Relvar Ellipta inhalation powder 22mcg + 92mcg/dose + inhaler 30 doses 1pc

Composition

Powder for inhalation

Active ingredient:

vilanterol triphenate micronized 40 mcg (equivalent to 25 mcg of vilanterol);

Auxiliary substances:

magnesium stearate-125 mcg;

lactose monohydrate-up to 12.5 mg

Pharmacological action

Mechanism of action

Vilanterol and fluticasone furoate belong to two different classes of drugs — a synthetic glucocorticoid and a selective long-acting betag-adrenomimetic.

Pharmacodynamic effects

Vilanterol belongs to the class of selective long-acting beta-2-adrenomimetics (DDBA).

The pharmacological effects of beta-2-adrenergic agonists, including vilanterol, are at least partially related to the stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) B cyclic 3′,5′ – adenosine monophosphate (cyclic AMP). An increase in the level of cyclic AMP leads to relaxation of the smooth muscles of the bronchi and inhibition of the release of mediators of immediate hypersensitivity reactions from cells (primarily from mast cells).

Fluticasone furoate is a synthetic trifluoride glucocorticosteroid with a pronounced anti-inflammatory effect. The exact mechanism of action that helps to stop the symptoms of bronchial asthma and chronic obstructive pulmonary disease (COPD) is not known.

Glucocorticosteroids have shown a wide range of effects on various cell types (for example, eosinophils, macrophages, lymphocytes) and mediators (for example, cytokines and chemokines involved in the inflammatory process).

There are molecular interactions between glucocorticosteroids and DDBL, as a result of which steroid hormones activate the beta-2-adrenergic receptor gene, increasing the number of susceptible adrenergic receptors. DDBA binds to the glucocorticoid receptor, providing its steroid-dependent activation and stimulating translocation into the cell nucleus.

These synergistic interactions lead to increased anti-inflammatory activity, which is revealed in experiments in vitro and in vivo with various inflammatory cells involved in the pathophysiological processes of the development of bronchial asthma and COPD. The results of clinical studies using airway biopsies also demonstrated the synergy of gducocorticosteroids and DDBA, which occurs when these drugs are prescribed to patients with COPD in therapeutic doses.

Pharmacokinetics

Suction

The absolute bioavailability of vilanterol and fluticasone furoate with inhaled use of a combination of vilanterol and fluticasone furoate averaged 15.2% and 27.3%, respectively. The oral bioavailability of both substances was low, with an average of 1.26% and accordingly. Taking into account the low oral bioavailability, the systemic effect of vilanterol and fluticasone furoate after inhalation is primarily due to the absorption of part of the inhaled dose that entered the lungs.

Distribution

After intravenous use, vilanterol and fluticasone furoate are actively distributed in the body, with average volumes of distribution at steady state being 165 liters and 661 liters, respectively.

Both substances have a low ability to bind to red blood cells. In vitro studies, the binding of vilanterol and fluticasone furoag to human plasma proteins was high and averaged > 93.9% and 99.6%, respectively. The degree of binding to plasma proteins in vitro did not decrease in patients with impaired liver and kidney function.

Despite the fact that vilanterol and fluticasone furoate are substrates of P-glycoprotein (P-gp), when a combination of vilanterol and fluticasone furoate is co-administered with P-gp inhibitors, a change in the systemic exposure of vilanterol or fluticasone furoate is considered unlikely, since both substances have good absorption capacity.

Metabolism

Based on in vitro experiments, it can be concluded that the key pathways of vilanterol and fluticasone furoate metabolism in the human body are primarily mediated through the cytochrome CYP3A4 isoenzyme.

Vilanterol is mainly metabolized by O-dealkylation to form a number of metabolites with significantly lower beta-1 and beta – 2 adrenomimetic activity.

Fluticasone furoate is mainly metabolized by hydrolysis of the S-fluoromethylcarbothioate group to form metabolites with significantly lower glucocorticosteroid activity.

A clinical study of drug interactions with the cytochrome CYP3A4 isoenzyme was conducted with long-term use of a combination of vilanterol and fluticasone furoate (22 mcg + 184 mcg / dose) and a strong inhibitor of the cytochrome CYP3A4 isoenzyme — ketoconazole (400 mg) in healthy volunteers. Co-use of drugs resulted in an increase in the average area under the pharmacokinetic curve (AUC (0-24)) and the average Cmax of fluticasone furoate by 36% and 33%. accordingly. Increased exposure to fluticasone furoate was associated with a 27% decrease in mean serum cortisol concentrations. measured over a period of 0-24 hours.

Co-use of a combination of vilanterol and fluticasone furoate and ketoconazole resulted in an increase in mean AUC (0-t) and vilanterol Cmax by 65 and 22%, respectively. Increased exposure to vilanterol did not lead to an increase in the systemic effects characteristic of beta-agonists — the effect on heart rate, blood potassium content, or corrected QT interval(QTcF).

Deduction

After oral use of fluticasone furoate in humans, mainly metabolized to form metabolites that are mainly excreted through the gastrointestinal tract, with the exception of the dose of the radioactive substance The estimated plasma half-life of fluticasone furoate after inhaled use of the drug was an average of 24 hours.

After oral use, vilanterol was mainly metabolized in the human body to form metabolites that were excreted in the urine and faeces, in a ratio of approximately 70% and 30% of the dose of the radioactive substance, respectively. The plasma half-life of vilanterol after inhaled use of the drug was on average 2.5 hours.

Special patient groups

A population-based meta-analysis of the pharmacokinetics of vilanterol and fluticasone furoate in patients with asthma and COPD was conducted in the third phase of clinical trials. This analysis evaluated the effect of demographic covariates (age, gender, weight, body mass index (BMI), race and ethnicity) on the pharmacokinetics of vilanterol and fluticasone furoate.

Race

The AUC(0-24)of fluticasone furoate was evaluated in elderly patients with asthma or COPD. According to the data obtained, patients of the East Asian, Japanese and South Asian races (12-14% of patients) had on average higher AUC values(0-24) (no more than 53% higher) compared to patients of the Caucasian race. However, there were no signs of higher systemic exposure in these populations, with a more pronounced effect on urinary cortisol excretion over a 24-hour period. In patients with COPD, the effect of race on the pharmacokinetic parameters of vilanterol was not revealed.

On average, vilanterol Cmax was 220-287% higher, and AUC(0-24)was comparable in Asian patients compared to other racial groups. However, a higher vilanterol Cmax had no clinically significant effect on heart rate.

Children

There are no recommendations for changing the dosage regimen for adolescents (12 years or older). The pharmacokinetics of the combination of vilanterol and fluticasone furoate in patients younger than 12 years of age have not been studied. The safety and efficacy of the combination of vilanterol and fluticasone furoate in children under 12 years of age has not yet been established.

Elderly patients

The effect of age on the pharmacokinetics of vilanterol and fluticasone furoate was studied in phase 3 clinical trials involving patients with COPD and bronchial asthma.

In patients with bronchial asthma, there were no signs of age (12-84 years) influencing the pharmacokinetic profile of fluticasone furoate and vilanterol.

Despite a 37% increase in vilanterol AUC in COPD patients over the entire observed age range from 41 to 84 years, there were no signs of the effect of patient age on the pharmacokinetic profile of fluticasone furoate. In an elderly patient (aged 84 years) with a low body weight (35 kg), the AUC (0-24) of vilanterol will be 35% higher than the result calculated for the population (on average, a COPD patient aged 60 years and a body weight of 70 kg), while the Cmax of Vilanterol will remain unchanged. It is unlikely that these differences are clinically relevant.

Patients with impaired renal function

According to a clinical and pharmacological study, severe renal impairment (creatinine clearance Individual dose adjustment is not required for patients with impaired renal function.

The effect of hemodialysis has not been studied.

Patients with impaired liver function

After continuous use of a combination of vilanterol and fluticasone furoate for 7 days, patients with impaired liver function showed an increase in systemic exposure to fluticasone furoate (measured AUC ” >-24>> UP to three times) compared to healthy volunteers (according to the Child-Pugh classification of cirrhosis: stage of cirrhosis A. B or C). Increased systemic exposure to fluticasone furoate (when the combination of vilanterol and fluticasone furoate was administered at a dosage of 22 mcg + 184 mcg/dose) in patients with moderate hepatic impairment (Child-Pugh stage B) was associated with a decrease in serum cortisol concentration by an average of 34% compared with healthy volunteers. Indicators of dose-normalized systemic exposure to fluticasone furoate in patients with moderate to severe hepatic impairment (stages B and C according to the Child-Pugh classification) were similar. Therefore, although patients with hepatic impairment do not require individual dose selection, caution should be exercised when prescribing this medication.

After continuous use of the combination of vilanterol and fluticasone furoag for 7 days, patients with mild, moderate or severe hepatic impairment (stages A B and C according to the Child-Pugh classification) did not show a significant increase in systemic exposure to vilanterol (Cmax and AUC(0-24)).

In comparison with healthy volunteers, patients with mild or moderate hepatic impairment (taking vilanterol at a dose of 22 mcg) or severe (taking vilanterol at a dose of 11 mcg) did not experience clinically significant beta-adrenergic systemic effects (changes in heart rate or serum potassium concentration) caused by taking a combination of vilanterol and fluticasone furoate.

Gender, Body weight, Body Mass index (BMI)

According to the third phase of a population pharmacokinetic analysis that included 1,213 patients with bronchial asthma (712 women) and 1,225 patients with COPD (392 women), there were no signs of gender, body weight, or BMI influencing the pharmacokinetic profile of fluticasone furoate.

According to a population-based pharmacokinetic analysis involving 856 patients with asthma (500 women) and 1,091 patients with COPD (340 women), there were no signs of gender, body weight, or BMI influencing the pharmacokinetic profile of vilanterol.

Individual dose selection based on gender, body weight, or BMI is not required.

Indications

-bronchial asthma;

– COPD (chronic obstructive pulmonary disease).

Relvar Ellipta reduces the number of COPD exacerbations in patients with a history of recurrent exacerbations.

Contraindications

-severe allergic reactions to milk protein or hypersensitivity to active substances or any other component of the drug in the anamnesis;

– children under 12 years of age for the treatment of bronchial asthma;

– treatment of COPD at a dose of 22 mcg+184 mcg/dose.

With caution: when taking sympathomimetics, including Relvar Ellipta, adverse events such as arrhythmia (for example, supraventricular tachycardia and extrasystole) may occur from the cardiovascular system. In this regard, patients suffering from severe forms of cardiovascular diseases, Relvar Ellipta should be prescribed with caution.

Side effects

Infectious and parasitic diseases: often — pneumonia, upper respiratory tract infections, bronchitis, flu, candidiasis of the oral cavity and pharynx.

Nervous system disorders: very often — a headache.

From the side of the heart: infrequently — extrasystole.

Respiratory, thoracic and mediastinal disorders: very often — nasopharyngitis; often-oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia.

From the gastrointestinal tract: often-abdominal pain.

Musculoskeletal and connective tissue disorders: often-arthralgia, back pain, fractures.

General disorders and disorders at the injection site: often-fever.

Interaction

When prescribing the drug in therapeutic doses, clinically significant drug interactions of vilanterol or fluticasone furoate are considered unlikely due to the low plasma concentrations of the latter when inhaled.

Beta-blockers may weaken or antagonize the effects of beta-2-adrenomimetics. Concomitant use of non-selective and selective beta-blockers should be avoided, unless strictly necessary.

Vilanterol and fluticasone furoate undergo rapid primary metabolism in the liver by the cytochrome CYP3A4 isoenzyme.

Caution should be exercised when concomitantly prescribing the drug with strong inhibitors of the cytochrome CYP3A4 isoenzyme (for example, ketoconazole, ritonavir), since it is possible to increase the systemic exposure of vilanterol and fluticasone furoate, which in turn can lead to an increased risk of adverse reactions (see “Pharmacokinetics”).

Vilanterol and fluticasone furoate are substrates of P-gp. According to the results of a clinical and pharmacological study involving healthy volunteers who were simultaneously prescribed vilanterol and a strong P-gp inhibitor and a moderate inhibitor of the cytochrome CYP3A4 isoenzyme verapamil, no significant effect on the pharmacokinetics of vilanterol was found. Clinical and pharmacological studies of co-use of a specific P-gp inhibitor and fluticasone furoate have not been conducted.

How to take, course of use and dosage

By inhalation.

Relvar Ellipta® should be used once a day at the same time, in the morning or in the evening. After inhalation, rinse your mouth with water without swallowing.

Bronchial asthma

The patient should be informed about the need for regular use of Relvar Ellipta® even in the case of an asymptomatic course of the disease. If symptoms of the disease occur between doses of the drug, inhaled forms of short-acting beta-2 agonists should be used as emergency therapy. The doctor should regularly assess the patient’s condition to ensure that the optimal dosage of Relvar Ellipta is prescribed in a timely manner. The dosage can only be changed on the recommendation of a doctor.

Adults and teenagers 12 years and older. The recommended dose of Relvar Ellipta is one inhalation of 22 mcg of vilanterol and 92 mcg of fluticasone furoate once daily, or one inhalation of 22 mcg of vilanterol and 184 mcg of fluticasone furoate once daily.

The initial dose of Relvar Ellipta ® 22 mcg of vilanterol and 92 mcg of fluticasone furoate is prescribed to patients who require low or medium doses of inhaled corticosteroids used in combination with long-acting beta-2 agonists.

Relvar Ellipta® in a dosage of 22 mcg of vilanterol and 184 mcg of fluticasone furoate should be prescribed to patients who require a higher dose of inhaled corticosteroids used in combination with long-acting beta-2 agonists. If Relvar Ellipta® at a dosage of 22 mcg of vilanterol and 92 mcg of fluticasone furoate does not provide adequate disease control, an increase in the dose to 22 mcg of vilanterol and 184 mcg of fluticasone furoate is considered, which may improve the level of control over the course of bronchial asthma.

Children. The safety and efficacy of Relvar Ellipta in children under 12 years of age has not been established.

COPD

Adults. The recommended dose of Relvar Ellipta is one inhalation of 22 mcg of vilanterol and 92 mcg of fluticasone furoate once a day.

Relvar Ellipta® at a dosage of 22 mcg of vilanterol and 184 mcg of fluticasone furoate is not indicated for the treatment of patients with COPD.

 The drug is not indicated for COPD in children.

Special patient groups

Elderly patients. Patients over 65 years of age do not need an individual dose adjustment..

Patients with impaired renal function. Patients with impaired renal function do not need an individual dose adjustment of the drug.

Patients with impaired liver function. According to a clinical and pharmacological study, patients with mild, moderate and severe hepatic impairment experienced a threefold increase in the degree of systemic exposure to fluticasone furoate (with an increase in such indicators as Cmax and AUC) (see “Pharmacokinetics”). Patients with impaired liver function should be prescribed the drug with caution, because this group of patients has a higher risk of developing systemic adverse reactions caused by taking corticosteroids.

Recommendations for use

When using the Ellipta® inhaler for the first time, there is no need to check its correct operation or prepare the inhaler for special use. You should consistently follow the recommendations for use listed below.

The Ellipta ® inhaler is packaged in a container containing a moisture-absorbing silica gel bag that is not intended for food or inhalation. This bag should be disposed of. After removing the inhaler from the container, its lid is in the closed position. Do not open it before taking the drug.

Detailed instructions for using the Ellipta®Inhaler

When opening and closing the lid of the Ellipta ® inhaler without taking medication, one dose is lost. This dose remains sealed inside the inhaler, but it will not be available for use. It is not possible to accidentally get a large dose or a double dose in one inhalation.

One dose of the drug is ready for inhalation after each opening of the lid.

The dose counter shows how many doses of the drug are left in the inhaler. Before you start using the inhaler, the dose counter shows the number 30. Each time the lid is opened, the number of doses decreases by 1. When there are less than 10 doses left, half of the counter turns red. After the last dose of the drug is consumed, half of the counter is highlighted in red, and the counter shows the number 0. This means that the inhaler is empty. When you open the lid afterwards, the dose counter will turn completely red.

Dose preparation

Do not open the lid until you are ready to take the drug. Do not shake the inhaler.

1. Slide the lid down until it clicks into place.

2. The dose of the drug is ready for inhalation, and in confirmation of this, the counter reduces the number of doses by one.

3. If the counter does not reduce the number of doses after clicking, the inhaler is not ready to deliver the dose of the drug. In this case, you should contact us by phone or at the address specified in the “Contact us for additional information”subsection.

4. Do not shake the inhaler.

Inhalation of the drug

1. While holding the inhaler at a certain distance from the mouth, exhale as deeply as possible. Do not exhale into the inhaler.

2. Place the mouthpiece between your lips and wrap it tightly around your lips. Do not cover the air vent with your fingers.

The lips should exactly follow the shape of the mouthpiece of the inhaler.

3. Take one deep, long, even breath. Hold your breath as long as possible (at least 3-4 seconds).

4. Remove the inhaler from your mouth.

5. Exhale slowly and calmly.

If the inhaler is used correctly, the patient may not be able to taste or feel the intake of the drug.

Closing the inhaler and rinsing the mouth

If it is necessary to clean the mouthpiece, use a dry paper towel before closing the lid.

1. Lift the lid all the way up until the mouthpiece is completely closed.

2. After inhalation, rinse your mouth with water. This will reduce the likelihood of side effects such as sore throat and oral cavity.

Overdose

Symptoms: in clinical studies, no overdose data were obtained for the combination of vilanterol and fluticasone furoate. It is possible to develop symptoms and signs due to the action of individual components of the drug and characteristic of overdose with beta-2 agonists and inhaled corticosteroids.

Treatment: there is no specific treatment. Symptomatic therapy is prescribed and, if necessary, appropriate monitoring of the patient is provided. The use of cardioselective beta-blockers should be considered only in cases of severe effects of vilanterol overdose, which are clinically manifested by immunity to maintenance therapy. Cardioselective beta-blockers should be used with caution in patients who have had a history of bronchospasm episodes.

Special instructions

Relvar Ellipta® is not intended for the relief of acute symptoms of bronchial asthma or exacerbation of COPD, in such cases, the appointment of short-acting bronchodilators is required. An increase in the frequency of taking short-acting bronchodilators to relieve symptoms indicates a deterioration in disease control and the need for medical advice. Patients with asthma or COPD should not discontinue Relvar Ellipta without a doctor’s supervision, as discontinuation of therapy may lead to an exacerbation of the disease.

As with other types of inhalation therapy, paradoxical bronchospasm may develop after taking the drug, accompanied by a rapid increase in wheezing. In this case, urgent use of a short-acting inhaled bronchodilator and immediate discontinuation of Relvar Ellipta are indicated. The patient should be examined by a doctor, and alternative therapy may be prescribed if necessary.

Against the background of treatment with Relvar Ellipta®, adverse events may develop associated with the course of bronchial asthma or exacerbation of the disease. Patients should be advised to continue treatment. In case of lack of control over the disease or deterioration of the condition after starting therapy with Relvar Ellipta®, a doctor’s consultation is necessary.

When using inhaled corticosteroids (especially when taken for a long time in high doses), systemic side effects may develop. Such side effects develop much less frequently than with oral corticosteroids. Possible adverse systemic effects include: suppression of the hypothalamic-pituitary-adrenal system, decreased bone mineral density, slower growth rate in children and adolescents, cataracts and glaucoma.

Patients with COPD receiving Relvar Ellipta® experienced an increase in the incidence of pneumonia, as well as the incidence of severe forms of pneumonia requiring hospitalization. In some cases, clinical episodes of pneumonia were fatal. Doctors should be aware of the possibility of developing pneumonia in patients with COPD, not forgetting that the clinical signs of such an infectious disease are masked by symptoms of COPD exacerbation. The following groups of patients with COPD have the highest risk of developing pneumonia while taking Relvar Ellipta®: smokers, patients who have previously had pneumonia, patients with a BMI <25 kg / m2, and patients with forced expiratory volume in the first second (FEV₁) When prescribing Relvar Ellipta therapy, the above factors should be taken into account, and in case of pneumonia, treatment should be reviewed.

In patients with bronchial asthma, cases of pneumonia were observed infrequently. Patients with bronchial asthma who received Relvar Ellipta® at a dose of 22 + 184 mcg / dose may have had a higher risk of developing pneumonia compared to patients who received a lower dose of Relvar Ellipta® (22 + 92 mcg/dose), or with the placebo group. No risk factors have been identified.

Clinical studies in patients with COPD revealed a low incidence of bone fractures in all treatment groups, but in all groups receiving a combination of vilanterol and fluticasone furoate, it was slightly higher (2%) than in the group receiving monotherapy with vilanterol 22 mcg (

Influence on the ability to drive vehicles and work with mechanisms. Studies on the effect of Relvar Ellipta® the ability to drive motor vehicles and work with mechanisms was not tested. Based on the pharmacological data of vilanterol or fluticasone furoate, an adverse effect of the drug on these activities is not expected.

Storage conditions

 In a dark place, at a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Vilanterol, Fluticasone Furoate

Conditions of release from pharmacies

By prescription

Dosage form

powder for inhalation

Purpose

For adults as prescribed by a doctor, Children over 12 years of age

Indications

Chronic obstructive pulmonary disease, Bronchial asthma