Atectura Jun2020.SINv1 App020721

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Tradename(s)

ATECTURA® BREEZHALER® (indacaterol/mometasone furoate) 150/80 micrograms inhalation


powder, hard capsules
ATECTURA® BREEZHALER® (indacaterol/mometasone furoate) 150/160 micrograms inhalation
powder, hard capsules
ATECTURA® BREEZHALER® (indacaterol/mometasone furoate) 150/320 micrograms inhalation
powder, hard capsules

1 Description and composition


Pharmaceutical form(s)
Indacaterol/mometasone furoate 150/80 micrograms, inhalation powder, hard capsules.
Capsules with natural transparent (uncolored) cap and body containing a white to practically white
powder, with the product code “IM150-80” printed in blue on the body and the printed in blue
on the cap.

Indacaterol/mometasone furoate 150/160 micrograms, inhalation powder, hard capsules.


Capsules with natural transparent (uncolored) cap and body containing a white to practically white
powder, with the product code “M150-160” printed in grey on the body and the printed in grey
on the cap.

Indacaterol/mometasone furoate 150/320 micrograms, inhalation powder, hard capsules.


Capsules with natural transparent (uncolored) cap and body containing a white to practically white
powder, with the product code “IM150-320” printed in black on the body and the printed in
black on the cap.

Active substance(s)
Each capsule of Atectura Breezhaler 150/80 micrograms, contains 173 micrograms of indacaterol
acetate equivalent to 150 micrograms of indacaterol and 80 micrograms of mometasone furoate.
Each capsule of Atectura Breezhaler 150/160 micrograms, contains 173 micrograms of indacaterol
acetate equivalent to 150 micrograms of indacaterol and 160 micrograms of mometasone furoate.
Each capsule of Atectura Breezhaler 150/320 micrograms, contains 173 micrograms of indacaterol
acetate equivalent to 150 micrograms of indacaterol and 320 micrograms of mometasone furoate
The delivered dose of Atectura Breezhaler 150/80 micrograms (the dose that leaves the mouthpiece
of the inhaler) is equivalent to 125 micrograms indacaterol, and 62.5 micrograms mometasone furoate.
The delivered dose of Atectura Breezhaler 150/160 micrograms (the dose that leaves the mouthpiece
of the inhaler) is equivalent to 125 micrograms indacaterol, and 127.5 micrograms mometasone
furoate.
The delivered dose of Atectura Breezhaler 150/320 micrograms (the dose that leaves the mouthpiece
of the inhaler) is equivalent to 125 micrograms indacaterol, and 260 micrograms mometasone furoate.

Atectura Jun 2020.SINv1 Page 1 of 22


Excipients
Capsule fill: Lactose (as monohydrate).
Capsule shell components: Gelatin.

2 Indications
Atectura Breezhaler is indicated as a once-daily maintenance treatment of asthma in adults and
adolescents 12 years of age and older where use of a combination of long-acting beta2-agonist and
inhaled corticosteroid is appropriate.

3 Dosage regimen and administration


Dosage regimen

General target population


Inhalation of the content of one capsule of Atectura Breezhaler 150/80 micrograms once daily is
recommended in patients who require a combination of a long-acting beta2-agonist and a low dose of
inhaled corticosteroid.
Inhalation of the content of one capsule of Atectura Breezhaler 150/160 micrograms or 150/320
micrograms once-daily is recommended in patients who require a combination of a long-acting beta2-
agonist and a medium or high dose of inhaled corticosteroid.
Patients usually experience an improvement in lung function within 5 minutes of inhaling Atectura
Breezhaler. However, the patient should be informed that regular daily use is necessary to maintain
control of asthma symptoms and that use should be continued even when asymptomatic.
The maximum recommended dose is Atectura Breezhaler 150/320 micrograms once daily.

Special populations

Renal impairment
No dose adjustment is required in patients with renal impairment.

Hepatic impairment
No dose adjustment is required in patients with mild or moderate hepatic impairment. No data are
available for Atectura Breezhaler in subjects with severe hepatic impairment, therefore Atectura
Breezhaler should be used in these patients only if the expected benefit outweighs the potential risk
(see section 11 Clinical pharmacology).

Pediatric patients (below 12 years)


Atectura Breezhaler may be used in pediatric patients (12 years of age and older) at the same posology
as in adults. The safety and efficacy of Atectura Breezhaler in pediatric patients below 12 years of
age have not been established.

Geriatric patients (65 years or above)


No dose adjustment is required in elderly patients 65 years of age or older (see section 11 Clinical
pharmacology).

Atectura Jun 2020.SINv1 Page 2 of 22


Method of administration
For inhalation use only. Atectura 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 Atectura Breezhaler inhaler. The inhaler provided
with each new prescription should be used.
Atectura Breezhaler should be administered at the same time of the day each day. It can be
administered irrespective of the time of the day.
The capsules must always be stored in the blister to protect from moisture and light, and only removed
immediately before use (see section 14 Pharmaceutical information).
After inhalation, patients should rinse their mouth with water without swallowing.
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.

4 Contraindications
Atectura Breezhaler is contraindicated in patients with hypersensitivity to any of the active substances
or excipients.

5 Warnings and precautions


Deterioration of disease
Atectura Breezhaler should not be used to treat acute asthma symptoms including acute episodes of
bronchospasm, for which a short-acting bronchodilator is required. Increasing use of short-acting
bronchodilators to relieve symptoms indicates deterioration of control and patients should be
reviewed by a physician.
Patients should not stop Atectura Breezhaler treatment without physician supervision since
symptoms may recur after discontinuation.
Asthma-related adverse events and exacerbations may occur during treatment with Atectura
Breezhaler. Patients should be asked to continue treatment but to seek medical advice if asthma
symptoms remain uncontrolled or worsen after initiation of treatment with Atectura Breezhaler.
Hypersensitivity
Immediate hypersensitivity reactions have been observed after administration of Atectura Breezhaler.
If signs suggesting allergic reactions occur, in particular angioedema (including difficulties in
breathing or swallowing, swelling of the tongue, lips, and face), urticaria, or skin rash, Atectura
Breezhaler should be discontinued immediately and alternative therapy instituted.
Paradoxical bronchospasm
As with other inhalation therapy, administration of Atectura Breezhaler may result in paradoxical
bronchospasm which can be life-threatening. If paradoxical bronchospasm occurs, Atectura
Breezhaler should be discontinued immediately and alternative therapy instituted.
Cardiovascular effects of beta agonists
Like other medicinal products containing beta2-adrenergic agonists, Atectura Breezhaler may
produce a clinically significant cardiovascular effect in some patients as measured by increases in

Atectura Jun 2020.SINv1 Page 3 of 22


pulse rate, blood pressure, and/or symptoms. If such effects occur, treatment may need to be
discontinued.
Atectura Breezhaler should be used with caution in patients with cardiovascular disorders (coronary
artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), convulsive disorders
or thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists.
While beta2-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, the clinical
significance of these findings is unknown.
Therefore, long-acting beta2-adrenergic agonists (LABA) or LABA containing combination products
such as Atectura Breezhaler should be used with caution in patients with known or suspected
prolongation of the QT interval or who are treated with medicinal products affecting the QT interval.
Hypokalemia with beta agonists
Beta2-adrenergic agonists may produce significant hypokalemia 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 condition, hypokalemia may be
potentiated by hypoxia and concomitant treatment which may increase the susceptibility to cardiac
arrhythmias (see section 8 Interactions).
Clinically relevant hypokalemia has not been observed in clinical studies of Atectura Breezhaler at
the recommended therapeutic dose.
Hyperglycemia
Inhalation of high doses of beta2-adrenergic agonists and corticosteroids may produce increases in
plasma glucose. Upon initiation of treatment with Atectura Breezhaler, plasma glucose should be
monitored more closely in diabetic patients.

Prevention of oropharyngeal infections


In order to reduce the risk of oropharyngeal candida infection, patients should be advised to rinse
their mouth or gargle with water without swallowing it or brush their teeth after inhaling the
prescribed dose.
Systemic effects of corticosteroids
Systemic effects may occur with inhaled corticosteroids, particularly at high doses prescribed for
prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may
vary in individual patients and between different corticosteroid preparations.
Possible systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal
suppression, growth retardation in children and adolescents, decrease in bone mineral density,
cataracts, glaucoma, and, more rarely, a range of psychological or behavioural effects including
psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in
children). It is therefore important that the dose of inhaled corticosteroid is titrated to the lowest dose
at which effective control of asthma is maintained.
Visual disturbance may be reported with systemic and topical (including intranasal, inhaled and
intraocular) corticosteroid use. Patients presenting with symptoms such as blurred vision or other
visual disturbances should be considered for referral to an ophthalmologist for evaluation of possible
causes of visual disturbances, which may include cataract, glaucoma or rare diseases such as central
serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical
corticosteroids.

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Atectura Breezhaler should be administered with caution in patients with pulmonary tuberculosis or
in patients with chronic or untreated infections.

6 Adverse drug reactions


Summary of the safety profile
The safety profile of Atectura Breezhaler was based on safety data from three phase 3 studies with a
total of 2497 adult or adolescent patients with asthma treated with Atectura Breezhaler 150/80,
150/160 or 150/320 micrograms once daily for up to 52 weeks.
The most common adverse drug reaction related to Atectura Breezhaler was headache.

Tabulated summary of adverse drug reactions from clinical trials


Adverse drug reactions are listed by MedDRA system organ class. The frequency of the ADRs are
based on the 52-week clinical study PALLADIUM (Table 7-1). Similar adverse event profile was
observed in a 12-week clinical study (QUARTZ) except that no events of angioedema, myalgia, rash
or tachycardia were observed. Within each system organ class, the adverse drug reactions are ranked
by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug
reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency
category for each adverse drug reaction is based on the following convention (CIOMS III): very
common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to
<1/1,000); very rare (<1/10,000).

Table 6-1 Estimated cumulative incidence (%) of adverse drug reactions in study
PALLADIUM at 52 weeks
Adverse drug Atectura Breezhaler Mometasone furoate Frequency
reactions 150/160 150/320 400 400 category
micrograms micrograms micrograms micrograms [based on
once daily once daily once daily twice daily the higher
Medium dose High dose Medium dose High dose frequency
between
Rate (%) Rate (%) Rate (%) Rate (%)
the two
[number of [number of [number of [number of
arms]
events] events] events] events]
(95% CI) (95% CI) (95% CI) (95% CI)
N=437 N=443 N=443 N=440
Infections and infestations
0.48 [2] 0.25 [1] 1.25 [5] 0.71 [5] Uncommon
Candidiasis*1
(0.10, 1.63) (0.02, 1.34) (0.48, 2.75) (0.20, 1.94)
Immune system disorders
1.20 [6] 1.88 [8] 2.26 [10] 0 [0] Common
Hypersensitivity*2
(0.46, 2.64) (0.89, 3.53) (1.12, 4.10)
0.47 [2] 0 [0] 0.48 [2] 0.48 [2] Uncommon
Angioedema*3 (0.10, 1.58) (0.10, 1.62) (0.10, 1.62)

Metabolism and nutrition disorders


0.98 [4] 0.97 [5] 1.52 [6] 0.23 [1] Uncommon
Hyperglycaemia*4
(0.33, 2.36) (0.33, 2.33) (0.63, 3.13) (0.02, 1.21)
Nervous system disorders
5.29 [25] 6.22 [39] 5.84 [33] 5.75 [37] Common
Headache*5
(3.42, 7.73) (4.18, 8.82) (3.85, 8.40) (3.79, 8.27)

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Adverse drug Atectura Breezhaler Mometasone furoate Frequency
reactions 150/160 150/320 400 400 category
micrograms micrograms micrograms micrograms [based on
once daily once daily once daily twice daily the higher
Medium dose High dose Medium dose High dose frequency
between
Rate (%) Rate (%) Rate (%) Rate (%)
the two
[number of [number of [number of [number of
arms]
events] events] events] events]
(95% CI) (95% CI) (95% CI) (95% CI)
N=437 N=443 N=443 N=440
Cardiac disorders
0.23 [1] 0.73 [3] 0.25 [1] 0.25 [1] Uncommon
Tachycardia*6
(0.02, 1.25) (0.21, 2.00) (0.02, 1.31) (0.02, 1.32)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal 1.92 [9] 3.11 [14] 2.87 [14] 2.41 [10] Common
7
Pain* (0.91, 3.60) (1.74, 5.10) (1.57, 4.81) (1.24, 4.24)
1.64 [7] 1.86 [9] 0.69 [3] 0.68 [4] Common
Dysphonia
(0.73, 3.22) (0.88, 3.49) (0.19, 1.88) (0.19, 1.88)
Skin and subcutaneous tissue disorders
0 [0] 0.93 [4] 0.51 [2] 0 [0] Uncommon
Rash*8
(0.31, 2.23) (0.10, 1.71)
0.25 [1] 0.48 [2] 0.71 [3] 0 [0] Uncommon
Pruritus*9
(0.02, 1.32) (0.10, 1.62) (0.20, 1.96)
Musculoskeletal and connective tissue disorders
Musculoskeletal 4.53 [24] 2.65 [11] 2.16 [9] 2.62 [17] Common
10
Pain* (2.83, 6.83) (1.41, 4.54) (1.07, 3.91) (1.39, 4.50)
0.47 [2] 0.47 [2] 0 [0] 0.72 [3] Uncommon
Muscle Spasms
(0.10, 1.58) (0.10, 1.57) (0.20, 1.96)
* Indicates grouping of preferred terms (PTs) observed in the three Phase 3 studies.
1
oral candidiasis, oropharyngeal candidiasis.
2
drug eruption, drug hypersensitivity, hypersensitivity, rash, rash erythematous, rash pruritic, urticaria.
3
allergic oedema, angioedema, periorbital swelling, swelling of eyelid.
4
blood glucose increased, hyperglycaemia.
5
headache, tension headache.
6
heart rate increased, tachycardia, sinus tachycardia, supraventricular tachycardia.
7
oral pain, oropharyngeal discomfort, oropharyngeal pain, throat irritation, odynophagia.
8
drug eruption, rash, rash erythematous, rash pruritic.
9
anal pruritus, eye pruritus, nasal pruritus, pruritus, pruritus genital.
10
back pain, musculoskeletal pain, myalgia, neck pain, musculoskeletal chest pain.

7 Interactions
Interactions linked to Atectura Breezhaler
No specific interaction studies were conducted with Atectura Breezhaler. Information on the potential
for interactions is based on the potential for each of the monotherapy components.
Clinically significant pharmacokinetic drug interactions mediated by Atectura Breezhaler at clinical
doses are considered unlikely due to the low plasma concentrations achieved after inhaled dosing.
Concomitant administration of orally inhaled indacaterol and mometasone furoate under steady-state
conditions did not affect the pharmacokinetics of either active substances.

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Medicinal products known to prolong the QTc interval
Atectura Breezhaler, like other medicinal products containing beta2-adrenergic agonists, should be
administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic
antidepressants or medicinal products known to prolong the QT interval, as any effect of these on the
QT interval may be potentiated. Medicinal products known to prolong the QT interval may increase
the risk of ventricular arrhythmia (see section 6 Warnings and precautions).
Hypokalemic treatment
Concomitant treatment with methylxanthine derivatives, steroids or non-potassium-sparing diuretics
may potentiate the possible hypokalemic effect of beta2-adrenergic agonists (see section 6 Warnings
and precautions).
Beta-adrenergic blockers
Beta-adrenergic blockers may weaken or antagonize the effect of beta2-adrenergic agonists.
Therefore, Atectura Breezhaler should not be given together with beta-adrenergic blockers unless
there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers
should be preferred, although they should be administered with caution.
Interaction with CYP3A4 and P-glycoprotein inhibitors
Inhibition of CYP3A4 and P-glycoprotein (P-gp) has no impact on safety of therapeutic doses of
Atectura Breezhaler.
Inhibition of the key contributors of indacaterol clearance (CYP3A4 and P-gp) or mometasone
furoate clearance (CYP3A4) raises the systemic exposure of indacaterol or mometasone furoate up
to two-fold.
The magnitude of exposure increases for indacaterol 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 of 600 micrograms.
Due to the very low plasma concentration achieved after inhaled dosing, clinically significant drug
interactions with mometasone furoate are unlikely. However, there may be a potential for increased
systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole,
itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.
Other long acting beta2-adrenergic agonists
The co-administration of Atectura Breezhaler with other medicinal products containing long-acting
beta2-adrenergic agonists has not been studied and is not recommended as it may potentiate adverse
reactions (see sections 7 Adverse drug reactions and 10 Overdosage).

8 Pregnancy, lactation, females and males of reproductive


potential
8.1 Pregnancy
Risk Summary
There are insufficient data on the use of Atectura Breezhaler or its individual components (indacaterol
and mometasone furoate) in pregnant women to inform a drug-associated risk.
Indacaterol was not teratogenic in rats or rabbits following subcutaneous administration (see Animal
data). In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate
caused increased fetal malformations and decreased fetal survival and growth.

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Atectura Breezhaler should only be used during pregnancy if the expected benefit to the patient
justifies the potential risk to the fetus.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal
adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small
for gestational age in the neonate. Pregnant women with asthma should be closely monitored and
medication adjusted as necessary to maintain optimal asthma control.
Labor and Delivery
Like other medicinal products containing beta2-adrenergic agonists, indacaterol may inhibit labor due
to a relaxant effect on uterine smooth muscle.

Animal data
The combination of indacaterol and mometasone furoate has not been studied in pregnant animals.
Indacaterol
Following subcutaneous administration in a rabbit study, adverse effects of indacaterol with respect
to pregnancy and embryonal/fetal development could only be demonstrated at doses more than 500-
fold than achieved following the daily inhalation of 150 micrograms in humans (based on AUC0-24h).
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-natal
developmental rat study.
Mometasone furoate
Like other glucocorticoids, mometasone furoate is a teratogen in rodents and rabbits. Effects noted
were umbilical hernia in rats, cleft palate in mice and gallbladder agenesis, umbilical hernia and
flexed front paws in rabbits. There were also reductions in maternal body weight gains, effects on
fetal growth (lower fetal body weight and/or delayed ossification) in rats, rabbits and mice, and
reduced offspring survival in mice. In studies of reproductive function, subcutaneous mometasone
furoate at 15 micrograms/kg prolonged gestation and difficult labor occurred with a reduction in
offspring survival and body weight.

8.2 Lactation
Risk summary
There is no information available on the presence of indacaterol or mometasone furoate in human
milk, on the effects on a breastfed child, or on the effects on milk production. Other inhaled
corticosteroids, similar to mometasone furoate, are transferred into human milk. Indacaterol
(including its metabolites) and mometasone furoate have been detected in the milk of lactating rats.
The developmental and health benefits of breastfeeding should be considered along with the mother’s
clinical need for Atectura Breezhaler and any potential adverse effects on the breast-fed child from
Atectura Breezhaler or from the underlying maternal condition

8.3 Females and males of reproductive potential


Infertility
Reproduction studies and other data in animals did not indicate a concern regarding fertility in either
males or females.

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9 Overdosage
There is limited experience with overdose in clinical studies with Atectura Breezhaler. General
supportive measures and symptomatic treatment should be initiated in cases of suspected overdose.
An overdose will likely produce signs, symptoms or adverse effects associated with the
pharmacological actions of the individual components (e.g. tachycardia, tremor, palpitations,
headache, nausea, vomiting, drowsiness, ventricular arrhythmias, metabolic acidosis, hypokalemia,
hyperglycemia, 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 beta-adrenergic blockers may provoke
bronchospasm. In serious cases, patients should be hospitalized.

10 Clinical pharmacology
Pharmacotherapeutic group, ATC
Pharmacotherapeutic group: Long-acting inhaled therapy (beta-agonists and glucocorticosteroids)

Mechanism of action (MOA)


Atectura Breezhaler is a combination of indacaterol, a long-acting beta2-adrenergic agonist (LABA),
and mometasone furoate, an inhaled synthetic corticosteroid (ICS). Following oral inhalation,
indacaterol acts locally on airways to produce bronchodilation and mometasone furoate reduces
pulmonary inflammation.
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 catalyzes 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 is a weak partial agonist at beta1-receptors with a potency more than 24-fold greater at
beta2-receptors compared to beta1-receptors and is a full agonist at beta3-receptors with a potency 20-
fold greater at beta2-receptors compared to beta3-receptors.
When inhaled, indacaterol acts locally in the lung as a bronchodilator. Indacaterol is a nearly full
agonist at the human beta2-adrenergic receptor with nanomolar potency. In isolated human bronchus,
indacaterol has a rapid onset of action and a long duration of action.
Although beta2-adrenergic receptors are the predominant adrenergic receptors in bronchial smooth
muscle and beta1-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.
The precise function of beta2-adrenergic receptors in the heart is not known, but their presence raises
the possibility that even highly selective beta2-adrenergic agonists may have cardiac effects.
Mometasone furoate
Mometasone furoate is a synthetic corticosteroid with high affinity for glucocorticoid receptors and
local anti-inflammatory properties. Studies in asthmatic patients have demonstrated that inhaled
mometasone furoate provides a favorable ratio of pulmonary to systemic activity. It is likely that
much of the mechanism for the effects of mometasone furoate lies in its ability to inhibit the release
of mediators of the inflammatory cascade. In vitro, mometasone furoate inhibits the release of
leukotrienes (LT) from leukocytes of allergic patients. In cell culture, mometasone furoate
demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNF-alpha.

Atectura Jun 2020.SINv1 Page 9 of 22


It is also a potent inhibitor of LT production and an extremely potent inhibitor of the production of
the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.

Pharmacodynamics (PD)
The primary pharmacodynamics of Atectura Breezhaler in obstructive airway disease reflects the
complementary mechanisms of action of the individual components of Atectura Breezhaler.
Clinical data confirmed the hypothesis that bronchodilation with indacaterol coupled with the anti-
inflammatory action of mometasone furoate results in improved lung function and asthma control.
The Atectura Breezhaler clinical program showed consistently superior lung function when Atectura
Breezhaler 150/80, 150/160, 150/320 micrograms once daily were compared to mometasone furoate
(MF) 200, 400 micrograms once daily and 400 micrograms twice daily, and placebo.
The pharmacodynamic response profile of Atectura Breezhaler is characterized by rapid onset of
action within 5 minutes after dosing (see section 12 Clinical studies) and sustained effect over the 24
h dosing interval as evidenced by improvements in trough forced expiratory volume in the first
second (FEV1) versus comparators, 24 hours after dosing.
No tachyphylaxis to the lung function benefits of Atectura Breezhaler were observed over time.

Effects on the QTc interval


The effect of Atectura Breezhaler on the QTc interval has not been evaluated in a thorough QT (TQT)
study.
For mometasone furoate, no QTc prolonging properties are known.

Pharmacokinetics (PK)

Absorption
Following inhalation of Atectura Breezhaler, the median time to reach peak plasma concentrations
of indacaterol and mometasone furoate was approximately 15 minutes and 1 hour, respectively.
Based on the in vitro performance data, the dose of each of the monotherapy components delivered
to the lung is expected to be similar for Atectura Breezhaler and the monotherapy products. Steady-
state plasma exposure to indacaterol and mometasone furoate after Atectura Breezhaler inhalation
was similar to the systemic exposure after inhalation of indacaterol maleate or mometasone furoate
as monotherapy products.
Following inhalation of Atectura Breezhaler, the absolute bioavailability was estimated to be about
45% for indacaterol and less than 10% for mometasone furoate.
Indacaterol
Indacaterol concentrations increased with repeated once-daily administration. Steady state was
achieved within 12 to 14 days. The mean accumulation ratio of indacaterol, i.e. AUC over the 24-
hour dosing interval on Day 14 compared to Day 1, was in the range of 2.9 to 3.8 for once-daily
inhaled doses between 75 and 600 micrograms. Systemic exposure results from a composite of
pulmonary and gastrointestinal absorption; about 75% of systemic exposure was from pulmonary
absorption and about 25% from gastrointestinal absorption.
Mometasone furoate
Mometasone furoate concentrations increased with repeated once-daily administration via the
Breezhaler device. Steady state was achieved after 12 days. The mean accumulation ratio of

Atectura Jun 2020.SINv1 Page 10 of 22


mometasone furoate, i.e. AUC0-24hr on Day 14 compared to Day 1, was in the range of 1.61 to 1.71
for once-daily inhaled doses of between 80 and 320 micrograms as part of Atectura Breezhaler.
Following oral administration of mometasone furoate, the absolute oral systemic bioavailability of
mometasone furoate was estimated to be very low (<2%).

Distribution
Indacaterol
After intravenous infusion the volume of distribution (Vz) of indacaterol was 2,361 to 2,557L
indicating an extensive distribution. The in vitro human serum and plasma protein binding were 94.1
to 95.3% and 95.1 to 96.2%, respectively.
Mometasone furoate
After intravenous bolus administration, the Vd is 332L. The in vitro protein binding for mometasone
furoate is high, 98 % to 99 % in concentration range of 5 to 500 ng/ml.

Biotransformation/metabolism
Indacaterol
After oral administration of radiolabelled indacaterol in a human absorption, distribution, metabolism,
excretion (ADME) 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, an N-glucuronide
of indacaterol, and C- and N-dealkylated products were further metabolites identified.
In vitro investigations indicated that UGT1A1 was the only UGT isoform that metabolized
indacaterol to the phenolic O-glucuronide. The 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.
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.
Mometasone furoate
The portion of an inhaled mometasone furoate dose that is swallowed and absorbed in the
gastrointestinal tract undergoes extensive metabolism to multiple metabolites. There are no major
metabolites detectable in plasma. In human liver microsomes, mometasone furoate is metabolized by
CYP3A4.

Elimination
Indacaterol
In clinical studies which included urine collection, the amount of indacaterol excreted unchanged via
urine was generally lower than 2% of the dose. Renal clearance of indacaterol was, on average,
between 0.46 and 1.20 L/h. When compared with the serum clearance of indacaterol of 18.8 to 23.3
L/h, it is evident that renal clearance plays a minor role (about 2 to 6% of systemic clearance) in the
elimination of systemically available indacaterol.
In a human ADME study where indacaterol was given orally, the fecal route of excretion was
dominant over the urinary route. Indacaterol was excreted into human feces primarily as unchanged

Atectura Jun 2020.SINv1 Page 11 of 22


parent substance (54% of the dose) and, to a lesser extent, hydroxylated indacaterol metabolites (23%
of the dose). Mass balance was complete with ≥90% of the dose recovered in the excreta.
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 to 14 days.
Mometasone furoate
After intravenous bolus administration, mometasone furoate has a terminal elimination T1/2 of
approximately 4.5 hours. A radiolabelled, orally inhaled dose is excreted mainly in the feces (74 %)
and to a lesser extent in the urine (8 %)

Linearity/non-linearity
Systemic exposure of mometasone furoate increased in a dose proportional manner following single
and multiple doses of Atectura Breezhaler 150/80 and 150/320 micrograms in healthy subjects. A
less than proportional increase in steady state systemic exposure was noted in patients with asthma
over the dose range of 150/80 to 150/320 micrograms. Dose proportionality assessments were not
performed for indacaterol as only one dose was used across all dose strengths of Atectura
Breezhaler.

Special populations
A population PK analysis in patients with asthma after inhalation of Atectura Breezhaler indicated
no significant effect of age, gender, body weight, smoking status, baseline estimated glomerular
filtration rate (eGFR) and FEV1 at baseline on the systemic exposure to indacaterol and mometasone
furoate.

Race/Ethnicity
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.

Pediatric patients (below 12 years)


Atectura Breezhaler may be used in pediatric patients (12 years of age and older) at the same posology
as in adults. The safety and efficacy of Atectura Breezhaler in pediatric patients below 12 years of
age have not been established.

Renal impairment
Due to the very low contribution of the urinary pathway to total body elimination of indacaterol and
mometasone furoate, the effects of renal impairment on their systemic exposure have not been
investigated.

Hepatic impairment
The effect of indacaterol/mometasone furoate has not been evaluated in subjects with hepatic
impairment. However, studies have been conducted with the mono-components.
Indacaterol: Patients with mild or moderate hepatic impairment showed no relevant changes in Cmax
or AUC of indacaterol, nor did protein binding differ between mild and moderate hepatic impaired
subjects and their healthy controls. No data are available for subjects with severe hepatic impairment.

Atectura Jun 2020.SINv1 Page 12 of 22


Mometasone furoate: A study evaluating the administration of a single inhaled dose of 400
micrograms mometasone furoate by dry powder inhaler to subjects with mild (n=4), moderate (n=4),
and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable
peak plasma concentrations of mometasone furoate (ranging from 50 to 105 pcg/mL). The observed
peak plasma concentrations appear to increase with severity of hepatic impairment; however, the
numbers of detectable levels (assay Lower Limit of Quantification was 50pcg/mL) were few.

11 Clinical studies
Two phase III randomized, double-blind studies (PALLADIUM and QUARTZ) of different
durations evaluated the safety and efficacy of Atectura Breezhaler in adults and adolescent patients
with asthma.
Study PALLADIUM was a 52-week pivotal study evaluating Atectura Breezhaler 150/160
micrograms once daily (N=439) and 150/320 micrograms once-daily (N=445) via Breezhaler over
mometasone furoate (MF) 400 micrograms once daily (N=444) and 800 micrograms per day given
as 400 micrograms twice daily (N=442), respectively. A third active control arm included subjects
treated with salmeterol xinafoate /fluticasone propionate (SAL/FP) 50/500 micrograms twice daily
(N=446). All subjects were required to be asthma symptomatic and on asthma maintenance therapy
using an inhaled corticosteroid (ICS) with or without LABA for at least 3 months prior to study entry.
At screening, 30% of patients had a history of exacerbation in the previous year. At study entry, the
most common asthma medications reported were medium and high dose of ICS (27%) or LABA and
low dose of ICS (69%).
The primary objective of the study was to demonstrate superiority of either Atectura Breezhaler
150/160 micrograms once daily to MF 400 micrograms once daily or Atectura Breezhaler 150/320
micrograms once daily to MF 400 micrograms twice daily in terms of trough FEV1 at week 26.
Mometasone furoate (MF) 160 (medium dose) and 320 (high dose) micrograms in Atectura
Breezhaler once daily are comparable to MF 400 micrograms once daily (medium dose) and 800
micrograms (given as 400 micrograms twice daily, high dose) using multi-dose dry powder inhaler,
respectively.
Atectura Breezhaler 150/160 and 150/320 micrograms once daily both demonstrated statistically
significant improvements in trough FEV1 at week 26 and Asthma Control Questionnaire (ACQ-7)
score compared to MF 400 micrograms once or twice daily, respectively (see Table 12-1). A greater
percentage of subjects were ACQ responders (defined as achieving minimal clinical important
difference (MCID) from baseline with ACQ ≥ 0.5) for both doses of Atectura Breezhaler compared
to MF 400 micrograms once or twice daily, respectively (see Table 12-1). Findings at week 52 were
consistent with week 26.
Atectura Breezhaler 150/160 and 150/320 micrograms once daily both demonstrated a clinically
meaningful reduction in the annual rate of moderate or severe exacerbations, 53% and 35%
respectively, compared to MF 400 micrograms once and twice daily (see Table 12-3).
For information on other endpoints see Table 12-1 and 12-3.
Lung function and symptoms

Table 11-1 Results of primary and secondary endpoints


Endpoint Time Atectura Breezhaler vs MF* Atectura
point/Duration Breezhaler vs
SAL/FP*
Medium dose High dose High dose
(150/160 od)

Atectura Jun 2020.SINv1 Page 13 of 22


versus (150/320 od) (150/320 od)
medium dose versus versus
(400 od) high dose high dose
(400 bid) (50/500 bid)
Lung Function
Trough FEV1**
Week 26 211 mL 132 mL 36 mL
Treatment (Primary <0.001 <0.001 0.101
difference endpoint) (167, 255) (88, 176) (-7, 80)
P value Week 52 209 mL 136 mL 48 mL
(95% CI) <0.001 <0.001 0.040
(163, 255) (90, 183) (2, 94)
Mean Morning Peak Expiratory Flow (PEF)
Week 1-26*** 32.2 L/min 29.6 L/min 13.3 L/min
Treatment <0.001 <0.001 <0.001
difference (26.4, 38.1) (23.8, 35.4) (7.5, 19.1)
P value Week 1-52*** 30.2 L/min 28.7 L/min 13.8 L/min
(95% CI) <0.001 <0.001 <0.001
(24.2, 36.3) (22.7, 34.8) (7.7, 19.8)
Mean Evening Peak Expiratory Flow (PEF)
Week 1-26*** 30.4 L/min 24.8 L/min 8.6 L/min
Treatment <0.001 <0.001 0.002
difference (24.8, 35.9) (19.3, 30.3) (3.1, 14.2)
P value Week 1-52*** 29.1 L/min 23.7 L/min 9.1 L/min
(95% CI) <0.001 <0.001 0.002
(23.3, 34.8) (18.0, 29.5) (3.3, 14.9)
Symptoms
ACQ-7
Week 26 (key -0.248 -0.171 -0.054
secondary <0.001 <0.001 0.214
endpoint) (-0.334, -0.162) (-0.257, -0.086) (-0.140, 0.031)
Treatment
difference
P value Week 52 -0.266 -0.141 0.010
(95% CI) <0.001 0.002 0.824
(-0.354, -0.177) (-0.229, -0.053) (-0.078, 0.098)

ACQ responders (percentage of patients achieving minimal clinical important difference (MCID)
from baseline with ACQ ≥ 0.5)
Percentage Week 26 76% vs 67% 76% vs 72% 76% vs 76%
Odds Ratio Week 26 1.73 1.31 1.06
P value <0.001 0.094 0.746
(95% CI) (1.26, 2.37) (0.95, 1.81) (0.76, 1.46)
Percentage Week 52 82% vs 69% 78% vs 74% 78% vs 77%
Odds Ratio Week 52 2.24 1.34 1.05
P value <0.001 0.088 0.771
(95% CI) (1.58, 3.17) (0.96, 1.87) (0.75, 1.49)
Mean number of daily puffs of rescue medication
Treatment Week 1-26*** -0.19 -0.31 -0.09
difference 0.017 <0.001 0.290

Atectura Jun 2020.SINv1 Page 14 of 22


P value (-0.35, -0.03) (-0.46, -0.15) (-0.24, 0.07)
(95% CI)
Week 1-52*** -0.23 -0.28 -0.09
0.004 <0.001 0.245
(-0.39,-0.07) (-0.44,-0.12) (-0.25,0.06)
Percentage of rescue medication free days
Week 1-26*** 8.3 10.1 4.1
Treatment <0.001 <0.001 0.045
difference (4.3, 12.3) (6.2, 14.1) (0.1, 8.0)
P value Week 1-52*** 8.6 9.6 4.3
(95% CI) <0.001 <0.001 0.034
(4.7, 12.6) (5.7, 13.6) (0.3, 8.3)
Percentage of days with no symptoms
Week 1-26*** 7.8 6.6 3.7
Treatment <0.001 0.002 0.082
difference (3.7, 12.0) (2.5, 10.7) (-0.5, 7.9)
P value Week 1-52*** 9.1 5.8 3.4
(95% CI) <0.001 0.012 0.135
(4.6, 13.6) (1.3, 10.2) (-1.1, 7.9)
Percentage of nights with no night-time awakenings
Week 1-26*** 4.1 2.7 0.6
Treatment 0.013 0.103 0.713
difference (0.9, 7.4) (-0.5, 5.9) (-2.6, 3.9)
P value Week 1-52*** 3.9 2.8 0.9
(95% CI) 0.024 0.104 0.588
(0.5, 7.3) (-0.6, 6.2) (-2.5, 4.3)
Quality of life as assessed by Asthma Quality of Life Questionnaire (S) (AQLQ-S+12)
Week 26 0.156 0.127 0.085
Treatment 0.003 0.016 0.103
difference (0.053, 0.260) (0.023, 0.230) (-0.017, 0.188)
P value Week 52 0.191 0.079 0.041
(95% CI) <0.001 0.154 0.455
(0.082, 0.299) (-0.030, 0.187) (-0.067, 0.148)
* MF: mometasone furoate; SAL/FP: salmeterol xinafoate /fluticasone propionate;
** Trough FEV1: the mean of the two FEV1, values measured at 23 hour 15 min and 23 hour 45 min after the
evening dose.
*** Mean value for the treatment duration.
Onset of action
In study PALLADIUM, Atectura Breezhaler demonstrated a rapid onset of bronchodilator effect
within 5 minutes after administration (see Table 12-2).

Table 11-2 Onset of action on Day 1 based on treatment difference in FEV1 by time points
in study PALLADIUM
Treatment difference Day 1
Atectura Breezhaler (medium dose) vs MF* (medium dose)
5 min 152 mL**
15 min 174 mL**
30 min 185 mL**

Atectura Jun 2020.SINv1 Page 15 of 22


Atectura Breezhaler (high dose) vs MF* (high dose)
5 min 142 mL**
15 min 162 mL**
30 min 175 mL**
Atectura Breezhaler (high dose) vs SAL/FP* (high dose)
5 min 55 mL**
15 min 44 mL**
30 min 27 mL (p=0.038)
* MF: mometasone furoate; SAL/FP: salmeterol xinafoate /fluticasone propionate
** p-value <0.001
Exacerbations

Table 11-3 Analysis of Exacerbation endpoints


Endpoint Atectura Breezhaler vs MF* Atectura Breezhaler vs
SAL/FP*
Medium dose High dose High dose
(150/160 od) versus (150/320 od) (150/320 od)
medium dose versus versus
(400 od) high dose high dose
(400 bid) (50/500 bid)
Annualized rate of asthma exacerbations
Moderate or severe exacerbations
Annualized 0.27 vs 0.56 0.25 vs 0.39 0.25 vs 0.27
rate
Rate Ratio 0.47 0.65 0.93
(RR) <0.001 0.008 0.669
p-value (0.35, 0.64) (0.48, 0.89) (0.67, 1.29)
(95% CI)
Severe exacerbations
Annualized 0.13 vs 0.29 0.13 vs 0.18 0.13 vs 0.14
rate
Rate Ratio 0.46 0.71 0.89
(RR) <0.001 0.108 0.597
p-value (0.31, 0.67) (0.47, 1.08) (0.58, 1.37)
(95% CI)
All exacerbations (mild, moderate or severe)
Annualized 0.48 vs 1.05 0.49 vs 0.74 0.49 vs 0.52
rate
Rate Ratio 0.46 0.67 0.95
(RR) <0.001 0.002 0.681
p-value (0.36, 0.59) (0.52, 0.87) (0.72, 1.23)
(95% CI)
* MF: mometasone furoate; SAL/FP: salmeterol xinafoate /fluticasone propionate

Atectura Breezhaler 150/160 and 150/320 micrograms once daily were also studied as active
comparators in another Phase III study (IRIDIUM) in an asthma development program for
indacaterol/glycopyrronium/mometasone furoate in adult patients with asthma. To enroll in this study,
all subjects were required to be symptomatic on asthma maintenance therapy with a medium or high
dose ICS and LABA combination therapy for at least 3 months prior to study entry. All subjects had

Atectura Jun 2020.SINv1 Page 16 of 22


a history of asthma exacerbation requiring systemic corticosteroids in the past year. A pre-specified
pooled analysis across both IRIDIUM and PALLADIUM studies was conducted to compare Atectura
Breezhaler 150/320 micrograms once daily to salmeterol/fluticasone 50/500 micrograms twice daily
for the endpoints of trough FEV1 and ACQ-7 at week 26 and annualized rate of exacerbations. The
pooled analysis demonstrated that Atectura Breezhaler improved trough FEV1 by 43 mL (95% CI:
17, 69; p=0.001) and ACQ-7 score by -0.091 (95% CI: -0.153, -0.030; p=0.004) at week 26 versus
salmeterol/fluticasone. The pooled analysis also demonstrated that Atectura Breezhaler reduced the
annualized rate of moderate or severe asthma exacerbations by 22% (RR: 0.78; 95% CI: 0.66, 0.93;
p=0.006) and of severe exacerbations by 26% (RR: 0.74; 95% CI: 0.61, 0.91; p=0.004) versus
salmeterol/fluticasone.
Study QUARTZ was a 12-week study evaluating Atectura Breezhaler 150/80 micrograms once daily
(N=398) via Breezhaler over MF 200 micrograms once daily (N=404). All subjects were required to
be symptomatic and on asthma maintenance therapy using a low dose ICS (with or without LABA)
for at least 1 month prior to study entry. At study entry, the most common asthma medications
reported were low dose of ICS (43%) and LABA/low dose ICS (56%). The primary endpoint of the
study was to demonstrate superiority of Atectura Breezhaler 150/80 micrograms once daily to MF
200 micrograms once daily in terms of trough FEV1 at week 12.
MF 80 micrograms (low dose) in Atectura Breezhaler once daily is comparable to MF 200
micrograms once daily (low dose) using multi-dose dry powder inhaler.
Atectura Breezhaler 150/80 micrograms once daily demonstrated a statistically significant
improvement in baseline trough FEV1 at week 12 and Asthma Control Questionnaire (ACQ-7) score
compared to MF 200 micrograms once daily. For additional details, see Table 12-4.

Table 11-4 Results of primary and secondary endpoints in study QUARTZ at week 12
Endpoints Atectura Breezhaler low dose (150/80 od)
vs
MF* low dose (200 od)
P value
(95% CI)
Lung Function
Trough FEV1** 182 mL
<0.001
(148, 217)
Mean Morning PEF 27.2 L/min
<0.001
(22.1, 32.4)
Evening PEF 26.1 L/min
<0.001
(21.0, 31.2)
Symptoms
ACQ-7 (key secondary endpoint) -0.218
<0.001
(-0.293, -0.143)
Percentage of patients achieving MCID from baseline with 75% vs 65%
ACQ ≥ 0.5 1.69
0.001
(1.23, 2.33)
Mean number of daily puffs of rescue medication -0.26

Atectura Jun 2020.SINv1 Page 17 of 22


<0.001
(-0.37, -0.14)
Percentage of rescue medication free days 8.1
<0.001
(4.3, 11.8)
Percentage of days with no symptoms 2.7
0.153
(-1.0, 6.4)
Percentage of nights with no night-time awakenings 4.8
0.002
(1.8, 7.7)
Quality of life as assessed by Asthma Quality of Life 0.149
Questionnaire (S) (AQLQ-S+12) <0.001
(0.064, 0.234)
* MF: mometasone furoate.
** Trough FEV1: the mean of the two FEV1, values measured at 23 hour 15 min and 23 hour 45 min after the
evening dose.

12 Non-clinical safety data


For information on reproductive toxicity, see section 9 Pregnancy, lactation, females and males of
reproductive potential.
The in vivo studies of each monotherapy and combination products are presented below.
Indacaterol and mometasone furoate combination
The findings during the 13-week inhalation toxicity studies were predominantly attributable to the
mometasone furoate and were typical pharmacological effects of glucocorticoids. Increased heart
rates associated with indacaterol were apparent in dogs after administration of
indacaterol/mometasone furoate or indacaterol alone.

Indacaterol
Effects on the cardiovascular system attributable to the beta2-agonistic properties of indacaterol
included tachycardia, arrhythmias and myocardial lesions in dogs. Mild irritation of the nasal cavity
and larynx were seen in rodents.
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 beta2-adrenergic agonists. No evidence
of carcinogenicity was seen in mice.
All these findings occurred at exposures sufficiently in excess of those anticipated in humans.

Mometasone furoate
All observed effects are typical of the glucocorticoid class of compounds and are related to
exaggerated pharmacologic effects of glucocorticoids. Mometasone furoate showed no genotoxic
activity in a standard battery of in vitro and in vivo tests.
In carcinogenicity studies in mice and rats, inhaled mometasone furoate demonstrated no statistically
significant increase in the incidence of tumours.

Atectura Jun 2020.SINv1 Page 18 of 22


13 Pharmaceutical information
Incompatibilities
Not applicable.

Special precautions for storage


Do not store above 30C.
Protect from moisture and light.
Keep this medicine out of the sight and reach of children.

Instructions for use and handling


For correct administration/use of the product, please refer to Section 4 Method of administration and
the Instruction for use (IFU) below.

Instructions for use Atectura Breezhaler


This part of the leaflet explains how to use and care for your Atectura Breezhaler inhaler. Please read
carefully and follow these instructions.
If you have any questions, ask your doctor or pharmacist.
Please read the full Instructions for Use before using the Atectura 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.

Atectura Jun 2020.SINv1 Page 19 of 22


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 3d.

Step 1b: Step 3b:


Open inhaler Inhale medicine
deeply
Hold the inhaler as
shown in the picture. Powder Empty
Place the mouthpiece
remaining
in your mouth and
close your lips firmly
around it.
Step 2b: Do not press the side
Release side buttons buttons.
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
card. Close the inhaler and
replace the cap.
Peel open the blister and
remove the capsule. Step 3c:
Do not push the capsule Hold breath
through the foil. Hold your breath for
Do not swallow the up to 5 seconds.
capsule.

Step 3d :
Rinse mouth
Rinse your mouth with
water after each dose
and spit it out.

Atectura Jun 2020.SINv1 Page 20 of 22


Important Information
 Atectura Breezhaler
capsules must always be
stored in the blister card
and only removed
immediately before use.
 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  Do not swallow the
mouthpiece. capsule.
 Do not use the Atectura
Breezhaler capsules
with any other inhaler.
 Do not use the Atectura
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.
 Do not press the side
buttons more than once.
 Do not blow into the
mouthpiece.
 Do not press the side
buttons while inhaling
through the mouthpiece.
 Do not handle capsules
with wet hands.
 Never wash your inhaler
with water.

Your Atectura Breezhaler Inhaler pack contains: Frequently Asked Cleaning the inhaler
 One Atectura Breezhaler inhaler Questions Wipe the mouthpiece
 One or more blister cards each containing either inside and outside with a
10 Atectura Breezhaler capsules to be used in the Why didn’t the inhaler clean, dry, lint-free cloth to
inhaler make a noise when I remove any powder
Capsule Mouthpiece
inhaled? residue. Keep the inhaler
Cap
chamber dry. Never wash your
Screen
inhaler with water.
Side
buttons Blister
Base

Inhaler Inhaler base Blister card

Atectura Jun 2020.SINv1 Page 21 of 22


The capsule may be stuck Disposing of the inhaler
in the capsule chamber. If after use
this happens, carefully Each inhaler should be
loosen the capsule by disposed of after all
tapping the base of the capsules have been used.
inhaler. Inhale the Ask your pharmacist how
medicine again by to dispose of medicines
repeating steps 3a to 3d. and inhalers that are no
longer required.
What should I do if there
is powder left inside the
capsule?
You have not received
enough of your medicine.
Close the inhaler and
repeat steps 3a to 3d.

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.

Manufacturer
See folding box.

Presentation
Atectura Breezhaler 150/80, 150/160, 150/320 micrograms:
Single pack 10 capsules (1x10’s) or 30 capsules (3x10’s), together with one inhaler.
Not all pack sizes may be available locally.

Information issued: June 2020.SINv1

Novartis Pharma AG, Basel, Switzerland

Atectura Jun 2020.SINv1 Page 22 of 22

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