Trimbow 87 micrograms/5 micrograms/9 micrograms solution for inhalation in pressurised container

Patient Information Leaflet

Introduction

Patient Information Leaflet

Trimbow 87 micrograms/5 micrograms/9 micrograms pressurised inhalation solution

beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet as 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, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Trimbow is and what it is used for

Trimbow is a medicine to help you breathe that contains three active substances:

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

Beclometasone dipropionate belongs to a group of medicines called corticosteroids, which work by reducing inflammation and irritation in the lungs.

Formoterol and glycopyrronium are medicines called long-acting bronchodilators. They work in different ways to relax the muscles in the airways, helping to widen them and allowing you to breathe more easily.

Regular treatment with these three active substances helps to relieve and prevent symptoms such as breathlessness, wheezing and cough in adult patients with obstructive lung disease.

Trimbow is used for the regular treatment of:

• chronic obstructive pulmonary disease (COPD) in adults,
• asthma in adults.

Trimbow may reduce exacerbations (worsening episodes) of COPD symptoms and asthma symptoms.

COPD is a serious, long-term disease in which the airways become blocked and the air sacs inside the lungs are damaged, causing difficulty in breathing.

Asthma is a serious, chronic disease in which the muscles surrounding the airways tighten (bronchoconstriction) and become swollen and irritated (inflammation). Symptoms come and go and include shortness of breath, wheezing, chest tightness and cough.

You must use Trimbow every day, not only when you have breathing problems or other asthma symptoms. This will ensure that the medicine properly controls your asthma. Do not use this medicine to relieve a sudden attack of breathlessness or wheezing.

2. What you need to know before using Trimbow

Do not use Trimbow

If you are allergic to beclometasone dipropionate, formoterol fumarate dihydrate, glycopyrronium, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Trimbow is used as maintenance treatment for obstructive lung disease. Do not use this medicine to treat a sudden episode of breathing difficulty or wheezing.

If your breathing worsens

If you experience a worsening of breathing difficulties or wheezing (breathing with a whistling sound) immediately after inhaling the medicine, stop treatment with the Trimbow inhaler and use your fast-acting "rescue" inhaler immediately. You must contact your doctor without delay. Your doctor will assess your symptoms and, if necessary, may change your 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 are using your "rescue" inhaler more frequently) or if your "rescue" inhaler fails to improve your symptoms, contact your doctor immediately. Your lung disease may be worsening, and your doctor may need to prescribe a different treatment.

Consult your doctor or pharmacist before starting Trimbow:

• if you have any heart problems, such as angina (chest pain), a recent heart attack (myocardial infarction), heart failure, narrowing of the heart arteries (coronary artery disease), heart valve disease, or any other heart abnormality, or if you have a condition called obstructive hypertrophic cardiomyopathy (also known as HCM, a disease in which the heart muscle is abnormal).

• if you have heart rhythm disorders, such as irregular heartbeat, rapid pulse, or palpitations, or if you have been told that your electrocardiogram (ECG) is abnormal.

• if you have narrowed arteries (also known as atherosclerosis), high blood pressure, or an aneurysm (an abnormal bulge in the wall of a blood vessel).

• if you have an overactive thyroid gland.

• if you have low levels of potassium in your blood (hypokalaemia). The combination of Trimbow with certain other lung medicines or medicines such as diuretics (medicines that cause your body to lose water, used to treat heart disease or high blood pressure) may cause a marked decrease in blood potassium levels. Therefore, your doctor may wish to check your blood potassium levels from time to time.

• if you have any liver or kidney disease.

• if you have diabetes. High doses of formoterol may increase blood glucose levels, so additional blood tests to monitor your blood sugar levels may be needed when you start this medicine and periodically during treatment.

• if you have a tumour of the adrenal gland (known as phaeochromocytoma).

• if you are due to receive an anaesthetic. Depending on the type of anaesthetic, it may be necessary to stop treatment with Trimbow at least 12 hours before anaesthesia.

• if you are receiving or have ever received treatment for tuberculosis (TB) or if you have a chest infection.

• if you have a narrow-angle glaucoma (an eye condition).

• if you have difficulty passing urine.

• if you have an infection in your mouth or throat.

If you are in any of the above situations, inform your doctor before starting to use Trimbow.

If you have or have had any health problems or allergies, or if you are unsure whether you can use Trimbow, consult your doctor or pharmacist before starting to use the inhaler.

If you are already using Trimbow

If you are using Trimbow or high doses of other inhaled corticosteroids for prolonged periods and experience a stressful situation (e.g., if you are admitted to hospital following an accident, have a serious injury, or before surgery), you may require additional medication. In such situations, your doctor may need to increase your corticosteroid dose to cope with the stress and may prescribe them 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 Trimbow

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes medicines similar to Trimbow used for your lung condition.

Some medicines may increase the effects of Trimbow, so your doctor will monitor you closely if you are taking these medicines (including some used for HIV: ritonavir, cobicistat).

Do not use this medicine with a beta-blocker (used to treat certain heart problems such as angina or to lower blood pressure) unless your doctor has chosen a beta-blocker that does not affect your breathing. Beta-blockers (including beta-blocker eye drops) may reduce or completely counteract the effects of formoterol. On the other hand, using other beta2 agonists (which work in the same way as formoterol) may increase the effects of formoterol.

The combined use of Trimbow with:

• medicines to treat

• abnormal heart rhythms (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), and phenothiazines

may cause changes in the electrocardiogram (ECG, heart tracing). They may also increase the risk of heart rhythm disturbances (ventricular arrhythmias).

• medicines to treat Parkinson's disease (levodopa), medicines to treat an underactive thyroid gland (levotyroxine), medicines containing oxytocin (which causes uterine contractions), and alcohol may increase the likelihood of formoterol-related adverse effects on the heart.

• monoamine oxidase inhibitors (MAOIs), including medicines with similar properties such as furazolidone and procarbazine, used to treat mental disorders, may cause an increase in blood pressure.

• medicines to treat heart disease (digoxin) may cause a decrease in blood potassium levels. This may increase the likelihood of abnormal heart rhythms.

• other medicines used to treat obstructive lung disease (theophylline, aminophylline, or corticosteroids) and diuretics may also cause a drop in potassium levels.

• certain anaesthetics may increase the risk of abnormal heart rhythms.

• disulfiram, a medicine used in the treatment of alcoholism (alcohol problems), or metronidazole, an antibiotic used to treat infections in the body, may cause adverse effects (e.g., nausea, vomiting, stomach pain) due to the small amount of alcohol contained in Trimbow.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

You should only use Trimbow during pregnancy if your doctor advises you to do so. It is preferable to avoid using Trimbow during labour due to the formoterol's inhibitory effect on uterine contractions.

You should not use Trimbow while breastfeeding. You and your doctor must decide whether to stop breastfeeding or stop treatment, taking into account the benefit of breastfeeding for your child and the benefit of treatment for you.

Driving and using machines

It is unlikely that Trimbow will affect your ability to drive or use machines.

Trimbow contains ethanol

Trimbow contains 8.856 mg of alcohol (ethanol) per actuation, equivalent to 17.712 mg per dose of two actuations. The amount in two actuations of this medicine is equivalent to less than 1 ml of wine or beer. The small amount of alcohol contained in this medicine does not produce any noticeable effect.

3. How to use Trimbow

Follow exactly the instructions for administering this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose is two doses in the morning and two doses at night.

Do not use more than the amount indicated by your doctor.

You must use Trimbow every day, even when your asthma is not causing problems.

Do not use this medicine to relieve a sudden attack of breathing difficulty or wheezing.

If you think the medicine is not working well enough, consult your doctor.

If you have previously been using another inhaler containing beclometasone dipropionate, consult your doctor, as the effective dose of beclometasone dipropionate in Trimbow for the treatment of obstructive lung disease may be lower than that of other inhalers.

Route of administration

Trimbow is for inhalation use only.

You should inhale the medicine through your mouth, which delivers the medicine directly to the lungs.

This medicine comes in a pressurized container within a plastic inhaler with a mouthpiece.

Trimbow is available in two pack sizes:

• a pack providing 120 doses
• a pack providing 180 doses

If you have been prescribed a pack providing 120 doses

There is a counter on the back of the inhaler that shows how many doses remain. Each time you press the canister, one dose of medicine is released and the counter decreases by one. Avoid dropping the inhaler, as this could cause the counter to decrement.

If you have been prescribed a pack providing 180 doses

There is an indicator on the back of the inhaler that shows how many doses remain. Each time you press the canister, one dose of medicine is released and the counter rotates slightly. The number of remaining doses is displayed in increments of 20. Avoid dropping the inhaler, as this could cause the counter to decrement.

Checking the inhaler

Before using the inhaler for the first time, check it as follows to ensure it is working properly.

1. Depending on the pack size prescribed to you, check that the dose counter reads 121 and that the dose indicator reads 180
2. Remove the protective cap from the mouthpiece
3. Hold the inhaler upright with the mouthpiece at the bottom
4. Point the mouthpiece away from you and firmly press down on the canister to release one dose
5. Check the dose counter or dose indicator. When checking the inhaler for the first time, the counter should display:

120 if you are using the container providing 120 doses	180 if you are using the container providing 180 doses

How to use the inhaler

Stand up or sit upright to inhale.

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, i.e. free from dust or debris.
2. Breathe out slowly and as fully as possible to empty your lungs.
3. Hold the inhaler upright with the mouthpiece pointing downwards. Place the mouthpiece between your teeth without biting it. Then close your lips around the mouthpiece, with your tongue lying flat underneath it.
4. Breathe in slowly and deeply through your mouth to fill your lungs with air (this should take about 4–5 seconds). Just after starting to inhale, press firmly down on the top of the pressurized canister to release one dose.
5. Hold your breath for as long as you can, then remove the inhaler from your mouth and breathe out slowly. Do not exhale through the inhaler.
6. Check that the dose counter (120 doses) has decreased by one unit or that the dose indicator (180 doses) has rotated slightly.

For a second dose, keep the inhaler upright for approximately half a minute, then repeat steps 2 to 5.

If some of the gas escapes from the top of the inhaler or from the corners of your mouth, this means Trimbow will not reach your lungs properly. Take another dose by following the instructions again, starting from step 2.

After use, replace the protective cap.

To prevent a fungal infection in the mouth and throat, rinse your mouth or gargle with water (without swallowing) or brush your teeth after each use of the inhaler.

When to get a new inhaler

You should get a replacement when the counter or indicator shows the number 20. Stop using the inhaler when the counter or indicator shows 0, as any remaining medicine in the inhaler may be insufficient to deliver a full dose.

If you have difficulty gripping, you may find it 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 find it difficult to use the inhaler while starting to inhale, you may use the AeroChamber Plus spacer device. Consult your doctor or pharmacist about this device.

It is important that you read the leaflet provided with the AeroChamber Plus spacer device and follow its instructions for use and cleaning carefully.

Cleaning the Trimbow inhaler

You should clean the inhaler once a week.

1. Do not remove the pressurized canister from the inhaler and do not use water or other liquids to clean it.
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 cloth or tissue.
4. Replace the mouthpiece cap.

If you use more Trimbow than you should

It is important to take the dose as prescribed by your doctor. Do not exceed the prescribed dose without first consulting your doctor.

If you use more Trimbow than you should, the adverse effects described in section 4 may occur.

Inform your doctor if you have used more Trimbow than you should and if you experience any of these symptoms. Your doctor may wish to carry out some blood tests.

If you forget to use Trimbow

Use it as soon as you remember. If it is almost time for your next dose, do not take the missed dose; instead, take only the next dose at the correct time. Do not double the dose.

If you stop using Trimbow

It is important to use Trimbow every day. Do not stop treatment with Trimbow 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 further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

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

There is a risk of worsening breathing difficulty and wheezing immediately after using Trimbow, known as paradoxical bronchospasm (may affect up to 1 in 1,000 people). If this occurs, you must stop treatment with Trimbow and immediately use your fast-acting "rescue" inhaler to treat the breathing difficulty and wheezing. You must contact your doctor immediately.

Inform your doctor immediately

• if you experience allergic reactions such as skin allergies, hives, skin itching, skin rash (may affect up to 1 in 100 people), skin redness, swelling of the skin or mucous membranes, especially 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, visual 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 you notice any of the following symptoms while using Trimbow, as they may be due to a lung infection (may affect up to 1 in 10 people):

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

The possible adverse effects are listed below according to their frequency.

Frequent (may affect up to 1 in 10 people)

• sore throat
• nasal discharge or congestion and sneezing
• fungal infections of the mouth. Rinsing your mouth or gargling with water and brushing your teeth immediately after inhalation may help prevent these adverse effects
• hoarseness
• headache
• urinary tract infection

Uncommon (may affect up to 1 in 100 people)

flu sinus inflammation nasal itching, discharge, or congestion fungal infections of the throat or food pipe (esophagus) fungal infections of the vagina agitation tremor dizziness disturbances or reduction in taste sensation numbness ear inflammation irregular heartbeat changes in electrocardiogram (ECG) unusually fast heartbeat and heart rhythm disorders palpitations (awareness of abnormal heartbeats) facial redness increased blood flow to certain body tissues asthma attack dry cough and productive cough

throat irritation nosebleeds redness of the pharynx dry mouth diarrhea difficulty swallowing nausea upset stomach stomach discomfort after meals burning sensation in the lips dental caries skin rash, hives, skin itching inflammation of the mucous membrane of the mouth, with or without ulcers increased sweating muscle cramps and muscle pain pain in arms or legs chest muscle, bone, or joint pain fatigue increased blood pressure decreased levels of certain blood components: certain 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 in the chest decreased appetite sleep disorders (sleeping too little or too much) crushing chest pain sensation of missed heartbeat or extra heartbeats, unusually slow heartbeat asthma attack

bleeding from a blood vessel into the surrounding tissues decrease in blood pressure weakness pain in the back of the mouth and throat inflammation of the pharynx dry throat painful and frequent urination difficulty and pain when urinating inflammation of the kidneys

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

• low level of certain blood cells called platelets
• feeling of suffocation or difficulty breathing
• swelling of hands and feet
• growth retardation in children and adolescents

Frequency not known (cannot be estimated from available data)

• blurred vision

The use of inhaled corticosteroids at high doses over a prolonged period of time may, in very rare cases, cause systemic effects:

• problems with adrenal gland function (adrenal suppression)
• decreased bone mineral density (thinning of the bones)
• clouding of the eye lens (cataract)

Trimbow does not contain a high-dose inhaled corticosteroid, but your doctor may occasionally wish to measure your blood cortisol levels.

The following adverse effects may also occur when inhaled corticosteroids are used at high doses over a prolonged period of time, but their frequency is currently unknown (cannot be estimated from available data):

• depression
• feelings of anxiety, nervousness, overexcitement, or irritability

These effects are more likely in children.

Reporting of adverse reactions

If you experience any type of adverse reaction, talk to your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Trimbow

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 on the carton after CAD/EXP. The expiry date refers to the last day of the month indicated.

Do not freeze.

Do not expose to temperatures above 50°C.

Do not puncture the pressurized container.

Before dispensing:

Store in a refrigerator (between 2°C and 8°C).

After dispensing (after receiving this medicine from your pharmacist):

Pressurized container of 120 actuations (taken from a single or multiple container) and 180 actuations:

Store the inhaler below 25 °C for a maximum of 4 months.

Medicines should not be disposed of via sewage systems or in household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and additional information

Composition of Trimbow

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 from the 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 medicine contains fluorinated greenhouse gases.

Each 120-actuation inhaler contains 10.37 g of norflurane (HFC-134a), equivalent to 0.015 tonnes of CO2 (global warming potential GWP = 1430).

Each 180-actuation inhaler contains 14.259 g of norflurane (HFC-134a), equivalent to 0.02 tonnes of CO2 (global warming potential GWP = 1430).

Nature of the product and contents of the container

Trimbow is a solution for inhalation in a pressurized container.

Trimbow is supplied as a pressurized container (aluminum coated), equipped with a metering valve. The pressurized container is inserted into a plastic inhaler. This includes a mouthpiece fitted with a plastic protective cap and either a dose counter (packages with 120 doses) or a dose indicator (packages with 180 doses).

Each package contains one pressurized container delivering 120 doses or 180 doses. Multiple-pack containers are also available, containing 240 doses (2 pressurized containers with 120 doses each) or 360 doses (3 pressurized containers with 120 doses each).

Only certain package sizes may be marketed.

Marketing Authorization 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 Authorization Holder:

Belgium/Belgium/Belgium Chiesi sa/nv Tel/Tel: + 32 (0)2 788 42 00	Lithuania Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919
	Luxembourg/Luxembourg Chiesi sa/nv Tél/Tel: + 32 (0)2 788 42 00
Czech Republic Chiesi CZ s.r.o. Tel: + 420 261221745	Hungary Chiesi Hungary Kft. Tel.: + 36-1-429 1060
Denmark Chiesi Pharma AB Tlf: + 46 8 753 35 20	Malta Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791
Germany Chiesi GmbH Tel: + 49 40 89724-0	Netherlands Chiesi Pharmaceuticals B.V. Tel: + 31 88 501 64 00
Estonia Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919	Norway Chiesi Pharma AB Tlf: + 46 8 753 35 20
Greece Chiesi Hellas AEBE Tel: + 30 210 6179763	Austria Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919
Spain Chiesi España, S.A.U. Tel: + 34 93 494 8000	Poland Chiesi Poland Sp. z.o.o. Tel.: + 48 22 620 1421
France Chiesi S.A.S. Tél: + 33 1 47688899	Portugal Tecnifar- Indústria Técnica Farmacêutica S.A. Tel.: +351 210330700
Croatia Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919	Romania Chiesi Romania S.R.L. Tel: + 40 212023642
Ireland Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791	Slovenia Chiesi Slovenija d.o.o. Tel: + 386-1-43 00 901
Iceland Chiesi Pharma AB Sími: +46 8 753 35 20	Slovakia Chiesi Slovakia s.r.o. Tel: + 421 259300060
Italy Chiesi Italia S.p.A. Tel: + 39 0521 2791	Finland/Suomi Chiesi Pharma AB Puh/Tel: +46 8 753 35 20
Cyprus Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791	Sweden Chiesi Pharma AB Tel: +46 8 753 35 20
Latvia Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.