Prospecto:Information for the Patient

Vantobra 170 mg Solution for Inhalation by Nebulizer

tobramycin

Read this prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospectus. See section 4.

1.What is Vantobra and for what it is used

2.What you need to know before starting to use Vantobra

3.How to use Vantobra

4.Possible adverse effects

5.Storage of Vantobra

6.Contents of the package and additional information

What is Vantobra

Vantobra contains an antibiotic called tobramycin. It belongs to a class of antibiotics known as aminoglycosides.

How is Vantobra used

Vantobra is used in patients with cystic fibrosis aged 6 years and older for the treatment of lung infections caused by a bacterium calledPseudomonas aeruginosa.

Pseudomonas aeruginosais a bacterium that frequently infects the lungs of patients with cystic fibrosis at some point in their lives. If the infection is not properly treated, it continues to damage the lungs and causes further respiratory problems.

How Vantobra works

When inhaled, Vantobra allows the antibiotic to enter the lungs directly to fight the bacteria causing the infection. This medication acts by altering the production of proteins that the bacteria need to build their cell walls. This damages the bacteria and ultimately kills them.

Do not use Vantobra:

• if you are allergic (hypersensitive) to tobramycin, or to any aminoglycoside antibiotic or to any of the other components of Vantobra (listed in section 6).

Inform your doctor before using Vantobra if you are in any of the above circumstances.

Warnings and precautions

Consult your doctor if you have ever suffered from any of the following conditions:

• hearing problems (including ringing in the ears and dizziness)
• kidney problems
• chest discomfort
• blood in sputum (the substance that is expelled when coughing)
• persistent or worsening muscle weakness, a symptom often associated with conditions such as myasthenia (muscle weakness) or Parkinson's disease.

Inform your doctor before using Vantobra if you are in any of the above circumstances.

If you have hearing problems or kidney function problems, your doctor may take blood samples to monitor the amount of Vantobra present in your body.

If you or your maternal family members have a mitochondrial disease (a genetic disorder) or hearing loss due to antibiotics, you are recommended to inform your doctor or pharmacist before taking this medicine. Certain mitochondrial mutations may increase your risk of hearing loss with this product. Your doctor may recommend genetic tests before administering Vantobra.

Inhalation of medicines can cause chest discomfort due to narrowing of the airways; this can occur with Vantobra. Your doctor may ask you to use other suitable medicines to widen the airways before using Vantobra.

Strains ofPseudomonascan become resistant to antibiotic treatment over time. This means that, over time, Vantobra may not work as it should. If you have doubts about this, consult your doctor.

If you are also taking tobramycin or another aminoglycoside antibiotic administered by injection, this may increase the risk of adverse effects. Your doctor will monitor you as necessary.

Children

This medicine is not indicated for use in children under 6 years of age.

Other medicines and Vantobra

Inform your doctor or pharmacist if you are using or have recently used other medicines, including those purchased without a prescription.

You should not take the following medicines while using Vantobra:

• furosemide, a diuretic (medicine that increases urine volume)
• other medicines with potential diuretic effects, such as urea or mannitol
• other medicines that may damage your kidneys or hearing:

• amphotericin B, cephalothin, polymyxins (used to treat microbial infections), ciclosporin, tacrolimus (used to reduce the activity of the immune system). These medicines may damage the kidneys;
• platinum-based compounds, such as carboplatin and cisplatin (used to treat certain types of cancer). These medicines may damage the kidneys or hearing.

The following medicines may increase the risk of adverse effects if administered when you are already receiving tobramycin or another aminoglycoside antibiotic administered by injection:

• anticholinesterases, such as neostigmine and pyridostigmine (used to treat muscle weakness) or botulinum toxin. These medicines may cause muscle weakness to appear or worsen.

Inform your doctor before using Vantobra if you are taking any of the above medicines.

Do not mix or dilute Vantobra with any other medicine in the hand-held nebulizer Tolero that is supplied with Vantobra.

If you are taking different medicines for cystic fibrosis, you will take them in the following order:

1. bronchodilator treatment, such as salbutamol
2. respiratory physiotherapy
3. other inhaled medicines
4. Vantobra

Consult your doctor about the order.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor before using this medicine.

The effects of inhaling this medicine during pregnancy are unknown. When administered by injection, tobramycin and other aminoglycoside antibiotics may cause fetal damage, such as hearing loss and kidney problems.

If you are breastfeeding, you should consult your doctor before using this medicine.

Driving and operating machinery

Vantobra is not expected to affect your ability to drive or operate machinery.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

The recommended dose istwoampoules per day (one in the morning and one at night) for 28 days.

• The dose is the same for all people aged 6 years and above.
• Inhale the complete content of one ampoule through the mouth in the morning and another ampoule in the night using the hand-held nebulizer Tolero.
• It is recommended that the interval between doses be as close as possible to 12 hours, in any case, this interval must beat least 6 hours.
• After using the medication for 28 days, you will start a 28-day rest period, during which you will not inhale any dose of Vantobra. Then, you will have to start a new cycle after the rest period (as illustrated).
• It is essential that you continue using the medication twice a day during the 28 days of treatment and respect the28-day cycle with treatment and 28 days without treatment.

Repeat the cycle

Continue using Vantobra following the same scheme until your doctor tells you otherwise.

If you have any doubts about how long you should continue using Vantobra, consult your doctor or pharmacist.

Preparation of Vantobra for inhalation

• Use Vantobra only with the hand-held nebulizer Tolero shown in the following image to ensure that you inhale the correct dose. Do not use the hand-held nebulizer Tolero with any other medication.
• Read the usage instructions included with the hand-held nebulizer before using it.

• Make sure you have a controllereTrackor eBase to which to connect the hand-held nebulizer Tolero. The corresponding controller can be prescribed by your doctor or purchased separately.
• Wash your hands thoroughly with water and soap.
• Remove one ampoule of Vantobra from the aluminum foil package just before inhalation.
• Keep the rest of the medication refrigerated in the original box.
• Place all the parts of the hand-held nebulizer Tolero on a clean and dry paper or cloth. Make sure the nebulizer is on a flat and stable surface.
• Assemble the hand-held nebulizer Tolero according to its usage instructions.
• Hold the ampoule upright and gently tap it before removing the top to prevent spillage. Empty the content of one ampoule into the medication container of the nebulizer.
• Begin treatment by sitting upright in a well-ventilated room. Hold the nebulizer in a horizontal position and breathe normally through the mouth. Avoid breathing through the nose. Continue inhaling and exhaling comfortably until the treatment is completed. When all the medication has been administered, you will hear an acoustic signal indicating that the administration has ended.
• If you need to interrupt the treatment for any reason before completing it, press and hold the On/Off button for a second. To restart the treatment, press and hold the On/Off button for a second again.
• The hand-held nebulizer Tolero must be cleaned and disinfected as described in the usage instructions.
• Use a new hand-held nebulizer Tolero for each treatment cycle (28 days of active treatment), including the medication.

Do not use an alternative and untested nebulizer system, as this may alter the amount of medication that reaches the lungs, which in turn may alter the safety and efficacy of the medication.

If you use more Vantobra than you should

If you inhale too much Vantobra, your voice may become very hoarse. Inform your doctor as soon as possible. If you swallow Vantobra, it is unlikely to cause serious problems, as tobramycin is poorly absorbed in the stomach, but you should inform your doctor as soon as possible.

If you forget to use Vantobra

If you forget to use Vantobra and there are at least 6 hours until the next dose, take the dose as soon as possible. Otherwise, wait until the next dose. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Vantobra

Do not interrupt the treatment with Vantobra unless your doctor tells you to, as the lung infection may not be sufficiently controlled and could worsen.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects can be serious

• Chest discomfort with difficulty breathing (rare, may affect up to 1 in 1,000 people)
• Allergic reactions, such as urticaria and pruritus (very rare, may affect up to 1 in 10,000 people)

If you experience any of these side effects, stop using Vantobra and immediately contact your doctor.

People with cystic fibrosis may experience various symptoms of this disease. These symptoms may continue to be present while using Vantobra, but they should not be as frequent or severe as before.

If your underlying lung disease appears to worsen while taking Vantobra, inform your doctor immediately.

Other side effects may be:

Uncommon (may affect up to 1 in 100 people)

• Difficulty breathing
• Voice alteration (hoarse voice)
• Increased frequency of coughing
• Throat pain

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

• Laryngitis (inflammation of the vocal cords that may cause voice alteration, throat pain, and difficulty swallowing)
• Loss of voice
• Headache, weakness
• Nasal bleeding, nasal discharge
• Tinnitus in the ears (usually transient), hearing loss, dizziness
• Coughing up blood, producing more sputum than normal, chest discomfort, asthma, fever
• Alterations in taste, feeling unwell (nausea), mouth ulcers, feeling unwell (vomiting), decreased appetite
• Rash
• Chest pain or generalized pain
• Worsening of lung function test results

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

• Fungal infections in the mouth or throat, such as aphthae
• Lymph node inflammation
• Drowsiness
• Ears pain, ear problems
• Hyperventilation, low oxygen levels in the blood, sinusitis
• Diarrhea, stomach pain or discomfort
• Red pustules, papules on the skin
• Urticaria, pruritus
• Back pain
• General feeling of being unwell

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial, on the blister pack, or on the box after «CAD». The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2°C and 8°C). If you do not have a refrigerator (for example, when transporting the medication), you can store the box with the medication (even if the blisters are open) below 25°C for a maximum of 4 weeks. If the medication is stored at room temperature for more than 4 weeks, it will be disposed of in accordance with local regulations.

Do not use this medication if you observe a cloudy appearance or particles in the solution.

Never store an opened vial.Once a vial is opened, it must be used immediately, and the remaining product will be discarded.

Medications should not be thrown away in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This way, you will help protect the environment.

Composition of Vantobra

• The active principle is tobramycin. A vial contains 170mg of tobramycin as a single dose.
• The other components (excipients) are: sodium chloride, calcium chloride, magnesium sulfate, water for injection, sulfuric acid and sodium hydroxide for pH adjustment.

Appearance of Vantobra and contents of the packaging

Vantobra solution for inhalation via nebulizer is supplied in a ready-to-use vial.

Vantobra is a clear to yellowish solution, which may vary to dark yellow. This does not affect the action of Vantobra as long as the storage instructions have been followed.

The vials are packaged in sachets, and each sachet contains 8 vials, corresponding to four days of treatment.

Vantobra is available with a hand-held nebulizer Tolero. It is presented in a box that also contains two inner boxes, one with the medication (56 vials with solution for inhalation via nebulizer in 7 sachets) and another containing the hand-held nebulizer. A package is sufficient for a 28-day treatment cycle.

Holder of the marketing authorization and responsible manufacturer

PARI Pharma GmbH

Moosstrasse 3

D-82319 Starnberg

Germany

Phone:+49 (0) 89 – 74 28 46 - 10

Fax:+49 (0) 89 – 74 28 46 30

Email:[email protected]

Date of the last review of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.