Package leaflet: Information for the user

Bromiduo, (0.5 mg + 0.25 mg)/ml, solution for nebulization
Fenoteroli hydrobromidum + Ipratropii bromidum
Please read carefully the entire leaflet before using this medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Table of contents:

What Bromiduo is and what it is used for
Important information before using Bromiduo
How to use Bromiduo
Possible side effects
How to store Bromiduo
Contents of the pack and other information

1. What Bromiduo is and what it is used for

Bromiduo contains two active substances: fenoterol, which belongs to a group of substances called
"selective beta-2 adrenergic receptor agonists", and ipratropium bromide, which belongs to a group of substances called
"anticholinergic agents". The different mechanisms of action of these two substances in dilating the airways make them useful in the treatment of asthma and other inflammatory conditions associated with reversible airway obstruction. Bromiduo acts rapidly after administration and is therefore used for the treatment of acute asthma attacks.
The medicine is indicated as a bronchodilator for the prophylaxis (prevention) and treatment of symptoms in chronic obstructive airway diseases with reversible bronchospasm: bronchial asthma, and particularly chronic bronchitis. If the patient has bronchial asthma or chronic obstructive pulmonary disease (COPD), the doctor may prescribe an additional anti-inflammatory medicine, in accordance with current treatment standards for these diseases.

2. Important information before using Bromiduo

When not to use Bromiduo:

if the patient is allergic to fenoterol hydrobromide, ipratropium bromide, substances with anticholinergic properties, or any of the other ingredients of this medicine (listed in section 6).
if the patient has tachyarrhythmia (heart rhythm disorder with rapid heartbeat).
if the patient has a heart condition known as obstructive hypertrophic cardiomyopathy.

Warnings and precautions
Before starting treatment with Bromiduo, discuss the following with your doctor or pharmacist:

in case of sudden narrowing of the airways after inhalation: immediately discontinue use of Bromiduo and consult your doctor, who will recommend alternative treatment.
in case of acute, rapidly worsening shortness of breath, the patient should contact a doctor immediately.
if the patient has narrow-angle glaucoma (increased pressure within the eye): protect the eyes during inhalation.
if the patient experiences visual disturbances such as eye pain or discomfort, blurred vision, seeing halos (colored rings) or colored images, together with redness of the eyes, immediate consultation with an ophthalmologist is necessary, as these symptoms may indicate complications (dilated pupils, increased intraocular pressure, narrow-angle glaucoma).
if the patient has recently suffered a myocardial infarction (heart attack).
if the patient has diabetes.
if the patient has heart or blood vessel disorders.
if the patient has severe heart disease: immediate medical consultation is required in case of chest pain or other signs of worsening heart disease.
if the patient develops symptoms such as difficulty breathing or chest pain: immediate medical evaluation is necessary, as these symptoms may indicate diseases of both the respiratory and cardiovascular systems.
if the patient has a pheochromocytoma (a type of adrenal gland tumor).
if the patient has hyperthyroidism (overactive thyroid gland).
if the patient has previously experienced urinary obstruction or if such obstruction is suspected.
if the patient experiences loss of appetite, constipation, fluid retention or leg swelling, irregular pulse, or muscle weakness: these may be signs of low potassium levels. Special precautions may be required (e.g. blood tests).
if the patient has cystic fibrosis: gastrointestinal motility disorders may occur.
if breathing difficulties persist or worsen: medical advice should be sought, as current treatment may need to be reviewed. Additional medications may be necessary. Never increase the prescribed dose, as this may lead to serious adverse effects.
if the patient is using other medicines belonging to the group of "selective beta-2 adrenergic receptor agonists": these should be used only under strict medical supervision (see section "Bromiduo with other medicines").

Immediate hypersensitivity reactions may occur after using Bromiduo, such as:
rare cases of urticaria, angioedema (sudden swelling of the throat, skin, and mucous membranes of the oral cavity and pharynx, potentially causing breathing difficulties), rash, bronchospasm, swelling of lips and throat, and rapidly progressing, life-threatening allergic reactions. In case of such symptoms, immediate medical attention or hospitalization is required.
Extreme caution should be taken when nebulizing Bromiduo to prevent the medicine from entering the eye. Use of a mouthpiece is recommended. If this is not possible, a tightly fitting face mask for nebulization should be used.
If long-term use of Bromiduo is necessary for asthma treatment, the doctor will recommend using Bromiduo only for acute symptoms, not on a regular basis. If long-term treatment with Bromiduo is required for mild forms of other conditions with reversible airway obstruction, the doctor may recommend using Bromiduo only for acute symptoms and on an irregular basis. The doctor may also decide to prescribe an additional medication or higher doses of anti-inflammatory drugs.
Use of Bromiduo may result in positive test results for fenoterol in doping tests (non-therapeutic use of performance-enhancing substances).

Bromiduo with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines planned for future use.
Other bronchodilator medicines may enhance the effect of Bromiduo. Concurrent use of other beta-2 adrenergic receptor agonists, oral anticholinergic drugs, or xanthine derivatives (theophylline) may also increase the risk of adverse effects. Since long-term concurrent use of other anticholinergic drugs with Bromiduo has not been studied, consult your doctor for advice.
Certain medicines used to treat high blood pressure (called "beta-blockers") may reduce the effectiveness of Bromiduo.
Using beta-2 adrenergic agonists, such as those contained in Bromiduo, together with theophylline, corticosteroids, or diuretics (medicines that increase urine excretion) may lead to decreased potassium levels, especially in cases of severe asthma. Low potassium levels may make the patient more susceptible to irregular heartbeat, particularly if taking digoxin or if the blood carries insufficient oxygen. In such cases, the doctor may decide to take special precautions (e.g. blood tests).
It is important that the doctor knows if the patient is taking antidepressants (monoamine oxidase inhibitors or tricyclic antidepressants). In such cases, caution is advised when using beta-2 adrenergic receptor agonists, as their effects may be enhanced.
Inhalation of halogenated anesthetic agents, such as halothane, trichloroethylene, and enflurane, may enhance the cardiovascular effects of beta-2 adrenergic agonists (e.g. may cause irregular heartbeat).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Although non-clinical studies on fenoterol hydrobromide and ipratropium bromide, as well as human data, have not shown risk to the unborn child, Bromiduo should be used only if clearly recommended by a doctor. This is particularly important during the first trimester and immediately before delivery (Bromiduo has an inhibitory effect on uterine contractions).
Non-clinical studies have shown that fenoterol hydrobromide passes into breast milk. It is not known whether ipratropium bromide passes into breast milk. Therefore, Bromiduo should be used during pregnancy and breastfeeding only if clearly recommended by a doctor.

Driving and operating machinery
No studies have been conducted on the effect of Bromiduo on the ability to drive or operate machinery.
During treatment with Bromiduo, adverse effects such as dizziness, muscle tremor, accommodation disorders (blurred vision), pupil dilation, and blurred vision may occur. If any of these adverse effects occur, the patient should avoid potentially dangerous activities such as driving or operating machinery.

Bromiduo contains benzalkonium chloride
The medicine contains 0.04 mg of benzalkonium chloride per ml. Benzalkonium chloride may cause wheezing (whistling breath) or respiratory disturbances (bronchospasm), especially in patients with asthma.

3. How to use Bromiduo

This medicine should always be used as directed by the physician. If in doubt, consult your doctor or pharmacist.
Patients should be under medical supervision during initiation of treatment and throughout therapy, for example, in a hospital setting. However, the physician may decide in certain cases to allow treatment at home.
Dosage adjustment depends on the physician's decision and will be tailored to the individual needs of the patient. Treatment should always begin with the lowest recommended dose. Administration should be discontinued once sufficient symptom relief has been achieved. The following dosing is recommended:

Adults (including elderly patients) and adolescents over 12 years of age:
Treatment of acute asthma attacks:
Depending on the severity of the acute attack, the physician will determine the appropriate dose, which may range from 1 ml (20 drops) to 2.5 ml (50 drops). In particularly severe cases, e.g., under medical supervision in a hospital emergency department, doses up to 4 ml (80 drops) may be used.

Children aged 6 to 12 years:
Treatment of acute asthma attacks:
Depending on the severity of the acute attack, the physician will determine the appropriate dose, which may range from 0.5 ml (10 drops) to 2 ml (40 drops).

Children under 6 years of age (with body weight less than 22 kg):
Bromiduo should be administered only under medical supervision. The physician will adjust the dose according to the child's body weight: 0.1 ml (2 drops) per kg of body weight, up to a maximum of 0.5 ml (10 drops).

Method of administration
The Bromiduo nebulizing solution should be used according to the following instructions:
The nebulizing solution must be inhaled using nebulizers. Do not take orally.
The medicine can be administered using various commercially available nebulizers. Patients should follow the manufacturer's instructions regarding proper use, storage, and maintenance of the nebulizer in a clean condition.
If an oxygen wall outlet is available, a flow rate of 6–8 litres per minute should be used.
The amount of drug delivered to the lungs and the quantity absorbed into the bloodstream may vary depending on the type of nebulizer and its efficiency. Inhalation time can be adjusted by the volume of the solution.
The recommended dose should be diluted with 0.9% sodium chloride solution to a final volume of 3 to 4 ml and inhaled until the entire solution is used up. The medicine must not be diluted with distilled water. The nebulizing solution should be diluted immediately before each use, and any unused diluted solution should be discarded. A fresh diluted solution must be prepared each time before use.
The diluted solution should be used immediately after preparation.

If the effect of the medicine seems too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Bromiduo
If a higher than recommended dose of Bromiduo is used, consult your doctor or pharmacist.
Symptoms of overdose are mainly related to the effects of fenoterol bromide and include: tachycardia (increased heart rate), palpitations, tremor, elevated or lowered blood pressure, increased difference between systolic and diastolic pressure, coronary pain (chest pain), cardiac arrhythmias, facial flushing.
Metabolic acidosis (disturbance of acid-base balance in the body) and hypokalaemia (decreased potassium levels in the blood) have also been observed during fenoterol administration at doses higher than those recommended for approved indications of Bromiduo.
Potential symptoms of ipratropium bromide overdose (such as dryness of the oral mucosa, accommodation disturbances) are mild.

Missing a dose of Bromiduo
If Bromiduo has been prescribed for regular use and a dose is missed, it should be taken as soon as possible. However, do not use a double dose to make up for the missed dose. The next dose should be taken at the usual time. If the patient has asthma, Bromiduo should be used only during acute attacks.

Stopping treatment with Bromiduo
If a patient stops using Bromiduo, breathing problems may recur or even worsen. Therefore, Bromiduo should be used for as long as directed by the physician. Always consult your doctor before discontinuing treatment with Bromiduo.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
After administration of Bromiduo, immediate hypersensitivity reactions may occur, such as:
rare cases of urticaria, angioedema (sudden swelling of the throat, skin and mucous membranes
of the oral cavity and pharynx, potentially impairing breathing), rash, airway constriction, swelling
of lips and throat, and rapidly progressing, life-threatening allergic reactions. If any of these symptoms
occur, seek immediate medical attention from a doctor or go to hospital.
As with other inhaled medicines, Bromiduo may cause local irritation. The most commonly reported
adverse reactions during clinical trials were cough, dry mouth, headache, skeletal muscle tremor,
pharyngitis, nausea, dizziness, dysphonia (voice disturbances), tachycardia (increased heart rate),
palpitations, vomiting, increased systolic blood pressure, and nervousness.

Common (may affect fewer than 1 in 10 people)

Cough
N uncommon (may affect fewer than 1 in 100 people)
fast heartbeat
increased pulse rate
palpitations
increased systolic blood pressure
muscle tremor
nervousness
headache
dizziness
local irritation, such as upper throat inflammation
voice disturbances
dry mouth
nausea
vomiting

Rare (may affect fewer than 1 in 1000 people)

life-threatening allergic (anaphylactic) reactions
hypersensitivity (allergy-type reactions)
decreased potassium levels
irregular heartbeat
atrial fibrillation (very rapid, irregular heart rhythm)
supraventricular tachycardia (abnormal rapid heart rhythm)
inadequate blood supply to the heart muscle
decreased diastolic blood pressure
agitation
psychiatric disorders
increased intraocular pressure (glaucoma)
elevated intraocular pressure
accommodation disorder
dilated pupils
blurred vision
eye pain
redness of the white part of the eye
swelling of the outer protective layer of the eye
halos around lights (halos)
throat irritation
airway constriction
throat swelling (swelling of the upper part of the throat)
sudden laryngospasm (may affect breathing and speech)
inhalation-induced (paradoxical) bronchoconstriction
dry throat
mucosal inflammation of the oral cavity
glossitis (inflammation of the tongue)
diarrhoea associated with gastrointestinal motility disorder
constipation
oral cavity swelling
skin rash
urticaria
itching
angioedema (rapidly progressive swelling of skin or mucous membranes, potentially causing breathing difficulties)
excessive sweating
muscle pain
muscle cramps
muscle weakness
urinary retention

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49-21-301, fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder. Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Bromiduo

Keep the medicine out of the sight and reach of children.
There are no special storage requirements for this medicine.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the stated month.
Shelf-life after first opening the bottle: 1 year.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This practice will help protect the environment.

6. Contents of the pack and other information

What Bromiduo contains

The active substances are: fenoterol hydrobromide and ipratropium bromide. 1 ml (20 drops) of nebuliser solution contains 0.5 mg of fenoterol hydrobromide and 0.25 mg of ipratropium bromide.
Other components are: benzalkonium chloride, disodium edetate (E 386), sodium chloride, hydrochloric acid 1M solution, purified water.

What Bromiduo looks like and contents of the pack
An amber glass bottle (type III) with a HDPE screw cap, child-resistant closure, and a dropper made of LDPE, placed in a cardboard box.
Pack size: 25 ml.
Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel.: +48 22 732 77 00
Importer:
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
„Nord Farm” Sp. z o.o.
Al. Piłsudskiego 141
92-318 Łódź

Information intended exclusively for healthcare professionals:
Overdose

Symptoms
Symptoms of overdose are mainly related to the effects of fenoterol. Potential overdose symptoms due to excessive beta-adrenergic stimulation include in particular: tachycardia, palpitations, muscle tremor, increased or decreased blood pressure, widened pulse pressure, angina pain, cardiac arrhythmias, facial flushing. Metabolic acidosis and hypokalaemia have also been observed during fenoterol administration at doses higher than recommended for approved indications of Bromiduo.

Potential symptoms of ipratropium bromide overdose (such as dryness of the oral mucosa, accommodation disturbances) are mild, since systemic bioavailability of inhaled ipratropium is very low.

Treatment
Treatment with Bromiduo should be discontinued. Monitoring of acid-base and electrolyte balance should be considered.
Administration of sedatives, and in severe cases, intensive therapy.
Beta-adrenergic receptor blocking agents, preferably beta1-selective, may be used as specific antidotes; however, one must remember about the possible reduction in bronchial patency and the need for particularly careful dose adjustment in patients with bronchial asthma or chronic obstructive pulmonary disease due to the risk of sudden severe bronchospasm, which may be fatal.