COLIXIN 1 IU POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Colixin 1 MIU Powder for Solution for Injection

Sodium Colistimethate

The active substance is sodium colistimethate. Each vial contains 1 million International Units (IU), which is equivalent to approximately 80 mg of sodium colistimethate. It does not contain any other ingredients.

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you experience any serious side effects or any side effect not mentioned in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the Package Leaflet:

1. What is COLIXIN and what is it used for
2. Before you use COLIXIN
3. How to use COLIXIN
4. Possible side effects

5 Conservation of COLIXIN

1. Additional information

1. What is Colixin and what is it used for

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

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as the flu or the common cold.

It is important that you follow the instructions regarding dosage, administration interval, and treatment duration indicated by your doctor.

Do not store or reuse this medicine. If you have any leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Do not throw away medicines via wastewater or household waste.

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

Colixin is administered by inhalation to treat chronic respiratory infections in patients with cystic fibrosis. Colixin is used when such infections are caused by a specific bacterium called Pseudomonas aeruginosa.

2. Before you use Colixin

Do not use Colixin:

• If you are allergic (hypersensitive) to sodium colistimethate, 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 need treatment with other antibiotics that may also damage the kidneys or cause cerebral disorders such as dizziness or visual disturbances.
  • If you have cystic fibrosis, you may receive this medicine by inhalation. In this case, coughing and bronchospasm (difficulty breathing) may occur, which is why the first administration by 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 disease known as pseudo-Bartter syndrome.

In premature infants and newborns, special caution should be exercised when using Colixin because the kidneys are not yet fully developed.

Using Colixin with other medicines

• medicines that may affect kidney function. Taking these medicines at the same time as Colixin may increase the risk of kidney damage
• medicines that may affect the nervous system. Taking these medicines at the same time as Colixin may increase the risk of adverse effects on your nervous system
• medicines called muscle relaxants, often used during general anesthesia. Colixin may increase the effects of these medicines. If you are going to be administered 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, or ciprofloxacin), taking Colixin increases the risk of muscle weakness and respiratory difficulties.

Receiving Colixin by perfusion at the same time as receiving Colixin by inhalation may increase your risk of experiencing side effects.

Pregnancy and breastfeeding

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

If administered to a breastfeeding woman, the patient should stop breastfeeding while receiving Colixin.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

Colixin may cause dizziness, confusion, or visual problems, which is why you should not drive or use any tool or machinery that may be hazardous in these cases.

Colixin contains sodium

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

3. How to use Colixin

Follow your doctor's instructions for administering Colixin exactly.

Consult your doctor if you have any doubts. Remember to take your medicine. Your doctor will indicate the duration of treatment with Colixin. Do not stop treatment before completing it, as there is a risk that the infection may recur.

Colixin can be administered systemically by intravenous route (perfusion or single injection) or by inhalation route, using a nebulizer.

• Intravenous route

Your doctor has prescribed Colixin as a perfusion 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 severely ill, you will be administered a larger dose, 9 million units, once at the beginning of treatment.

In some cases, your doctor may decide to give you a higher daily dose, 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 been administered occasionally.

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

Your doctor will regularly monitor your kidney function while you are receiving Colixin.

• Inhalation route

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

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

If the patient receives other care for cystic fibrosis, such as physiotherapy or other treatments administered by inhalation (e.g., bronchodilators), it should be remembered that sodium colistimethate should be administered after them.

In any case, if there is an alteration of kidney function, it will be necessary to adjust the dose, i.e., decrease the dose and/or prolong the administration interval.

If you use more Colixin than you should

If you have used more Colixin than you should, you may experience breathing problems, 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 medicine and the amount ingested.

If you forget to use Colixin

Do not administer a double dose to make up for forgotten doses.

If you are receiving this medicine by intravenous route and it has not been more than 3 hours since the time you should have received your dose, you can ask to be administered the corresponding dose. If more than 3 hours have passed after the forgotten dose, wait until the next administration.

In the case of inhalation administration, 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.

4. Possible side effects

Like all medicines, Colixin can cause side effects, although not everybody gets them.

In the case of sodium colistimethate, these affect mainly the nervous system and kidney function. The most frequent side effects after nebulization are coughing and difficulty breathing.

Nervous system disorders

Numbness or tingling around the lips and face, dizziness, difficulty speaking, visual disturbances, confusion, mental changes, or flushing (redness of the face).

Respiratory disorders

Nebulization of Colixin through a nebulizer can cause coughing and may cause chest tightness, wheezing, or a feeling of shortness of breath in some people.

Kidney and urinary disorders

Colixin may affect the kidneys, especially if the dose is high or you are taking other medication that may affect the kidneys.

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 stop treatment.

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

After intravenous administration, you may experience the following symptoms that may be related to a disease known as 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 an allergic reaction to the medicine or an added fungal infection.

Reporting of side effects:

If you experience any side effect, tell your doctor or pharmacist or nurse, even if it is possible that it is not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Colixin

Keep out of the reach and sight of children.

Store below 25°C. Protect from light.

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

Do not use Colixin if you notice any visible signs of deterioration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package contents and additional information

Instructions for use and handling.

Systemic administration

For bolus injection:

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

For perfusion:

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

For intrathecal and intraventricular use:

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

A visual inspection should be performed to detect the presence of particles in the solution before administration and discard it if particles are present.

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

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

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

Solutions below this concentration should be used immediately.

In solutions for bolus injection or nebulization, chemical and physical stability of the reconstituted solution in the original vial has been demonstrated for 24 hours in the range of 2 to 8°C.

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

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

In solutions for perfusion, which have been diluted more than the original vial volume and/or with a concentration <80,000 IU/ml, they should be used immediately.

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

Nebulization

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

The reconstitution volume should be in accordance with the instructions for use of the nebulizer device and is normally no more than 4 ml.

The solution may be slightly turbid and may form foam when shaken. It is generally preferable to administer Colixin using jet or ultrasonic nebulizers, as they produce respirable solutions with particle diameters between 0.5-5.0 micras when administered with a suitable compressor. The manufacturer's instructions for maintenance and care of the nebulizer and compressor should be followed.

It is likely that some of the nebulized medicine will be released into the environment. To avoid the discarded aerosol passing into the environment, a filter can be fitted. Colixin should be administered in a well-ventilated room.

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

Composition of Colixin

• The active substance is sodium colistimethate.
• It does not contain any other ingredients.

Appearance and package contents

Colixin is presented in vials containing powder for solution for injection/nebulization. It is available in packages containing 10 or 30 vials.

Expiration date

Do not use Colixin after the expiration date stated on the packaging.

Marketing authorization holder and manufacturer

Pharmis Biofarmacêutica, Lda.

Praceta do Farol, 77

2750-610 Cascais

Portugal

Tel.: 00351 21 4823850 Fax: 00351 21 4823859

e-mail: [email protected]

You can request more information about this medicine by contacting the local representative of the marketing authorization holder in Spain:

Pharmis Biofarmacéutica, S.L.

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

Tel.: 91 640 22 88

Fax: 91 640 08 45

Manufacturer

Alfasigma S.p.A.

Via Enrico Fermi 1,

65020 Alanno (PE)

Italy

This leaflet was approved in March 2023

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.