Bufomix Easyhaler, 160 micrograms/4.5 micrograms/inhalation, inhalation powder

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Budesonide; Formoterol fumarate dihydrate
Available from:
Orion Corporation
ATC code:
R03AK; R03AK07
INN (International Name):
Budesonide; Formoterol fumarate dihydrate
Dosage:
160/4.5 microgram(s)
Pharmaceutical form:
Powder for Inhalation
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Adrenergics in combination with corticosteroids or other drugs, excl. anticholinergics; formoterol and budesonide
Authorization status:
Marketed
Authorization number:
PA1327/015/002
Authorization date:
2014-04-11

QR Code to URL: oeh.fi/bfie

Scan this code or visit www.oeh.fi/bfie to see instructions on how to use Easyhaler

Package leaflet: Information for the patient

Bufomix Easyhaler, 160 micrograms/4.5 micrograms/inhalation, Inhalation Powder

Budesonide/formoterol fumarate dihydrate

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

What is in this leaflet

What Bufomix Easyhaler 160/4.5 is and what it is used for

What you need to know before you use Bufomix Easyhaler 160/4.5

How to use Bufomix Easyhaler 160/4.5

Possible side effects

How to store Bufomix Easyhaler 160/4.5

Contents of the pack and other information

1.

What Bufomix Easyhaler 160/4.5 is and what it is used for

Bufomix Easyhaler is an inhaler that is used to treat asthma in adults and adolescents aged 12 - 17 years. It is

also used to treat the symptoms of Chronic Obstructive Pulmonary Disease (COPD) in adults aged 18 years

and older. It contains two different medicines: budesonide and formoterol fumarate dihydrate.

Budesonide belongs to a group of medicines called ‘corticosteroids’. It works by reducing and

preventing swelling and inflammation in your lungs.

Formoterol fumarate dihydrate belongs to a group of medicines called ‘long-acting beta

adrenoceptor

agonists’ or ‘bronchodilators’. It works by relaxing the muscles in your airways. This helps you to

breathe more easily.

Asthma

Bufomix Easyhaler 160/4.5 can be prescribed for asthma in two different ways.

a) Some people are prescribed two asthma inhalers: Bufomix Easyhaler 160/4.5 and a separate

‘reliever inhaler’.

They use Bufomix Easyhaler every day. This helps to prevent asthma symptoms from happening.

They use their ‘reliever inhaler’ when they get asthma symptoms, to make it easier to breathe again.

b) Some people are prescribed Bufomix Easyhaler 160/4.5 as their only asthma inhaler.

They use Bufomix Easyhaler every day. This helps to prevent asthma symptoms from happening.

They also use Bufomix Easyhaler when they need extra doses for relief of asthma symptoms, to make

it easier to breathe again and if agreed with the doctor also to prevent asthma symptoms from

happening (for example, when exercising or on exposure to allergens). They do not need a separate

inhaler for this.

Chronic obstructive pulmonary disease (COPD)

Bufomix Easyhaler 160/4.5 can also be used to treat the symptoms of COPD in adults. COPD is a long-term

disease of the airways in the lungs, which is often caused by cigarette smoking.

2.

What you need to know before you use Bufomix Easyhaler 160/4.5

Do not use Bufomix Easyhaler 160/4.5:

if you are allergic to budesonide, formoterol or to the other ingredient of this medicine (listed in section

6) which is lactose (which contains small amounts of milk protein).

Warnings and precautions

Talk to your doctor or pharmacist before using Bufomix Easyhaler if you:

are diabetic

have a lung infection

have high blood pressure or you have ever had a heart problem (including an uneven heart beat, a very

fast pulse, narrowing of the arteries or heart failure)

have problems with your thyroid or adrenal glands

have low levels of potassium in your blood

have severe liver problems.

Contact your doctor if you experience blurred vision or other visual disturbances.

Rinse your mouth after inhaling your dose in order to avoid fungal infection in the mouth.

Other medicines and Bufomix Easyhaler

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines,

including medicines obtained without a prescription.

Some medicines may increase the effects of Bufomix Easyhaler and your doctor may wish to monitor you

carefully if you are taking these medicines (including some medicines for HIV: ritonavir, cobicistat).

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

Beta-blocker medicines (such as atenolol or propranolol for high blood pressure), including eyedrops

(such as timolol for glaucoma).

Medicines for a fast or uneven heart beat (such as quinidine).

Medicines like digoxin, often used to treat heart failure.

Diuretics, also known as ‘water tablets’ (such as furosemide). These are used to treat high blood

pressure.

Steroid medicines that you take by mouth (such as prednisolone).

Xanthine medicines (such as theophylline or aminophylline). These are often used to treat asthma.

Other bronchodilators (such as salbutamol).

Tricyclic anti-depressants (such as amitriptyline) and the anti-depressant nefazodone.

Phenothiazine medicines (such as chlorpromazine and prochlorperazine).

Medicines

treat

infections

(such

ketoconazole,

itraconazole,

voriconazole,

posaconazole,

clarithromycin and telithromycin).

Medicines for Parkinson’s disease (such as leva-dopa).

Medicines for thyroid problems (such as levo-thyroxine).

If any of the above applies to you, or if you are not sure, talk to your doctor or pharmacist before using Bufomix

Easyhaler.

Also tell your doctor or pharmacist if you are going to have a general anaesthetic for an operation or for dental

work.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or pharmacist for advice before using this medicine.

Do not use Bufomix Easyhaler unless your doctor tells you to.

If you get pregnant while using Bufomix Easyhaler, do not stop using Bufomix Easyhaler but talk to

your doctor immediately.

Driving and using machines

Bufomix Easyhaler has no or negligible effect on your ability to drive or to use tools or machines.

Bufomix Easyhaler contains lactose

which is a type of sugar. If you have been told by your doctor that you

have an intolerance to some sugars, talk to your doctor before using this medicine. The amount of lactose in

this medicine does not normally cause problems in people who are lactose intolerant.

The excipient lactose contains small amounts of milk proteins, which may cause allergic reaction.

3.

How to use Bufomix Easyhaler 160/4.5

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if

you are not sure.

It is important to use Bufomix Easyhaler every day, even if you have no asthma or COPD symptoms at

the time.

Your doctor will want to regularly check your asthma symptoms.

If you have been taking steroid tablets for your asthma or COPD, your doctor may reduce the number of tablets

that you take, once you start to use Bufomix Easyhaler. If you have been taking oral steroid tablets for a long

time, your doctor may want you to have blood tests from time to time. When reducing oral steroid tablets, you

may feel generally unwell even though your chest symptoms may be improving. You might experience

symptoms such as a stuffy or runny nose, weakness or joint or muscle pain and rash (eczema). If any of these

symptoms bother you, or if symptoms such as headache, tiredness, nausea (feeling sick) or vomiting (being

sick) occur, please contact your doctor immediately. You may need to take other medication if you develop

allergic or arthritic symptoms. Speak to your doctor if you are concerned as to whether you should continue to

use Bufomix Easyhaler.

Your doctor may consider adding steroid tablets to your usual treatment during periods of stress (for example,

when you have a chest infection or before an operation).

Important information about your asthma or COPD symptoms

If you feel you are getting breathless or wheezy while using Bufomix Easyhaler, you should continue to use

Bufomix Easyhaler but go to see your doctor as soon as possible, as you may need additional treatment.

Contact your doctor immediately if:

your breathing is getting worse or you often wake up at night with asthma.

your chest starts to feel tight in the morning or your chest tightness lasts longer than usual.

These signs could mean that your asthma or COPD is not being properly controlled and you may need different

or additional treatment immediately.

ASTHMA

Bufomix Easyhaler 160/4.5 can be prescribed for asthma in two different ways. The amount of Bufomix

Easyhaler to use and when to use it depends on how it has been prescribed for you.

If you have been prescribed Bufomix Easyhaler and a separate reliever inhaler, read the section called

‘A) Using Bufomix Easyhaler and a separate reliever inhaler’.

If you have been prescribed Bufomix Easyhaler as your only inhaler, read the section called ‘B) Using

Bufomix Easyhaler as your only asthma inhaler’.

A) Using Bufomix Easyhaler and a separate reliever inhaler

Use your Bufomix Easyhaler every day.

This helps to prevent asthma symptoms from happening.

Adults (18 years and above)

The usual dose is 1 or 2 inhalations, twice a day.

Your doctor may increase this to 4 inhalations, twice a day.

If your symptoms are well controlled, your doctor may ask you to take your medicine once a day.

Adolescents (12 to 17 years)

The usual dose is 1 or 2 inhalations, twice a day.

If your symptoms are well controlled, your doctor may ask you to take your medicine once a day.

A lower strength of Bufomix Easyhaler is available for children aged from 6 to 11 years.

Bufomix Easyhaler is not recommended to be used in children who are younger than 6 years.

Your doctor (or asthma nurse) will help you to manage your asthma. They will adjust the dose of this medicine

to the lowest dose that controls your asthma. However, do not adjust the dose without talking to your doctor

(or asthma nurse) first.

Use your separate ‘reliever inhaler’ to treat asthma symptoms when they happen.

Always keep your

‘reliever inhaler’ with you to use when you need it. Do not use Bufomix Easyhaler to treat asthma symptoms

- use your reliever inhaler.

B) Using Bufomix Easyhaler as your only asthma inhaler

Only use Bufomix Easyhaler in this way if your doctor has told you to and if you are aged 12 or above.

Use your Bufomix Easyhaler 160/4.5 every day.

This helps to prevent asthma symptoms from happening.

You can take:

1 inhalation in the morning

and

1 inhalation in the evening

or

2 inhalations in the morning

or

2 inhalations in the evening.

Your doctor may increase this to 2 inhalations twice a day.

Also use Bufomix Easyhaler 160/4.5 as a ‘reliever inhaler’

to treat asthma symptoms when they happen and

to prevent asthma symptoms from happening (for example, when exercising or on exposure to allergens).

If you get asthma symptoms, take 1 inhalation and wait a few minutes.

If you do not feel better, take another inhalation.

Do not take more than 6 inhalations at a single time.

Always keep your Bufomix Easyhaler with you, so you can use it when you need it.

A total daily dose of more than 8 inhalations is not normally needed. However, your doctor may allow you to

take up to 12 inhalations a day for a limited period.

If you regularly need to use 8 or more inhalations a day, make an appointment to see your doctor or nurse.

They may need to change your treatment.

Do not use more than 12 inhalations in total in 24 hours.

If you are doing exercise and you get asthma symptoms, use Bufomix Easyhaler as described here. It is

important that you discuss with your doctor the use of Bufomix Easyhaler to prevent

asthma symptoms from happening; how often you exercise or how often you are exposed to allergens could

impact the treatment that it is prescribed to you.

COPD (Chronic Obstructive Pulmonary Disease)

Only to be used by adults (aged 18 years and above).

The usual dose is 2 inhalations twice a day.

Your doctor may also prescribe other bronchodilator drugs, for example anticholinergics (such as tiotropium

or ipratropium bromide) for your COPD disease.

If you use more Bufomix Easyhaler than you should

It is important that you take your dose as stated on the pharmacist’s label or as advised by your doctor. You

should not exceed your prescribed dose without seeking medical advice.

The most common symptoms that may occur after if you use more Bufomix Easyhaler 160/4.5 than you

should are trembling, headache or a rapid heart beat.

If you forget to use Bufomix Easyhaler

If you forget to take a dose, take it as soon as you remember. However, if it is nearly time for your next

dose, skip the missed dose.

not

take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

The instructions how to use the inhaler are at the end of the leaflet.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If either of the following happen to you, stop using Bufomix Easyhaler and talk to your doctor

immediately:

Swelling of your face, particularly around your mouth (tongue and/or throat and/or difficulty to swallow)

or hives together with difficulties to breath (angioedema) and/or sudden feeling of faintness. This may

mean that you are having an allergic reaction. This happens rarely, may affect up to 1 in 1,000 people.

Sudden acute wheezing or shortness of breath immediately after using your inhaler.

If either of these

symptoms occur, stop using your Bufomix Easyhaler inhaler straightaway and use your ‘reliever’

inhaler. Contact your doctor immediately

as you may need to have your treatment changed.

This

happens very rarely, may affect up to 1 in 10,000 people.

Tell your doctor if you have any of the following while taking Bufomix Easyhaler as they could be

symptoms of a lung infection:

fever or chills,

increased mucus production, change in mucus colour,

increased cough or increased breathing difficulties.

Pneumonia (infection of the lung) in COPD patients is a common side effect (may affect up to 1 in 10

people).

Other possible side effects:

Common (may affect up to 1 in 10 people)

Palpitations (awareness of your heart beating), trembling or shaking. If these effects occur, they are

usually mild and usually disappear as you continue to use Bufomix Easyhaler.

Thrush (a fungal infection) in the mouth. This is less likely if you rinse your mouth out with water after

using your Bufomix Easyhaler.

Mild sore throat, coughing and a hoarse voice.

Headache.

Uncommon (may affect up to 1 in 100 people)

Feeling restless, nervous or agitated.

Disturbed sleep.

Feeling dizzy.

Nausea (feeling sick).

Fast heart beat.

Bruising of the skin.

Muscle cramps.

Blurred vision.

Rare (may affect up to 1 in 1,000 people)

Rash, itching.

Bronchospasm (tightening of the muscles in the airways which causes wheezing). If the wheezing

comes on suddenly after using Bufomix Easyhaler stop using Bufomix Easyhaler and talk to your

doctor immediately.

Low levels of potassium in your blood.

Uneven heart beat.

Very rare (may affect up to 1 in 10,000 people)

Depression.

Changes in behaviour, especially in children.

Chest pain or tightness in the chest (angina pectoris).

An increase in the amount of sugar (glucose) in your blood.

Taste changes, such as an unpleasant taste in the mouth.

Changes in your blood pressure.

Inhaled corticosteroids can affect the normal production of steroid hormones in your body, particularly if you

use high doses for a long time. The effects include:

changes in bone mineral density (thinning of the bones)

cataract (clouding of the lens in the eye)

glaucoma (increased pressure in the eye)

a slowing of the rate of growth of children and adolescents

an effect on the adrenal gland (a small gland next to the kidney).

These effects are much less likely to happen with inhaled corticosteroids than with corticosteroid tablets.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed

in this leaflet. You can also report side effects directly via the HPRA website: www.hpra.ie or email:

medsafety@hpra.ie. By reporting side effects, you can help provide more information on the safety of this

medicine.

5.

How to store Bufomix Easyhaler 160/4.5

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date that is stated on the carton, foil bag and label of your

inhaler after EXP. The expiry date refers to the last day of that month.

After opening the foil bag do not store above 25

C and store protected from moisture. It is recommended

to keep the Easyhaler in its protective cover.

If your Bufomix Easyhaler gets damp you need to replace it with a new one.

Replace Bufomix Easyhaler 4 months after you opened the foil bag

.

Write down the date you opened the

bag to help you remember.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help to protect the environment.

6.

Contents of the pack and other information

What Bufomix Easyhaler 160/4.5 contains

The active substances are budesonide and formoterol fumarate dihydrate. Each inhaled dose contains

160 micrograms of budesonide and 4.5 micrograms of formoterol fumarate dihydrate.

The other ingredient is lactose monohydrate (which contains milk proteins).

What Bufomix Easyhaler 160/4.5 looks like and contents of the pack

Bufomix Easyhaler 160/4.5 is an inhaler containing your medicine. The inhalation powder is white to

yellowish in colour. Each inhaler contains 60 or 120 doses and has a white body with red upper part.

Bufomix Easyhaler 160/4.5 is available in packs of 1 or 3 inhaler(s), 120 doses also in pack of 2 inhalers.

Not all pack sizes may be marketed.

Your pack may contain a protective cover. If you need a protective cover, please contact the Marketing

Authorisation Holder (details given below).

Marketing Authorisation Holder

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

Manufacturer

Orion Corporation Orion Pharma

Orionintie 1

FI-02200 Espoo

Finland

This leaflet was last revised in May 2020

Detailed and updated information on how to use this product is available by scanning this QR code (included

also on outer carton and inhaler label) with a smartphone. The same information is also available on the

following URL: www.oeh.fi/bfie.

QR code to www.oeh.fi/bfie.

How to use the Easyhaler inhaler

About your Easyhaler

Bufomix Easyhaler may be different to inhalers you have used in the past. Therefore it is very important that

you use it properly as using incorrectly can lead to you not receiving the right amount of medicine. This

could make you very unwell or could lead to your asthma and COPD not being treated as it should.

Your doctor, nurse or pharmacist will show you how to use your inhaler properly. Make sure you understand

the correct way to use the inhaler. If you are unsure contact your doctor, nurse or pharmacist. As with all

inhalers, caregivers should ensure that children prescribed Bufomix Easyhaler use correct inhalation

technique, as described below. You can also use the instruction video at www.oeh.fi/bfie

When you first get your Easyhaler

The Easyhaler comes in a foil bag. Do not open the foil bag until

you are ready to start using the medicine as it helps to keep the

powder dry in the inhaler.

When you are ready to start treatment open the bag and record the

date e.g., in your calendar.

Use the inhaler within 4 months of removing from the foil bag.

HOW TO USE CORRECTLY

Step 1:

SHAKE

Remove the dustcap

Shake the inhaler

3

5

times

holding it in the

upright

position

SHAKE x 3-5

Important points to remember

It is important to keep the

inhaler in the upright position

If you accidentally click while

you shake the inhaler, empty the

powder from the mouthpiece as

shown below

Step 2

CLICK

Keep holding the inhaler

upright between your forefinger

and thumb

Press down until you hear a

click, and let the inhaler click

back again. This releases a dose

Only click down once

CLICK x 1

Important points to remember

The inhaler will not click if the

dustcap is still on

Only click down once

If you accidentally click more

than once, empty the powder

from the mouthpiece, see below

Click to release dose before

you inhale, not at the same time

Keep the inhaler

upright

when you click it and when you

inhale the dose. If you tip it, the

powder could fall out before

you are able to inhale it

Step 3

INHALE

Keep holding the inhaler

upright

Breathe out normally

Place the mouthpiece in your

mouth between your teeth and

close your lips tightly around

the mouthpiece

Take a strong and deep breath

Take the inhaler out of your

mouth, then breathe out

normally.

INHALE

Important points to remember

Make sure the whole

mouthpiece is well inside your

mouth, so that the medication

gets into your lungs

Make sure your lips make a

good seal around the

mouthpiece

Do not breathe out into the

inhaler. This is important: it

could clog up the inhaler. If you

breathed out into the inhaler,

empty the powder from

mouthpiece, see below

If you need to take another inhalation, please repeat the steps 1-3 Shake-Click-Inhale.

After you have used the inhaler:

Put the dust cap back on the mouthpiece. It stops the inhaler going off by accident.

After you have taken the dose, rinse your mouth with water, and spit it out.

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17 September 2020

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Page 1 of 13

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Bufomix Easyhaler, 160 micrograms/4.5 micrograms/inhalation, inhalation powder

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each delivered dose (the dose that leaves the mouthpiece) contains: budesonide

160 micrograms/inhalation and formoterol fumarate dihydrate 4.5 micrograms/inhalation.

With the Easyhaler device the delivered dose (ex-actuator) contains similar quantity of active substance as the metered dose

(ex-reservoir).

Excipients with a known effect: Lactose monohydrate 3800 micrograms per delivered dose.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Inhalation powder in a device metered inhaler (Easyhaler).

White to yellowish powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Asthma

Bufomix Easyhaler is indicated in adults and adolescents (12 years and older) for the regular treatment of asthma, where use of

a combination (inhaled corticosteroid and long-acting β

-adrenoceptor agonist) is appropriate:

- patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short‑acting

-adrenoceptor agonists.

- patients already adequately controlled on both inhaled corticosteroids and long‑acting β

-adrenoceptor agonists.

Chronic Obstructive Pulmonary Disease (COPD)

Bufomix Easyhaler is indicated in adults, aged 18 years and older, for the symptomatic treatment of patients with COPD with

forced expiratory volume in 1 second (FEV

) < 70% predicted normal (post-bronchodilator) and an exacerbation history despite

regular bronchodilator therapy (see also section 4.4).

4.2 Posology and method of administration

Posology

Asthma

Bufomix Easyhaler is not intended for the initial management of asthma. The dosage of the components of Bufomix Easyhaler

is individual and should be adjusted to the severity of the disease. This should be considered not only when treatment with

combination products is initiated but also when the maintenance dose is adjusted. If an individual patient should require a

combination of doses other than those available in the combination inhaler, appropriate doses of β

-adrenoceptor agonists

and/or corticosteroids by individual inhalers should be prescribed.

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The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Patients should be

regularly reassessed by their prescriber/healthcare provider so that the dosage of Bufomix Easyhaler remains optimal. When

long‑term control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of

inhaled corticosteroid alone.

For Bufomix Easyhaler there are two treatment approaches:

A. maintenance therapy: Bufomix Easyhaler is taken as regular maintenance treatment with a separate rapid‑acting

bronchodilator as rescue.

B. maintenance and reliever therapy: Bufomix Easyhaler is taken as regular maintenance treatment and as needed in

response to symptoms.

A. maintenance therapy

Patients should be advised to have their separate rapid‑acting bronchodilator available for rescue use at all times.

Recommended doses:

Adults (18 years and older): 1-2 inhalations twice daily. Some patients may require up to a maximum of 4 inhalations twice daily.

Adolescents (12‑17 years): 1-2 inhalations twice daily.

In usual practice when control of symptoms is achieved with the twice daily regimen, titration to the lowest effective dose

could include Bufomix Easyhaler given once daily, when in the opinion of the prescriber, a long‑acting bronchodilator in

combination with an inhaled corticosteroid would be required to maintain control.

Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition and warrants a

reassessment of the asthma therapy.

Children (6 years and older): A lower strength (80 micrograms/4.5 micrograms/inhalation) is available for children 6-11 years.

Children under 6 years: As only limited data are available, Bufomix Easyhaler is not recommended for children younger than 6

years.

B. maintenance and reliever therapy

Patients take a daily maintenance dose of Bufomix Easyhaler and in addition take Bufomix Easyhaler as needed in response to

symptoms. Patients should be advised to always have Bufomix Easyhaler available for rescue use.

For patients taking Bufomix Easyhaler as reliever, preventative use of Bufomix Easyhaler for allergen- or exercise-induced

bronchoconstriction should be discussed between physician and patient; the recommended use should take into consideration

the frequency of need. In case of frequent need of bronchodilation without corresponding need for an increased dose of

inhaled

corticosteroids,

alternative

reliever

should

used.

Maintenance and reliever therapy should especially be considered for patients with:

- inadequate asthma control and in frequent need of reliever medication

- asthma exacerbations in the past requiring medical intervention

Close monitoring for dose-related adverse effects is needed in patients who frequently take high numbers of Bufomix Easyhaler

as-needed inhalations.

Recommended doses:

Adults and adolescents (12 years and older): The recommended maintenance dose is 2 inhalations per day, given either as one

inhalation in the morning and evening or as 2 inhalations in either the morning or evening. For some patients a maintenance

dose of 2 inhalations twice daily may be appropriate. Patients should take 1 additional inhalation as needed in response to

symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations

should be taken on any single occasion.

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A total daily dose of more than 8 inhalations is not normally needed; however, a total daily dose of up to 12 inhalations could

be used for a limited period.Patients using more than 8 inhalations daily should be strongly recommended to seek medical

advice. They should be reassessed and their maintenance therapy should be reconsidered.

Children under 12 years: maintenance and reliever therapy is not recommended for children.

For dosages which cannot be achieved with Bufomix Easyhaler, other strengths of budesonide/formoterol medicinal products

are available.

COPD

Recommended doses:

Adults: 2 inhalations twice daily.

General information

Special patient groups:

There are no special dosing requirements for elderly patients. There are no data available for use of Bufomix Easyhaler in

patients with hepatic or renal impairment. As budesonide and formoterol are primarily eliminated via hepatic metabolism, an

increased exposure can be expected in patients with severe liver cirrhosis.

Method of administration

For inhalation use

Instructions for correct use of Bufomix Easyhaler:

The inhaler is inspiratory flow-driven, which means that when the patient inhales through the mouthpiece, the substance will

follow the inspired air into the airways.

Note: It is important to instruct the patient

- To carefully read the instructions for use in the patient information leaflet which is packed together with each Bufomix

Easyhaler.

- To shake and actuate the inhaler prior to each inhalation.

- To breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is delivered to the lungs.

- Never to breathe out through the mouthpiece as this will result in a reduction in the delivered dose. Should this happen the

patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat

the dosing procedure.

- Never to actuate the device more than once without inhalation of the powder. Should this happen the patient is instructed to

tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.

- To always replace the dust cap (and, if in use, close the protective cover) after use to prevent accidental actuation of the

device (which could result in either overdosing or under dosing the patient when subsequently used).

- To rinse the mouth out with water after inhaling the maintenance dose to minimise the risk of oropharyngeal thrush. If

oropharyngeal thrush occurs, patients should also rinse their mouth with water after the as-needed inhalations.

- To clean the mouthpiece with a dry cloth at regular intervals. Water should never be used for cleaning because the powder is

sensitive to moisture.

- To replace Bufomix Easyhaler when the counter reaches zero even though powder can still be observed within the inhaler.

4.3 Contraindications

Hypersensitivity to the active substances or to the excipient listed in section 6.1 (lactose, which contains small amounts of milk

protein).

4.4 Special warnings and precautions for use

It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped abruptly. Complete

withdrawal of inhaled corticosteroids should not be considered unless it is temporarily required to confirm diagnosis of asthma.

If patients find the treatment ineffective, or exceed the highest recommended dose of Bufomix Easyhaler, medical attention

must be sought (see section 4.2). Sudden and progressive deterioration in control of asthma or COPD is potentially life

threatening and the patient should undergo urgent medical assessment. In this situation, consideration should be given to the

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need for increased therapy with corticosteroids, e.g. a course of oral corticosteroids, or antibiotic treatment if an infection is

present.

Patients should be advised to have their rescue inhaler available at all times, either Bufomix Easyhaler (for asthma patients

using Bufomix Easyhaler as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for all patients using

Bufomix Easyhaler as maintenance therapy only).

Patients should be reminded to take their Bufomix Easyhaler maintenance dose as prescribed, even when asymptomatic.

Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Bufomix Easyhaler.

Regular review of patients as treatment is stepped down is important. The lowest effective dose of Bufomix Easyhaler should

be used (see section 4.2).

Patients should not be initiated on Bufomix Easyhaler during an exacerbation, or if they have significantly worsening or acutely

deteriorating asthma.

Serious asthma-related adverse events and exacerbations may occur during treatment with Bufomix Easyhaler. Patients should

be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation

of Bufomix Easyhaler.

There are no clinical study data on budesonide/formoterol combination products available in COPD patients with a

pre-bronchodilator FEV

>50% predicted normal and with a post-bronchodilator FEV

<70% predicted normal (see section 5.1).

As with other inhalation therapy, paradoxical bronchospasm may occur, with an immediate increase in wheezing and shortness

of breath after dosing. If the patient experiences paradoxical bronchospasm Bufomix Easyhaler should be discontinued

immediately, the patient should be assessed and an alternative therapy instituted, if necessary. Paradoxical bronchospasm

responds to a rapid‑acting inhaled bronchodilator and should be treated straightaway (see section 4.8).

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects

are much less likely to occur with inhalation treatment than with oral corticosteroids. Possible systemic effects include

Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in

bone mineral density, cataract and glaucoma, and more rarely, a range of psychological or behavioural effects including

psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children) (see section 4.8).

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as

blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation

of possible causes 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.

Potential effects on bone density should be considered, particularly in patients on high doses for prolonged periods that have

coexisting risk factors for osteoporosis. Long-term studies with inhaled budesonide in children at mean daily doses of

400 micrograms (metered dose) or in adults at daily doses of 800 micrograms (metered dose) have not shown any significant

effects on bone mineral density. No information regarding the effect at higher doses is available.

If there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy, care should be taken

when transferring patients to Bufomix Easyhaler therapy.

The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients transferring from

oral steroids may remain at risk of impaired adrenal reserve for a considerable time. Recovery may take a considerable amount

of time after cessation of oral steroid therapy and hence oral steroid‑dependent patients transferred to inhaled budesonide

may remain at risk from impaired adrenal function for some considerable time. In such circumstances HPA axis function should

be monitored regularly.

Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than recommended doses, may also result

in clinically significant adrenal suppression. Therefore additional systemic corticosteroid cover should be considered during

periods of stress such as severe infections or elective surgery. Rapid reduction in the dose of steroids can induce acute adrenal

crisis. Symptoms and signs which might be seen in acute adrenal crisis may be somewhat vague but may include anorexia,

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abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension

and hypoglycaemia.

Treatment with supplementary systemic steroids or inhaled budesonide should not be stopped abruptly.

During transfer from oral therapy to Bufomix Easyhaler a generally lower systemic steroid action will be experienced which may

result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment

should be initiated for these conditions. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases,

symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of

oral glucocorticosteroids is sometimes necessary.

To minimise the risk of oropharyngeal candida infection, (see section 4.8), the patient should be instructed to rinse their mouth

out with water after inhaling the maintenance dose. If oropharyngeal thrush occurs, patients should also rinse their mouth with

water after the as-needed inhalations.

Concomitant treatment with itraconazole, ritonavir or other potent CYP3A inhibitors should be avoided (see section 4.5). If this

is not possible the time interval between administration of the interacting drugs should be as long as possible. In patients

using potent CYP3A inhibitors, maintenance and reliever therapy approach is not recommended.

Bufomix Easyhaler should be administered with caution in patients with thyrotoxicosis, phaeochromocytoma, diabetes mellitus,

untreated hypokalaemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension,

aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.

Caution should be observed when treating patients with prolongation of the QTc‑interval. Formoterol itself may induce

prolongation of the QTc‑interval.

The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent pulmonary

tuberculosis, fungal and viral infections in the airways.

Potentially serious hypokalaemia may result from high doses of β

-adrenoceptor agonists. Concomitant treatment of

-adrenoceptor agonists with drugs which can induce hypokalaemia or potentiate a hypokalaemic effect, e.g

xanthine-derivatives, steroids and diuretics, may add to a possible hypokalaemic effect of the β

-adrenoceptor agonist.

Particular caution is recommended in unstable asthma with variable use of rescue bronchodilators, in acute severe asthma as

the associated risk may be augmented by hypoxia and in other conditions when the likelihood for hypokalaemia is increased. It

is recommended that serum potassium levels are monitored during these circumstances.

As for all β

-adrenoceptor agonists, additional blood glucose controls should be considered in diabetic patients.

Pneumonia in patients with COPD

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with

COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose

but this has not been demonstrated conclusively across all studies.

There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled

corticosteroid products.

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 include current smoking, older age, low body mass index (BMI) and severe

COPD.

Bufomix Easyhaler contains approx. 4 mg of lactose per inhalation. This amount does not normally cause problems in lactose

intolerant people. The excipient lactose contains small amounts of milk proteins, which may cause allergic reactions.

Paediatric populations

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It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly

monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of inhaled corticosteroid to

the lowest dose at which effective control of asthma is maintained, if possible. The benefits of the corticosteroid therapy and

the possible risks of growth suppression must be carefully weighed. In addition consideration should be given to referring the

patient to a paediatric respiratory specialist.

Limited data from long-term studies suggest that most children and adolescents treated with inhaled budesonide will

ultimately achieve their adult target height. However, an initial small but transient reduction in growth (approximately 1 cm)

has been observed. This generally occurs within the first year of treatment.

4.5 Interaction with other medicinal products and other forms of interactions

Pharmacokinetic interactions

Potent inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin,

nefazodone, cobicistat and HIV protease inhibitors) are likely to markedly increase plasma levels of budesonide and

concomitant use should be avoided. If this is not possible the time interval between administration of the inhibitor and

budesonide should be as long as possible (see section 4.4). In patients using potent CYP3A inhibitors, maintenance and reliever

therapy is not recommended.

The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased plasma levels of concomitantly orally administered

budesonide (single dose of 3 mg) on average six-fold. When ketoconazole was administered 12 hours after budesonide the

concentration was on average increased only three-fold showing that separation of the administration times can reduce the

increase in plasma levels. Limited data about this interaction for high-dose inhaled budesonide indicates that marked increases

in plasma levels (on average four fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled

budesonide (single dose of 1000 mcg).

Co-treatment with cobicistat-containing products is expected to increase the risk of systemic side-effects. The combination

should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients

should be monitored for systemic corticosteroid side-effects.

Pharmacodynamic interactions

Beta‑adrenergic blockers can weaken or inhibit the effect of formoterol. Bufomix Easyhaler should therefore not be given

together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.

Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine) and tricyclic

antidepressants can prolong the QTc‑interval and increase the risk of ventricular arrhythmias.

In addition L‑Dopa, L‑thyroxine, oxytocin and alcohol can impair cardiac tolerance towards β

‑sympathomimetics.

Concomitant treatment with monoamine oxidase inhibitors including agents with similar properties such as furazolidone and

procarbazine may precipitate hypertensive reactions.

There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.

Concomitant use of other beta-adrenergic drugs or anticholinergic drugs can have a potentially additive bronchodilating effect.

Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.

Hypokalaemia may result from beta

-agonist therapy and may be potentiated by concomitant treatment with xanthine

derivatives, corticosteroids and diuretics (see section 4.4).

Budesonide and formoterol have not been observed to interact with any other drugs used in the treatment of asthma.

Paediatric populations

Interaction studies have only been performed in adults.

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4.6 Fertility, pregnancy and lactation

Pregnancy

For Bufomix Easyhaler or the concomitant treatment with formoterol and budesonide, no clinical data on exposed pregnancies

are available. Data from an embryo-fetal development study in the rat showed no evidence of any additional effect from the

combination.

There are no adequate data from use of formoterol in pregnant women. In animal studies formoterol has caused adverse

effects in reproduction studies at very high systemic exposure levels (see section 5.3).

Data on approximately 2000 exposed pregnancies indicate no increased teratogenic risk associated with the use of inhaled

budesonide. In animal studies glucocorticosteroids have been shown to induce malformations (see section 5.3). This is not

likely to be relevant for humans given recommended doses.

Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for intrauterine growth

retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover

and behaviour at exposures below the teratogenic dose range.

During pregnancy, Bufomix Easyhaler should only be used when the benefits outweigh the potential risks. The lowest effective

dose of budesonide needed to maintain adequate asthma control should be used.

Breastfeeding

Budesonide is excreted in breast milk. However, at therapeutic doses no effects on the suckling child are anticipated. It is not

known whether formoterol passes into human breast milk. In rats, small amounts of formoterol have been detected in maternal

milk. Administration of Bufomix Easyhaler to women who are breastfeeding should only be considered if the expected benefit

to the mother is greater than any possible risk to the child.

Fertility

There is no data available on the potential effect of budesonide on fertility. Animal reproduction studies with formoterol have

shown a somewhat reduced fertility in male rats at high systemic exposure (see section 5.3).

4.7 Effects on ability to drive and use machines

Bufomix Easyhaler has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Since Bufomix Easyhaler contains both budesonide and formoterol, the same pattern of undesirable effects as reported for

these substances may occur. No increased incidence of adverse reactions has been seen following concurrent administration of

the two compounds. The most common drug related adverse reactions are pharmacologically predictable side-effects of β

agonist therapy, such as tremor and palpitations. These tend to be mild and usually disappear within a few days of treatment.

Adverse reactions, which have been associated with budesonide or formoterol, are given below, listed by system organ class

and frequency. Frequencies are defined as: 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) and very rare (< 1/10 000).

Table 1

SOC

Frequency

Adverse Drug Reaction

Infections and infestations

Common

Candida infections in the oropharynx, pneumonia (in COPD

patients)

Immune system disorders

Rare

Immediate and delayed hypersensitivity reactions, e.g.

exanthema, urticaria, pruritus, dermatitis, angioedema and

anaphylactic reaction

Endocrine disorders

Very rare

Cushing’s syndrome, adrenal suppression, growth retardation,

decrease in bone mineral density

Metabolism and nutrition disorders

Rare

Hypokalaemia

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Very rare

Hyperglycaemia

Psychiatric disorders

Uncommon

Aggression, psychomotor hyperactivity, anxiety, sleep

disorders

Very rare

Depression, behavioural changes (predominantly in children)

Nervous system disorders

Common

Headache, tremor

Uncommon

Dizziness

Very rare

Taste disturbances

Eye disorders

Uncommon

Vision, blurred (see also section 4.4)

Very rare

Cataract and glaucoma

Cardiac disorders

Common

Palpitations

Uncommon

Tachycardia

Rare

Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular

tachycardia, extrasystoles

Very rare

Angina pectoris. Prolongation of QTc‑ interval

Vascular disorders

Very rare

Variations in blood pressure

Respiratory, thoracic and mediastinal disorders

Common

Mild irritation in the throat, coughing, dysphonia

includinghoarseness

Rare

Bronchospasm

Gastrointestinal disorders

Uncommon

Nausea

Skin and subcutaneous tissue disorders

Uncommon

Bruises

Musculoskeletal and connective tissue disorders

Uncommon

Muscle cramps

Candida infection in the oropharynx is due to drug deposition. Advising the patient to rinse the mouth out with water after

each maintenance dose will minimise the risk. Oropharyngeal Candida infection usually responds to topical anti-fungal

treatment without the need to discontinue the inhaled corticosteroid. If oropharyngeal thrush occurs, patients should also rinse

their mouth with water after the as-needed inhalations.

As with other inhalation therapy, paradoxical bronchospasm may occur very rarely, affecting less than 1 in 10,000 people, with

an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting

inhaled bronchodilator and should be treated straightaway. Bufomix Easyhaler should be discontinued immediately, the patient

should be assessed and an alternative therapy instituted if necessary (see section 4.4).

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects

are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s Syndrome, Cushingoid

features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and

glaucoma. Increased susceptibility to infections and impairment of the ability to adapt to stress may also occur. Effects are

probably dependent on dose, exposure time, concomitant and previous steroid exposure and individual sensitivity.

Treatment with β

agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

Paediatric populations

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly

monitored (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions viathe HPRA website: www.hpra.ie or email: medsafety@hpra.ie.

4.9 Overdose

An overdose of formoterol would likely lead to effects that are typical for β

-adrenoceptor agonists: tremor, headache,

palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc‑interval,

arrhythmia, nausea and vomiting. Supportive and symptomatic treatment may be indicated. A dose of 90 micrograms

administered during three hours in patients with acute bronchial obstruction raised no safety concerns.

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Acute overdosage with budesonide, even in excessive doses, is not expected to be a clinical problem. When used chronically in

excessive doses, systemic glucocorticosteroid effects, such as hypercorticism and adrenal suppression, may appear.

If Bufomix Easyhaler therapy has to be withdrawn due to overdose of the formoterol component of the drug, provision of

appropriate inhaled corticosteroid therapy must be considered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for obstructive airway diseases: Adrenergics in combination with corticosteroids or other

drugs, excl. anticholinergics.

ATC‑code: R03AK07

Mechanisms of action and Pharmacodynamic effects

Bufomix Easyhaler contains formoterol and budesonide, which have different modes of action and show additive effects in

terms of reduction of asthma exacerbations. The specific properties of budesonide and formoterol allow the combination to be

used either as maintenance and reliever therapy or as maintenance treatment of asthma.

Budesonide

Budesonide is a glucocorticosteroid which when inhaled has a dose-dependent anti-inflammatory action in the airways,

resulting in reduced symptoms and fewer asthma exacerbations. Inhaled budesonide has less severe adverse effects than

systemic corticosteroids. The exact mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.

Formoterol

Formoterol is a selective β

-adrenoceptor adrenergic agonist that when inhaled results in rapid and long-acting relaxation of

bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect is dose-dependant, with an

onset of effect within 1‑3 minutes. The duration of effect is at least 12 hours after a single dose.

Clinical efficacy and safety

Asthma

Clinical efficacy for budesonide/formoterol maintenance therapy

Clinical studies in adults have shown that the addition of formoterol to budesonide improved asthma symptoms and lung

function, and reduced exacerbations. In two 12‑week studies the effect on lung function of budesonide/formoterol was equal

to that of the free combination of budesonide and formoterol, and exceeded that of budesonide alone. All treatment arms

used a short-acting β

-adrenoceptor agonist as needed. There was no sign of attenuation of the anti‑asthmatic effect over

time.

Two 12‑week paediatric studies have been performed in which 265 children aged 6–11 years were treated with a maintenance

dose of budesonide/formoterol (2 inhalations of 80 micrograms/4.5 micrograms/inhalation twice daily), and a short acting

-adrenoceptor agonist as needed. In both studies, lung function was improved and the treatment was well tolerated

compared to the corresponding dose of budesonide alone.

Clinical efficacy for budesonide/formoterol maintenance and reliever therapy

A total of 12076 asthma patients were included in 5 double‑blind efficacy and safety studies (4447 were randomised to

budesonide/formoterol maintenance and reliever therapy) for 6 or 12 months. Patients were required to be symptomatic

despite use of inhaled glucocorticosteroids.

Budesonide/formoterol maintenance and reliever therapy provided statistically significant and clinically meaningful reductions

in severe exacerbations for all comparisons in all 5 studies. This included a comparison with budesonide/formoterol at a higher

maintenance dose with terbutaline as reliever (study 735) and budesonide/formoterol at the same maintenance dose with

either formoterol or terbutaline as reliever (study 734) (Table 2). In Study 735, lung function, symptom control, and reliever use

were similar in all treatment groups. In Study 734, symptoms and reliever use were reduced and lung function improved,

compared with both comparator treatments. In the 5 studies combined, patients receiving budesonide/formoterol

maintenance and reliever therapy used, on average, no reliever inhalations on 57% of treatment days. There was no sign of

development of tolerance over time.

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