Breva

Package leaflet: Information for the patient

Breva 0,375% + 0,075%

nebuliser solution
Salbutamol and ipratropium bromide
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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, 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, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Breva is and what it is used for

Breva is a medicine containing two active substances used in the treatment of obstructive (narrowing) bronchial diseases: salbutamol (a beta-agonist) and ipratropium bromide (an anticholinergic).
Breva is indicated for the treatment of bronchospasm (contraction of the bronchial muscles) in adult patients with chronic obstructive pulmonary disease (a disease that makes it difficult to exhale air from the lungs).

2. What you need to know before using Breva

Do not use Breva

• if you are allergic to salbutamol and/or ipratropium bromide or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to atropine or to active substances similar to atropine;
• if you have severe heart disease;
• if you have a disease of the eye called glaucoma;
• if you have prostatic hypertrophy (enlargement of the prostate);
• if you have urinary retention (difficulty in emptying the bladder of urine);
• if you have intestinal obstruction (blockage of the passage of intestinal contents).

Warnings and precautions
Talk to your doctor or pharmacist before using Breva if:

• you have blockage of the blood vessels supplying the heart (coronary artery disease);
• you have an irregular heartbeat;
• you have high blood pressure (hypertension);
• you have a thyroid disorder due to overactivity of the gland (hyperthyroidism);
• you have phaeochromocytoma, a tumour that produces chemicals causing increased blood pressure and rapid heartbeat;
• you have diabetes (a condition characterized by high levels of glucose in the blood due to reduced insulin production by the pancreas);
• you have cystic fibrosis. Treatment with Breva may increase the risk of gastrointestinal disorders. Contact your doctor if you experience chest pain, severe breathing difficulties with worsening wheezing or shortness of breath, visual disturbances such as eye pain, blurred vision, coloured images, pupil dilation, or if you notice a worsening of your condition, especially if:
  • you have ischaemic heart disease (a heart condition occurring due to reduced blood flow caused by narrowing of the coronary arteries),
  • you have tachyarrhythmia (irregular and rapid heartbeat),
  • you have severe heart failure (inability of the heart to pump sufficient blood to meet the body's needs). Breva therapy may cause low potassium levels in the blood (hypokalaemia), which can be severe; therefore, your doctor will prescribe periodic monitoring.

A condition known as lactic acidosis has been reported in association with high therapeutic doses of salbutamol, particularly in patients treated for acute bronchospasm (see sections 3 and 4). Increased plasma lactate levels may lead to shortness of breath and hyperventilation, even though wheezing improves. If you feel that the medicine is no longer effective and you need to use the nebulizer more often than prescribed by your doctor, contact your doctor immediately.
Immediate hypersensitivity reactions may occur during treatment, including, rarely, urticaria, angioedema, paradoxical bronchospasm (sudden involuntary contraction of the airways and difficulty breathing), and anaphylaxis.
Be careful not to spray the solution into the eyes, especially if you are at risk of glaucoma (an eye condition caused by increased intraocular pressure). When ipratropium bromide (one of the active ingredients in Breva) has come into contact with the eye, isolated cases of ocular complications have been reported (such as mydriasis, blurred vision, visual halos or coloured images, increased intraocular pressure, acute angle-closure glaucoma, eye pain).

Children and adolescents
Breva is not indicated for use in children and adolescents (under 18 years of age).

For those engaged in sports
Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Breva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Inform your doctor if you are being treated with:

• beta-blockers, such as propranolol (medicines used for heart conditions and to lower blood pressure);
• xanthine derivatives, for example theophylline and aminophylline (medicines that relax bronchial muscles);
• corticosteroids (medicines used to treat inflammatory conditions);
• diuretics (medicines that lower blood pressure);
• antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors);
• anticholinergic medicines;
• digoxin – a medicine used to treat heart failure;
• if you are scheduled for surgery. Some anaesthetics may affect the actions of Breva. If you are undergoing surgery, inform your doctor, dentist, or anaesthetist that you are being treated with Breva.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Your doctor will prescribe Breva only if clearly necessary.

Driving and using machines
During treatment, dizziness, blurred vision, pupil dilation (mydriasis), and blurred vision may occur. If this happens, avoid driving or operating machinery.

Breva contains methyl 4-hydroxybenzoate, ethyl 4-hydroxybenzoate and butyl 4-hydroxybenzoate.
It may cause allergic reactions (including delayed reactions) and, very rarely, bronchospasm (narrowing of the airways and difficulty breathing).

3. How to use Breva

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Dosage
The recommended dose is 5 drops diluted in 2 ml of sterile physiological solution in the nebulizer, 2–3 times daily.
The maximum daily dose is 15 drops.
Do not exceed the recommended maximum dose.
Use in children and adolescents
Breva is not indicated in children and adolescents (under 18 years of age).
Method of administration
Dilute with sterile physiological solution in the nebulizer.
Duration of treatment
The duration of nebulization is 10–15 minutes.
The maximum dose and duration of therapy are determined by the doctor according to your clinical condition.
Instructions for use
To open the bottle, press simultaneously on the collar of the dropper and turn it counterclockwise. To close the bottle, screw the collar clockwise.
If you take more Breva than you should
If you have taken/ingested an excessive dose of Breva, contact your doctor or go to the nearest hospital immediately.
In case of overdose, symptoms such as tremors, increased heart rate, increased respiratory rate (tachypnea), and metabolic acidosis (alteration of blood acidity) may occur.
If you forget to take Breva
Do not take a double dose to make up for the forgotten dose.
If you stop using Breva
Do not stop using this medicine without consulting 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 will experience them.
Conditions you should pay attention to

• Chest pain
• Severe breathing difficulties
• Eye pain with blurred vision, pupil dilation

Contact your doctor immediately if you experience any of these symptoms and stop treatment.

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

• Headache,
• Tension,
• Peripheral vasodilation (red, warm skin) at high doses,
• Dizziness (sensation of movement or spinning),
• Drowsiness, muscle tremors, agitation, psychomotor hyperactivity,
• Dry mouth, nausea, irritation of the mouth and throat, gastrointestinal motility disorders (diarrhea, constipation, and vomiting), stomatitis,
• Hypersensitivity, anaphylaxis and angioedema,
• Visual accommodation disorders (blurred vision), pupil dilation (mydriasis), eye pain, dilation of superficial ocular blood vessels (conjunctival hyperemia), glaucoma, increased intraocular pressure.

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

• Cardiac arrhythmias (irregular heartbeat), including atrial fibrillation, supraventricular tachycardia and extrasystoles,
• Myocardial ischemia (reduced oxygen supply to the heart),
• Angina (chest pain).

Side effects not known (frequency cannot be established from available data):

• Irritability,
• Hypokalaemia (reduced potassium levels in the blood),
• Paradoxical bronchospasm (bronchial constriction), hyperventilation (increased respiratory rate immediately after inhalation),
• Cough, dysphonia, throat irritation, dry throat,
• Increased systolic blood pressure/decreased diastolic blood pressure,
• Asthenia,
• Urticaria, pruritus, excessive sweating (hyperhidrosis),
• Muscle pain, cramps, muscle weakness,
• Urinary retention,
• A condition known as lactic acidosis which may cause stomach ache, hyperventilation, shortness of breath despite improvement in wheezing, cold hands and feet, irregular heartbeat or thirst.

Following the instructions contained in this leaflet reduces the risk of side effects.
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 at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Breva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month. The expiry date applies to the product in its original unopened packaging, correctly stored.
Store at a temperature not exceeding 25°C.
Use within 3 months after first opening the bottle. After this period, dispose of any remaining residue.
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 Breva contains
The active substances are: salbutamol and ipratropium bromide. 100 ml of solution contain:
salbutamol sulfate equivalent to 375 mg of salbutamol and ipratropium bromide monohydrate
equivalent to 75 mg of ipratropium bromide.
The other components are: ethyl parahydroxybenzoate, methyl parahydroxybenzoate, butyl parahydroxybenzoate, sodium chloride, sulfuric acid 1N, purified water.
Description of the appearance of Breva and the contents of the pack
Nebuliser solution in 15 ml polyethylene vials with dropper.
The solution is clear, colourless or slightly yellowish.
Marketing Authorisation Holder
NEOPHARMED GENTILI S.p.A. – Via San Giuseppe Cottolengo 15 – 20143 Milan
Manufacturer
Valeas S.p.A. - Chemical and Pharmaceutical Industry - Via Vallisneri, 10 - 20133 Milan
Lachifarma S.r.l. - Salento Pharmaceutical Chemical Laboratory SS 16 – Industrial Zone 73010
Zollino (LE)

Patient Information Leaflet: Information for the patient

Breva 15 mg + 3 mg

metered-dose aerosol
Salbutamol and ipratropium bromide
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, consult 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 could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Breva is and what it is used for

Breva is a medicinal product containing two active substances used in the treatment of obstructive (narrowing) bronchial diseases: salbutamol (a beta-agonist) and ipratropium bromide (an anticholinergic).
Breva is indicated for the treatment of bronchospasm (contraction of the bronchial muscles) in adult patients with chronic obstructive pulmonary disease (a condition that makes it difficult to empty air from the lungs).

2. What you need to know before using Breva

Do not use Breva

• if you are allergic to salbutamol and/or ipratropium bromide or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to atropine or to active substances similar to atropine;
• if you have severe heart disease;
• if you have a disease of the eye called glaucoma;
• if you have prostatic hypertrophy (enlargement of the prostate);
• if you have urinary retention (difficulty of the bladder to empty urine);
• if you have intestinal obstruction (blockage of the passage of intestinal contents).

Warnings and precautions
Talk to your doctor or pharmacist before using Breva if:

• you have blockage of the blood vessels supplying the heart (coronary artery disease);
• you have an irregular heartbeat;
• you have high blood pressure (hypertension);
• you suffer from a thyroid disease caused by overactivity of the gland (hyperthyroidism);
• you have a phaeochromocytoma, a tumour that produces chemicals causing increased blood pressure and rapid heartbeat;
• you suffer from diabetes (a condition characterized by high blood glucose levels due to reduced insulin production by the pancreas);
• you suffer from cystic fibrosis. Treatment with Breva may increase the risk of gastrointestinal disturbances. Contact your doctor if you experience chest pain, severe breathing difficulties with worsening wheezing or shortness of breath, visual disturbances such as eye pain, blurred vision, coloured images, pupil dilation, or if you notice a worsening of your condition, especially if:
  • you have ischaemic heart disease (a heart condition occurring due to reduced blood flow caused by narrowing of the coronary arteries),
  • you have tachyarrhythmia (irregular and rapid heartbeat),
  • you have severe heart failure (inability of the heart to pump sufficient blood to meet the body's needs).
    Treatment with Breva may cause low potassium levels in the blood (hypokalaemia), which can be severe; therefore, your doctor will prescribe periodic monitoring.

A condition known as lactic acidosis has been reported in association with high therapeutic doses of salbutamol, particularly in patients treated for acute bronchospasm (see sections 3 and 4). Increased plasma lactate levels may lead to shortness of breath and hyperventilation, even if your wheezing improves. If you feel that the medicine is no longer effective and you need to use the nebulizer more often than your doctor recommended, contact your doctor immediately.
During treatment, immediate hypersensitivity reactions may occur, rarely including urticaria, angioedema, paradoxical bronchospasm (sudden involuntary contraction of the bronchi and difficulty breathing), and anaphylaxis.
Be careful not to spray the solution into the eyes, especially if you are at risk of glaucoma (an eye condition caused by increased intraocular pressure). When ipratropium bromide (one of the active substances in Breva) has come into contact with the eye, isolated cases of ocular complications have been reported (such as mydriasis, blurred vision, halos or coloured images, increased intraocular pressure, closed-angle glaucoma, eye pain).

Children and adolescents
Breva is not indicated in children and adolescents (under 18 years of age).

For athletes
Using this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Breva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Inform your doctor if you are being treated with:

• beta-blockers, such as propranolol (medicines used for heart conditions and to lower blood pressure);
• xanthine derivatives, for example theophylline and aminophylline (medicines that relax bronchial muscles);
• corticosteroids (medicines used to treat inflammatory conditions);
• diuretics (medicines that lower blood pressure);
• antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors);
• anticholinergic medicines;
• digoxin – a medicine used to treat heart failure;
• if you are scheduled for surgery. Some anaesthetics may affect the effects of Breva. If you are undergoing surgery, inform your doctor, dentist, or anaesthetist that you are being treated with Breva.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Your doctor will prescribe Breva only if clearly needed.

Driving and using machines
During treatment, dizziness, blurred vision, pupil dilation (mydriasis), or blurred vision may occur. If this happens, avoid driving or operating machinery.

3. How to use Breva

Use this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Dosing
The recommended dose is 2 sprays, 3–6 times daily.
Duration of treatment
The maximum dose and duration of therapy will be determined by your doctor according to your
clinical condition.
Use in children and adolescents
Breva is not indicated in children and adolescents (under 18 years of age).
Instructions for use
Shake well before use.

1. Remove the cap from the mouthpiece. (fig.1)

fig.1

2. Hold the inhaler with your thumb and index finger and, without pressing the canister, shake it vigorously. (fig.2)

fig.2

3. Close your lips firmly around the mouthpiece. (fig.3)

fig.3

4. Breathe out deeply, blowing directly into the mouthpiece. (fig.4)

5. Then, breathe in slowly and deeply, pressing once with your index finger on the base of the canister at the same time, so that the release of the medicine coincides with the beginning of the inhalation. (fig.5)

fig.5

6. Hold your breath as long as possible, remove the mouthpiece from your lips and breathe out slowly.
7. For the next inhalation, wait at least one minute and repeat steps 2, 3, 4, 5 and 6.
8. Replace the cap on the mouthpiece. (fig.8)

fig.8
Keep the mouthpiece and valve clean at all times.
To clean, remove the canister from the inhaler, wash the mouthpiece with lukewarm water, dry it thoroughly, and reinsert the canister into the clean mouthpiece.
Always protect the device from dust and store it away from sources of heat. Do not throw the
device into fire, even if it is empty.
If you take more Breva than you should
If you ingest or take an excessive dose of Breva, contact your doctor or go to the nearest
hospital immediately.
In case of overdose, symptoms such as tremors, increased heart rate, increased respiratory rate (tachypnea), and metabolic acidosis (alteration of blood acidity) may occur.
If you forget to take Breva
Do not take a double dose to make up for a forgotten dose.
If you stop using Breva
Do not stop using this medicine without consulting 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 everybody gets them.
Conditions you should pay attention to:

• Chest pain
• Severe breathing difficulties
• Eye pain with blurred vision, pupil dilation

Contact your doctor immediately if you experience any of these symptoms and stop treatment.

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

• Headache,
• Tension,
• Peripheral vasodilation (red, warm skin) at high doses,
• Dizziness (sensation of movement or spinning),
• Drowsiness, muscle tremors, agitation, psychomotor hyperactivity,
• Dry mouth, nausea, mouth and throat irritation, gastrointestinal motility disorders (diarrhea, constipation, and vomiting), stomatitis,
• Hypersensitivity, anaphylaxis and angioedema,
• Visual accommodation disorders (blurred vision), pupil dilation (mydriasis), eye pain, dilation of superficial ocular blood vessels (conjunctival hyperemia), glaucoma, increased eye pressure

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

• Cardiac arrhythmias (irregular heartbeat), including atrial fibrillation, supraventricular and extrasystolic tachycardia,
• Myocardial ischemia (reduced oxygen supply to the heart),
• Angina (chest pain).

Side effects frequency not known (cannot be estimated from available data)

• Irritability,
• Hypokalaemia (reduced potassium levels in the blood),
• Paradoxical bronchospasm (bronchoconstriction) and hyperventilation (increased respiratory rate immediately after inhalation),
• Cough, dysphonia, throat irritation, sore throat,
• Increased systolic blood pressure/decreased diastolic blood pressure,
• Asthenia,
• Urticaria, pruritus, excessive sweating (hyperhidrosis),
• Muscle pain, cramps, muscle weakness,
• Urinary retention,
• A condition known as lactic acidosis which may cause stomach ache, hyperventilation, shortness of breath despite improvement in wheezing, cold hands and feet, irregular heartbeat, or thirst.

Following the instructions contained in this leaflet reduces the risk of side effects.
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 at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Breva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month. The expiry date applies to the product in its original, unopened packaging, stored correctly.
Store below 25°C.
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 Breva contains
The active substances are: salbutamol and ipratropium bromide. One aerosol can contains 15 mg of salbutamol and 3 mg of ipratropium bromide. Each spray delivers 75 µg of salbutamol and 15 µg of ipratropium bromide.
The other components are: oleic acid, trichlorofluoromethane, dichlorodifluoromethane.

Description of the appearance of Breva and contents of the pack
Pressurised metered-dose aerosol in an aluminium can for 200 sprays, with metering valve and inhalation mouthpiece.

Marketing Authorisation Holder and Manufacturer
NEOPHARMED GENTILI S.p.A – Via San Giuseppe Cottolengo 15 – 20143 Milan, Italy