Fluticasone

Pharmacological properties

fluticasone furoate is a synthetic fluorinated corticosteroid with a very high affinity for glucocorticoid receptors and a strong anti-inflammatory effect.

Pharmacokinetics Fluticasone furoate undergoes an extensive first-pass metabolism and incomplete absorption in the liver and intestines, which causes a very slight systemic effect of the drug. Typically, with intranasal use of 110 μg once a day, a concentration of the drug in blood plasma is reached that cannot be measured (10 pg / ml). The absolute bioavailability of fluticasone furoate when applied is 880 mcg 3 times a day (total daily dose is 2640 mcg) is 0.5%.

The binding level of fluticasone furoate to plasma proteins is 99%. The drug is widely distributed, the volume of distribution averages 608 liters.

Fluticasone furoate is rapidly excreted (total plasma clearance 58 l / h) from the systemic circulation, mainly through hepatic metabolism with the participation of the CYP 3A4 cytochrome P450 enzyme to an inactive carboxy metabolite (GW694301X). The main mechanism of metabolism is the hydrolysis of S-fluoromethylcarbionate to a metabolite of 17β-carboxylic acid. It is excreted after oral and intravenous administration, mainly with feces with signs of excretion of fluticasone furoate and its metabolites in bile. After the on / in application of T_½ - 15.1 hours. The level of urinary excretion is about 1 and 2% after oral and iv use, respectively.

Indications

Symptomatic treatment of allergic rhinitis.

Application

Avamis is used only intranasally.

Adults and children over 12 years of age: the recommended initial dose is 2 injections (27.5 μg per 1 injection) in each nasal passage 1 time per day (total daily dose - 110 μg).

After achieving control of the symptoms of rhinitis, the maintenance dose of the drug can be reduced to 1 injection in each nasal passage 1 time per day (total daily dose - 55 mcg).

Children aged 6-11 years: the recommended initial dose is 1 injection in each nasal passage 1 time per day (total daily dose - 55 mcg). In the case of insufficient control of the symptoms of rhinitis when injected into each nasal passage 1 time per day (total daily dose - 55 μg), the dose can be increased to 2 injections into each nasal passage 1 time per day (total daily dose - 110 μg). After achieving control over the symptoms of rhinitis, the dose is reduced to 1 injection in each nasal passage 1 time per day (total daily dose - 55 mcg).

In elderly patients, the same doses are used as in adults.

In renal failure, dose adjustment is not required.

Hepatic failure does not require dose adjustment.

To achieve the full therapeutic effect, the drug must be used regularly, which should be reported to the patient. The onset of action is observed 8 hours after the first application, the maximum therapeutic effect occurs within a few days from the start of treatment. The duration of treatment should be limited to the period of exposure to the allergen.

Terms of use for nasal spray. The nasal dosed spray consists of a glass bottle placed in a plastic case with a protective cap that covers the tip of the sprayer (a special device on the upper end of the spray). In the lower part of the case there are small holes through which the presence of the drug in a glass bottle is visible. On one of the sides of the plastic case there is a large metering button, when pressed, the spray is fed through a spray gun.

Before the first use (and if the drug has not been used for 1 month), you should check the device:

• shake the vial thoroughly for about 10 seconds (without removing the protective cap);
• remove the cap by pulling it up, lightly pressing with fingers on both sides;
• press the dispensing button firmly (at least 6 times) to release a sufficient amount of spray into the air.

Before each use, it is necessary to clean the nasal passages, gently shake the spray and perform the following steps:

• tilt your head slightly forward;
• keeping the spray upright, carefully place the atomizer in one nasal passage;
• point the spray tip to the side opposite from the nose, so that the drug is evenly distributed in the nasal cavity;
• inhale through the nose and simultaneously press the metering button on the plastic case to spray the spray into the nasal cavity;
• Avoid contact with the spray; if this happens, flush eyes with water;
• remove the spray tip from the nose and exhale with your mouth.

To introduce the spray into another nasal passage, the procedure is repeated in the same sequence.

After use, always close the device with a protective cap.

After each use, the spray tip and protective cap are wiped with a clean, dry cloth.

Contraindications

Hypersensitivity to the components of the drug.

Side effects

Adverse reactions are distributed in frequency into the following categories: very often (≥1 / 10), often (≥1 / 100 and 1/10), infrequently (≥1 / 1000 and 1/100), rarely (≥1 / 10,000 and 1/1000), very rarely (1/10 000).

From the respiratory system: very often - nosebleeds; often - ulcers on the nasal mucosa. Epistaxis was usually mild or moderate. In adults and adolescents, nosebleeds occurred more often with prolonged use (6 weeks) than with up to 6 weeks. In pediatric clinical trials of up to 12 weeks, cases of nosebleeds were similar in the group where fluticasone furoate was used, and in the placebo group. Infrequently - nose pain, discomfort (including burning, irritation, soreness in the nose), dry nose. Very rarely - perforation of the nasal septum.

On the part of the immune system: rarely - hypersensitivity reactions, including anaphylaxis, angioedema, rash and urticaria.

From the nervous system: often - headache.

From the side of the organs of vision: the frequency is unknown - transient visual impairment.

Children

From the musculoskeletal system and connective tissue: frequency unknown - growth retardation.

special instructions

It is not recommended to use the drug with ritonavir in connection with an increased risk of systemic effects of fluticasone furoate.

Exceeding the recommended dose of intranasal GCS can cause clinically significant adrenal suppression. During periods of stress or planned surgery, consider the need for additional use of systemic corticosteroids in the presence of signs of exceeding the recommended dose of corticosteroids. The use of 110 mcg / day of fluticasone furoate is not associated with inhibition of the hypothalamic-pituitary-adrenal system in adults and children. However, the dose of intranasal fluticasone furoate is reduced to the minimum effective. As with the use of other intranasal GCS, in the case of concomitant use of any other types of corticosteroid therapy, their general systemic effect is taken into account.

When using nasal GCS, a systemic effect may occur, especially when using drugs in high doses for a long time. The likelihood of such an effect is less than with oral GCS and varies depending on different GCS and the individual patient response. Potential systemic effects may include Cushings syndrome, cushingoid symptoms, adrenal suppression, growth retardation in children and adolescents, cataracts, glaucoma, and much less often - a number of psychological or behavioral effects, including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression (especially in children )

The use of nasal and inhaled corticosteroids may cause the development of glaucoma and / or cataracts.Therefore, patients with visual impairment or increased intraocular pressure, glaucoma and / or cataracts should be closely monitored.

In the treatment of children with intranasal corticosteroids in the recommended doses, cases of stunting were observed. According to a clinical study evaluating the growth rate of prepubertal children who took 110 μg of fluticasone furoate 1 time per day for 1 year, there was a difference in growth rate of −0.27 cm per year compared with the placebo group. It is recommended to regularly measure the growth of children with prolonged therapy with intranasal corticosteroids. If the child is stunted, therapy should be reviewed to reduce the dose, if possible, to the minimum effective for controlling the symptoms of the disease.

During pregnancy and breastfeeding. Data on the use of the drug during pregnancy or lactation are insufficient. Fluticasone furoate is used during this period only if the expected benefit to the mother outweighs the possible risk to the fetus / child.

With the intranasal use of fluticasone furoate at the maximum recommended doses (110 μg / day), a concentration is achieved that is generally not measurable, therefore, the expected potential for reproductive toxicity is very low. The penetration of fluticasone furoate into human breast milk has not been studied.

There are no data on the effect on human fertility.

In children under the age of 6, Avamis is not recommended, because the efficacy and safety of the drug have not been established by patients of this age category ..

The ability to influence the reaction rate when driving vehicles or working with mechanisms is unlikely.

Interactions

Fluticasone furoate is rapidly excreted by extensive first-pass metabolism in the liver using cytochrome p450 3a4.

According to the results of the use of another GCS - fluticasone propionate, which is also metabolized by CYP 3A4, its combined use with ritonavir is not recommended due to an increase in the systemic effect of fluticasone furoate.

The use of fluticasone furoate in combination with strong CYP 3A4 inhibitors should be used with caution in connection with the increased systemic effect of fluticasone furoate. In a clinical study of the drug interaction of fluticasone furoate with a potent CYP 3A4 inhibitor ketoconazole, the number of individuals whose measurable plasma fluticasone furoate concentration was measurable was higher in the group using ketoconazole (6/20) compared with the placebo group (1 per twenty). This slight increase in systemic effect did not cause a statistically significant difference in 24-hour serum cortisol levels in these 2 groups.

Data on the study of enzymatic induction and inhibition suggest that there is no reason to expect a metabolic interaction between fluticasone furoat and other mediators of cytochrome P450 metabolism in appropriate intranasal doses for clinical use. Therefore, clinical studies to study the interaction of fluticasone furoate and other drugs have not been conducted.

Overdose

According to clinical studies with intranasal use, up to 2640 mcg of the drug per day for 3 days, no side effects were noted. in the event of an acute overdose, treatment other than medical supervision will be necessary.

Storage conditions

At a temperature of ≤30 ° c. Do not store in the refrigerator. do not freeze. after the first opening, the shelf life is 2 months.

Information for the professional activities of medical and pharmaceutical workers.

You can obtain complete instructions for the medical use of the drug by contacting GlaxoSmithKline Pharmaceutical Ukraine LLC: 02152, Kiev, ave. Pavlo Tychyna, 1B, tel .: (044) 585-51–85, www.ua.gsk.com.You can report an undesirable phenomenon to GlaxoSmithKline Pharmaceuticals Ukraine LLC by phone: (044) 585-51-55 or e-mail: [email protected], you can report a complaint about the quality of the drug by phone: (044 ) 585–51–85, +38 (050) 381–43–49 or e-mail: [email protected]. Trademarks are owned or used under license by GSK.

© 2018 GSK Group of Companies or their licensor.

UA / VAL / 0009 / 18.12.30