Avamis

General characteristics. Structure:

Active ingredient: a flutikazona the furoate (micronized) 27.5 mkg

Excipients: the dextrose, cellulose dispersed (contains 11% of a karmelloza of sodium), polysorbate 80, a benzalkoniya chloride (50% solution), dinatrium эдетат, the water purified.

Pharmacological properties:

GKS for topical administration. Flutikazona furoate - a synthetic triftorirovanny glucocorticosteroid with high affinity to glucocorticoid receptors, possesses the expressed antiinflammatory action.

Pharmacokinetics. Absorption

Flutikazona furoate is not completely absorbed, being exposed to primary metabolism in a liver that leads to insignificant system influence. Intranasal introduction in a dose of 110 mkg of 1 times / usually does not lead to achievement of the defined concentration in plasma (<10 pg/ml). Absolute bioavailability of a flutikazon of furoate at intranasal introduction in a dose of 880 mkg 3 (a daily dose of 2640 mkg) makes 0.5%.

Distribution

Flutikazona furoate contacts proteins of a blood plasma more than for 99%. At achievement of equilibrium concentration of Vd of a flutikazon of furoate makes, on average, 608 l.

Metabolism

Flutikazona furoate is quickly brought from a system blood-groove (the general plasma clearance of 58.7 l), generally by means of metabolism in a liver with education inactive 17β-карбоксильного a metabolite (GW694301X) with participation of an isoenzyme of CYP3A4 of system of P450 cytochrome. The main way of metabolism - hydrolysis of S-ftormetilkabrotioatnoy of group with education 17β-карбоксильного a metabolite. The researches in vivo showed that splitting of a flutikazon of furoate to a flutikazon does not happen.

Removal

Removal of a flutikazon of furoate and its metabolites at peroral introduction and in introduction happens preferential through intestines that reflects their excretion with bile. At intake and in introduction it is removed by kidneys: 1% and 2% respectively.

Special groups of patients

Pharmacokinetic data are submitted only for a small number of patients of advanced age (n=23/872; 2.6%). There are no data, confirmatory that the concentration of a flutikazon of furoate which are giving in to quantitative definition at patients of advanced age are higher, than at young patients.

At intranasal use in a dose of 110 mkg 1 time / flutikazona furoate usually is not found in children in the concentration which are giving in to quantitative definition (<10 pg/ml). The concentration defined quantitatively are registered less than at 16% of children at intranasal use in a dose of 110 mkg of 1 time(s) less than at 7% of children, at intranasal use in a dose of 55 mkg of 1 times / there are no data testimonial of the fact that at children is younger than 6 years more often increase in concentration of a flutikazon of furoate is observed.

Patients with a renal failure

Flutikazona furoate was not defined in urine at healthy volunteers at intranasal reception. Less than 1% of metabolites is removed by kidneys, thus, renal failures theoretically cannot influence pharmacokinetics of a flutikazon of furoate.

Patients with an abnormal liver function

In a research at patients with a moderate abnormal liver function, at inhalation use of a flutikazon of furoate in a dose of 400 mkg increase in Cmax for 42% and increase in AUC0-∞ for 172%, in comparison with healthy volunteers was once shown. Proceeding from results of a research, on average, alleged influence of a flutikazon of furoate in a dose of 110 mkg at intranasal use for this group of patients will not lead to cortisol suppression. Therefore, moderate abnormal liver functions will possibly not result in clinically significant effects at purpose of a standard dose for adults.

Other pharmacokinetic parameters

Concentration of a flutikazon of furoate usually are not defined (<10 pg/ml) at intranasal introduction in a dose of 110 mkg of 1 times / the Defined concentration were observed only less than at 31% of patients at the age of 12 years and are more senior and less than at 16% of patients 12 years at appointment in a dose of 110 mkg of 1 times are younger / intranazalno. Dependence on a sex, age (including children's age), race was not noted in cases when concentration were higher or lower than a definition threshold.

Indications to use:

The symptomatic treatment of seasonal and year-round allergic rhinitis at adults and children is more senior than 2 years.

Route of administration and doses:

Drug is used intranazalno.

For achievement of the maximum therapeutic effect it is necessary to adhere to the regular scheme of use. The beginning of action can be observed during 8 h after the first introduction. For achievement of the maximum effect several days can be required. It is necessary to explain carefully to the patient the reason of lack of immediate effect.

For a symptomatic treatment of seasonal and year-round allergic rhinitis to adults and teenagers aged from 12 years the recommended initial dose - on 55 mkg (2 sprayings) in each nostril of 1 times / is also more senior (110 mkg/).

At achievement of adequate control of symptoms the dose decline to 27.5 mkg (1 spraying) in each nostril of 1 times / (55 mkg/) can be effective for the supporting treatment.

To children aged from 2 up to 11 years the recommended initial dose - on 27.5 mkg (1 spraying) in each nostril of 1 times / (55 mkg/).

In the absence of desirable effect at a dose of 27.5 mkg (1 spraying) in each nostril of 1 times / increase in a dose to 55 mkg (2 sprayings) in each nostril of 1 times / is possible (110 mkg/). At achievement of adequate control of symptoms it is recommended to lower a dose to 27.5 mkg (1 spraying) in each nostril of 1 times / (55 mkg/).

Not enough data for the recommendation of use of a flutikazon of furoate intranazalno for treatment of seasonal and year-round allergic rhinitises at children are aged younger than 2 years.

It is not required to patients of advanced age of dose adjustment.

Dose adjustment is not required to patients with a renal failure.

With easy and moderate abnormal liver functions dose adjustment is not required from patients. There are no data on use for patients with heavy abnormal liver functions.

Rules of use and treatment of drug

The indicator window in plastic packaging allows to control drug level in a bottle. In bottles on 30 or 60 doses the level of drug will be visible at once, and on 120 doses the initial level of drug is in bottles above the upper bound of an observation port. Nasal spray is produced in bottles of orange glass which are in plastic cases. To check drug level in a bottle, it is necessary to look at it on light. Level will be visible in an observation port.

Preparation for use should be carried out when using spray for the first time, and also if the bottle was left open. The correct preparation for use will provide injection of a necessary dose of drug.

1. Without removing a cap, it is good to shake a bottle during 10 sec. Drug represents quite dense suspension and becomes more liquid when stirring. Spraying is possible only after stirring.

2. To remove a cap, having smoothly pulled its big and index fingers.

3. To hold a bottle vertically and to direct a tip from itself.

4. With a force to press the button, to make several pressing (at least 6) until from a tip the small cloudlet appears (if it is not possible to press the button one thumb, then it is necessary to press it thumbs of both hands).

5. Spray is ready to use.

Use of nasal spray

1. To carefully stir up a bottle.

2. To remove a cap.

3. To clean a nose and to incline the head a little forward.

4. To enter a tip into one nostril, continuing to hold a bottle vertically.

5. To direct a sprayer tip to an external wall of a nose, not to a nasal partition. It will provide the correct injection of drug.

6. To begin to take a breath through a nose and to make single pressing by fingers for drug spraying.

7. To take out the sprayer from a nostril and to exhale through a mouth.

8. If it is necessary to make two injections in each nostril (on doctor's orders), it is necessary to repeat points 4-6.

9. To repeat the procedure for other nostril.

10. To close a bottle a cap.

11. It is necessary to avoid hit of spray in eyes. At hit of drug in eyes, carefully to wash out them water.

Care of the sprayer

After each use:

1. To blot a tip and an internal surface of a cap with a dry pure napkin. To avoid water hit.

2. Not to try to clean a tip opening a pin or other sharp objects.

3. It is always necessary to close a bottle and to store it closed. The cap protects the sprayer from dust and a contamination, pressurizes a bottle, prevents accidental pressing the button.

If the sprayer does not work:

1. To check the level of the remained drug in a bottle through an observation port. If there was absolutely small amount of liquid, it can be insufficiently for operation of the sprayer.

2. To check a bottle for existence of damages.

3. To check whether the tip opening got littered. Not to try to clean a tip opening a pin or other sharp objects.

4. To try to put the device in action, having repeated the procedure of preparation of nasal spray for use.

Features of use:

Flutikazona furoate is exposed to metabolism at "the first passing" through a liver with the participation of CYP3A4 isoenzyme. Therefore at patients with heavy abnormal liver functions the pharmacokinetics of a flutikazon of furoate can change.

Influence on ability to driving of motor transport and to control of mechanisms

Based on pharmacological properties of a flutikazon of furoate and other GKS for topical administration, influence on ability to control of motor transport or other mechanisms is not supposed.

Side effects:

The undesirable phenomena given below are listed depending on anatomo-physiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000); very seldom (<1/10 000, including separate cases). Categories of frequency were created on the basis of clinical trials of drug and post-marketing observation.

From respiratory system, bodies of a thorax and a mediastinum: very often - nasal bleeding: at adults and teenagers cases of nasal bleeding were noted more often at prolonged use (more than 6 weeks), than at a short course (to 6 weeks). In researches children lasting therapy up to 12 weeks had a similar quantity of cases of nasal bleedings in group of a flutikazon of furoate and placebo.

Often - ulcerations of a mucous membrane of a nasal cavity.

From immune system: hypersensitivity reactions, including an anaphylaxis, a Quincke's edema, rash, urticaria.

Interaction with other medicines:

Flutikazona furoate is quickly metabolized in a liver with the participation of an isoenzyme of CYP3A4 of system of P450 cytochrome. In a research of medicinal interaction of a flutikazon of furoate and CYP3A4 inhibitor of a ketokonazol more cases of definition of plasma concentration of a flutikazon of furoate which values were higher threshold, in group of the patients receiving кетоконазол (6 of 20 patients), in comparison with placebo (1 of 20 patients) were observed. This small increase does not result in statistically significant distinction of maintenance of cortisol in plasma during 24 h between two groups.

On the basis of theoretical data any medicinal interaction of a flutikazon of furoate at intranasal use with other medicines which are metabolized with the participation of isoenzymes of system of P450 cytochrome is not supposed. Therefore clinical trials for studying of interaction of a flutikazon of furoate and other medicines were not carried out.

On the basis of the data obtained in a research with other GKS which is also exposed to CYP3A4 - the mediated metabolism and also on the basis of the literary data concerning other GKS which are exposed to CYP3A4 - the mediated metabolism joint purpose of drug Avamis with ritonaviry because of potential risk of increase in system exposure of a flutikazon of furoate is not recommended.

Contraindications:

— hypersensitivity to a flutikazon to furoate and other components of drug.

With care it is necessary to use drug at patients with heavy abnormal liver functions since the pharmacokinetics of a flutikazon of furoate can change.

Use of drug AVAMIS at pregnancy and feeding by a breast
Data on use of a flutikazon of furoate at pregnancy and in the period of a lactation are not enough. Flutikazon furoate can be applied at pregnancy only in cases when the expected advantage of therapy for mother exceeds potential risk for a fruit.

Excretion of a flutikazon of furoate with female breast milk was not studied. Flutikazona furoate can be applied at the feeding women only if the expected advantage for mother exceeds potential risk for the child.

Use at abnormal liver functions
With easy and moderate abnormal liver functions dose adjustment is not required from patients. There are no data on use for patients with heavy abnormal liver functions.

Use at renal failures
Dose adjustment is not required to patients with a renal failure.

Use for elderly patients
It is not required to patients of advanced age of dose adjustment.

Use for children
To children aged from 2 up to 11 years the recommended initial dose - on 27.5 mkg (1 spraying) in each nostril of 1 times / (55 mkg/).

In the absence of desirable effect at a dose of 27.5 mkg (1 spraying) in each nostril of 1 times / increase in a dose to 55 mkg (2 sprayings) in each nostril of 1 times / is possible (110 mkg/). At achievement of adequate control of symptoms it is recommended to lower a dose to 27.5 mkg (1 spraying) in each nostril of 1 times / (55 mkg/).

Not enough data for the recommendation of use of a flutikazon of furoate intranazalno for treatment of seasonal and year-round allergic rhinitises at children are aged younger than 2 years.

Overdose:

Symptoms: in a research of bioavailability of drug doses of the 24 times higher recommended dose were intranazalno applied to adults within more than 3 days, at the same time undesirable system reactions were not observed.

Treatment: it is improbable that the acute overdose will demand other treatment, except medical observation.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 30 °C; not to freeze. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

30 doses - the bottles of orange glass supplied with the spraying device (1) - a plastic case with an indicator window, the press valve and a cap with the limiter from elastomer.
60 doses - the bottles of orange glass supplied with the spraying device (1) - a plastic case with an indicator window, the press valve and a cap with the limiter from elastomer.
120 doses - the bottles of orange glass supplied with the spraying device (1) - a plastic case with an indicator window, the press valve and a cap with the limiter from elastomer.