Symbicort mite Turbuhaler 80 mikrogram/4,5 mikrogram/inhalation Inhalationspulver

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

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Bipacksedel Bipacksedel (PIL)

04-06-2020

Produktens egenskaper Produktens egenskaper (SPC)

16-11-2018

Aktiva substanser:
budesonid; formoterolfumaratdihydrat
Tillgänglig från:
Orifarm AB
ATC-kod:
R03AK07
INN (International namn):
budesonide; formoterol
Dos:
80 mikrogram/4,5 mikrogram/inhalation
Läkemedelsform:
Inhalationspulver
Sammansättning:
budesonid 80 mikrog Aktiv substans; formoterolfumaratdihydrat 4,5 mikrog Aktiv substans; laktosmonohydrat Hjälpämne
Klass:
Apotek
Receptbelagda typ:
Receptbelagt
Terapiområde:
Formoterol och budesonid
Produktsammanfattning:
Förpacknings: Inhalator, 120 doser; Inhalator, 360 (3 x 120) doser
Bemyndigande status:
Avregistrerad
Godkännandenummer:
22523
Tillstånd datum:
2005-09-28

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25-02-2013

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B. PACKAGE LEAFLET

Package leaflet: Information for the user

Symbicort mite Turbuhaler 80 micrograms/4.5 micrograms /inhalation, Inhalation Powder

Budesonide/Formoterol fumarate dihydrate

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

important information for you.

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

If you have any further questions, ask your doctor 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 Symbicort mite Turbuhaler is and what it is used for

What you need to know before you use Symbicort mite Turbuhaler

How to use Symbicort mite Turbuhaler

Possible side effects

How to store Symbicort mite Turbuhaler

Contents of the pack and other information

1.

What Symbicort mite Turbuhaler is and what it is used for

Symbicort mite Turbuhaler is an inhaler that is used to treat asthma in adults, adolescents and children

aged 6 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.

This medicine is not suitable for people with severe asthma. It can be prescribed for asthma in two

different ways.

a) Some people are prescribed two asthma inhalers: Symbicort mite Turbuhaler and a separate

‘reliever inhaler’.

They use Symbicort mite Turbuhaler 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 Symbicort mite Turbuhaler as their only asthma inhaler.

They use Symbicort mite Turbuhaler every day. This helps to prevent asthma symptoms from

happening.

They also use Symbicort mite Turbuhaler when they need extra doses for relief of asthma

symptoms, to make it easier to breathe again. They do not need a separate inhaler for this.

2.

What you need to know before you use Symbicort mite Turbuhaler

Do not use Symbicort mite Turbuhaler:

if you are allergic to budesonide, formoterol or 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 Symbicort mite Turbuhaler if:

You are diabetic.

You have a lung infection.

You 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).

You have problems with your thyroid or adrenal glands.

You have low levels of potassium in your blood.

You have severe liver problems.

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

Other medicines and Symbicort mite Turbuhaler

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

In particular, tell your doctor or pharmacist if you are using 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 called ‘HIV-protease inhibitors’ (such as ritonavir) to treat HIV infection.

Medicines to treat infections (such as 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

Symbicort mite Turbuhaler.

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

for dental work.

Pregnancy, breast-feeding and fertility

If you are pregnant, or planning to get pregnant, talk to your doctor before using Symbicort mite

Turbuhaler - do not use Symbicort mite Turbuhaler unless your doctor tells you to.

If you get pregnant while using Symbicort mite Turbuhaler, do not stop using Symbicort mite

Turbuhaler but talk to your doctor immediately.

If you are breast-feeding, talk to your doctor before using Symbicort mite Turbuhaler.

Driving and using machines

Symbicort mite Turbuhaler has no or negligible effect on your ability to drive or to use tools or

machines.

Symbicort mite Turbuhaler contains lactose

Symbicort mite Turbuhaler 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 Symbicort mite Turbuhaler

Always use this medicine exactly as your doctor has told you. You should check with your

doctor or pharmacist if you are not sure.

It is important to use Symbicort mite Turbuhaler every day, even if you have no asthma

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 Symbicort mite Turbuhaler. 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.

You should speak to your doctor if you are concerned as to whether you should continue to use

Symbicort mite Turbuhaler.

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 symptoms

If you feel you are getting breathless or wheezy while using Symbicort mite Turbuhaler, you should

continue to use Symbicort mite Turbuhaler 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 is not being properly controlled and you may need different

or additional treatment immediately.

Asthma

Symbicort mite Turbuhaler can be prescribed for asthma in two different ways. The amount of

Symbicort mite Turbuhaler to use and when to use it depends on how it has been prescribed for you.

If you have been prescribed Symbicort mite Turbuhaler and a separate reliever inhaler, read the

section called ‘a) Using Symbicort mite Turbuhaler and a separate reliever inhaler’.

If you have been prescribed Symbicort mite Turbuhaler as your only inhaler, read the section

called ‘b) Using Symbicort mite Turbuhaler as your only asthma inhaler’.

a) Using Symbicort mite Turbuhaler and a separate reliever inhaler

Use your Symbicort mite Turbuhaler 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.

Children (6 to 11 years)

The usual dose is 2 inhalations, twice a day.

Symbicort mite Turbuhaler 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 Symbicort mite Turbuhaler to

treat asthma symptoms - use your reliever inhaler.

b) Using Symbicort mite Turbuhaler as your only asthma inhaler

Only use Symbicort mite Turbuhaler in this way if your doctor has told you to and if you are aged 12

or above.

Use your Symbicort mite Turbuhaler 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.

Also use Symbicort mite Turbuhaler as a ‘reliever inhaler’ to treat asthma symptoms when they

happen.

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 Symbicort mite Turbuhaler Inhaler 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 Symbicort mite Turbuhaler as described

here. However, do not use Symbicort mite Turbuhaler just before exercise to stop asthma symptoms

from happening.

Preparing your new Symbicort mite Turbuhaler Inhaler

Before using your

new

Symbicort mite Turbuhaler Inhaler

for the first time

, you need to prepare it

for use as follows:

Unscrew the cover and lift it off. You may hear a rattling sound.

Hold your Symbicort mite Turbuhaler Inhaler upright with the red grip at the bottom.

Turn the red grip as far as it will go in one direction. Then turn it as far as it will go in the other

direction (it does not matter which way you turn it first). You should hear a click sound. It does

not matter whether the click comes on the first or the second twist.

Do this again, turning the red grip in both directions.

Your Symbicort mite Turbuhaler Inhaler is now loaded and ready for use.

How to take an inhalation

Every time you need to take an inhalation, follow the instructions below.

Unscrew the cover and lift it off. You may hear a rattling sound.

Hold your Symbicort mite Turbuhaler Inhaler upright

with the red grip at the bottom.

Do not

hold the mouthpiece when you load your Symbicort mite Turbuhaler Inhaler. To load

your Symbicort mite Turbuhaler Inhaler with a dose, turn the red grip as far as it will go in one

direction.

Then turn it as far as it will go in the other direction

(it does not matter which way you turn it

first). You should hear a click sound. It does not matter whether the click comes on the first or

the second twist. Your Symbicort mite Turbuhaler Inhaler is now loaded and ready to use. Only

load your Symbicort mite Turbuhaler Inhaler when you need to use it.

Hold your Symbicort mite Turbuhaler Inhaler away from your mouth. Breathe out gently (as far

as is comfortable). Do not breathe out through your Symbicort mite Turbuhaler Inhaler.

Place the mouthpiece gently between your teeth. Close your lips. Breathe in as deeply and as

hard as you can through your mouth. Do not chew or bite on the mouthpiece.

Remove your Symbicort mite Turbuhaler Inhaler from your mouth. Then breathe out

gently.

The amount of medicine that is inhaled is very small. This means you may not be able to

taste it after inhalation. If you have followed the instructions, you can still be confident that you

have inhaled the dose and the medicine is now in your lungs.

If you are to take a second inhalation, repeat steps 2 to 6.

Replace the cover tightly after use.

Rinse your mouth with water after your daily morning and/or evening doses, and spit it out.

Do not try to remove or twist the mouthpiece. It is fixed to your Symbicort mite Turbuhaler Inhaler

and must not be taken off. Do not use your Symbicort mite Turbuhaler Inhaler if it has been damaged

or if the mouthpiece has come apart from your Symbicort mite Turbuhaler Inhaler.

As with all inhalers, caregivers should ensure that children prescribed Symbicort mite Turbuhaler use

correct inhalation technique, as described above.

Cleaning your Symbicort mite Turbuhaler Inhaler

Wipe the outside of the mouthpiece once a week with a dry tissue. Do not use water or liquids.

When to start using a new inhaler

The dose indicator tells you how many doses (inhalations) are left in your Symbicort mite

Turbuhaler Inhaler, starting with either 60 or 120 doses when it is full.

The dose indicator is marked in intervals of 10 doses. Therefore, it does not show every dose.

When you first see a red mark at the edge of the indicator window, there are approximately

20 doses left. For the last 10 doses, the background of the dose indicator is red. When the ‘0’ on

the red background has reached the middle of the window, you must start using your new

Symbicort mite Turbuhaler Inhaler.

Note:

The grip will still twist and ‘click’ even when your Symbicort mite Turbuhaler Inhaler is empty.

The sound that you hear as you shake your Symbicort mite Turbuhaler Inhaler is produced by a

drying agent and not the medicine. Therefore, the sound does not tell you how much medicine is

left in your Symbicort mite Turbuhaler Inhaler.

If you load your Symbicort mite Turbuhaler Inhaler more than once by mistake before taking

your dose, you will still only receive one dose. However, the dose indicator will register all the

loaded doses.

If you use more Symbicort mite Turbuhaler 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 Symbicort mite Turbuhaler than

you should are trembling, headache or a rapid heart beat.

If you forget to use Symbicort mite Turbuhaler

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.

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 Symbicort mite Turbuhaler 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 breathe (angioedema) and or sudden feeling if

faintness. This may mean that you are having an allergic reaction. This happens rarely, affecting

less than 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 Symbicort mite Turbuhaler Inhaler straightaway

and use your ‘reliever’ inhaler. Contact your doctor immediately

as you may need to have

your treatment changed.

This happens very rarely, affecting less than 1 in 10,000 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 Symbicort mite Turbuhaler.

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

water after using your Symbicort mite Turbuhaler.

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 Symbicort mite Turbuhaler stop using Symbicort

mite Turbuhaler 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 national reporting system

listed in Appendix V. By reporting side effects you can help provide more information on the safety of

this medicine.

5.

How to store Symbicort mite Turbuhaler

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 or on the label of your

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

This medicine does not require any special storage conditions.

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

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

6.

Contents of the pack and other information

What Symbicort mite Turbuhaler contains

The active substances are budesonide and formoterol. Each inhaled dose contains 80 micrograms of

budesonide and 4.5 micrograms of formoterol fumarate dihydrate.

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

What Symbicort mite Turbuhaler looks like and contents of the pack

Symbicort mite Turbuhaler is an inhaler containing your medicine. The inhalation powder is white in

colour. Each Inhaler contains either 60 or 120 doses and has a white body with a red turning grip. The

turning grip contains a Braille code with the number 6 for identification, to differ from other

AstraZeneca inhaled products.

Symbicort mite Turbuhaler is available in packs of 1, 2, 3, 10 or 18 inhaler(s) containing 60 (or

120) doses.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

This medicinal product is authorised in the Member States of the EEA under the following

names:

Country

Trade name and strength

Austria

Symbicort mite Turbohaler 80 μg/4.5 μg/inhalation

Belgium

Symbicort mite Turbohaler 80 μg/4.5 μg/inhalation

Bulgaria

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Croatia

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Cyprus

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Czech Republic

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Denmark

Symbicort mite Turbuhaler 80 μg/4.5 μg/inhalation

Estonia

Symbicort Turbuhaler, 80 μg/4.5 μg

Finland

Symbicort Turbuhaler mite 80 μg/4.5 μg/inhalation

France

Symbicort Turbuhaler 100 μg/6 μg/inhalation

Germany

Symbicort mite Turbohaler 80 μg/4.5 μg/inhalation

Greece

Symbicort Turbuhaler

80 μg/4.5 μg/inhalation

Hungary

Symbicort mite Turbuhaler 80 μg/4.5 μg/inhalation

Iceland

Symbicort mite Turbuhaler 80 μg/4.5 μg/inhalation

Ireland

Symbicort

Turbohaler 100 μg/6 μg/inhalation

Italy

Symbicort

mite 80 μg/4.5 μg/inhalation

Latvia

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Lithuania

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Luxembourg

Symbicort

mite Turbohaler 80 μg/4.5 μg/inhalation

Malta

Symbicort Turbohaler 100 μg/6 μg/inhalation

Netherlands

Symbicort

Turbuhaler 100 μg/6 μg/inhalation

Norway

Symbicort mite Turbuhaler 80 μg/4.5 μg/inhalation

Poland

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Portugal

Symbicort

Turbohaler 80 μg/4.5 μg/inhalation

Romania

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Slovakia

Symbicort Turbuhaler 100 μg/6 μg/inhalation

Slovenia

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Spain

Symbicort Turbuhaler 80 μg/4.5 μg/inhalation

Sweden

Symbicort mite Turbuhaler 80 μg/4.5 μg/inhalation

United Kingdom

Symbicort Turbohaler

100 μg/6 μg/inhalation

This leaflet was last revised in 2020-12-17

[To be completed nationally]

Detailed and updated information on this product

is available by scanning the QR Code included in

the PIL and outer carton with a smartphone. The

same information is also available on the

following URL: <[country specific URL to be

included]>

<and the <NCA> website, to be

completed nationally>

QR code area

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Symbicort mite Turbuhaler, 80 micrograms/4.5 micrograms/inhalation, inhalation powder.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each delivered dose (the dose that leaves the mouthpiece) contains: budesonide 80 micrograms/inhalation

and formoterol fumarate dihydrate 4.5 micrograms/inhalation.

Each metered dose contains: budesonide 100 micrograms/inhalation and formoterol fumarate dihydrate

6 micrograms/inhalation.

Excipient with known effect

Lactose monohydrate 810 micrograms per delivered dose.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Inhalation powder.

White powder.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Symbicort mite Turbuhaler is indicated in adults, adolescents, and children aged 6 years and older.

Symbicort is indicated in 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 β

adrenoceptor agonists.

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

adrenoceptor

agonists.

Note:

Symbicort mite (80 micrograms/4.5 micrograms/inhalation) is not appropriate in patients with severe

asthma.

4.2

Posology and method of administration

Route of administration: For inhalation use

Posology

Symbicort is not intended for the initial management of asthma.

The dosage of the components of Symbicort 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.

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/health care provider so that the dosage of Symbicort

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 Symbicort there are two treatment approaches:

A. Symbicort maintenance therapy:

Symbicort is taken as regular maintenance treatment with a separate

rapid-acting bronchodilator as rescue.

B. Symbicort maintenance and reliever therapy:

Symbicort is taken as regular maintenance treatment and

as needed in response to symptoms.

A. Symbicort 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.

Children (6 years and older):

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 Symbicort mite 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 under 6 years

: As only limited data are available, Symbicort mite is not recommended for children

younger than 6 years.

B. Symbicort maintenance and reliever therapy

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

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

Symbicort 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

Symbicort 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. 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.

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:

Symbicort maintenance and reliever therapy is not recommended for children.

General information

Special patient groups:

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

Symbicort 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

Instructions for correct use of Symbicort mite Turbuhaler:

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 Symbicort mite Turbuhaler Inhaler.

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.

to replace the cover of the Symbicort mite Turbuhaler Inhaler after use.

to rinse their 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.

The patient may not taste or feel any medication when using Symbicort mite Turbuhaler Inhaler due to the

small amount of drug dispensed.

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

Dosing advice

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

Symbicort. Regular review of patients as treatment is stepped down is important. The lowest effective dose

of Symbicort should be used (see section 4.2).

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

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

using Symbicort as maintenance therapy only).

Patients should be reminded to take their Symbicort maintenance dose as prescribed, even when

asymptomatic. The prophylactic use of Symbicort, e.g. before exercise, has not been studied. The reliever

inhalations of Symbicort should be taken in response to asthma symptoms but are not intended for regular

prophylactic use, e.g. before exercise. For such use, a separate rapid-acting bronchodilator should be

considered.

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.

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

abruptly.

Deterioration of disease

Serious asthma-related adverse events and exacerbations may occur during treatment with Symbicort.

Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain

uncontrolled or worsen after initiation of Symbicort.

If patients find the treatment ineffective, or exceed the highest recommended dose of Symbicort, medical

attention must be sought (see section 4.2). Sudden and progressive deterioration in control of asthma is

potentially life threatening and the patient should undergo urgent medical assessment. In this situation

consideration should be given to the need for increased therapy with corticosteroids, e.g. a course of oral

corticosteroids, or antibiotic treatment if an infection is present.

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

or acutely deteriorating asthma.

Transfer from oral therapy

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 Symbicort 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.

During transfer from oral therapy to Symbicort mite Turbuhaler, 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.

Excipients

Symbicort Turbuhaler contains lactose monohydrate (< 1 mg/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.

Interactions with other medicinal products

Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 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 CYP3A4 inhibitors, Symbicort maintenance and

reliever therapy is not recommended.

Caution with special diseases

Symbicort 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.

Potentially serious hypokalaemia may result from high doses of β

adrenoceptor agonists. Concomitant

treatment of β

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.

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.

Systemic effects

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).

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 of Symbicort at higher doses is available.

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.

Adrenal function

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

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, abdominal pain, weight loss,

tiredness, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension and

hypoglycaemia.

Paradoxical bronchospasm

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

Symbicort 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).

Paediatric population

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 interaction

Pharmacokinetic interactions

Potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin,

telithromycin, nefazodone 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 CYP3A4 inhibitors, Symbicort 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 increase 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 μg).

Pharmacodynamic interactions

Beta-adrenergic blockers can weaken or inhibit the effect of formoterol. Symbicort 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

-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 population

Interaction studies have only been performed in adults.

4.6

Fertility, pregnancy and lactation

Pregnancy

For Symbicort 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, Symbicort 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 Symbicort 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

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

4.8

Undesirable effects

Since Symbicort 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

adrenoceptor 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 < 1/1000) and very rare (< 1/10 000).

Table 1

SOC

Frequency

Adverse Drug reaction

Infections and infestations

Common

Candida infections in the oropharynx

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

Rare

Hypokalaemia

disorders

Very rare

Hyperglycaemia

Uncommon

Aggression, psychomotor hyperactivity, anxiety,

sleep disorders

Psychiatric disorders

Very rare

Depression, behavioural changes (predominantly

in children)

Common

Headache, tremor

Uncommon

Dizziness

Nervous system disorders

Very rare

Taste disturbances

Uncommon

Vision blurred (see also section 4.4)

Eye disorders

Very rare

Cataract and glaucoma

Common

Palpitations

Uncommon

Tachycardia

Rare

Cardiac arrhythmias, e.g. atrial fibrillation,

supraventricular tachycardia, extrasystoles

Cardiac disorders

Very rare

Angina pectoris. Prolongation of QTc-interval

Vascular disorders

Very rare

Variations in blood pressure

Common

Mild irritation in the throat, coughing, dysphonia

including hoarseness

Respiratory, thoracic and

mediastinal disorders

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 out 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.

Symbicort 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

adrenoceptor agonists may result in an increase in blood levels of insulin, free fatty acids,

glycerol and ketone bodies.

Paediatric population

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 via the national reporting system listed in Appendix V.

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.

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 Symbicort 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, Inhalants.

ATC-code: R03AK07

Mechanisms of action and Pharmacodynamic effects

Symbicort 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 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

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 β

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.

Table 2

Overview of severe exacerbations in clinical studies

Severe exacerbations

Study No.

Duration

Treatment groups

n

Events

Events/

patient-year

Budesonide/formoterol 160/4.5 µg bd + as needed

1103

125

0.23

Budesonide/formoterol 320/9 µg bd + terbutaline 0.4 mg as

needed

1099

0.32

Study 735

6 months

Salmeterol/fluticasone 2 x 25/125 µg bd + terbutaline 0.4 mg as

needed

1119

0.38

Budesonide/formoterol 160/4.5 µg bd + as needed

1107

194

0.19

Budesonide/formoterol 160/4.5 µg bd + formoterol 4.5 µg as

needed

1137

0.29

Study 734

12 months

Budesonide/formoterol 160/4.5 µg bd + terbutaline 0.4 mg as

needed

1138

0.37

Hospitalisation/emergency room treatment or treatment with oral steroids

Reduction in exacerbation rate is statistically significant (P value <0.01) for both comparisons

Comparable efficacy and safety in adolescents and adults was demonstrated in 6 double-blind studies,

comprising the 5 studies mentioned above and an additional study using a higher maintenance dose of

160/4.5 micrograms, two inhalations twice daily. These assessments were based on a total of 14385 asthma

patients of whom 1847 were adolescents. The number of adolescent patients taking more than 8 inhalations

on at least one day as part of budesonide/formoterol maintenance and reliever therapy was limited, and such

use was infrequent.

In 2 other studies with patients seeking medical attention due to acute asthma symptoms,

budesonide/formoterol provided rapid and effective relief of bronchoconstriction similar to salbutamol and

formoterol.

5.2

Pharmacokinetic properties

Absorption

The fixed-dose combination of budesonide and formoterol, and the corresponding monoproducts have been

shown to be bioequivalent with regard to systemic exposure of budesonide and formoterol, respectively. In

spite of this, a small increase in cortisol suppression was seen after administration of the fixed-dose

combination compared to the monoproducts. The difference is considered not to have an impact on clinical

safety.

There was no evidence of pharmacokinetic interactions between budesonide and formoterol.

Pharmacokinetic parameters for the respective substances were comparable after the administration of

budesonide and formoterol as monoproducts or as the fixed-dose combination. For budesonide, AUC was

slightly higher, rate of absorption more rapid and maximal plasma concentration higher after administration

of the fixed combination. For formoterol, maximal plasma concentration was similar after administration of

the fixed combination. Inhaled budesonide is rapidly absorbed and the maximum plasma concentration is

reached within 30 minutes after inhalation. In studies, mean lung deposition of budesonide after inhalation

via the powder inhaler ranged from 32% to 44% of the delivered dose. The systemic bioavailability is

approximately 49% of the delivered dose. In children 6-16 years of age the lung deposition falls in the same

range as in adults for the same given dose. The resulting plasma concentrations were not determined.

Inhaled formoterol is rapidly absorbed and the maximum plasma concentration is reached within 10 minutes

after inhalation. In studies the mean lung deposition of formoterol after inhalation via the powder inhaler

ranged from 28% to 49% of the delivered dose. The systemic bioavailability is about 61% of the delivered

dose.

Distribution and biotransformation

Plasma protein binding is approximately 50% for formoterol and 90% for budesonide. Volume of

distribution is about 4 l/kg for formoterol and 3 l/kg for budesonide. Formoterol is inactivated via

conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are seen

mainly as inactivated conjugates). Budesonide undergoes an extensive degree (approximately 90%) of

biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity. The

glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and

16-alfa-hydroxy-prednisolone, is less than 1% of that of budesonide. There are no indications of any

metabolic interactions or any displacement reactions between formoterol and budesonide.

Elimination

The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination.

After inhalation, 8% to 13% of the delivered dose of formoterol is excreted unmetabolised in the urine.

Formoterol has a high systemic clearance (approximately 1.4 l/min) and the terminal elimination half-life

averages 17 hours.

Budesonide is eliminated via metabolism mainly catalysed by the enzyme CYP3A4. The metabolites of

budesonide are eliminated in urine as such or in conjugated form. Only negligible amounts of unchanged

budesonide have been detected in the urine. Budesonide has a high systemic clearance (approximately

1.2 l/min) and the plasma elimination half-life after i.v. dosing averages 4 hours.

The pharmacokinetics of formoterol in children have not been studied. The pharmacokinetics of budesonide

and formoterol in patients with renal failure are unknown. The exposure of budesonide and formoterol may

be increased in patients with liver disease.

Linearity/non-linearity

Systemic exposure for both budesonide and formoterol correlates in a linear fashion to administered dose.

5.3

Preclinical safety data

The toxicity observed in animal studies with budesonide and formoterol, given in combination or separately,

were effects associated with exaggerated pharmacological activity.

In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations

(cleft palate, skeletal malformations). However, these animal experimental results do not seem to be relevant

in humans at the recommended doses. Animal reproduction studies with formoterol have shown a somewhat

reduced fertility in male rats at high systemic exposure and implantation losses as well as decreased early

postnatal survival and birth weight at considerably higher systemic exposures than those reached during

clinical use. However, these animal experimental results do not seem to be relevant in humans.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate (which contains milk proteins).

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

3 years.

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container

Symbicort Turbuhaler is an inspiratory flow driven, multidose powder inhaler. The inhaler is white with a

red turning grip. The inhaler is made of different plastic materials (PP, PC, HDPE, LDPE, LLDPE, PBT). In

each secondary package there are 1, 2, 3, 10 or 18 inhaler(s) containing 60 (or 120) doses.

Not all pack-sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

7.

MARKETING AUTHORISATION HOLDER

[To be completed nationally]

For Sweden (RMS):

AstraZeneca AB

151 85 Södertälje

Sweden

8.

MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10.

DATE OF REVISION OF THE TEXT

2020-12-17

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