Avamys nasal spray dosed 27.5 mcg/dose in vial No. 1

Name:
Avamys nasal spray dosing. 27.5 mcg dose in vial with dosing device in pack No. 1
Description:
Homogeneous suspension of white color. The main active ingredient Fluticasone furoate Release form Spray Dosage 27.5 mcg Pharmacological action Means for the treatment of nasal diseases. Decongestants and other agents for external use in rhinology. Corticosteroids. ATX code: R01AD12 Fluticasone furoate is a synthetic trifluorinated corticosteroid with a very high affinity for glucocorticoid receptors, which has a pronounced anti-inflammatory effect. Pharmacokinetics Absorption Fluticasone furoate is not completely absorbed and undergoes extensive first pass metabolism in the liver and intestines, resulting in little systemic exposure. Intranasal administration at a dose of 110 micrograms once a day usually does not lead to the achievement of a quantitatively measurable plasma concentration (i.e. <10 pg / ml). The absolute bioavailability of fluticasone furoate when administered intranasally at a dose of 110 μg is 0.50%. Distribution Fluticasone furoate binds to plasma proteins by more than 99%. When an equilibrium concentration is reached, the volume of distribution of fluticasone furoate is, on average, 608 liters. Metabolism Fluticasone furoate is rapidly excreted from the systemic circulation (total plasma clearance 58.7 l/h), mainly through metabolism in the liver, with the formation of an inactive 17?-carboxylic metabolite (GW694301X), with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system. The main metabolic pathway is the hydrolysis of the S-fluoromethylcarbothiate group with the formation of the 17α-carboxylic acid metabolite. In vivo studies have shown that there is no degradation of fluticasone furoate to fluticasone. Withdrawal Withdrawal of fluticasone furoate and its metabolites when administered orally and intravenously is carried out mainly by excretion with bile through the intestines. With intravenous administration of fluticasone furoate, the half-life is 15.1 hours. About 1% and 2% are excreted by the kidneys when taken orally and intravenously, respectively. Special patient groups Elderly patients Pharmacokinetic data are available only for a small number of elderly patients (S 65 years, n=23/872; 2.6%). There is no evidence that quantifiable concentrations of fluticasone furoate are more common in elderly patients than in younger patients. Children With intranasal use of fluticasone furoate in most patients, it is not detected in plasma at concentrations that can be quantified (< 10 pg / ml). So, when taken intranasally at a dose of 110 μg 1 time per day and 55 μg 1 time per day, fluticasone furoate was detected in blood plasma at concentrations that can be quantified in 15.1% and 6.8% of children, respectively. There is no evidence that infants (under 6 years of age) have higher plasma concentrations of fluticasone furoate that can be quantified. Mean plasma concentrations in patients with measurable levels of fluticasone furoate after administration of 55 mcg were 18.4 pg/ml for children aged 2-5 years and 18.9 pg/ml for children aged 6-11 years; after application of 110 mcg - 14.3 pg / ml and 14.4 pg / ml, respectively. These figures are similar to those observed in adults and children over 12 years of age (mean plasma fluticasone furoate concentration in these patients with measurable levels was 15.4 pg / ml and 21.8 pg / ml, when taking 55 mcg and 110 mcg , respectively). Patients with impaired renal function Fluticasone furoate was not detected in the urine of healthy volunteers when administered intranasally. Less than 1% of metabolites are excreted through the kidneys; thus, impaired renal function theoretically cannot affect the pharmacokinetics of fluticasone furoate. Patients with impaired liver function There are no data on the use of intranasal fluticasone furoate in patients with impaired liver function. A study in patients with moderate hepatic impairment (Child-Pugh class B) who took 400 μg of fluticasone furoate as a single inhalation showed an increase in the maximum concentration of Cmax (42%) and an increase in the area under the concentration-time pharmacokinetic curve AUC (0-? ) (172%), as well as a modest (average 23%) decrease in cortisol levels compared with healthy volunteers. Following repeated dosing of inhaled fluticasone furoate/vilanterol for 7 days, there was an increase in systemic exposure to fluticasone furoate (average two-fold, measured by AUC(0-24)) in patients with moderate or severe hepatic impairment (class B or C according to Child-Pugh score) compared with healthy volunteers. An increase in systemic exposure to fluticasone furoate in patients with moderate hepatic impairment treated with fluticasone furoate/vilanterol 200/25 mcg resulted in a decrease (mean 34%) in serum cortisol levels compared with healthy volunteers. In patients with severe hepatic impairment, fluticasone furoate/vilanterol 100/12.5 mcg had no effect on serum cortisol levels. Based on the data obtained, it is not expected that intranasal administration of fluticasone furoate at a dose of 110 μg per day in patients in this group will lead to suppression of cortisol synthesis. Indications for use Treatment of symptoms of allergic rhinitis in adults, adolescents and children from 6 years of age. Method of application and doses Only intranasally. To achieve the full therapeutic effect, it is recommended to adhere to a regular regimen of application. The onset of action can be observed as early as 8 hours after the first injection. It may take several days to achieve maximum effect. It should be explained to the patient that the symptoms of the disease will improve with continued regular use. The duration of treatment should be limited to the period of exposure to the allergen. Adults and adolescents (aged 12 years and older) The recommended starting dose is 2 sprays (27.5 micrograms of fluticasone furoate per spray) in each nostril once a day (110 micrograms per day). When adequate symptom control is achieved, a dose reduction to 1 spray in each nostril 1 time per day (55 mcg per day) may be sufficient to maintain the effect. The dose should be titrated to the lowest dose that provides effective control of symptoms. Children aged 6 to 11 years The recommended initial dose is 1 spray (27.5 micrograms of fluticasone furoate in one spray) in each nostril 1 time per day (55 micrograms per day). In the absence of the desired effect when using 1 spray in each nostril 1 time per day, it is possible to increase the dose to 2 sprays in each nostril 1 time per day (110 mcg per day). When adequate control of symptoms is achieved, it is recommended to reduce the dose to 1 spray in each nostril 1 time per day (55 mcg per day). Children under the age of 6 years The safety and efficacy of fluticasone furoate in this category of patients have not been established. It is not possible to give recommendations on dosing. Elderly patients Dose adjustment is not required. Patients with impaired renal function Dose adjustment is not required. Patients with impaired liver function Dose adjustments in patients with impaired function; liver is not required (see section "Pharmacokinetics"), Use during pregnancy and lactation Pregnancy Data on the use of fluticasone furoate during pregnancy is not enough. In animal studies, glucocorticoids have caused malformations including cleft palate and intrauterine growth retardation. It is unlikely that these data will be the same in humans if the drug is taken intranasally at the recommended doses. Fluticasone furoate should only be used in pregnant women if the expected benefit to the mother outweighs the potential risk to the fetus or child. Lactation It is not known whether fluticasone furoate administered intranasally is excreted in breast milk. The appointment of fluticasone furoate to lactating women should be considered only if the expected benefit to the mother outweighs the potential risk to the child. Fertility There are no data on the effect on fertility in humans. Precautions Systemic effects of corticosteroids Systemic effects have been reported with the use of nasal corticosteroids, particularly at high doses for a long time. These effects are much less likely than with oral corticosteroids and may vary between individual patients and among different corticosteroid preparations. Possible systemic effects include Cushing's syndrome, Cushingoid symptoms, adrenal suppression, growth retardation in children and adolescents, cataracts, glaucoma, and, more rarely, a range of psychiatric or behavioral disorders, including psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression. (particularly in children). Treatment with nasal corticosteroids at higher than recommended doses may result in clinically significant adrenal suppression. If there are data on the use of doses exceeding the recommended ones, the use of an additional systemic corticosteroid during periods of stress or surgery should be considered. Fluticasone furoate once daily at a dose of 110 mcg did not lead to suppression of the hypothalamic-pituitary-adrenal axis in adults, adolescents and children, however, the dose of intranasal fluticasone furoate should be reduced to the minimum effective dose that controls the symptoms of rhinitis. As with other intranasal corticosteroids, when co-administered with other forms of corticosteroids, the total corticosteroid systemic load should be assessed. In the presence of signs of adrenal insufficiency, care must be taken when transferring patients from systemic steroid therapy to fluticasone furoate. Eye disorders The use of nasal or inhaled corticosteroids may lead to the development of glaucoma and/or cataracts. Therefore, patients with visual changes or elevated intraocular pressure, glaucoma and/or cataracts in history should be carefully monitored. Growth retardation There have been reports of growth retardation in children receiving intranasal corticosteroids at recommended doses. In children who received fluticasone furoate daily at a dose of 110 mcg for one year, there were cases of a decrease in the growth rate. Therefore, children should be given the lowest effective dose to control symptoms. It is recommended to regularly monitor the growth of children receiving long-term nasal corticosteroids. If growth is retarded, the therapy regimen should be reconsidered to reduce, if possible, the dose of nasal corticosteroid to the lowest effective dose that controls the symptoms of the disease. In addition, specialist advice may be required. Patients receiving ritonavir Co-administration with ritonavir is not recommended due to the risk of increased systemic exposure to fluticasone furoate. Interaction with other drugs Interaction with CYP3A4 inhibitors Fluticasone furoate is rapidly eliminated from the systemic circulation, undergoing primary metabolism with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system. According to the results of the use of another glucocorticoid (fluticasone propionate), which is also metabolized with the participation of the CYP3A4 isoenzyme, the combined use of ritonavir and fluticasone furoate is not recommended due to an increased risk of systemic effects of the latter. Fluticasone furoate should be used with caution in combination with strong CYP3A4 inhibitors, since the possibility of increased systemic exposure cannot be ruled out. In a drug interaction study between fluticasone furoate and the strong CYP3A4 inhibitor ketoconazole, there were more cases of fluticasone furoate above the plasma threshold in the ketoconazole group (6 of 20 patients) compared with placebo (1 of 20 patients). This slight increase does not result in a statistically significant difference in plasma cortisol over 24 hours between the two groups. Data on the induction and inhibition of enzyme action do not provide theoretical grounds for expecting metabolic interactions between fluticasone furoate, administered intranasally at recommended doses, and other drugs that are metabolized with the participation of the cytochrome P450 system. Therefore, clinical studies on the interaction of fluticasone furoate and other drugs have not been conducted. Contraindications Hypersensitivity to fluticasone furoate or any other components of the drug. Composition Active substance: fluticasone furoate (micronized) 27.5 mcg/dose. Excipients: anhydrous glucose, dispersible cellulose (11% carmellose sodium), polysorbate 80, benzalkonium chloride solution, disodium edetate, purified water. OverdoseSymptoms In a bioavailability study, no adverse systemic reactions were observed when administered intranasally up to 2640 μg of fluticasone furoate per day for more than 3 days. It is unlikely that an acute overdose will require treatment other than medical supervision. Side effectsSummary of the safety profile The most common adverse reactions during treatment with fluticasone furoate are epistaxis, nasal mucosal ulceration and headache. The most serious adverse events are rare reports of hypersensitivity reactions, including anaphylaxis (less than 1 in 1000 patients). List of adverse reactions In studies of the safety and efficacy of fluticasone furoate in the treatment of seasonal and perennial rhinitis, the drug was used by more than 2700 patients, including 243 patients aged 12-18 years, 790 patients aged 6-12 years and 241 patients aged 2-6 years . Data from large clinical trials were used to determine the frequency of adverse reactions. The adverse events presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: very often (?1/10), often (?1/100 and <1/10), infrequently (?1/1000 and <1/100), rarely (?1/10000 and <1 /1000), very rarely (<1/10000). Respiratory, thoracic and mediastinal disorders: Very common - epistaxis, usually mild or moderate; in adults and adolescents, cases of epistaxis were observed more often with long-term use (more than 6 weeks) than with a short course (up to 6 weeks). In clinical studies in children with a duration of therapy up to 12 weeks, the incidence of epistaxis was similar in the fluticasone furoate and placebo groups. Often - ulceration of the nasal mucosa. Infrequently - rinalgia, nasal discomfort (including burning, irritation and soreness in the nose), dryness in the nose. Very rarely - perforation of the nasal septum. Immune system disorders: Rarely, hypersensitivity reactions, including anaphylaxis, Quincke's edema, rash, urticaria. Nervous system disorders: Often - headache. On the part of the organs of vision: the frequency is unknown - transient ophthalmic changes (increased intraocular pressure, posterior subcapsular clouding of the lens). Musculoskeletal and connective tissue disorders: Frequency unknown - growth retardation. Systemic effects of nasal corticosteroids may occur, especially with prolonged use at high doses. Growth retardation has been reported in children with nasal corticosteroids. The safety of nasal corticosteroids in children under 6 years of age has not been established. The frequency, type and severity of adverse reactions observed in children are similar to those observed in adults. In a one-year clinical study assessing the growth of prepubertal children treated with 110 mcg of fluticasone furoate once daily, the mean difference in growth rate was -0.27 cm per year compared with the placebo group. Storage conditions At a temperature not higher than 30 °C. Do not refrigerate. Do not freeze. Store upright. Keep out of the reach of children. #1