Anoro Ellipta inhalation powder dosed 77 mcg/dose inhaler 30 doses No. 1

Instructions for Anoro Ellipta inhalation powder dosed 77 mcg/dose inhaler 30 doses No. 1

Composition

active substances: umeclidinium, vilanterol;

1 delivered dose contains 55 mcg of umeclidinium (as bromide) and 22 mcg of vilanterol (as trifenatate);

this corresponds to a pre-dispensed dose of 74.2 mcg umeclidinium bromide and 25 mcg vilanterol (as trifenatate);

Excipients: lactose monohydrate; magnesium stearate.

Dosage form

Inhalation powder.

Main physicochemical properties: plastic inhaler with a light grey body, a red spray cap and a dose counter, packed in a foil tray containing a desiccant sachet. The tray is sealed with a peel-off lid. The inhaler contains two strips of 30 evenly distributed blisters, each containing a white powder.

Pharmacotherapeutic group

Drugs used in obstructive airway diseases. Adrenergic drugs in combination with anticholinergic drugs. Vilanterol and umeclidinium bromide.

ATX code R03A L03.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Umeclidinium/vilanterol is a combination of a long-acting inhaled muscarinic receptor antagonist and a long-acting beta2-adrenergic agonist. After oral inhalation, both compounds act locally on the airways, resulting in bronchodilation through different mechanisms of action.

Umeclidinium

Umeclidinium is a long-acting muscarinic receptor antagonist (anticholinergic). It is a quinuclidine derivative with activity at multiple muscarinic receptor subtypes. Umeclidinium exerts its bronchodilator effects by competitively inhibiting the binding of acetylcholine to muscarinic receptors in airway smooth muscle. It has been shown to have slow reversibility at the human muscarinic receptor subtype M3 in vitro and a long-lasting effect in vivo when administered directly to the lung in preclinical models.

Vilanterol

Vilanterol is a long-acting, selective beta2-adrenergic receptor agonist (beta2-adrenergic agonist). The pharmacological effects of beta2-adrenergic agonists, including vilanterol, are at least partly due to stimulation of intracellular adenylate cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Elevated levels of cAMP cause relaxation of bronchial smooth muscle and inhibit the release of immediate-type hypersensitivity mediators from cells, particularly mast cells.

Pharmacodynamic effects

In 6-month phase III studies, umeclidinium/vilanterol demonstrated clinically meaningful improvements in lung function compared to placebo (measured as forced expiratory volume in one second (FEV1)) over 24 hours after once-daily dosing, which was observed 15 minutes after the first dose (improvement over placebo was 112 mL (p < 0.001*). The maximum improvement in FEV1 over the first 6 hours after dosing compared to placebo was 224 mL (p < 0.001*) on average at week 24 of the study. There was no evidence of tachyphylaxis due to Anoro Ellipta during the studies.

Cardioelectrophysiology

The effect of umeclidinium/vilanterol on the QT interval was evaluated in a placebo- and moxifloxacin-controlled study in 103 healthy volunteers who received umeclidinium/vilanterol once daily at 113/22 mcg or 500/100 mcg for 10 days (pre-measured dose of umeclidinium eight times the recommended dose and vilanterol four times the recommended dose). The maximum mean difference in QTcF (Frederic-corrected) compared to placebo after adjustment for baseline was 4.3 (90% CI 2.2-6.4) milliseconds at 10 minutes after inhalation of umeclidinium/vilanterol 113/22 mcg and 8.2 (90% CI 6.2-10.2) milliseconds at 30 minutes after inhalation of umeclidinium/vilanterol 500/100 mcg. Therefore, no clinically relevant proarrhythmic effect associated with QTc prolongation was observed with inhalation of umeclidinium/vilanterol 113/22 mcg.

A dose-dependent increase in heart rate was also observed. The maximum mean difference in heart rate was observed 10 minutes after inhalation compared with placebo and after adjustment for baseline was 8.4 (90% CI 7.0–9.8) bpm and 20.3 (90% CI 18.9–21.7) bpm for umeclidinium/vilanterol at 113/22 mcg and 500/100 mcg, respectively.

In addition, no clinically meaningful effects on heart rate were observed with 24-hour Holter monitoring in 53 COPD patients treated with umeclidinium/vilanterol 55/22 mcg once daily in one 6-month study, 55 patients treated with umeclidinium/vilanterol 113/22 mcg once daily in another 6-month study, and 226 patients treated with 113/22 mcg once daily in a 12-month study.

The clinical efficacy of umeclidinium/vilanterol once daily was evaluated in eight phase III clinical studies in 6,835 adult patients with a clinical diagnosis of COPD: 5,618 patients in five 6-month studies (two placebo-controlled and three with tiotropium as active comparator), 655 patients in two 3-month endurance/pulmonary function studies, and 562 patients in a 12-month confirmatory study.

Impact on pulmonary function

In several studies, Anoro Ellipta demonstrated improvements in lung function (as measured by change from baseline in FEV1). In one 6-month phase III study, the Anoro Ellipta group demonstrated a statistically significant improvement in FEV1 (primary endpoint) at week 24 compared with placebo and each monotherapy group. In addition, Anoro Ellipta demonstrated clinically meaningful and statistically significant increases in FEV1 compared with tiotropium in two of the three 6-month studies (see Table 1). No attenuation of the bronchodilator effect was observed over time.

Impact on symptoms

Dyspnea

Anoro Ellipta demonstrated statistically significant and clinically meaningful reductions in dyspnea as assessed by the Transient Dyspnea Index (TDI) at Week 24 (a key secondary endpoint) compared to placebo (see Table 1). The improvement in TDI compared to the monotherapy and tiotropium groups was not statistically significant (see Table 1).

The proportion of patients with a change in TDI of at least 1 unit (minimum clinically important difference (MICD) for TDI) at week 24 was greater in the Anoro Ellipta group (58%) compared to placebo (41%) and monotherapy (53% for umeclidinium and 51% for vilanterol).

Health-related quality of life

Anoro Ellipta also demonstrated improvements in quality of life as measured by the St. George's Hospital Respiratory Questionnaire (SGRQ), as evidenced by a reduction in SGRQ scores at week 24 compared to placebo and monotherapy (see Table 1). Anoro Ellipta demonstrated a statistically significant reduction in SGRQ compared to tiotropium in one of the three active comparator studies (see Table 1).

The proportion of patients who achieved at least a 4-point reduction in SGRQ (4 points = SGRQ MIC) at week 24 was greater in the Anoro Ellipta group (49%) compared to placebo (34%) and monotherapy (44% for umeclidinium and 48% for vilanterol). In one active comparator study, a higher proportion of patients treated with Anoro Ellipta responded with a clinically meaningful improvement in SGRQ at week 24 (53%) compared to patients treated with tiotropium (46%). In the other two active comparator studies, a similar proportion of patients achieved at least an MIC with Anoro Ellipta and tiotropium: 49% and 54% with Anoro Ellipta 55/22 mcg, and 52% and 55% with tiotropium.

Using medications to relieve symptoms

Anoro Ellipta reduced the use of reliever medications (salbutamol) over weeks 1–24 of the study compared to placebo and umeclidinium (see Table 1) and demonstrated an increase in the number of days without reliever medications (mean 11.1%) compared to placebo, which had a mean reduction of 0.9%.

In three 6-month, active-controlled studies, Anoro Ellipta reduced the use of reliever medications compared to tiotropium, with statistically significant reductions in two studies (see Table 1). Anoro Ellipta also demonstrated an increase in the proportion of days when reliever medication was not required in all three studies (mean range 17.6% to 21.5%) compared to tiotropium (mean range 11.7% to 13.4%).

Table 1. Lung function, symptoms, and health-related quality of life at week 24

N – size of the ITT population (ITT – population of all patients randomized to treatment), µg – micrograms, n/a – not evaluated.

1R.m.s. average.

2Combined data from study DB2113360 and study DB2113374.

3Difference in average number of drug applications per day during weeks 1–24.

A higher dose of umeclidinium/vilanterol (113/22 mcg) was also studied in a 24-week placebo-controlled clinical trial and in two of three 24-week active-controlled trials. The results were similar to those of Anoro Ellipta 55/22 mcg and further supported the efficacy of Anoro Ellipta.

COPD exacerbation

In a 24-week placebo-controlled study in patients with symptomatic COPD, Anoro Ellipta reduced the risk of moderate/severe COPD exacerbation by 50% compared to placebo (based on time to first exacerbation analysis: hazard ratio (HR) 0.5; 95% CI 0.3, 0.8; p = 0.004*); by 20% compared to umeclidinium (HR 0.8; 95% CI 0.5, 1.3; p = 0.391) and by 30% compared to vilanterol (HR 0.7; 95% CI 0.4, 1.1; p = 0.121).

In one of the three studies in patients with symptomatic COPD, Anoro Ellipta reduced the risk of moderate/severe COPD exacerbation by 50% compared with tiotropium (HR 0.5; 95% CI 0.3, 1.0; p = 0.044). In the other two studies, the risk of moderate/severe COPD exacerbation in patients with symptomatic COPD was 20% and 90% higher, respectively (HR 1.2; 95% CI 0.5, 2.6; p = 0.709 and HR 1.9; 95% CI 1.0, 3.6; p = 0.062). These studies were not designed to assess the effect of treatment on COPD exacerbations, and patients were excluded from the study after developing an exacerbation.

Studies confirming effectiveness

A randomized, double-blind, 52-week study (CTT116855, IMPACT) in 10,355 adult patients with symptomatic COPD who had experienced 1 or more moderate or severe exacerbations in the previous 12 months compared treatment with umeclidinium/vilanterol (UMEC/VI 55/22 mcg), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 99/55/22 mcg), or fluticasone furoate/vilanterol (FF/VI 99/22 mcg) once daily in a single inhaler. The primary endpoint of the study was the annualized rate of moderate or severe exacerbations in those receiving FF/UMEC/VI compared with FF/VI or UMEC/VI. The mean annualized rate of exacerbations was 0.91; 1.07 and 1.21 for FF/UMEK/VI, FF/VI and UMEK/VI, respectively.

Comparison of FF/UMEC/VI with FF/VI and UMEC/VI showed a statistically significant reduction in the risk of moderate/severe exacerbation by 14.8% (based on time to first exacerbation analysis) (HR 0.85; 95% CI 0.80, 0.91; p < 0.001) and 16%, respectively (based on time to first exacerbation analysis) (HR 0.84; 95% CI 0.78, 0.91; p < 0.001).

Endurance and lung capacity

In one of the two studies, Anoro Ellipta 55/22 mcg improved exercise endurance time compared with placebo, as assessed by the step-down shuttle test. Both studies showed increases in lung volumes compared with placebo in adult patients with hyperinflation (functional residual capacity (FRC) > 120%). In the first study, Anoro Ellipta 55/22 mcg demonstrated a statistically significant and clinically meaningful improvement in exercise endurance time (69.4 seconds, p = 0.003) compared with placebo, as assessed at week 12 of the study 3 hours after dosing (minimum clinically important difference (MICD) for the shuttle test is 45–85 s). Improvements in exercise endurance time compared to placebo were observed at day 2 and were maintained at weeks 6 and 12. In the second study, the difference in exercise endurance time between Anoro Ellipta 55/22 mcg and placebo at week 12 was 21.9 seconds (p=0.234).

Anoro Ellipta 55/22 mcg also showed statistically significant improvements from baseline in lung volume compared with placebo. In the first study, measurements were made at week 12 before and 3 hours after inhalation: inspiratory capacity was 237 mL and 316 mL, respectively, residual volume was 466 mL and 643 mL, respectively, and functional residual capacity was 351 mL and 522 mL, respectively (all p < 0.001). In the second study, measurements were also made at week 12 before and 3 hours after inhalation: inspiratory capacity was 198 mL and 238 mL, respectively, residual volume was 295 mL and 351 mL, respectively, and functional residual capacity was 238 mL and 302 mL, respectively (all p < 0.001).

When the combination of umeclidinium and vilanterol was administered by inhalation, the pharmacokinetics of each component were similar to those observed when each active substance was administered separately. Therefore, for pharmacokinetic purposes, each component can be considered separately.

Absorption.

Umeclidinium

Following inhalation of umeclidinium to healthy volunteers, Cmax was achieved within 5–15 minutes. The absolute bioavailability of umeclidinium administered by inhalation was on average 13% of the dose, with little contribution from oral absorption. Following repeated doses of umeclidinium administered by inhalation, steady state was achieved within 7–10 days with a 1.5–1.8-fold accumulation.

Vilanterol

Following inhalation of vilanterol to healthy volunteers, Cmax was achieved within 5–15 minutes. The absolute bioavailability of vilanterol administered by inhalation was 27%, with little contribution from oral absorption. Following repeated doses of vilanterol administered by inhalation, steady state was achieved within 6 days with a 2.4-fold accumulation.

Distribution.

Umeclidinium

After intravenous administration to healthy volunteers, the mean volume of distribution was 86 liters. In vitro binding to human plasma proteins averaged 89%.

Vilanterol

After intravenous administration to healthy volunteers, the mean volume of distribution at steady state was 165 liters. In vitro binding to human plasma proteins averaged 94%.

Biotransformation.

Umeclidinium

In vitro studies have shown that umeclidinium is primarily metabolized by cytochrome P450 2D6 (CYP2D6) and is a substrate for the transporter P-glycoprotein (P-gp). The primary metabolic pathways for umeclidinium are oxidative (hydroxylation, O-dealkylation) followed by conjugation (glucuronidation, etc.), resulting in the formation of a number of metabolites with either reduced pharmacological activity or undetermined pharmacological activity. The systemic exposure of the metabolites is low.

Vilanterol

In vitro studies have shown that vilanterol is primarily metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate for the transporter P-gp. The primary metabolic pathways for vilanterol are O-dealkylation with subsequent formation of a number of metabolites with significantly reduced activity towards beta1- and beta2-adrenoceptors. The plasma metabolic profile after oral administration of vilanterol in a radioisotope study in humans is consistent with high first-pass metabolism. Systemic exposure to metabolites is low.

Breeding.

Umeclidinium

Plasma clearance after intravenous administration was 151 liters/hour. After intravenous administration, approximately 58% of the administered labeled dose (or 73% of the recovered radioactivity) was excreted in the feces by 192 hours post-dose. 22% of the administered labeled dose was excreted in the urine by 168 hours (27% of the recovered radioactivity). The excretion of drug-related material in the feces after intravenous administration is indicative of biliary secretion. After oral administration to healthy male volunteers, total radioactivity was excreted primarily in the feces (92% of the administered labeled dose or 99% of the recovered radioactivity) by 168 hours post-dose. Less than 1% of the orally administered dose (1% of the recovered radioactivity) was excreted in the urine, indicating little absorption after oral administration. The elimination half-life of umeclidinium following inhalation administration for 10 days averaged 19 hours in healthy volunteers, with 3–4% excreted unchanged in the urine at steady state.

Vilanterol

The plasma clearance of vilanterol after intravenous administration was 108 liters/hour. After oral administration of labeled vilanterol, 70% of the labeled dose was recovered in the urine and 30% in the feces. The primary elimination of vilanterol is metabolism with subsequent excretion of metabolites in the urine and feces. The elimination half-life of vilanterol after inhalation administration for 10 days averaged 11 hours.

Special patient groups

Elderly patients (> 65 years)

Population pharmacokinetic analysis showed that the pharmacokinetics of umeclidinium and vilanterol were similar in COPD patients aged 65 years and older and patients aged <65 years.

Renal impairment: In patients with severe renal impairment, there was no evidence of increased systemic exposure to umeclidinium or vilanterol (Cmax and AUC) following administration of umeclidinium/vilanterol at twice the recommended dose of umeclidinium and vilanterol at the recommended dose, with no evidence of altered plasma protein binding compared to healthy volunteers.

Hepatic impairment: In patients with moderate hepatic impairment (Child-Pugh Class B), there was no evidence of increased systemic exposure to umeclidinium or vilanterol (Cmax and AUC) following administration of umeclidinium/vilanterol at twice the recommended dose and vilanterol at the recommended dose, with no evidence of altered plasma protein binding compared to healthy volunteers. Umeclidinium/vilanterol has not been evaluated in patients with severe hepatic impairment.

Population pharmacokinetic analysis indicated that no dose adjustment of umeclidinium or vilanterol is required based on age, race, gender, use of inhaled corticosteroids, or body weight. A study conducted in CYP2D6 poor metabolizers did not reveal any evidence of a clinically meaningful effect of CYP2D6 genetic polymorphisms on the systemic exposure of umeclidinium.

Indication

For maintenance bronchodilator therapy to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Contraindication

Hypersensitivity to the active substances or to any of the excipients.

Interaction with other medicinal products and other types of interactions

Beta-blockers

Beta-blocker-containing medicinal products may attenuate or antagonize the effect of beta2-adrenergic agonists such as vilanterol. The concomitant use of both non-selective and selective beta-blockers should be avoided unless there are compelling reasons for their use.

Interactions based on metabolism and transport

Vilanterol is a substrate of cytochrome P450 3A4 (CYP3A4). Concomitant use of potent CYP3A4 inhibitors (such as ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin) may inhibit metabolism and increase systemic exposure to vilanterol. Co-administration with ketoconazole (400 mg) in healthy volunteers increased mean AUC(0-t) and Cmax of vilanterol by 65% and 22%, respectively. The increased exposure to vilanterol was not associated with increased systemic exposure associated with beta-blockers, and did not affect heart rate, blood potassium, or the QT interval (corrected interval calculated using the Frederick formula). Caution should be exercised when umeclidinium/vilanterol is co-administered with ketoconazole and other known potent CYP3A4 inhibitors as there is a potential for increased systemic exposure to vilanterol, which may lead to an increased risk of adverse reactions. Verapamil, a moderate CYP3A4 inhibitor, did not significantly affect the pharmacokinetics of vilanterol.

Umeclidinium is a substrate of cytochrome P450 2D6 (CYP2D6). The steady-state pharmacokinetics of umeclidinium were evaluated in healthy volunteers with CYP2D6 deficiency (poor metabolizers). No effect on umeclidinium AUC or Cmax was observed at a dose of 8 times the normal dose. An approximately 1.3-fold increase in umeclidinium AUC was observed at a dose of 16 times the normal dose, with no effect on umeclidinium Cmax. Given the magnitude of these changes, no clinically significant drug interactions are expected when umeclidinium/vilanterol is co-administered with CYP2D6 inhibitors or when administered to patients genetically deficient in CYP2D6 activity (poor metabolizers).

Both umeclidinium and vilanterol are substrates of the P-glycoprotein (P-gp) transporter. The effect of the moderate P-gp inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of umeclidinium and vilanterol was evaluated in healthy volunteers. There was no effect of verapamil on the Cmax of umeclidinium or vilanterol. An approximately 1.4-fold increase in umeclidinium AUC was observed with no effect on vilanterol AUC. Given the magnitude of these changes, no clinically significant drug interactions are expected when umeclidinium/vilanterol are co-administered with P-gp inhibitors.

Other antimuscarinics and sympathomimetics

Concomitant use of umeclidinium/vilanterol with other long-acting muscarinic antagonists, long-acting beta2-adrenergic agonists, or medicinal products containing any of these agents has not been studied. Such use is not recommended as it may increase the known adverse reactions of inhaled muscarinic antagonists or beta2-adrenergic agonists (see sections 4.4 and 4.8).

Hypokalemia

Concomitant hypokalemic treatment with methylxanthine derivatives, steroids or non-potassium-sparing diuretics may potentiate the possible hypokalemic effect of beta2-adrenergic agonists, therefore umeclidinium/vilanterol should be used with caution (see section 4.2).

Other medicines for COPD

Although no conventional in vivo drug interaction studies have been performed, inhaled umeclidinium/vilanterol has been used concomitantly with other COPD medicinal products, including short-acting sympathomimetic bronchodilators and inhaled corticosteroids, without clinical evidence of drug interactions.

Application features

Asthma

Umeclidinium/vilanterol should not be used in patients with asthma as this medicine has not been studied in this patient population.

Paradoxical bronchospasm

As with other inhaled therapies, umeclidinium/vilanterol may cause paradoxical bronchospasm, which may be life-threatening. Umeclidinium/vilanterol should be discontinued immediately if paradoxical bronchospasm occurs and alternative therapy should be initiated, if necessary.

Not for use during an acute condition

Umeclidinium/vilanterol is not indicated for the treatment of acute episodes of bronchospasm.

An increase in the frequency of use of short-acting bronchodilators for symptom relief indicates worsening disease control. If COPD worsens while on umeclidinium/vilanterol, the patient's condition and treatment strategy should be re-evaluated.

Effects on the cardiovascular system

Cardiovascular effects, such as cardiac arrhythmias such as atrial fibrillation and tachycardia, may occur following administration of muscarinic receptor antagonists and sympathomimetics, including umeclidinium/vilanterol. Patients with clinically significant uncontrolled cardiovascular disease were excluded from clinical studies. Therefore, umeclidinium/vilanterol should be used with caution in patients with severe cardiovascular disease.

Antimuscarinic activity

Due to its antimuscarinic activity, umeclidinium/vilanterol should be used with caution in patients with urinary retention or angle-closure glaucoma.

Hypokalemia

Beta2-adrenergic agonists may cause significant hypokalemia in some patients, which may lead to the development of adverse reactions from the cardiovascular system. The decrease in serum potassium is usually transient.

No clinically significant effects of hypokalaemia were observed in clinical studies with umeclidinium/vilanterol at the recommended therapeutic dose. Caution should be exercised when umeclidinium/vilanterol is used with other medicinal products that may also contribute to the development of hypokalaemia (see section 4.5).

Hyperglycemia

Beta2-adrenergic agonists may cause transient hyperglycemia in some patients.

No clinically relevant effects on plasma glucose levels were observed in clinical studies with umeclidinium/vilanterol at the recommended therapeutic dose. Plasma glucose levels should be monitored more closely in patients with diabetes mellitus after initiation of treatment with umeclidinium/vilanterol.

Comorbidities

Umeclidinium/vilanterol should be used with caution in patients with seizure disorders or with thyrotoxicosis, as well as in patients who are unusually responsive to beta2-adrenergic agonists.

Excipients

This medicinal product contains lactose. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy: There are currently no data from the use of umeclidinium/vilanterol in pregnant women.

Umeclidinium/vilanterol should be used during pregnancy only if the expected benefit to the pregnant woman outweighs the potential risk to the fetus.

Breast-feeding. It is not known whether umeclidinium or vilanterol are excreted in human milk. However, other beta2-adrenergic agonists are excreted in human milk. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue umeclidinium/vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effects of umeclidinium/vilanterol on human reproductive function.

Ability to influence reaction speed when driving vehicles or other mechanisms

Umeclidinium/vilanterol has no or negligible influence on the ability to drive and use machines.

Method of administration and doses

Doses

Adults

The recommended dose is one inhalation of Anoro Ellipta 55/22 mcg once daily.

Anoro Ellipta should be used once daily at the same time each day to maintain bronchodilation. The maximum dose is one inhalation of Anoro Ellipta 55/22 mcg once daily.

Special patient groups

Elderly patients

No dose adjustment is required for patients over 65 years of age.

Patients with renal impairment

No dose adjustment is required for patients with renal impairment.

Patients with hepatic impairment

No dose adjustment is required for patients with mild to moderate hepatic impairment. Anoro Ellipta has not been studied in patients with severe hepatic impairment and should be used with caution.

Children

Anoro Ellipta has not been used in children (under 18 years of age) to treat COPD.

Method of application

Anoro Ellipta is for inhalation use only.

Instructions for use

The Ellipta inhaler contains pre-dispensed doses and is ready to use.

The inhaler is in the “closed” position in the tray. Once the tray is opened, it can be thrown away. The expiry date of the inhaler is 6 weeks from the date the tray is opened. The expiry date should be written in the space provided, marked “Do not use after:”. The inhaler should not be used after the expiry date.

Packaging of the medicine Anoro Ellipta and its contents:

Instructions for using the inhaler

1. Read before use

If the inhaler lid is opened and closed without inhaling the medicine, the dose will be lost. The lost dose is securely stored in the inhaler, but is no longer available for inhalation.

It is impossible to accidentally take an excessive or double dose of the drug in one inhalation.

2. How to prepare a dose

Do not open the cap until you are ready to take your dose. Do not shake the inhaler.

Pull the cover down until you hear a "click".

The medicine is now ready to be inhaled. The dose counter counts down to 1, confirming that it is ready.

If the dose counter has not counted down the dose after you hear the “click”, the inhaler is not working. You should take the inhaler to a pharmacy for advice. In any case, do not shake the inhaler.

3. How to inhale the drug

Hold the inhaler away from your mouth and breathe out as deeply as is comfortable for you.

Do not exhale into the inhaler.

Place the mouthpiece between your lips and press them tightly around the mouthpiece.

Do not cover the air valves with your fingers.

Take one long, steady, deep breath, then hold your breath for as long as possible (at least 3–4 seconds).

Remove the inhaler from your mouth.

Exhale slowly and carefully.

Even when using the inhaler correctly, you may not feel the medicine, including its taste.

4. Close the inhaler

If there is a need to clean the mouthpiece, use a dry cloth before closing the lid.

To cover the mouthpiece, replace the lid by sliding it upwards until it stops.

Children: Anoro Ellipta has not been used in children (under 18 years of age) to treat COPD.

Overdose

Overdose with umeclidinium/vilanterol is likely to present with signs and symptoms related to the actions of the individual components, consistent with known adverse reactions of inhaled muscarinic antagonists (e.g., dry mouth, visual accommodation disorders, and tachycardia) or with reactions seen with overdose of other beta2-adrenergic agonists (e.g., arrhythmia, tremor, headache, palpitations, nausea, hyperglycemia, and hypokalemia).

In the event of overdose, the patient should be treated symptomatically with appropriate monitoring as necessary.

Side effects

Safety profile overview

The most frequently reported adverse reaction during use is