Trydonis

Package leaflet: Information for the user

Trydonis 87 micrograms/5 micrograms/9 micrograms pressurised solution for

inhalation
beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Trydonis is and what it is used for
2. What you need to know before using Trydonis
3. How to use Trydonis
4. Possible side effects
5. How to store Trydonis
6. Contents of the pack and other information

1. What Trydonis is and what it is used for

Trydonis is a medicine that helps you breathe and contains three active substances:

• beclometasone dipropionate,
• formoterol fumarate dihydrate, and
• glycopyrronium.

Beclometasone dipropionate belongs to a group of medicines called corticosteroids, which exert an anti-inflammatory action by reducing swelling and irritation in the lungs.
Formoterol and glycopyrronium are medicines known as long-acting bronchodilators. They relax the muscles of the airways through different mechanisms, thereby widening the airways and making breathing easier.
Regular treatment with these three active substances helps to relieve and prevent symptoms such as shortness of breath, wheezing and cough in adult patients with chronic obstructive pulmonary disease (COPD). Trydonis is able to reduce exacerbations (sudden worsening) of COPD symptoms. COPD is a serious chronic disease characterised by obstruction of the airways and damage to the lung alveoli, resulting in difficulty breathing.

2. What you should know before using Trydonis

Do not use Trydonis
If you are allergic to beclometasone dipropionate, formoterol fumarate dihydrate, glycopyrronium, or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Trydonis is used as maintenance therapy for chronic obstructive pulmonary disease (COPD). Do not use this medicine to treat an acute episode of breathlessness or wheezing.

If breathing worsens
If you experience worsening shortness of breath or wheezing (a whistling sound during breathing) immediately after inhaling the medicine, stop using the Trydonis inhaler and use your "reliever" (rescue) inhaler with rapid action immediately. Contact your doctor right away, who will assess your symptoms and, if necessary, prescribe a different treatment.
See also section 4, "Possible side effects".

If lung disease worsens
If your symptoms worsen or become difficult to control (e.g. if you need to use your "reliever" inhaler more often), or if your "reliever" inhaler fails to improve your symptoms, contact your doctor immediately. Your lung condition may be deteriorating, and your doctor may prescribe a different treatment.

Talk to your doctor or pharmacist before using Trydonis:

• if you have heart problems, such as angina (chest pain), a recent heart attack (myocardial infarction), heart failure, narrowing of the arteries around the heart (coronary heart disease), a heart valve disorder, or any other heart abnormality, or if you have a condition called obstructive hypertrophic cardiomyopathy (or HCM, a disease characterized by an abnormality of the heart muscle).
• if you have heart rhythm disorders such as irregular heartbeat, rapid pulse, or palpitations, or if your electrocardiogram (ECG) is abnormal.
• if you have narrowing of the arteries (known as atherosclerosis), high blood pressure, or an aneurysm (an abnormal widening of the wall of a blood vessel).
• if you have an overactive thyroid gland.
• if you have low levels of potassium in your blood (hypokalaemia). Using Trydonis together with other medicines for COPD or diuretics (medicines that remove fluid from the body, used to treat heart conditions or high blood pressure) may cause a marked decrease in blood potassium levels. Therefore, your doctor may periodically check your blood potassium levels.
• if you have any liver or kidney disease.
• if you have diabetes. High doses of formoterol may increase blood glucose levels; therefore, you may need additional blood tests to monitor your blood sugar levels when you start using this medicine and periodically during treatment.
• if you have a tumour of the adrenal glands (called a phaeochromocytoma).
• if you are due to undergo anaesthesia. Depending on the type of anaesthetic, you may need to stop treatment with Trydonis at least 12 hours before anaesthesia.
• if you have or have been treated for tuberculosis (TB) or if you have a chest infection.
• if you have a condition affecting the eyes called closed-angle glaucoma.
• if you have difficulty urinating.
• if you have an infection of the mouth or throat.

If any of these conditions apply to you, inform your doctor before using Trydonis.
If you have or have had any medical condition or allergy, or if you are unsure whether you can use Trydonis, talk to your doctor or pharmacist before using the inhaler.

If you are already using Trydonis
If you are using Trydonis or high doses of other inhaled corticosteroids for prolonged periods and find yourself in a stressful situation (e.g. hospitalization after an injury, severe injuries, or before surgery), you may need a higher dose of this medicine. In such cases, your doctor may need to increase your corticosteroid dose to help your body cope with stress and may prescribe it in the form of tablets or injections.

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

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age.

Other medicines and Trydonis
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines similar to Trydonis used for your lung condition.

Some medicines may increase the effects of Trydonis, and your doctor may want to monitor you closely if you are taking these medicines (including some medicines for human immunodeficiency virus (HIV): ritonavir, cobicistat).

Do not use this medicine with a beta-blocker (used to treat certain heart conditions such as angina, or to lower blood pressure), unless your doctor has prescribed a beta-blocker that does not interfere with breathing. Beta-blockers (including beta-blocker eye drops) may reduce or completely block the effects of formoterol. On the other hand, using other beta2-agonist medicines (which have a similar action to formoterol) may increase the effects of formoterol.

Using Trydonis together with:

• medicines used to treat
  • heart rhythm disorders (quinidine, disopyramide, procainamide),
  • allergic reactions (antihistamines),
  • symptoms of depression or mental disorders such as monoamine oxidase inhibitors (e.g. phenelzine and isocarboxazid), tricyclic antidepressants (e.g. amitriptyline and imipramine), phenothiazines may cause changes in the electrocardiogram (ECG). They may also increase the risk of heart rhythm disorders (ventricular arrhythmias).
• medicines used to treat Parkinson's disease (levodopa), underactive thyroid gland (levothyroxine), medicines containing oxytocin (which cause uterine contractions), and alcohol may increase the likelihood of cardiac side effects due to formoterol.
• monoamine oxidase inhibitors (MAOIs), including medicines with similar properties such as furazolidone and procarbazine, used to treat mental disorders, may increase blood pressure.
• medicines used to treat heart conditions (digoxin) may reduce blood potassium levels. This may increase the risk of heart rhythm abnormalities.
• other medicines used to treat COPD (theophylline, aminophylline, or corticosteroids) and diuretics may reduce blood potassium levels.
• certain anaesthetics may increase the risk of heart rhythm abnormalities.
• disulfiram, a medicine used to treat alcoholism (alcohol dependence), or metronidazole, an antibiotic used to treat infection, may cause side effects (e.g. nausea, vomiting, stomach upset) due to the small amount of alcohol present in Trydonis.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Use Trydonis during pregnancy only if advised by your doctor. It is preferable to avoid using Trydonis during labour due to the uterine contraction-inhibiting effect of formoterol.
Do not use Trydonis while breastfeeding. You and your doctor must decide whether to stop breastfeeding or to stop/abstain from treatment with Trydonis, taking into account the benefits of breastfeeding for the child and the benefits of treatment for you.

Driving and using machines
It is unlikely that Trydonis will affect your ability to drive or operate machinery.

Trydonis contains ethanol
Trydonis contains 8.856 mg of alcohol (ethanol) per actuation, equivalent to 17.712 mg per two-actuation dose. The amount in two actuations of this medicine is equivalent to that contained in less than 1 mL of wine or beer. The small amount of alcohol in this medicine will not produce any significant effects.

3. How to use Trydonis

Use this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is two inhalations in the morning and two inhalations in the evening.
If you feel that the medicine is not very effective, consult your doctor.
If you have previously used a different inhaler containing beclometasone dipropionate, ask your
doctor for advice, as the effective dose of beclometasone dipropionate contained in Trydonis for the treatment
of COPD may be lower than that of other inhalers.
Route of administration
Trydonis is for inhalation use only.
You must inhale the medicine through your mouth: this way, the medicine reaches directly to the
lungs.
This medicine is contained in a pressurised canister within a plastic inhaler
with a mouthpiece.
Trydonis is available in three different canisters:

• a 60-dose canister
• a 120-dose canister
• a 180-dose canister.

If you have been prescribed a 60-dose or 120-dose canister
On the back of the inhaler there is a dose counter indicating the number of doses remaining. Each time
you press on the pressurised canister, a dose of the medicine is released, causing the
dose counter to decrease by one unit. Be careful not to drop the inhaler, as this may cause
the dose counter to decrease by one unit.
If you have been prescribed a 180-dose canister
On the back of the inhaler there is an indicator showing the number of doses remaining. Each time
you press on the pressurised canister, a dose of the medicine is released, and the dose
indicator rotates slightly. The number of remaining doses is shown at intervals of 20. Be careful not to
drop the inhaler, as this may cause a decrease in the numbering of the dose indicator.
Checking the inhaler is working
Before using it for the first time, you must test the inhaler as described below to ensure it is
working correctly.

1. Depending on the type of canister prescribed to you, check that the dose counter shows the number 61 or 121 and that the dose indicator shows the number 180.
2. Remove the protective cap from the mouthpiece.
3. Hold the inhaler upright, with the mouthpiece pointing downwards.
4. Point the mouthpiece away from yourself and press firmly on the pressurised canister to release one dose.
5. Check the dose counter or dose indicator. If you are using the inhaler for the first time, the counter should indicate:

60 120 180

• if using the 60-dose canister - if using the 120-dose canister - if using the 180-dose canister

How to use the inhaler
While inhaling, stand or sit upright.
IMPORTANT: do not perform steps 2 to 5 too quickly.

1. Remove the protective cap from the mouthpiece and check that the mouthpiece is clean and free of dust and dirt.
2. Breathe out as slowly and deeply as possible to empty your lungs.
3. Hold the inhaler upright, with the mouthpiece pointing downwards, and place the mouthpiece between your teeth without biting it. Close your lips around the mouthpiece, keeping your tongue lowered beneath it.
4. Breathe in slowly and deeply through your mouth to fill your lungs with air (this inhalation should last about 4–5 seconds). Immediately after starting to inhale, press firmly on the top of the pressurised canister to release one dose.
5. Hold your breath for as long as possible, then remove the inhaler from your mouth and breathe out slowly. Do not breathe out into the inhaler.
6. Check that the dose counter (60/120 doses) has decreased by one unit or that the dose indicator (180 doses) has rotated slightly.

To take the second dose, hold the inhaler upright for about half a minute, then repeat
steps 2 to 5.
If you see a kind of "mist" escaping from the top of the inhaler or from the sides of your mouth,
this means that Trydonis is not reaching your lungs properly. Take another dose following the
instructions from step 2.
After use, replace the protective cap.
To prevent fungal infection in the mouth and throat, rinse your mouth or gargle with
water without swallowing, or brush your teeth each time you have used the inhaler.
When to get a new inhaler
Replace the inhaler when the dose counter or dose indicator shows the number 20. Do not use
the inhaler any longer when the dose counter or dose indicator shows 0, as the medicine remaining
in the inhaler may be insufficient to deliver a full dose.
If you have a weak grip, it may be easier to hold the inhaler with both hands: place both index fingers on the top of the inhaler and both thumbs on the bottom.
If you have difficulty using the inhaler while starting to inhale, you may use the AeroChamber Plus spacer. Ask your doctor or pharmacist for information about this device.
It is important to read the instruction leaflet provided with the AeroChamber Plus spacer and to carefully follow the instructions for use and cleaning of the AeroChamber Plus spacer.
Cleaning the Trydonis inhaler
Clean the inhaler once a week.

1. Do not remove the pressurised canister from the inhaler and do not use water or other liquids to clean the inhaler.
2. Remove the protective cap from the mouthpiece by pulling it off the inhaler.
3. Clean the inside and outside of the mouthpiece and inhaler with a clean, dry wipe or cloth.
4. Replace the protective cap on the mouthpiece.

If you use more Trydonis than you should
It is important that you take the dose as prescribed by your doctor. Do not take a higher dose than
prescribed without consulting your doctor.
If you use more Trydonis than you should, side effects may occur, as described in section 4.
Inform your doctor if you have used more Trydonis than you should and if any of these
symptoms occur. Your doctor may decide to perform some blood tests.
If you forget to use Trydonis
Use it as soon as you remember. If it is almost time for your next dose, do not take the missed dose,
but take the next dose at the scheduled time. Do not double the dose.
If you stop using Trydonis
It is important to use Trydonis every day. Do not stop treatment with Trydonis and do not reduce the
dose, even if you feel better or have no symptoms. If you wish to do so, consult your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Immediately after using Trydonis, there is a risk that shortness of breath and wheezing may worsen. This effect is known as paradoxical bronchospasm (may affect up to 1 in 1,000 people). If this occurs, stop treatment with Trydonis immediately and use your "reliever" inhaler with fast action to treat shortness of breath and wheezing. Seek medical advice immediately.

Inform your doctor immediately:

• if you experience any allergic reaction such as skin allergies, hives, skin itching, rash (may affect up to 1 in 100 people), skin redness, swelling of the skin or mucous membranes, and particularly of the eyes, face, lips, and throat (may affect up to 1 in 1,000 people).
• if you experience eye pain or discomfort, temporary blurred vision, seeing halos or colored images, associated with red eyes. These may be signs of an acute attack of narrow-angle glaucoma (may affect up to 1 in 10,000 people).

Inform your doctor if any of the following symptoms occur during treatment with Trydonis, as they may be symptoms of a lung infection (may affect up to 1 in 10 people):

• fever or chills
• increased mucus production, change in mucus color
• worsening cough or difficulty breathing.

The possible side effects are listed below in order of frequency.

Common (may affect up to 1 in 10 people)

• sore throat
• runny or stuffy nose and sneezing
• fungal infections of the mouth. These side effects can be prevented by rinsing your mouth or gargling with water or brushing your teeth immediately after inhalation
• hoarseness
• headache
• urinary tract infection.

Uncommon (may affect up to 1 in 100 people)

• influenza • sore throat irritation
• sinus inflammation • nosebleeds
• nasal itching, runny or stuffy nose • redness of the pharynx
• fungal infections of the throat or • dry mouth esophagus • diarrhea
• fungal infections of the vagina • difficulty swallowing
• restlessness • feeling unwell
• tremor • stomach discomfort
• dizziness • stomach pain after meals
• taste disturbance or reduced sense of taste • burning sensation in the lips
• numbness • tooth decay
• ear inflammation • skin rash, hives, skin itching
• irregular heartbeat • inflammation of the mouth mucosa
• changes in electrocardiogram (ECG), with or without ulcers
• rapid heartbeat and heart rhythm disorders • muscle cramps and muscle pain
• palpitations (awareness of abnormal heartbeat) • pain in arms or legs
• redness of the face • pain in muscles, bones, or chest joints
• increased blood flow to certain tissues • fatigue
• asthma attack • reduced levels of certain blood components: granulocytes (a type of white blood cell), potassium, or cortisol
• increased levels of certain blood components: glucose, C-reactive protein, platelet count, insulin, free fatty acids, or ketones.

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

• fungal infections in the chest • bleeding from a blood vessel into surrounding tissues
• loss of appetite
• sleep disorder (sleeping too little or too much) • low blood pressure
• sharp chest pain • pain at the back of the mouth and throat
• sensation of missed heartbeats or extra heartbeats, slow heartbeat • dry throat
• painful and frequent urination
• worsening of asthma • difficulty and pain during urination
• kidney inflammation.

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

• low number of certain blood cells called platelets
• breathlessness or shortness of breath
• swelling of hands and feet
• growth retardation in children and adolescents.

Not known (frequency cannot be estimated from the available data)

• blurred vision

Long-term use of inhaled corticosteroids may, in very rare cases, cause systemic effects:

• problems with adrenal gland function (adrenal suppression)
• reduced bone mineral density (thinning of the bones)
• lens opacity (cataract).

Trydonis does not contain high doses of inhaled corticosteroid, but your doctor may wish to periodically monitor blood cortisol levels.

With long-term use of high-dose inhaled corticosteroids, the following side effects may also occur, but the frequency is not known (frequency cannot be estimated from the available data):

• depression
• feelings of anxiety, nervousness, hyperexcitability, or irritability. These events are more likely in children.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Trydonis

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after
Exp. The expiry date refers to the last day of that month.
Do not freeze.
Do not expose to temperatures above 50°C.
Do not pierce the pressurised container.

Before dispensing to the patient:
Store in a refrigerator (2°C–8°C).

After dispensing (once the patient has received the medicine from the pharmacist):
Pressurised container with 60 actuations: store the inhaler at a temperature below 25°C for up to 2 months.
Pressurised container with 120 (from a single or multi-pack) and 180 actuations: store the inhaler at a temperature below 25°C for up to 4 months.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Trydonis contains
The active substances are beclometasone dipropionate, formoterol fumarate dihydrate and glycopyrronium.
Each delivered dose (the dose exiting the mouthpiece) contains 87 micrograms of beclometasone
dipropionate, 5 micrograms of formoterol fumarate dihydrate and 9 micrograms of glycopyrronium
(as 11 micrograms of glycopyrronium bromide).
Each metered dose (the dose released by the metering valve) contains 100 micrograms of
beclometasone dipropionate, 6 micrograms of formoterol fumarate dihydrate and 10 micrograms of
glycopyrronium (as 12.5 micrograms of glycopyrronium bromide).
The other components are anhydrous ethanol (see section 2), hydrochloric acid, propellant:
norflurane.
This medicinal product contains fluorinated greenhouse gases.
Each 60-dose inhaler contains 6.481 g of norflurane (HFC-134a), equivalent to 0.009 tonnes of CO₂
equivalent (global warming potential = 1430).
Each 120-dose inhaler contains 10.37 g of norflurane (HFC-134a), equivalent to 0.015 tonnes of CO₂
equivalent (global warming potential = 1430).
Each 180-dose inhaler contains 14.259 g of norflurane (HFC-134a), equivalent to 0.02 tonnes of CO₂
equivalent (global warming potential = 1430).

Description of the appearance of Trydonis and contents of the pack
Trydonis is a pressurised solution for inhalation.
Trydonis is supplied in a pressurised container (aluminium coated), equipped with a metering valve. The pressurised container is placed inside a plastic inhaler device. This includes a mouthpiece with a protective plastic cap and either a dose counter (60- or 120-dose packs) or a dose indicator (180-dose packs).
Each pack contains one pressurised container delivering 60, 120 or 180 doses. Multi-pack cartons are also available, containing 240 doses (2 pressurised containers of 120 doses each) or 360 doses (3 pressurised containers of 120 doses each).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma
Italy

Manufacturer
Chiesi Farmaceutici S.p.A.
Via San Leonardo 96
43122 Parma
Italy
Chiesi SAS
2 rue des Docteurs Alberto et Paolo Chiesi
41260 La Chaussée Saint Victor
France
Chiesi Pharmaceuticals GmbH
Gonzagagasse 16/16
1010 Wien
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Chiesi sa/nv Chiesi Pharmaceuticals GmbH
Tél/Tel: + 32 (0)2 788 42 00 Tel: + 43 1 4073919

България Luxembourg/Luxemburg
Chiesi Bulgaria EOOD Chiesi sa/nv
Teл.: + 359 29201205 Tél/Tel: + 32 (0)2 788 42 00

Česká republika Magyarország
Chiesi CZ s.r.o. Chiesi Hungary Kft.
Tel: + 420 261221745 Tel.: + 36-1-429 1060

Danmark Malta
Chiesi Pharma AB Chiesi Farmaceutici S.p.A.
Tlf: + 46 8 753 35 20 Tel: + 39 0521 2791

Deutschland Nederland
Chiesi GmbH Chiesi Pharmaceuticals B.V.
Tel: + 49 40 89724-0 Tel: + 31 88 501 64 00

Eesti Norge
Chiesi Pharmaceuticals GmbH Chiesi Pharma AB
Tel: + 43 1 4073919 Tlf: + 46 8 753 35 20

Ελλάδα Österreich
Chiesi Hellas AEBE Chiesi Pharmaceuticals GmbH
Τηλ: + 30 210 6179763 Tel: + 43 1 4073919

España Polska
Laboratorios BIAL, S.A. Chiesi Poland Sp. z.o.o.
Tel: + 34 91 562 41 96 Tel.: + 48 22 620 1421

France Portugal
Chiesi S.A.S. Chiesi Farmaceutici S.p.A.
Tél: + 33 1 47688899 Tel: + 39 0521 2791

Hrvatska România
Chiesi Pharmaceuticals GmbH Chiesi Romania S.R.L.
Tel: + 43 1 4073919 Tel: + 40 212023642

Ireland Slovenija
Chiesi Farmaceutici S.p.A. CHIESI SLOVENIJA, d.o.o.
Tel: + 39 0521 2791 Tel: + 386-1-43 00 901

Ísland Slovenská republika
Chiesi Pharma AB Chiesi Slovakia s.r.o.
Sími: +46 8 753 35 20 Tel: + 421 259300060

Italia Suomi/Finland
Chiesi Italia S.p.A. Chiesi Pharma AB
Tel: + 39 0521 2791 Puh/Tel: +46 8 753 35 20

Κύπρος Sverige
Chiesi Farmaceutici S.p.A. Chiesi Pharma AB
Τηλ: + 39 0521 2791 Tel: +46 8 753 35 20

Latvija
Chiesi Pharmaceuticals GmbH
Tel: + 43 1 4073919

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu .

Package leaflet: Information for the user

Trydonis 88 micrograms/5 micrograms/9 micrograms inhalation powder

beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Trydonis is and what it is used for
2. What you need to know before using Trydonis
3. How to use Trydonis
4. Possible side effects
5. How to store Trydonis
6. Contents of the pack and other information

1. What Trydonis is and what it is used for

Trydonis is a medicine that helps you breathe and contains three active substances:

• beclometasone dipropionate,
• formoterol fumarate dihydrate,
• glycopyrronium.

Beclometasone dipropionate belongs to a group of medicines called corticosteroids, which exert an anti-inflammatory action by reducing swelling and irritation in the lungs.
Formoterol and glycopyrronium are medicines called long-acting bronchodilators. They relax the muscles of the airways through different mechanisms, thereby widening the airways and making breathing easier.
Regular treatment with these three active substances helps to relieve and prevent symptoms such as shortness of breath, wheezing and cough in adult patients with chronic obstructive pulmonary disease (COPD). Trydonis is able to reduce exacerbations (sudden worsening) of COPD symptoms. COPD is a serious chronic disease characterised by obstruction of the airways and damage to the lung alveoli, resulting in difficulty breathing.

2. What you need to know before using Trydonis

Do not use Trydonis
If you are allergic to beclometasone dipropionate, formoterol fumarate dihydrate and/or glycopyrronium or to
any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Trydonis is used as maintenance therapy for obstructive lung disease. Do not use this
medicine to treat an acute episode of breathlessness or wheezing.

If your breathing worsens
If you experience worsening shortness of breath or wheezing (a whistling sound during breathing) immediately after inhaling the medicine, stop using the Trydonis inhaler and use your "reliever" (rescue) inhaler with rapid action immediately. Contact your doctor right away; they will assess your symptoms and, if necessary, prescribe a different treatment.
See also section 4, "Possible side effects".

If your lung disease worsens
If your symptoms worsen or become difficult to control (e.g. if you need to use your "reliever" inhaler more frequently), or if your "reliever" inhaler fails to improve your symptoms, contact your doctor immediately. Your lung condition may be worsening, and your doctor may prescribe a different treatment.

Talk to your doctor or pharmacist before using Trydonis:

• if you have heart problems, such as angina (chest pain), recent heart attack (myocardial infarction), heart failure, narrowing of the arteries around the heart (coronary heart disease), heart valve disease or any other heart abnormality, or if you have a condition called obstructive hypertrophic cardiomyopathy (or HCM, a disease characterized by an abnormality of the heart muscle).
• if you have heart rhythm disorders such as irregular heartbeat, rapid pulse or palpitations, or if your electrocardiogram (ECG) is abnormal.
• if you have narrowed arteries (known as arteriosclerosis), high blood pressure, or an aneurysm (an abnormal bulging of a blood vessel wall).
• if you have an overactive thyroid gland.
• if you have low levels of potassium in your blood (hypokalaemia). Using Trydonis together with other lung medicines or diuretics (medicines that remove water from the body, used to treat heart conditions or high blood pressure) may cause a marked decrease in blood potassium levels. Therefore, your doctor may periodically check your blood potassium levels.
• if you have any liver or kidney disease.
• if you have diabetes. High doses of formoterol may increase blood glucose levels; therefore, you may need additional blood tests to monitor your blood sugar when starting this medicine and periodically during treatment.
• if you have a tumour of the adrenal glands (called phaeochromocytoma).
• if you are due to undergo anaesthesia. Depending on the type of anaesthetic, you may need to stop treatment with Trydonis at least 12 hours before the anaesthesia.
• if you currently have or have previously been treated for tuberculosis (TB) or have a chest infection.
• if you have a condition affecting the eyes called closed-angle glaucoma.
• if you have difficulty urinating.
• if you have a mouth or throat infection.

If any of these conditions apply to you, inform your doctor before using Trydonis.
If you have or have had any medical condition or allergy, or if you are unsure whether you can
use Trydonis, talk to your doctor or pharmacist before using the inhaler.

If you are already using Trydonis
If you are using Trydonis or high doses of other inhaled corticosteroids over a long period and find yourself under stress (e.g. hospitalization after an injury, serious injuries, or prior to surgery), you may need a higher dose of this medicine. In such cases, your doctor may need to increase your corticosteroid dose to help manage the stress and may prescribe it in the form of tablets or injections.
Contact your doctor if you experience blurred vision or other visual disturbances.

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age.

Other medicines and Trydonis
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This also includes medicines similar to Trydonis used for your lung condition.
Some medicines may increase the effects of Trydonis, and your doctor may want to monitor you closely if you are taking these medicines (including some medicines for human immunodeficiency virus (HIV): ritonavir, cobicistat).

Do not use this medicine with a beta-blocker (used to treat certain heart conditions such as angina, or to lower blood pressure), unless your doctor has chosen a beta-blocker that does not interfere with breathing. Beta-blockers (including beta-blocker eye drops) may reduce or completely counteract the effects of formoterol. On the other hand, using other beta2-agonist medicines (which have a similar action to formoterol) may increase the effects of formoterol.

The use of Trydonis together with:

• medicines used to treat
  • heart rhythm disorders (quinidine, disopyramide, procainamide),
  • allergic reactions (antihistamines),
  • symptoms of depression or mental disorders such as monoamine oxidase inhibitors (e.g. phenelzine and isocarbazide), tricyclic antidepressants (e.g. amitriptyline and imipramine), phenothiazines may cause changes in the electrocardiogram (ECG). They may also increase the risk of heart rhythm disorders (ventricular arrhythmias).
• medicines used to treat Parkinson's disease (levodopa), underactive thyroid gland (levotyroxine), medicines containing oxytocin (which cause uterine contractions), and alcohol may increase the likelihood of cardiac side effects due to formoterol.
• monoamine oxidase inhibitors (MAOIs), including medicines with similar properties such as furazolidone and procarbazine, used to treat mental disorders, may increase blood pressure.
• medicines used to treat heart conditions (digoxin) may reduce potassium levels in the blood. This may increase the risk of heart rhythm abnormalities.
• other medicines used to treat chronic obstructive pulmonary disease (theophylline, aminophylline or corticosteroids) and diuretics may reduce potassium levels in the blood.
• certain anaesthetics may increase the risk of heart rhythm abnormalities.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Use Trydonis during pregnancy only if your doctor has advised you to do so. It is preferable to avoid using Trydonis during labour due to the uterine contraction-inhibiting effect of formoterol.
Do not use Trydonis while breastfeeding. You and your doctor must decide whether to stop breastfeeding or discontinue/abstain from treatment with Trydonis, taking into account the benefits of breastfeeding for the child and the benefits of treatment for you.

Driving and using machines
It is unlikely that Trydonis will affect your ability to drive or use machines.

Trydonis contains lactose
Lactose contains small amounts of milk proteins that may cause allergic reactions.

3. How to use Trydonis

Use this medicine exactly as instructed by your doctor or pharmacist. If you
have
any doubts, consult your doctor or pharmacist.
The recommended dose is two inhalations in the morning and two inhalations in the evening.
If you feel that the medicine is not very effective, contact your doctor.
If you have previously used a different inhaler containing beclometasone dipropionate, ask your
doctor for advice, as the effective dose of beclometasone dipropionate contained in Trydonis for the treatment
of your chronic obstructive pulmonary disease may be lower than that of other inhalers.
Route of administration
Trydonis is for inhalation use only.
You must inhale the medicine through the mouth: in this way, the medicine reaches the
lungs directly.
Instructions for use
For information on the contents of the pack, see section 6.
If the contents of the pack differ from those described in section 6, return
the inhaler to the person who supplied it and obtain a new one.

• Do not remove the inhaler from the pouch if you do not intend to use it immediately.
• Use the inhaler only as directed.
• Keep the cover closed until you are ready to take a dose from the inhaler.
• When not in use, store the inhaler in a clean and dry place.
• Do not under any circumstances attempt to dismantle the inhaler.

A. Main features of the inhaler

Window
Cover Mouthpiece Air outlet
of the
dose counter
Taking a dose from the inhaler involves three steps: Opening, Inhaling, Closing.
B. Before using a new inhaler

1. Open the pouch and remove the inhaler.

o Do not use the inhaler if the pouch is not sealed or is damaged; return it to the
pharmacist who supplied it and obtain a new one.
o Use the label on the box to record the date on which the pouch was opened.

2. Inspect the inhaler.

o If the inhaler appears broken or damaged, return it to the pharmacist who supplied it and obtain a new one.

3. Check the dose counter window. If the inhaler is new, the dose counter window should display “120”.
   o Do not use a new inhaler if the number shown is less than “120”; return it to the pharmacist who supplied it and obtain a new one.

C. How to use the inhaler
C.1. Opening
1. Hold the inhaler firmly in an upright position.
2. Check the number of doses remaining: any number between “1” and “120” indicates
how many doses are left.
o If the dose counter window displays “0”, no doses remain; dispose of the inhaler and obtain a new one.

3. Open the lid completely.

4. Before inhaling, breathe out as fully as possible without effort.

o Do not breathe out through the inhaler.
C.2. Inhalation
If possible, remain standing or sitting in an upright position during inhalation.

1. Lift the inhaler, bring it to your mouth and place your lips around the mouthpiece.

o Do not cover the air vent when holding the inhaler.
o Do not inhale through the air vent.

2. Take a strong, deep breath in through the mouth.

o A particular taste may be noticed when taking the dose.
o A click may be heard or felt when taking the dose.
o Do not inhale through the nose.
o Do not remove the inhaler from the lips during inhalation.

3. Remove the inhaler from the mouth.
4. Hold the breath for 5–10 seconds, or as long as possible without discomfort.
5. Breathe out slowly.
o Do not breathe out through the inhaler.

• If unsure whether the dose has been taken correctly, consult the pharmacist or doctor.

C.3. Closing
1. Return the inhaler to the upright position and close the cover completely.
2. Check that the dose counter shows one unit less.

• If it is not certain that the dose counter has decreased by one unit after inhalation, wait until the next scheduled dose and take it as usual. Do not take an extra dose.

3. If another dose is required, repeat steps C.1 to C.3.

D. Cleaning

• Generally, there is no need to clean the inhaler.
• If necessary, you may clean the inhaler after use with a dry cloth or tissue. Do not clean the inhaler with water or other liquids. Keep it dry.

If you use more Trydonis than you should
It is important that you take the dose as prescribed by your doctor. Do not take a higher dose than prescribed without consulting your doctor.
If you use more Trydonis than you should, side effects may occur, as described in section 4.
Inform your doctor if you have used more Trydonis than you should and if any of these symptoms occur. Your doctor may decide to carry out some blood tests.

If you forget to use Trydonis
Use it as soon as you remember. If it is almost time for your next dose, do not take the missed dose, but take the next dose at the scheduled time. Do not double the dose.

If you stop using Trydonis
It is important to use Trydonis every day. Do not stop using Trydonis or reduce the dose, even if you feel better or have no symptoms. If you wish to do so, consult your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Immediately after using Trydonis, there is a risk that shortness of breath and wheezing may worsen. This effect is known as paradoxical bronchospasm (may affect up to 1 in 1,000 people). If this occurs, stop treatment with Trydonis and use your "reliever" inhaler immediately to treat shortness of breath and wheezing. Seek medical advice immediately.

Inform your doctor immediately:

• if you experience any allergic reaction such as skin allergies, hives, skin itching, rash (may affect up to 1 in 100 people), skin redness, swelling of the skin or mucous membranes, and particularly of the eyes, face, lips and throat (may affect up to 1 in 1,000 people).
• if you experience eye pain or discomfort, transient blurred vision, seeing halos or coloured images, associated with red eyes. These may be signs of an acute attack of closed-angle glaucoma (may affect up to 1 in 10,000 people).

Inform your doctor if any of the following symptoms occur while using Trydonis, as they may be symptoms of a lung infection (may affect up to 1 in 10 people):

• fever or chills
• increased mucus production, change in the colour of mucus
• increased coughing or worsening difficulty in breathing.

The possible side effects are listed below, grouped by frequency.

Common (may affect up to 1 in 10 people)

• sore throat
• runny or blocked nose and sneezing
• fungal infections of the mouth. These side effects can be prevented by rinsing your mouth or gargling with water, or brushing your teeth immediately after inhalation
• hoarseness
• headache
• urinary tract infection.

Uncommon (may affect up to 1 in 100 people)

• influenza • sore throat
• sinus inflammation • nosebleeds
• nasal itching, runny or blocked nose • redness of the pharynx
• fungal infections of the throat or • dry mouth oesophagus • diarrhoea
• vaginal fungal infections • difficulty swallowing
• restlessness • feeling unwell
• tremor • stomach disturbances
• dizziness • stomach discomfort after meals
• altered or reduced sense of taste • burning sensation of the lips
• numbness • dental caries
• ear inflammation • skin rash, hives, skin itching
• irregular heartbeat • inflammation of the mouth mucosa,
• changes in electrocardiogram (ECG) with or without ulcers
• abnormally fast heartbeat and heart rhythm disturbances • increased sweating
• muscle cramps and muscle pain • palpitations (awareness of abnormal heartbeat)
• pain in arms or legs • pain in muscles, bones or chest joints
• facial flushing • increased blood flow to certain tissues in the body
• asthma attack • cough and productive cough
• reduced levels of certain blood components: a type of white blood cells called granulocytes, potassium, or cortisol
• increased levels of certain blood components: glucose, C-reactive protein, platelet count, insulin, free fatty acids or ketones.

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

• fungal infections of the chest • bleeding from a blood vessel into surrounding tissues
• loss of appetite
• sleep disturbance (sleeping too little or too much) • low blood pressure
• sharp chest pain • pain at the back of the mouth and throat
• sensation of missed heartbeats or extra heartbeats, slow heartbeat • dry throat
• painful and frequent urination • difficulty or pain when urinating
• worsening of asthma • kidney inflammation.

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

• low number of certain blood cells called platelets
• breathlessness or shortness of breath
• swelling of hands and feet
• growth retardation in children and adolescents.

Not known (frequency cannot be estimated from the available data):

• blurred vision

Long-term use of inhaled corticosteroids may very rarely cause systemic effects:

• problems with adrenal gland function (adrenal suppression)
• reduced bone mineral density (thinning of the bones)
• lens opacity (cataract).

Trydonis does not contain high doses of inhaled corticosteroid, but your doctor may wish to periodically monitor blood cortisol levels.
The following side effects may also occur with long-term use of high-dose inhaled corticosteroids, but the frequency is not known (cannot be estimated from the available data):

• depression
• feelings of anxiety, nervousness, hyperexcitability or irritability. These events are more likely in children.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Trydonis

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after
Exp. The expiry date refers to the last day of that month.
Do not store above 25 °C.
Keep the inhaler in the original packaging to protect the medicine from moisture, and remove it from
the pouch only immediately before first use.
After first opening the pouch, the medicine must be used within 6 weeks and stored in a dry place. Use
the adhesive label on the outer carton to record the date you open the pouch, and attach this label to
the bottom of the inhaler.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose
of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Trydonis contains
The active substances are beclometasone dipropionate, formoterol fumarate dihydrate and glycopyrronium.
Each delivered dose (the dose that exits the mouthpiece) contains 88 micrograms of beclometasone
dipropionate, 5 micrograms of formoterol fumarate dihydrate and 9 micrograms of glycopyrronium
(as 11 micrograms of glycopyrronium bromide).
Each pre-metered dose contains 100 micrograms of beclometasone dipropionate, 6 micrograms of
formoterol fumarate dihydrate and 10 micrograms of glycopyrronium (as 12.5 micrograms of
glycopyrronium bromide).
The other components are lactose monohydrate (see section 2) and magnesium stearate.

Description of the appearance of Trydonis and contents of the pack
Trydonis is a powder for inhalation, white to almost white in colour.
It is supplied in a white plastic inhaler called NEXThaler, fitted with a grey cap and a dose counter.
Each inhaler is packaged in a sealed protective pouch.
Trydonis is available in packs containing one inhaler and in multiple packs containing two or three inhalers, each providing 120 inhalations (120, 240 or 360 inhalations in total).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma
Italy

Manufacturer
Chiesi Farmaceutici S.p.A.
Via San Leonardo 96
43122 Parma
Italy
Chiesi SAS
2 rue des Docteurs Alberto et Paolo Chiesi
41260 La Chaussée Saint Victor
France

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Chiesi sa/nv Chiesi Pharmaceuticals GmbH
Tél/Tel: + 32 (0)2 788 42 00 Tel: + 43 1 4073919

България Luxembourg/Luxemburg
Chiesi Bulgaria EOOD Chiesi sa/nv
Teл.: + 359 29201205 Tél/Tel: + 32 (0)2 788 42 00

Česká republika Magyarország
Chiesi CZ s.r.o. Chiesi Hungary Kft.
Tel: + 420 261221745 Tel.: + 36-1-429 1060

Danmark Malta
Chiesi Pharma AB Chiesi Farmaceutici S.p.A.
Tlf: + 46 8 753 35 20 Tel: + 39 0521 2791

Deutschland Nederland
Chiesi GmbH Chiesi Pharmaceuticals B.V.
Tel: + 49 40 89724-0 Tel: + 31 88 501 64 00

Eesti Norge
Chiesi Pharmaceuticals GmbH Chiesi Pharma AB
Tel: + 43 1 4073919 Tlf: + 46 8 753 35 20

Ελλάδα Österreich
Chiesi Hellas AEBE Chiesi Pharmaceuticals GmbH
Τηλ: + 30 210 6179763 Tel: + 43 1 4073919

España Polska
Laboratorios BIAL, S.A. Chiesi Poland Sp. z.o.o.
Tel: + 34 91 562 41 96 Tel.: + 48 22 620 1421

France Portugal
Chiesi S.A.S. Chiesi Farmaceutici S.p.A.
Tél: + 33 1 47688899 Tel: + 39 0521 2791

Hrvatska România
Chiesi Pharmaceuticals GmbH Chiesi Romania S.R.L.
Tel: + 43 1 4073919 Tel: + 40 212023642

Ireland Slovenija
Chiesi Farmaceutici S.p.A. CHIESI SLOVENIJA, d.o.o.
Tel: + 39 0521 2791 Tel: + 386-1-43 00 901

Ísland Slovenská republika
Chiesi Pharma AB Chiesi Slovakia s.r.o.
Sími: +46 8 753 35 20 Tel: + 421 259300060

Italia Suomi/Finland
Chiesi Italia S.p.A. Chiesi Pharma AB
Tel: + 39 0521 2791 Puh/Tel: +46 8 753 35 20

Κύπρος Sverige
Chiesi Farmaceutici S.p.A. Chiesi Pharma AB
Τηλ: + 39 0521 2791 Tel: +46 8 753 35 20

Latvija
Chiesi Pharmaceuticals GmbH
Tel: + 43 1 4073919

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu