ENERZAIR BREEZHALER

1 Dosing Considerations Patients should be made aware that ENERZAIR BREEZHALER should be used regularly, even when asymptomatic. When treating patients with asthma, physicians should only prescribe ENERZAIR BREEZHALER for patients not adequately controlled on a long-term asthma control medication containing a LABA and a medium or high dose inhaled corticosteroid and who experienced one or more asthma exacerbations in the previous year.

As with other inhaled drugs containing beta2-adrenergic agents, ENERZAIR BREEZHALER should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result.

d) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief if they develop acute respiratory symptoms while taking ENERZAIR BREEZHALER. ENERZ AIR® BREEZHALER® Product Monograph Page 5 of 43 It is crucial to inform patients that ENERZAIR BREEZHALER should not be used to treat acute symptoms of asthma.

, salbutamol) to relieve acute symptoms such as shortness of breath and advised to have this available for use at all times. 2 Recommended Dose and Dosage Adjustment The recommended dose of ENERZAIR BREEZHALER for patients 18 years of age and older is:  Inhalation of the content of one capsule of ENERZAIR BREEZHALER 150/50/160 micrograms once-daily in patients not adequately controlled with a combination of a long-acting beta2- agonist and a medium or high dose of an inhaled corticosteroid.

The maximum recommended dose is ENERZAIR BREEZHALER 150/50/160 micrograms once-daily. 3 Pharmacokinetics). No dose adjustment is required in patients with mild to moderate renal impairment. Hepatic impairment No data are available for ENERZAIR BREEZHALER in subjects with hepatic impairment.

Based on PK data available for the monocomponents, no dose adjustment is required in patients with mild or moderate hepatic impairment. 3 Pharmacokinetics). 3 Pharmacokinetics).

Pediatrics (<18 years of age):

The safety and efficacy of ENERZAIR BREEZHALER in pediatric patients below 18 years of age have not been established. 4 Administration For inhalation use only. ENERZAIR BREEZHALER capsules must not be swallowed. Patients should be instructed on how to administer the medicinal product correctly.

Patients who do not experience improvement in breathing should be asked if they are swallowing the capsule rather than inhaling it. The capsules must be administered only using the ENERZAIR BREEZHALER inhaler. The inhaler provided with each new prescription should be used.

ENERZAIR BREEZHALER should be administered at the same time of the day each day. It can be administered irrespective of the time of the day. ENERZ AIR® BREEZHALER® Product Monograph Page 6 of 43 The capsules must always be stored in the blister to protect from moisture and light, and only removed immediately before use (see 11 STORAGE, STABILITY AND DISPOSAL and 12 SPECIAL HANDLING INSTRUCTIONS).

After inhalation, patients should rinse their mouth with water without swallowing. 5 Missed Dose If a dose is missed, it should be taken as soon as possible. Patients should be instructed not to take more than one dose in a day.

1 Adverse Reaction Overview Use of LABA monotherapy (without ICS treatment) increases the risk of serious asthma-related events (death, hospitalizations, and intubations) (see General). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

The safety of ENERZAIR BREEZHALER was evaluated in a phase 3 study (B2302) with a total of 616 adult patients with asthma treated with ENERZAIR BREEZHALER 150/50/160 micrograms once-daily for up to 52 weeks. Adverse drug reactions from the 52-week study (B2302) are listed by MedDRA system organ class (Table 3).

The most common adverse drug reactions related to ENERZAIR BREEZHALER were headache, cough and dysphonia. 86 * Grouping of preferred terms (PTs). 1 asymptomatic bacteriuria, bacteriuria, cystitis, urethritis, urinary tract infection, urinary tract infection viral.

2 drug eruption, drug hypersensitivity, hypersensitivity, rash, rash pruritic, urticaria. ENERZ AIR® BREEZHALER® Product Monograph Page 16 of 43 3 headache, tension headache. 4 sinus tachycardia, supraventricular tachycardia, tachycardia.

5 odynophagia, oropharyngeal discomfort, oropharyngeal pain, throat irritation. 6 chronic gastritis, enteritis, gastritis, gastroenteritis, gastrointestinal inflammation 7 back pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain.

5 Post-Market Adverse Reactions No post marketing Adverse Drug Reactions have been identified to date for ENERZAIR BREEZHALER.

3 Pharmacokinetics). No dose adjustment is required in patients with mild to moderate renal impairment. Hepatic impairment No data are available for ENERZAIR BREEZHALER in subjects with hepatic impairment. Based on PK data available for the monocomponents, no dose adjustment is required in patients with mild or moderate hepatic impairment.

3 Pharmacokinetics). 3 Pharmacokinetics).

Pediatrics (<18 years of age):

The safety and efficacy of ENERZAIR BREEZHALER in pediatric patients below 18 years of age have not been established. 4 Administration For inhalation use only. ENERZAIR BREEZHALER capsules must not be swallowed. Patients should be instructed on how to administer the medicinal product correctly.

Patients who do not experience improvement in breathing should be asked if they are swallowing the capsule rather than inhaling it. The capsules must be administered only using the ENERZAIR BREEZHALER inhaler. The inhaler provided with each new prescription should be used.

ENERZAIR BREEZHALER should be administered at the same time of the day each day. It can be administered irrespective of the time of the day. ENERZ AIR® BREEZHALER® Product Monograph Page 6 of 43 The capsules must always be stored in the blister to protect from moisture and light, and only removed immediately before use (see 11 STORAGE, STABILITY AND DISPOSAL and 12 SPECIAL HANDLING INSTRUCTIONS).

After inhalation, patients should rinse their mouth with water without swallowing. 5 Missed Dose If a dose is missed, it should be taken as soon as possible. Patients should be instructed not to take more than one dose in a day. 5 OVERDOSAGE There is limited experience with overdose in clinical studies with ENERZAIR BREEZHALER.

General supportive measures and symptomatic treatment should be initiated in cases of suspected overdose. g. tachycardia, tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia, increased intraocular pressure (causing pain, vision disturbances or reddening of the eye), constipation, difficulties in voiding, suppression of hypothalamic pituitary adrenal axis function].

Use of cardioselective beta blockers may be considered for treating beta2-adrenergic effects, but only under the supervision of a physician and with extreme caution since the use of beta2-adrenergic blockers may provoke bronchospasm.

In serious cases, patients should be hospitalized. For management of a suspected drug overdose, contact your regional poison control centre. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, Composition and Packaging Each capsule of ENERZAIR BREEZHALER 150/50/160 micrograms contains 173 micrograms of indacaterol acetate equivalent to 150 micrograms of indacaterol, 63 micrograms of glycopyrronium bromide equivalent to 50 micrograms glycopyrronium and 160 micrograms mometasone furoate The delivered dose (the dose that leaves the mouthpiece of the inhaler) for 150/50/160 micrograms is equivalent to 114 micrograms indacaterol, 46 micrograms glycopyrronium, and 136 micrograms mometasone furoate.

The following pack types are available:  Carton of 30 ENERZAIR BREEZHALER capsules (3 blister cards of 10 capsules) and one ENERZAIR BREEZHALER device. Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral inhalation Inhalation powder hard capsules containing 150 mcg indacaterol (as acetate), 50 mcg glycopyrronium (as bromide) and 160 mcg mometasone furoate Carrageenan, hypromellose, lactose (as monohydrate), magnesium stearate, potassium chloride, purified water ENERZ AIR® BREEZHALER® Product Monograph Page 7 of 43 7 WARNINGS AND PRECAUTIONS General Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma- related death (see Salmeterol Multicenter Asthma Research Trial (SMART)).

Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma- related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.

When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta2-adrenergic Agonist Combination Products).

Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta2-adrenergic Agonist Combination Products Four (4) large, 26-week, randomized, double-blind, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed-dose combination with ICS compared with ICS alone in subjects with asthma.

Three (3) trials included adult and adolescent subjects aged 12 years and older: 1 trial compared budesonide/formoterol with budesonide, 1 trial compared fluticasone propionate/salmeterol with fluticasone propionate, and 1 trial compared mometasone furoate/formoterol with mometasone furoate.

The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol with fluticasone propionate. No safety study was conducted with ENERZAIR BREEZHALER. The primary safety endpoint for all 4 trials was serious asthma-related events (hospitalizations, intubations, death).

A single, blinded, […]

 ENERZAIR BREEZHALER is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.