Nebulin

Package leaflet: Information for the patient

NEBULIN, 0.5 mg/2 mL, suspension for nebulization
NEBULIN, 1 mg/2 mL, suspension for nebulization
Budesonidum
Please read all of this leaflet carefully before using the medicine, because it contains
important information for the patient.
Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others.
The medicine may harm another person, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist.
See section 4.

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

1. What Nebulin is and what it is used for

Budesonide, the active substance in Nebulin, belongs to a group of medicines called glucocorticosteroids. Medicines in this group have local anti-inflammatory action.
Nebulin is used in the treatment of:

• Bronchial asthma in patients who require long-term glucocorticosteroid therapy to control inflammation in the respiratory tract, when the use of pressurized metered-dose inhalers (pMDI) or dry powder inhalers (DPI) is unsatisfactory or not justified;
• Croup syndrome – acute inflammation of the larynx, trachea, and bronchi, regardless of etiology (cause), associated with significant narrowing of the upper airways, breathing difficulty, or "barking" cough leading to breathing disturbances;
• Exacerbation of chronic obstructive pulmonary disease (COPD), when the use of budesonide as a nebulized suspension is justified. COPD is a chronic lung disease causing breathlessness and cough.

2. Important information before using Nebulin

When not to use Nebulin
Do not use Nebulin if the patient is allergic (hypersensitive) to budesonide or to any of the other ingredients of this medicine (listed in section 6).
Inform your doctor about any concerning reactions that occurred after taking a medicine containing budesonide or any other ingredient of this medicine.

Warnings and precautions
Before starting treatment with Nebulin, discuss it with your doctor.
Nebulin is intended for long-term treatment and does not provide rapid relief of acute asthma attacks, for which short-acting bronchodilators are indicated.
If there is no noticeable improvement after using short-acting bronchodilators, or if their use becomes more frequent than usual, contact your doctor.
In such cases, the doctor may consider more effective anti-inflammatory treatment, for example by increasing the inhaled dose of budesonide or initiating oral glucocorticosteroid therapy.
Special caution is required when switching from oral glucocorticosteroids to inhaled products. During this period, transient adrenal cortex insufficiency may occur.
Patients who have required emergency treatment with high doses of oral glucocorticosteroids or long-term treatment with the highest recommended doses of inhaled glucocorticosteroids are also at increased risk of adrenal cortex insufficiency during severe stress situations.
Inform your doctor about anticipated stressful situations (e.g., exams) or planned surgical procedures. The doctor may consider increasing the dose of oral glucocorticosteroids.

Note: When switching from oral glucocorticosteroid therapy to treatment with Nebulin suspension for nebulization, the following symptoms may temporarily occur: watery nasal discharge, rash, muscle and joint pain. In case of allergic reactions, such as nasal discharge or rash, the doctor may recommend antihistamines and/or locally acting medicines. If any of these symptoms are severe and disturbing, or if symptoms such as headache, fatigue, nausea, or vomiting occur, contact your doctor. The doctor may recommend a temporary increase in the dose of oral glucocorticosteroids.

Regular monitoring of growth in children and adolescents receiving glucocorticosteroids, regardless of the route of administration, is recommended due to the risk of growth retardation. If growth is slowed, the doctor may review the treatment regimen by reducing the dose of glucocorticosteroids.

Before starting treatment, inform your doctor about any other diseases or conditions besides asthma, especially:

• active or recent infections;
• liver function disorders.

Consult your doctor also if the above warnings apply to past medical history.

As with other inhaled medicines, paradoxical bronchospasm may occur immediately after using Nebulin. If a severe reaction occurs, stop using the medicine immediately and contact your doctor without delay.

Fungal infections of the oral cavity may occur during inhaled glucocorticosteroid therapy. Such infections may require appropriate antifungal treatment, and in some patients, discontinuation of inhaled glucocorticosteroids.

Also contact your doctor if symptoms of the disease do not improve despite regular use of the recommended doses of the medicine.

If the patient experiences blurred vision or other visual disturbances, contact your doctor.

Children
Nebulin may be used in the treatment of bronchial asthma in children from 6 months of age. The treating doctor determines the dose individually for each patient.

Nebulin and other medicines
Inform your doctor about all medicines currently or recently taken, including those obtained without a prescription, and about any medicines the patient plans to use.
Inform your doctor about any concerning reactions experienced after taking other medicines.

Especially inform your doctor about currently used antifungal medicines such as ketoconazole or itraconazole (strong inhibitors of CYP3A4 isoenzyme) and HIV protease inhibitors such as ritonavir and atazanavir, which may increase budesonide plasma concentrations. If concomitant use of such medicines with Nebulin is necessary, the interval between doses of each medicine should be as long as possible, and the doctor may recommend reducing the budesonide dose. Some medicines may enhance the effect of Nebulin, and the doctor may wish to closely monitor the patient taking such medicines (including certain HIV medicines: ritonavir, cobicistat).

No interactions between budesonide and other medicines used in the treatment of bronchial asthma have been observed.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
If a woman treated with Nebulin becomes pregnant, she should not discontinue treatment on her own but must inform her doctor as soon as possible.

Driving and operating machinery
Nebulin has no effect on the ability to drive or operate machinery.

3. How to use Nebulin

This medicine should always be used as directed by the physician. In case of doubt, consult the
physician or pharmacist.
The dosage of Nebulin suspension for nebulisation is individually determined by the physician for
each patient.
In case of doubt, contact the physician again.
Nebulin suspension for nebulisation may only be used with a nebuliser (inhalation device). The medicine is delivered to the lungs during breathing through a mouthpiece or a face mask.
Before starting to use the medicine, carefully read the "Instructions for use of Nebulin suspension for nebulisation" provided at the end of this leaflet and follow the instructions given.
Remember to rinse the mouth with water after each inhalation. If a face mask was used, wash the face after each inhalation as well.
Not every inhalation device (nebuliser) is suitable for administering Nebulin suspension for nebulisation.
Do not use ultrasonic nebulisers.

Asthma
Initial dose
The recommended initial dose for children from 6 months of age: the total daily dose ranges from
0.25 mg to 0.5 mg. If the child is taking an oral glucocorticosteroid, the physician may increase the
daily dose up to 1 mg, if necessary.
The recommended initial dose for adults and elderly patients: 1 mg to 2 mg per day.
The treating physician may adjust the dosage after some time.

Maintenance dose
It is recommended to use the lowest effective maintenance dose.
Children from 6 months of age: the total daily dose ranges from 0.25 mg to 2 mg.
Adults, including elderly patients: the total daily dose ranges from 0.5 mg to 4 mg.
If symptoms are very severe, the physician may increase the dose.
If the daily dose is up to 1 mg, the medicine may be administered once daily, either in the morning or in the evening.
If the effect of the medicine seems too strong or too weak, consult the physician.
If the patient's condition improves, the treating physician may decide to reduce the dose.
Improvement in the patient's condition after using Nebulin may occur within a few hours of starting
treatment. Full therapeutic effect is achieved after several weeks of treatment.
Nebulin should be used even when there are no symptoms of the disease.

Patients treated with oral glucocorticosteroids
Nebulin suspension for nebulisation may be prescribed to a patient who is taking glucocorticosteroids in oral tablet form.
Nebulin suspension for nebulisation may partially or completely replace oral glucocorticosteroids, maintaining the same or increased treatment efficacy. The gradual reduction of the orally administered medicine should be advised by the physician.
When switching from oral glucocorticosteroids to inhaled therapy, the patient should be clinically stable.
For the first 10 days, it is recommended to use high doses of Nebulin in combination with the previously used oral glucocorticosteroid at the unchanged dose. Then, the dose of the oral glucocorticosteroid should be gradually reduced by approximately 2.5 mg of prednisolone or an equivalent dose of another glucocorticosteroid per month, down to the lowest dose that maintains control of disease symptoms. Often, treatment with oral glucocorticosteroids can be completely discontinued.
Budesonide administered to the patient as a suspension for nebulisation is delivered to the lungs during inhalation. It is very important that the patient inhales calmly and evenly through the nebuliser mouthpiece or face mask while using the medicine.

Croup syndrome
The usual dose in infants and children with croup syndrome is 2 mg of budesonide administered as nebulisation. This dose may be given as a single dose or divided into two doses of 1 mg each, administered 30 minutes apart. This dosing regimen may be repeated every 12 hours, for up to 36 hours or until improvement in the patient's condition is achieved.

Exacerbations of COPD
Based on limited clinical trial data, the recommended dosage of Nebulin suspension for nebulisation is 4 to 8 mg per day, divided into 2 to 4 doses. Treatment should continue until clinical improvement is achieved, but treatment longer than 10 days is not recommended.

Method of administration
Nebulin may be mixed with sodium chloride 9 mg/mL (0.9%) solution for injection.
The prepared mixture should be used within 30 minutes.
The volume contained in the container may be divided to achieve the appropriate dose.
Unit-dose containers are marked with a horizontal line (Nebulin 0.5 mg/2 mL and 1 mg/2 mL). When the container is inverted, this line indicates a volume of 1 mL. If only 1 mL is to be used, remove the liquid above the indicator line. An opened container should be stored in its protective foil, protected from light. The contents of an opened container should be used within 24 hours.

*It should be diluted to 2 mL with 0.9% sodium chloride solution.
Please read the instructions for cleaning and disinfecting the nebulizer.
Nebulin can be mixed with 9 mg/mL (0.9%) sodium chloride injection solution.
Use of a higher than recommended dose of Nebulin
It is important that the patient uses the medicine according to the instructions in the leaflet or as
advised by the physician. Do not increase or decrease the dose without consulting your doctor.
If a higher than recommended dose has been taken, seek immediate advice from a doctor or
pharmacist.
If an overdose of Nebulin was administered only once, it should not cause harmful effects.
However, if higher than recommended doses have been used for a prolonged period, effects
similar to those of oral glucocorticosteroids may occur, such as increased blood levels of adrenal
cortex hormones and suppression of adrenal function. In such cases, the doctor should recommend
continuing treatment with Nebulin at a dose sufficient to maintain control of bronchial asthma
symptoms.
Missed dose of Nebulin
If a prescribed dose of Nebulin suspension for nebulization has been missed, there is no need to
make up for the missed dose. The next dose should be taken as directed by the physician. Do not
take a double dose to compensate for the missed dose.
If you have any further questions regarding 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.
If any of the symptoms listed below occur, stop using Nebulin immediately
and contact your doctor without delay:
facial swelling, especially around the mouth, tongue, eyes and ears, rash, itching, contact
dermatitis, urticaria and bronchospasm (constriction of the muscles in the airways causing
wheezing). These may indicate an allergic reaction. This adverse reaction is rare (may occur in less than 1 in 1,000 people);
sudden onset of wheezing after inhalation of the medicine. This adverse reaction is rare (may occur in less than 1 in 1,000 people).

Other possible adverse reactions:

Common (may occur in less than 1 in 10 people)
Oral fungal infections (thrush). To reduce the risk of developing these, rinse the mouth with water after using Nebulin.
Sore throat, cough, hoarseness and loss of voice.
Pneumonia (lung infection) in patients with COPD.
Tell your doctor if any of the following symptoms occur during budesonide use; these may be signs of lung infection:
fever or chills;
increased mucus production, change in mucus colour;
worsening cough or increased difficulty breathing.

Uncommon (may occur in less than 1 in 100 people)
Cataracts (clouding of the eye lens).
Blurred vision.
Muscle spasms.
Muscle tremors.
Depression.
Anxiety.

Rare (may occur in less than 1 in 1,000 people)
Facial rash after using a face mask. This can be prevented by washing the face with water after using the face mask.
Nervousness, behavioural changes (mainly in children).
Easy bruising.
Hoarseness and loss of voice (in children).

Adverse reactions for which frequency is not known (frequency cannot be estimated from available data)
Sleep disturbances, anxiety, excessive excitability, aggression.
Inhaled glucocorticosteroids may affect the normal production of steroid hormones in the body, particularly if used long-term and at high doses. Such symptoms may include:
glaucoma (increased intraocular pressure), frequency not known;
slowed growth in children and adolescents (rare);
effects on the adrenal glands (small glands near the kidneys) (rare).
These symptoms are less likely to occur with inhaled glucocorticosteroids than with oral glucocorticosteroid tablets.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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 the medicine.

5. How to store the medicine Nebulin

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following "EXP:".
The expiry date refers to the last day of the specified month.
Store in the original packaging to protect from light.
Shelf life after opening the sachet: 3 months
Shelf life after opening the container: 24 hours
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Nebulin contains

• The active substance is budesonide. 1 mL of nebuliser suspension contains: 0.25 mg or 0.5 mg micronised budesonide. Each single-dose container contains 0.5 mg or 1 mg budesonide in 2 mL of nebuliser suspension.
• Other ingredients are: disodium edetate, sodium chloride, polysorbate 80, citric acid, sodium citrate, water for injections, hydrochloric acid 10% or sodium hydroxide 10% (to adjust pH).

What Nebulin looks like and contents of the pack
Nebulin is a white, homogeneous suspension with pH 4.0–5.0, contained in a single-dose container.
Pack sizes:
10 or 20 single-dose containers of 2 mL.
Single-dose container made of LDPE, packed in a foil sachet (PET/Aluminium/PE), placed in a cardboard box.
2 or 4 sachets, each containing 5 containers.

Marketing Authorisation Holder and Manufacturer
Polfarmex S.A.
ul. Józefów 9
99-300 Kutno
Tel.: + 48 24 357 44 44
Fax: + 48 24 357 45 45
e-mail: [email protected]

Manufacturer
GENETIC S.p.A.
Contrada Canfora
84084 Fisciano (SA)
Italy

Instructions for use of Nebulin nebuliser suspension
Before use, gently shake the container for 30 seconds.
Hold the container in an upright position and open it by twisting the "wings" off.
Attach the open end of the container securely to the nebuliser reservoir and slowly squeeze the entire contents into it.

Single-dose containers containing 0.5 mg/2 mL and 1 mg/2 mL are marked with a horizontal line. When the container is inverted, this line indicates a volume of 1 mL. If only 1 mL is to be used, remove the liquid above the marking line.
Before using the remaining medication, gently mix the contents of the container.

• Record the date of opening the aluminium foil sachet. Do not use individual containers more than 3 months after opening the aluminium foil sachet.
• The prepared mixture should be used within 30 minutes.
• Store the medicine below 30°C.
• Always store the containers in the aluminium foil sachet to protect from light. If the entire contents of a container are not used at once, protect the remaining portion from light.
• Store the containers in an upright position.

WARNING

1. Rinse the mouth after each use of the medicine.
2. If the patient uses a face mask, ensure that the mask fits tightly against the face during inhalation. Wash the face after using the medicine.

CLEANING
The nebuliser chamber, mouthpiece, or face mask should be cleaned after each use.
These parts should be washed with warm running water using a mild cleaning agent recommended by the nebuliser manufacturer. The nebuliser chamber should then be thoroughly rinsed and dried by connecting the compressor to the outlet.