VANTOBRA 170 mg SOLUTION FOR NEBULIZER INHALATION

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

Do not use Vantobra:

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

If you are in any of the above circumstances, inform your doctor before using Vantobra.

Warnings and precautions

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

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

If you are in any of the above circumstances, inform your doctor before using Vantobra.

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

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

Inhaling medications can cause chest discomfort due to the narrowing of the airways; this can happen with Vantobra. Your doctor may ask you to use other medications suitable for widening the airways before using Vantobra.

Pseudomonasstrains can become resistant to antibiotic treatment over time. This means that, over time, Vantobra may stop working 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 experiencing side 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

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

Do not take the following medicines while using Vantobra:

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

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

The following medicines may increase the risk of harmful 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 can cause or worsen muscle weakness.

If you take any of the above medicines, consult your doctor before using Vantobra.

Do not mix or dilute Vantobra with any other medicine in the Tolero handheld nebulizer provided 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, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

It is not known if inhaling this medicine during pregnancy can cause side 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 consult your doctor before using this medicine.

Driving and using machines

Vantobra is not expected to affect your ability to drive or use machines.

3. How to use Vantobra

Follow your doctor's instructions for administering this medicine exactly. If in doubt, consult your doctor again.

The recommended dose is two ampoules per day (one in the morning and one in the evening) for 28 days.

• The dose is the same for all people from 6 years of age.
• Inhale the complete contents of one ampoule through the mouth in the morning and another ampoule in the evening using the Tolero handheld nebulizer.
• It is recommended that the interval between doses be as close as possible to 12 hours, but in any case, this interval should be at least 6 hours.
• After using the medicine 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 medicine twice a day during the 28 days of treatment and respect the cycle of 28 days with treatment and 28 days without treatment.

Repeat the cycle

Continue using Vantobra following this 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.

Preparing Vantobra for inhalation

• Use Vantobra only with the Tolero handheld nebulizer provided with Vantobra to ensure that you inhale the correct dose. Do not use the Tolero handheld nebulizer with any other medicine.
• Read the instructions for use included with the Tolero handheld nebulizer before using it.

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

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

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, since tobramycin is hardly absorbed in the stomach, but still, 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 you can. Otherwise, wait until the next dose. Do not use a double dose to make up for forgotten doses.

If you interrupt treatment with Vantobra

Do not interrupt 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 using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets 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 hives and itching (very rare, may affect up to 1 in 10,000 people)

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

People with cystic fibrosis have various symptoms of this disease. These symptoms may continue to occur while using Vantobra, but they should not be as frequent or worse than before.

If your underlying lung disease seems 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 (hoarseness)
• increased frequency of coughing
• sore throat

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

• Laryngitis (inflammation of the vocal cords that can cause voice alteration, sore throat, and difficulty swallowing)
• Loss of voice
• Headache, weakness
• Nasal bleeding, nasal discharge
• Ringing in the ears (usually transient), hearing loss, dizziness
• Coughing up blood, producing more sputum than usual, chest discomfort, asthma, fever
• Taste disturbances, feeling unwell (nausea), mouth ulcers, discomfort (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 thrush
• Inflammation of the lymph nodes
• Drowsiness
• Ear pain, ear problems
• Hyperventilation, low oxygen levels in the blood, sinusitis
• Diarrhea, pain in or around the stomach
• Red-colored pustules, papules on the skin
• Hives, itching
• Back pain
• General discomfort

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vantobra

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

Do not use this medicine after the expiration date that appears on the ampoule, on the pouch, or on the box after "EXP". The expiration date is the last day of the month indicated.

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

Do not use this medicine if it appears cloudy or particles are observed in the solution.

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

Medicines should not be thrown away in the trash. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Vantobra

• The active ingredient is tobramycin. One ampoule contains 170 mg of tobramycin as a single dose.
• The other components (excipients) are: sodium chloride, calcium chloride, magnesium sulfate, water for injectable preparations, sulfuric acid, and sodium hydroxide to adjust the pH.

Appearance of Vantobra and package contents

Vantobra solution for inhalation by nebulizer is supplied in a ready-to-use ampoule.

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 ampoules are packaged in pouches, and each pouch contains 8 ampoules, which corresponds to four days of treatment.

Vantobra is available together with a Tolero handheld nebulizer. It is presented in a box that contains two boxes inside, one with the medicine (56 ampoules with solution for inhalation by nebulizer in 7 pouches) and another that contains the Tolero handheld nebulizer. One package is sufficient for a 28-day treatment cycle.

Marketing authorization holder and manufacturer

PARI Pharma GmbH

Moosstrasse 3

D-82319 Starnberg

Germany

Tel.: +49 (0) 89 – 74 28 46 - 10

Fax: +49 (0) 89 – 74 28 46 30

E-mail: [email protected]

Date of the last revision of this leaflet:

Other sources of information

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