Breo™ Ellipta®

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Fluticasone furoate 200 µg;  ; Vilanterol trifenatate 40 µg equivalent to vilanterol 25 mcg;  
Available from:
GlaxoSmithKline NZ Limited
INN (International Name):
Fluticasone furoate 200 µg
Dosage:
200mcg/25mcg
Pharmaceutical form:
Powder for inhalation
Composition:
Active: Fluticasone furoate 200 µg   Vilanterol trifenatate 40 µg equivalent to vilanterol 25 mcg   Excipient: Lactose monohydrate Magnesium stearate
Prescription type:
Prescription
Manufactured by:
Glaxo Operations UK Limited t/a Glaxo Welcome Operations
Therapeutic indications:
Indicated for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate.
Product summary:
Package - Contents - Shelf Life: Inhaler, metered, Plastic with dose counter, inside a sealed aluminium foil tray with desiccant - 14 dose units - 24 months from date of manufacture stored at or below 30°C protect from moisture 1 months opened stored at or below 30°C protect from moisture - Inhaler, metered, Plastic with dose counter, inside a sealed aluminium foil tray with desiccant - 30 dose units - 24 months from date of manufacture stored at or below 30°C protect from moisture 1 months opened stored at or below 30°C protect from moisture
Authorization number:
TT50-9114a
Authorization date:
2012-08-27

Read the complete document

BREO ELLIPTA

BREO

ELLIPTA

Fluticasone furoate 100 or 200 micrograms and vilanterol (as trifenatate) 25 micrograms per inhalation

New Zealand Consumer Medicine Information

What is in this leaflet

Please read this leaflet carefully

before you start using BREO

ELLIPTA.

This leaflet answers some common

questions about BREO ELLIPTA.

It does not contain all the available

information.

It does not take the place of talking to

your doctor or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you taking BREO

ELLIPTA against the benefits they

expect it will have for you.

If you have any concerns about

taking this medicine, ask your

doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What BREO ELLIPTA

is used for

BREO ELLIPTA is used to treat

asthma and chronic obstructive

pulmonary disease (COPD). To use

BREO ELLIPTA, you breathe it into

your lungs through your mouth using

the ELLIPTA inhaler.

Asthma is when the muscles

surrounding the smaller airways

become tight (bronchoconstriction),

swollen and irritated (inflammation).

Symptoms come and go and include

shortness of breath, wheezing, chest

tightness and cough.

COPD is a long-term condition that

slowly gets worse. Symptoms

include shortness of breath, cough,

chest discomfort and coughing up

mucus. BREO ELLIPTA has been

shown to reduce flare-ups of COPD

symptoms.

BREO ELLIPTA contains two active

ingredients: fluticasone furoate and

vilanterol trifenatate.

Fluticasone furoate belongs to a

group of medicines called

corticosteroids

, often simply called

steroids

. Corticosteroids are used to

reduce inflammation. They reduce

the swelling and irritation in the

small air passages in the lungs and

can ease breathing problems.

Corticosteroids also help to prevent

attacks of asthma.

Vilanterol trifenatate belongs to a

group of medicines called

bronchodilators

. It relaxes the

muscles of the small air passages in

the lungs. This helps to open the

airways and makes it easier for air to

get in and out of the lungs. When it is

taken regularly, it helps the small air

passages to remain open.

When you take these two medicines

together regularly, they will help to

control your breathing difficulties.

BREO ELLIPTA should not be

used to relieve a sudden attack of

breathlessness or wheezing. If you

get this sort of attack you must use

a quick-acting inhaler (such as

VENTOLIN).

Your doctor may have prescribed

BREO ELLIPTA for another reason.

Ask your doctor if you have any

questions about why this medicine

has been prescribed for you.

This medicine is not addictive.

This medicine is available only with

a doctor's prescription.

This medicine is not expected to

affect your ability to drive a car or

operate machinery.

There is not enough information to

recommend the use of this medicine

for children under the age of 12

years.

Before you use BREO

ELLIPTA

When you must not use it

Don’t use BREO ELLIPTA

if you are allergic

(hypersensitive) to lactose or

milk protein

if you are allergic

(hypersensitive) to

fluticasone furoate,

vilanterol or any other

ingredients of BREO

ELLIPTA (listed at the end

of this leaflet)

If you think either of these apply to

you, don’t use BREO ELLIPTA

until you have checked with your

doctor.

Some of the symptoms of an allergic

reaction may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin

BREO ELLIPTA contains lactose.

If you have been diagnosed with an

intolerance to some sugars, or to

BREO ELLIPTA

milk protein, talk to your doctor

before you use BREO ELLIPTA.

BREO ELLIPTA is not usually

recommended for use during

pregnancy.

If you are pregnant, if you think

you may be pregnant don’t use

BREO ELLIPTA without asking

your doctor.

Your doctor will consider the benefit

to you and the risk to your baby of

taking BREO ELLIPTA while you

are pregnant.

If you are breast-feeding, check

with your doctor before you take

BREO ELLIPTA.

It is not known whether the

ingredients of BREO ELLIPTA can

pass into breast milk.

Do not give this medicine to a child

under the age of 12 years.

Safety and effectiveness in children

younger than 12 years have not been

established.

Do not take this medicine after the

expiry date printed on the pack or

if the packaging is torn or shows

signs of tampering.

If it has expired or is damaged, return

it to your pharmacist for disposal.

If you are not sure whether you

should start taking this medicine,

talk to your doctor.

Before you start to use it

Talk to your doctor before you use

BREO ELLIPTA:

if you have liver disease, as you

may be more likely to have side

effects. If you have moderate or

severe liver disease, your doctor

will limit your dose to the lower

strength of BREO ELLIPTA

(100/25 micrograms once daily).

if you have heart problems or

high blood pressure

if you have ever been told you

have diabetes or high blood

sugar

you are being or have ever been

treated for tuberculosis (TB) or

pneumonia

weak bones (osteoporosis)

Check with your doctor before you

use BREO ELLIPTA if you think

any of these apply to you.

Tell your doctor if you are

pregnant or plan to become

pregnant or are breast-feeding.

Your doctor can discuss with you the

risks and benefits involved.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including any that you

get without a prescription from

your pharmacy, supermarket or

health food shop.

Some medicines may affect how

BREO ELLIPTA works, or make it

more likely that you’ll have side

effects. These include:

ketoconazole, to treat fungal

infections

ritonavir, to treat HIV infection

A class of medicines known as “beta-

blockers” used to treat high blood

pressure or a heart condition should

be avoided.

Your doctor and pharmacist have

more information on medicines to be

careful with or avoid while taking

this medicine.

How to use BREO

ELLIPTA

Follow all directions given to you

by your doctor or pharmacist

carefully.

If you do not understand the

instructions in the user leaflet, ask

your doctor or pharmacist for

help.

How much to use

Always use BREO ELLIPTA

exactly as your doctor has told you.

Check with your doctor, nurse or

pharmacist if you’re not sure.

The usual dose of BREO ELLIPTA

for asthma and COPD is one

inhalation 100 micrograms of

fluticasone furoate and

25 micrograms of vilanterol once

daily at the same time each day.

If you have severe asthma, your

doctor may decide that you should

use one inhalation of the higher

strength BREO ELLIPTA inhaler

(200 micrograms fluticasone furoate

and 25 micrograms of vilanterol).

If you have moderate or severe liver

disease, the maximum dose is one

inhalation of BREO ELLIPTA

(100 micrograms fluticasone furoate

and 25 micrograms of vilanterol)

once daily.

How to use the inhaler

The full instructions for using

BREO ELLIPTA are given on a

leaflet inside the pack.

BREO ELLIPTA is ready to use

straight away. No preparation or

checks of the inhaler are required.

Do not open BREO ELLIPTA

until you are ready to use it for the

first time.

After using BREO ELLIPTA, you

may clean the mouthpiece, using a

dry tissue, before you close the

cover. Do not immerse BREO

ELLIPTA in water.

When to use it

Use BREO ELLIPTA regularly.

It is very important that you use

BREO ELLIPTA every day, as

instructed by your doctor. This will

help to keep you free of symptoms

throughout the day and night.

If you feel you are getting breathless

or wheezy more often than normal,

or if you are using your quick-acting

inhaler more than usual, see your

doctor.

BREO ELLIPTA

How long to use it

Don’t stop BREO ELLIPTA

without medical advice.

Use BREO ELLIPTA for as long

as your doctor recommends. It will

only be effective as long as you are

using it. Don’t stop unless your

doctor advises you to, even if you

feel better.

If you forget to take it

If it is almost time for your next

dose, skip the dose you missed and

use your next dose when you are

meant to. Otherwise, use it as soon

as you remember, then go back to

using it as you would normally.

Don't take an extra dose to make

up for a missed dose.

If you are not sure what to do, ask

your doctor or pharmacist.

If you become wheezy or

breathless, or develop any other

symptoms of an asthma attack, use

your quick-acting inhaler (e.g.

VENTOLIN), then seek medical

advice.

If you have trouble remembering

to take your medicine, ask your

pharmacist for some hints.

If you take too much

(overdose)

In New Zealand, immediately

telephone your doctor or the

National Poisons Centre (telephone

0800 POISON or 0800 764 766) if

you think that you or anyone else

may have taken too much BREO

ELLIPTA.

If you accidentally take a larger dose

of BREO ELLIPTA than your doctor

has instructed, you may notice that

your heart is beating faster than

usual, you feel shaky or have a

headache.

If you have used larger doses than

instructed for a long period of time, it

is particularly important that you ask

your doctor or pharmacist for advice.

This is because larger doses of

BREO ELLIPTA may reduce the

amount of steroid hormones

produced naturally by your body.

While you

are using

BREO ELLIPTA

Things you must do

Contact your doctor if you

experience blurred vision or other

visual disturbances.

Contact your doctor if you

experience increased thirst,

frequent urination or unexplained

tiredness (signs of high blood

sugar).

If you are about to be started on

any new medicine, remind your

doctor and pharmacist that you

are taking BREO ELLIPTA.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are taking this medicine.

If you are going to have surgery,

tell the surgeon or anaesthetist that

you are taking this medicine.

If you become pregnant while

taking this medicine, tell your

doctor immediately.

Keep all of your doctor's

appointments so that your progress

can be checked.

Things you must not do

Do not take BREO ELLIPTA to

treat any other complaints unless

your doctor tells you to.

Do not give your medicine to

anyone else, even if they have the

same condition as you.

Do not stop taking your medicine

or lower the dosage without

checking with your doctor.

Do not take any other medicines

for your breathing problems

without checking with your doctor.

Things to be careful of

Be careful driving or operating

machinery until you know how

BREO ELLIPTA affects you.

BREO ELLIPTA may cause

weakening of the bones

(osteoporosis) and increase your

risk of fractures.

Infection of the lungs (pneumonia)

after using BREO ELLIPTA is

common (it may affect up to 1 in 10

people). You must tell your doctor

if you have any of the following

symptoms while taking BREO

ELLIPTA: fever, chills, increased

mucus production, change in

mucus colour, increased cough or

increased breathing difficulties.

These may be symptoms of

pneumonia.

Side effects

Like all medicines, BREO ELLIPTA

can cause side effects, although not

everybody gets them. To reduce the

chance of side effects, your doctor

will prescribe the lowest effective

dose of BREO ELLIPTA to control

your asthma or COPD.

If your breathing or wheezing gets

worse straight after using BREO

ELLIPTA, stop using it

immediately, and tell your doctor

as soon as possible.

Do not be alarmed by the following

lists of side effects. You may not

experience any of them.

Ask your doctor or pharmacist to

answer any questions you may

have.

Very Common side effects

These may affect

more than 1 in 10

people:

headache

common cold

BREO ELLIPTA

Common side effects

These may affect

up to 1 in 10

people:

sore, raised patches in the mouth

or throat caused by a fungal

infection (

candidiasis

). Rinsing

your mouth out with water

immediately after using BREO

ELLIPTA may help stop this side

effect developing

infection of the lungs

pneumonia)

. You must

tell your

doctor

if you have any of the

following symptoms while taking

BREO ELLIPTA: fever, chills,

increased mucus production,

change in mucus colour,

increased cough or increased

breathing difficulties

inflammation of the lungs

(bronchitis)

infection of the nose sinuses or

throat

flu (influenza)

pain and irritation in the back of

the mouth and throat

inflammation of the sinuses

itchy, runny or blocked nose

cough

voice disorders

weakening of the bones, leading

to risk of fractures

stomach pain

high temperature (fever)

joint and back pain

muscle spasms

Uncommon side effects

These may affect

up to 1 in 100

people:

irregular heartbeat

increase in blood sugar

(hyperglycaemia). This may lead

to increased thirst, frequent

urination or unexplained

tiredness.

If you think you are having an

allergic reaction to BREO

ELLIPTA, stop using this medicine

and tell your doctor immediately

or go the accident and emergency

department at your nearest

hospital. Symptoms of an allergic

reaction usually include some or all

of the following:

wheezing

swelling of the lips/mouth,

tongue or throat

difficulty in breathing

hay fever lumpy rash

(“hives”)

fainting

It is possible that some peole

particularly those taking higher

doses of BREO ELLIPTA for a

long time, may rarely suffer from

the following side effects:

rounded face

loss of bone density

eye problems (e.g. cateract,

glaucoma)

slowing of growth in

children. It is unclear what,

if any, difference this makes

to a child’s final height

If you get any side effects, talk to

your doctor, pharmacist or nurse.

This includes any possible side

effects not listed in this leaflet.

Rarely the person taking the

medicine may experience immediate

breathing difficulties and wheezing,

feel anxious, have disturbed sleep,

feel depressed or notice increased

irritability (mainly in children).

After using BREO

ELLIPTA

Storage

Do not use BREO ELLIPTA after

the expiry date shown on the pack.

Store in the original package

container in order to protect from

moisture and do not open the foil

lid until ready to inhale.

Safely throw away BREO

ELLIPTA one month after you

open the foil tray or when your

counter reads “0”, whichever

comes first. Write the date the

inhaler should be discarded on the

label in the space provided. The

date should be added as soon as the

inhaler has been removed from the

tray.

Keep your inhaler in cool dry place

where the temperature stays below

30°C.

If you store in a refrigerator, allow

the inhaler to return to room

temperature for at least an hour

before use.

Do not store BREO ELLIPTA or

any other medicine in the

bathroom or near a sink. Do not

leave it on a window sill or in the

car.

Heat and dampness can destroy some

medicines.

Keep it where children cannot

reach it.

A locked cupboard at least one-and-

a-half metres above the ground is a

good place to store medicines.

Disposal

If your doctor tells you to stop

taking this medicine or the expiry

date has passed, ask your

pharmacist what to do with any

medicine that is left over.

Product description

What it looks like

BREO ELLIPTA is inhaled through

the mouth using the ELLIPTA

device. The active substances are in

separate blisters in powder form

inside the device. There are 30

blisters on each strip, and so each

device contains 30 doses.

The ELLIPTA device itself is a

plastic inhaler with a light grey body,

a pale blue mouthpiece cover and a

dose counter. It is packaged in a foil

laminate tray with a peelable foil lid.

The tray contains a desiccant sachet,

BREO ELLIPTA

to reduce the moisture in the

packaging. Once you have opened

the lid of the tray, throw the

desiccant away – do not open, eat or

inhale it.

Ingredients

The active ingredients in BREO

ELLIPTA are fluticasone furoate and

vilanterol (as trifenatate).

Each dose contains 100 or 200

micrograms of the active ingredient

fluticasone furoate. Each dose also

contains 25 micrograms of the active

ingredient vilanterol. The amount

depends on which strength of BREO

ELLIPTA you have been given.

BREO ELLIPTA also contains the

inactive ingredients:

lactose monohydrate

magnesium stearate

Supplier

Your BREO ELLIPTA is supplied

by:

GlaxoSmithKline NZ Ltd

Private Bag 106600

Downtown Auckland

New Zealand

Ph (09) 367 2900

Fax (09) 367 2910

Where to go for further

information

Pharmaceutical companies are not in

a position to give people an

individual diagnosis or medical

advice. Your doctor or pharmacist is

the best person to give you advice on

the treatment of your condition. You

may also be able to find general

information about your disease and

its treatment from patient information

groups and books, for example in

public libraries.

This leaflet was prepared on 13 June

2018.

The information provided applies

only to: BREO ELLIPTA.

Trade marks are owned by or

licensed to the GSK group of

companies.

© 2018 GSK group of companies or

its licensor.

Version 6.0

Read the complete document

NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

BREO ELLIPTA fluticasone furoate (100 micrograms or 200 micrograms)/vilanterol (as

trifenatate) (25 micrograms), powder for inhalation

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

BREO ELLIPTA 100 micrograms/25 micrograms: Each single inhalation provides a

delivered dose (the dose leaving the mouthpiece) of 92 micrograms of fluticasone furoate

and 22 micrograms of vilanterol (as trifenatate). This corresponds to a pre-dispensed dose

of 100 micrograms of fluticasone furoate and 25 micrograms vilanterol (as trifenatate).

BREO ELLIPTA 200 micrograms/25 micrograms: Each single inhalation provides a

delivered dose (the dose leaving the mouthpiece) of 184 micrograms of fluticasone furoate

and 22 micrograms of vilanterol (as trifenatate). This corresponds to a pre-dispensed dose

of 200 micrograms of fluticasone furoate and 25 micrograms vilanterol (as trifenatate).

Excipients with known effect:

Each delivered dose contains approximately 25 mg of lactose (as monohydrate).

For the full list of excipients, see Section 6.1 - List of excipients.

3.

PHARMACEUTICAL FORM

Powder for inhalation.

White powder in a light grey inhaler (Ellipta) with a pale blue mouthpiece cover and a dose

counter.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications

Asthma

BREO ELLIPTA is indicated for the regular treatment of asthma in adults and adolescents

aged 12 years and older where use of a combination product (long-acting beta

-agonist

and inhaled corticosteroid) is appropriate.

Chronic Obstructive Pulmonary Disease (COPD)

BREO ELLIPTA is indicated for symptomatic treatment of adult patients with COPD with a

< 70% predicted normal (post-bronchodilator) in patients with an exacerbation

history.

4.2.

Dosage and method of administration

Dose

Asthma

Adults and adolescents aged 12 years and over

One inhalation of BREO ELLIPTA 100/25 micrograms once daily

One inhalation of BREO ELLIPTA 200/25 micrograms once daily

Patients usually experience an improvement in lung function within 15 minutes of inhaling

BREO ELLIPTA.

However, the patient should be informed that regular daily usage is necessary to maintain

control of asthma symptoms and that use should be continued even when asymptomatic.

If symptoms arise in the period between doses, an inhaled, short-acting beta

-agonist

should be taken for immediate relief.

A starting dose of BREO ELLIPTA 100 micrograms/25 micrograms should be considered

for adults and adolescents 12 years and over who require a low to mid-dose of inhaled

corticosteroid (ICS) in combination with a long-acting beta

-agonist (LABA). If patients are

inadequately controlled on BREO ELLIPTA 100 micrograms/25 micrograms, consider

increasing the dose to 200 micrograms/25 micrograms, which may provide additional

improvement in asthma control.

Patients should be regularly reassessed by a healthcare professional so that the strength

of fluticasone furoate/vilanterol they are receiving remains optimal and is only changed on

medical advice. The dose should be titrated to the lowest dose at which effective control of

symptoms is maintained.

BREO ELLIPTA 200 micrograms/25 micrograms should be considered for adults and

adolescents 12 years and over who require a higher dose of ICS in combination with a

LABA.

The maximum recommended dose is BREO ELLIPTA 200 micrograms/25 micrograms

once daily.

Prescribers should be aware that in patients with asthma, 100 micrograms of fluticasone

furoate taken once daily produces similar effects to fluticasone propionate 250 micrograms

taken twice daily.

Children aged under 12 years:

The safety and efficacy of BREO ELLIPTA has not been established in children less than

12 years of age.

COPD

Adults aged 18 years and over

One inhalation of BREO ELLIPTA 100/25 micrograms once daily.

BREO ELLIPTA 200/25 micrograms is not indicated for patients with COPD.

Patients usually experience an improvement in lung function within 16-17 minutes of

inhaling BREO ELLIPTA.

Children

The use in children is not relevant given the COPD indication for this product.

Special Populations

Elderly

No dosage adjustment is required in patients over 65 years (see Section 5.2 –

Pharmacokinetic properties, Special Patient Populations).

Renal impairment

No dose adjustment is required for patients with renal impairment (see Section 5.2

Pharmacokinetic properties, Special Patient Populations).

Hepatic impairment

A clinical pharmacology study in subjects with mild, moderate and severe hepatic

impairment showed up to 3-fold increase in systemic exposure to fluticasone furoate (area

under the curve [AUC]) (see Section 5.2 - Pharmacokinetic properties).

Caution should be exercised when dosing patients with hepatic impairment who may be

more at risk of systemic adverse reactions associated with corticosteroids.

For patients with moderate or severe hepatic impairment, the maximum dose is one

inhalation of BREO ELLIPTA 100/25 micrograms once daily.

Paediatric population

The safety and efficacy of BREO ELLIPTA for the treatment of asthma has not been

established in children less than 12 years of age. No data are available.

The use in children is not relevant given the COPD indication for this product.

Method of administration

BREO ELLIPTA is for (oral) inhalation only.

BREO ELLIPTA should be administered once daily either morning or evening but at the

same time every day.

If a dose is missed, the next dose should be taken at the usual time the next day.

The final decision on evening or morning dosing should be left to the discretion of the

physician.

After inhalation, the patient should rinse their mouth with water without swallowing.

For instructions on the use and handling of this medicine, please refer to Section 6.6 -

Special precautions for disposal and other handling.

4.3.

Contraindications

BREO ELLIPTA is contraindicated in patients with severe milk-protein allergy or who have

demonstrated hypersensitivity to fluticasone furoate, vilanterol or any of the excipients.

4.4.

Special warnings and precautions for use

Exacerbations

BREO ELLIPTA should not be used to treat acute asthma symptoms or an acute

exacerbation in COPD, 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 therapy with BREO ELLIPTA, in asthma or COPD, without

physician supervision since symptoms may recur after discontinuation.

Asthma-related adverse events and exacerbations may occur during treatment with BREO

ELLIPTA. Patients should be asked to continue treatment but to seek medical advice if

asthma symptoms remain uncontrolled or worsen after initiation of BREO ELLIPTA.

Paradoxical bronchospasm

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate

increase in wheezing after dosing. This should be treated immediately with a short-acting

inhaled bronchodilator. BREO ELLIPTA should be discontinued immediately, the patient

assessed and alternative therapy instituted if necessary.

Cardiovascular effects

Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and

extrasystoles may be seen with sympathomimetic drugs, including BREO ELLIPTA. In a

placebo-controlled study in subjects with a history of, or an increased risk of

cardiovascular disease, there was no increase in the risk of cardiovascular events, serious

cardiovascular events, or adjudicated cardiovascular deaths in patients receiving

fluticasone furoate/vilanterol compared with placebo (see Section 4.8 - Undesirable

effects). However, BREO ELLIPTA should be used with caution in patients with severe

cardiovascular disease.

Patients with hepatic impairment

For patients with moderate to severe hepatic impairment, the 100/25 micrograms dose

should be used and patients should be monitored for systemic corticosteroid-related

adverse reactions (see Section 5.2 – Special Patient Populations).

Systemic corticosteroid effects

Systemic effects may occur with any ICS, particularly at high doses prescribed for long

periods. These effects are much less likely to occur than with oral corticosteroids. Possible

systemic effects include hypothalamic-pituitary-adrenal (HPA) axis suppression, decrease

in bone mineral density, growth retardation in children and adolescents, cataract,

glaucoma, central serous chorioretinopathy (CSCR) and more rarely, a range of

psychological or behavioural effects including psychomotor hyperactivity, sleep disorders,

anxiety, depression or aggression (particularly in children).

As with all medication containing corticosteroids, BREO ELLIPTA should be administered

with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated

infections.

Hyperglycaemia

There have been reports of increases in blood glucose levels with fluticasone

furoate/vilanterol. This should be considered in patients with a history of, or with risk

factors for, diabetes mellitus (see Section 4.8 - Undesirable effects).

Pneumonia

An increase in pneumonia has been observed in patients with COPD receiving BREO

ELLIPTA. There was also an increased incidence of pneumonias resulting in

hospitalisation. In some incidences, these pneumonia events were fatal (see Section 5.1 –

Pharmacodynamic properties, Clinical efficacy and safety, and Section 4.8 - Undesirable

effects). Physicians should remain vigilant for the possible development of pneumonia in

patients with COPD as the clinical features of such infections overlap with the symptoms

of COPD exacerbations. Risk factors for pneumonia in patients with COPD receiving

BREO ELLIPTA include current smokers, patients with a history of prior pneumonia,

patients with a body mass index < 25 kg/m

and patients with a (forced expiratory volume)

< 50% predicted. These factors should be considered when BREO ELLIPTA is

prescribed and treatment should be re-evaluated if pneumonia occurs.

Patients with asthma taking BREO ELLIPTA 200/25 micrograms may be at an increased

risk of pneumonia compared with those receiving BREO ELLIPTA 100/25 or placebo (see

Section 4.8 - Undesirable effects). No risk factors were identified.

4.5.

Interaction with other medicines and other forms of interaction

Interaction studies have only been conducted in adults. Clinically significant drug

interactions mediated by fluticasone furoate or vilanterol at clinical doses are considered

unlikely due to the low plasma concentrations achieved after inhaled dosing.

Interaction with beta-blockers

Beta-adrenergic blockers may weaken or antagonise the effect of beta

-adrenergic

agonists. Concurrent use of both non-selective and selective beta-blockers should be

avoided unless there are compelling reasons for their use.

Interaction with CYP3A4 inhibitors

Fluticasone furoate and vilanterol are both rapidly cleared by extensive first-pass

metabolism mediated by the liver enzyme CYP3A4.

Care is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole,

ritonavir) as there is potential for an increased systemic exposure to both fluticasone

furoate and vilanterol, which could lead to an increase in the potential for adverse

reactions (see Section 5.2 - Pharmacokinetic properties).

Interaction with P-glycoprotein inhibitors

Fluticasone furoate and vilanterol are both substrates of P-glycoprotein (P-gp). A clinical

pharmacology study in healthy subjects with co-administered vilanterol and the potent

P-gp and moderate CYP3A4 inhibitor, verapamil, did not show any significant effect on the

pharmacokinetics of vilanterol. Clinical pharmacology studies with a specific P-gp inhibitor

and fluticasone furoate have not been conducted.

4.6.

Fertility, pregnancy and lactation

Pregnancy

There has been limited pregnancy exposure in humans.

Animal studies have shown reproductive toxicity after administration of beta

-agonists and

corticosteroids (see Section 5.3 - Preclinical safety data).

Administration of BREO ELLIPTA to pregnant women should only be considered if the

expected benefit to the mother is greater than any possible risk to the foetus.

Breast-feeding

There is limited information on the excretion of fluticasone furoate or vilanterol or their

metabolites in human milk. However, other corticosteroids and beta

-agonists are detected

in human milk (see Section 5.3 - Preclinical safety data). A risk to breastfed

newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue BREO

ELLIPTA therapy taking into account the benefit of breast-feeding for the child and the

benefit of therapy for the woman.

Fertility

There are no fertility data in humans. Animal studies showed no effect of vilanterol or

fluticasone furoate on fertility (see Section 5.3 - Preclinical safety data).

4.7.

Effects on ability to drive and use machines

There have been no studies to investigate the effect of BREO ELLIPTA on driving

performance or the ability to operate machinery. A detrimental effect on such activities

would not be anticipated from the pharmacology of fluticasone furoate or vilanterol.

4.8.

Undesirable effects

Summary of the safety profile

Data from large asthma and COPD clinical trials were used to determine the frequency of

adverse reactions associated with BREO ELLIPTA. In the asthma clinical development

program, a total of 7,034 patients were included in an integrated assessment of adverse

reactions. In the COPD clinical development program, a total of 6,237 subjects were

included in an integrated assessment of adverse reactions.

With the exception of pneumonia and fractures, the safety profile was similar in patients

with asthma and COPD. During clinical studies, pneumonia and fractures were more

frequently observed in patients with COPD.

Tabulated list of adverse reactions

Adverse reactions noted in clinical trials are listed in the table below by system organ class

and frequency. The following convention has been used for the classification of adverse

reactions:

Very common: ≥1/10

Common:

≥1/100 to <1/10

Uncommon:

≥1/1000 to <1/100

Rare:

≥1/10000 to <1/1000

Very rare:

<1/10000

Within each frequency grouping, adverse reactions are presented in order of decreasing

seriousness.

System organ class

Adverse reaction(s)

Frequency

Infections and

infestations

Pneumonia*,

Upper Respiratory Tract Infection,

Bronchitis, Influenza,

Candidiasis of mouth and throat

Common

Nervous system

disorders

Headache

Very Common

Cardiac disorders

Extrasystoles**

Uncommon

Respiratory, thoracic &

mediastinal disorders

Nasopharyngitis,

Oropharyngeal pain,

Sinusitis, Pharyngitis,

Rhinitis, Cough, Dysphonia

Very Common

Common

Gastrointestinal

disorders

Abdominal pain

Common

System organ class

Adverse reaction(s)

Frequency

Musculoskeletal and

connective tissue

disorders

Arthralgia, Back pain

Fractures***

Common

General disorders and

administration site

conditions

Pyrexia

Common

Description of selected adverse reactions

*Pneumonia (see Section 4.4 – Special warnings and precautions for use)

In two replicate, 12-month studies in a total of 3,255 patients with COPD (mean post-

bronchodilator screening FEV

45% of predicted, standard deviation [SD] 13%) who had

experienced a COPD exacerbation in the previous year, there was a higher incidence of

pneumonia (6%-7%) reported in patients receiving the fluticasone furoate (at strengths of

50, 100, and 200 micrograms)/vilanterol 25 micrograms combination than in those

receiving vilanterol 25 micrograms alone (3%). Pneumonia which required hospitalisation

occurred in 3% of patients receiving BREO ELLIPTA (all strengths) and in < 1% of patients

receiving vilanterol. In these studies, nine fatal cases of pneumonia were reported. Of

these, seven were reported during treatment with BREO ELLIPTA 200/25 micrograms,

one during treatment with BREO ELLIPTA 100/25 micrograms and one post-treatment

with vilanterol monotherapy.

In SUMMIT, a multi-centre, randomised study (HZC113782), 16,568 subjects received

fluticasone furoate/vilanterol 100/25 micrograms, fluticasone furoate 100 micrograms,

vilanterol 25 micrograms, or placebo for a mean of 1.7 years. Subjects had moderate

COPD (mean post-bronchodilator screening FEV

60% of predicted, SD 6%) and a history

of, or an increased risk of, cardiovascular disease. The adverse events of pneumonia are

noted in the table below.

On-treatment Events

Number (%) of Subjects

[Event Rate Per 1000 Treatment Years]

FF/VI

100/25

N=4,140

FF 100

N=4,157

VI 25

N=4,140

Placebo

N=4,131

Pneumonia

237 (6)

[39.5]

228 (5)

[42.4]

163 (4)

[27.7]

214 (5)

[38.4]

Serious pneumonia

140 (3)

[22.4]

146 (4)

[25.1]

104 (3)

[16.4]

127 (3)

[22.2]

Adjudicated pneumonia deaths

13 (<1)

[1.8]

10 (<1)

[1.5]

6 (<1)

[0.9]

9 (<1)

[1.4]

In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of

pneumonia (adjusted for exposure, due to low numbers and limited number of patients on

placebo) seen with BREO ELLIPTA 100/25 microgram strength (9.6/1000 patient years)

was similar to placebo (8.0/1000 patient years). There was a higher incidence of

pneumonia in the 200/25 microgram strength (18.4/1000 patient years) compared to the

100/25 microgram strength. Few of the pneumonia events led to hospitalisation with either

strength, and there were no observed differences in the incidence of serious events

between the two treatment strengths.

**Cardiovascular events (see Section 4.4 – Special warnings and precautions for use)

For the SUMMIT study (see description above), cardiovascular adverse events are noted

in the table below.

On-treatment Events

Number (%) of Subjects

[Event Rate Per 1000 Treatment Years]

FF/VI

100/25

N=4,140

FF 100

N=4,157

VI 25

N=4,140

Placebo

N=4,131

Cardiovascular

735 (18)

[163]

699 (17)

[157]

707 (17)

[157]

695 (17)

[164]

Serious cardiovascular

350 (8)

[64.5]

320 (8)

[58.1]

337 (8)

[59.2]

318 (8)

[63.2]

Adjudicated cardiovascular deaths

82 (2)

[11.7]

80 (2)

[11.6]

90 (2)

[12.9]

86 (2)

[13.0]

***Fractures

In two replicate, 12-month studies in a total of 3,255 patients with COPD, the incidence of

bone fractures overall was low in all treatment groups, with a higher incidence in all BREO

ELLIPTA groups (2%) compared with the vilanterol 25 micrograms group (< 1%). Although

there were more fractures in the BREO ELLIPTA groups compared with the vilanterol

25 micrograms group, fractures typically associated with corticosteroid use (e.g., spinal

compression/thoracolumbar vertebral fractures, hip and acetabular fractures) occurred in

< 1% of the BREO ELLIPTA and vilanterol treatment arms.

For the SUMMIT study (see description above), fractures are noted in the table below.

On-treatment Events

Number (%) of Subjects

[Event Rate Per 1000 Treatment Years]

FF/VI

100/25

N=4,140

FF 100

N=4,157

VI 25

N=4,140

Placebo

N=4,131

All fractures

82 (2)

[13.6]

66 (2)

[12.8]

74 (2)

[13.2]

69 (2)

[11.5]

Fractures commonly associated with

ICS use

23 (<1)

[3.4]

24 (<1)

[3.9]

17 (<1)

[2.4]

13 (<1)

[2.1]

In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of

fractures was < 1%, and usually associated with trauma.

Post-Marketing Experience

System organ class

Adverse reaction(s)

Frequency

Immune system

disorders

Hypersensitivity reactions including

anaphylaxis, angioedema, rash, and

urticaria

Rare

Metabolism and

Hyperglycaemia

Uncommon

System organ class

Adverse reaction(s)

Frequency

nutrition disorders

Psychiatric disorders

Anxiety

Rare

Nervous system

disorders

Tremor

Rare

Cardiac disorders

Palpitations,

Tachycardia

Rare

Rare

Respiratory, thoracic

and mediastinal

disorders

Paradoxical bronchospasm

Rare

Musculoskeletal and

connective tissue

disorders

Muscle spasms

Common

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It

allows continued monitoring of the benefit/risk balance of the medicine. Healthcare

professionals are asked to report any suspected adverse reactions via:

https://nzphvc.otago.ac.nz/reporting/

4.9.

Overdose

Symptoms and signs

There are no data available from clinical trials on overdose with BREO ELLIPTA.

An overdose of BREO ELLIPTA may produce signs and symptoms due to the individual

components’ actions, including those seen with overdose of other beta

-agonists and

consistent with the known ICS class effects (see Section 4.4 – Special warnings and

precautions for use).

Treatment

There is no specific treatment for an overdose with BREO ELLIPTA. If overdose occurs,

the patient should be treated supportively with appropriate monitoring as necessary.

Cardioselective beta-blockade should only be considered for profound vilanterol overdose

effects that are clinically concerning and unresponsive to supportive measures.

Cardioselective beta-blocking drugs should be used with caution in patients with a history

of bronchospasm.

Further management should be as clinically indicated or as recommended by the national

poisons centre, where available. For advice on the management of overdose please

contact the National Poisons Centre on 0800 POISON (0800 764766).

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for obstructive airways diseases, Adrenergics and

other drugs for obstructive airway diseases, ATC code: R03AK10.

Chemical structure of fluticasone furoate

Chemical structure of vilanterol trifenatate

.Ph

Mechanism of action

Fluticasone furoate and vilanterol represent two classes of medications (a synthetic

corticosteroid and a selective LABA).

Pharmacodynamic effects

Fluticasone Furoate:

Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory

activity. The precise mechanism through which fluticasone furoate affects asthma and

COPD symptoms is not known. Corticosteroids have been shown to have a wide range of

actions on multiple cell types (e.g. eosinophils, macrophages, lymphocytes) and mediators

(e.g. cytokines and chemokines involved in inflammation).

Vilanterol trifenatate:

Vilanterol trifenatate is a selective LABA.

The pharmacologic effects of beta

-adrenoceptor agonist drugs, including vilanterol

trifenatate, are at least in part attributable to stimulation of intracellular adenylate 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 and inhibition of release of mediators of immediate

hypersensitivity from cells, especially from mast cells.

Molecular interactions occur between corticosteroids and LABAs, whereby steroids

activate the beta

-receptor gene, increasing receptor number and sensitivity; and LABAs

prime the glucocorticoid receptor for steroid-dependent activation and enhance cell

nuclear translocation. These synergistic interactions are reflected in enhanced anti-

inflammatory activity, which has been demonstrated in vitro and in vivo in a range of

inflammatory cells relevant to the pathophysiology of both asthma and COPD. In

peripheral blood mononuclear cells from subjects with COPD, a larger anti-inflammatory

effect was seen in the presence of the combination of fluticasone furoate/vilanterol

compared with fluticasone furoate alone at concentrations achieved with clinical doses.

Clinical efficacy and safety

Asthma

Three phase III randomised, double-blind studies (HZA106827, HZA106829 and

HZA106837) of different durations evaluated the safety and efficacy of BREO ELLIPTA in

adult and adolescent patients with persistent asthma. All subjects were using an ICS with

or without LABA for at least 12 weeks prior to visit 1. In HZA106837, all patients had at

least one exacerbation that required treatment with oral corticosteroids in the year prior to

visit 1. HZA106827 was 12 weeks in duration and evaluated the efficacy of BREO

ELLIPTA 100 micrograms/25 micrograms [n=201] and FF (fluticasone furoate)

100 micrograms [n=205]) compared with placebo [n=203], all administered once daily.

HZA106829 was 24 weeks in duration and evaluated the efficacy of BREO ELLIPTA

200 micrograms/25 micrograms [n=197] and FF 200 micrograms [n=194]) both

administered once daily compared with fluticasone propionate (FP) 500 micrograms twice

daily [n=195].

In HZA106827/HZA106829, the co-primary efficacy endpoints were change from baseline

in clinic visit trough (pre-bronchodilator and pre-dose) FEV

at the end of the treatment

period in all subjects and weighted mean serial FEV

over 0-24 hours post-dose calculated

in a subset of subjects at the end of the treatment period. Change from baseline in the

percentage of rescue-free 24-hour periods during treatment was a powered secondary

endpoint. Results for the primary and key secondary endpoints in these studies are

described in Table 1.

Table 1 - Results of primary and key secondary endpoints in HZA106827 and

HZA106829

Study No.

HZA106829

HZA106827

Treatment Dose of

FF/VI*(micrograms)

FF/VI 200/25

Once Daily

vs FF 200

Once Daily

FF/VI 200/25

Once Daily

vs FP 500

Twice Daily

FF/VI 100/25

Once Daily

vs FF 100

Once Daily

FF/V1/100/25

Once Daily

vs placebo

Once Daily

Change from Baseline in Trough FEV

Last Observation Carried Forward (LOCF)

Treatment difference

P value

(95% CI)

193 mL

p < 0.001

(108, 277)

210 mL

p < 0.001

(127, 294)

36 mL

p=0.405

(-48, 120)

172 mL

p < 0.001

(87, 258)

Weighted Mean Serial FEV

over 0-24 hours post-dose

Treatment difference

136 mL

206 mL

116 mL

302 mL

Study No.

HZA106829

HZA106827

P value

(95% CI)

p=0.048

(1, 270)

p=0.003

(73, 339)

p=0.06

(-5, 236)

p < 0.001

(178, 426)

Change from Baseline in Percentage of Rescue-Free 24-hour Periods

Treatment difference

P value

(95% CI)

11.7%

p<0.001

(4.9, 18.4)

6.3%

p=0.067

(-0.4, 13.1)

10.6%

p<0.001

(4.3, 16.8)

19.3%

p<0.001

(13.0, 25.6)

Change from Baseline in Percentage of Symptom-Free 24-hour Periods

Treatment difference

P value

(95% CI)

8.4%

p=0.010

(2.0, 14.8)

4.9%

p=0.137

(-1.6, 11.3

12.1%

p < 0.001

(6.2, 18.1)

18.0%

p < 0.001

(12.0, 23.9)

Change from Baseline in AM Peak Expiratory Flow

Treatment difference

P value

(95% CI)

33.5 L/min

p < 0.001

(25.3, 41.7)

32.9 L/min

p < 0.001

(24.8, 41.1)

14.6 L/min

p < 0.001

(7.9, 21.3)

33.3 L/min

p < 0.001

(26.5, 40.0)

Change from Baseline in PM Peak Expiratory Flow

Treatment difference

P value

(95% CI)

30.7 L/min

p < 0.001

(22.5, 38.9)

26.2 L/min

p < 0.001

18.0, 34.3)

12.3 L/min

P < 0.001

(5.8, 18.8)

28.2 L/min

p < 0.001

(21.7, 34.8)

*FF/VI = fluticasone furoate/vilanterol

HZA106837 was of variable treatment duration (from a minimum of 24 weeks to a

maximum of 76 weeks with the majority of patients treated for at least 52 weeks). In

HZA106837, patients were randomised to receive either BREO ELLIPTA

100 micrograms/25 micrograms [n=1009] or FF 100 micrograms [n=1010] both

administered once daily. The primary endpoint was the time to first severe asthma

exacerbation. A severe asthma exacerbation was defined as deterioration of asthma

requiring the use of systemic corticosteroids for at least 3 days or an inpatient

hospitalisation or emergency department visit due to asthma that required systemic

corticosteroids. Adjusted mean change from baseline in trough FEV

was also evaluated

as a secondary endpoint.

In HZA106837, the risk of experiencing a severe asthma exacerbation in patients receiving

BREO ELLIPTA 100 micrograms/25 micrograms was reduced by 20% compared with FF

100 micrograms alone (hazard ratio 0.795, p=0.036 95% CI [0.642, 0.985]). The rate of

severe asthma exacerbations per patient per year was 0.19 in the FF 100 group

(approximately 1 in every 5 years) and 0.14 in the BREO ELLIPTA

100 micrograms/25 micrograms group (approximately 1 in every 7 years). The ratio of the

exacerbation rate for BREO ELLIPTA 100 micrograms/25 micrograms versus FF 100 was

0.755 (95% CI 0.603, 0.945). This represents a 25% reduction in the rate of severe

asthma exacerbations for subjects treated with BREO ELLIPTA

100 micrograms/25 micrograms compared with FF 100 (p=0.014). The 24-hour

bronchodilator effect of BREO ELLIPTA was maintained throughout a one-year treatment

period with no evidence of loss in efficacy (no tachyphylaxis). BREO ELLIPTA

100 micrograms/25 micrograms consistently demonstrated 83 mL to 95 mL improvements

in trough FEV

at Weeks 12, 36 and 52 and Endpoint compared with FF 100 micrograms

(p<0.001 95% CI 52, 126mL at Endpoint). Forty-four percent of patients in the BREO

ELLIPTA 100 micrograms/25 micrograms group were well controlled (ACQ7 ≤ 0.75) at end

of treatment compared to 36% of subjects in the FF 100 microgram group (p < 0.001 95%

CI [1.23, 1.82]).

Studies versus salmeterol/fluticasone propionate

In a 24-week study (HZA113091) in adult and adolescent patients with persistent asthma,

both BREO ELLIPTA 100 micrograms/25 micrograms given once daily in the evening and

salmeterol/FP 50/250 micrograms given twice daily demonstrated improvements from

baseline in lung function. Adjusted mean treatment increases from baseline in weighted

mean 0-24 hours FEV

of 341 mL (BREO ELLIPTA) and 377 mL (salmeterol/FP)

demonstrated an overall improvement in lung function over 24 hours for both treatments.

The adjusted mean treatment difference of 37 mL between the groups was not statistically

significant (p=0.162).

Fluticasone furoate monotherapy

A 24-week randomised, double-blind placebo controlled study (FFA112059) evaluated the

safety and efficacy of FF 100 micrograms once daily [n=114] and FP 250 micrograms

twice daily [n=114] versus placebo [n=115] in adult and adolescent patients with persistent

asthma. All subjects had to have been on a stable dose of an ICS for at least 4 weeks

prior to visit 1 (screening visit) and the use of LABAs was not permitted within 4 weeks of

visit 1. The primary efficacy endpoint was change from baseline in clinic visit trough (pre-

bronchodilator and pre-dose) FEV

at the end of the treatment period. Change from

baseline in the percentage of rescue-free 24-hour periods during the 24-week treatment

period was a powered secondary. At the 24-week time point, FF 100 and FP increased

trough FEV

by 146 mL (95% CI 36, 257 mL, p=0.009) and 145 mL (95% CI 33, 257 mL,

p=0.011), respectively, compared to placebo. FF and FP both increased the percentage of

24-hour rescue-free periods by 14.8% (95% CI 6.9, 22.7, p<0.001) and 17.9% (95% CI

10.0, 25.7, p < 0.001) respectively versus placebo.

Allergen Challenge study

The bronchoprotective effect of BREO ELLIPTA 100 micrograms/25 micrograms on the

early and late asthmatic response to inhaled allergen was evaluated in a repeat dose,

placebo-controlled four-way crossover study (HZA113126) in patients with mild asthma.

Patients were randomised to receive BREO ELLIPTA 100/25 micrograms, FF

100 micrograms, VI (vilanterol) 25 micrograms or placebo once daily for 21 days followed

by challenge with allergen 1 hour after the final dose. The allergen was house dust mite,

cat dander, or birch pollen; the selection was based on individual screening tests. Serial

measurements were compared with pre-allergen challenge values taken after saline

inhalation (baseline). Overall, the greatest effects on the early asthmatic response were

seen with BREO ELLIPTA 100 micrograms/25 micrograms compared with FF

100 micrograms or vilanterol 25 micrograms alone. Both BREO ELLIPTA

(100 micrograms/25 micrograms) and FF 100 micrograms virtually abolished the late

asthmatic response compared with vilanterol alone. BREO ELLIPTA 100/25 micrograms

provided significantly greater protection against allergen-induced bronchial hyper-reactivity

compared with monotherapies FF and VI as assessed on Day 22 by methacholine

challenge.

Bronchoprotective and HPA-axis effects study

The bronchoprotective and HPA-axis effects of FF versus FP or budesonide (BUD) were

evaluated in an escalating repeat-dose, placebo-controlled, crossover study (203162) in

54 adults with a history of asthma, characterised by airway hyperresponsiveness and

FEV1 ≥65% predicted. Patients were randomised to one or two treatment periods,

comprising five 7-day dose-escalation phases of FF (25, 100, 200, 400, 800

micrograms/day), FP (50, 200, 500, 1,000, 2,000 micrograms/day), BUD (100, 400, 800,

1,600, 3,200 micrograms/day), or placebo. After each dose-escalation phase,

bronchoprotection via airway hyperresponsiveness to adenosine-5'-monophosphate

(AMP) challenge (provocative concentration causing ≥20% decline in FEV1 [AMP PC20])

and 24-hour weighted mean plasma cortisol were assessed.

Overall, and within approved dose ranges for asthma, FF (100 to 200 micrograms/day)

provided more protection against airway hyperresponsiveness (higher AMP PC20) with

less systemic activity (less cortisol suppression) than FP or BUD. Bronchoprotection (AMP

PC20, mg/mL) and HPA-axis effects (cortisol suppression, %) across the therapeutic dose

ranges were 81 to 116 mg/mL and 7 to 14% for FF (100 to 200 micrograms/day), 20 to 76

mg/mL and 7 to 50% for FP (200 to 2,000 micrograms/day), and 24 to 54 mg/mL and 13 to

44% for BUD (400 to 1,600 micrograms/day), respectively. The therapeutic index (dose for

50% cortisol suppression/dose for 50% maximum bronchoprotection) was higher for FF

(18.55) compared with FP (1.84) or BUD (1.31).

Chronic Obstructive Pulmonary Disease

The COPD clinical development programme included a 12-week (HZC113107), two 6-

month (HZC112206, HZC112207), two one-year randomised controlled studies

(HZC102970, HZC102871), and one long-term study (SUMMIT) in patients with a clinical

diagnosis of COPD. These studies included measures of lung function, dyspnoea and

moderate and severe exacerbations.

Six-month studies

HZC112206 and HZC112207 were 24-week randomised, double-blind, placebo controlled,

parallel group studies comparing the effect of the combination to vilanterol and FF alone

and placebo. HZC112206 evaluated the efficacy of BREO ELLIPTA

50 micrograms/25 micrograms [n=206] and BREO ELLIPTA

100 micrograms/25 micrograms [n=206]) compared with FF (100 micrograms [n=206]),

vilanterol (25 micrograms [n=205]) and placebo (n = 207), all administered once daily.

HZC112207 evaluated the efficacy of BREO ELLIPTA 100 micrograms/25 micrograms

[n=204] and BREO ELLIPTA 200 micrograms/25 micrograms [n=205]) compared with FF

(100 micrograms [n=204], 200 micrograms [n=203]) and vilanterol (25 micrograms

[n=203]) and placebo (n = 205), all administered once daily.

All patients were required to have a smoking history of at least 10 pack years; a post-

salbutamol FEV

/FVC ratio less than or equal to 0.70; post-salbutamol FEV

less than or

equal to 70% predicted and have a Modified Medical Research Council (mMRC) dyspnoea

score

2 (scale 0-4) at the screening. At screening, the mean pre-bronchodilator FEV

was 42.6% and 43.6% predicted, and the mean reversibility was 15.9% and 12.0% in

HZC112206 and HZC112207, respectively. The co-primary endpoints in both studies were

weighted mean FEV

from zero to 4 hours post-dose at Day 168 and change from

baseline in pre-dose trough FEV

at Day 169.

In an integrated analysis of both studies, BREO ELLIPTA 100 micrograms/25 micrograms

showed clinically meaningful improvements in lung function. At Day 169, BREO ELLIPTA

100 micrograms/25 micrograms and vilanterol increased adjusted mean trough FEV

129 mL (95% CI: 91, 167 mL, p < 0.001) and 83 mL (95% CI: 46, 121 mL, p < 0.001),

respectively, compared to placebo. BREO ELLIPTA 100 micrograms/25 micrograms

increased trough FEV

by 46 mL compared to vilanterol (95% CI: 8, 83 mL, p=0.017). At

Day 168, BREO ELLIPTA 100 micrograms/25 micrograms and vilanterol increased

adjusted mean weighted mean FEV

over 0-4 hours by 193 mL (95% CI: 156, 230 mL,

p < 0.001) and 145 mL (95% CI: 108, 181 mL, p < 0.001) respectively compared to

placebo. BREO ELLIPTA 100/25 increased adjusted mean weighted mean FEV

over 0-

4 hours by 148 mL compared to FF alone (95% CI: 112, 184 mL, p < 0.001).

In both the HZC112206 and HZC112207 studies, at Day 168, differences were seen in the

adjusted mean change from baseline CRQ-SAS dyspnoea scores between the BREO

ELLIPTA 100 micrograms/25 micrograms and placebo groups (HZC112206: 0.30, (95% CI

0.06,0.54 p=0.014); HZC112207: 0.24, (95% CI 0.02,0.46 p=0.029) and between the

BREO ELLIPTA 100 micrograms/25 micrograms and FF 100 microgram groups

(HZC112206: 0.24, (95% CI 0.01,0.48, p=0.044); HZC112207: 0.36, (95% CI (0.14,0.57),

p=0.001). For all the other pair-wise treatment comparisons at Day 168 for the CRQ-SAS

dyspnoea score, the p-value was > 0.05. In both studies, none of the treatment

comparisons at Day 168 achieved a minimal clinically important difference (>0.5 point

improvement) in mean CRQ-SAS Dyspnoea Domain scores. Patients treated with BREO

ELLIPTA 100 micrograms/25 micrograms also had significantly less cough and sputum,

required significantly less rescue medication as measured by number of occasions of

rescue salbutamol use (per 24-hour period) and number of night time awakenings

requiring salbutamol (per 24-hour period) compared to placebo.

12-month studies

Studies HZC102970 and HZC102871 were 52-week randomised, double-blind, parallel-

group studies comparing the effect of BREO ELLIPTA 200 micrograms/25 micrograms,

BREO ELLIPTA 100 micrograms/25 micrograms, BREO ELLIPTA

50 micrograms/25 micrograms with vilanterol 25 micrograms, all administered once daily,

on the annual rate of moderate/severe exacerbations in subjects with COPD with a

smoking history of at least 10 pack years and a post-salbutamol FEV

/FVC ratio less than

or equal to 0.70 and post-salbutamol FEV

less than or equal to 70% predicted and

documented history of ≥ 1 COPD exacerbation that required antibiotics and/or oral

corticosteroids or hospitalisation in the 12 months prior to visit 1. The primary endpoint

was the annual rate of moderate and severe exacerbations. Moderate/severe

exacerbations were defined as worsening symptoms that required treatment with oral

corticosteroids and/or antibiotics or in-patient hospitalisation. Both studies had a 4-week

run-in period during which all subjects received open-label FP/salmeterol 250/50 twice

daily to standardise COPD pharmacotherapy and stabilise disease prior to randomisation

to blinded study medication for 52 weeks. Prior to run-in, subjects discontinued use of

previous COPD medications except short-acting bronchodilators. The use of concurrent

inhaled long-acting bronchodilators (beta

-agonist and anticholinergic),

ipratropium/salbutamol combination products, oral beta

-agonists, and theophylline

preparations were not allowed during the treatment period. Oral corticosteroids and

antibiotics were allowed for the acute treatment of COPD exacerbations with specific

guidelines for use. Subjects used salbutamol on an as-needed basis throughout the

studies.

The results of both studies showed that treatment with BREO ELLIPTA

100 micrograms/25 micrograms once daily resulted in a lower annual rate of

moderate/severe COPD exacerbations compared with vilanterol (p ≤ 0.024). Reductions in

risk of time to first moderate or severe exacerbation and rate of exacerbations requiring

corticosteroid use were also observed with fluticasone furoate/vilanterol

100/25 micrograms once daily compared with vilanterol.

Table 2: Analysis of Exacerbation Rates following 12 months of treatment

Endpoint

HZC102970

HZC102871

HZC102970 and

HZC102871

integrated

Vilantero

l (n=409)

Breo Ellipta

100/25

(n=403)

Vilanterol

(n=409)

Breo Ellipta

100/25

(n=403)

Vilant

erol

(n=81

Breo Ellipta

100/25

(n=806)

Moderate and severe exacerbations

Adjusted

mean annual

rate

1.14

0.90

1.05

0.70

1.11

0.81

Ratio vs VI

95% CI

p-value

% reduction

95% CI

0.79

(0.64,0.97)

0.024

(3,36)

0.66

(0.54, 0.81)

< 0.001

(19,46)

0.73

(0.63, 0.84)

< 0.001

(16,37)

Time to first

exacerbation

Hazard ratio

(95% CI)

% risk

reduction

p-value

0.80

(0.66, 0.99)

0.036

0.72

(0.59, 0.89)

0.002

0.76

(0.66, 0.88)

< 0.001

Exacerbations requiring systemic/oral corticosteroids

Annual rate

0.86

0.66

0.84

0.52

0.87

0.61

Ratio vs VI

95% CI

p-value

% reduction

95% CI

0.77

(0.60,0.99)

0.041

(1, 40)

0.62

(0.49, 0.78)

< 0.001

(22, 51)

0.70

(0.59, 0.83)

< 0.001

(17, 41)

In an integrated analysis of HZC102970 and HZC102871 at Week 52, an improvement

was seen when comparing the BREO ELLIPTA 100 micrograms/25 micrograms vs.

vilanterol 25 micrograms in adjusted mean trough FEV

(42 mL 95% CI: 19, 64 mL,

p < 0.001). The 24-hour bronchodilator effect of BREO ELLIPTA was maintained from the

first dose throughout a one-year treatment period with no evidence of loss in efficacy (no

tachyphylaxis).

Overall, across the two studies combined 2009 (62%) patients had cardiovascular

history/risk factors at screening. The incidence of cardiovascular history/risk factors was

similar across the treatment groups with patients in the cardiovascular history/risk factors

subgroup most commonly suffering from hypertension (46%), followed by

hypercholesterolemia (29%) and diabetes mellitus (12%). Similar effects in reduction of

moderate and severe exacerbations were observed in this subgroup as compared with the

overall population. In patients with a cardiovascular history/risk factors, BREO ELLIPTA

100 micrograms/25 micrograms resulted in a significantly lower annual rate of

moderate/severe COPD exacerbations compared with vilanterol (adjusted mean annual

rates of 0.83 and 1.18 respectively, 30% reduction (95% CI 16, 42%, p < 0.001).

Improvements were also seen in this subgroup at week 52 when comparing the BREO

ELLIPTA 100 micrograms/25 micrograms vs. vilanterol 25 micrograms in adjusted mean

trough FEV

(44 mL 95% CI: 15, 73 mL, p=0.003).

Long-term study

SUMMIT was a multi-centre, randomised, double-blind study evaluating the effect on

survival of fluticasone furoate/vilanterol 100/25 micrograms compared with placebo in

16,568 subjects. Subjects were treated for up to 4 years (mean 1.7 years) with either

fluticasone furoate/vilanterol 100/25 micrograms, fluticasone furoate 100 micrograms,

vilanterol 25 micrograms, or placebo. All subjects had COPD with moderate airflow

limitation (≥ 50% and ≤ 70% predicted FEV

) and a history of, or an increased risk of,

cardiovascular disease.

Survival with fluticasone furoate/vilanterol was not significantly improved compared with

placebo (HR 0.878; 95% CI: 0.739, 1.042; p=0.137), FF (HR 0.964; 95% CI: 0.808, 1.149;

p=0.681) or VI (HR 0.912; 95% CI: 0.767, 1.085; p=0.299). All-cause mortality was:

fluticasone furoate/vilanterol, 6.0%; placebo, 6.7%; fluticasone furoate, 6.1%; vilanterol,

6.4%).

Fluticasone furoate/vilanterol slowed the rate of decline in lung function as measured by

, by 8 mL/year compared with placebo (95% CI: 1, 15; p=0.019). There was no

impact (0 mL/year; 95% CI: -6, 7; p=0.913) on the rate of decline for fluticasone

furoate/vilanterol compared with fluticasone furoate; there was a difference of 10 mL/year

for fluticasone furoate/vilanterol compared with vilanterol (95% CI: 3, 16; p=0.004). The

mean rate of decline in FEV

was: fluticasone furoate/vilanterol, 38 mL/year; placebo,

46 mL/year; fluticasone furoate, 38 mL/year; vilanterol, 47 mL/year.

The risk of a cardiovascular composite event (on-treatment cardiovascular death,

myocardial infarction, stroke, unstable angina, or transient ischemic attack) with

fluticasone furoate/vilanterol was not significantly lower than placebo (HR 0.926; 95% CI:

0.750, 1.143; p=0.475), FF (HR 1.033; 95% CI: 0.834, 1.281; p=0.763) or VI (HR 0.938;

95% CI: 0.761, 1.155; p=0.545). The incidence of cardiovascular composite events was:

fluticasone furoate/vilanterol, 4.2%; placebo, 4.2%; fluticasone furoate, 3.9%; vilanterol

4.4%.

Fluticasone furoate/vilanterol demonstrated a larger mean change from baseline in post-

bronchodilator FEV

at Day 360 compared with placebo (89 mL; 95% CI: 76, 102;

p<0.001), FF (40 mL; 95% CI: 27, 53; p < 0.001), and VI (26 mL; 95% CI: 13, 39;

p < 0.001). The adjusted mean change from baseline was: fluticasone furoate/vilanterol

50 mL, placebo, -39 mL; fluticasone furoate, 9 mL; vilanterol, 24 mL.

Fluticasone furoate/vilanterol reduced the annual rate of moderate or severe

exacerbations by 29% (95% CI: 22, 35; p < 0.001) compared with placebo, by 19%

compared with FF (95% CI: 12, 26; p < 0.001) and by 21% compared with VI (95% CI: 14,

28; p < 0.001). The annual rate of moderate or severe exacerbations was 0.25 for

fluticasone furoate/vilanterol, 0.35 for placebo, 0.31 for fluticasone furoate, and 0.31 for

vilanterol.

Fluticasone furoate/vilanterol reduced the annual rate of severe exacerbations (i.e.

requiring hospitalisation) by 27% (95% CI: 13, 39; p < 0.001) compared with placebo, by

11% compared with FF (95% CI: -6, 25; p=0.204) and by 9% compared with VI (95% CI: -

8, 24; p=0.282). The annual rate of exacerbations requiring hospitalisation was 0.05 for

fluticasone furoate/vilanterol, 0.07 for placebo, 0.06 for fluticasone furoate, and 0.06 for

vilanterol.

Studies versus salmeterol/fluticasone propionate combinations

In a 12-week study (HZC113107) in COPD patients both BREO ELLIPTA

100 micrograms/25 micrograms given once daily in the morning and FP/salmeterol

500/50 micrograms given twice daily, demonstrated improvements from baseline in lung

function. Adjusted mean treatment increases from baseline in weighted mean 0-24 hours

of 130 mL (BREO ELLIPTA) and 108 mL (FP/salmeterol) demonstrated an overall

improvement in lung function over 24 hours for both treatments. The adjusted mean

treatment difference of 22 mL (95% CI: -18, 63 mL) between the groups was not

statistically significant (p=0.282). A clinically meaningful mean improvement was achieved

for mean change from baseline in SGRQ Total Score after 12 weeks of treatment for the

BREO ELLIPTA 100 micrograms/25 micrograms once daily treatment group (-4.78) but

not for the FP/salmeterol 500/50 twice daily treatment group (-3.29). The adjusted mean

treatment difference was -1.50 (p=0.215. 95% CI (-3.86, 0.87).

5.2.

Pharmacokinetic properties

Absorption

The absolute bioavailability for fluticasone furoate and vilanterol when administered by

inhalation as BREO ELLIPTA was on average 15.2% and 27.3%, respectively. The oral

bioavailability of both fluticasone furoate and vilanterol was low, on average 1.26% and

< 2%, respectively. Given this low oral bioavailability, systemic exposure for fluticasone

furoate and vilanterol following inhaled administration is primarily due to absorption of the

inhaled portion of the dose delivered to the lung.

Distribution

Following intravenous dosing, both fluticasone furoate and vilanterol are extensively

distributed with average volumes of distribution at steady state of 661 L and 165 L,

respectively.

Both fluticasone furoate and vilanterol have a low association with red blood cells. In vitro

plasma protein binding in human plasma of fluticasone furoate and vilanterol was high, on

average > 99.6% and 93.9%, respectively. There was no decrease in the extent of in vitro

plasma protein binding in subjects with renal or hepatic impairment.

Fluticasone furoate and vilanterol are substrates for P-gp, however, concomitant

administration of BREO ELLIPTA with P-gp inhibitors is considered unlikely to alter

fluticasone furoate or vilanterol systemic exposure since they are both well absorbed

molecules.

Biotransformation

Based on in vitro data, the major routes of metabolism of both fluticasone furoate and

vilanterol in human are mediated primarily by CYP3A4.

Fluticasone furoate is primarily metabolised through hydrolysis of the S-fluoromethyl

carbothioate group to metabolites with significantly reduced corticosteroid activity.

Vilanterol is primarily metabolised by O-dealkylation to a range of metabolites with

significantly reduced

- and

-agonist activity.

A repeat-dose CYP3A4 drug interaction study was performed in healthy subjects with the

fluticasone furoate/vilanterol combination (200 micrograms/25 micrograms) and the strong

CYP3A4 inhibitor ketoconazole (400 mg). Co-administration increased mean fluticasone

furoate AUC

(0-24)

and C

by 36% and 33%, respectively. The increase in fluticasone

furoate exposure was associated with a 27% reduction in 0-24 hours weighted mean

serum cortisol. Co-administration increased mean vilanterol AUC

(0-t)

and C

65% and

22%, respectively. The increase in vilanterol exposure was not associated with an

increase in beta-agonist related systemic effects on heart rate, blood potassium or QTcF

interval.

Elimination

Following oral administration fluticasone furoate was eliminated in humans mainly by

metabolism with metabolites being excreted almost exclusively in faeces, with < 1% of the

recovered radioactive dose eliminated in the urine. The apparent plasma elimination half-

life of fluticasone furoate following inhaled administration of BREO ELLIPTA was, on

average, 24 hours.

Following oral administration, vilanterol was eliminated in humans mainly by metabolism

followed by excretion of metabolites in urine and faeces of approximately 70% and 30% of

the radioactive dose, respectively. The apparent plasma elimination half-life of vilanterol

following inhaled administration of BREO ELLIPTA was, on average, 2.5 hours.

Special Patient Populations

Children

In adolescents (12 years or older), there are no recommended dose modifications.

The pharmacokinetics of BREO ELLIPTA in patients less than 12 years of age has not

been studied. The safety and efficacy of BREO ELLIPTA in children under the age of

12 years has not yet been established.

Elderly

The effects of age on the pharmacokinetics of fluticasone furoate and vilanterol were

determined in phase III studies in COPD and asthma.

There was no evidence for age (12-84) to affect the PK of fluticasone furoate or vilanterol

in subjects with asthma.

There was no evidence for age to affect the PK of fluticasone furoate in subjects with

COPD while there was an increase (37%) in AUC

(0-24)

of vilanterol over the observed age

range of 41 to 84 years. For an elderly subject (aged 84 years) with low bodyweight

(35 kg), vilanterol AUC

(0-24)

is predicted to be 35% higher than the population estimate

(subject with COPD aged 60 years and bodyweight of 70 kg), whilst C

was unchanged.

These differences are unlikely to be of clinical relevance.

In subjects with asthma and subjects with COPD there are no recommended dose

modifications.

Renal impairment

A clinical pharmacology study of BREO ELLIPTA showed that severe renal impairment

(creatinine clearance < 30 mL/min) did not result in significantly greater exposure to

fluticasone furoate or vilanterol or more marked corticosteroid or beta

-agonist systemic

effects compared with healthy subjects. No dose adjustment is required for patients with

renal impairment.

The effects of haemodialysis have not been studied.

Hepatic Impairment

Following repeat dosing of BREO ELLIPTA for 7 days, there was an increase in

fluticasone furoate systemic exposure (up to three-fold as measured by AUC

(0–24)

) in

subjects with hepatic impairment (Child-Pugh A, B or C) compared with healthy subjects.

The increase in fluticasone furoate systemic exposure (BREO ELLIPTA

200/25 micrograms) in subjects with moderate hepatic impairment (Child-Pugh B) was

associated with an average 34% reduction in serum cortisol compared with healthy

subjects. In subjects with severe hepatic impairment (Child-Pugh C) that received a lower

dose of 100/12.5 micrograms there was no reduction in serum cortisol. For patients with

moderate or severe hepatic impairment, the maximum dose is 100/25 micrograms (see

Section 4.2 - Dosage and method of administration).

Following repeat dosing of BREO ELLIPTA for 7 days, there was no significant increase in

systemic exposure to vilanterol (C

and AUC) in subjects with mild, moderate, or severe

hepatic impairment (Child-Pugh A, B or C).

There were no clinically relevant effects of the BREO ELLIPTA combination on beta-

adrenergic systemic effects (heart rate or serum potassium) in subjects with mild or

moderate hepatic impairment (vilanterol, 25 micrograms) or with severe hepatic

impairment (vilanterol, 12.5 micrograms) compared with healthy subjects.

For patients with moderate to severe hepatic impairment, the 100/25 micrograms dose

should be used (see Section 4.2 - Dosage and method of administration).

Other Special Populations

In subjects with asthma, estimates of fluticasone furoate AUC

(0-24)

for East Asian,

Japanese and South East Asian subjects (12-13% of subjects) were on average 33% to

53% higher compared with other racial groups. However, there was no evidence for the

higher systemic exposure in this population to be associated with greater effect on 24-hour

urinary cortisol excretion. On average, vilanterol C

is predicted to be 220 to 287%

higher and AUC

(0-24)

comparable for those subjects from an Asian heritage compared with

subjects from other racial groups. However, there was no evidence that this higher

vilanterol C

resulted in clinically significant effects on heart rate.

In subjects with COPD estimates of fluticasone furoate AUC

(0-24)

for East Asian, Japanese

and South East Asian subjects (13-14% subjects) were on average 23% to 30% higher

compared with Caucasian subjects. However, there was no evidence for the higher

systemic exposure in this population to be associated with greater effect on 24-hour

urinary cortisol excretion. There was no effect of race on pharmacokinetic parameter

estimates of vilanterol in subjects with COPD.

Gender, Weight and BMI

There was no evidence for gender, weight or BMI to influence the pharmacokinetics of

fluticasone furoate based on a population pharmacokinetic analysis of phase III data in

1213 subjects with asthma (712 females) and 1225 subjects with COPD (392 females).

There was no evidence for gender, weight or BMI to influence the pharmacokinetics of

vilanterol based on a population pharmacokinetic analysis in 856 subjects with asthma

(500 females) and 1091 subjects with COPD (340 females).

No dosage adjustment is necessary based on gender, weight or body mass index (BMI).

5.3.

Preclinical safety data

Pharmacological and toxicological effects seen with fluticasone furoate or vilanterol in

nonclinical studies were those typically associated with either glucocorticoids or beta

agonists. Administration of fluticasone furoate combined with vilanterol did not result in any

significant new toxicity.

Carcinogenesis/mutagenesis

Fluticasone furoate was not genotoxic in a standard battery of studies and was not

carcinogenic in lifetime inhalation studies in rats or mice at exposures similar to those at

the maximum recommended human dose, based on AUC.

Genetic toxicity studies indicate vilanterol does not represent a genotoxic hazard to

humans. Consistent with findings for other beta

-agonists, in lifetime inhalation studies

vilanterol caused proliferative effects in the female rat and mouse reproductive tract and

rat pituitary gland. There was no increase in tumour incidence in rats or mice at exposures

2- or 30-fold, respectively, those at the maximum recommended human dose, based on

AUC.

Reproductive Toxicology

Effects seen following inhalation administration of fluticasone furoate in combination with

vilanterol in rats were similar to those seen with fluticasone furoate alone.

Fluticasone furoate was not teratogenic in rats or rabbits, but delayed development in rats

and caused abortion in rabbits at maternally toxic doses. There were no effects on

development in rats at exposures approximately 3-times greater than those at the

maximum recommended human dose, based on AUC.

Vilanterol was not teratogenic in rats. In inhalation studies in rabbits, vilanterol caused

effects similar to those seen with other beta

-agonists (cleft palate, open eyelids,

sternebral fusion and limb flexure/malrotation). When given subcutaneously there were no

effects at exposures 84-times greater than those at the maximum recommended human

dose, based on AUC.

Neither fluticasone furoate nor vilanterol had any adverse effects on fertility or pre- and

post-natal development in rats.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients

Lactose monohydrate (which contains milk protein)

Magnesium stearate

6.2.

Incompatibilities

None reported.

6.3.

Shelf life

2 years

Following removal from the tray, the product may be stored for a maximum period of

1 month.

6.4.

Special precautions for storage

Store below 30°C. If stored in the refrigerator, allow the inhaler to return to room

temperature for at least an hour before use.

Write the date the inhaler should be discarded on the label in the space provided. The

date should be added as soon as the inhaler has been removed from the tray.

6.5.

Nature and contents of container

The plastic Ellipta inhaler consists of a light grey body, a pale blue mouthpiece cover and

a dose counter, packed into a foil laminate tray containing a desiccant sachet. The tray is

sealed with a peelable foil lid.

The inhaler contains two strips of 14 or 30 regularly distributed blisters, each containing a

white powder.

BREO ELLIPTA 100 micrograms/25 micrograms: Packs containing a single inhaler

providing either 14 or 30 doses.

BREO ELLIPTA 200 micrograms/25 micrograms: Packs containing a single inhaler

providing either 14 or 30 doses.

Not all pack sizes may be distributed in New Zealand.

6.6.

Special precautions for disposal and other handling

Disposal

Any unused medicine or water material should be disposed of in accordance with local

requirements.

Instructions for handling

The Ellipta inhaler is provided in a foil laminate tray containing a desiccant sachet. The

tray provides moisture protection and should only be opened when you are ready to use it

for the first time. Once opened the desiccant sachet should be discarded.

Only open the Ellipta inhaler cover when you are ready to take a dose.

If you open and close the cover of the Ellipta inhaler without inhaling the medicine, you will

lose the dose. The dose will be securely held inside the inhaler, but it will be no longer

available. It is not possible to accidently take extra medicine or a double dose in one

inhalation.

When you first use the Ellipta inhaler you do not need to check that it is working properly,

and you do not need to prepare it for use in any special way.

Your device may contain either 30 or 14 starting doses.

Important

The dose-counter indicates the number of doses left. Patients should consider getting a

replacement when the counter shows the number 05. When the counter shows a full solid

red background it must be replaced.

7.

MEDICINE SCHEDULE

Prescription Medicine

8.

SPONSOR

GlaxoSmithKline NZ Limited

Private Bag 106600

Downtown

Auckland

New Zealand

Phone:

(09) 367 2900

Facsimile:

(09) 367 2910

9.

DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine:

12 December 2013

10.

DATE OF REVISION OF THE TEXT

17 September 2020

Summary table of changes:

Section changed

Summary of new information

Addition of information from Bronchoprotective and

HPA-axis effects study (Clinical Study 203162)

Version 9.0

Trade marks are owned by or licensed to the GSK group of companies.

BREO ELLIPTA was developed in collaboration with Innoviva.

© 2020 GSK group of companies or its licensor.

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