Brimica Genuair

Package leaflet: Information for the patient

Brimica Genuair 340 micrograms/12 micrograms inhalation powder

aclidinium/formoterol fumarate dihydrate
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of this leaflet:

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

1. What Brimica Genuair is and what it is used for

What Brimica Genuair is
This medicine contains two active substances, aclidinium and formoterol fumarate dihydrate. Both
belong to a group of medicines called bronchodilators. Bronchodilators relax the muscles in the airways, allowing the airways to open wider and helping you breathe more easily. The Genuair inhaler releases the active substances directly into your lungs when you inhale.
What Brimica Genuair is used for
Brimica Genuair is used in adult patients with breathing difficulties due to a lung disease called chronic obstructive pulmonary disease (COPD), in which the airways and air sacs in the lungs are damaged or become blocked. By opening the airways, the medicine helps relieve symptoms such as shortness of breath. Regular use of Brimica Genuair reduces the impact of COPD on daily life.

2. What you need to know before using Brimica Genuair

Do not use Brimica Genuair:

• if you are allergic to aclidinium, formoterol fumarate dihydrate, or any of the other ingredients of this medicine (listed in Section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Brimica Genuair if you experience any of the following symptoms/conditions:

• if you have asthma. This medicine must not be used for the treatment of asthma;
• if you have heart problems;
• if you suffer from epilepsy;
• if you have a problem with your thyroid gland (thyrotoxicosis);
• if you have a tumour in one of your adrenal glands (phaeochromocytoma);
• if you have problems urinating or problems due to an enlarged prostate;
• if you have a condition of the eye called narrow-angle glaucoma, which causes increased eye pressure.

Stop taking Brimica Genuair and contact your doctor immediately if you experience
any of the following conditions:

• if you experience sudden chest tightness, cough, wheezing, or shortness of breath immediately after using the medicine. See Section 4.

Brimica Genuair is indicated as a maintenance (long-term) treatment for COPD. You must not use this medicine to treat sudden attacks of breathlessness or wheezing.
If the common symptoms of COPD (shortness of breath, wheezing, cough) do not improve or worsen while using Brimica Genuair, you may continue using it but must consult your doctor as soon as possible, as you may need another medicine.
If you see halos around lights or coloured images, experience eye pain or disturbances, or suffer from temporary blurred vision, you must consult your doctor as soon as possible.
Dry mouth, which may occur with medicines such as Brimica Genuair, may over time be associated with dental caries; therefore, it is important to maintain good oral hygiene.

Children and adolescents
Brimica Genuair must not be used in children or adolescents under 18 years of age.

Other medicines and Brimica Genuair
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. If you use Brimica Genuair with other medicines, the effect of Brimica Genuair or of the other medicines may be altered.
Inform your doctor or pharmacist if you are taking:

• Any medicine that may be similar to Brimica Genuair for treating breathing difficulties.
• Medicines that reduce the amount of potassium in the blood. These include:
  o oral corticosteroids (such as prednisolone);
  o diuretics (such as furosemide or hydrochlorothiazide);
  o some medicines used to treat respiratory conditions (such as theophylline).
• Medicines known as beta-blockers, which may be used to treat high blood pressure or other heart problems (such as atenolol or propranolol) or to treat glaucoma (such as timolol).
• Medicines that may cause a type of change in the heart's electrical activity known as QT interval prolongation (seen on an electrocardiogram). These include medicines used to treat:
  o depression (such as monoamine oxidase inhibitors or tricyclic antidepressants);
  o bacterial infections (such as erythromycin, clarithromycin, telithromycin);
  o allergic reactions (antihistamines).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor, pharmacist, or nurse for advice before using this medicine. You must not use Brimica Genuair if you are pregnant or breastfeeding, unless your doctor has specifically instructed you to do so.

Driving and using machines
Brimica Genuair does not affect or has a negligible effect on the ability to drive or use machines. In some patients, this medicine may cause blurred vision or dizziness. If you experience any of these effects, do not drive or use machines until the dizziness has passed or your vision has returned to normal.

Brimica Genuair contains lactose
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.

3. How to use Brimica Genuair

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 one inhalation in the morning and one inhalation in the evening.
• You may use Brimica Genuair at any time before or after food or drink.
• The effects of Brimica Genuair last for 12 hours; therefore, you should try to use Brimica Genuair at the same time each morning and each evening. This ensures that a sufficient amount of the medicine is always present in your body, helping you to breathe more easily throughout the day and night. Taking your medicine at regular intervals will also help you remember to use it.
• The recommended dose can be used in elderly patients and in patients with renal or hepatic impairment. Dose adjustments are not required for these patients.
• Brimica Genuair is for inhalation use only.
• Instructions for use: for instructions on how to use the Genuair inhaler, please refer to the Instructions for Use. If you have any doubts about how to use Brimica Genuair, consult your doctor or pharmacist.
• .

COPD is a chronic disease; therefore, Brimica Genuair is intended for long-term use. You are
advised to use the medicine every day, twice daily, and not only when you experience
breathing difficulties or other COPD symptoms.

If you use more Brimica Genuair than you should
If you think you have used more Brimica Genuair than you should, you are more likely to experience
some of its side effects, such as blurred vision, dry mouth, feeling unwell, tremors/shaking, headache, palpitations, or increased blood pressure. In this case, contact your doctor immediately or go to the nearest emergency room. Show the Brimica Genuair packaging. Medical treatment may be necessary.

If you forget to take Brimica Genuair
If you forget a dose of Brimica Genuair, take it as soon as you remember, and then take the next dose at your usual time. Do not take a double dose to make up for the forgotten dose.

If you stop using Brimica Genuair
This medicine is intended for long-term use. If you wish to stop treatment, speak to your doctor first, as your symptoms may worsen.

If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking the medicine and contact your doctor immediately if:

• You experience swelling of the face, throat, lips or tongue (with or without breathing or swallowing difficulties), or severe itchy rash on the skin (urticaria), as these may
  be symptoms of an allergic reaction. The frequency of this reaction cannot be estimated
  from the available data.

• You experience chest tightness, cough, wheezing or shortness of breath immediately after using the medicine. These may be signs of a condition called "paradoxical bronchospasm", which is an excessive and prolonged contraction of the airway muscles occurring immediately after treatment with a bronchodilator. This reaction may occur rarely (affecting up to 1 in 1,000 people).

Some of these could be serious: if you experience any of these side effects, consult your doctor immediately.
Uncommon (may affect up to 1 in 100 people)

• Muscle weakness or muscle cramps and/or changes in heart rhythm, as these could be signs of low potassium levels in the blood
• Fatigue, increased thirst and/or increased need to urinate, as these could be signs of elevated blood sugar levels
• Palpitations, as these could be a sign of abnormally fast heartbeat or irregular heart rhythm

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

• Sudden difficulty breathing or swallowing, swelling of the tongue, throat, lips or face, skin rash and/or itching – these could be signs of an allergic reaction.

Other side effects that may occur during use of Brimica Genuair:
Common (may affect up to 1 in 10 people)

• Combination of sore throat and runny nose – these could be signs of nasopharyngitis
• Headache
• Painful and/or frequent urination – these could be signs of a urinary tract infection
• Cough
• Diarrhea
• Blocked, runny or congested nose, and/or pain or pressure sensation in the cheeks or forehead – these could be signs of sinusitis
• Dizziness
• Muscle cramps
• Nausea (feeling unwell)
• Difficulty falling asleep
• Dry mouth
• Muscle pain
• Abscess (infection) of the tissues at the base of a tooth
• Increased blood levels of a protein found in muscle known as creatine phosphokinase
• Chills/tremors
• Anxiety

Uncommon

• Fast heartbeat (tachycardia)
• Abnormal or irregular heartbeat (cardiac arrhythmias)
• Chest pain or feeling of chest tightness (angina pectoris)
• Blurred vision
• Changes in voice (dysphonia)
• Difficulty urinating or sensation that the bladder is not completely emptied (urinary retention)
• Changes in the heart trace (prolongation of the QT interval) which could lead to irregular heart rhythm
• Taste disturbances (dysgeusia)
• Throat irritation
• Inflammation of the mouth mucosa (stomatitis)
• Increased blood pressure
• Restlessness
• Skin rash
• Itching

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

5. How to store Brimica Genuair

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the inhaler, on the box and on the inhaler pouch after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature conditions.
Keep the Genuair inhaler protected inside the sealed pouch until the start of the treatment period.
Use within 60 days of opening the pouch.
Do not use Brimica Genuair if you notice that the packaging is damaged or shows any visible signs of deterioration.
After taking the last dose, the inhaler must be discarded. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required.
This will help protect the environment.

6. Package contents and other information

What Brimica Genuair contains

• The active substances are aclidinium and formoterol fumarate dihydrate. Each delivered dose (the dose exiting the mouthpiece) contains 396 micrograms of aclidinium bromide, equivalent to 340 micrograms of aclidinium and 11.8 micrograms of formoterol fumarate dihydrate.
• The other component is lactose monohydrate (for further information, see the end of section 2 under "Brimica Genuair contains lactose").

Description of the appearance of Brimica Genuair and contents of the pack
Brimica Genuair is a white or almost white inhalation powder.
The Genuair inhaler is a white device with an integrated dose indicator and an orange actuation button. The mouthpiece is covered by a removable orange protective cap.
It is supplied sealed inside a laminated aluminium protective pouch containing a desiccant sachet. After removing the inhaler from the pouch, the pouch and desiccant should be discarded.
Pack sizes supplied:
Box containing 1 inhaler with 30 doses.
Box containing 1 inhaler with 60 doses.
Box containing 3 inhalers, each with 60 doses.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Covis Pharma Europe B.V.
Gustav Mahlerplein 2
1082MA Amsterdam
The Netherlands

Manufacturer:
Industrias Farmacéuticas Almirall, S.A.
Ctra. de Martorell 41-61
08740 Sant Andreu de la Barca, Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Covis Pharma Europe B.V. UAB “BERLIN CHEMIE MENARINI BALTIC”
Tél/Tel: 80013067 Tel: +370 52 691 947

България Luxembourg/Luxemburg
“Берлин-Хеми/А. Менарини България” EOOD Covis Pharma Europe B.V.
тел.: +359 2 454 09 50 Tél/Tel: 80024119

Česká republika Magyarország
Berlin-Chemie/A.Menarini Ceska republika s.r.o. Berlin-Chemie/A. Menarini Kft.
Tel: +420 267 199 333 Tel.: +36 1799 7320

Danmark Malta
Covis Pharma Europe B.V. Covis Pharma Europe B.V.
Tlf: 80711260 Tel: 80065149

Deutschland Nederland
Berlin-Chemie AG Covis Pharma Europe B.V.
Tel: +49 (0) 30 67070 Tel: 08000270008
Covis Pharma Europe B.V.
Tel: +49 (0) 3031196978

Eesti Norge
OÜ Berlin-Chemie Menarini Eesti Covis Pharma Europe B.V.
Tel: +372 667 5001 Tlf: 80031492

Ελλάδα Österreich
MENARINI HELLAS AE A. Menarini Pharma GmbH
Τηλ: +30 210 8316111-13 Tel: +43 1 879 95 85-0

España Polska
Laboratorios Menarini S.A. Covis Pharma Europe B.V.
Tel: +34-93 462 88 00 Tel.: 0800919353

France Portugal
MENARINI France A. Menarini Portugal – Farmacêutica, S.A.
Tél: +33 (0)1 45 60 77 20 Tel: +351 210 935 500

Hrvatska România
Berlin-Chemie Menarini Hrvatska d.o.o. Berlin-Chemie A.Menarini S.R.L.
Tel: + 385 1 4821 361 Tel: +40 21 232 34 32

Ireland Slovenija
A. Menarini Pharmaceuticals Ireland Ltd Berlin-Chemie / A. Menarini Distribution
Tel: +353 1 284 6744 Ljubljana d.o.o.
Tel: +386 01 300 2160

Ísland Slovenská republika
Covis Pharma Europe B.V. Berlin-Chemie / A. Menarini Distribution
Sími: 8007279 Slovakia s.r.o.
Tel: +421 2 544 30 730

Italia Suomi/Finland
Istituto Luso Farmaco d’Italia S.p.A. Covis Pharma Europe B.V.
Tel: +39 02 5165551 Puh/Tel: 0800413687

Κύπρος Covis Pharma Europe B.V. Sverige
Τηλ: 80091079 Covis Pharma Europe B.V.
Tel: 0200898678

Latvija United Kingdom (Northern Ireland)
SIA Berlin-Chemie/Menarini Baltic Covis Pharma Europe B.V.
Tel: +371 67103210 Tel: 08004334029

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

Instructions for Use
This section contains information on how to use the Genuair inhaler. It is important to read these instructions, as Genuair may work differently from inhalers you have used previously. If you have any doubts about how to use the inhaler, please consult your doctor, pharmacist, or nurse for assistance.
The Instructions for Use are divided into the following sections:

• Preliminary steps
• Step 1: Prepare the dose
• Step 2: Inhale the medicine
• Additional information

Preliminary steps
Read these Instructions for Use before starting to use this medicine.
Familiarize yourself with the components of the Genuair inhaler.

Control window
Dose indicator Orange button
Green = inhaler ready for use

Protective cap
Control window
Red = confirms correct inhalation
Mouthpiece
Figure A

Before use:
a) Before first use, open the sealed pouch and remove the inhaler. Discard the pouch and desiccant.
b) Do not press the orange button until you are ready to take a dose.
c) Remove the protective cap by gently pressing the arrows on both sides (Figure B).

Press here and pull
Figure B

STEP 1: Prepare the dose:
1.1 Look into the mouthpiece opening and ensure nothing is blocking it (Figure C).
1.2 Check the control window (it should be red, Figure C).

Figure C
1.3 Hold the inhaler horizontally with the mouthpiece facing you and the orange button pointing straight upwards (Figure D).

Figure D
1.4 Press the orange button fully down to load the dose (Figure E).
When the button is pressed fully, the control window changes from red to green.
Ensure the orange button is pointing straight upwards. Do not tilt.
1.5 Release the orange button (Figure F).
Ensure you have fully released the button so that the inhaler can function correctly.

Figure E Figure F

Stop and Check:
1.6 Ensure the control window is now green (Figure G).
Your medicine is now ready to be inhaled.
Proceed to ‘STEP 2: Inhale the medicine’.

Figure G

What to do if the control window is still red after pressing the button (Figure H).

Figure H
The dose has not been prepared. Go back to ‘STEP 1: Prepare the dose’ and repeat steps 1.1 to 1.6.

STEP 2: Inhale the medicine
Read steps 2.1 to 2.7 completely before use. Do not tilt.
2.1 Hold the inhaler away from your mouth and breathe out fully. Never breathe out into the inhaler (Figure I).

Figure I
2.2 Keep your head upright, place the mouthpiece between your lips, and close your lips firmly around it (Figure J).
Do not press the orange button while inhaling.

Figure J
2.3 Take a strong, deep breath in through your mouth. Hold your breath as long as possible.
You will hear a ‘click’ indicating that you are inhaling correctly. Hold your breath as long as possible after hearing the ‘click’. Some patients may not hear the ‘click’. Use the control window to confirm that inhalation was successful.
2.4 Remove the inhaler from your mouth.
2.5 Hold your breath as long as possible.
2.6 Breathe out slowly, away from the inhaler.
Some patients may experience a granular sensation in the mouth, or a slightly sweet or bitter taste. Do not take an additional dose even if you do not taste anything or feel nothing after inhalation.

Stop and Check:
2.7 Ensure the control window is now red (Figure K). This means you have correctly inhaled the medicine.

Figure K

What to do if the control window is still green after inhalation (Figure L).

Figure L
This means you did not inhale the medicine correctly. Go back to ‘STEP 2: Inhale the medicine’ and repeat steps 2.1 to 2.7.
If the control window still does not turn red, you may have forgotten to release the orange button before inhaling, or you may not have inhaled strongly enough. If this occurs, try again. Make sure you have released the orange button and that you breathed out fully. Then take a strong, deep breath in through the mouthpiece.
Contact your doctor if the control window remains green after repeated attempts.

After each use, press the protective cap back over the mouthpiece (Figure M) to prevent contamination of the inhaler with dust or other materials. You must dispose of your inhaler if you lose the cap.

Figure M

Additional information
What to do if you accidentally prepared a dose?
Store your inhaler with the protective cap in place until you are ready to inhale the medicine, then remove the cap and start from step 1.6.

How does the dose indicator work?

• The dose indicator shows the total number of doses remaining in the inhaler (Figure N).
• At first use, each inhaler contains at least 60 doses or at least 30 doses, depending on the pack size.
• Each time a dose is loaded by pressing the orange button, the dose indicator moves in small increments to the next number (50, 40, 30, 20, 10, or 0).

When should you request a new inhaler?
You should request a new inhaler:

• If your inhaler appears damaged or if you have lost the cap, or
• When a red band appears in the dose indicator, meaning it is nearly empty (Figure N), or
• If your inhaler is empty (Figure O).

Figure N

How do you know when the inhaler is empty?
When the orange button does not return fully upwards and remains stuck in an intermediate position, the last dose has been reached (Figure O). Although the orange button is stuck, the last dose can still be inhaled. After this dose, the inhaler can no longer be used and you must start using a new inhaler.

Figure O

How to clean the inhaler?
NEVER use water to clean the inhaler, as this may damage the medicine.
If you wish to clean your inhaler, wipe the outer part of the mouthpiece with a dry cloth or tissue.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATION

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the final report of the non-interventional PASS study mandated for the medicinal products mentioned above, the scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) are as follows:
The study results show that aclidinium increases the risk of cardiac arrhythmias and atrial fibrillation compared to LABAs and other LAMAs. Furthermore, the results also show that aclidinium/formoterol FDC increases the risk of any cardiac arrhythmias and atrial fibrillation compared to LABAs or other LAMA/LABA combinations. Therefore, in light of the available data from the final PASS study report, the PRAC considered that changes to the product information are required.
The CHMP agrees with the scientific conclusions of the PRAC.

Grounds for the variation of the terms of the marketing authorisation
Based on the scientific conclusions of the study results for the medicinal products mentioned above, the CHMP considers that the benefit-risk balance of these medicinal products remains unchanged, subject to the proposed changes to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation for the medicinal products mentioned above.