SODIUM COLISTIMETHATE ACCORD 1 Million IU POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

2. What you need to know before you use Sodium Colistimethate Accord

Do not use Sodium Colistimethate Accord

• 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 sodium colistimethate

• If you have or have had kidney problems
• If you suffer from myasthenia gravis
• If you suffer from porphyria
• If you suffer from asthma (when used by inhalation route).
• 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, caution should be exercised when using sodium colistimethate because the kidneys are not yet fully developed.

Use of Sodium Colistimethate Accord with other medicines

• medicines that may affect how your kidneys work. Taking these medicines at the same time as sodium colistimethate may increase the risk of kidney damage
• medicines that may affect the nervous system. Taking these medicines at the same time as sodium colistimethate may increase the risk of side effects on your nervous system
• medicines called muscle relaxants, often used during general anesthesia. Sodium colistimethate may increase the effects of these medicines. If you are going to be given a general anesthetic, inform your anesthesiologist that you are using sodium colistimethate.

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 this medicine increases the risk of muscle weakness and breathing difficulties.

Receiving sodium colistimethate by infusion at the same time as receiving sodium colistimethate by inhalation may increase your risk of side effects.

Pregnancy, breastfeeding, and fertility

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

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

Breastfeeding should be interrupted during treatment with this medicine, as this medicine may pass into breast milk.

Driving and using machines

Sodium Colistimethate Accord may cause dizziness, confusion, or vision problems, so you should not drive or use any tool or machinery in these cases.

Sodium Colistimethate Accord contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per dose, which is essentially "sodium-free"

3. How to use Sodium Colistimethate Accord

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist.

• Intravenous route:

Your doctor has prescribed sodium colistimethate as 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 very ill, you will be given a larger dose, 9 million units, once at the start 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 who weigh 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 monitor your kidney function regularly while you are receiving sodium colistimethate.

• Inhalation route:

The usual dose in adults, adolescents, and children over 2 years 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 is 0.5-1 million units, twice a day (up to 2 million units per day).

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

If you use more Sodium Colistimethate Accord than you should:

If you have used more Sodium Colistimethate Accord than you should, you may have breathing problems, muscle weakness, and kidney problems.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or nurse immediately, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to use Sodium Colistimethate Accord:

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

In case you are receiving this medicine by intravenous route and as long as it has not been more than 3 hours since the time you should have received your dose, you can ask to be given the corresponding dose. If more than 3 hours have passed since 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 stop treatment with Sodium Colistimethate Accord

Your doctor will indicate the duration of treatment with Sodium Colistimethate Accord. Do not stop treatment before, as there is a risk that the infection will recur.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

The side effects observed have been classified by organs and systems and by frequencies using the following convention: very common (may affect more than 1 in 10 people); common (may affect up to 1 in 10 people); uncommon (may affect up to 1 in 100 people); rare (may affect up to 1 in 1,000 people); very rare (may affect up to 1 in 10,000 people); frequency not known (cannot be estimated from the available data).

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

Possible side effects after intravenous administration:

Nervous system disorders

• Very common: Tingling or numbness around the lips and face, headache.
• Unknown: Difficulty speaking, visual disturbances, confusion, mental changes or flushing (redness of the face), psychosis, dizziness, vertigo, difficulty controlling movements.

Renal and urinary disorders

• Very common: This medicine may affect the kidneys, especially if the dose is high or you are taking other medication that may affect the kidneys (including increased results of certain special kidney tests, such as urea and creatinine).
• Rare: Kidney failure.

General disorders and administration site conditions

• Very common: Muscle weakness, itching.
• Unknown: Allergic reactions such as skin rashes or swelling (of lips, mouth, throat). If this happens, tell your doctor immediately because it may be necessary to stop treatment. 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

Possible side effects after inhalation administration:

Respiratory, thoracic, and mediastinal disorders

• Very common: Nebulization of this medicine may cause cough and wheezing, and may cause chest tightness, wheezing, or shortness of breath in some people.

General disorders and administration site conditions

• Unknown: Allergic reactions such as skin rashes. If this happens, tell your doctor immediately because it may be necessary to stop treatment. Sore throat and irritation in the mouth that may be due to allergy to the medicine or an additional fungal infection when this medicine is administered through a nebulizer.

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects 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. Storage of Sodium Colistimethate Accord

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

Do not use this medicine after the expiry date which is stated on the carton as "EXP". The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Sodium Colistimethate Accord does not contain preservatives. After preparation, it should be used immediately. Solutions for injection diluted with more volume than the original vial volume and/or with a concentration <80,000 IU/ml should be used immediately, as sodium colistimethate is significantly hydrolyzed below this concentration.

In case of intrathecal and intraventricular administration, the volume of solution administered should not exceed 1 ml (reconstituted concentration of 125,000 IU/ml). The reconstituted solution should be administered immediately.

Any remaining solution should be discarded.

Do not use this medicine if you notice any signs of deterioration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Sodium Colistimethate Accord

• The active substance is sodium colistimethate.

Each vial contains 1 million international units (IU) of sodium colistimethate, which weighs approximately 80 milligrams (mg) of sodium colistimethate.

• There are no other ingredients.

Appearance and pack contents

Sodium Colistimethate Accord is a white to off-white powder supplied in a glass vial.

The powder must be dissolved in a solution for injection or infusion.

Sodium Colistimethate Accord is supplied in packs of 10 vials.

Marketing authorization holder

Accord Healthcare, S.L.U.

Moll de Barcelona s/n,

World Trade Center Edifici Est 6ªplanta

08039 Barcelona

Manufacturer

Xellia Pharmaceuticals ApS

Dalslandsgade 11

2300 Copenhagen S

Denmark

Date of last revision of this leaflet: June 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.es/.

The following information is intended exclusively for healthcare professionals:

• Intravenous route:

For bolus injection:

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

For infusion:

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

Reconstitute the vial contents with water for injection or sodium chloride 9 mg/ml (0.9% solution). The reconstituted Sodium Colistimethate is a clear and particle-free solution. Discard the solution if particles are observed.

When using the intrathecal and intraventricular routes of administration, the administered volume should not exceed 1 ml (reconstituted concentration of 125,000 IU/ml).

• Inhalation route with nebulizer:

Reconstitute the vial contents with water for injection, with a 50:50 mixture of water for injection and sodium chloride 0.9%, or with sodium chloride 9 mg/ml (0.9% solution).

The reconstitution volume will be adjusted according to the instructions for use provided with the nebulizer device and normally does not exceed 4 ml.

Once reconstituted, Sodium Colistimethate Accord can be administered with any conventional nebulizer suitable for the administration of antibiotic solutions.

The reconstituted Sodium Colistimethate is a clear and particle-free solution. Discard the solution if particles are observed.

The solutions are for single use and any remaining solution should be discarded.