Tobrineb

Tobrineb 300mg/4ml Solution for Nebuliser
Tobramycin

Please read this leaflet carefully before using this medicine, as 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, please contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Tobrineb is and what it is used for

Tobrineb contains an active substance called tobramycin, an antibiotic belonging to a family known as aminoglycosides. It fights infections caused by Pseudomonas aeruginosa.
Tobrineb is used for the long-term treatment of chronic lung infections caused by Pseudomonas bacteria in patients with cystic fibrosis. It kills the bacteria and helps improve breathing. Pseudomonas is a very common bacterium that, at some point in their lives, infects almost all patients with cystic fibrosis. Some people acquire this infection only at an older age, while others become infected at a very young age. If the infection is not adequately controlled, it continues to damage the lungs, leading to further complications. Since Tobrineb is administered by inhalation, the antibiotic tobramycin can enter the lungs directly and act against the bacteria causing the infection.
Tobrineb is indicated only for patients aged 6 years and older.
To achieve the best results, carefully follow the instructions for correct use of the medicine.

2. What you need to know before using Tobrineb

Do not use Tobrineb

• If you are allergic (hypersensitive) to tobramycin or to any of the other ingredients of this medicine (listed in section 6) or to any other type of aminoglycoside antibiotic.
• If you are taking any of the medicines listed in the section below, Other medicines and Tobrineb.

Warnings and precautions
Talk to your doctor or pharmacist before using Tobrineb.
The tobramycin contained in Tobrineb belongs to a group of medicines that
occasionally cause hearing loss, dizziness, and kidney damage (see also section 4 on the reverse of this leaflet, Possible side effects). It is important that you inform your doctor if any of the following apply to you:

• If you experience a feeling of tightness in the chest after using Tobrineb. Your doctor will monitor your first dose of Tobrineb and check your lung function before and after administration. If you are not already doing so, your doctor may advise you to use a bronchodilator (e.g. salbutamol) before using Tobrineb.
• If you have suffered from neuromuscular disorders such as parkinsonism or other conditions characterized by muscle weakness, including myasthenia gravis.
• If you have previously had kidney problems. Before starting Tobrineb, your doctor may check that your kidneys are functioning properly through blood or urine tests. Your doctor may repeat these tests regularly during treatment.
• If you have previously experienced:
  • ringing in the ears;
  • any other hearing problems;
  • dizziness. Your doctor may perform hearing tests before starting treatment with Tobrineb or at any time during treatment.
• If you notice blood in your sputum. Inhaled medicines can cause cough reflex, and your doctor may advise you to stop using Tobrineb until blood in the sputum is minimal or absent.
• If you notice that Tobrineb is not as effective as it should be. Bacteria may sometimes develop resistance to antibiotic treatment.

Other medicines and Tobrineb
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

• Do not use Tobrineb if you are taking diuretics (used to remove fluid from the body by increasing urine production) containing furosemide or ethacrynic acid, unless you have discussed this with your doctor.
• Do not use Tobrineb if you are taking intravenous or oral urea or mannitol (used to treat serious conditions in hospitalized patients).
• Some other medicines may sometimes cause kidney or hearing damage, which could worsen with treatment with Tobrineb.

You may be treated with injections of tobramycin or other aminoglycosides at the same time as inhaling Tobrineb. These injections, which could increase the very low levels of aminoglycoside in the body caused by inhaling Tobrineb, should be avoided when taking the following medicines:

• Amphotericin B, cephalothin, cyclosporine, tacrolimus, polymyxin
• Platinum compounds (e.g., carboplatin and cisplatin)
• Anticholinesterases (e.g., neostigmine and pyridostigmine), botulinum toxin

If any of these apply to you, you must inform your doctor.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
It is not known whether inhaling this medicine during pregnancy causes adverse effects. When administered by injection, tobramycin and other aminoglycoside antibiotics can cause harm to the fetus, such as deafness and kidney problems.
If you are breastfeeding, you should speak with your doctor before using this medicine.
Driving and using machines
Tobrineb has a minor influence on the ability to drive or operate machinery. In rare cases, Tobrineb may cause dizziness. Therefore, Tobrineb may affect your ability to drive or use machinery.

3. How to use Tobrineb

Use this medicine exactly as directed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
Instructions for use of Tobrineb are provided after the "Dosage" section.
Do not dilute or mix Tobrineb in the nebulizer with any other medicine.
If you are receiving other treatments for cystic fibrosis, follow them in the following order:

• bronchodilator (e.g. salbutamol), followed by
• chest physiotherapy, followed by
• other inhaled medications, followed by
• Tobrineb. Confirm the correct order with your doctor.

Tobrineb must be used with a reusable PARI LC PLUS or PARI LC SPRINT nebulizer, dry and clean (for your personal use only), and with a suitable compressor. Ask your doctor or physiotherapist for advice regarding the appropriate compressor to use.
The single-dose container of Tobrineb must be opened immediately before use. Any unused solution must be discarded immediately.
Dosage

• The dose (one 4 ml container) is the same for all patients aged 6 years and older.

• Use two single-dose containers per day for 28 days. Inhale the contents of one container in the morning and one in the evening. There must be a 12-hour interval between doses.

• After this, a 28-day period without the medicine must elapse before starting a new 28-day treatment cycle.

• It is important that you continue using the product twice daily for the full 28-day treatment period and maintain the alternating treatment cycle of 28 days on / 28 days off. Continue taking Tobrineb in this manner until your doctor tells you to stop.

If you use more Tobrineb than you should
If you inhale too much Tobrineb, your voice may become very hoarse. Inform your doctor as soon as possible.
If you forget to use Tobrineb

• If more than 6 hours remain before your next dose, use Tobrineb as soon as you remember.
• If less than 6 hours remain before your next dose, skip the missed dose.

Then continue with your next dose as usual.
Instructions for use

Tobrineb is intended for use in a nebulizer; do not use it in any other way.

1. Wash your hands thoroughly with soap and water before opening the single-dose container, following the instructions below.
2. Bend the single-dose container in both directions (Figure A).
3. Carefully separate a new single-dose container from the strip, first above and then in the center (Figure B), leaving the remainder in the aluminum pouch.
4. Open the single-dose container by rotating the tab in the direction indicated by the arrow (Figure C).
5. Gently squeeze the sides of the single-dose container to dispense the medication, and pour it into the nebulizer chamber (Figure D).

6. Turn on the compressor.
7. Check that a constant mist is emitted from the mouthpiece.
8. Sit or stand in a comfortable position to breathe normally.
9. Place the mouthpiece between your teeth and on top of your tongue. Breathe normally, but only through your mouth (a nose clip may be helpful). Try not to block the end of the mouthpiece with your tongue.
10. Continue until all of Tobrineb has been used, which will take approximately 15 minutes.
11. If treatment is interrupted, or if you need to cough or rest during the treatment, turn off the compressor to preserve the medication. Turn the compressor back on when you are ready to resume treatment.

If you have any further questions about the use of this product, consult your doctor or pharmacist.
Nebulizer and compressor maintenance:
Follow the manufacturer's instructions for the care and use of the nebulizer and compressor.

4. Possible side effects

Like all medicines, Tobrineb may cause side effects, although not everyone experiences them.
If you are unsure about the side effects listed below, please consult your doctor for clarification.

The most common side effects of Tobrineb, which may occur in more than 1 out of 100 patients, are: cough, hoarseness.

Uncommon side effects of Tobrineb, which may occur in more than 1 out of 1,000 patients, are: oral thrush (candida infection), dizziness, hearing loss, increased salivation, inflammation of the tongue, skin rash, throat irritation, increased levels of liver enzymes in the blood, noisy breathing, nausea, dryness of the mucous membranes, blood in sputum, sore throat (oropharyngitis) or chest pain, headache, shortness of breath, weakness, increased production of sputum (the substance expelled when coughing), upper abdominal pain, and fungal infection.

Rare side effects, which may occur in more than 1 out of 10,000 patients, are: loss of appetite, ringing in the ears, chest tightness or breathing difficulty, loss of voice, nosebleeds, runny nose, mouth ulcers, vomiting, altered taste, asthma, dizziness, loss of strength, fever and pain, laryngitis (voice changes with irritated throat and difficulty swallowing).

Very rare side effects, which may occur in fewer than 1 out of 10,000 patients, are: swollen lymph nodes, drowsiness, ear problems, ear pain, hyperventilation, sinusitis, diarrhoea, allergic reactions including urticaria and itching, lack of oxygen available in the blood and body tissues (hypoxia), back pain, abdominal pain, and general malaise.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You may 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 Tobrineb

• Keep this medicine out of the sight and reach of children.

• For single use only. Do not use Tobrineb after the expiry date stated on the carton and label after “Exp.”. The expiry date refers to the last day of the month.
  You may use Tobrineb even if the colour of the solution has changed.
  Shelf life after first opening of the packaging: the sachets containing TOBRINEB
  may be stored (unopened or opened) at a temperature not exceeding 25°C for a maximum of 3 months.

• Store Tobrineb in the refrigerator between +2 and +8°C. If a refrigerator is not available or for transport purposes, the single-dose container may be stored for a maximum of 3 months at a temperature not exceeding 25°C.

• Keep the containers in the original packaging to protect them from light.

• After first opening of the single-dose container: use it immediately.

• After first use: immediately dispose of the used single-dose container.

• Do not dispose of any medicine 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 Tobrineb contains

• The active substance is tobramycin. Each 4 ml single-dose container contains 300 mg of tobramycin.
• The other components are sodium chloride, sulfuric acid, sodium hydroxide (to adjust pH), water for injections.

Description of the appearance of Tobrineb and package contents
Tobrineb appears as a clear solution with a pale yellow to yellow colour.
Tobrineb nebuliser solution is supplied in 4 ml single-dose containers. There are 4 single-dose containers in each sealed pouch, in cartons containing 4, 16, 28 or 56 containers.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Promedica S.r.l., Via Palermo, 26/A – 43122 Parma, Italy

Manufacturer (batch release):
Chiesi Farmaceutici S.p.A., Via San Leonardo, 96 – 43122 Parma, Italy or Genetic S.p.A., Contrada Canfora – 84084 Fisciano (SA), Italy

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: Bramitob
Denmark: Bramitob
Finland: Bramitob
Germany: Bramitob
Greece: Bramitob
Ireland: Bramitob
Italy: Tobrineb
Norway: Bramitob
Netherlands: Bramitob
Poland: Bramitob
Portugal: Bramitob
Czech Republic: Bramitob
Slovakia: Bramitob
United Kingdom (Northern Ireland): Bramitob
Spain: Bramitob
Sweden: Bramitob
Hungary: Bramitob