Ultibro Breezhaler Epar Product Information en

ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
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1. NAME OF THE MEDICINAL PRODUCT
Ultibro Breezhaler 85 micrograms/43 micrograms inhalation powder hard capsules
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 143 micrograms of indacaterol maleate equivalent to 110 micrograms of
indacaterol and 63 micrograms of glycopyrronium bromide equivalent to 50 micrograms of
glycopyrronium.
Each delivered dose (the dose that leaves the mouthpiece of the inhaler) contains 110 micrograms of
indacaterol maleate equivalent to 85 micrograms of indacaterol and 54 micrograms of glycopyrronium
bromide equivalent to 43 micrograms of glycopyrronium.
Excipient(s) with known effect
Each capsule contains 23.5 mg lactose (as monohydrate).
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Inhalation powder, hard capsule (inhalation powder).
Capsules with transparent yellow cap and natural transparent body containing a white to almost white
powder, with the product code “IGP110.50” printed in blue under two blue bars on the body and the
company logo ( ) printed in black on the cap.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Ultibro Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult

patients with chronic obstructive pulmonary disease (COPD).
4.2 Posology and method of administration
Posology
The recommended dose is the inhalation of the content of one capsule once daily using the Ultibro
Breezhaler inhaler.
Ultibro Breezhaler is recommended to be administered at the same time of the day each day. If a dose
is missed, it should be taken as soon as possible on the same day. Patients should be instructed not to
take more than one dose in a day.
Special populations
Elderly population
Ultibro Breezhaler can be used at the recommended dose in elderly patients (75 years of age and
older).
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Renal impairment
Ultibro Breezhaler can be used at the recommended dose in patients with mild to moderate renal
impairment. In patients with severe renal impairment or end-stage renal disease requiring dialysis it
should be used only if the expected benefit outweighs the potential risk (see sections 4.4 and 5.2).
Hepatic impairment
Ultibro Breezhaler can be used at the recommended dose in patients with mild and moderate hepatic
impairment. There are no data available for the use of Ultibro Breezhaler in patients with severe
hepatic impairment, therefore caution should be observed in these patients (see section 5.2).
Paediatric population
There is no relevant use of Ultibro Breezhaler in the paediatric population (under 18 years) in the
indication COPD. The safety and efficacy of Ultibro Breezhaler in children have not been established.
No data are available.
Method of administration
For inhalation use only. The capsules must not be swallowed.
The capsules must be administered only using the Ultibro Breezhaler inhaler (see section 6.6). The
inhaler provided with each new prescription should be used.
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 medicinal
product rather than inhaling it.
For instructions on use of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Ultibro Breezhaler should not be administered concomitantly with medicinal products containing other
long-acting beta-adrenergic agonists or long-acting muscarinic antagonists, the pharmacotherapeutic
groups to which the components of Ultibro Breezhaler belong (see section 4.5).
Asthma
Ultibro Breezhaler should not be used for the treatment of asthma due to the absence of data in this
indication.
Long-acting beta2-adrenergic agonists may increase the risk of asthma-related serious adverse events,
including asthma-related deaths, when used for the treatment of asthma.
Not for acute use
Ultibro Breezhaler is not indicated for the treatment of acute episodes of bronchospasm.
Hypersensitivity
Immediate hypersensitivity reactions have been reported after administration of indacaterol or

glycopyrronium, which are the active substances of Ultibro Breezhaler. If signs suggesting allergic
reactions occur, in particular, angioedema (difficulties in breathing or swallowing, swelling of the
tongue, lips and face) urticaria or skin rash, treatment should be discontinued immediately and
alternative therapy instituted.
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Paradoxical bronchospasm
Administration of Ultibro Breezhaler may result in paradoxical bronchospasm which can be

life-threatening. If this occurs, treatment should be discontinued immediately and alternative therapy
instituted.
Anticholinergic effects related to glycopyrronium
Narrow-angle glaucoma
No data are available in patients with narrow-angle glaucoma, therefore Ultibro Breezhaler should be
used with caution in these patients.
Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and
should be informed to stop using Ultibro Breezhaler should any of these signs or symptoms develop.
Urinary retention
No data are available in patients with urinary retention, therefore Ultibro Breezhaler should be used
with caution in these patients.
Patients with severe renal impairment
A moderate mean increase in total system exposure (AUC last) to glycopyrronium of up to 1.4-fold was
seen in subjects with mild and moderate renal impairment and up to 2.2-fold in subjects with severe
renal impairment and end-stage renal disease. In patients with severe renal impairment (estimated
glomerular filtration rate below 30 ml/min/1.73 m2), including those with end-stage renal disease
requiring dialysis, Ultibro Breezhaler should be used only if the expected benefit outweighs the
potential risk (see section 5.2). These patients should be monitored closely for potential adverse
reactions.
Cardiovascular effects
Ultibro Breezhaler should be used with caution in patients with cardiovascular disorders (coronary
artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension).
Beta2-adrenergic agonists may produce a clinically significant cardiovascular effect in some patients
as measured by increases in pulse rate, blood pressure, and/or symptoms. In case such effects occur
with this medicinal product, treatment may need to be discontinued. In addition, beta-adrenergic
agonists have been reported to produce electrocardiographic (ECG) changes, such as flattening of the
T wave, prolongation of QT interval and ST segment depression, although the clinical significance of
these observations is unknown. Therefore, long-acting beta2-adrenergic agonists (LABA) or
LABA-containing combination products such as Ultibro Breezhaler should be used with caution in
patients with known or suspected prolongation of the QT interval or treated with medicinal products
affecting the QT interval.
Patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction,
arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc
(Fridericia method) was prolonged (>450 ms) were excluded from the clinical trials, and therefore
there is no experience in these patient groups. Ultibro Breezhaler should be used with caution in these
patient groups.
Hypokalaemia
Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the
potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually
transient, not requiring supplementation. In patients with severe COPD, hypokalaemia may be
potentiated by hypoxia and concomitant treatment, which may increase the susceptibility to cardiac
arrhythmias (see section 4.5).
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Clinically relevant effects of hypokalaemia have not been observed in clinical studies of Ultibro
Breezhaler at the recommended therapeutic dose (see section 5.1).
Hyperglycaemia
Inhalation of high doses of beta2-adrenergic agonists may produce increases in plasma glucose. Upon
initiation of treatment with Ultibro Breezhaler plasma glucose should be monitored more closely in
diabetic patients.
During long-term clinical studies, more patients on Ultibro Breezhaler experienced clinically notable
changes in blood glucose (4.9%) at the recommended dose than on placebo (2.7%). Ultibro Breezhaler
has not been investigated in patients for whom diabetes mellitus is not well controlled, therefore
caution and appropriate monitoring are advised in such patients.
General disorders
Ultibro Breezhaler should be used with caution in patients with convulsive disorders or thyrotoxicosis,
and in patients who are unusually responsive to beta 2-adrenergic agonists.
Excipients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal
product.
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant administration of orally inhaled indacaterol and glycopyrronium, under steady-state

conditions of both active substances, did not affect the pharmacokinetics of either active substance.
No specific interaction studies were conducted with Ultibro Breezhaler. Information on the potential
for interactions is based on the potential for each of its two active substances.
Concomitant use not recommended
Beta-adrenergic blockers
Beta-adrenergic blockers may weaken or antagonise the effect of beta 2-adrenergic agonists. Therefore
Ultibro Breezhaler should not be given together with beta-adrenergic blockers (including eye drops)
unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic
blockers should be preferred, although they should be administered with caution.
Anticholinergics
The co-administration of Ultibro Breezhaler with other anticholinergic-containing medicinal products
has not been studied and is therefore not recommended (see section 4.4).
Sympathomimetics
Concomitant administration of other sympathomimetics (alone or as part of combination therapy) may
potentiate the adverse events of indacaterol (see section 4.4).
Caution required with concomitant use
Hypokalaemic treatment
Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium-
sparing diuretics may potentiate the possible hypokalaemic effect of beta 2-adrenergic agonists,
therefore use with caution (see section 4.4).
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To be taken into account with concomitant use
Metabolic and transporter based interactions

Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp), raises
the systemic exposure of indacaterol up to two-fold. The magnitude of exposure increases due to
interactions does not raise any safety concerns given the safety experience of treatment with
indacaterol in clinical studies of up to one year at doses up to twice the maximum recommended
indacaterol dose.
Cimetidine or other inhibitors of organic cation transport

In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is
thought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) to
glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these
changes, no clinically relevant drug interaction is expected when glycopyrronium is co-administered
with cimetidine or other inhibitors of the organic cation transport.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no data from the use of Ultibro Breezhaler in pregnant women available. Animal studies do
not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant
exposures (see section 5.3).
Indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle. Therefore, Ultibro
Breezhaler should only be used during pregnancy if the expected benefit to the patient justifies the
potential risk to the foetus.
Breast-feeding
It is not known whether indacaterol, glycopyrronium and their metabolites are excreted in human milk.
Available pharmacokinetic/toxicological data have shown excretion of indacaterol, glycopyrronium
and their metabolites in the milk of lactating rats. The use of Ultibro Breezhaler by breast-feeding
women should only be considered if the expected benefit to the woman is greater than any possible
risk to the infant (see section 5.3).
Fertility
Reproduction studies and other data in animals do not indicate a concern regarding fertility in either
males or females.
4.7 Effects on ability to drive and use machines
This medicinal product has no or negligible influence on the ability to drive and use machines.
However, the occurrence of dizziness may influence the ability to drive and use machines (see
section 4.8).
4.8 Undesirable effects
The presentation of the safety profile is based on the experience with Ultibro Breezhaler and the
individual active substances.
Summary of the safety profile
The safety experience with Ultibro Breezhaler was comprised of exposure of up to 15 months at the
recommended therapeutic dose.
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Ultibro Breezhaler showed similar adverse reactions to the individual components. As it contains
indacaterol and glycopyrronium, the type and severity of adverse reactions associated with each of
these components may be expected in the combination.
The safety profile is characterised by typical anticholinergic and beta-adrenergic symptoms related to
the individual components of the combination. Other most common adverse reactions related to the
medicinal product (at least 3% of patients for Ultibro Breezhaler and also greater than placebo) were
cough, nasopharyngitis and headache.
Tabulated summary of adverse reactions
Adverse reactions detected during clinical trials and from post-marketing sources are listed by
MedDRA system organ class (Table 1). Within each system organ class, the adverse reactions are
ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse
reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency
category for each adverse reaction is based on the following convention: very common (≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare
(<1/10,000); not known (cannot be estimated from the available data).
Table 1 Adverse reactions
Adverse reactions Frequency category

Infections and infestations
Upper respiratory tract infection Very common
Nasopharyngitis Common
Urinary tract infection Common
Sinusitis Common
Rhinitis Common
Immune system disorders
Hypersensitivity Common
Angioedema2 Uncommon
Metabolism and nutrition disorders
Hyperglycaemia and diabetes mellitus Common
Psychiatric disorders
Insomnia Uncommon
Nervous system disorders
Dizziness Common
Headache Common
Paraesthesia Rare
Eye disorders
Glaucoma1 Uncommon
Cardiac disorders
Ischaemic heart disease Uncommon
Atrial fibrillation Uncommon
Tachycardia Uncommon
Palpitations Uncommon
Respiratory, thoracic and mediastinal disorders
Cough Common
Oropharyngeal pain including throat irritation Common
Paradoxical bronchospasm Uncommon
Dysphonia2 Uncommon
Epistaxis Uncommon
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Gastrointestinal disorders
Dyspepsia Common
Dental caries Common
Gastroenteritis Uncommon
Dry mouth Uncommon
Skin and subcutaneous tissue disorders
Pruritus/rash Uncommon
Musculoskeletal and connective tissue disorders
Musculoskeletal pain Uncommon
Muscle spasm Uncommon
Myalgia Uncommon
Pain in extremity Uncommon
Renal and urinary disorders
Bladder obstruction and urinary retention Common
General disorders and administration site conditions
Pyrexia1 Common
Chest pain Common
Oedema peripheral Uncommon
Fatigue Uncommon
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Adverse reaction observed with Ultibro Breezhaler, but not with the individual components.
2
Reports received from post-marketing experience; frequencies calculated, however, on the basis of
clinical trial data.
Description of selected adverse reactions
Cough was common, but usually of mild intensity.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the national reporting system
listed in Appendix V.
4.9 Overdose
There is no information on clinically relevant overdosing with Ultibro Breezhaler.
An overdose could lead to exaggerated effects typical of beta 2-adrenergic stimulants, i.e. tachycardia,
tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmias, metabolic
acidosis, hypokalaemia and hyperglycaemia or could induce anticholinergic effects such as increased
intraocular pressure (causing pain, vision disturbances or reddening of the eye), obstipation or
difficulties in voiding. Supportive and symptomatic treatment is indicated. In serious cases, patients
should be hospitalised. 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 beta-adrenergic blockers may provoke bronchospasm.
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5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs for obstructive airway diseases, adrenergics in combination with
anticholinergics, ATC code: R03AL04
Mechanism of action
Ultibro Breezhaler
When indacaterol and glycopyrronium are administered together in Ultibro Breezhaler, they provide
additive efficacy due to their different mode of action targeting different receptors and pathways to
achieve smooth muscle relaxation. Due to the differential density of beta 2-adrenoceptors and
M3-receptors in central versus peripheral airways, beta2-agonists should be more effective in relaxing
peripheral airways, whilst an anticholinergic compound may be more effective in central airways.
Thus for bronchodilation in both peripheral and central airways of the human lung a combination of a
beta2-adrenergic agonist and a muscarinic antagonist may be beneficial.
Indacaterol
Indacaterol is a long-acting beta2-adrenergic agonist for once-daily administration. The
pharmacological effects of beta2-adrenoceptor agonists, including indacaterol, are at least in part
attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyses the conversion of
adenosine triphosphate (ATP) to cyclic-3’, 5’-adenosine monophosphate (cyclic AMP). Increased
cyclic AMP levels cause relaxation of bronchial smooth muscle. In vitro studies have shown that
indacaterol has multi-fold greater agonist activity at beta 2-receptors compared to beta1 and
beta3-receptors.
When inhaled, indacaterol acts locally in the lung as a bronchodilator. Indacaterol is a partial agonist
at the human beta2-adrenergic receptor with nanomolar potency.
Although beta2-adrenergic receptors are the predominant adrenergic receptors in bronchial smooth
muscle and beta1-adrenergic receptors are the predominant receptors in the human heart, there are also
beta2-adrenergic receptors in the human heart comprising 10% to 50% of the total adrenergic
receptors. Their presence in the heart raises the possibility that even highly selective beta 2-adrenergic
agonists may have cardiac effects.
Glycopyrronium
Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (anticholinergic) for
once-daily maintenance bronchodilator treatment of COPD. Parasympathetic nerves are the major
bronchoconstrictive neural pathway in airways, and cholinergic tone is the key reversible component
of airflow obstruction in COPD. Glycopyrronium works by blocking the bronchoconstrictor action of
acetylcholine on airway smooth muscle cells, thereby dilating the airways.
Glycopyrronium bromide is a high affinity muscarinic receptor antagonist. A greater than 4-fold
selectivity for the human M3 receptors over the human M2 receptor has been demonstrated using
radioligand binding studies.
Pharmacodynamic effects
The combination of indacaterol and glycopyrronium in Ultibro Breezhaler showed a rapid onset of
action within 5 minutes after dosing. The effect remains constant over the whole 24-h dosing interval.
The mean bronchodilator effect derived from serial FEV1 measurements over 24 h was 320 ml after
26 weeks of treatment. The effect was significantly greater for Ultibro Breezhaler, when compared to
indacaterol, glycopyrronium or tiotropium alone (difference 110 ml, for each comparison).
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There was no evidence for tachyphylaxis to the effect of Ultibro Breezhaler over time when compared
to placebo or its monotherapy components.
Effects on heart rate

Heart rate effects in healthy volunteers were investigated after a single dose of 4 times the
recommended therapeutic dose of Ultibro Breezhaler administered in four dose steps each separated
by one hour and compared to the effects of placebo, indacaterol, glycopyrronium and salmeterol.
The largest time-matched heart rate increase compared to placebo was +5.69 bpm (90% CI [2.71,
8.66]), the largest decrease was -2.51 bpm (90% CI [-5.48, 0.47]). Overall the effect on heart rate over
time did not show a consistent pharmacodynamic effect of Ultibro Breezhaler.
Heart rate in COPD patients at supratherapeutic dose levels was investigated. There were no relevant
effects of Ultibro Breezhaler on mean heart rate over 24 h and heart rate assessed after 30 minutes, 4 h
and 24 h.
QT interval
A thorough QT (TQT) study in healthy volunteers with high doses of inhaled indacaterol (up to twice
the maximum recommended therapeutic dose) did not demonstrate a clinically relevant effect on the
QT interval. Similarly, for glycopyrronium no QT prolongation was observed in a TQT study after an
inhaled dose of 8 times the recommended therapeutic dose.
The effects of Ultibro Breezhaler on QTc interval were investigated in healthy volunteers after
inhalation of Ultibro Breezhaler up to 4 times the recommended therapeutic dose in four dose steps
each separated by one hour. The largest time-matched difference versus placebo was 4.62 ms (90% CI
0.40, 8.85 ms), the largest time-matched decrease was -2.71 ms (90% CI -6.97, 1.54 ms), indicating
that Ultibro Breezhaler had no relevant impact on the QT interval, as was expected by the properties of
its components.
In COPD patients, supratherapeutic doses between 116 micrograms/86 micrograms and

464 micrograms/86 micrograms of Ultibro Breezhaler showed a higher proportion of patients with
QTcF increases vs. baseline between 30 ms and 60 ms (ranging from 16.0% to 21.6% vs. 1.9% for
placebo), but there were no QTcF increases >60 ms from baseline. The highest dose level of
464 micrograms/86 micrograms Ultibro Breezhaler also showed a higher proportion of absolute QTcF
values >450 ms (12.2% vs. 5.7% for placebo).
Serum potassium and blood glucose

In healthy volunteers, after the administration of 4 times the recommended therapeutic dose of Ultibro
Breezhaler, the effect on serum potassium was very small (maximal difference –0.14 mmol/l when
compared to placebo). The maximal effect on blood glucose was 0.67 mmol/l.
Clinical efficacy and safety
The Ultibro Breezhaler clinical Phase III development programme included six studies in which over
8,000 patients were enrolled: 1) a 26-week placebo- and active-controlled (indacaterol once daily,
glycopyrronium once daily, open-label tiotropium once daily) study; 2) a 26-week active-controlled
(fluticasone/salmeterol twice daily) study; 3) a 64-week active-controlled (glycopyrronium once daily,
open-label tiotropium once daily) study; 4) a 52-week placebo-controlled study; 5) a 3-week placebo-
and active-controlled (tiotropium once daily) exercise tolerance study; and 6) a 52-week active-
controlled (fluticasone/salmeterol twice daily) study.
In four of these studies patients were enrolled who had a clinical diagnosis of moderate to severe
COPD. In the 64-week study patients were enrolled who had severe to very severe COPD with a
history of ≥1 moderate or severe COPD exacerbation in the previous year. In the 52-week active-
controlled study, patients were enrolled who had moderate to very severe COPD with a history of
≥1 moderate or severe COPD exacerbation in the previous year.
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Effects on lung function
Ultibro Breezhaler showed clinically meaningful improvements in lung function (as measured by the
forced expiratory volume in one second, FEV1) in a number of clinical studies. In Phase III studies,
bronchodilator effects were seen within 5 minutes after the first dose and were maintained over the
24-hour dosing interval from the first dose. There was no attenuation of the bronchodilator effect over
time.
The magnitude of the effect was dependent on the degree of reversibility of airflow limitation at
baseline (tested by administration of a short-acting muscarinic antagonist bronchodilator and a
short-acting beta2-agonist bronchodilator): Patients with the lowest degree of reversibility at baseline
(<5%) generally exhibited a lower bronchodilator response than patients with a higher degree of
reversibility at baseline (≥5%). At 26 weeks (primary endpoint), Ultibro Breezhaler increased trough
FEV1 by 80 ml in patients (Ultibro Breezhaler n=82; placebo n=42) with the lowest degree of
reversibility (<5%) (p=0.053) and by 220 ml in those patients (Ultibro Breezhaler n=392, placebo
n=190) with a higher degree of reversibility at baseline (≥5%) compared to placebo (p<0.001).
Trough and peak FEV1:

Ultibro Breezhaler increased post-dose trough FEV1 by 200 ml compared to placebo at the 26-week
primary endpoint (p<0.001) and showed statistically significant increases compared to each
monotherapy component treatment arm (indacaterol and glycopyrronium) as well as the tiotropium
treatment arm, as shown in the below table.
Post-dose trough FEV1 (least squares mean) at day 1 and week 26 (primary endpoint)
Treatment difference Day 1 Week 26

Ultibro Breezhaler – placebo 190 ml (p<0.001) 200 ml (p<0.001)
Ultibro Breezhaler – indacaterol 80 ml (p<0.001) 70 ml (p<0.001)
Ultibro Breezhaler – glycopyrronium 80 ml (p<0.001) 90 ml (p<0.001)
Ultibro Breezhaler – tiotropium 80 ml (p<0.001) 80 ml (p<0.001)
The mean pre-dose FEV1 (average of the values taken at -45 and -15 minutes prior to the morning
dose of study medication) was statistically significant in favour of Ultibro Breezhaler at week 26
compared to fluticasone/salmeterol (least squares [LS] mean treatment difference 100 ml, p<0.001), at
week 52 compared to placebo (LS mean treatment difference 189 ml, p<0.001) and at all visits up to
week 64 compared to glycopyrronium (LS mean treatment difference 70-80 ml, p<0.001) and
tiotropium (LS mean treatment difference 60-80 ml, p<0.001). In the 52-week active-controlled study,
the mean pre-dose FEV1 was statistically significant in favour of Ultibro Breezhaler at all visits up to
week 52 compared to fluticasone/salmeterol (LS mean treatment difference 62-86 ml, p<0.001). At
week 26, Ultibro Breezhaler produced statistically significant improvement in peak FEV 1 compared to
placebo in the first 4 hours post dose (LS mean treatment difference 330 ml) (p<0.001).
FEV1 AUC:
Ultibro Breezhaler increased post-dose FEV1 AUC0-12 (primary endpoint) by 140 ml at 26 weeks
(p<0.001) compared to fluticasone/salmeterol.
Symptomatic outcomes
Breathlessness:
Ultibro Breezhaler statistically significantly reduced breathlessness as evaluated by the Transitional
Dyspnoea Index (TDI); it demonstrated a statistically significant improvement in the TDI focal score
at week 26 compared to placebo (LS mean treatment difference 1.09, p<0.001), tiotropium (LS mean
treatment difference 0.51, p=0.007) and fluticasone/salmeterol (LS mean treatment difference 0.76,
p=0.003). Improvements versus indacaterol and glycopyrronium were 0.26 and 0.21, respectively.
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A statistically significantly higher percentage of patients receiving Ultibro Breezhaler responded with
a 1 point or greater improvement in the TDI focal score at week 26 compared to placebo (68.1% and
57.5% respectively, p=0.004). A higher proportion of patients demonstrated clinically meaningful
response at week 26 on Ultibro Breezhaler as compared to tiotropium (68.1% Ultibro Breezhaler
versus 59.2% tiotropium, p=0.016) and fluticasone/salmeterol (65.1% Ultibro Breezhaler versus
55.5% fluticasone/salmeterol, p=0.088).
Health-related quality of life:

Ultibro Breezhaler has also shown a statistically significant effect on health-related quality of life
measured using the St. George’s Respiratory Questionnaire (SGRQ) as indicated by a reduction in
SGRQ total score at 26 weeks compared to placebo (LS mean treatment difference -3.01, p=0.002)
and tiotropium (LS mean treatment difference -2.13, p=0.009) and reductions versus indacaterol and
glycopyrronium were -1.09 and -1.18, respectively. At 64 weeks, the reduction compared to
tiotropium was statistically significant (LS mean treatment difference -2.69, p<0.001). At 52 weeks,
the reduction compared to fluticasone/salmeterol was statistically significant (LS mean treatment
difference -1.3, p=0.003).
A higher percentage of patients receiving Ultibro Breezhaler responded with a clinically meaningful
improvement in SGRQ score (defined as a decrease of at least 4 units from baseline) at week 26
compared to placebo (63.7% and 56.6% respectively, p=0.088) and tiotropium (63.7% Ultibro
Breezhaler vs. 56.4% tiotropium, p=0.047), at week 64 compared to glycopyrronium and tiotropium
(57.3% Ultibro Breezhaler versus 51.8% glycopyrronium, p=0.055; versus 50.8% tiotropium,
p=0.051, respectively), and at week 52 compared to fluticasone/salmeterol (49.2% Ultibro Breezhaler
vs. 43.7% fluticasone/salmeterol, odds ratio: 1.30, p<0.001).
Daily activities
Ultibro Breezhaler demonstrated a statistically superior improvement versus tiotropium in the
percentage of “days able to perform usual daily activities” over 26 weeks (LS mean treatment
difference 8.45%, p<0.001). At week 64, Ultibro Breezhaler showed numerical improvement over
glycopyrronium (LS mean treatment difference 1.95%; p=0.175) and statistical improvement over
tiotropium (LS mean treatment difference 4.96%; p=0.001).
COPD exacerbations
In a 64-week study comparing Ultibro Breezhaler (n=729), glycopyrronium (n=739) and tiotropium
(n=737), Ultibro Breezhaler reduced the annualised rate of moderate or severe COPD exacerbations by
12% compared to glycopyrronium (p=0.038) and by 10% compared to tiotropium (p=0.096). The
number of moderate or severe COPD exacerbations/patient-years was 0.94 for Ultibro Breezhaler
(812 events), 1.07 for glycopyrronium (900 events) and 1.06 for tiotropium (898 events). Ultibro
Breezhaler also statistically significantly reduced the annualised rate of all COPD exacerbations (mild,
moderate or severe) by 15% as compared to glycopyrronium (p=0.001) and 14% as compared to
tiotropium (p=0.002). The number of all COPD exacerbations/patient-years was 3.34 for Ultibro
Breezhaler (2,893 events), 3.92 for glycopyrronium (3,294 events) and 3.89 for tiotropium
(3,301 events).
In the 52-week study comparing Ultibro Breezhaler (n=1,675) and fluticasone/salmeterol (n=1,679),
Ultibro Breezhaler met the primary study objective of non-inferiority in rate of all COPD
exacerbations (mild, moderate or severe) compared to fluticasone/salmeterol. The number of all
COPD exacerbations/patient-years was 3.59 for Ultibro Breezhaler (4,531 events) and 4.03 for
fluticasone/salmeterol (4,969 events). Ultibro Breezhaler further showed superiority in reducing the
annualised rate of all exacerbations by 11% versus fluticasone/salmeterol (p=0.003).
12
Compared to fluticasone/salmeterol, Ultibro Breezhaler reduced the annualised rate of both moderate
or severe exacerbations by 17% (p<0.001), and of severe exacerbations (requiring hospitalisation) by
13% (not statistically significant, p=0.231). The number of moderate or severe COPD
exacerbations/patient-years was 0.98 for Ultibro Breezhaler (1,265 events) and 1.19 for
fluticasone/salmeterol (1,452 events). Ultibro Breezhaler prolonged time to first moderate or severe
exacerbation with a 22% reduction in risk of an exacerbation (p<0.001) and prolonged time to first
severe exacerbation with a 19% reduction in risk of an exacerbation (p=0.046).
The incidence of pneumonia was 3.2% in the Ultibro Breezhaler arm compared to 4.8% in the
fluticasone/salmeterol arm (p=0.017). Time to first pneumonia was prolonged with Ultibro Breezhaler
compared to fluticasone/salmeterol (p=0.013).
In another study comparing Ultibro Breezhaler (n=258) and fluticasone/salmeterol (n=264), for
26 weeks, the number of moderate or severe COPD exacerbations/patient-years was 0.15 versus 0.18
(18 events versus 22 events), respectively (p=0.512), and the number of all COPD
exacerbations/patients-years (mild, moderate or severe) was 0.72 versus 0.94 (86 events versus
113 events), respectively (p=0.098).
Use of rescue medication

Over 26 weeks, Ultibro Breezhaler statistically significantly reduced the use of rescue medication
(salbutamol) by 0.96 puffs per day (p<0.001) compared to placebo, 0.54 puffs per day (p<0.001)
compared to tiotropium and 0.39 puffs per day (p=0.019) compared to fluticasone/salmeterol. Over
64 weeks, this reduction was 0.76 puffs per day (p<0.001) compared to tiotropium. Over 52 weeks,
Ultibro Breezhaler reduced the use of rescue medication by 0.25 puffs per day compared to
fluticasone/salmeterol (p<0.001).
Exercise tolerance
Ultibro Breezhaler, dosed in the morning, reduced dynamic hyperinflation and improved the length of
time exercise could be maintained from the first dose onwards. On the first day of treatment,
inspiratory capacity under exercise was significantly improved (LS mean treatment difference 250 ml,
p<0.001) compared to placebo. After three weeks of treatment, the improvement in inspiratory
capacity with Ultibro Breezhaler was greater (LS mean treatment difference 320 ml, p<0.001) and
exercise endurance time increased (LS mean treatment difference 59.5 seconds, p=0.006) compared to
placebo.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with
Ultibro Breezhaler in all subsets of the paediatric population in chronic obstructive pulmonary disease
(COPD) (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Absorption
Ultibro Breezhaler
Following inhalation of Ultibro Breezhaler, the median time to reach peak plasma concentrations of
indacaterol and glycopyrronium was approximately 15 minutes and 5 minutes, respectively.
Based on the in vitro performance data, the dose of indacaterol delivered to the lung is expected to be
similar for Ultibro Breezhaler and indacaterol monotherapy product. Steady-state exposure to
indacaterol after Ultibro Breezhaler inhalation was either similar or slightly lower than systemic
exposure after indacaterol monotherapy product inhalation.
Following inhalation of Ultibro Breezhaler, the absolute bioavailability of indacaterol has been
estimated to range from 61 to 85% of the delivered dose, and that of glycopyrronium was about 47%
of the delivered dose.
13
Steady-state exposure to glycopyrronium after Ultibro Breezhaler inhalation was similar to systemic
exposure after glycopyrronium monotherapy product inhalation.
Indacaterol
Steady state concentrations of indacaterol were achieved within 12 to 15 days following once-daily
administration. The mean accumulation ratio of indacaterol, i.e. AUC over the 24-h dosing interval on
day 14 or day 15 compared to day 1, was in the range of 2.9 to 3.8 for once-daily inhaled doses
between 60 micrograms and 480 micrograms (delivered dose).
Glycopyrronium
In patients with COPD, pharmacokinetic steady-state of glycopyrronium was reached within one week
of the start of treatment. The steady-state mean peak and trough plasma concentrations of
glycopyrronium at the recommended once-daily dosing regimen were 166 picograms/ml and
8 picograms/ml, respectively. Steady-state exposure to glycopyrronium (AUC over the 24-hour dosing
interval) was about 1.4- to 1.7-fold higher than after the first dose.
Distribution
Indacaterol
After intravenous infusion the volume of distribution of indacaterol during the terminal elimination
phase was 2557 litres indicating an extensive distribution. The in vitro human serum and plasma
protein binding was about 95%.
Glycopyrronium
After intravenous dosing, the steady-state volume of distribution of glycopyrronium was 83 litres and
the volume of distribution in the terminal phase was 376 litres. The apparent volume of distribution in
the terminal phase following inhalation was almost 20-fold larger, which reflects the much slower
elimination after inhalation. The in vitro human plasma protein binding of glycopyrronium was 38%
to 41% at concentrations of 1 to 10 nanograms/ml.
Biotransformation
Indacaterol
After oral administration of radiolabelled indacaterol in a human ADME (absorption, distribution,
metabolism, excretion) study, unchanged indacaterol was the main component in serum, accounting
for about one third of total drug-related AUC over 24 hours. A hydroxylated derivative was the most
prominent metabolite in serum. Phenolic O-glucuronides of indacaterol and hydroxylated indacaterol
were further prominent metabolites. A diastereomer of the hydroxylated derivative, a N-glucuronide of
indacaterol, and C- and N-dealkylated products were further metabolites identified.
In vitro the UGT1A1 isoform is a major contributor to the metabolic clearance of indacaterol.
However, as shown in a clinical study in populations with different UGT1A1 genotypes, systemic
exposure to indacaterol is not significantly affected by the UGT1A1-genotype.
Oxidative metabolites were found in incubations with recombinant CYP1A1, CYP2D6, and CYP3A4.
CYP3A4 is concluded to be the predominant isoenzyme responsible for hydroxylation of indacaterol.
In vitro investigations further indicated that indacaterol is a low affinity substrate for the efflux pump
P-gp.
Glycopyrronium
In vitro metabolism studies showed consistent metabolic pathways for glycopyrronium bromide
between animals and humans. Hydroxylation resulting in a variety of mono- and bis-hydroxylated
metabolites and direct hydrolysis resulting in the formation of a carboxylic acid derivative (M9) were
seen. In vivo, M9 is formed from the swallowed dose fraction of inhaled glycopyrronium bromide.
Glucuronide and/or sulfate conjugates of glycopyrronium were found in urine of humans after
repeated inhalation, accounting for about 3% of the delivered dose.
14
Multiple CYP isoenzymes contribute to the oxidative biotransformation of glycopyrronium. Inhibition
or induction of the metabolism of glycopyrronium is unlikely to result in a relevant change of systemic
exposure to the active substance.
In vitro inhibition studies demonstrated that glycopyrronium bromide has no relevant capacity to
inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5, the
efflux transporters MDR1, MRP2 or MXR, and the uptake transporters OCT1 or OCT2. In vitro
enzyme induction studies did not indicate a clinically relevant induction by glycopyrronium bromide
for any of the cytochrome P450 isoenzymes tested or for UGT1A1 and the transporters MDR1 and
MRP2.
Elimination
Indacaterol
In clinical studies, the amount of indacaterol excreted unchanged via urine was generally lower than
2.5% of the delivered dose. Renal clearance of indacaterol was, on average, between 0.46 and
1.2 litres/hour. When compared with the serum clearance of indacaterol of 23.3 litres/hour, it is
evident that renal clearance plays a minor role (about 2 to 5% of systemic clearance) in the elimination
of systemically available indacaterol.
In a human ADME study, indacaterol given orally was excreted into human faeces primarily as
unchanged parent substance (54% of the dose) and, to a lesser extent, hydroxylated indacaterol
metabolites (23% of the dose).
Indacaterol serum concentrations declined in a multi-phasic manner with an average terminal half-life
ranging from 45.5 to 126 hours. The effective half-life, calculated from the accumulation of
indacaterol after repeated dosing ranged from 40 to 52 hours which is consistent with the observed
time-to-steady state of approximately 12-15 days.
Glycopyrronium
After intravenous administration of [3H]-labelled glycopyrronium bromide, the mean urinary excretion
of radioactivity in 48 hours amounted to 85% of the dose. A further 5% of the dose was found in the
bile.
Renal elimination of parent drug accounts for about 60 to 70% of total clearance of systemically
available glycopyrronium whereas non-renal clearance accounts for about 30 to 40%. Biliary
clearance contributes to the non-renal clearance, but the majority of non-renal clearance is thought to
be due to metabolism.
Mean renal clearance of glycopyrronium following inhalation was in the range of 17.4 and
24.4 litres/h. Active tubular secretion contributes to the renal elimination of glycopyrronium. Up to
23% of the delivered dose was found in urine as parent drug.
Glycopyrronium plasma concentrations declined in a multi-phasic manner. The mean terminal

elimination half-life was much longer after inhalation (33 to 57 hours) than after intravenous
(6.2 hours) and oral (2.8 hours) administration. The elimination pattern suggests sustained lung
absorption and/or transfer of glycopyrronium into the systemic circulation at and beyond 24 h after
inhalation.
Linearity/non-linearity
Indacaterol
Systemic exposure to indacaterol increased with increasing (delivered) dose (120 micrograms to
480 micrograms) in a dose proportional manner.
15
Glycopyrronium
In COPD patients both systemic exposure and total urinary excretion of glycopyrronium at
pharmacokinetic steady state increased about dose-proportionally over the (delivered) dose range of 44
to 176 micrograms.
Special populations
Ultibro Breezhaler
A population pharmacokinetic analysis of data in COPD patients after inhalation of Ultibro Breezhaler
indicated no significant effect of age, gender and (lean body) weight on the systemic exposure to
indacaterol and glycopyrronium. Lean body weight (which is a function of weight and height) was
identified as a covariate. A negative correlation between systemic exposure and lean body weight (or
body weight) was observed; however, no dose adjustment is recommended due to the magnitude of the
change or the predictive precision of lean body weight.
Smoking status and baseline FEV1 had no apparent effect on systemic exposure to indacaterol and
glycopyrronium after inhalation of Ultibro Breezhaler.
Indacaterol
A population pharmacokinetic analysis showed that there is no clinically relevant effect of age (adults
up to 88 years), sex, weight (32-168 kg) or race on the pharmacokinetics of indacaterol. It did not
suggest any difference between ethnic subgroups in this population.
Glycopyrronium
A population pharmacokinetic analysis of data in COPD patients identified body weight and age as
factors contributing to inter-patient variability in systemic exposure. Glycopyrronium at the
recommended dose can be safely used in all age and body weight groups.
Gender, smoking status and baseline FEV1 had no apparent effect on systemic exposure.
Patients with hepatic impairment

Ultibro Breezhaler:
Based on the clinical pharmacokinetic characteristics of its monotherapy components, Ultibro
Breezhaler can be used at the recommended dose in patients with mild and moderate hepatic
impairment. No data are available for subjects with severe hepatic impairment.
Indacaterol:
Patients with mild and moderate hepatic impairment showed no relevant changes in C max or AUC of
indacaterol, nor did protein binding differ between mild and moderate hepatic impaired subjects and
their healthy controls. Studies in subjects with severe hepatic impairment were not performed.
Glycopyrronium:
Clinical studies have not been conducted in patients with hepatic impairment. Glycopyrronium is
cleared predominantly from the systemic circulation by renal excretion. Impairment of the hepatic
metabolism of glycopyrronium is not thought to result in a clinically relevant increase of systemic
exposure.
16
Patients with renal impairment
Ultibro Breezhaler:
Based on the clinical pharmacokinetic characteristics of its monotherapy components, Ultibro
Breezhaler can be used at the recommended dose in patients with mild to moderate renal impairment.
In patients with severe renal impairment or end-stage renal disease requiring dialysis, Ultibro
Breezhaler should be used only if the expected benefit outweighs the potential risk.
Indacaterol:
Due to the very low contribution of the urinary pathway to total body elimination of indacaterol
maleate, a study in renal impaired subjects was not performed.
Glycopyrronium:
Renal impairment has an impact on the systemic exposure to glycopyrronium bromide. A moderate
mean increase in total systemic exposure (AUC last) of up to 1.4-fold was seen in subjects with mild and
moderate renal impairment and up to 2.2-fold in subjects with severe renal impairment and end-stage
renal disease. In COPD patients with mild and moderate renal impairment (estimated glomerular
filtration rate, eGFR ≥30 ml/min/1.73 m2) glycopyrronium bromide can be used at the recommended
dose.
Ethnicity
Ultibro Breezhaler:
There were no major differences in total systemic exposure (AUC) for both compounds between
Japanese and Caucasian subjects. Insufficient pharmacokinetic data is available for other ethnicities or
races.
Indacaterol:
No difference between ethnic subgroups was identified. Limited treatment experience is available for
the black population.
Glycopyrronium:
There were no major differences in total systemic exposure (AUC) between Japanese and Caucasian
subjects. Insufficient pharmacokinetic data is available for other ethnicities or races.
5.3 Preclinical safety data
Ultibro Breezhaler
Pre-clinical studies included in vitro and in vivo safety pharmacology assessments, repeated-dose
inhalation toxicity studies in rats and dogs and an inhalation embryo-foetal development study in rats.
Increased heart rates were apparent in dogs at all doses of Ultibro Breezhaler and each monotherapy
component. The effects on heart rate for Ultibro Breezhaler increased in magnitude and duration when
compared with the changes observed for each component alone consistent with an additive response.
Shortening of electrocardiograph intervals and decreased systolic and diastolic blood pressure were
also apparent. Indacaterol administered to dogs alone or in Ultibro Breezhaler was associated with a
similar incidence and severity of myocardial lesions. Systemic exposures (AUC) at the
no-observed-adverse-effect level (NOAEL) for myocardial lesions were 64- and 59-fold higher than in
humans, for each component respectively.
No effects on the embryo or foetus were seen at any dose level of Ultibro Breezhaler during an
embryo-foetal development study in rats. Systemic exposures (AUC) at the
no-observed-adverse-effect level (NOAEL) were 79- and 126-fold higher than in humans, for
indacaterol and glycopyrronium respectively.
17
Indacaterol
Effects on the cardiovascular system attributable to the beta 2-agonistic properties of indacaterol
included tachycardia, arrhythmias and myocardial lesions in dogs. Mild irritancy of the nasal cavity
and larynx were seen in rodents. All these findings occurred at exposures sufficiently in excess of
those anticipated in humans.
Although indacaterol did not affect general reproductive performance in a rat fertility study, a decrease
in the number of pregnant F1 offspring was observed in the peri- and post-developmental rat study at
an exposure 14-fold higher than in humans treated with indacaterol. Indacaterol and its metabolites
transferred rapidly into the milk of lactating rats.Indacaterol was not embryotoxic or teratogenic in rats
or rabbits.
Genotoxicity studies did not reveal any mutagenic or clastogenic potential. Carcinogenicity was
assessed in a two-year rat study and a six-month transgenic mouse study. Increased incidences of
benign ovarian leiomyoma and focal hyperplasia of ovarian smooth muscle in rats were consistent
with similar findings reported for other beta 2-adrenergic agonists. No evidence of carcinogenicity was
seen in mice. Systemic exposures (AUC) in rats and mice at the no-observed-adverse-effect levels in
these studies were at least 7- and 49-fold higher, respectively, than in humans treated with indacaterol
once a day at the maximum recommended therapeutic dose.
Glycopyrronium
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction
and development.
Effects attributable to the muscarinic receptor antagonist properties of glycopyrronium bromide

included mild to moderate increases in heart rate in dogs, lens opacities in rats and, reversible changes
associated with reduced glandular secretions in rats and dogs. Mild irritancy or adaptive changes in the
respiratory tract were seen in rats. All these findings occurred at exposures sufficiently in excess of
those anticipated in humans.
Glycopyrronium was not teratogenic in rats or rabbits following inhalation administration. Fertility
and pre- and post-natal development were not affected in rats. Glycopyrronium bromide and its
metabolites did not significantly cross the placental barrier of pregnant mice, rabbits and dogs.
Glycopyrronium bromide (including its metabolites) was excreted into the milk of lactating rats and
reached up to 10-fold higher concentrations in the milk than in the blood of the dam.
Genotoxicity studies did not reveal any mutagenic or clastogenic potential for glycopyrronium
bromide. Carcinogenicity studies in transgenic mice using oral administration and in rats using
inhalation administration revealed no evidence of carcinogenicity at systemic exposures (AUC) of
approximately 53-fold higher in mice and 75-fold higher in rats than the maximum recommended dose
once daily for humans.
18
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule content
Lactose monohydrate
Magnesium stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
The inhaler in each pack should be disposed of after all capsules in that pack have been used.
6.4 Special precautions for storage
Do not store above 25°C.
The capsules must always be stored in the original blister to protect from moisture and only removed
immediately before use.
6.5 Nature and contents of container
Inhaler body and cap are made from acrylonitrile butadiene styrene, push buttons are made from
methyl metacrylate acrylonitrile butadiene styrene. Needles and springs are made from stainless steel.
PA/Alu/PVC – Alu perforated unit-dose blister. Each blister contains either 6 or 10 hard capsules.
Single pack containing 6x1, 10x1, 12x1, 30x1 or 90x1 hard capsules, together with 1 inhaler.
Multipacks containing 96 (4 packs of 24x1) hard capsules and 4 inhalers.

Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The inhaler provided with each new prescription should be used. The inhaler in each pack should be
disposed of after all capsules in that pack have been used.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
19
Instructions for handling and use
Please read the full Instructions for Use before using the Ultibro Breezhaler.
Insert Pierce and release Inhale deeply Check capsule is empty
1 2 3 Check
Step 1a: Step 2a: Step 3a: Check capsule is empty

Pull off cap Pierce capsule once Breathe out fully Open the inhaler to see if
Hold the inhaler upright. Do not blow into the any powder is left in the
Pierce capsule by firmly inhaler. capsule.
pressing both side
buttons at the same time.
You should hear a noise If there is powder left in
as the capsule is pierced. the capsule:
Only pierce the capsule  Close the inhaler.
once.  Repeat steps 3a to 3c.
Powder Empty
remaining
Step 1b: Step 3b:

Open inhaler Inhale medicine deeply
Hold the inhaler as
shown in the picture.
Place the mouthpiece in
your mouth and close
your lips firmly around
it.
Step 2b: Do not press the side
Release side buttons buttons.
20
Breathe in quickly and as
deeply as you can.
During inhalation you
will hear a whirring
noise.
You may taste the
medicine as you inhale.
Step 1c: Remove empty capsule

Remove capsule Put the empty capsule in
Separate one of the your household waste.
blisters from the blister Close the inhaler and
card. replace the cap.
Peel open the blister and
remove the capsule.
Do not push the capsule
Step 3c:
through the foil.
Do not swallow the Hold breath
capsule. Hold your breath for up
to 5 seconds.
Important Information
 Ultibro Breezhaler
capsules must always be
stored in the blister card
and only removed
 Do not push the capsule
Step 1d:
through the foil to
Insert capsule
remove it from the
Never place a capsule
blister.
directly into the
mouthpiece.  Do not swallow the
capsule.
 Do not use the Ultibro
Breezhaler capsules with
any other inhaler.
Breezhaler inhaler to
take any other capsule
medicine.
Step 1e:  Never place the capsule
Close inhaler into your mouth or the
mouthpiece of the
inhaler.
 Do not press the side
buttons more than once.
 Do not blow into the
mouthpiece.
buttons while inhaling
through the mouthpiece.
 Do not handle capsules
with wet hands.
 Never wash your inhaler
with water.
21
Your Ultibro Breezhaler Inhaler pack contains: Frequently Asked Cleaning the inhaler
 One Ultibro Breezhaler inhaler Questions Wipe the mouthpiece
 One or more blister cards, each containing either inside and outside with a
6 or 10 Ultibro Breezhaler capsules to be used in Why didn’t the inhaler clean, dry, lint-free cloth to
the inhaler Capsule Mouthpiece make a noise when I remove any powder
chamber inhaled? residue. Keep the inhaler
Cap
The capsule may be stuck dry. Never wash your
Screen
Side in the capsule chamber. If inhaler with water.
buttons
this happens, carefully
Base Blister loosen the capsule by
Inhaler Inhaler base Blister card
tapping the base of the
inhaler. Inhale the
medicine again by
repeating steps 3a to 3c.
Disposing of the inhaler
What should I do if there after use
is powder left inside the Each inhaler should be
capsule? disposed of after all
You have not received capsules have been used.
enough of your medicine. Ask your pharmacist how
Close the inhaler and to dispose of medicines
repeat steps 3a to 3c. and inhalers that are no
longer required.
I coughed after inhaling
– does this matter?
This may happen. As long
as the capsule is empty
you have received enough
of your medicine.
I felt small pieces of the

capsule on my tongue –
does this matter?
This can happen. It is not
harmful. The chances of
the capsule breaking into
small pieces will be
increased if the capsule is
pierced more than once.
22
7. MARKETING AUTHORISATION HOLDER
Novartis Europharm Limited

Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/13/862/001-008
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 19 September 2013

Date of latest renewal: 22 May 2018
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu.
23
ANNEX II
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY

AND USE
C. OTHER CONDITIONS AND REQUIREMENTS OF THE

MARKETING AUTHORISATION
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE

SAFE AND EFFECTIVE USE OF THE MEDICINAL
PRODUCT
24
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
Name and address of the manufacturer responsible for batch release
Novartis Pharma GmbH

Roonstraße 25
D-90429 Nuremberg
Germany
Novartis Farmacéutica SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
Medicinal product subject to medical prescription.
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING

AUTHORISATION
 Periodic safety update reports (PSURs)
The requirements for submission of PSURs for this medicinal product are set out in the list of Union
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any
subsequent updates published on the European medicines web-portal.
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

EFFECTIVE USE OF THE MEDICINAL PRODUCT
 Risk management plan (RMP)
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing
authorisation and any agreed subsequent updates of the RMP.
An updated RMP should be submitted:

 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information
being received that may lead to a significant change to the benefit/risk profile or as the result of
an important (pharmacovigilance or risk minimisation) milestone being reached.
25
ANNEX III
LABELLING AND PACKAGE LEAFLET
26
A. LABELLING
27
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON OF UNIT PACK
Ultibro Breezhaler 85 micrograms/43 micrograms inhalation powder, hard capsules

indacaterol/glycopyrronium
2. STATEMENT OF ACTIVE SUBSTANCE(S)
Each capsule contains 110 microgram indacaterol and 50 microgram glycopyrronium. The amount of
indacaterol and glycopyrronium inhaled is 85 micrograms (equivalent to 110 micrograms of
indacaterol maleate) and 43 micrograms (equivalent to 54 micrograms of glycopyrronium bromide),
respectively.
3. LIST OF EXCIPIENTS
Also contains: lactose and magnesium stearate.

See package leaflet for further information.
4. PHARMACEUTICAL FORM AND CONTENTS
Inhalation powder, hard capsule
6 x 1 capsules + 1 inhaler
5. METHOD AND ROUTE(S) OF ADMINISTRATION
For use only with the inhaler provided in the pack.

Do not swallow capsules.
Read the package leaflet before use.
Inhalation use
Treatment for 90 days [90 x 1 capsules + 1 inhaler only].
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
28
8. EXPIRY DATE
EXP
9. SPECIAL STORAGE CONDITIONS

Store the capsules in the original blister in order to protect from moisture and do not remove until
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Vista Building
Dublin 4
Ireland
EU/1/13/862/001 6 capsules + 1 inhaler

13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Ultibro Breezhaler
29
17. UNIQUE IDENTIFIER – 2D BARCODE
2D barcode carrying the unique identifier included.
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA
PC
SN
NN
30
OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX)

respectively.

Multipack: 96 (4 packs of 24 x 1) capsules + 4 inhalers.


Inhalation use

31
8. EXPIRY DATE
EXP


APPROPRIATE

Vista Building
Dublin 4
Ireland
EU/1/13/862/005 Multipack comprising 4 packs (24 capsules + 1 inhaler)

13. BATCH NUMBER
Lot
Ultibro Breezhaler
32
2D barcode carrying the unique identifier included.
PC
SN
NN
33
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX)

respectively.

24 x 1 capsules + 1 inhaler. Component of a multipack. Not to be sold separately.


Inhalation use

34
8. EXPIRY DATE
EXP


APPROPRIATE

Vista Building
Dublin 4
Ireland

13. BATCH NUMBER
Lot
Ultibro Breezhaler
35
36
INNER LID OF OUTER CARTON OF UNIT PACK AND OF INTERMEDIATE CARTON OF

MULTIPACK
1. OTHER
1 Insert
2 Pierce and release
3 Inhale deeply
Check Check capsule is empty
Read the leaflet before use.
37
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
BLISTERS
Ultibro Breezhaler 85 mcg/43 mcg inhalation powder

2. NAME OF THE MARKETING AUTHORISATION HOLDER
3. EXPIRY DATE
EXP
4. BATCH NUMBER
Lot
5. OTHER
Inhalation use only
38
B. PACKAGE LEAFLET
39
Package leaflet: Information for the user

Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,
even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What Ultibro Breezhaler is and what it is used for

2. What you need to know before you use Ultibro Breezhaler
3. How to use Ultibro Breezhaler
4. Possible side effects
5. How to store Ultibro Breezhaler
6. Contents of the pack and other information
Instructions for use of Ultibro Breezhaler inhaler
1. What Ultibro Breezhaler is and what it is used for
What Ultibro Breezhaler is

This medicine contains two active substances called indacaterol and glycopyrronium. These belong to
a group of medicines called bronchodilators.
What Ultibro Breezhaler is used for

This medicine is used to make breathing easier for adult patients who have breathing difficulties due to
a lung disease called chronic obstructive pulmonary disease (COPD). In COPD the muscles around the
airways tighten. This makes breathing difficult. This medicine blocks the tightening of these muscles
in the lungs, making it easier for air to get in and out of the lungs.
If you use this medicine once a day, it will help to reduce the effects of COPD on your everyday life.
2. What you need to know before you use Ultibro Breezhaler
Do not use Ultibro Breezhaler

- if you are allergic to indacaterol or glycopyrronium or any of the other ingredients of this
medicine (listed in section 6).
40
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Ultibro Breezhaler if any of the following
applies to you:
- you have asthma - this medicine should not be used as a treatment for asthma.
- you have heart problems.
- you have seizure or fits.
- you have thyroid gland problems (thyrotoxicosis).
- you have diabetes.
- you are using any medicines for your lung disease which contain active substances similar
(same class) to those in Ultibro Breezhaler (see section “Other medicines and Ultibro
Breezhaler”).
- you have kidney problems.
- you have severe liver problems.
- you have an eye problem called narrow-angle glaucoma.
- you have difficulty passing urine.
If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse
before using this medicine.
During treatment with Ultibro Breezhaler

- Stop using this medicine and seek medical help immediately if you experience any of the
following:
- eye pain or discomfort, temporary blurring of vision, visual halos or coloured images in
association with red eyes – these may be signs of an acute attack of narrow-angle
glaucoma.
- difficulty breathing or swallowing, swelling of the tongue, lips or face, skin rash, itching
and hives (signs of an allergic reaction).
- tightness of the chest, coughing, wheezing or breathlessness immediately after using this
medicine – these may be signs of a condition called paradoxical bronchospasm.
- Tell your doctor immediately if your COPD symptoms such as breathlessness, wheezing or
cough do not improve or get worse.
Ultibro Breezhaler is used as an ongoing treatment for your COPD. Do not use this medicine to treat a
sudden attack of breathlessness or wheezing.
Children and adolescents

Do not give this medicine to children or adolescents below the age of 18 years. This is because it has
not been studied in this age group.
Other medicines and Ultibro Breezhaler

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
In particular, please tell your doctor or pharmacist if you are using:
- any medicines that may be similar to Ultibro Breezhaler (contain similar active substances).
- medicines called beta blockers that may be used for high blood pressure or other heart problems
(such as propranolol), or for an eye problem called glaucoma (such as timolol).
- medicines that lower the amount of potassium in your blood. These include:
- steroids (such as prednisolone),
- diuretics (water tablets) used for high blood pressure (such as hydrochlorothiazide),
- medicines for breathing problems (such as theophylline).
Pregnancy and breast-feeding

There are no data on the use of this medicine in pregnant women and it is not known whether the
active substances of this medicine pass into human milk. Indacaterol, one of the active substances in
Ultibro Breezhaler, may prevent labour due to its effect on the uterus.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask
your doctor or pharmacist for advice before using this medicine. You should not use Ultibro
Breezhaler unless your doctor tells you to do so.
41
Driving and using machines
It is unlikely that this medicine will affect your ability to drive and use machines. However, this
medicine may cause dizziness (see section 4). If you feel dizzy while taking this medicine, do not
drive or use machines.
Ultibro Breezhaler contains lactose

This medicine contains lactose (23.5 mg per capsule). If you have been told by your doctor that you
have an intolerance to some sugars, contact your doctor before using this medicine.
Ask your doctor or pharmacist for advice before using any medicine.
3. How to use Ultibro Breezhaler
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor
or pharmacist if you are not sure.
How much Ultibro Breezhaler to use

The usual dose is to inhale the content of one capsule each day.
You only need to inhale once a day because the effect of this medicine lasts for 24 hours. Do not use
more than your doctor tells you to use.
Elderly (age 75 years and over)

You can use this medicine if you are aged 75 years and over at the same dose as for other adults.
When to inhale Ultibro Breezhaler

Use this medicine at the same time each day. This will also help you to remember to use it.
You can inhale Ultibro Breezhaler any time before or after food or drink.
How to inhale Ultibro Breezhaler

- Ultibro Breezhaler is for inhalation use.
- In this pack, you will find an inhaler and capsules (in blisters) that contain the medicine as
inhalation powder. Only use the capsules with the inhaler provided in this pack (Ultibro
Breezhaler inhaler). The capsules should remain in the blister until you need to use them.
- Peel the backing away from the blister to open it - do not push the capsule through the foil.
- When you start a new pack, use the new Ultibro Breezhaler inhaler that is supplied in the pack.
- Dispose of the inhaler in each pack after all capsules in that pack have been used.
- Do not swallow the capsules.
- Please read the instructions at the end of this leaflet for more information on how to use the
inhaler.
If you use more Ultibro Breezhaler than you should

If you have inhaled too much of this medicine or if someone else accidentally uses your capsules, you
must immediately either tell your doctor or go to the nearest emergency unit. Show the pack of Ultibro
Breezhaler. Medical attention may be needed. You may notice that your heart is beating faster than
usual, or you may have a headache, feel drowsy, feel nauseous or have to vomit, or you may notice
visual disturbances, feel constipated or have difficulty when passing urine.
If you forget to use Ultibro Breezhaler

If you forget to inhale a dose at the usual time, inhale one as soon as possible that day. Then, inhale
the next dose as usual the next day. Do not inhale more than one dose on the same day.
42
How long to continue your treatment with Ultibro Breezhaler
 Keep using Ultibro Breezhaler for as long as your doctor tells you.
 COPD is a long-term disease and you should use Ultibro Breezhaler every day and not only
when you have breathing problems or other symptoms of COPD.
If you have questions about how long to continue your treatment with this medicine, talk to your
doctor or pharmacist.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects may be serious:
Common (may affect up to 1 in 10 people)

 difficulty breathing or swallowing, swelling of tongue, lips or face, urticaria, skin rash – these
may be signs of an allergic reaction.
 feeling tired or very thirsty, having an increased appetite without gaining weight and passing
more urine than usual – these may be signs of high level of sugar in the blood (hyperglycaemia).
Uncommon (may affect up to 1 in 100 people)

 crushing chest pain with increased sweating – this may be a serious heart problem (ischaemic
heart disease).
 swelling mainly of the tongue, lips, face or throat (possible signs of angioedema).
 difficulty breathing with wheezing or coughing.
 eye pain or discomfort, temporary blurring of vision, visual halos or coloured images in
association with red eyes – these may be signs of glaucoma.
 irregular heartbeat.
If you get any of these serious side effects, seek medical help immediately.
Other side effects may include:
Very common (may affect more than 1 in 10 people)

 blocked nose, sneezing, cough, headache with or without fever - these may be signs of an upper
respiratory tract infection.
Common
 combination of sore throat and runny nose - these may be signs of nasopharyngitis.
 painful and frequent urination – these may be signs of a urinary tract infection called cystitis.
 feeling of pressure or pain in the cheeks and forehead – these may be signs of inflammation of
the sinuses called sinusitis.
 runny or stuffy nose.
 dizziness.
 headache.
 cough.
 sore throat.
 upset stomach, indigestion.
 dental caries.
 difficulty and pain when passing urine – these may be signs of a bladder obstruction or urinary
retention.
 fever.
 chest pain.
43
Uncommon
 difficulty sleeping.
 fast heart beat.
 palpitations – signs of abnormal heart beat.
 voice alteration (hoarseness).
 nose bleeds.
 diarrhoea or stomach ache.
 dry mouth.
 itching or rash.
 pain that affects the muscles, ligaments, tendons, joints and bones.
 muscle spasm.
 muscle pain, aches or tenderness.
 pain in arms or legs.
 swollen hands, ankles and feet.
 tiredness.
Rare (may affect up to 1 in 1000 people)

 tingling or numbness.
Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on the
safety of this medicine.
5. How to store Ultibro Breezhaler
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after “EXP”.
The expiry date refers to the last day of that month.
Do not use this medicine if you notice that the pack is damaged or shows signs of tampering.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to
throw away medicines you no longer use. These measures will help protect the environment.
44
6. Contents of the pack and other information
What Ultibro Breezhaler contains

- The active substances are indacaterol (as maleate) and glycopyrronium bromide. Each capsule
contains 143 micrograms of indacaterol maleate equivalent to 110 micrograms of indacaterol
and 63 micrograms of glycopyrronium bromide equivalent to 50 micrograms of
glycopyrronium. The delivered dose (the dose that leaves the mouthpiece of the inhaler) is
equivalent to 85 micrograms of indacaterol (equivalent to 110 micrograms of indacaterol
maleate) and 43 micrograms of glycopyrronium (equivalent to 54 micrograms of
glycopyrronium bromide).
- The other ingredients of the inhalation powder are lactose monohydrate and magnesium stearate
(see section 2 under “Ultibro Breezhaler contains lactose”).
What Ultibro Breezhaler looks like and contents of the pack
Ultibro Breezhaler 85 micrograms/43 micrograms inhalation powder, hard capsules are transparent
and yellow and contain a white to almost white powder. They have the product code “IGP110.50”
printed in blue under two blue bars on the body and the company logo ( ) printed in black on the cap.
In this pack, you will find a device called an inhaler together with capsules in blister strips. Each
blister contains either 6 or 10 hard capsules.
The following pack sizes are available:

Single pack containing 6x1, 10x1, 12x1, 30x1 or 90x1 hard capsules, together with 1 inhaler.

Not all pack sizes may be available in your country.
Marketing Authorisation Holder

Vista Building
Dublin 4
Ireland
Manufacturer
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
Novartis Farmacéutica SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
45
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50
България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11
Česká republika Magyarország

Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00
Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872
Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111
Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00
Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570
España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888
France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600
Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01
Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50
Ísland Slovenská republika

Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439
Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200
46
Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00
Latvija United Kingdom (Northern Ireland)

SIA Novartis Baltics Novartis Ireland Limited
Tel: +371 67 887 070 Tel: +44 1276 698370
This leaflet was last revised in
Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.
47
Please read the full Instructions for Use before using the Ultibro Breezhaler.
Insert Pierce and release Inhale deeply Check capsule is empty
1 2 3 Check
Step 1a: Step 2a: Step 3a: Check capsule is empty

Pull off cap Pierce capsule once Breathe out fully Open the inhaler to see if
Hold the inhaler upright. Do not blow into the any powder is left in the
Pierce capsule by firmly inhaler. capsule.
pressing both side
buttons at the same time.
You should hear a noise If there is powder left in
as the capsule is pierced. the capsule:
Only pierce the capsule  Close the inhaler.
once.  Repeat steps 3a to 3c.
Powder Empty
remaining
Step 1b: Step 3b:

Open inhaler Inhale medicine deeply
Hold the inhaler as
shown in the picture.
Place the mouthpiece in
your mouth and close
your lips firmly around
it.
Step 2b: Do not press the side
Release side buttons buttons.
48
Breathe in quickly and as
deeply as you can.
During inhalation you
will hear a whirring
noise.
You may taste the
medicine as you inhale.
Step 1c: Remove empty capsule

Remove capsule Put the empty capsule in
Separate one of the your household waste.
blisters from the blister Close the inhaler and
card. replace the cap.
Peel open the blister and
remove the capsule.
Do not push the capsule
Step 3c:
through the foil.
Do not swallow the Hold breath
capsule. Hold your breath for up
to 5 seconds.
Important Information
 Ultibro Breezhaler
capsules must always be
stored in the blister card
and only removed
Step 1d:  Do not push the capsule
Insert capsule through the foil to
Never place a capsule remove it from the
directly into the blister.
mouthpiece.  Do not swallow the
capsule.
Breezhaler capsules with
any other inhaler.
Breezhaler inhaler to
take any other capsule
medicine.
 Never place the capsule
into your mouth or the
Step 1e: mouthpiece of the
Close inhaler inhaler.
buttons more than once.
 Do not blow into the
mouthpiece.
buttons while inhaling
through the mouthpiece.
 Do not handle capsules
with wet hands.
 Never wash your inhaler
with water.
49
Your Ultibro Breezhaler Inhaler pack contains: Frequently Asked Cleaning the inhaler
 One Ultibro Breezhaler inhaler Questions Wipe the mouthpiece
 One or more blister cards, each containing either inside and outside with a
6 or 10 Ultibro Breezhaler capsules to be used in Why didn’t the inhaler clean, dry, lint-free cloth to
the inhaler make a noise when I remove any powder
Mouthpiece
inhaled? residue. Keep the inhaler
Capsule
chamber The capsule may be stuck dry. Never wash your
in the capsule chamber. If inhaler with water.
Cap
Screen this happens, carefully
Side loosen the capsule by
buttons
tapping the base of the
Blister
Base inhaler. Inhale the
Blister card
Inhaler Inhaler base medicine again by
repeating steps 3a to 3c.
Disposing of the inhaler
What should I do if there after use
is powder left inside the Each inhaler should be
capsule? disposed of after all
You have not received capsules have been used.
enough of your medicine. Ask your pharmacist how
Close the inhaler and to dispose of medicines
repeat steps 3a to 3c. and inhalers that are no
longer required.
I coughed after inhaling
– does this matter?
This may happen. As long
as the capsule is empty
you have received enough
of your medicine.
I felt small pieces of the

capsule on my tongue –
does this matter?
This can happen. It is not
harmful. The chances of
the capsule breaking into
small pieces will be
increased if the capsule is
pierced more than once.
50

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

Ultibro Breezhaler 85 micrograms/43 micrograms inhalation powder hard capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Excipient(s) with known effect

Each capsule contains 23.5 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Inhalation powder, hard capsule (inhalation powder).

4.1 Therapeutic indications

Ultibro Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult

4.2 Posology and method of administration

For inhalation use only. The capsules must not be swallowed.

4.4 Special warnings and precautions for use

Not for acute use

Immediate hypersensitivity reactions have been reported after administration of indacaterol or

Administration of Ultibro Breezhaler may result in paradoxical bronchospasm which can be

Anticholinergic effects related to glycopyrronium

Patients with severe renal impairment

Concomitant administration of orally inhaled indacaterol and glycopyrronium, under steady-state

Concomitant use not recommended

Caution required with concomitant use

Metabolic and transporter based interactions

Cimetidine or other inhibitors of organic cation transport

4.6 Fertility, pregnancy and lactation

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

Summary of the safety profile

Tabulated summary of adverse reactions

Table 1 Adverse reactions

Adverse reactions Frequency category

Description of selected adverse reactions

Cough was common, but usually of mild intensity.

Reporting of suspected adverse reactions

There is no information on clinically relevant overdosing with Ultibro Breezhaler.

5.1 Pharmacodynamic properties

Effects on heart rate

In COPD patients, supratherapeutic doses between 116 micrograms/86 micrograms and

Serum potassium and blood glucose

Clinical efficacy and safety

Trough and peak FEV1:

Treatment difference Day 1 Week 26

Health-related quality of life:

Use of rescue medication

5.2 Pharmacokinetic properties

Glycopyrronium plasma concentrations declined in a multi-phasic manner. The mean terminal

Patients with hepatic impairment

5.3 Preclinical safety data

Effects attributable to the muscarinic receptor antagonist properties of glycopyrronium bromide

6.1 List of excipients

6.3 Shelf life

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Multipacks containing 96 (4 packs of 24x1) hard capsules and 4 inhalers.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Insert Pierce and release Inhale deeply Check capsule is empty

Step 1a: Step 2a: Step 3a: Check capsule is empty

Step 1b: Step 3b: