Package Insert: Information for the User

Colobreathe 1.662.500 UI Powder for Inhalation, Hard Capsules

Colistimethate Sodium

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

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others who 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 package insert. See section 4.

Colobreathe contains colistimethate sodium, a type of antibiotic called polymyxin.

Colobreathe is used to control persistent respiratory infections caused by the bacteriaPseudomonas aeruginosain adult and pediatric patients aged 6 years and older with cystic fibrosis.Pseudomonas aeruginosais a very common bacteria that infects almost all patients with cystic fibrosis at some point in their lives. Some people contract this infection while very young, but for others it occurs much later. If this infection is not controlled properly, it will cause damage to the lungs.

How it works

Colobreathe acts by destroying the bacterial cell membrane, with a lethal effect on these bacteria.

Do not use Colobreathe:

• if you or your child is allergic to sodium colistimethate, colistin sulfate, or polymyxins.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Colobreathe.

Inform your doctor if you or your childhas ever experienced any of the following conditions:

• has had a severe reaction to dry powder inhalation medications, unless this has already been discussed with your doctor.
• already has a known muscle disease called myasthenia gravis or the hereditary disease, porphyria
• blood in sputum (the substance that is expelled when coughing)

After each inhalation of Colobreathe, the mouth should be rinsed with water. The rinse should not be swallowed. The rinse may reduce the risk of developing oral fungal overinfections during treatment, and also may reduce the unpleasant taste associated with sodium colistimethate.

When you or your child starts using Colobreathe, you or your child may find that you have cough, difficulty breathing, chest tightness, or wheezing (a high-pitched sound that occurs when breathing). The number of these adverse effects may be reduced as you continue to use the inhaler or your doctor may prescribe a bronchodilator to use before or after taking Colobreathe. If any of these effects become a problem, please contact your doctor who may modify your treatment.

If you or your child experiences any kidney or nerve problems, precautions should be taken when administering Colobreathe, although your doctor will already be aware of this.

If you or your child requires other forms of colistimethate, either by injection or nebulization, precautions should be taken, although your doctor will already be aware of this.

Children

Do not administer Colobreathe to children under 6 years of age, as it is not suitable for them.

Other medications and Colobreathe

Inform your doctor if you or your child is taking, has taken recently, or may need to take any other medication, and in particular:

• if you or your child is taking aminoglycoside antibiotics, used to treat infections, precautions should be taken;
• if you or your child has myasthenia gravis and is taking macrolide antibiotics such as azithromycin and clarithromycin, or fluoroquinolone antibiotics such as norfloxacin and ciprofloxacin. Taking these at the same time as Colobreathe may cause muscle weakness problems;
• if you or your child is taking colistimethate by injection or nebulization, precautions should be taken;
• if you or your child requires general anesthesia, precautions should be taken.

Pregnancy and breastfeeding

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

There is no information on the safety of Colobreathe in pregnant women. Your doctor should advise you before using Colobreathe about whether the benefits of the medication outweigh the risks.

Sodium colistimethate may pass into breast milk. Discuss the use of Colobreathe with your doctor.

Driving and operating machines

You may experience dizziness, confusion, or vision problems while using Colobreathe. Do not drive or operate machines until the symptoms have disappeared.

Colobreathe contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per capsule; this is, essentially “sodium-free”.

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor.Ask your doctor if you/your child has any doubts.

The first dose must be administered under medical supervision.

The recommended dose is

Adults and children aged 6 years and older

• The contents of a Colobreathe capsule must be inhaled twice a day using the Turbospin inhaler.
• There must be a 12-hour interval between doses.

The order in which treatments should be taken or performed

If you/your child is taking other treatments for cystic fibrosis, you/your child must take them in the following order:

• Inhaled bronchodilators
• Respiratory physiotherapy
• Other inhaled medications
• Then Colobreathe

You/your child must confirm the order of treatments with your doctor.

Administration method

Colobreathe is inhaled into the lungs in the form of powder from the capsule using the manual inhaler called Turbospin. Colobreathe can only be administered using this device.

Do not swallow Colobreathe capsules.

To inhale Colobreathe from the capsule using the Turbospin inhaler, follow the procedure described below. Your doctor, pharmacist, or nurse must show you/your child how to inhale the medication when you/your child start treatment:

Using Colobreathe with the Turbospin inhaler

Turbospin preparation

1. Remove the cap. Pull it out gently.

1. Unscrew the mouthpiece, exposing the Turbospin inhaler chamber.

1. Extract a single capsule from the blister. Once you have extracted the capsule, you must use it immediately.

1. Insertthe capsule gentlyinto the chamberwith the wider end first.Do not apply force.

1. Now put the mouthpiece back on by screwing it in place.

Perforating the capsule and inhaling the medication

1. To perforate the capsule:

• Hold the inhaler with the mouthpiece up, push the piston gently upwards until you reach the visible line; you will feel resistance at this point and this will fix the capsule in place, ready to be perforated. Keep that position before proceeding to perforation.
• Now, with the capsule fixed in place, continue pushing the piston until you reach the top and then release it.
• The capsule is now perforated and the contents can be inhaled.
• Do not perforate the capsule more than once. You may see a little powder coming out of the capsule chamber after perforating it, which is normal

1. Breathe slowly. Place the mouthpiece between your lips and teeth. Make sure to create a tight seal between your lips and the mouthpiece. Be careful not to cover the air outlets with your fingers or mouth during inhalation.
2. Then, inhale slowly and deeply through the mouth at a sufficient rate to allow you to hear or feel the capsule rotating.
3. Remove theTurbospin inhalerfrom your mouth and hold your breath for about 10 seconds, or for as long as you feel comfortable, then exhale slowly.
4. If you do not hear the capsule rotating, it may have become stuck in the compartment. If this happens, you can release it by gently tapping the inhaler chamber. Do not try to release the capsule by repeatedly pressing the piston. If the capsule cannot be released and the powder cannot be inhaled, dispose of the broken capsule and any remaining powder in it and use another.
5. Inhale the medication again by repeating steps 7 and 8 to ensure that the capsule is empty.
6. You can check if the capsule is empty by unscrewing the mouthpiece and checking the capsule. If it is not empty, repeat steps 7, 8, and 9 until you have inhaled all the contents.
7. When you have inhaled all the contents, rinse your mouth thoroughly with water and then spit it out.

Removing the empty capsule from the Turbospin

1. When the capsule is empty, unscrew the mouthpiece, then remove and dispose of the empty capsule.

Additional information

When you breathe slowly, you inhale air through the body of the Turbospin inhaler inside the capsule chamber.The tiny medication particles from the capsule are collected by the airflow and transported through your respiratory tract to your lungs.

Occasionally, very small pieces of the capsule wrapper may enter your mouth or respiratory tract.

• If this happens, you may notice these pieces on your tongue or in your respiratory tract.
• The capsule wrapper is made of gelatin, which is harmless to humans if swallowed or inhaled.

• The chances of the capsule breaking into pieces increase if the capsule is perforated more than once during step 6.

Cleaning the Turbospin device

Clean the Turbospin inhaler after each dose using the following procedure:

1. Push the piston all the way down a couple of times while holding the chamber upside down.
2. Clean the chamber with a cloth or cotton swab. Do not use water.
3. Re-tighten the mouthpiece firmly in place, put the cap on, and the inhaler will be ready to be used for the next dose.

If you/your child uses more Colobreathe than you should, or if you/your child has accidentally swallowed the capsule,contact your doctor immediately for help.

If you/your child forgets to use Colobreathe

If you/your child forgets to administer a dose of Colobreathe, then you/your child should administer the missed dose as soon as you/your child remember. Do not administer two doses in less than 12 hours. Continue as instructed.

If you/your child interrupts Colobreathe treatment

Do not stop treatment prematurely unless your doctor tells you to. Your doctor will decide how long your treatment/your child's treatment should last.

If you/your child has any other doubts about using this medication, ask your doctor.

Like all medications,this medicationmay cause side effects, although not everyone will experience them.

Allergic Reactions

An allergic reaction to Colobreathe is possible (usually severe allergic reactions can cause skin rashes, facial swelling, tongue and neck swelling, difficulty breathing due to airway constriction, and loss of consciousness).If you/your child experiences signs of an allergic reaction, seek urgent medical attention.

Other possible side effects

You/your child may experience an unpleasant taste in the mouth after inhaling Colobreathe.

Very common (may affect more than 1 in 10 people):

• Difficulty breathing
• Cough, throat irritation
• Hoarse or weak voice, or even loss of voice
• Unpleasant taste

Common (may affect up to 1 in 10 people):

• Headache
• Tinnitus or ringing in the ears, balance problems
• Cough with blood, wheezing (a whistling sound when breathing), chest discomfort, asthma, productive cough (cough that produces mucus), lung infection, lung crepitations (the doctor hears this when listening to the lungs with a stethoscope)
• Vomiting, nausea
• Changes in lung function (found in tests)
• Joint pain
• Lack of energy, fatigue
• Increased temperature

Rare (may affect up to 1 in 100 people):

• Allergic reactions (hypersensitivity); symptoms may include rash and itching
• Weight fluctuations, decreased appetite

• Anxiety

• Seizures
• Tendency to sleep
• Ear blockage
• Chest pain
• Difficulty breathing
• Nasal bleeding, nasal congestion (mucus in the nose, which can make you feel blocked) cough with thick green mucus, throat and nasal sinus pain
• Strange sounds in the chest (your doctor will hear this when listening to the lungs with a stethoscope)
• Diarrhea, gas
• Excessive saliva production
• Toothache
• Protein in the urine (found in tests)
• Thirst

The side effects described above have been observed in people of all ages with a similar frequency.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it's a possible side effect not listed in this prospectus.You can

also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medicationout of the reach and sight of children.

Do not usethis medicationafter the expiration date that appears on the outer packaging and on the blister pack after EXP. The expiration date is the last day of the month indicated.

Do not store Colobreathe at a temperature above 25°C.

Store in the original packaging until immediately before use to protect it from moisture.

If you/your child accidentally removes the metal foil and a capsule is exposed, please discard that capsule.

Discard the Turbospin inhaler after completion of a treatment package.

Medicines should not be disposed ofthrough the drains or in the trash. Ask your pharmacisthow to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Colobreathe

The active principle is colistimethate sodium. Each capsule contains 1,662,500 IU (approximately equivalent to 125 mg) of colistimethate sodium.

The other components are:

Capsule coating

Gelatin

Polietilenglycol

Sodium lauryl sulfate

Purified water

Appearance of the product and contents of the container

Colobreathe dry powder for inhalation, hard gelatin capsules (dry powder for inhalation) are supplied in small, hard, transparent gelatin capsules containing a fine white powder.

The Turbospin is a dry powder inhaler driven by inspiratory flow, manufactured in polipropylene and stainless steel.

The capsules are packaged in blisters, which are supplied in boxes containing:

• 56 hard capsules and a dry powder inhaler Turbospin device, sufficient for 4 weeks of use.
• 8 hard capsules and a dry powder inhaler Turbospin device, sufficient for 4 days of use.

Only some container sizes may be marketed.

Marketing Authorization Holder

Essential Pharma Limited,

Vision Exchange Building,

Triq it-Territorjals, Zone 1,

Central Business District,

Birkirkara, CBD 1070,

Malta

Responsible for manufacturing

Teva Pharmaceuticals Europe BV

Swensweg 5

2031 GA Haarlem

Netherlands.

Millmount Healthcare Limited

Block 7, City North Business Campus

Stamullen

Co Meath

K32 YD60

Ireland

Merckle GmbH

Ludwig-Merckle-Str-3

89143 Blaubeuren

Germany

Laboratorios Liconsa, S.A.

Avda. Miralcampo, 7, Pol. Ind.

Miralcampo

19200 Azuqueca de Henares (Guadalajara)

Spain

Last revision date of this leaflet: February 2024.

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