 mcg (1 spray) in each nostril 1 time/(55 mcg/). If there is no desired effect at a dose of 27.5 mcg (1 spray) in each nostril 1 time/, the dose can be increased to 55 mcg (2 sprays) in each nostril 1 time/ (110 mcg/). Once adequate control of symptoms is achieved, it is recommended to reduce the dose to 27.5 mcg (1 spray) in each nostril 1 time/(55 mcg/). There is insufficient data to recommend the use of intranasal fluticasone furoate for the treatment of seasonal and perennial allergic rhinitis in children under 2 years of age. Elderly patients do not require dose adjustment. In patients with impaired renal function, no dose adjustment is required. In patients with mild to moderate liver dysfunction, no dose adjustment is required. There are no data on use in patients with severe liver dysfunction. Rules for use and handling of the drug An indicator window in a plastic package allows you to control the level of the drug in the bottle. In 30- or 60-dose vials, the drug level will be visible immediately, and in 120-dose vials, the initial drug level is above the upper limit of the viewing window. The nasal spray is available in orange glass bottles, which are in plastic cases. To check the level of the drug in the bottle, you need to hold it up to the light. The level will be visible through the viewing window.

Preparation for use should be carried out when using the spray for the first time, as well as if the bottle was left open. Proper preparation for use will ensure that the required dose of the drug is injected. 1. Without removing the cap, shake the bottle well for 10 seconds. The drug is a rather thick suspension and becomes more liquid when shaken. Spraying is only possible after shaking. 2. Remove the cap by gently pulling it with your thumb and forefinger. 3. Hold the bottle vertically and point the tip away from you. 4. Press the button firmly and make several presses (minimum 6) until a small cloud appears from the tip (if you cannot press the button with one thumb, you should press it with the thumbs of both hands). 5. The spray is ready for use.

Using nasal spray 1. Shake the bottle thoroughly. 2. Remove the cap. 3. Clear your nose and tilt your head slightly forward. 4. Insert the tip into one nostril, continuing to hold the bottle vertically. 5. Point the tip of the sprayer at the outer wall of the nose, not at the nasal septum. This will ensure proper injection of the drug. 6. Start inhaling through your nose and press once with your fingers to spray the drug. 7. Remove the atomizer from your nostril and exhale through your mouth. 8. If it is necessary to make two injections into each nostril (as prescribed by a doctor), you should repeat steps 4-6. 9. Repeat the procedure for the other nostril. 10. Close the bottle with a cap. 11. Avoid getting the spray in your eyes. If the drug gets into your eyes, rinse them thoroughly with water.

Caring for the sprayer After each use: 1. Blot the tip and the inner surface of the cap with a dry, clean cloth. Avoid contact with water. 2. Do not try to clean the tip hole with a pin or other sharp objects. 3. Always cap the bottle and keep it closed. The cap protects the sprayer from dust and clogging, seals the bottle, and prevents accidental pressing of the button. If the sprayer does not work: 1. Check the level of the remaining drug in the bottle through the inspection window. If there is only a small amount of liquid left, it may not be enough to operate the sprayer. 2. Check the bottle for damage. 3. Check if the tip hole is clogged. Do not attempt to clean the tip hole with a pin or other sharp object. 4. Try to activate the device by repeating the procedure for preparing the nasal spray for use.

Side effects Determination of the frequency of adverse reactions: very often (≥1/10), often (≥1/100, From the respiratory system: very often - nosebleeds, often - ulceration of the nasal mucosa. In adults and adolescents, cases of nosebleeds were observed more common with long-term use (more than 6 weeks) than with short-term use (up to 6 weeks).In studies in children with treatment durations of up to 12 weeks, the number of cases of nosebleeds was similar in the fluticasone furoate group and placebo.Allergic reactions: rash, urticaria, Quincke's edema, anaphylaxis.

Contraindications to the use of the drug AVAMIS are hypersensitivity to fluticasone furoate and other components of the drug. The drug should be used with caution in patients with severe liver dysfunction, because The pharmacokinetics of fluticasone furoate may vary.

Use of the drug AVAMIS during pregnancy and lactation There is insufficient data on the use of fluticasone furoate during pregnancy and lactation. Fluticasone furoate can be used during pregnancy only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus. The excretion of fluticasone furoate in human breast milk has not been studied. Fluticasone furoate can be used in nursing women only if the expected benefit to the mother outweighs the potential risk to the baby.

Use for liver dysfunction: No dosage adjustment is required in patients with mild to moderate liver dysfunction. There are no data on use in patients with severe liver dysfunction. Use for impaired renal function: Patients with impaired renal function do not require dose adjustment. Use in elderly patients Elderly patients do not require dose adjustment.

Use in children For children aged 2 to 11 years, the recommended initial dose is 27.5 mcg (1 spray) in each nostril 1 time/(55 mcg/). If there is no desired effect at a dose of 27.5 mcg (1 spray) in each nostril 1 time/, the dose can be increased to 55 mcg (2 sprays) in each nostril 1 time/ (110 mcg/). Once adequate control of symptoms is achieved, it is recommended to reduce the dose to 27.5 mcg (1 spray) in each nostril 1 time/(55 mcg/). There is insufficient data to recommend the use of intranasal fluticasone furoate for the treatment of seasonal and perennial allergic rhinitis in children under 2 years of age.

Special instructions Fluticasone furoate undergoes first-pass metabolism through the liver with the participation of the CYP3A4 isoenzyme. Therefore, in patients with severe hepatic impairment, the pharmacokinetics of fluticasone furoate may be altered.

Effect on the ability to drive vehicles and operate machinery Based on the pharmacological properties of fluticasone furoate and other corticosteroids for topical use, an effect on the ability to drive vehicles or operate other mechanisms is not expected.

Overdose Symptoms: In a bioavailability study, doses 24 times the recommended adult dose were used intranasally for more than 3 days, and no adverse systemic reactions were observed. Treatment: Acute overdose is unlikely to require treatment other than medical supervision.

Drug interactions Fluticasone furoate is rapidly metabolized in the liver with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system. In a drug interaction study between fluticasone furoate and the CYP3A4 inhibitor ketoconazole, there were more cases of fluticasone furoate plasma concentrations above the threshold in patients receiving ketoconazole (6 of 20 patients) compared with placebo (1 of 20 patients). This small increase did not result in a statistically significant difference in 24-hour plasma cortisol between the two groups. Based on theoretical data, no drug interaction of fluticasone furoate when administered intranasally with other drugs that are metabolized with the participation of isoenzymes of the cytochrome P450 system is not expected. Therefore, clinical studies have not been conducted to study the interaction of fluticasone furoate and other drugs. Based on data obtained in a study with another GCS that is also subject to CYP3A4-mediated metabolism, as well as based on literature data regarding other GCS that are subject to CYP3A4-mediated metabolism, coadministration of Avamys with ritonavir is not recommended due to the potential risk increased systemic exposure of fluticasone furoate.

Conditions for dispensing from pharmacies The drug is dispensed with a prescription.

Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 30°C, and do not freeze. Shelf life: 3 years.

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.

Use of the drug Fluticasone

It is used as a basic therapy for a long time, even in the absence of asthma attacks. The therapeutic effect usually develops within 4–7 days, although in some patients who have not previously received inhaled corticosteroids, the effect may be observed as early as 24 hours after the start of treatment. The dose is set individually, trying to achieve complete control over the course of asthma, and then reduced to the minimum effective. The initial dose of fluticasone may be equal to half the daily dose of beclomethasone dipropionate or equivalent to it when administered by inhalation. Adults and children over 16 years of age are usually prescribed from 100 to 1000 mcg 2 times a day; The initial dose is determined taking into account the severity of the disease: mild asthma - 100-250 mcg 2 times a day; moderate severity - 250–500 mcg 2 times a day; severe - 500–1000 mcg 2 times a day. Children over 4 years of age are prescribed taking into account the severity of the disease, usually at a dose of 50–100 mcg 2 times a day. No dose adjustment is required in the elderly or in patients with liver or kidney disease. Nasal aerosol for adults and children over 12 years of age: 100 mcg in each nasal passage, preferably in the morning. If necessary, 100 mcg 2 times a day. The maximum daily dose is 400 mcg (100 mcg in each nasal passage 2 times a day). Elderly patients are recommended to be prescribed at an average therapeutic dose for adults. Children aged 4 to 12 years are prescribed 100 mcg in each nasal passage 1 time per day, preferably in the morning; if necessary, you can increase the frequency of use to 2 times a day. To achieve greater effectiveness, regular use of the aerosol is important. The maximum effect appears on the 3rd–4th day of treatment. The ointment and cream are applied in a thin layer to the affected area of the skin 2 times a day.

Relvar Ellipta, 1 piece, 22 mcg+184 mcg/dose, dosed powder for inhalation

Suction

The absolute bioavailability of vilanterol and fluticasone furoate after inhalation administration of the combination of vilanterol and fluticasone furoate averaged 15.2 and 27.3%, respectively. The oral bioavailability of both substances was low, averaging 1.26 and <2%, respectively. Taking into account the low oral bioavailability, the systemic effect of vilanterol and fluticasone furoate after inhalation is primarily due to the absorption of the portion of the inhalation dose that reaches the lungs.

Distribution

After IV administration, vilanterol and fluticasone furoate are actively distributed in the body, with average Vss being 165 and 661 L, respectively. Both substances have a low ability to bind to red blood cells. in vitro studies

The binding of vilanterol and fluticasone furoate to human plasma proteins was high and reached an average of >93.9 and 99.6%, respectively.
The degree of binding to plasma proteins in vitro
was not reduced in patients with impaired liver or kidney function.
Although vilanterol and fluticasone furoate are P-glycoprotein ( P-gp

changes in the systemic exposure of vilanterol or fluticasone furoate are considered unlikely when coadministering a combination of vilanterol and fluticasone furoate with
P-gp both substances have good absorption capacity.

Metabolism

Based on in vitro

experiments, it can be concluded that the key metabolic pathways of vilanterol and fluticasone furoate in the human body are primarily mediated through the cytochrome CYP3A4 isoenzyme.

Vilanterol is predominantly metabolized by O-dealkylation to form a number of metabolites with significantly lower beta1- and beta2-adrenomimetic activity.

Fluticasone furoate is predominantly metabolized by hydrolysis of the S-fluoromethylcarbothioate group to form metabolites with significantly lower GCS activity.

A clinical study of drug interactions with the cytochrome CYP3A4 isoenzyme was conducted with long-term administration of a combination of vilanterol and fluticasone furoate (22 + 184 mcg/dose) and a strong inhibitor of the cytochrome CYP3A4 isoenzyme - ketoconazole (400 mg) - using healthy volunteers as an example. Coadministration of the drugs resulted in an increase in the mean AUC0-24 and mean Cmax of fluticasone furoate by 36 and 33%, respectively. Increased exposure to fluticasone furoate was associated with a 27% decrease in mean serum cortisol concentrations measured over a period of 0–24 hours. Coadministration of the combination of vilanterol and fluticasone furoate and ketoconazole resulted in an increase in mean vilanterol AUC0-t and Cmax by 65 and 22%, respectively. Increased exposure to vilanterol did not lead to an increase in the systemic effects characteristic of beta-agonists - effects on heart rate, blood potassium levels, or corrected QT interval (QTcF).

Removal

Following oral administration of fluticasone furoate in humans, it was primarily metabolized to form metabolites that were predominantly excreted through the gastrointestinal tract, with the exception of <1% radioactive dose excreted in the urine. The estimated plasma T1/2 of fluticasone furoate after inhalation of the drug averaged 24 hours.

Following oral administration, vilanterol was primarily metabolized in humans to form metabolites that were excreted in urine and feces at approximately 70% and 30% of the radioactive dose, respectively. T1/2 of vilanterol plasma after inhalation of the drug averaged 2.5 hours.

Special patient groups

During the third phase of clinical trials, a population-based meta-analysis of the pharmacokinetics of vilanterol and fluticasone furoate in patients with bronchial asthma and COPD was conducted. This analysis assessed the effect of demographic covariates (age, sex, weight, body mass index (BMI), race and ethnicity) on the pharmacokinetics of vilanterol and fluticasone furoate.

Race.

The AUC0–24 of fluticasone furoate was assessed in elderly patients with asthma or COPD. According to the data obtained, patients of East Asian, Japanese and South Asian races (12-14% of patients) had on average higher AUC0-24 scores (no more than 53%) compared to Caucasian patients. However, in these populations there was no evidence of higher systemic exposure manifested by a greater effect on urinary cortisol excretion over a 24-hour period. In patients suffering from COPD, the influence of race on the pharmacokinetic parameters of vilanterol was not detected. On average, vilanterol Cmax was 220% to 287% higher and AUC0-24 was comparable in Asian patients to other racial groups. However, the higher Cmax of vilanterol did not have a clinically significant effect on heart rate.

Children.

For adolescents (12 years of age or older), there are no recommendations for changing the dosage regimen. The pharmacokinetics of the combination of vilanterol and fluticasone furoate in patients under 12 years of age have not been studied. The safety and effectiveness of the combination of vilanterol and fluticasone furoate in children under 12 years of age have not yet been established.

Elderly patients.

The effect of age on the pharmacokinetics of vilanterol and fluticasone furoate was studied in phase 3 clinical studies that included patients with COPD and bronchial asthma. In patients with bronchial asthma, there was no evidence of an effect of age (12–84 years) on the pharmacokinetic profile of fluticasone furoate and vilanterol. Despite an increase (37%) in the AUC0-24 of vilanterol in patients with COPD throughout the observed age range from 41 to 84 years, there was no evidence of an effect of patient age on the pharmacokinetic profile of fluticasone furoate. In an elderly patient (aged 84 years) with a low body weight (35 kg), the AUC0-24 of vilanterol would be 35% higher than that calculated for the population (average COPD patient aged 60 years and weighing 70 kg), in while the Cmax of vilanterol will remain unchanged. It is unlikely that these differences are clinically relevant.

Renal dysfunction.

According to a clinical pharmacological study, severe renal impairment (Cl creatinine <30 ml/min) does not lead to a significant increase in the systemic exposure of vilanterol or fluticasone furoate or to the development of more pronounced systemic effects of GCS or beta2-agonists compared to healthy volunteers. Individual dose selection for patients with impaired renal function is not required. The effect of hemodialysis has not been studied.

Liver dysfunction.

After continuous administration of the combination of vilanterol and fluticasone furoate for 7 days, patients with hepatic impairment experienced up to a threefold increase in systemic exposure to fluticasone furoate (as measured by AUC0-24) compared with healthy volunteers (according to the Child-Pugh classification of liver cirrhosis: stages cirrhosis A, B or C). An increase in systemic exposure to fluticasone furoate (when prescribing a combination of vilanterol and fluticasone furoate at a dosage of 22 + 184 mcg / dose) in patients with moderate hepatic impairment (Child-Pugh stage B) was associated with a decrease in serum cortisol concentrations by an average of 34 % compared to healthy volunteers. Dose-normalized systemic exposure to fluticasone furoate was similar in patients with moderate to severe hepatic impairment (Child-Pugh stages B and C). Therefore, although patients with impaired liver function do not require individual dosing, caution should be exercised when prescribing this drug to them. After continuous administration of the combination of vilanterol and fluticasone furoate for 7 days in patients with mild, moderate or severe hepatic impairment (Child-Pugh stages A, B and C), there was no significant increase in the systemic exposure of vilanterol (as measured by Cmax and AUC0- 24). Compared with healthy volunteers, patients with mild to moderate hepatic impairment (vilanterol 22 mcg) or severe hepatic impairment (vilanterol 11 mcg) did not experience clinically significant beta-adrenergic systemic effects (changes in heart rate or serum potassium concentrations). ) caused by taking a combination of vilanterol and fluticasone furoate.

Gender, body weight, BMI.

According to the third phase of population pharmacokinetic analysis, which included 1213 patients with bronchial asthma (712 women) and 1225 patients with COPD (392 women), there was no evidence of the influence of gender, body weight or BMI on the pharmacokinetic profile of fluticasone furoate. According to a population pharmacokinetic analysis involving 856 patients with bronchial asthma (500 women) and 1091 patients with COPD (340 women), there was no evidence of an effect of gender, body weight or BMI on the pharmacokinetic profile of vilanterol. Individual dose selection is not required based on gender, body weight or BMI.

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.

Vilanterol + Fluticasone furoate ()

Suction

The absolute bioavailability of vilanterol and fluticasone furoate after inhalation administration of the combination of vilanterol and fluticasone furoate averaged 15.2% and 27.3%, respectively. The oral bioavailability of both substances was low, averaging 1.26% and <2%, respectively. Taking into account the low oral bioavailability, the systemic effect of vilanterol and fluticasone furoate after inhalation is primarily due to the absorption of the portion of the inhalation dose that reaches the lungs.

Distribution

After intravenous administration, vilanterol and fluticasone furoate are actively distributed in the body, with average volumes of distribution at steady state being 165 L and 661 L, respectively.

Both substances have a low ability to bind to red blood cells. in vitro studies

The binding of vilanterol and fluticasone furoate to human plasma proteins was high and reached an average of > 93.9% and 99.6%, respectively.
The degree of binding to plasma proteins in vitro
was not reduced in patients with impaired liver or kidney function.

Despite the fact that vilanterol and fluticasone furoate are P-glycoprotein substrates, when a combination of vilanterol and fluticasone furoate is administered concomitantly with P-glycoprotein inhibitors, a change in the systemic exposure of vilanterol or fluticasone furoate is considered unlikely, since both substances have good absorption capacity.

Metabolism

Based on in vitro

It can be concluded that the key metabolic pathways of vilanterol and fluticasone furoate in the human body are primarily mediated through the cytochrome CYP3A4 isoenzyme.

Vilanterol is predominantly metabolized by O-dealkylation with the formation of a number of metabolites with significantly lower beta1- and beta2-adrenomimetic activity.

Fluticasone furoate is predominantly metabolized by hydrolysis of the S-fluoromethylcarbothioate group to form metabolites with significantly lower glucocorticosteroid activity.

Co-administration of a combination of vilanterol and fluticasone furoate and ketoconazole resulted in an increase in mean AUC(0-t) and maximum plasma concentrations of vilanterol by 65% and 22%, respectively. Increased exposure to vilanterol did not result in increased systemic effects typical of beta-agonists - effects on heart rate, blood potassium, or corrected QT interval (QTcF).

Removal

Following oral administration of fluticasone furoate in humans, it was primarily metabolized to form metabolites that were predominantly excreted through the gastrointestinal tract, with the exception of <1% radioactive dose excreted in the urine. The estimated plasma half-life of fluticasone furoate after inhalation administration of the drug averaged 24 hours.

Following oral administration, vilanterol in humans was primarily metabolized to form metabolites that were excreted in urine and feces at approximately 70% and 30% of the radioactive dose, respectively. The plasma half-life of vilanterol after inhalation administration of the drug averaged 2.5 hours.

Special patient groups

During the third phase of clinical trials, a population-based meta-analysis of the pharmacokinetics of vilanterol and fluticasone furoate in patients with bronchial asthma and chronic obstructive pulmonary disease was conducted. This analysis assessed the effect of demographic covariates (age, sex, weight, body mass index, race and ethnicity) on the pharmacokinetics of vilanterol and fluticasone furoate.

Race

In elderly patients with bronchial asthma or chronic obstructive pulmonary disease, the AUC(0-24) of fluticasone furoate was assessed. According to the data obtained, patients of the East Asian, Japanese and South Asian race (12-14% of patients) had on average higher AUC (0-24) scores (no more than 53% higher) compared to Caucasian patients. However, in these populations there was no evidence of higher systemic exposure manifested by a greater effect on urinary cortisol excretion over a 24-hour period. In patients suffering from chronic obstructive pulmonary disease, the influence of race on the pharmacokinetic parameters of vilanterol was not detected.

On average, the maximum plasma concentrations of vilanterol were 220-287% higher and the AUC(0-24) was comparable in Asian patients compared to other racial groups. However, the higher maximum plasma concentration of vilanterol did not have a clinically significant effect on heart rate.

Children

Elderly patients

The effect of age on the pharmacokinetics of vilanterol and fluticasone furoate was studied in phase 3 clinical studies that included patients with chronic obstructive pulmonary disease and bronchial asthma.

In patients with bronchial asthma, there was no evidence of an effect of age (12-84 years) on the pharmacokinetic profile of fluticasone furoate and vilanterol.

Despite an increase (37%) in the AUC of vilanterol in patients with chronic obstructive pulmonary disease throughout the observed age range from 41 to 84 years, there was no evidence of an effect of patient age on the pharmacokinetic profile of fluticasone furoate. In an elderly patient (aged 84 years) with a low body weight (35 kg), the AUC(0-24) of vilanterol would be 35% higher than that calculated for the population (average patient with chronic obstructive pulmonary disease aged 60 years and body weight 70 kg), while the maximum plasma concentration of vilanterol will remain unchanged. It is unlikely that these differences are clinically relevant.

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.

Buy Avamys nasal spray 27.5 mcg/dose 120 doses in pharmacies

Release form, composition and packaging Dosed nasal spray in the form of a homogeneous white suspension.

1 dose of fluticasone furoate (micronized) 27.5 mcg

Excipients: dextrose, dispersible cellulose (contains 11% carmellose sodium), polysorbate 80, benzalkonium chloride (50% solution), disodium edetate, purified water. 30 doses - dark glass bottles with a dispensing spray device (1) - cardboard packs. 60 doses - dark glass bottles with a dispensing spray device (1) - cardboard packs. 120 doses - dark glass bottles with a dispensing spray device (1) - cardboard packs.

Clinical and pharmacological group of GCS for intranasal use

Pharmacological action of GCS for local use. Fluticasone furoate is a synthetic trifluorinated glucocorticosteroid with high affinity for glucocorticoid receptors and has a pronounced anti-inflammatory effect.

Pharmacokinetics Absorption Fluticasone furoate is not completely absorbed, undergoing primary metabolism in the liver, resulting in negligible systemic exposure. Intranasal administration at a dose of 110 mcg 1 time / day usually does not lead to the achievement of detectable plasma concentrations (

Distribution Fluticasone furoate is more than 99% bound to plasma proteins. When the equilibrium concentration of fluticasone furoate reaches an equilibrium concentration, the Vd is, on average, 608 l. Metabolism Fluticasone furoate is rapidly eliminated from the systemic circulation (total plasma clearance 58.7 L), mainly through metabolism in the liver to form an inactive 17β-carboxyl metabolite (GW694301X) with the participation of the CYP3A4 isoenzyme. The main route of metabolism is hydrolysis of the S-fluoromethylcabrothioate group with the formation of a 17β-carboxyl metabolite. In vivo studies have shown that fluticasone furoate is not degraded to fluticasone.

Excretion Elimination of fluticasone furoate and its metabolites following oral and intravenous administration occurs primarily through the intestine, reflecting their excretion in the bile. When taken orally and intravenously, 1% and 2% are excreted by the kidneys, respectively.

Pharmacokinetics in special clinical situations 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. In children, when administered intranasally at a dose of 110 mcg 1 time / day, fluticasone furoate is usually not detected in concentrations that can be quantified (Fluticasone furoate was not detected in the urine of healthy volunteers when administered intranasally. Less than 1% of metabolites are excreted by the kidneys, thus disorders renal function theoretically cannot affect the pharmacokinetics of fluticasone furoate. In a study in patients with moderate hepatic impairment, inhaled use of fluticasone furoate at a dose of 400 mcg 1 time / day showed an increase in Cmax by 42% and an increase in AUC0-∞ by 172%, according to 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 liver dysfunction would likely not result in clinically significant effects when prescribing a standard dose for adults. Concentrations of fluticasone furoate are usually undetectable (

Indications for use of the drug are symptomatic treatment of seasonal and year-round allergic rhinitis in adults and children over 2 years of age. Dosage regimen The drug is used intranasally. To achieve maximum therapeutic effect, it is necessary to adhere to a regular regimen of use. The onset of action can be observed within 8 hours after the first administration. It may take several days to achieve maximum effect. The reason for the lack of immediate effect should be carefully explained to the patient. For the symptomatic treatment of seasonal and year-round allergic rhinitis in adults and adolescents aged 12 years and older, the recommended initial dose is 55 mcg (2 sprays) in each nostril 1 time / day (110 mcg / day). Once adequate symptom control is achieved, dose reduction to 27.5 mcg (1 spray) in each nostril once a day (55 mcg/day) may be effective for maintenance treatment. For children aged 2 to 11 years, the recommended initial dose is 27.5 mcg (1 spray) in each nostril 1 time / day (55 mcg / day). If there is no desired effect at a dose of 27.5 mcg (1 spray) in each nostril 1 time/day, the dose can be increased to 55 mcg (2 sprays) in each nostril 1 time/day (110 mcg/day). When adequate control of symptoms is achieved, it is recommended to reduce the dose to 27.5 mcg (1 spray) in each nostril 1 time / day (55 mcg / day). There is insufficient data to recommend the use of intranasal fluticasone furoate for the treatment of seasonal and perennial allergic rhinitis in children under 2 years of age. Elderly patients do not require dose adjustment. In patients with impaired renal function, no dose adjustment is required. In patients with mild to moderate liver dysfunction, no dose adjustment is required. There are no data on use in patients with severe liver dysfunction.

Rules for use and handling of the drug An indicator window in a plastic package allows you to control the level of the drug in the bottle. In 30- or 60-dose vials, the drug level will be visible immediately, and in 120-dose vials, the initial drug level is above the upper limit of the viewing window. To check the level of the drug in the bottle, you need to hold it up to the light. The level will be visible through the viewing window. Preparation for use should be carried out when using the spray for the first time, as well as if the bottle was left open.

Proper preparation for use will ensure that the required dose of the drug is injected. 1. Without removing the cap, shake the bottle well for 10 seconds. The drug is a rather thick suspension and becomes more liquid when shaken. Spraying is only possible after shaking. 2. Remove the cap by gently pulling it with your thumb and forefinger. 3. Hold the bottle vertically and point the tip away from you. 4. Press the button firmly and make several presses (minimum 6) until a small cloud appears from the tip (if you cannot press the button with one thumb, you should press it with the thumbs of both hands). 5. The spray is ready for use.

Using nasal spray 1. Shake the bottle thoroughly. 2. Remove the cap. 3. Clear your nose and tilt your head slightly forward. 4. Insert the tip into one nostril, continuing to hold the bottle vertically. 5. Point the tip of the sprayer at the outer wall of the nose, not at the nasal septum. This will ensure proper injection of the drug. 6. Start inhaling through your nose and press once with your fingers to spray the drug. 7. Remove the atomizer from your nostril and exhale through your mouth. 8. If it is necessary to make two injections into each nostril (as prescribed by a doctor), you should repeat steps 4-6. 9. Repeat the procedure for the other nostril. 10. Close the bottle with a cap. 11. Avoid getting the spray in your eyes. If the drug gets into your eyes, rinse them thoroughly with water.

Caring for the sprayer After each use: 1. Blot the tip and the inner surface of the cap with a dry, clean cloth. Avoid contact with water. 2. Do not try to clean the tip hole with a pin or other sharp objects. 3. Always cap the bottle and keep it closed. The cap protects the sprayer from dust and clogging, seals the bottle, and prevents accidental pressing of the button. If the sprayer does not work: 1. Check the level of the remaining drug in the bottle through the inspection window. If there is only a small amount of liquid left, it may not be enough to operate the sprayer. 2. Check the bottle for damage. 3. Check if the tip hole is clogged. Do not attempt to clean the tip hole with a pin or other sharp object. 4. Try to activate the device by repeating the procedure for preparing the nasal spray for use.

Side effects Determination of the frequency of adverse reactions: very often (≥ 1/10); often (≥ 1/100, From the respiratory system: very often - nosebleeds; often - ulceration of the nasal mucosa. In adults and adolescents, cases of nosebleeds were observed more often with long-term use (more than 6 weeks) than with a short course (up to 6 weeks).In studies in children with treatment durations of up to 12 weeks, the number of cases of nosebleeds was similar in the fluticasone furoate and placebo groups.Allergic reactions: rash, urticaria, Quincke's edema, anaphylaxis.

Contraindications to the use of the drug are hypersensitivity to the components of the drug. The drug should be used with caution in patients with severe liver dysfunction, because The pharmacokinetics of fluticasone furoate may vary.

Use of the drug during pregnancy and breastfeeding Fluticasone furoate can be used during pregnancy and lactation (breastfeeding) only in cases where the expected benefit of therapy for the mother outweighs the potential risk for the fetus or infant. There is insufficient clinical data on the use of fluticasone furoate during pregnancy and lactation (breastfeeding). It is not known whether fluticasone furoate is excreted into breast milk in humans.

Use for liver dysfunction: No dosage adjustment is required in patients with mild to moderate liver dysfunction. There are no data on use in patients with severe liver dysfunction. Use for impaired renal function: Patients with impaired renal function do not require dose adjustment.

Special instructions Fluticasone furoate undergoes first-pass metabolism through the liver with the participation of the CYP3A4 isoenzyme. Therefore, in patients with severe hepatic impairment, the pharmacokinetics of fluticasone furoate may be altered. Effect on the ability to drive vehicles and operate machinery Based on the pharmacological properties of fluticasone furoate and other corticosteroids for topical use, an effect on the ability to drive vehicles or operate other mechanisms is not expected.

Overdose Symptoms: In a bioavailability study, doses 24 times the recommended adult dose were used intranasally for more than 3 days, and no adverse systemic reactions were observed. Treatment: Acute overdose is unlikely to require treatment other than medical supervision.

Drug interactions Fluticasone furoate is rapidly metabolized in the liver with the participation of the CYP3A4 isoenzyme. In a drug interaction study between fluticasone furoate and the CYP3A4 inhibitor ketoconazole, there were more cases of fluticasone furoate plasma concentrations above the threshold in patients receiving ketoconazole (6 of 20 patients) compared with placebo (1 of 20 patients). This small increase did not result in a statistically significant difference in 24-hour plasma cortisol between the two groups. Based on theoretical data, no drug interaction of fluticasone furoate when administered intranasally with other drugs that are metabolized with the participation of isoenzymes of the cytochrome P450 system is not expected. Therefore, clinical studies have not been conducted to study the interaction of fluticasone furoate and other drugs. Based on data obtained in a study with another GCS that is also subject to CYP3A4-mediated metabolism, as well as based on literature data regarding other GCS that are subject to CYP3A4-mediated metabolism, coadministration of Avamys with ritonavir is not recommended due to the potential risk increased systemic exposure of fluticasone furoate.

Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 30°C; do not freeze. Shelf life: 3 years.