Label: information for the user

Colixin 1 MUI Powder for injectable solution

Colestimate sodium

The active ingredient is colestimate sodium. Each vial contains 1 million International Units (UI), which is approximately equivalent to 80 mg of colestimate sodium. It does not contain other components.

Read the entire label carefully before starting to use the medication.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you and should not be given to others, even if they have the same symptoms, as it may harm them.

If you experience severe adverse effects or any adverse effect not mentioned in this label, inform your doctor or pharmacist. See section 4.

5Storage of COLIXIN

6.Additional information

This medication is an antibiotic belonging to the group of polymyxins.

Colixinis administered via injection to treat certain severe infections caused by specific bacteria.Colixinis used when other antibiotics are not suitable.

Colixinis administered in the form of inhalation to treat chronic respiratory infections in patients with cystic fibrosis.Colixinis used when such infections are caused by a specific bacteria calledPseudomonas aeruginosa.

Do not use Colixin:

- If you are allergic (hypersensitive) to colistimethate sodium, colistin, or other polymyxins.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Colixin

- If you have or have had kidney problems

- If you have myasthenia gravis

- If you have porphyria

- If you have asthma

• If you require treatment with other antibiotics that may also damage the kidneys or cause brain disturbances of the type of dizziness or visual disturbances.
• If you have cystic fibrosis, you may receive this medication via inhalation. In this case, cough and bronchospasm (difficulty breathing) may occur, so the first administration via this route should always be done under medical supervision.

- If you experience muscle spasms, fatigue, or increased urine production at any time, inform your doctor immediately, as these episodes may be related to a condition known as pseudo-Bartter syndrome.

Special caution should be exercised when using Colixin in premature infants and newborns, as their kidneys are not yet fully developed.

Use of Colixin with other medications

- Medications that may affect the way your kidneys function. Taking these medications at the same time as Colixin may increase the risk of kidney damage

- Medications that may affect the nervous system. Taking these medications at the same time as Colixin may increase the risk of adverse effects on your nervous system

- Medications called muscle relaxants, often used during general anesthesia. Colixin may increase the effects of these medications. If you are to receive general anesthesia, inform your anesthesiologist that you are using Colixin.

If you have myasthenia gravis and are also taking other antibiotics called macrolides (such as azithromycin, clarithromycin, or erythromycin), or antibiotics called fluoroquinolones (such as ofloxacin, norfloxacin, and ciprofloxacin), taking Colixin increases the risk of muscle weakness and respiratory difficulties even further.

Receiving Colixin via infusion at the same time as receiving Colixin via inhalation may increase your risk of adverse effects.

Pregnancy and breastfeeding

Colixin should only be administered to pregnant patients if the expected benefit outweighs any potential risk.

If administered to a lactating patient, she should discontinue breastfeeding while receiving Colixin.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

Colixin may cause dizziness, confusion, or visual problems, so you should not drive or use any hazardous tools or machinery in these cases.

Colixin contains sodium

This medication contains 5.27 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 0.26% of the maximum daily sodium intake recommended for an adult.

Follow exactly the administration instructions forColixinprescribed by your doctor.

Consult your doctor if you have doubts. Remember to take your medication. Your doctor will indicate the duration of treatment withColixin. Do not discontinue treatment beforehand, as there is a risk of the infection reappearing.

Colixincan be administered via systemic intravenous (infusion or single injection) or via inhalation, using a nebulizer for this purpose.

• Intravenous route

Your doctor has prescribedColixinas an infusion in a vein for 30 to 60 minutes.

The usual dose in adults is 9 million units, divided into two or three doses. If you are quite ill, you will be administered a single dose of 9 million units at the beginning of treatment.

In some cases, your doctor may decide to give you a daily dose of up to 12 million units.

The usual daily dose in children weighing up to 40 kg is 75,000 to 150,000 units per kilogram of body weight, divided into three doses.

In cases of cystic fibrosis, higher doses have occasionally been administered.

Children and adults with kidney problems, including those on dialysis, are usually given lower doses.

Your doctor will regularly monitor your renal function while you are receivingColixin.

- Inhalation route

The usual dose in adults, adolescents, and children 2 years of age or older is 1-2 million units two to three times a day (up to 6 million units per day).

The usual dose in children under 2 years of age is 0.5-1 million units, twice a day (up to 2 million units per day).

Your doctor may decide to adjust the dose based on your circumstances. If you are also taking other inhaled medications, your doctor will indicate the order in which you should take them.

If you are receiving additional care for cystic fibrosis, such as physical therapy or other treatments administered via inhalation (e.g., bronchodilators), remember that colistimethate sodium should be administered after them.

In any case, if there is a change in renal function, the dose will need to be adjusted, i.e., reduced and/or prolonged administration interval.

If you use more Colixin than you should

If you have used moreColixinthan you should, you may experience breathing difficulties, muscle weakness, and kidney function problems.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 5620420, indicating the medication and the amount ingested.

If you forgot to use Colixin

Do not administer a double dose to compensate for the missed doses.

If you are receiving this medication via intravenous route and it has not been more than 3 hours since you should have received your dose, you can request that they administer the corresponding dose. If more than 3 hours have passed since the missed dose, wait until the next administration.

If the administration is via inhalation, take the corresponding dose as soon as you remember and continue with the next dose normally.

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

Like all medications, Colixin may produce adverse effects, although not everyone will experience them.

For colistimethate sodium, these effects primarily affect the nervous system and kidney function. The most common adverse effects after nebulization are cough and difficulty breathing.

Nervous System Disorders

Tingling or numbness around the lips and face, dizziness, difficulty speaking, visual disturbances, confusion, mental alterations, or flushing (face redness).

Respiratory Disorders

Nebulization of Colixin through a nebulizer may produce cough and in some individuals cause chest tightness, wheezing, or a sensation of choking.

Renal and Urinary Tract Disorders

Colixin may affect the kidney, especially if the dose is high or you are taking another medication that can affect the kidney.

General Disorders and Administration Site Conditions

Colixin may cause allergic reactions such as skin rashes. If this occurs, inform your doctor immediately as it may be necessary to discontinue treatment.

After intravenous injection, you may feel a mild pain at the injection site.

After intravenous administration, you may experience the following symptoms that may be related to a known disease called pseudo-Bartter syndrome (see section 2):

− Muscle spasms

− Increased urine production

− Fatigue

Colixin administered through a nebulizer may cause mouth or throat pain that may be due to medication allergy or an added fungal infection.

Reporting Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance for Human Use Medications: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of the reach and sight of children.

Store below 25°C. Protect from light.

Do not use Colixin after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

Do not use Colixin if you observe any visible sign of deterioration.

Drugs should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Instructions for use and handling.

Systemic administration

To administer by bolus injection:

Reconstitute the contents of the vial with no more than 10 ml of injectable water or 0.9% sodium chloride.

To administer by infusion:

The reconstituted vial contents can be diluted, usually with 50 ml of 0.9% sodium chloride.

To administer by intrathecal and intraventricular routes:

The administered volume must not exceed 1 ml (concentration of the reconstituted solution 125,000 IU/ml).

Visual inspection must be performed to detect the presence of particles in the solution before administration and discard the solution if particles are present.

The solution is clear and for single use only, and any unused solution must be discarded.

Compatible infusion solutions are: 0.9% sodium chloride, 5% dextrose, 5% fructose, Ringer's solution, and 10% dextrose in 0.9% sodium chloride.

Colistimethate hydrolysis increases significantly when reconstituted and diluted below the critical micellar concentration, approximately 80,000 IU/ml.

Solutions below this concentration must be used immediately.

In solutions for bolus injection or nebulization, chemical and physical stability has been demonstrated in the original vial with a concentration ≥ 80,000 IU/ml for 24 hours at a temperature range of 2 to 8°C.

From a microbiological point of view, unless the opening/reconstitution/dilution method excludes the risk of microbial contamination, the product must be used immediately.

If not used immediately, the time and storage conditions in use are the responsibility of the user.

In infusion solutions that have been diluted beyond the original vial volume and/or with a concentration <80,000 IU/ml, they must be used immediately.

For intrathecal and intraventricular administration routes, the reconstituted product must be used immediately.

Nebulization

Reconstitute the vial contents well with injectable water to produce a hypotonic solution or with a 50:50 mixture of injectable water and 0.9% sodium chloride to produce an isotonic solution or with 0.9% sodium chloride to produce a hypertonic solution.

The reconstitution volume must comply with the usage instructions of the nebulizer administration device and is usually not more than 4 ml.

The solution may be slightly turbid and may form foam when agitated. It is generally recommended to administer Colixin using nebulizers with motors or ultrasonics, as they produce respirable solutions with particles with a diameter between 0.5-5.0 microns when administered with an appropriate compressor. Follow the manufacturer's instructions for the maintenance and care of the nebulizer and compressor.

It is likely that some of the nebulized medication will be released into the environment. To prevent the discarded aerosol from entering the environment, a filter can be adapted. Colixin must be administered in a well-ventilated room.

Any unused solution remaining in the nebulizer must be discarded after treatment.

Colixin Composition

• The active ingredient is colistimethate sodium.
• It does not contain other components.

Appearance of the product and contents of the package

Colixin is presented in vials containing powder for injectable solution/inhalation by nebulizer.

It is available in packages containing 10 or 30 vials.

Expiration date

Do not use Colixin after the expiration date indicated on the package.

Marketing authorization holder and responsible manufacturer

Pharmis Biofarmacêutica, Lda.

Praceta do Farol, 77

2750-610 Cascais

Portugal

Phone: 00351 21 4823850 Fax: 00351 21 4823859

e-mail: [email protected]

For more information about this medication, please contact the local representative of the marketing authorization holder in Spain:

Pharmis Biofarmacéutica, S.L.

C/ General Yagüe, nº 52, piso 1º D, 28020 - Madrid.

Phone: 91 640 22 88

Fax: 91 640 08 45

Responsible manufacturer

Alfasigma S.p.A.

Via Enrico Fermi 1,

65020 Alanno (PE)

Italy

This leaflet was approved in March 2023

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.