Asmaneks® Tvistkheyler®

General characteristics. Structure:

Active ingredient: 200 mkg or 400 mkg of a mometazon of furoate in 1 dose.

Excipients: lactose anhydrous.

Pharmacological properties:

Pharmacodynamics. GKS for inhalation use, has local antiinflammatory effect.

The mechanism of antiallergic and antiinflammatory action of a mometazon of furoate is caused by its ability to inhibit release of mediators of an inflammation. In vitro of a mometazon furoate significantly inhibits release of leukotrienes from leukocytes. In cultures of cells of a mometazon furoate showed high ability to inhibit synthesis and release of interleykin of 1, 5 and 6 (IL-1,IL-5, IL-6), and also ФНОα; it is also inhibitor of products of leukotrienes, and also extremely powerful Th2-tsitokinov inhibitor, interleykin 4 and 5, CD4+ T-cells of the person.

At a mometazon of furoate affinity and ability to linkng with GKS receptors of the person are 16 times higher, than at dexamethasone, is 7 times higher, than at Triamcinolonum of acetonide, 5 times are higher, than at a budesonid and 1.5 times above, than at a flutikazon.

Use of the drug Asmaneks® Tvistkheyler® in doses from 100 to 800 mkg/days improves function of external respiration (on indicators of a peak expiratory rate and OFV1), leads to more complete control of symptoms of bronchial asthma, and reduced the need for use of inhalation beta2-adrenomimetik. Improvement of function of breath is observed at some patients already in 24 h after the beginning of therapy, however the maximum effect is usually reached not earlier than in 1-2 weeks. Improvement of function of breath remains throughout the entire period of treatment.

At patients with bronchial asthma at regular use of the drug Asmaneks® Tvistkheyler® within 4 weeks in doses from 200 mkg of 2 times/days to 1200 mkg suppression signs гипоталамо - pituitary and adrenal system do not come to light, and system effects are shown only at use in a dose of 1600 mkg/days.

Pharmacokinetics. After inhalation system bioavailability of a mometazon of furoate low, in particular, because of small absorption and considerable presistemny metabolism of this medicine at its proglatyvaniye. In different researches of assessment of influence of a mometazon of furoate in an equilibrium state at appointment it in the form of inhalation, and also after single in/in introductions absolute bioavailability made about 16% at healthy patients and about 10% - at patients with asthma. At use concentration of drug in plasma is in the recommended doses about or below a definition threshold (50 pg/ml). Thereof it is impossible to define neither T1/2, nor Vd of a mometazon of furoate after inhalation.

Indications to use:

— basic therapy of bronchial asthma of any severity (including at the patients applying earlier both inhalation, and system GKS and also at insufficient efficiency of the therapy applied earlier without use of GKS);

— the chronic obstructive pulmonary disease (COPD) - from moderate severity to very heavy.

Route of administration and doses:

Drug is used in the form of inhalations. The recommended doses depend on disease severity. At the stable course of bronchial asthma easy and moderate severity the recommended initial dose of the drug Asmaneks® Tvistkheyler® makes 400 mkg of 1 times/days. Inhalation is recommended to be carried out in the evening. At some patients (for example, GKS receiving before inhalation in high doses) more adequate control of a course of a disease is reached when the daily dose of 400 mkg is divided into 2 inhalations. At a number of patients when carrying out a maintenance therapy decrease in a daily dose to 200 mkg of 1 times/days is possible in the evening. In these cases it is necessary to apply Asmaneks® Tvistkheyler® with the maintenance of a mometazon of furoate of 200 mkg in 1 dose.

The dose should be selected individually (before achievement of the minimum dose providing adequate control of a course of bronchial asthma).

At a severe form of bronchial asthma the recommended initial dose makes 400 mkg of 2 times/days that corresponds to the maximum daily dose of 800 mkg. After achievement of effective control of symptoms of asthma it is necessary to reduce a dose of the drug Asmaneks® Tvistkheyler® to the minimum effective gradually.

Upon transition from oral administration of GKS to therapy by the drug Asmaneks® Tvistkheyler® in an initiation of treatment both drugs apply at the same time. Approximately in a week of combined use begin to cancel gradually peroral GKS, reducing its daily dose or missing one reception. The following dose decline is carried out in 1 or 2 weeks, depending on a condition of the patient. It is not necessary to reduce a dose more than by 2.5 mg of Prednisolonum a day (or its equivalent). Cancellation should be carried out surely gradually. At the same time it is necessary to control carefully a condition of the patient, including breath function indicators (not to miss the moment of deterioration in a course of bronchial asthma) and functions of adrenal glands (for an exception of insufficiency of function of bark of adrenal glands).

At HOBL the recommended dose makes 800 mkg/days. Most of patients can accept all dose once a day - in the evening. At some patients reception on 400 mkg of 2 times/days is more effective.

Instructions for use inhaler of Tvistkheyler®. Before opening Tvistkheyler®, it is necessary to be convinced that the counter and the index on a cover are combined. Tvistkheyler open, shifting a white cover counterclockwise, at the same time holding Tvistkheyler's basis in the fixed situation. The counter of doses at the same time notes use of 1 dose. Further Tvistkheyler® should be placed in an oral cavity and, having clasped with lips a mouthpiece, quickly and deeply to inhale. Then to take out a mouthpiece from a mouth and to hold the breath on 10 sec. or so for a long time as far as it is convenient to the patient. The patient should not exhale through Tvistkheyler®.

To close Tvistkheyler®, it is necessary to return a cover to the place of right after inhalation and to turn a cover clockwise, at the same time softly pressing a cover down, the click will not sound yet, and the cover completely will not be closed. The arrow on a cover at the same time will completely be combined with a counter window. At the same time there is a loading of a new dose of drug for the following inhalation.

The patient should advise to rinse a mouth after each inhalation. It reduces risk of development of candidiasis of an oral cavity.

The display of the counter will show when the last dose is loaded. After a dose 01 on the counter it will be highlighted 00 and the cover will be blocked. After that performing inhalations will become impossible and Tvistkheyler® should be thrown out.

Твистхейлер® it is necessary to contain dry and pure. The mouthpiece outside can be cleaned a dry gauze or fabric. Твистхейлер® it is impossible to wash with water.

Features of use:

Use at pregnancy and feeding by a breast. Adequate and well controlled drug use studies at pregnancy were not conducted, and there are no data on whether the mometazona furoate gets into breast milk. However after inhalation use concentration of a mometazon of furoate in a blood plasma is very low; impact on a fruit is probably not enough, the probability of toxic impact on reproductibility is very low.

Use of the drug Asmaneks® Tvistkheyler® (as well as other inhalation GKS) at pregnancy and during breastfeeding is possible only if the estimated advantage for mother exceeds potential risk for a fruit or the child.

Newborns whose mothers received GKS during pregnancy demand observation for identification of signs of insufficiency of function of bark of adrenal glands.

Use for children. Safety and efficiency of use of Asmaneks Tvistkheyler for children up to 12 years are up to the end not studied.

Recommend to control regularly growth of the teenagers receiving long therapy of GKS for inhalations. At delay of growth it is necessary to reconsider the carried-out therapy for the purpose of a dose decline of inhalation GKS to minimum at which effective control behind disease symptoms is achievable.

Special instructions. As well as at use of other corticosteroids, it is necessary to remember a possibility of development of hypersensitivity reactions, including rash, urticaria, an itch, an erythema, and also an eye, persons, lips and a throat swelled.

Asmaneks® Tvistkheyler® is not intended for bystry stopping of a bronchospasm. The patient should be warned that for this purpose it is necessary to use high-speed inhalation bronchial spasmolytics.

The patient should be warned also about need of the immediate address to the doctor if against the background of therapy by the drug Asmaneks® Tvistkheyler® attacks of a bronchospasm do not manage to be stopped use of bronchial spasmolytics. In these cases increase in a dose of the drug Asmaneks® Tvistkheyler® (can be required up to the maximum recommended daily) or/and purpose of GKS for system use.

It is necessary to explain to the patient need of constant use of the drug Asmaneks® Tvistkheyler® (even in the absence of disease symptoms) and inadmissibility of the sharp termination of inhalations.

Upon transition from GKS system use on inhalation of the drug Asmaneks® Tvistkheyler® requires extra care because of possible risk of development of adrenal insufficiency. After cancellation of system GKS function recovery гипоталамо - pituitary and adrenal system requires several months.

During stressful situations, including injuries, surgical interventions, infectious diseases or a heavy attack of bronchial asthma, the patients who were earlier receiving GKS for system use need additional purpose of a short course of system GKS which then, in process of subsiding of symptoms, gradually cancel. Such patients should recommend to carry at themselves a small amount of GKS for intake together with the warning card. On it it is necessary to designate need of use at stressful situations of system GKS and their recommended doses. At this category of patients it is regularly necessary to control function of adrenal glands (in particular, the morning maintenance of cortisol in a blood plasma).

Upon transition from system GKS to Asmaneks® Tvistkheyler® display of the accompanying allergic diseases which symptoms were suppressed with use of system corticosteroids earlier is possible. During this period at some patients emergence of signs of cancellation of system GKS, including muscle pain and/or joints, a depression, feeling of fatigue is possible in spite of the fact that indicators of function of lungs at the same time are stable or even improve. Such patients should be convinced of need of continuation of therapy by the drug Asmaneks® Tvistkheyler®, but at the same time carefully to control their state in connection with possible development of insufficiency of bark of adrenal glands. If there are signs of insufficiency of adrenal glands, it is necessary to increase temporarily GKS dose for system use, and further to carry out their cancellation more smoothly.

As well as when using other inhalation drugs, after use of the drug Asmaneks® Tvistkheyler® development of a paradoxical bronchospasm is possible. In this case immediate use of inhalation high-speed bronchodilators with the subsequent drug withdrawal of Asmaneks® Tvistkheyler® and purpose of alternative therapy is required.

The patients receiving GKS or other immunodepressants should advise to avoid contacts with sick some infections (chicken pox, measles) and it is obligatory to consult with the doctor if such contact happened (especially important at use for teenagers 12 years are more senior).

For maintenance of low potential of suppression гипоталамо - pituitary and adrenal system it is not necessary to exceed the recommended doses, and at each patient the dose of the drug Asmaneks® Tvistkheyler® should be titrated, trying to obtain the minimum effective. At purpose of the drug Asmaneks® Tvistkheyler® the doctor should consider that impact of drug on products of cortisol can vary at different patients.

Data that use of the drug Asmaneks® Tvistkheyler® in the doses exceeding recommended leads to strengthening of its therapeutic effect are not available. Developing of candidiasis can demand performing the corresponding antifungal therapy or phase-out of Asmaneks Tvistkheyler.

Use in pediatrics. Safety and efficiency of use of the drug Asmaneks® Tvistkheyler® for children up to 12 years are not studied.

Recommend to control regularly growth of the teenagers receiving long therapy of GKS for inhalations. At delay of growth it is necessary to reconsider the carried-out therapy for the purpose of a dose decline of inhalation GKS to minimum at which effective control behind disease symptoms is achievable.

Side effects:

Most often: oral cavity candidiasis, pharyngitis, dysphonia, headache.

Seldom: dryness in a mouth and a throat, dyspepsia, increase in body weight, heartbeat.

There are no data which specify that the risk of development of side reactions is higher at teenagers or patients at the age of 65 years and is more senior.

From respiratory system: at use of inhalation GKS for treatment of bronchial asthma development of a bronchospasm and increase in number of rattles in lungs right after inhalation is possible.

System effects (especially at use in high doses and for an appreciable length of time): oppression of function of bark of adrenal glands, a growth inhibition at children and teenagers, demineralization of a bone tissue, glaucoma, increase in intraocular pressure, development of a cataract.

Post-marketing use.

Allergic reactions: in isolated cases - hypersensitivity manifestations, such as rash, a skin itch, a Quincke's disease and anaphylactic reaction. It was reported about deterioration in a course of asthma which can be shown by cough, an asthma, goose breathing and a bronchospasm.

Interaction with other medicines:

At simultaneous use of the drug Asmaneks® Tvistkheyler® and inhibitor of CYP3A4 enzyme of a ketokonazol increase in concentration of a mometazon of furoate in a blood plasma is noted. However it is improbable that these changes have clinical value.

Contraindications:

— children's age up to 12 years;

— the established hypersensitivity to drug components (a mometazona furoate and lactose).

With care: active or latent pulmonary tuberculosis, fungal, bacterial or system viral infections, herpetic damage of eyes (Herpes simplex), pregnancy, lactation period.

Overdose:

Symptoms: it is necessary to consider that prolonged use of GKS for inhalations in the raised doses can lead to function suppression гипоталамо - pituitary and adrenal system.

Treatment: in connection with low system bioavailability of the drug Asmaneks® Tvistkheyler® the overdose does not demand any special methods of therapy, except control of a condition of the patient. Then it is necessary to resume use of drug in a therapeutic dose.

At function suppression гипоталамо - pituitary and adrenal system carry out symptomatic therapy, gradual drug withdrawal, correction of electrolytic disturbances.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature from 8 °C to 30 °C. A period of validity - 2 years. To use within 3 months after opening of packaging from a foil.

Issue conditions:

According to the recipe

Packaging:

240 mg (30 doses) - the inhalers dosing Tvistkheyler (1) - the aluminum foil laminated by a film polymeric (1) - a pack cardboard.
240 mg (60 doses) - the inhalers dosing Tvistkheyler (1) - the aluminum foil laminated by a film polymeric (1) - a pack cardboard.