Anoro ellipta powder for inhalation 22 + 55 mcg/dose 30 pcs. in Moscow

Anoro ellipta powder for inhalation 22 + 55 mcg/dose 30 pcs. in Moscow

Inhalation.

Anoro Ellipta® should be used daily at the same time, once a day. Recommended dose of Anoro Ellipta®: one inhalation of 22 + 55 mcg/dose 1 time per day. In some patients, Anoro Ellipta 22 + 113 mcg/dose once daily has been found to provide additional benefit on pulmonary function and rescue medication use. The maximum dose is one inhalation of Anoro Ellipta® at a dosage of 22 + 113 mcg/dose once a day.

Special patient groups

Children.

This drug is not used to treat patients under 18 years of age, taking into account the indications for its use.

Elderly patients.

Patients over 65 years of age do not require dose adjustment (see “Pharmacokinetics”).

Renal dysfunction.

Patients with impaired renal function do not require dose adjustment (see “Pharmacokinetics”).

Liver dysfunction.

Patients with mild or moderate hepatic impairment do not require dose adjustment. No studies have been conducted on the use of the combination of vilanterol and umeclidinium in patients with severe hepatic impairment (see Pharmacokinetics).

Recommendations for use

When using the Ellipta® inhaler for the first time, there is no need to check its correct operation or special preparation of the inhaler for use. The recommendations for use below should be followed consistently.

The Ellipta® inhaler is packaged in a container containing a desiccant sachet of silica gel, which is not intended for food or inhalation. This bag should be discarded. After removing the inhaler from the container, its lid is in the closed position. You should not open it until you are ready to take the drug.

Instructions for using the Ellipta® inhaler

Opening and closing the cap of the Ellipta® inhaler without taking the drug will result in one dose being lost. This dose remains sealed inside the inhaler but will not be available for administration. It is impossible to accidentally receive 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 you open the cap, 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 has been used up, 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 after this, 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. Lower the cover down until it clicks.

2. The dose of the drug is ready for inhalation, and to confirm this, the counter decreases the number of doses by one.

3. If the counter does not decrease the number of doses after the click, then the inhaler is not ready to deliver a dose of the drug. In this case, you should contact the phone number or address indicated in the subsection “Contact for additional information.”

4. Do not shake the inhaler.

Inhalation of a drug

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

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

The lips must 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 taste or feel the delivery of the drug.

Closing the inhaler

If you need to clean the mouthpiece, use a dry paper towel before closing the lid.

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

Vilanterol + Umeclidinium bromide (Vilanterolum + Umeclidinii bromidum)

When administered in combination with umeclidinium and vilanterol by inhalation, the pharmacokinetics of each compound were similar to those observed when each active substance was administered separately. For this reason, the pharmacokinetics of each substance will be considered separately.

Suction

In healthy volunteers, after inhalation of vilanterol, the average maximum concentration of the substance in the blood plasma was reached within 5-15 minutes. The absolute bioavailability of inhaled vilanterol averaged 27%, taking into account very little absorption of the substance in the oral cavity. After repeated inhalations of vilanterol after 6 days, a steady state was reached with a 2.4-fold accumulation.

In healthy volunteers, after inhalation of umeclidinium, the maximum concentration of the substance in the blood plasma was reached within 5-15 minutes. The absolute bioavailability of inhaled umeclidinium averaged 13%, taking into account very little absorption of the substance in the oral cavity. After repeated inhalations of umeclidinium, after 7-10 days an equilibrium state was reached with a 1.5-2-fold accumulation. After inhalation of 113 mcg of umeclidinium, systemic exposure was approximately twice that observed after inhalation of the drug at a dosage of 55 mcg.

Distribution

Following intravenous administration of vilanterol to healthy volunteers, the mean volume of distribution at steady state was 165 L. Binding to human plasma proteins in vitro

the average is 94%.

Following intravenous administration of umeclidinium to healthy volunteers, the mean volume of distribution was 86 L. Binding to human plasma proteins in vitro

the average is 89%.

Metabolism

In vitro studies

showed that vilanterol is metabolized primarily by the cytochrome P450 isoenzyme CYP3A4 and that it is a substrate of the P-glycoprotein (P-gp) transporter. The main route of metabolism is O-dealkylation with the formation of a number of metabolites with significantly lower beta1- and beta2-adrenomimetic activity. The plasma metabolic profile determined in humans in a radioisotope study following oral administration of vilanterol is consistent with high first-pass metabolism. Systemic exposure to metabolites is negligible.

In vitro studies

showed that umeclidinium is metabolized primarily by the cytochrome P450 isoenzyme CYP2D6 and that it is a substrate of the P-gp transporter. The main route of metabolism of umeclidinium is oxidation (hydroxylation, O-dealkylation) followed by conjugation (glucuronidation, etc.), leading to the formation of a number of metabolites with lower pharmacological activity or metabolites whose pharmacological activity has not been established. The systemic exposure of such metabolites is low.

Available pharmacokinetic data from studies in healthy volunteers and patients with chronic obstructive pulmonary disease indicate no change in systemic exposure (maximum plasma concentration and mean area under the curve (AUC)) and predicted exposure in population pharmacokinetics studies of vilanterol and umeclidinium when used together compared to similar indicators obtained when both components were used separately. When co-administered with a strong inhibitor of the CYP3A4 isoenzyme, ketoconazole (400 mg), an increase in mean AUC (0-1) and maximum plasma concentration of vilanterol was observed by 65 and 22%, respectively. Increased exposure to vilanterol did not increase the systemic effects associated with beta-agonists on heart rate, blood potassium, or QT interval (Frederick's method).

Both umeclidinium and vilanterol are P-gp substrates. The effect of the moderate P-gp transporter inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of vilanterol and umeclidinium was determined in healthy volunteers. There was no effect of verapamil on the maximum plasma concentrations of vilanterol or umeclidinium. There was an approximately 1.4-fold increase in the area under the pharmacokinetic curve of umeclidinium, while the area under the pharmacokinetic curve of vilanterol did not change.

Removal

Plasma clearance of vilanterol after intravenous administration was 108 L per hour. After oral administration of radiolabeled vilanterol, mass balance showed that 70% of the radioactive substance was excreted by the kidneys and 30% by the intestines. Elimination of vilanterol mainly occurred through the metabolic route, followed by excretion of metabolites by the kidneys and intestines. After inhalation of vilanterol for 10 days, the plasma half-life averaged 11 hours.

Plasma clearance of umeclidinium after intravenous administration was 151 L per hour. At 192 hours after intravenous administration, approximately 58% of the radiolabeled dose (or 73% of the radioactive substance released) was excreted by the intestine, indicating secretion of the compound into bile. The kidneys excreted 22% of the radiolabeled dose (27% of the excreted radioactive substance) after 168 hours. 168 hours after oral administration of the drug to healthy men, the bulk of the radioactive substance was excreted mainly by the intestines (92% of the ingested dose of the radiolabeled substance or 99% of the excreted radioactive substance). When administered orally, less than 1% of the dose is excreted by the kidneys (1% of the radioactive substance released), indicating very little absorption by this route of administration. After repeated inhalations of umeclidinium for 10 days, the plasma half-life averaged 19 hours, with 3 to 4% of unchanged drug excreted by the kidneys at steady state.

Special patient groups

Elderly patients

Population pharmacokinetic analysis showed similarity in the pharmacokinetics of vilanterol and umeclidinium determined in patients with chronic obstructive pulmonary disease in the age group 65 years and older and in the age group under 65 years.

Patients with impaired renal function

In a study of patients with severe renal impairment, there was no data indicating an increase in the systemic exposure of vilanterol or umeclidinium (maximum plasma concentration and area under the pharmacokinetic curve). There is no evidence of changes in protein binding in patients with renal impairment compared with healthy volunteers.

Liver dysfunction

In a study of patients with moderate hepatic impairment, there was no data indicating an increase in the systemic exposure of vilanterol or umeclidinium (maximum plasma concentration and area under the pharmacokinetic curve). There is no evidence of changes in protein binding in patients with hepatic impairment compared with healthy volunteers. The combination of vilanterol and umeclidinium has not been studied in patients with severe hepatic impairment.

Other patient groups

Data from a population pharmacokinetic analysis showed no need for dose adjustment of vilanterol or umeclidinium depending on age, race, gender, use of inhaled corticosteroids, or body weight. In a study of patients with weak metabolic activity of the CYP2D6 isoenzyme, no data were obtained indicating a clinically significant effect of the genetic polymorphism of the CYP2D6 isoenzyme on systemic exposure to umeclidinium.