Symbicort 200micrograms/dose / 6micrograms/dose pressurised inhaler

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Formoterol fumarate dihydrate; Budesonide
Available from:
AstraZeneca UK Ltd
ATC code:
R03AK07
INN (International Name):
Formoterol fumarate dihydrate; Budesonide
Dosage:
6microgram/1dose ; 200microgram/1dose
Pharmaceutical form:
Pressurised inhalation
Administration route:
Inhalation
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: ; GTIN: 5000456011679
Authorization number:
PL 17901/0293

Read the complete document

Package leaflet: Information for the user

Symbicort

®

200 micrograms/6 micrograms per actuation pressurised inhalation, suspension

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 is and what it is used for

What you need to know before you use Symbicort

How to use Symbicort

Possible side effects

How to store Symbicort

Contents of the pack and other information

1.

What Symbicort is and what it is used for

Symbicort is an inhaler that is used to treat the symptoms of Chronic Obstructive Pulmonary Disease

(COPD) in adults aged 18 and older. COPD is a long-term disease of the airways in the lungs, which is often

caused by cigarette smoking. Symbicort 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.

Do not use this medicine as a “reliever” inhaler.

2.

What you need to know before you use Symbicort

Do not use Symbicort:

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

section 6).

Warnings and precautions

Talk to your doctor or pharmacist before using Symbicort 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.

Children and adolescents

Symbicort is not recommended for children and adolescents under 18 years.

Other medicines and Symbicort

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 COPD or

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.

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 - do not use

Symbicort unless your doctor tells you to.

If you get pregnant while using Symbicort, do not stop using Symbicort but talk to your doctor

immediately.

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

Driving and using machines

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

3.

How to use Symbicort

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 Symbicort every day, even if you have no COPD symptoms at the time.

The usual dose is 2 inhalations twice a day. Symbicort is not recommended for children or adolescents under

18 years of age.

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

you take, once you start to use Symbicort. 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.

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 COPD symptoms

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

Symbicort 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 feeling breathless.

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

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

or additional treatment immediately.

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

or ipratropium bromide) for your COPD disease.

Information about your Symbicort

Before starting to use your Symbicort, remove it from the foil wrapper. Throw away the wrapper as well

as the drying agent which is inside the wrapper. If the drying agent has leaked out of its packet, do not

use the inhaler.

After you have taken the inhaler out of its foil wrapper, you should use it within 3 months. Write the use

by date (3 months from opening the wrapper) on the inhaler label to remind you when to stop using the

inhaler.

The parts of your inhaler are shown in the picture. The inhaler will already be assembled when you first

receive it. Do not take it apart. If the canister becomes loose, put it back in the inhaler and keep using the

inhaler.

Preparing your Symbicort

You need to prepare your inhaler for use in the following situations:

If you are using your new Symbicort for the first time.

If you have not used it for more than 7 days.

If it has been dropped.

To prepare your inhaler for use, follow the instructions below:

Shake the inhaler well for at least 5 seconds to mix the contents of the aerosol canister.

Remove the mouthpiece cover by pressing lightly on the bumps on the side. The strap on the mouthpiece

cover will stay attached to the inhaler.

Hold the inhaler upright. Then press the counter (on the top of the inhaler) to release a puff into the air.

You can use one or both hands, as shown in the pictures.

Release your finger(s) from the counter.

Wait for 10 seconds, shake well and then repeat steps 3 and 4.

Your inhaler is now ready for use.

How to take an inhalation

Each time you need to take an inhalation, follow the instructions below:

Shake the inhaler well for at least 5 seconds to mix the contents of the aerosol canister.

Remove the mouthpiece cover by pressing lightly on the bumps on the side. Check that the mouthpiece

is not blocked.

Hold your inhaler upright (using one or both hands). Breathe out gently.

Place the mouthpiece gently between your teeth. Close your lips.

Start to breathe in slowly and deeply through your mouth. Press the counter (on the top of the inhaler)

firmly to release a puff. Keep breathing in for a short while after pressing the counter. Breathing in at the

same time as pressing the counter ensures that the medicine reaches your lungs.

Hold your breath for 10 seconds, or for as long as it is comfortable.

Before you breathe out, release your finger from the counter and remove the inhaler from your mouth.

Keep the inhaler upright.

Then

breathe out slowly. To take another inhalation, shake the inhaler well for at least 5 seconds and

repeat steps 3 to 7.

Replace the mouthpiece cover.

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

Using a spacer device

Your doctor, nurse or pharmacist may suggest that you use a spacer device (e.g.

AeroChamber Plus Flow

Vu or AeroChamber Plus

). Follow the instructions in the leaflet that is packed with the spacer device.

Cleaning your Symbicort

Wipe the inside and outside of the mouthpiece at least once a week with a dry tissue.

Do not use water or liquids and do not remove the canister from the inhaler.

How will I know when to replace my Symbicort?

The counter on the top of your inhaler tells you how many puffs (actuations) are left in your Symbicort.

It starts with 120 puffs when it is full.

Each time you take an inhalation, or release a puff into the air, the arrow counts down towards zero (‘0’).

When the arrow first enters the yellow area, this means that there are about 20 puffs left.

When the arrow reaches ‘0’, you must stop using your new Symbicort. Your inhaler may not feel empty

and it may seem as though it still works. However, you will not get the right amount of medicine if you

keep using it.

If you use more Symbicort than you should

If you use more Symbicort than you should, contact your doctor or pharmacist for advice. The following

effects may happen: trembling, headache or a rapid heartbeat.

If you forget to use Symbicort

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 stop using Symbicort

Before you stop using Symbicort, you should talk to your doctor or your pharmacist. If you stop using

Symbicort the signs and symptoms of COPD may worsen.

If you have any further questions on the use of this medicine, 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 happens to you, stop using Symbicort straightaway and talk to your doctor

immediately:

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

rash or hives together with difficulties to breathe (angioedema) and/or sudden feeling of 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 occurs, stop using your Symbicort 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.

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

using your Symbicort.

Mild sore throat, coughing and a hoarse voice.

Headache.

Pneumonia (infection of the lung) in COPD patients.

Tell your doctor if you have any of the following while taking Symbicort, they could be symptoms of a lung

infection:

Fever or chills.

Increased mucus production, change in mucus colour.

Increased cough or increased breathing difficulties.

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 stop using Symbicort 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, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, Website:

www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the

safety of this medicine.

5.

How to store Symbicort

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

Do not use this medicine after the expiry date which is stated on the label, carton and foil wrapper after

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

As with most inhaled medicines in pressurised canisters, the effect of this medicine may decrease when

the canister is cold. For best results, this medicine should be at room temperature before use. Do not

refrigerate or freeze. Protect from frost and direct sunlight.

After you have taken the inhaler out of its foil wrapper, you should use it within 3 months. Write the use

by date (3 months from opening the wrapper) on the inhaler label to remind you when to stop using the

inhaler.

Always replace the mouthpiece cover firmly and snap into position after using your inhaler.

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.

Warning:

The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C. Do

not pierce the canister. The canister should not be broken, punctured or burnt, even when it seems empty.

6.

Contents of the pack and other information

What Symbicort contains

The active substances are budesonide and formoterol fumarate dihydrate. Each puff (actuation) contains

200 micrograms of budesonide and 6 micrograms of formoterol fumarate dihydrate.

The other ingredients are apaflurane (HFA 227), povidone and macrogol. This is a CFC-free inhaler.

What Symbicort looks like and contents of the pack

Symbicort is an inhaler containing your medicine. The pressurised canister, with attached dose indicator,

contains a white suspension for inhalation. The canister is fitted into a red plastic actuator with a white

plastic mouthpiece and an integrated grey plastic dust cap. Each inhaler contains 120 puffs (actuations) after

it has been prepared for use. Each inhaler is individually packed in a foil wrapper containing a drying agent.

Symbicort, 200 micrograms/6 micrograms/actuation pressurised inhalation, suspension

(Budesonide/Formoterol fumarate dihydrate) is available in packs of one inhaler.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation for Symbicort is held by AstraZeneca UK Ltd, 600 Capability Green, Luton,

LU1 3LU, UK.

Symbicort is manufactured by AstraZeneca Dunkerque Production (AZDP) 224 Avenue de la Dordogne,

59640, Dunkerque, France.

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

Country

Trade name and strength

Austria

Symbicort 160 Mikrogramm /4,5 Mikrogramm/Inhalation

Druckgasinhalation, Suspension

Belgium

Symbicort 160 microgram /4,5 microgram/inhalatie, aërosol, suspensie

Symbicort 160 microgrammes /4,5 microgrammes/inhalation, suspension

pour inhalation en flacon pressurisé

Symbicort 160 Mikrogramm /4,5 Mikrogramm/Inhalation,

Druckgasinhalation, Suspension

Bulgaria

Симбикорт 160 микрограма /4,5 микрограма/впръскване

Суспензия под налягане за инхалация

Croatia

Symbicort 160 mikrograma /4,5 mikrograma po potisku, stlačeni inhalat,

suspenzija

Cyprus

Symbicort 160 μικρογραμμάρια /4,5 μικρογραμμάρια/ψεκασμό

Czech Republic

Symbicort 160 micrograms /4,5 micrograms/inhalation, suspension in

pMDI

Denmark

Symbicort 160 mikrogram /4.5 mikrogram/inhalation

Estonia

Symbicort

Finland

Symbicort 160 mikrog /4.5 mikrog/inhalaatio

France

Symbicort 200/6 micro grammes par inhalation, suspension pour inhalation

en flacon préssurisé

Germany

Symbicort 160 Mikrogramm /4,5 Mikrogramm pro Inhalation

Druckgasinhalation, Suspension

Greece

Symbicort 160 μικρογραμμάρια /4,5 μικρογραμμάρια/ψεκασμό

Hungary

Symbicort 4,5 mikrogramm /160 mikrogramm/ adag túlnyomásos inhalációs

szuszpenzió

Iceland

Symbicort 160 míkrógrömm /4,5 míkrógrömm/ inhalation

Ireland

Symbicort 200 micrograms /6 micrograms/inhalation

Italy

Symbicort

Latvia

Symbicort 160 mikrogrami /4.5 mikrogrami/ inhalācijā, izsmidzinājumā,

aerosols inhalācijām zem spiediena

Lithuania

Symbicort 160 mikrogramo /4,5 mikrogramo/išpurškime suslėgtoji

įkvepiamoji suspensija

Luxembourg

Symbicort 160 microgrammes /4,5 microgrammes/inhalation, suspension

pour inhalation en flacon pressurisé

Malta

Symbicort 200 micrograms /6 micrograms/inhalation

Netherlands

Symbicort aërosol 200/6, 200 microgram /6 microgram per dosis, aërosol,

suspensie

Norway

Symbicort 160 mikrogram /4.5 mikrogram/ inhalasjon

Poland

Symbicort

Portugal

Symbicort 160 microgramas /4,5 microgramas/inalação

Suspensão pressurizada para inalação

Romania

Symbicort 160 micrograme /4.5 micrograme/inhalaţie,

suspensie de

inhalat presurizată

Slovakia

Symbicort 160 mikrogamov /4,5 mikrogamov/inhalačná dávka, inhalačná

suspenzia v tlakovom obale

Slovenia

Symbicort 160 mikrogramov /4,5 mikrograma na vdih, inhalacijska

suspenzija pod tlakom

Spain

Symbicort 160 microgramos /4,5 microgramos/inhalación suspensión para

inhalación en envase a presión

Sweden

Symbicort 160 mikrogram /4.5 mikrogram/inhalation

United Kingdom

Symbicort 200 micrograms/6 micrograms per actuation pressurised

inhalation, suspension

To listen to or request a copy of this leaflet in Braille, large print or audio

please call, free of charge:

0800 198 5000 (UK only)

Please be ready to give the following information:

Product name

Symbicort 200/6

Reference number

17901/0293

This is a service provided by the Royal National Institute of Blind People.

This leaflet was last revised in February 2018.

© AstraZeneca 2018

Symbicort is a trademark of the AstraZeneca group of companies.

RSP 18 0003

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Object 1

Symbicort, 200 micrograms/6 micrograms per

actuation, pressurised inhalation, suspension

Summary of Product Characteristics Updated 22-Jun-2018 | AstraZeneca UK Limited

1. Name of the medicinal product

Symbicort, 200 micrograms/6 micrograms per actuation, pressurised inhalation, suspension

2. Qualitative and quantitative composition

Each delivered dose (ex-actuator) contains: budesonide 160 micrograms/actuation and formoterol

fumarate dihydrate 4.5 micrograms/actuation.

This is equivalent to a metered dose containing budesonide 200 micrograms/actuation and formoterol

fumarate dihydrate 6 micrograms/actuation.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Pressurised inhalation, suspension.

White suspension in an aluminium canister fitted into a red actuator with a grey dust cap.

4. Clinical particulars

4.1 Therapeutic indications

Chronic Obstructive Pulmonary Disease (COPD)

Symbicort is indicated in adults, aged 18 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

Route of administration: Inhalation use.

COPD

Recommended dose:

Adults: 2 actuations twice daily.

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.

Paediatric Population

There is no relevant use of Symbicort 200 micrograms /6 micrograms in children 11 years of age and

under or in adolescents 12 to 17 years of age in the symptomatic treatment of COPD.

Instructions for the correct use of Symbicort

On actuation of Symbicort, a volume of the suspension is expelled from the canister at high velocity.

When the patient inhales through the mouthpiece at the same time as actuating the inhaler, the substance

will follow the inspired air into the airways.

Use of a spacer device (e.g. AeroChamber Plus Flow Vu or AeroChamber Plus) with Symbicort

(pressurised inhalation, suspension) is usually recommended, especially in patients who have, or are

likely to have difficulties to coordinate actuation with inhalation (see section 5.2).

Note: Patients should be instructed on the correct use and care of their inhaler and spacer, and their

inhalation technique checked to ensure optimum delivery of inhaled drugs to the lungs. 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 inhaler.

- If a spacer is to be used, carefully read the instructions for use in the instruction leaflet, which is packed

with each spacer device.

- If the drying agent, which is inside the wrapper, has leaked out of its packet, do not use the inhaler.

- Shake the inhaler well for at least 5 seconds prior to each use to mix its contents properly.

- Prime the inhaler by actuating it twice into the air when the inhaler is new, has not been used for more

than one week or if it has been dropped.

- Remove the mouthpiece cover.

- Hold the inhaler upright.

- Place the mouthpiece in the mouth. While breathing in slowly and deeply, press the device firmly to

release the medication. Continue to breathe in and hold the breath for approximately 10 seconds or as

long as is comfortable. Inhaling at the same time as actuating the inhaler ensures that active substances

reach the lungs.

- Shake the inhaler again and repeat.

- Replace the mouthpiece cover after use.

- Rinse the mouth with water after inhaling the prescribed dose to minimise the risk of oropharyngeal

thrush.

- Clean the mouthpiece of the inhaler regularly, at least once a week with a clean dry cloth.

- Do not put the inhaler into water.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Patients should be advised to have their rescue inhaler available at all times.

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

asymptomatic.

It is recommended that treatment with Symbicort is not stopped without supervision by a physician.

If patients find the treatment ineffective, medical attention must be sought. Sudden and progressive

deterioration in control of COPD 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.

There are no clinical study data on Symbicort available in COPD patients with a pre-bronchodilator

>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

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).

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).

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 of Symbicort 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 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.

The 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.

Treatment with supplementary systemic steroids should not be stopped abruptly.

During transfer from oral therapy to Symbicort, 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 dose.

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.

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.

The need for 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 beta

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. 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.

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.

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.

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 (section

4.4).

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 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.

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-foetal 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.

Breast-feeding

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, 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

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, hoarseness

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 dose will minimise the risk. Oropharyngeal Candida infection usually responds to

topical anti-fungal treatment without the need to discontinue the inhaled corticosteroid.

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.

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

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple

App Store

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 of formoterol 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 COPD exacerbations.

Budesonide

Budesonide is a glucocorticosteroid which when inhaled has a dose-dependent anti-inflammatory action

in the airways, resulting in reduced symptoms and fewer COPD 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 which when inhaled results in rapid and long-acting

relaxation of bronchial smooth muscle in patients with airway 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

The efficacy and safety of Symbicort (pressurised inhalation, suspension) 160 micrograms /4.5

micrograms in the symptomatic treatment of patients with COPD has been evaluated in two 12-month

studies (Studies 001 and 003) and one 6-month study (Study 002). Symbicort 160 micrograms /4.5

micrograms, 2 inhalations twice daily, was compared with the corresponding dose of formoterol fumarate

dihydrate (4.5 µg, 2 inhalations twice daily) in Studies 001, 002, and 003 and the corresponding dose of

budesonide (160 µg, 2 inhalations twice daily) in Study 002.

The primary endpoints were pre-dose FEV

and 1-hour post dose FEV

(Study 001 and 002) and COPD

exacerbations (Study 003). A total of 4887 patients with moderate to severe COPD were randomised into

the 3 trials of which 1178 were on Symbicort 160 micrograms /4.5 micrograms. The inclusion criteria for

all three studies was pre-bronchodilator FEV

<50% predicted normal. Median post-bronchodilator FEV

at screening in the trials was 39% predicted normal.

In Studies 001 and 002, Symbicort 160 micrograms /4.5 micrograms was superior to placebo for post-

dose FEV

(180 mL and 170 mL mean increase, respectively) and pre-dose (through) FEV

(90 mL and

80 mL mean increase, respectively).

In Studies 001 and 002, Symbicort 160 micrograms /4.5 micrograms was also superior to formoterol for

post-dose FEV

(30 mL and 40 mL mean increase, respectively) and pre-dose (through) FEV

(40 mL

and 40 mL mean increase, respectively).

In the 12-month study (001), Symbicort 160 micrograms /4.5 micrograms resulted in statistically

significant and clinically meaningful reductions in severe exacerbations (defined as a worsening of COPD

requiring oral steroid use and/or hospitalisation), with a 37% reduction in exacerbation rate (p<0.001)

compared with placebo and a 25% reduction in exacerbation rate (p=0.004) compared with formoterol.

Symbicort significantly reduced the risk of first severe exacerbation by 34% compared to placebo

(p<0.001) and by 23% compared to formoterol (p=0.015).

Symbicort 160 micrograms /4.5 micrograms also significantly reduced breathlessness, daily rescue

medication use, night-time awakenings and improved health-related quality of life (as measured by St.

George's Respiratory Questionnaire total score) compared with placebo in both studies.

Serial FEV

measures over 12 hours were obtained in subsets of patients in both Studies 001 and 002.

The median time to onset of bronchodilation (>15% improvement in FEV

) was seen at 5 minutes in

patients receiving Symbicort 160 micrograms/4.5 micrograms. Maximal improvement in FEV

occurred

at approximately 2 hours post-dose and post-dose bronchodilator effect was generally maintained over 12

hours.

In a second 12-month study (003), Symbicort 160 micrograms /4.5 micrograms resulted in statistically

significant reductions in the severe exacerbations compared with formoterol, with a 35% reduction in

number of exacerbations (P<0.001) and a 21% reduction in the risk of first exacerbation (p=0.026).

The treatment was well tolerated. Evaluation of safety in the 3 trials revealed a safety profile for

Symbicort that was consistent with the established profiles for Symbicort Turbohaler and the inhaled

budesonide and formoterol monoproducts.

Paediatric population

There is no relevant use of Symbicort 160 micrograms /4.5 micrograms in children or adolescents in the

symptomatic treatment of COPD.

5.2 Pharmacokinetic properties

Absorption

Following administration of Symbicort (pressurised inhalation, suspension) 160 micrograms /4.5

micrograms (two or four inhalations twice daily) for 5 days in healthy subjects, plasma concentration of

budesonide generally increased in proportion to dose. The accumulation index for the group that received

two inhalations twice daily was 1.32 for budesonide and 1.77 for formoterol.

In a single-dose study, 12 inhalations of Symbicort (pressurised inhalation, suspension) 80 micrograms /

4.5 micrograms (total dose 960/54 µg) were administered to patients with COPD. Mean budesonide peak

plasma concentration of 3.3 nmol/L occurred at 30 minutes following dosing whilst mean peak formoterol

plasma concentration of 167 pmol/L was rapidly achieved at 15 minutes after dosing.

In a single-dose study, 8 inhalations of Symbicort (pressurised inhalation, suspension) 160 micrograms /

4.5 micrograms (total dose 1280/36 µg) and Symbicort Turbuhaler 160 micrograms /4.5 micrograms

(total dose 1280/36 µg) were administered to healthy volunteers. Symbicort (pressurised inhalation,

suspension) delivered a comparable amount of active drug to the systemic circulation as Symbicort

Turbuhaler. The AUC for the budesonide component in Symbicort (pressurised inhalation, suspension)

was 90% of the Turbuhaler comparator. The AUC for the formoterol component in Symbicort

(pressurised inhalation, suspension) was 116% of the Turbuhaler comparator.

The systemic exposure to budesonide and formoterol from Symbicort (pressurised inhalation, suspension)

160 micrograms /4.5 micrograms with and without the AeroChamber Plus Flow Vu spacer device was

evaluated in a study conducted in healthy volunteers.

The total systemic exposure of Symbicort (pressurised inhalation, suspension) administered through the

AeroChamber Plus Flow Vu spacer was increased compared to no spacer, with mean AUC being 68%

and 77% higher for budesonide and formoterol, respectively. However, the highest increases in exposure

with spacer were observed in subjects showing low exposure without spacer (most probably due to poor

inhalation technique).

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

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 budesonide or formoterol in patients with renal failure is 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.

Pre-clinical data on the CFC-free propellant HFA 227 reveal no special hazard for humans based on

conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential

and toxicity to reproduction and development.

6. Pharmaceutical particulars

6.1 List of excipients

Apaflurane (HFA 227)

Povidone

Macrogol 1000

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

The shelf life for Symbicort as packaged for sale is 2 years. The shelf life after first opening is 3 months.

6.4 Special precautions for storage

For best results, this medicine should be at room temperature before use. Do not refrigerate or freeze.

Protect from frost and direct sunlight.

Replace the mouthpiece cover firmly and snap into position after use.

As with most inhaled medicinal products in pressurised containers, the therapeutic effect of this medicinal

product decreases when the container is cold. This medicine should be at room temperature before use.

The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C. Do not pierce

the canister. The canister should not be broken, punctured or burnt, even when it seems empty.

6.5 Nature and contents of container

A pressurised container comprising an internally coated aluminium can, sealed with a metering valve and

attached to a dose indicator. The can is fitted into a red plastic actuator incorporating a white plastic

mouthpiece and integrated grey plastic dust cap. Each inhaler delivers 120 actuations of

budesonide/formoterol fumarate dihydrate 200/6 micrograms after initial priming. Each inhaler is

individually wrapped in a foil laminate pouch containing a desiccant.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

AstraZeneca UK Limited,

600 Capability Green,

Luton, LU1 3LU, UK

8. Marketing authorisation number(s)

PL 17901/0293

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 30

March 2016

10. Date of revision of the text

June 2018

Company Contact Details

AstraZeneca UK Limited

Address

Horizon Place, 600 Capability Green, Luton, Bedfordshire, LU1 3LU

+44 (0)1582 838 000

Medical Information e-mail

[email

protected]

Medical Information Fax

+44 (0)1582 838 003

Telephone

+44 (0)1582 836 000

Medical Information Direct Line

0800 783 0033

Customer Care direct line

+44 (0)1582 837 837

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