COLISTIMETHATUM 1000000 IU Powder

Contents of the leaflet

1. LEAFLET SUPPLIED WITH THE PACKAGING
2. Leaflet supplied with the packaging: Information for the patient
   1. Before taking the medicine, carefully read the contents of the leaflet, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Colistimethate sodium Noridem and what is it used for
4. Important information before taking Colistimethate sodium Noridem
   1. When not to take Colistimethate sodium Noridem
   2. Warnings and precautions
   3. Children
   4. Colistimethate sodium Noridem and other medicines
   5. Pregnancy, breastfeeding, and fertility
   6. Driving and using machines
   7. Colistimethate sodium Noridem contains sodium
5. How to take Colistimethate sodium Noridem
   1. Using a higher dose of Colistimethate sodium Noridem than recommended
   2. Missing a dose of Colistimethate sodium Noridem
   3. Stopping treatment with Colistimethate sodium Noridem
6. Possible side effects
   1. In case of allergic reactions, the patient should immediately seek medical attention.
   2. In case of breathing difficulties, the patient should immediately seek medical attention.
   3. Reporting side effects
7. How to store Colistimethate sodium Noridem
8. Contents of the packaging and other information
   1. What Colistimethate sodium Noridem contains
   2. What Colistimethate sodium Noridem looks like and contents of the pack
   3. Marketing authorization holder:
   4. Manufacturer:
   5. This medicine is authorized in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the leaflet:
   7. Preparation and handling
   8. Instructions for preparation of the solution for injection/infusion
   9. Incompatibilities
   10. Dosage and administration
   11. Conversion table for colistimethate sodium
   12. Overdose

LEAFLET SUPPLIED WITH THE PACKAGING

Leaflet supplied with the packaging: Information for the patient

Colistimethate sodium Noridem, 1,000,000 IU, powder for solution for injection/infusion
Colistimethate sodium Noridem, 2,000,000 IU, powder for solution for injection/infusion
Colistimethate sodium

Before taking the medicine, carefully read the contents of the leaflet, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• If the patient experiences any adverse reactions, they should contact their doctor. This also applies to any adverse reactions not listed in this leaflet. See section 4.

Table of contents of the leaflet

• 1. What is Colistimethate sodium Noridem and what is it used for
• 2. Important information before taking Colistimethate sodium Noridem
• 3. How to take Colistimethate sodium Noridem
• 4. Possible side effects
• 5. How to store Colistimethate sodium Noridem
• 6. Contents of the packaging and other information

1. What is Colistimethate sodium Noridem and what is it used for

This medicine contains the active substance colistimethate sodium. Colistimethate sodium is an antibiotic belonging to a group of antibiotics called polymyxins.
This medicine is given by injection to treat certain types of severe infections caused by specific bacteria. The medicine is used when other antibiotics are not indicated.

2. Important information before taking Colistimethate sodium Noridem

When not to take Colistimethate sodium Noridem

• -if the patient is allergic to colistimethate sodium, colistin, or other polymyxins .

Warnings and precautions

Before starting treatment with Colistimethate sodium Noridem, the patient should discuss it with their doctor, pharmacist, or nurse if:

• the patient has or has had kidney problems
• the patient has myasthenia gravis
• the patient has porphyria
• the patient has asthma

If the patient experiences muscle spasms, fatigue, or increased urine production, they should immediately inform their doctor, as these events may be related to a condition known as pseudo-Bartter syndrome.

Children

In premature infants and newborns, particular caution should be exercised when using Colistimethate sodium Noridem, as their kidneys are not yet fully developed.

Colistimethate sodium Noridem and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
If the patient is taking any of the listed medicines, they may or may not be able to take them at the same time as Colistimethate sodium Noridem. In some cases, the doctor may decide to discontinue the use of other medicines (for a certain period) or may reduce the dose of Colistimethate sodium Noridem; it may also be necessary to monitor the patient during treatment with this medicine. In some cases, it may be necessary to control the concentration of Colistimethate sodium Noridem in the blood to ensure that the patient is taking the correct dose.

• Aminoglycoside antibiotics (such as gentamicin, tobramycin, amikacin, and netilmicin) and cephalosporins may affect kidney function. Taking these medicines and Colistimethate sodium Noridem at the same time may increase the risk of kidney damage (see section 4 of this leaflet).
• Aminoglycoside antibiotics (including gentamicin, tobramycin, amikacin, and netilmicin) and cephalosporins may affect the nervous system. Taking such medicines at the same time as Colistimethate sodium Noridem may increase the risk of adverse reactions in the ear and other parts of the nervous system (see section 4 of this leaflet).
• Muscle relaxants, often used during general anesthesia. Colistimethate sodium Noridem may enhance the effect of these medicines. If the patient is to undergo general anesthesia, they should inform the anesthesiologist that they are taking Colistimethate sodium Noridem.

If the patient has myasthenia gravis (muscle weakness) and is also taking other antibiotics called macrolides (such as azithromycin, clarithromycin, or erythromycin) or antibiotics called fluoroquinolones (such as ofloxacin, norfloxacin, and ciprofloxacin), taking Colistimethate sodium Noridem increases the risk of muscle weakness and breathing difficulties.
Taking Colistimethate sodium Noridem by infusion at the same time as taking Colistimethate sodium Noridem by inhalation may increase the risk of adverse reactions.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
Small amounts of Colistimethate sodium Noridem pass into breast milk, so breastfeeding is not contraindicated during treatment. If the patient cannot stop breastfeeding while taking Colistimethate sodium Noridem, they should carefully observe their child for signs of illness and inform their doctor if they notice any concerning symptoms.
There is no data on the effect of colistimethate sodium on human fertility.

Driving and using machines

When Colistimethate sodium Noridem is administered intravenously, adverse reactions such as dizziness, confusion, or vision disturbances may occur. If these adverse reactions occur, the patient should not drive or operate machinery.

Colistimethate sodium Noridem contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per vial, which means the medicine is considered "sodium-free).

3. How to take Colistimethate sodium Noridem

This medicine should always be used as directed by a doctor or pharmacist. If in doubt, the patient should consult their doctor or pharmacist.
Depending on the indication (see section 1 of this leaflet), Colistimethate sodium Noridem can be administered by rapid injection (lasting over 5 minutes into a special tube in a vein) or slow injection (infusion lasting approximately 30 to 60 minutes) into a vein. In some cases, Colistimethate sodium Noridem may be administered by injection into the spinal canal or brain (intrathecal administration).
The usual daily dose for adults is 9,000,000 IU in 2-3 divided doses. In cases of severe illness, a larger initial dose of 9 million units may be administered at the start of treatment.
In some cases, the doctor may decide to administer a higher daily dose of up to 12 million units.
The usual daily dose in children with a body weight of up to 40 kg is 75,000 to 150,000 IU/kg body weight, divided into 3 doses. In cases of cystic fibrosis, higher doses have been administered.
Children and adults with kidney problems, including those on dialysis, usually receive lower doses. While taking Colistimethate sodium Noridem, the doctor will regularly check the patient's kidney function.
Administration method
Intravenous, intrathecal, or intraventricular administration
Colistimethate sodium Noridem is administered by a doctor in an intravenous infusion over 30-60 minutes or by intravenous injection over at least 5 minutes. Colistimethate sodium Noridem is mainly administered in hospitals. If the patient is being treated at home, the doctor or nurse should demonstrate how to dilute the powder and inject the correct dose of the solution.
Duration of treatment
The doctor will decide how long the treatment should last, depending on the severity of the infection.
In the treatment of bacterial infections, it is essential to complete the full treatment cycle to prevent the worsening of the existing infection.

Using a higher dose of Colistimethate sodium Noridem than recommended

If the patient thinks they have taken a dose of Colistimethate sodium Noridem higher than recommended, they should immediately inform their doctor or nurse. If it is not possible to contact a doctor or nurse, the patient should contact the nearest emergency department or go to the nearest hospital emergency department.
Unintentional administration of an excessive dose of Colistimethate sodium Noridem may cause serious adverse reactions, such as kidney function disorders, muscle weakness, and breathing difficulties (or even cessation of breathing).

Missing a dose of Colistimethate sodium Noridem

In case of missing a dose during self-treatment, the patient should take the missed dose as soon as possible and then take the next dose after 8 hours if Colistimethate sodium Noridem is administered in three doses per day, or after 12 hours if Colistimethate sodium Noridem is administered in two doses per day.
Then, the patient should continue with the regular administration of the medicine. The patient should not take a double dose to make up for the missed dose.
If the patient is being treated in a hospital or at home by a doctor or nurse and thinks they may have missed a dose or received too much Colistimethate sodium Noridem, they should ask their doctor or nurse.

Stopping treatment with Colistimethate sodium Noridem

The patient should not stop treatment prematurely unless their doctor advises them to do so. The doctor will decide how long the treatment should last.
If the patient has any further doubts about taking this medicine, they should consult their doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
After intravenous administration of Colistimethate sodium Noridem, patients may experience allergic reactions.
Severe allergic reactions may occur immediately after the first dose of the medicine and may include symptoms such as sudden development of a rash, swelling of the face, tongue, and throat, difficulty breathing due to constriction of the airways, and loss of consciousness.

In case of allergic reactions, the patient should immediately seek medical attention.

Milder hypersensitivity reactions include skin rashes, which may appear later in the course of treatment.
After intravenous administration, the following symptoms may occur, which may be related to a condition known as pseudo-Bartter syndrome (see section 2):

• muscle spasms
• increased urine production
• fatigue

Adverse reactions affecting the nervous system are more likely to occur when the dose of Colistimethate sodium Noridem is too high, in patients with kidney failure, or in patients taking muscle relaxants or other medicines with a similar effect on the nervous system. The most serious adverse reaction affecting the nervous system is the inability to breathe due to paralysis of the chest muscles.

In case of breathing difficulties, the patient should immediately seek medical attention.

Other possible side effects: numbness or tingling (especially around the face), dizziness or loss of balance, sudden changes in blood pressure or blood flow (including fainting and hot flashes), slurred speech, vision problems, confusion, and mental problems (including loss of touch with reality). At the injection site, allergic reactions such as irritation may occur.
Kidney function disorders may also occur. The likelihood of their occurrence is particularly high in patients who already have poor kidney function or are administered Colistimethate sodium Noridem with other medicines that may cause adverse reactions in the kidneys or are administered too high a dose. These problems usually resolve after discontinuation of treatment or reduction of the Colistimethate sodium Noridem dose.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C
02-222 Warsaw,
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Colistimethate sodium Noridem

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton after the expiry date (EXP). The expiry date refers to the last day of the specified month.
This medicine does not require any special storage conditions.
Reconstituted/diluted solution:
Hydrolysis of colistimethate is significantly increased after dissolution and dilution below the critical micellar concentration of approximately 80,000 IU/ml. Solutions below this concentration should be used immediately.
In the case of bolus injection solutions, the chemical and physical stability of the reconstituted solution has been demonstrated in the original vial, at a concentration of ≥80,000 IU/ml for:

• 1,000,000 IU for 3 hours at a temperature of 2-8°C after dilution in 10 ml of sodium chloride injection solution at a concentration of 9 mg/ml (0,9%) or water for injection.
• 2,000,000 IU for 3 hours at a temperature of 2-8°C after dilution in 10 ml of sodium chloride injection solution at a concentration of 9 mg/ml (0,9%) or water for injection.

From a microbiological point of view, if the method of opening/reconstitution/dilution prevents the risk of microbiological contamination, the product should be used immediately.
If the product is not used immediately, the user is responsible for the storage time and conditions.
Solutions for infusion diluted outside the original vial volume and/or at a concentration <80,000 IU/ml should be used immediately.
In the case of solutions for intrathecal or intraventricular administration, the prepared medicinal product should be used immediately.
The solution should be carefully examined before use to ensure it does not contain solid particles. Only clear solutions without solid particles should be used.
Unused solution residues should be discarded.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Colistimethate sodium Noridem contains

The active substance is colistimethate sodium.
One vial contains 1,000,000 IU of colistimethate sodium.
One vial contains 2,000,000 IU of colistimethate sodium.
There are no other ingredients.

What Colistimethate sodium Noridem looks like and contents of the pack

Colistimethate sodium Noridem, powder for solution for injection/infusion, is a white or off-white powder in single-dose vials.
For 1,000,000 IU: A vial made of colorless glass (type I), with a 20 mm bromobutyl rubber stopper (type I) and a 20 mm white plastic pull-off cap and an aluminum seal.
For 2,000,000 IU: A vial made of colorless glass (type I), with a 20 mm bromobutyl rubber stopper (type I) and a 20 mm orange plastic pull-off cap and an aluminum seal.
Pack sizes: 1, 10, and 30 vials
Not all pack sizes may be marketed.

Marketing authorization holder:

Noridem Enterprises Limited, Evagorou & Makariou,
Mitsi Building 3, Office 115, Nicosia 1065, Cyprus

Manufacturer:

DEMO S.A. PHARMACEUTICAL INDUSTRY,
21st km National Road Athens-Lamia, 14568 Krioneri, Attiki, Greece,
T: +30 210 8161802, F: +30 2108161587.

This medicine is authorized in the Member States of the European Economic Area under the following names:

Germany
Colistimethat-Natrium Noridem 1 Million IU Powder for solution for injection/infusion
Colistimethat-Natrium Noridem 2 Million IU Powder for solution for injection/infusion
Ireland
Colistimethate sodium 1 million IU Powder for solution for injection/infusion
Colistimethate sodium 2 million IU Powder for solution for injection/infusion
Czech Republic
Colistimethate Noridem
Colistimethate Noridem
Greece
KOLELANG 1 MIU Powder for injection solution/infusion solution
KOLELANG 2 MIU Powder for injection solution/infusion solution
Austria
Colistimethat-Natrium DEMO 1 Mio. IU Powder for solution for injection/infusion
Colistimethat-Natrium DEMO 2 Mio. IU Powder for solution for injection/infusion
Italy
Colistimetato sodico Noridem Ltd
Colistimetato sodico Noridem Ltd
Poland
Colistimethatum natricum Noridem
Colistimethatum natricum Noridem
Slovakia
Colistimethate Noridem 1 MIU powder for injection/infusion solution
Colistimethate Noridem 2 MIU powder for injection/infusion solution

Date of last revision of the leaflet:

---------------------------------------------------------------------------------------------------------------------------
Information intended for healthcare professionals only:

Preparation and handling

Instructions for preparation of the solution for injection/infusion

For bolus injection:
Dissolve the contents of the vial in no more than 10 ml of water for injection or sodium chloride injection solution at a concentration of 9 mg/ml (0.9%).
For infusion:
After reconstitution, the contents of the vial should be diluted in 50 ml of sodium chloride injection solution at a concentration of 9 mg/ml (0.9%).
For intrathecal or intraventricular administration
In the case of intrathecal and intraventricular administration, the administered volume should not exceed 1 ml (concentration after reconstitution 125,000 IU/ml)
After reconstitution, the solution is clear and colorless or not more intensely colored than a Y6 solution, without visible solid particles.
Solutions are intended for single use only, and any remaining solution should be discarded.
The medicinal product should be carefully examined before use (also after dilution). Only clear solutions without solid particles should be used.

Incompatibilities

Solutions for infusion containing colistimethate sodium should not be mixed with other solutions.

Dosage and administration

Dosage
The dose is expressed in International Units (IU) of colistimethate sodium (CMS).
The following conversion table is provided for information purposes, and the values should be considered only as nominal and approximate.

Conversion table for colistimethate sodium

* Nominal potency of the active substance = 12,500 IU/mg

Overdose

Symptoms
Overdose may result in neuromuscular blockade, which may lead to muscle weakness, apnea, and possible cessation of breathing.
Additionally, colistimethate overdose may cause acute kidney failure, manifested by decreased urine output, increased blood urea nitrogen, and creatinine levels.
Treatment
There is no specific antidote, so symptomatic treatment should be used. Measures to increase the elimination of colistin, such as forced diuresis with mannitol, prolonged hemodialysis, or peritoneal dialysis, may be used, but their effectiveness is unknown.