Relvar® Ellipta® 184 .mu.g / 22 .mu.g doses of powder 30 for inhalation, metered dose

The instruction for medical use of Ellipta® Relvar® medicine the Trade name of Relvar® Ellipta® the International unlicensed name Is not present the Dosage form Powder for inhalations dosed, 92 mkg / 22 mkg, 184 mkg / 22 mkg, 30 doses Structure 1 dose contains active agents: 100 mkg1 or 200 mkg1 a flutikazona of the furoate micronized, 40 mkg of a vilanterol trifenatat micronized (25 mkg1 in terms of vilanterol), excipients: magnesium stearate, lactoses monohydrate. 1 The nominal amount of active ingredient put in the course of production Is specified, the brought quantity is 184 mkg or 92 mkg of a flutikazon of furoate and 22 mkg of a vilanterol that corresponds to the specified dosages. The description the Plastic inhaler of Ellipta® with the body of light gray color, a pale blue cover of a mouthpiece and the counter of doses packed into the container from a foil containing the moisture absorbing bag. The container is sealed by easily opening foil. The inhaler contains two strips, each strip consists of 30 evenly distributed cells, each of which contains powder of white color. Pharmacotherapeutic group Drugs for treatment of obstructive respiratory diseases. Inhalation sympathomimetics. Sympathomimetics in a combination with other drugs for treatment of obstructive respiratory diseases. Vilanterol and flutikazona furoate. The ATX R03AK10 code the Pharmacological Pharmacokinetics Absorption Absolute Bioavailability properties of a vilanterol and flutikazon of furoate at inhalation introduction of a combination of a vilanterol and flutikazon of furoate averaged 15.2% and 27.3%, respectively. The oral bioavailability of both substances was low, and averaged 1.26% and & lt, 2%, respectively. In view of low oral bioavailability, systemic action of a vilanterol and flutikazon of furoate after inhalation reception first of all it is caused by absorption of a part of the inhalation dose which came to lungs. Distribution After intravenous administration vilanterol and a flutikazona furoate is actively distributed in an organism, at the same time average volumes of distribution in an equilibrium state are 165 l and 661 l, respectively. Both substances have low ability to contact erythrocytes. In the researches in vitro the linking of a vilanterol and flutikazon of furoate with proteins of plasma of the person was high and reached on average & gt, 93.9% and 99.6%, respectively. Extent of linking with proteins of in vitro plasma did not decrease at patients with abnormal liver functions and kidneys. In spite of the fact that vilanterol and a flutikazona furoate are substrates of the R-glycoprotein (P-gp), at co-administration of a combination of a vilanterol and flutikazon of furoate with P-gp inhibitors the change of system exposure of a vilanterol or flutikazon of furoate is considered improbable as both substances have good absorbing capacity. Metabolism On the basis of in vitro of experiments can be concluded that key ways of metabolism of a vilanterol and a flutikazon of furoate in a human body first of all are mediated through CYP3A4 cytochrome isoenzyme. Vilanterol is mainly metabolized by O-dealkylation with formation of a number of the metabolites having significantly lower бета1st and beta2-adrenomimetichesky activity. Flutikazona furoate is mainly metabolized by hydrolysis of S-ftormetilkarbotiatnoy of group with formation of the metabolites having much lower glucocorticosteroid activity. Clinical trial of medicinal interactions of drug with CYP3A4 cytochrome isoenzyme at long introduction of a combination of a flutikazon of furoate and a vilanterol was conducted (184 mkg / a dose + 22 mkg) and strong inhibitor of an isoenzyme of CYP3A4 cytochrome – a ketokonazol (400 mg) on the example of healthy volunteers. Joint administration of drugs led to increase in average area under pharmacokinetic curve (AUC(0–24)) and average maximum concentration (Cmax) of a flutikazon of furoate for 36% and 33%, respectively. Increase in exposure of a flutikazon of furoate was associated with decrease in average concentration of the serumal cortisol by 27% measured during 0-24 hours. Joint introduction of a combination of a vilanterol and flutikazon of furoate and a ketokonazol led to increase in average AUC(0–t) and Cmax of a vilanterol for 65 and 22%, respectively. Increase in exposure of a vilanterol did not lead to strengthening of system effects, characteristic of beta-agonists, – influence on heart rate, potassium content in blood or an interval of QT. Removal After oral administration of a flutikazon furoate in a human body, mainly, was metabolized with formation of metabolites which were mainly removed through digestive tract, except for the dose of radioactive material & lt, 1% removed with urine. Expected plasma elimination half-life of a flutikazon of furoate after inhalation administration of drug averaged 24 hours. The effective elimination half-life at accumulation of a vilanterol determined at repeated use of a vilanterol by a dose in 25 mkg by inhalation makes 16.0 h at the patients having asthma, and the patients suffering from HOBL have 21.3 h. After oral administration vilanterol in a human body, mainly, it was metabolized with formation of metabolites which were excreted with urine and excrements, in the ratio about 70% and 30% of a dose of radioactive material, respectively. Plasma elimination half-life of a vilaterol after inhalation administration of drug averaged 2.5 hours. Special groups of patients during the third phase of clinical trials the population meta-analysis of pharmacokinetics of a vilanterol and a flutikazon of furoate at patients with bronchial asthma and the chronic obstructive pulmonary disease (COPD) was carried out. Within this analysis the influence of demographic indicators (age, sex, weight, body mass index, racial and ethnic origin) on pharmacokinetics of a vilanterol and flutikazon of furoate was estimated. The race At elderly patients with bronchial asthma or HOBL was estimated by AUC(0-24) of a flutikazon of furoate. According to the obtained data, patients of east Asian, Japanese and southern Asian race (12–14% of patients) had on average higher rates of AUC(0-24) (above on average on 33%-53%) in comparison with patients of Caucasian race. Nevertheless, in these populations of signs of higher system exposure which is shown more significant influence on excretion of cortisol with urine for the 24-hour period it is not revealed. At the patients suffering from HOBL, influence of race on pharmacokinetic parameters of a vilanterol is not revealed. On average, by results of assessment of Cmax of a vilanterol was 220-287% higher, and AUC(0–24) was comparable at patients of Asian origin in comparison with indicators at other racial groups. Nevertheless, higher Cmax of a vilanterol had no clinically significant influence on heart rate. Children For teenagers (12 years or are more senior) recommendations about change of the mode of dosing are absent. The pharmacokinetics of a combination of a flutikazon of furoate and a vilanterol at patients is younger than 12 years was not studied. Safety and efficiency of use of a combination of a vilanterol and flutikazon of furoate for children are younger than 12 years is not established yet. Patients of advanced age Influence of age on pharmacokinetics of a flutikazon of furoate and a vilanterol was studied in the third phase of the clinical trials including patients with HOBL and bronchial asthma. At patients with bronchial asthma, signs of influence of age (12–84 years) on a pharmacokinetic profile of a flutikazon of furoate and a vilanterol were not revealed. Despite increase (37%) in AUC(0-24) of a vilanterol at patients with HOBL throughout all observed age range from 41 to 84 years, signs of influence of age of patients on a pharmacokinetic profile of a flutikazon of furoate it is not revealed. Patients with a renal failure according to a kliniko-pharmacological research the heavy renal failure (clearance of creatinine & lt, 30 ml/min.) does not lead to significant increase in system exposure of a vilanterol or flutikazon of furoate or ment of more significant system effects of glucocorticosteroids or beta2-agonists in comparison with healthy volunteers. Individual selection of a dose for patients with a renal failure is not required. Influence of a hemodialysis was not studied. Patients with an abnormal liver function After continuous reception of a combination of a flutikazon of furoate and a vilanterol within 7 days at patients with an abnormal liver function (according to classification of cirrhosis by Chayld-Pyyu: stages of cirrhosis And, In or C) increase in system exposure of a flutikazon of furoate (on the measured AUC(0–24) to three times) in comparison with healthy volunteers was observed. Increase in system exposure of a flutikazon of furoate (when assigning a combination of a flutikazon of furoate and a vilanterol in a dosage of 184 mkg + 22 mkg / a dose) at patients with a moderately severe abnormal liver function (a stage In on classification of Chayld-Pyyu) was associated with decrease in concentration of serumal cortisol on average by 34% in comparison with healthy volunteers. At patients with heavy degree of a liver failure (a stage With on classification of Chayld-Pyyu), receiving combinations of a flutikazon of furoate and a vilanterol in a dosage of 92 mkg + 22 mkg / a dose the serumal level of cortisol did not decrease. At patients with an average and heavy liver failure the maximum dose of drug makes 92 mkg + 22 mkg / a dose After continuous reception of a combination of a vilanterol and a flutikazon of furoate during 7 days at patients with an abnormal liver function of easy, average or heavy degree (stages And, In and With on classification of Chayld-Pyyu) significant increase in system exposure of a vilanterol was not noted (on Cmax and AUC(0–24)). In comparison with healthy volunteers at patients with an abnormal liver function of easy or average degree (accepting vilanterol in a dose of 22 mkg) or heavy degree (accepting vilanterol in a dose of 11 mkg) was not observed clinically significant beta and adrenergic system effects (change of heart rate or the concentration of serumal potassium) caused by reception of a combination of a vilanterol and flutikazon of furoate. A floor, body weight, body mass index according to the third phase of the population analysis of data of pharmacokinetics including 1213 patients with bronchial asthma (712 women) and 1225 patients with HOBL (392 women), signs of influence of a floor, the body weight or body mass index on a pharmacokinetic profile of a flutikazon of furoate is not revealed. According to the population analysis with participation of 856 patients with bronchial asthma (500 women) and 1091 patients about HOBL (340 women) of signs of influence of a floor, body weight or body mass index on a pharmacokinetic profile of a vilanterol are not revealed. Individual selection of a dose on the basis of data on sex, the body weight or body mass index is not required. A pharmacodynamics the action Mechanism Vilanterol and a flutikazona furoate belong to two various classes of medicines — selection beta2-adrenomimetik long action and a synthetic glucocorticosteroid respectively. Pharmakodinamichesky effects Vilanterol belongs to the class of selection beta2-adrenomimetik of long action (DDBA). Pharmacological effects of agonists of beta2-adrenoceptors, including vilanterol, are at least partially connected with stimulation of intracellular adenylatecyclase — enzyme which catalyzes transformation of adenosine triphosphate (ATP) into cyclic 3’, 5 ’-adenosinemonophosphate (cyclic AMF). Increase in level of cyclic AMF leads to relaxation of smooth muscles of bronchial tubes and oppression of release from cells (first of all from mast cells) mediators of reactions of immediate hypersensitivity. Flutikazona furoate is a synthetic trifluoride glucocorticosteroid with the significant anti-inflammatory action. The exact mechanism of action allowing to stop symptoms of bronchial asthma and chronic obstructive pulmonary disease (COPD) is not known. Glucocorticosteroids showed a broad spectrum of activity on various types of cells (for example, eosinophils, macrophages, lymphocytes) and mediators (for example, the cytokines and chemokines participating in inflammation process). Between glucocorticosteroids and DDBA there are molecular interactions as a result of which steroid hormones activate a beta2-adrenoceptor gene, raising number of susceptible adrenoceptors. DDBA contact a glucocorticosteroid receptor, providing its steroido-dependent activation and stimulating a translocation in a cell kernel. These synergy interactions lead to strengthening of anti-inflammatory activity that comes to light in experiments of in vitro and in vivo with various cells of inflammation participating in pathophysiological developments of bronchial asthma and HOBL. Results of clinical trials with use of bioptat of airways also showed the synergy of glucocorticosteroids and DDBA arising when prescribing these drugs to patients with HOBL in therapeutic doses. Indications - basic therapy of patients with bronchial asthma at adults and teenagers at the age of 12 years are also more senior when use of a combination of medications (beta2-agonist of long action and an inhalation corticosteroid) is reasonablly: the patients with the insufficient level of control of a disease accepting inhalation glucocorticosteroids or short-range beta2-adrenomimetikam "on demand". - symptomatic therapy at HOBL (chronic obstructive pulmonary disease) at adult patients at HOBL with OFV1 (volume of the forced exhalation) & lt, 70% of the expected norm (post-broncholitic) with aggravations of HOBL in the anamnesis, despite continuous bronkhodilatiruyushchy therapy. The route of administration and doses the Drug Relvar® Ellipta® is intended only for inhalation use. The drug Relvar® Ellipta® should be used once a day at the same time, in the morning or in the evening. The final decision concerning administration of drug in evening or morning time is accepted by the doctor. In case of the admission of administration of drug, the following dose should be accepted in usual time next day. In case the inhaler is stored in the fridge, it is necessary to leave it at the room temperature, at least, for one hour before use. After inhalation it is necessary to rinse a mouth water, without swallowing the used water. Bronchial asthma the Patient has to be informed on need of regular use of the drug Relvar® Ellipta® even in case of an asymptomatic course of the disease. At emergence of symptoms of a disease during the period between administrations of drug as emergency treatment it is necessary to apply inhalation forms of beta2-agonists of short action. The doctor has to estimate regularly the patient's condition to provide timely purpose of an optimum dosage of the drug Relvar® Ellipta®. The dosage can be changed only according to the recommendation of the doctor. Adults and teenagers of 12 years are also more senior the Recommended dose of the drug Relvar® Ellipta®: - one inhalation of 92 mkg of a flutikazon of furoate and 22 mkg of a vilanterol once a day or - one inhalation of 184 mkg of a flutikazon of furoate and 22 mkg of a vilanterol once a day. The initial dose of drug Relvar® Эллипта® 92 of mkg of a flutikazon of furoate and 22 mkg of a vilanterol is appointed to patients for whom low or average doses of the inhalation glucocorticosteroids applied in a combination with beta2-agonists of long action are required. And 22 mkg of a vilanterol patients who need higher dose of the inhalation glucocorticosteroids applied in a combination with beta2-agonists of long action should appoint the drug Relvar® Ellipta® in a dosage of 184 mkg of a flutikazon of furoate. Patients usually feel improvement of function of lungs within 15 minutes after inhalation of the drug Relvar® Ellipta®. However the patient has to be informed on need of regular daily use for control of symptoms of asthma and also on need of continuation of use of drug even
in case of an asymptomatic course of the disease. Should appoint a dose of drug Relvar® Эллипта® 184/22 of mkg adults and teenagers at the age of 12 years and is more senior which need the highest dose of an inhalation corticosteroid in a combination with beta2-agonist of long action. To the patients having asthma, the drug Relvar® Ellipta® is appointed in the dosage containing the dose of the flutikazon of furoate (FF) corresponding to weight of their disease. The doctors appointing treatment have to know that for the patients having asthma, the dose of the flutikazon of furoate (FF) of 100 mkg is approximately equal to a dose of the flutikazon of propionate (FP) of 250 mkg two times a day once a day, at the same time the dose of FF of 200 mkg is approximately equal to a dose of FP of 500 mkg two times a day once a day. If the drug Relvar® Ellipta® in a dosage of 92 mkg of a flutikazon of furoate and 22 mkg of a vilanterol does not provide adequate control of a disease, the question of increase in a dose up to 184 mkg of a flutikazon of furoate and 22 mkg of a vilanterol is considered that can improve the level of control over a course of bronchial asthma. Children Safety and efficiency of use of the drug Relvar® Ellipta® in asthma at children are younger than 12 years is not established. HOBL Adult the Recommended dose of the drug Relvar® Ellipta® makes one inhalation of 92 mkg of a flutikazon of furoate and 22 mkg of a vilanterol once a day. The drug Relvar® Ellipta® in a dosage of 184 mkg of a flutikazon of furoate and 22 mkg of a vilanterol is not shown for treatment of patients with HOBL. At HOBL there are no additional benefits of a dosage of 184/22 mkg in comparison with 92/22 mkg, potential risk of developing pneumonia and system a corticosteroid - the connected side reactions also increases. Patients usually feel improvement of function of lungs within 16-17 minutes after inhalation of the drug Relvar® Ellipta®. Children Drug according to the indication of HOBL at children is not used. Special groups of patients Patients of advanced age to Patients are more senior than 65 years individual selection of a dose of drug is not required (see the section "Pharmacokinetics", the subsection "Special Groups of Patients"). Patients with a renal failure the Patients with a renal failure do not need individual selection of a dose of drug (see the section "Pharmacokinetics"). Patients with an abnormal liver function according to a kliniko-pharmacological research at patients with abnormal liver functions of easy, average and heavy degree the triple increase of extent of system exposure of a flutikazon of furoate is observed (with increase in such indicators as Cmax and AUC) (see the section "Pharmacokinetics"). Patients with abnormal liver functions should appoint drug with care, in connection with presence of higher risk of development of the system undesirable reactions caused by reception of glucocorticosteroids. At patients with an average and heavy liver failure the maximum dose of drug makes 92 mkg / 22 the mkg (see the section "Pharmacokinetics") Recommendations about use the Inhaler of Ellipta® contains previously measured doses and is ready to use. At the first use of an inhaler of Ellipta® there is no need for check of correctness of its work or special preparation of an inhaler for operation. Just consistently observe recommendations about use. The inhaler of Ellipta® is packed into the container containing the moisture absorbing bag of silica gel which is not intended for food or inhalations. This bag should be utilized. When you get an inhaler from a container, its cover is in a closed position. Do not open it until you are not ready to administration of drug. On the label of an inhaler Ellipta®, in the place allocated for this purpose "To use to", it is necessary to write expiration date of use of drug. Date "To use to" makes 6 weeks from the moment of opening of a container. After this date the inhaler of Ellipta® should not be used, the container can be utilized. The step-by-step iinstruktion of use of an inhaler of Ellipta® is given below: I. Read the following information before use. When opening and closing a cover of an inhaler of Ellipta® without intake of medicine there is a loss of one dose. This dose remains closed in an inhaler, but it will be inaccessible for reception. It is impossible to receive accidentally a high dose or a double dose for one inhalation. The counter of doses shows how many doses of medicine remained in an inhaler. Before use of an inhaler the counter of doses shows number 30. At each opening of a cover the quantity of doses decreases by 1. When there are less than 10 doses, a half of the counter becomes red. After the last dose of drug is spent, a half of the counter is highlighted in red color, the counter shows figure 0. It means that the inhaler is empty. If you open a cover after that, the counter of doses will become completely red. The counter of doses One dose of medicine is ready to inhalation after each opening of a cover the Cover of II. Preparation of a dose do not open a cover until you are ready to administration of drug. Do not stir up an inhaler. 1. Lower a cover down to click. 2. The dose of drug is ready to inhalation, and in confirmation of it the counter of doses reduces number of doses by unit. 3. If the counter of doses did not reduce number of doses after you heard click, then the inhaler is not ready to giving of a dose of medicine. In this case it is necessary to see a doctor or to the phone/address specified in the section "The Address of the Organization Accepting in the territory of the Republic of Kazakhstan Claims from Consumers on Quality of Products (Goods)". 4. Never stir up an inhaler. Mouthpiece Click Air vent of III. Inhalation of medicine 1. Holding an inhaler at some distance from a mouth, make an exhalation of the maximum depth. Do not exhale in an inhaler. 2. Place a mouthpiece between lips and densely clasp it with lips. Do not close fingers an air vent. 3. Make one deep, long, uniform breath. Hold the breath as far as possible (at least, for 3–4 seconds). 4. Remove an inhaler from a mouth. 5. Slowly and quietly exhale. Lips have to repeat precisely an inhaler mouthpiece form you can not feel taste or not feel intake of medicine even at the correct use of an inhaler. IV. Closing of an inhaler and rinsing of an oral cavity If you want to wipe a mouthpiece, use a dry tissue before closing of a cover. 1. Lift a cover against the stop, having achieved full closing of a mouthpiece. 2. After inhalation it is necessary to rinse a mouth water. It will lower a likelihood of development of such by-effects as a sore throat and oral cavities. Side effects For determination of frequency of development of the undesirable reactions connected with use of the drug Relvar® Ellipta® were used data of large clinical trials among patients with HOBL and bronchial asthma. The program of clinical development of drug for treatment of bronchial asthma included 7034 patients at whom the complex assessment of the undesirable phenomena was carried out. 6237 patients at whom the complex assessment of the undesirable phenomena was also carried out took part in the program of clinical development of drug for treatment of HOBL. The headache and a nasopharyngitis were the most widespread undesirable reactions at use of a flutikazon of furoate / vilanterola. Excepting such undesirable phenomena as pneumonia and fractures, a profile of safety of drug at patients to HOBL and bronchial asthma it was similar. According to clinical trials the pneumonia and fractures were more often observed at the patients suffering from HOBL. The undesirable phenomena given below are listed according to defeat of bodies and the systems of bodies and occurrence frequency. Frequency of occurrence is defined as follows: very often (≥ 1/10), it is frequent (≥ 1/100 and & lt, 1/10), infrequently (≥ 1/1000 and & lt, 1/100), is rare (≥ 1/10,000 and & lt, 1/1000), is very rare (& lt, 1/10,000, including separate cases). Very often - a headache - a nasopharyngitis Often - pneumonia *, upper respiratory tract infections, bronchitis, flu, candidiasis of a mouth and throat - oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, a dysphonia (voice osiplost) - an arthralgia, a dorsodynia, fractures ** - a paradoxical bronchospasm - a muscular spasm - an abdominal pain - fever Infrequently - premature ventricular contraction Seldom - reactions of hypersensitivity, including an anaphylaxis, a Quincke's disease, rash, urticaria - a tremor - heartbeat - tachycardia - feeling of alarm the Description of separate undesirable reactions * Pneumonia during performing two clinical trials with the repeating design lasting 12 months with participation of 3255 patients suffering from HOBL, quantity of cases of pneumonia on 1000 patients a year receiving a flutikazon furoate / vilanterol (184 mkg / 22 mkg) made 97.7, in group of a flutikazon furoate / vilanterol (92 mkg / 22 mkg) made 85.7 and 42.3 in group of a vilanterol (22 mkg). In hard cases of pneumonia, number of cases on 1000 patients a year made 33.6, 35.5, 7.6 respectively, for the cases demanding hospitalization, on 1000 patients a year made 35.1 for group receiving a flutikazon furoate / vilanterol (184 mkg / 22 mkg), 42.9 in group of a flutikazon furoate / vilanterol (92 mkg / 22 mkg) and 12.1 in group of a vilanterol (22 mkg). Pneumonia cases with a lethal outcome made 8.8 for group of the patients receiving a flutikazon furoate / vilanterol (184 mkg / 22 mkg) in comparison with 1.5 for group of a flutikazon furoate / vilanterol (92 mkg / 22 mkg) and 0 in group of a vilanterol (22 mkg). In complete analysis of 11 researches in the field of asthma (7034), the frequency of cases of pneumonia on 1000 patients a year was 18.4 for group of the patients accepting a flutikazon furoate / vilanterol (184 mkg / 22 mkg) in comparison with 9.6 for group of a flutikazon furoate / vilanterol (92 mkg / 22 mkg) and 8.0 in group of placebo. ** Changes during performing two clinical trials with the repeating design lasting 12 months with participation of 3,255 patients suffering from HOBL, the frequency of developing of bone fractures in general was low in all groups of treatment, but at the same time in all groups of a flutikazon of furoate / vilanterola it was slightly higher (2%), than in group, monotherapy vilanteroly in a dose of 25 mkg (& lt, 1%). Despite bigger number of changes in groups of treatment of a flutikazon of furoate / vilanterola in comparison with group of a vilanterol in a dose of 22 mkg, the typical changes connected with reception of glucocorticosteroids (for example, compression changes backbones/fractures of thoracic and lumbar vertebrae, fractures of a hip and the acetabular hollow), arose in & lt, 1% of cases in groups of treatment of a flutikazon furoate / vilanterolom and vilanteroly. In the complex analysis of results of 11 clinical trials with participation of the patients having bronchial asthma (7034 patients), the frequency of developing of fractures was also lt, 1%, and, as a rule, these changes were connected with an injury. The data obtained at post-registration use it is rare - palpitation (heart consciousness) - tachycardia - a tremor - uneasiness (concern) of the Contraindication - existence in the anamnesis of heavy allergic reactions to milk protein - hypersensitivity to active ingredients or any component which is a part of drug. With care: - the lactation period - to the persons suffering from severe forms of cardiovascular diseases at a concomitant use of sympathomimetics - to patients with a pulmonary tuberculosis - to patients with the chronic or not cured infections. Medicinal interactions When prescribing drug in therapeutic doses clinically significant medicinal interactions of a vilanterol or flutikazon of furoate are considered as improbable owing to low plasmatic concentration of the last at inhalation introduction. Beta blockers can weaken action of beta2-adrenomimetik. It is necessary to avoid a concomitant use of non-selective and selection beta-blockers, excepting cases when their appointment is strictly necessary. Vilanterol and a flutikazona furoate are exposed to fast primary metabolism in a liver by means of an isoenzyme of a system of CYP3A4 cytochrome. At co-administration of drug (for example, ketokonazol, ritonavir) it is necessary to be careful with strong inhibitors of an isoenzyme of CYP3A4 cytochrome as increase in system influence of a vilanterol and flutikazon of furoate is possible, and it is also necessary to avoid the combined use of drugs. The repeated research of interaction of a dose CYP3A4 and medicine was conducted with participation of healthy faces using a combination of a flutikazon of furoate / vilanterola (184/22 mkg) and strong CYP3A4 inhibitor of a ketokozanol (400 mg). The combined prescribing of drugs increased average values of a flutikazon of AUC (0‑24) and Cmax furoate by 36% and 33%, respectively. Increase in influence of a flutikazon of furoate was connected with reduction of the average level of cortisol in serum for 27% during 0-24 h. The combined prescribing of drugs increased average values of a vilanterol of AUC(0-t) and Cmax by 65% and 22%, respectively. Increase in influence of a vilanterol was not connected with increase in the system effects connected with use of beta2-agonists on a warm rhythm, potassium level in blood or an interval of QT. Vilanterol and a flutikazona furoate are P-gp substrates. By results of a kliniko-pharmacological research with participation of healthy volunteers which were at the same time appointed vilanterol both strong P-gp inhibitor and moderate inhibitor of an isoenzyme of CYP3A4 cytochrome verapamil the significant influence on pharmacokinetics of a vilanterol is not revealed. Kliniko-pharmakologichesky researches of joint prescribing of specific P-gp inhibitor and a flutikazon of furoate were not conducted. Sympathomimetic medicines Joint prescribing of other sympathomimetic medicines (separately or as a part of combination therapy) can strengthen side reactions of a flutikazon of furoate / vilanterola. Relvar® Ellipta®, it is not necessary to apply in a combination with other beta2-adrenomimetika of long action or medicines containing beta2-adrenomimetik of long action. Children of the Research of interaction were carried out only among adult patients. Special indications of Exacerbation of a disease the Drug Relvar® Ellipta® is not intended for stopping of acute symptoms of bronchial asthma or acute conditions at HOBL, in such cases the nazn is required
to be Developed