Avamis - instructions for use, doses, side effects, contraindications

Active substanceFluticasone furoateFluticasone furoate

Similar drugsTo uncover

spray nazal.

Dosage form: & nbspnasal dosing spray

Composition:

COMPOSITION Each dose contains:
Name	Content in mg / dose	Content in mcg / dose
*Active substance*
Fluticasone furoate (micronized)	0,0275	27,5
*Excipients*
Dextrose	2,750	2750
Cellulose dispersible¹	0,825	825
Polysorbate 80	0,01375	13,75
Benzalkonium chloride solution²	0,0165³	16,5
Disodium Edetate	0,00825	8,25
Purified water	up to 50 μl	up to 50 μl
^1.Viscosity of 65 cPs, 11% of sodium carmellose. ^2.Contains 50% benzalkonium chloride. ^3.The content of benzalkonium chloride is 0.00825 mg / dose or 0.015% (w / w) in the suspension.

Description:Homogeneous suspension of white color.

Pharmacotherapeutic group:Glucocorticosteroid for topical application

ATX: & nbsp

R.03.B.A.09 Fluticasone furoate

Pharmacodynamics:

Mechanism of action

Fluticasone furoate - synthetic trifluorinated glucocorticosteroid with a very high affinity for receptors of glucocorticosteroids, has a pronounced anti-inflammatory effect.

Pharmacokinetics:

Suction

Fluticasone furoate not completely is absorbed by undergoing primary metabolism in the liver and intestines, that leads to an insignificant systemic effects. Intranasal administration in dose of 110 μg once a day is usually not leads to the definition of measurable plasma concentrations (<10 pg / ml). Absolute bioavailability of fluticasone furoate with intranasal administration in a dose of 880 mcg 3 times a day (daily dose 2640 μg) is 0.5%.

Distribution

Fluticasone furoate binds to blood plasma proteins by more than 99%. When an equilibrium concentration volume distribution fluticasone furoate is, in average, 608 liters.

Metabolism

Fluticasone furoate is rapidly excreted from systemic blood flow (common plasma clearance 58.7 l / h), mainly, by metabolism in the liver with the formation of inactive 17 P-carboxyl metabolite (GW694301X) with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system. The main pathway of metabolism is the hydrolysis of the S-fluoromethylcarbothioate group with the formation of a metabolite 17 p-carboxylic acid.

In vivo studies have shown that splitting of fluticasone furoate to fluticasone does not occur.

Excretion

With oral administration and intravenous administration, the removal of fluticasone furoate and its metabolites is mainly through the intestines by excretion with bile.With intravenous administration, the elimination half-life is 15.1 hours. About 1% and 2% is excreted by the kidneys when taken orally and intravenously, respectively.

Special patient groups

Elderly patients

Pharmacokinetic data are presented only for a small number of elderly patients (n = 23/872; 2.6%). No data, confirming that in elderly patients the cases of determination of fluticasone furoate in concentrations that are amenable to quantitative definition, more often than in younger patients.

Children

Fluticasone furoate is usually not detected in concentrations that are susceptible quantitative definition of (< 10 pg / ml), at intranasal intake in a dose of 110 mcg once a day. Concentrations determined by quantitatively, registered in less than 16% of children with intranasal intake at a dose of 110 mcg once a day and less than 7% of children taking 55 mcg once a day. There is no evidence that children under the age of 6 are more likely to experience fluticasone furoate in concentrations, amenable quantitative definition.

Patients with impaired renal function

Fluticasone furoate was not detected in urine in healthy volunteers when administered intranasally.Less than 1% of metabolites are excreted through the kidneys, so it is not expected that impaired renal function can affect the pharmacokinetics of fluticasone furoate.

Patients with impaired hepatic function

Study in patients with moderate impairment of liver function, who received fluticasone furoate once inhalation at a dose of 400 μg, showed an increase in the maximum concentration (Cmax 42%) and an increase in the area under the pharmacokinetic curve "concentration-time" (AUC_0-_∞172%) in comparison with healthy volunteers. Based on the results of the study, it is not expected that the average expected exposure of fluticasone furoate at a dose of 110 μg when administered intranasally in this group of patients will lead to suppression of cortisol. Therefore, it is not expected that moderate impairment of liver function will result in clinically significant effects in the administration of a standard dose for adults.

Thus, dose adjustments in patients with mild and moderate impairment of liver function (Child-Pugh class A and B) are not required. There is no data on patients with severe impairment of liver function (Child-Pugh class C).Caution should be exercised in determining the dose for patients with severe impairment of liver function, since such patients may be more at risk of systemic adverse reactions associated with the use of glucocorticosteroids (see the section on "Dosage and administration" and "Special instructions").

Other pharmacokinetic parameters

The concentrations of fluticasone furoate are usually not determined (<10 pg / ml) with intranasal administration at a dose of 110 μg once a day. The defined concentrations were observed only in less than 31% of patients aged 12 years and older and less than 16% of patients younger than 12 years with the appointment of 110 μg once a day intranasal. There was no dependence on gender, age (including children's age), race in cases where concentrations were higher or lower than the threshold of the determination.

Indications:

Adults and adolescents (ages 12 years and older)

- Treatment of nasal and eye symptoms of seasonal allergic rhinitis.

- Treatment of nasal symptoms of year-round allergic rhinitis.

Children (aged 2 to 11 years)

- Treatment of nasal symptoms of seasonal and year-round allergic rhinitis.

Contraindications:

Hypersensitivity to fluticasone furoate or any other components of the drug.

Carefully:

In patients with severe impairment of liver function, the pharmacokinetics of fluticasone furoate may vary.

Pregnancy and lactation:Data on the use of fluticasone fructate during pregnancy and during breastfeeding in women is not enough.

Fertility

There is no evidence of the effect of the drug on human fertility.

Pregnancy

There is no data on the use of fluticasone furoate in pregnant women. As shown in animal studies, glucocorticosteroids caused malformations, including cleft palate and intrauterine growth retardation. It is unlikely that these data are relevant for people receiving glucocorticosteroids intranasally at recommended therapeutic doses (see subsection "Pharmacokinetics"). Fluticasone furoate can be used in pregnant women only if the expected benefit for the mother exceeds the potential risk to the fetus.

Breastfeeding period

Excretion of fluticasone furoate with human breast milk has not been studied.The use of fluticasone furoate in lactating women should be considered only if the expected benefit to the mother exceeds any possible risk to the child

Dosing and Administration:

The drug Avamis is intended only for intranasal use.

To achieve maximum therapeutic effect is necessary adhere to a regular scheme application. The start of action may observed within 8 hours after the first introduction. To achieve maximum effect may require several days. No immediate effect should be carefully explained patient.

Treatment of nasal and ophthalmic symptoms of seasonal allergies rhinitis, nasal symptoms year-round allergic rhinitis in adults and adolescents (in age 12 years and over).

The recommended initial dose is 2 nebulization (27.5 μg fluticasone furoate in one spray) into each nostril 1 time per day (110 mcg per day).

When adequate control is achieved symptoms lowering the dose to 1 spray into each nostril 1 time in day (55 mcg per day) may be effective for supporting treatment.

Treatment of nasal symptoms seasonal and year-round allergic rhinitis in children in ages 2 to 11 years

The recommended initial dose is 1 spray (27.5 μg fluticasone furoate in one spray) to each nostril once a day (55 μg per day).

In the absence of the desired effect, a dose of up to 2 sprays per each nostril 1 time per day (110 μg per day) may be administered to each nostril once a day, if there is no desired effect. When adequate control of symptoms is achieved, it is recommended to reduce the dose to 1 spray into each nostril once a day (55 micrograms per day).

Children under 2 years of age

There is no evidence to recommend the use of fluticasone furoate intranasally as a treatment for seasonal and allergic allergic rhinitis in children under 2 years of age.

Elderly patients

Correction of the dose is not required (see subsection "Pharmacokinetics"),

Patients with impaired renal function

Correction of the dose is not required (see subsection "Pharmacokinetics").

Patients with impaired hepatic function

Dose adjustments in patients with mild and moderate impairment of liver function (Child-Pugh class A and B) are not required.There is no data for patients with severe impairment of liver function (Child-Pugh class C). Caution should be exercised in determining the dose for patients with severe impairment of liver function, since such patients may be more at risk of systemic adverse reactions associated with the use of glucocorticosteroids (see subsection "Pharmacokinetics" and section "Special instructions").

Side effects:

The adverse events presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. 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, including individual cases).

Undesirable effects observed in clinical trials

Disturbances from the respiratory system, chest and mediastinal organs

Very often: epistaxis. In adults and teenagers cases Nasal bleeding was noted more often with long-term use (more 6 weeks) than with a short course (up to 6 weeks). In studies in children with duration of therapy up to 12 weeks number of cases of nasal bleeding was similar in the group fluticasone furoate and placebo.

Often: ulceration of the mucosa shell of the nasal cavity.

Disturbances from musculoskeletal and connective tissue

The frequency of growth retardation is unknown: children.

The results of a study conducted during the year in pre-pubertal children who received fluticasone furoate in a dose of 110 mcg once a day, do not allow to determine the statistical frequency of this undesirable phenomenon, since it is impossible to calculate the effect of the drug on the final growth rates in children participating in the study.

The delay in the growth of the skeleton in children refers to systemic undesirable phenomena characteristic of the class of glucocorticosteroids with prolonged oral or parenteral administration.

Undesirable phenomena observed during post-registration observation

Immune system disorders

Rarely: reactions Hypersensitivity, including anaphylaxis, Quincke's edema, rash, hives.

Disturbances from the nervous system

Often: headache.Disturbances from the respiratory system, chest and mediastinal organs

Rarely, discomfort in the nose (including burning, irritation in the nose and soreness), dryness in the nose.

Disturbances on the part of the organ of sight

The frequency of transient is unknown: visual impairment. Possible the emergence of systemic side effects, characteristic of glucocorticosteroids (see section "Special instructions").

Overdose:

Symptoms

In a study of the bioavailability of the drug intranasally, doses were applied 24 times higher than the recommended dose for adults for more than 3 days, with no undesirable systemic reactions observed.

Treatment

It is unlikely that an acute overdose will require other treatment other than medical supervision.

Interaction:

Fluticasone furoate is rapidly excreted by undergoing primary metabolism in

Liver by the CYP3A4 isoenzyme of the cytochrome P450 system. In the study of the drug interaction of fluticasone furoate and the highly active inhibitor of the isoenzyme CYP3A4-ketoconazole in the ketoconazole group (6 of 20 patients), more measurable plasma concentrations of fluticasone furoate in comparison with placebo (1 in 20 patients) were observed.This small increase did not result in a statistically significant difference in the plasma cortisol content within 24 hours between the two groups.

On the basis of theoretical data, there are no assumptions about any drug interactions of fluticasone furoate used intranasally according to the instructions for use and other drugs that are metabolized with the participation of the cytochrome P450 system. Thus, clinical studies to study the interaction of fluticasone furoate and other drugs have not been conducted (see section "Special instructions").

Special instructions:

The drug Avamis is intended only for intranasal use. Fluticasone furoate is exposed primary metabolism in the liver by isoenzyme CYP3A4 systems of cytochrome P450. In this way, pharmacokinetics of fluticasone furoate patients with severe impairment liver function may vary (see section "Interaction with other medicinal products "and subsection "Pharmacokinetics").

Dose adjustments in patients with lungs and moderate impairment of function Liver (class A and B by Child-Pugh) is not it takes.There is no data in patients with severe violations of liver function (class C by Child-Pugh). Caution should be exercised in determining the dose for patients with severe impairment of liver function, since such patients may be more at risk of systemic adverse reactions associated with the use of glucocorticosteroids (see the "Dosage and Administration" section and the "Pharmacokinetics" subsection).

Based on data on the use of another glucocorticosteroid, which is metabolized by cytochrome P450 isoenzyme CYP3A4, with ritonavir, the combined use of ritonavir with fluticasone furoate is not recommended because of the possible risk of increasing the systemic exposure of fluticasone furoate (see "Interactions with Other Drugs" and subsection "Pharmacokinetics"). Systemic effects characteristic of glucocorticosteroids (such as Itenko-Cushing syndrome, suppression of adrenal function, growth retardation in children and adolescents, cataracts, glaucoma), as well as a number of psychological or behavioral effects, including psychomotor hyperactivity, sleep disturbance, anxiety, depression or aggression (especially in children), can be observed with the use of intranasal glucocorticosteroids.The likelihood of such effects is much lower than when using oral forms of glucocorticosteroids and the combination of oral and intranasal glucocorticosteroids. Effects may vary in individual patients, as well as in various glucocorticosteroid preparations. If there are any grounds for suggesting possible disorders of the adrenal function, care must be taken when switching patients from systemic steroids to fluticasone furoate.

Children who received 110 μg of fluticasone furoate daily for one year experienced a decrease in growth rate. However, the results of this study do not allow us to determine the statistical frequency of this undesirable phenomenon, since it is not possible to calculate the effect of the drug on the final growth rates in children (see the "Side effect" section). As the maintenance dose in children, the smallest dose should be used to ensure adequate control of the symptoms of the disease (see section "Method of administration and dose"). It is recommended to regularly monitor the growth of children receiving long-term therapy with glucocorticosteroids intranasally.If growth slows, therapy should be revised if possible to reduce the intranasal dose of glucocorticosteroids to the lowest dose at which effective symptom control is maintained. In addition, attention should be paid to the patient's referral to the pediatrician.

As with other intranasal glucocorticosteroids, physicians should be vigilant about the possible systemic effects of glucocorticosteroids, including changes on the part of the organ of vision. Therefore, careful monitoring is justified in patients with visual impairment or with increased intraocular pressure, glaucoma and / or cataracts in the history.

Effect on the ability to drive transp. cf. and fur:

Based on the pharmacological properties of fluticasone furoate and other local glucocorticosteroids, no influence on the ability to drive or other mechanisms is expected.

Form release / dosage:Spray nasal dosed with 27.5 μg / dose.

Packaging:

For 30, 60 or 120 doses in a vial of orange glass, equipped with a dosing (50 μl) nebulization device.1 bottle per outer plastic case with indicator window, pressure valve and cap with elastomer restraint. For 1 bottle in a case with instructions for medical use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Do not freeze.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000477/10

Date of registration:28.01.2010

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia