Trimbow 172 micrograms/5 micrograms/9 micrograms solution for inhalation in pressurised container

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Trimbow 172micrograms/5micrograms/9micrograms solution for inhalation in pressurised container

beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium

Read the entire leaflet carefully before you start using this medicine, because 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 other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects 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 asthma in adults.

Trimbow can reduce exacerbations (flare-ups) of asthma symptoms. Asthma is a serious, chronic condition in which the muscles surrounding the airways tighten (bronchoconstriction) and the airways become swollen and irritated (inflammation). Symptoms come and go and include shortness of breath, wheezing, chest tightness and cough.

You should 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 and/or glycopyrronium or to 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 attack of breathing difficulty or wheezing.

If your breathing worsens

If you experience a worsening of breathing difficulty or wheezing immediately after inhaling the medicine (respirations with a whistling sound), stop treatment with the Trimbow inhaler and use your "rescue" fast-acting inhaler immediately. You must contact your doctor right away. 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 are difficult to control (e.g., if you are using your "rescue" inhaler more frequently) or if your "rescue" inhaler does not improve your symptoms, see 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 to use Trimbow:

• if you have any heart problems, such as angina (chest pain, heart 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 HOCM, a disease in which the heart muscle is abnormal).

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

• if you have narrowing of the arteries (also known as atherosclerosis), high blood pressure, or an aneurysm (an abnormal bulging 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). The combination of Trimbow with certain lung medications 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 measure 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, so additional blood tests may be needed to monitor your blood sugar levels when you start using 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 currently receiving or have previously received treatment for tuberculosis (TB), or if you have a chest infection.

• if you have a condition called narrow-angle glaucoma.

• 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 have any doubts about 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 prior to surgery), you may need additional medication. In such situations, your doctor may need to increase your corticosteroid dose to cope with 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 Trimbow

Tell 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 disease.

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

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

The combined use of Trimbow with:

• medicines used 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 isocarboxazide), tricyclic antidepressants (e.g., amitriptyline and imipramine), and phenothiazines

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

• medicines used to treat Parkinson's disease (levodopa), medicines used to treat an underactive thyroid gland (levothyroxine), 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 used 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 formoterol's inhibitory effects on uterine contractions.

You should not use Trimbow while breastfeeding. You and your doctor must decide whether to discontinue breastfeeding or discontinue 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 two-actuation dose. 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 puffs in the morning and two puffs in the evening.

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

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

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

If you think the medicine is not working effectively, 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 in other inhalers.

Route of administration

Trimbow is for inhalation use only.

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

This medicine is contained in a pressurized canister within a plastic inhaler with a mouthpiece.

Trimbow is available in one pack size only:

• a pack providing 120 doses

There is a counter on the back of the inhaler indicating 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 may 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. Check that the dose counter reads 121
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. If you are checking the inhaler for the first time, the counter should read:

120 - if you are using the container that provides 120 doses

How to use the inhaler

Stand up or sit upright to take the inhalation.

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 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. 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 breathe out through the inhaler.
6. Check that the dose counter has reduced by one unit.

For a second dose, keep the inhaler upright for about 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 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 obtain a replacement when the counter displays the number 20. Stop using the inhaler when the counter shows 0, as any remaining medication in the inhaler may be insufficient to provide a complete 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. Ask your doctor or pharmacist about this device.

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

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. Wipe the inside and outside of the mouthpiece and inhaler with a clean, dry cloth or dry tissue paper.
4. Replace the mouthpiece protective cap.

If you use more Trimbow than you should

It is important that you take the dose as instructed 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.

Tell your doctor if you have used more Trimbow than you should and if you experience any of these symptoms. Your doctor may want 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 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 using 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 use your fast-acting “rescue” inhaler without delay 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 worsening of 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 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 tube (esophagus) fungal infections of the vagina agitation tremor dizziness disturbance or reduction in taste sensation numbness ear inflammation irregular heartbeat changes in electrocardiogram (cardiac tracing) unusually fast heartbeat and heart rhythm disorders palpitations (awareness of abnormal heartbeat) 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) chest tightness or pressure sensation of missed heartbeat or extra heartbeats, unusually slow heartbeat asthma attack

bleeding from a blood vessel into surrounding tissues decreased blood pressure weakness pain at the back of the mouth and throat inflammation of the pharynx dry throat painful and frequent urination difficulty and pain during urination 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 the 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 (bone thinning)
• clouding of the eye lens (cataract)

Trimbow does not contain an inhaled corticosteroid in a high dose, 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, over-excitement or irritability

These effects are more likely in children.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the national reporting system included 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 pierce the pressurized container.

Before dispensing:

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

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

Aerosol container for 120 actuations: from a single container: from a multiple container:

Store the inhaler below 25 °C for a maximum of 3 months. Store the multiple container in the refrigerator (between 2 °C and 8 °C). Before use, remove an inhaler from the refrigerator for a few minutes to allow the solution to warm up. After use, store the inhaler below 25 °C for a maximum of 3 months.

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

6. Contents of the container and other information

Composition of Trimbow

The active substances are: beclometasone dipropionate, formoterol fumarate dihydrate and glycopyrronium.

Each delivered dose (the dose released from the mouthpiece) contains 172 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 200 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 120-dose inhaler contains 10.354 g of norflurane (HFC-134a), equivalent to 0.015 tonnes of CO2 (global warming potential GWP = 1430).

Nature and contents of the container

Trimbow is a pressurised solution for inhalation.

Trimbow is supplied in an aluminium pressurised container with a metering valve. The pressurised container is fitted into a plastic inhaler device incorporating a mouthpiece with a plastic protective cap and a dose counter.

Each pack contains one pressurised container delivering 120 doses. Multipacks are also available containing 240 doses (2 pressurised containers with 120 doses each) or 360 doses (3 pressurised containers with 120 doses each).

Only certain pack sizes may be commercially available.

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 on this medicinal product, please contact the local representative of the Marketing Authorisation 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 Chiesi Farmaceutici S.p.A. Tel: + 39 0521 2791
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 Tel: +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 Tel/Puh: +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 revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.