Package leaflet: Information for the user

Atrodil Combo, (0.5 mg + 0.25 mg)/ml, solution for nebulization
Fenoterol hydrobromide + Ipratropium bromide
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any doubts, 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 not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Table of contents

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

1. What Atrodil Combo is and what it is used for

Atrodil Combo contains two active substances: fenoterol hydrobromide, which belongs to a group of substances known as "selective beta-2 adrenergic receptor agonists", and ipratropium bromide, which belongs to a group of substances known as "anticholinergic drugs". The different mechanisms of action of these two substances in dilating the airways mean they are used in the treatment of asthma and other inflammatory conditions associated with reversible airway obstruction. Atrodil Combo acts rapidly after administration and is therefore used in the treatment of acute asthma attacks.
The medicine is indicated as a bronchodilator for the prevention (prophylaxis) and treatment of symptoms of chronic obstructive respiratory diseases with reversible bronchospasm: bronchial asthma, 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 Atrodil Combo

When not to use Atrodil Combo:

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 disorders with rapid heartbeat)
if the patient has a heart condition known as obstructive hypertrophic cardiomyopathy.

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

in case of sudden narrowing of the airways after inhalation: immediately discontinue use of Atrodil Combo and consult your doctor, who will recommend alternative treatment
in case of acute, rapidly worsening breathlessness, the patient should immediately contact a doctor
if the patient has narrow-angle glaucoma (increased pressure inside 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 along with redness of the eyes, immediate consultation with an ophthalmologist is required, as these symptoms may be related to 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 consultation with a doctor is required in case of chest pain or other symptoms indicating worsening heart condition
if the patient develops symptoms such as difficulty breathing or chest pain: immediate medical evaluation is required, as these symptoms may indicate disorders of both the respiratory system and the heart
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 retention or if its occurrence 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 necessary (e.g. blood tests)
if the patient has cystic fibrosis: gastrointestinal motility disorders may occur
if breathing difficulties persist or worsen: consult a doctor, as the current treatment should be reviewed. Additional medications may be needed. 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 "Atrodil Combo with other medicines").

Immediate hypersensitivity reactions may occur after using Atrodil Combo, such as:
rare cases of urticaria, angioedema (sudden swelling of the skin and mucous membranes of the mouth and throat, possibly impairing breathing), rash, bronchoconstriction, swelling of the lips and throat, and rapidly progressing, life-threatening allergic reactions. In case of such symptoms, immediate medical attention at a doctor's office or hospital is required.
Extreme care should be taken when nebulizing Atrodil Combo to prevent the medicine from entering the eye. Use of a mouthpiece is recommended. If this is not possible, a tightly fitting nebulization mask should be used.
If long-term treatment of asthma with Atrodil Combo is required, the doctor will recommend using Atrodil Combo only for acute symptoms, not on a regular basis. If long-term treatment of mild forms of other conditions with reversible airway obstruction requires the use of Atrodil Combo, the doctor may recommend using Atrodil Combo only for acute symptoms and irregularly. The doctor may also decide to prescribe an additional medication or higher doses of anti-inflammatory drugs.
Use of Atrodil Combo may lead to positive test results for fenoterol in doping tests (non-clinical use of substances to enhance athletic performance).

Atrodil Combo with other medicines
Inform your doctor about all medicines currently used, recently used, or planned for use.
Other bronchodilators may enhance the effect of Atrodil Combo. 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 Atrodil Combo has not been studied, consult your doctor for advice.
Some medicines used to treat high blood pressure (called "beta-blockers") reduce the effect of Atrodil Combo.
Using beta-2 adrenergic agonists such as those contained in Atrodil Combo together with theophylline, corticosteroids, or diuretics (medicines that increase urine excretion) may lead to decreased potassium levels, especially in severe asthma. Low potassium levels make the patient more susceptible to irregular heartbeats, particularly if the patient is taking digoxin or if the patient's 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 required when using beta-2 adrenergic receptor agonists, as their effects may be intensified.
Inhalation of halogenated anesthetic agents (medicines used for anesthesia before surgery), such as halothane, trichloroethylene, and enflurane, may enhance the cardiovascular effects of beta-2 adrenergic agonists (e.g. may cause irregular heartbeat).

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Although non-clinical studies on fenoterol hydrobromide and ipratropium bromide and human data have not shown a risk to the unborn child, Atrodil Combo should be used only if clearly recommended by a doctor. This is particularly important during the first trimester and immediately before delivery (Atrodil Combo has an inhibitory effect on uterine contractions).
Non-clinical studies have shown that fenoterol hydrobromide passes into breast milk. It is unknown whether ipratropium bromide passes into breast milk. Therefore, Atrodil Combo 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 the medicine on the ability to drive or operate machinery. During treatment with Atrodil Combo, adverse effects such as dizziness, muscle tremors, accommodation disorders (blurred vision), dilated pupils, and blurred vision may occur. If any of these adverse effects occur, the patient should avoid potentially hazardous activities such as driving or operating machinery.

Atrodil Combo 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 Atrodil Combo

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 the
course of 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, who will tailor it to the individual needs
of the patient. Treatment should always be initiated at 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):
Atrodil Combo should be administered only under medical supervision: the physician will adjust
the dose according to the child's body weight, at 0.1 ml (2 drops) per kg of body weight, up to a
maximum of 0.5 ml (10 drops).

Method of administration
The Atrodil Combo nebulizing solution should be used according to the following principles:

The nebulizing solution must be administered by inhalation using nebulizers;
Do not take orally.

The medicine may be administered using various commercially available nebulizers. Patients should
follow the instructions provided by the manufacturer of the specific nebulizer regarding proper
use, storage, and maintenance of cleanliness.
If an oxygen wall outlet is available, a flow rate of 6–8 liters per minute should be used.
The amount of drug delivered to the lungs and absorbed into the bloodstream may vary depending
on the type of nebulizer and its efficiency. The duration of inhalation may 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 solution is completely used up. Do not dilute the medicine 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 should be prepared each time
before use.
The diluted solution should be used immediately after preparation.

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

Missed dose of Atrodil Combo
If Atrodil Combo has been prescribed for regular use and the patient forgets to take a dose, it should
be taken as soon as possible. However, do not take 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, Atrodil Combo should be
used only during acute attacks.

Stopping Atrodil Combo
If the patient stops using Atrodil Combo, breathing problems may recur or even worsen. Therefore,
Atrodil Combo should be used for as long as directed by the physician. Always consult your doctor
before discontinuing treatment with Atrodil Combo.
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 everybody gets them.
Immediate hypersensitivity reactions may occur after administration of Atrodil Combo, such as:
rare cases of urticaria, angioedema (sudden swelling of the skin and mucous membranes of the
oral cavity and throat, which may impair breathing), rash, bronchoconstriction, swelling of the lips
and throat, and rapidly progressing, life-threatening allergic reactions. If any of these symptoms
occur, seek immediate medical attention from a doctor or the nearest hospital emergency
department.
As with other inhaled medicines, Atrodil Combo may cause local irritation.
The most commonly reported adverse reactions during clinical trials were cough, dry mouth,
headache, skeletal muscle tremor, pharyngitis (inflammation of the throat), nausea, dizziness,
dysphonia (voice disorders), tachycardia (increased heart rate), palpitations, vomiting, increased
systolic blood pressure, and nervousness.

Common (occurs in less than 1 in 10 patients)

Cough

Uncommon (occurs in less than 1 in 100 patients)

Fast heartbeat
Increased pulse rate
Palpitations
Increased systolic blood pressure
Muscle tremor
Nervousness
Headache, dizziness
Local irritation, such as upper throat inflammation
Voice disorders
Dry mouth
Nausea, vomiting

Rare (occurs in less than 1 in 1000 patients)

Life-threatening allergic (anaphylactic) reactions
Hypersensitivity (allergy-type reactions)
Decreased potassium levels
Irregular heartbeat
Atrial fibrillation (very fast, irregular heart rhythm)
Supraventricular tachycardia (abnormal fast heart rhythm)
Inadequate blood supply to the heart muscle
Decreased diastolic blood pressure
Excitation
Psychiatric disorders
Increased intraocular pressure (glaucoma)
Increased 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
Visual halos (halos around lights)
Sore throat
Bronchoconstriction
Throat swelling (swelling of the upper throat)
Sudden laryngospasm (may affect breathing and speech)
Inhalation-induced (paradoxical) bronchoconstriction
Dry throat
Inflammation of the oral mucosa
Glossitis (inflammation of the tongue)
Diarrhea associated with gastrointestinal motility disorder
Constipation
Oral cavity swelling
Skin rash
Urticaria, itching
Angioedema (rapid swelling of the skin or mucous membranes of the mouth and throat, which may cause 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, tell 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 Warszawa
Tel: +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 the medicine.

5. How to store Atrodil Combo

Keep the medicine out of the reach and sight of children.
No special storage conditions are required for this medicine.
Do not use the medicine after the expiry date stated on the container following the abbreviation "EXP".
The expiry date refers to the last day of the stated month.
The marking on the container following the abbreviation EXP indicates the expiry date, and following the abbreviation Lot indicates the batch number.
Shelf-life after first opening of the bottle: 1 year.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information
What Atrodil Combo contains

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

What Atrodil Combo looks like and contents of the pack
Orange type III glass bottle with HDPE screw cap, child-resistant closure, and LDPE dropper, placed in a cardboard box.
Pack sizes: 1 bottle of 20 ml and 25 ml.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01
Importer
Farmak International Sp. z o.o.
ul. Chełmżyńska 249, 04-458 Warszawa

Information intended exclusively for medical professionals:

Overdose
Symptoms
Symptoms of overdose are mainly related to the action of fenoterol. Potential symptoms due to excessive beta-adrenergic stimulation include, in particular: tachycardia, palpitations, muscle tremor, increased or decreased blood pressure, widening of the pulse pressure (difference between systolic and diastolic pressure), angina pain, cardiac arrhythmias, facial flushing. Metabolic acidosis and hypokalaemia have also been observed during fenoterol administration at doses higher than recommended for the approved indications of Atrodil Combo.
Potential symptoms of overdose with ipratropium bromide (such as dryness of the oral mucosa, accommodation disturbances) are mild due to the very low systemic bioavailability of inhaled ipratropium.

Treatment
Administration of Atrodil Combo should be discontinued. Monitoring of acid-base and electrolyte balance should be considered.
Administration of sedatives; in severe cases, intensive therapy is required.
Beta-adrenergic receptor blocking agents may be used as specific antidotes, preferably beta-selective blockers, but with caution due to the possible reduction in bronchial patency. Particular care must be taken when adjusting the dose in patients with bronchial asthma or chronic obstructive pulmonary disease because of the risk of sudden severe bronchospasm, which may be fatal.