COLISTIMETATO 1000000 IU Порошок для инъекционного/инфузионного раствора

Содержание инструкции

1. Sodium Colistimetate
   1. What is Colistimetato sodico Noridem Ltd and what it is used for
   2. What you need to know before you use Colistimetato sodico Noridem Ltd
   3. How to use Colistimetato sodico Noridem Ltd
   4. Possible side effects
   5. How to store Colistimetato sodico Noridem Ltd
   6. Contents of the pack and other information

Colistimetate Sodium Noridem Ltd 1 million IU powder for solution for injection/infusion
Colistimetate Sodium Noridem Ltd 2 million IU powder for solution for injection/infusion

Sodium Colistimetate

Read this leaflet carefully before you use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If any side effects occur, including possible side effects not listed in this leaflet, ask your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Colistimetate Sodium Noridem Ltd is and what it is used for
• 2. What you need to know before you use Colistimetate Sodium Noridem Ltd
• 3. How Colistimetate Sodium Noridem Ltd is administered
• 4. Possible side effects
• 5. How to store Colistimetate Sodium Noridem Ltd
• 6. Contents of the pack and other information

1. What is Colistimetato sodico Noridem Ltd and what it is used for

This medicine contains the active ingredient colistimetate sodium. Colistimetate sodium is an
antibiotic. It belongs to a group of antibiotics called polymyxins.
This medicine is given by injection to treat some types of serious infections caused
by specific bacteria. It is used when other antibiotics are not suitable.

2. What you need to know before you use Colistimetato sodico Noridem Ltd

Colistimetato sodico Noridem Ltd must not be used

• if you are allergic to colistimetate sodium, colistin or other polymyxins .

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Colistimetato sodico Noridem
Ltd if:

• if you have or have had kidney problems
• if you suffer from myasthenia gravis
• if you suffer from porphyria
• if you suffer from asthma

Children
In newborn and premature babies, particular caution should be exercised when using Colistimetato
sodico Noridem Ltd as their kidneys are not yet fully developed.

Other medicines and Colistimetato sodico Noridem Ltd
Tell your doctor if you are taking, have recently taken or might take any other
medicines.
If you are taking any of the following medicines, you may or may not be able to take
Colistimetato sodico Noridem Ltd. Sometimes other medicines may need to be stopped (even if only
for a short time) or you may need a lower dose of Colistimetato sodico Noridem Ltd or
you may need to be monitored while you are being treated with this medicine.
In some cases, your levels of Colistimetato
sodico Noridem Ltd in the blood may need to be measured from time to time to make sure you are taking the correct dosage.

• Medicines such as antibiotics called aminoglycosides (including gentamicin, tobramycin, amikacin and netilmicin) and cephalosporins which can affect your kidney function. Taking these medicines at the same time as Colistimetato sodico Noridem Ltd may increase the risk of kidney damage (see section 4 of this leaflet).
• Medicines such as antibiotics called aminoglycosides (including gentamicin, tobramycin, amikacin and netilmicin) which can affect your nervous system. Taking these medicines at the same time as Colistimetato sodico Noridem Ltd may increase the risk of side effects to the ear and other parts of your nervous system (see section 4 of this leaflet).
• Medicines called muscle relaxants, often used during general anesthesia. Colistimetato sodico Noridem Ltd may increase the effect of these medicines. If you are going to have general anesthesia, tell your anesthesiologist that you are taking Colistimetato sodico Noridem Ltd. If you suffer from myasthenia gravis (muscle weakness) 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 Colistimetato sodico Noridem Ltd may further increase the risk of muscle weakness and difficulty breathing.

Taking Colistimetato sodico INH Noridem via infusion at the same time as
administration of Colistimetato sodico INH Noridem by inhalation may increase the risk of
side effects.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are
breastfeeding, ask your doctor for advice before taking this medicine.
Small amounts of Colistimetato sodico Noridem Ltd are excreted in breast milk, therefore,
breastfeeding is not recommended. If you cannot stop breastfeeding while taking Colistimetato
sodico Noridem Ltd, you should carefully monitor your baby for any symptoms of illness and
inform the doctor if you notice any abnormalities.
There is no data available on the possible impact of colistimetate sodium on human fertility.

Driving and operating machinery
When Colistimetato sodico Noridem Ltd is given intravenously, there may be side effects
such as dizziness, confusion or vision problems. If these occur, you should not drive or operate
machinery.

Colistimetato sodico Noridem Ltd contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, which means that it is
essentially ‘sodium-free’.

3. How to use Colistimetato sodico Noridem Ltd

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
Depending on the reason (see paragraph 1 on this leaflet), Colistimetato sodico Noridem Ltd may be
administered by rapid injection (for over 5 minutes using a special tubing into a vein)
or slow injection (infusion ranging from more than 30 minutes to 60 minutes) into a vein. Colistimetato
sodico Noridem Ltd may occasionally be administered by injection into the
brain or spinal cord.
The recommended daily dose in adults is 9 million units, divided into two or three doses. If you feel
unwell, you will be given a higher dose of 9 million units at the beginning of treatment.
In some cases, your doctor may decide to administer a higher daily dose of up to
12 million units.
The recommended dose in children up to 40 kg of weight is from 75,000 to 150,000 units per kg of body
weight, divided into three doses. Higher dosages have been occasionally administered in cases of
cystic fibrosis.
Children and adults with kidney problems, including patients undergoing dialysis, typically receive lower dosages.
Your doctor will monitor your kidney function regularly while you receive Colistimetato sodico
Noridem Ltd.
Method of administration
Intravenous, intrathecal or intraventricular use.
Colistimetato sodico Noridem Ltd is administered to you by your doctor as an intravenous infusion
over 30 - 60 minutes or by injection over a minimum of 5 minutes. Colistimetato sodico Noridem Ltd is
mainly administered in hospital. If you are medicating yourself at home, your doctor or
nurse will show you how to dissolve the powder and inject the correct dosage of the solution.
Duration of treatment
Your doctor will decide how long the treatment should last based on the severity of the infection.
When treating bacterial infections it is important to complete the treatment in its entirety, so
as to avoid worsening of the existing infection.

If you take more Colistimetato sodico Noridem Ltd than you should
If you think you have taken too much Colistimetato sodico Noridem Ltd, you should contact your doctor or
nurse immediately for advice or, if they are not available, contact or go to the nearest emergency
room.
If too much Colistimetato sodico Noridem Ltd is accidentally administered, the side
effects may be serious and include kidney problems, muscle weakness and difficulty in (or
even cessation of) breathing.

If you forget to take Colistimetato sodico Noridem Ltd
If you are taking the medicine personally and forget a dose, take the forgotten dose as soon as
you remember and then take the next dose 8 hours later if you are using Colistimetato sodico
Noridem Ltd three times a day, or 12 hours apart if you are taking Colistimetato sodico Noridem
Ltd twice a day. Then continue as explained. Do not take a double dose to
make up for a missed dose.
If you are receiving treatment in hospital or at home by a doctor or nurse and think that
you may have missed a dose or received too much Colistimetato sodico Noridem Ltd, please
ask your doctor or nurse for clarification.

If you stop taking Colistimetato sodico Noridem Ltd
Do not stop treatment early unless directed by your doctor. Your doctor
will decide the duration of treatment.
If you have any doubts about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
When Colistimetato sodico Noridem Ltd is given intravenously, it is possible to experience
an allergic reaction.
Severe allergic reactions can also occur with the first dose and may include rapid
development of skin rash, swelling of the face, tongue and neck, difficulty breathing due to
narrowing of the airways and loss of consciousness.

If you experience signs of an allergic reaction, you should seek immediate medical attention.
Less severe allergic reactions include skin rashes that appear later during the
treatment.
Side effects affecting the nervous system are more likely to occur
when the dose of Colistimetato sodico Noridem Ltd is too high, in patients with poor
kidney function or who are also taking muscle relaxants and other medicines with similar effects on
nerve function. The most serious of these possible side effects on the nervous system is
inability to breathe due to paralysis of the chest muscles.

If you have difficulty breathing, you should seek immediate medical attention.
Other possible side effects may include numbness or tingling (especially on the
face), dizziness or loss of balance, rapid changes in blood pressure or blood
flow (including fainting and flushing), slurred speech, confusion and other mental
problems (including loss of sense of reality). Reactions may occur at the injection site, such as
irritation.
Kidney problems may also occur. These are particularly likely in patients with already diseased kidneys, or to whom Colistimetato sodico Noridem Ltd is administered simultaneously with
other drugs that can cause side effects at the kidney level or who receive treatments at doses
too high. These problems usually improve with discontinuation of treatment or if the
dose of Colistimetato sodico Noridem Ltd is reduced.

Reporting of side effects
If you get any side effects, even if not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national reporting system
at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Colistimetato sodico Noridem Ltd

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the
pack after “EXP”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Reconstituted / diluted solution:
The hydrolysis of colistimetate is significantly increased when reconstituted and diluted below
its critical micellar concentration of approximately 80,000 IU per ml. Solutions below this
concentration should be used immediately.
For bolus injection solutions, the chemical and physical stability in use of the reconstituted solution in the
original vial, with a concentration ≥ 80,000 IU/ml, has been demonstrated for:

• 1 MUI for 3 hours at 2-8°C when dissolved in 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or water for injection.
• 2 MUI for 3 hours at 2-8°C when dissolved in 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or water for injection.

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 user is responsible for the period and conditions of
storage of the product.
Infusion solutions, which have been diluted beyond the original volume of the vial and/or with a
concentration < 80,000 IU/ml must be used immediately.
For intrathecal and intraventricular administration solutions, the reconstituted medicinal
product must be used immediately.
Visually inspect the solution for the presence of particulate matter before
administration. Only a clear and practically particle-free solution should be
used.
Any remaining solution must be discarded.
Do not dispose of any medicine in the drain . Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Colistimetato sodico Noridem Ltd contains
The active ingredient is sodium colistimate.
Each vial contains 1 million IU of sodium colistimate.
Each vial contains 2 million IU of sodium colistimate.
There are no other ingredients.

Description of the appearance of Colistimetato sodico Noridem Ltd and contents of the pack
Colistimetato sodico Noridem Ltd powder for solution for injection/infusion, is supplied in the form
of white or off-white powder in vials for single dose.
for 1 million IU: Clear glass vial type I closed with bromobutyl rubber stopper type I of
20 mm and sealed with white 20 mm tear-off cap and aluminum disc.
for 2 million IU: Clear glass vial type I closed with bromobutyl rubber stopper type I of 20
mm and sealed with orange 20 mm tear-off plastic cap and aluminum disc.
Pack size: 1, 10 and 30 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Noridem Enterprises Limited
Evagorou & Makariou, Mitsi Building 3, Office 115,
1065 Nicosia, Cyprus

Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY,
14568 Krioneri, Attiki, Greece,

Τ:+30 210 8161802, F:+30 210 8161587.

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
Germany Colistimethat-Natrium Noridem 1 Million I.E. Pulver zur Herstellung einer
Injektions-/Infusionslösung
Colistimethat-Natrium Noridem 2 Millionen I.E. Pulver zur Herstellung
einer Injektions-/Infusionslösung
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 Κόνις για ενέσιμο διάλυμα/ διάλυμα προς έγχυση
KOLELANG 2 MIU Κόνις για ενέσιμο διάλυμα/ διάλυμα προς έγχυση
Austria Colistimethat-Natrium DEMO 1 Mio. I.E. Pulver zur Herstellung einer
Injektions-/Infusionslösung
Colistimethat-Natrium DEMO 2 Mio. I.E. Pulver zur Herstellung einer
Injektions-/Infusionslösung
Poland Colistimethatum natricum Noridem
Colistimethatum natricum Noridem
Slovakia Colistimethate Noridem 1 MIU Prášok na injekčný/infúzny roztok
Colistimethate Noridem 2 MIU Prášok na injekčný/infúzny roztok
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The following information is intended only for physicians or healthcare professionals:

Preparation and handling
Instructions for preparing the solution for injection / infusion

For bolus injection:
Reconstitute the contents of the vial with no more than 10 ml of water for injections or sodium chloride
solution 9 mg/ml (0.9%) for injections.

For infusion:
The reconstituted contents of the vial can be diluted, typically with 50 ml of sodium chloride
solution 9 mg/ml (0.9%) for injections.

For intrathecal / intracerebroventricular use:
When intrathecal and intracerebroventricular routes of administration are used, the volume
administered must not exceed 1 ml (reconstituted concentration 125,000 IU/ml)
After reconstitution, the solution is clear and colourless or no longer more coloured than a Y6
solution free from visible particles.
Solutions are for single use only and any remaining solution must be discarded.
The medicinal product must be visually inspected before use (even after dilution). Only
clear and practically particle-free solutions must be used.

Incompatibilities
Infusion and injection solutions mixed containing sodium colistimate.

Posology and method of administration
Posology
The dose is expressed in international units (IU) of sodium colistimate (CMS). A conversion table from CMS to IU to mg of CMS as well as to mg of colistin base activity (CBA) is
included at the end of this section.
The following dosage recommendations are based on limited population-pharmacokinetic data
in critically ill patients:

Adults and adolescents
Maintenance dose of 9 million IU/day divided into 2-3 doses
In critically ill patients, an initial dose of 9 million IU should be administered.
The most appropriate time interval to the first maintenance dose has not been established.
Models suggest that initial and maintenance doses up to 12 million IU may be
necessary, in some cases, in patients with good renal function. Clinical experience with such
dosages is however extremely limited, and safety has not been established.
The initial dose applies to patients with normal and impaired renal function, including patients
receiving renal replacement therapy.

Special populations

Elderly
No dosage adjustment is considered necessary in elderly patients with normal renal
function.

Renal impairment
In case of renal impairment, dosage adjustment is necessary, but the pharmacokinetic data
available for patients with renal impairment are very limited.
The following dosage adjustments are suggested as a guide.
A dose reduction is recommended for patients with creatinine clearance < 50 ml/min:
A twice-daily dose is recommended
Hemodialysis and continuous hemo(dia)filtration
Colistin appears to be dialyzable by conventional hemodialysis and continuous venovenous
hemo(dia)filtration (CVVHF, CVVHDF). There are extremely limited data from population PK studies from a very small number of patients receiving renal replacement therapy. No
firm recommendations can be provided. The following regimens should be considered.
Hemodialysis (HD)
Days without HD: 2.25 million IU/day (2.2-2.3 million IU/day).

Days of HD: 3 million IU/day on days of hemodialysis, to be administered after the HD session.
A twice-daily dose is recommended.
CVVHF/ CVVHDF
As in patients with normal renal function. A three times daily dose is recommended

Hepatic impairment
There are no data on patients with hepatic impairment. Caution is recommended when
administering sodium colistimate in these patients.

Paediatric population
The data supporting the dosage regimen in paediatric patients are very limited. Renal maturity
must be taken into consideration when selecting the dosage. The dosage should be
based on lean body mass.

Children ≤ 40kg

• 75,000-150,000 IU/kg/day divided into 3 doses.

For children weighing more than 40 kg, the use of the recommended dosage for adults should be considered.
The use of doses >150,000 IU/kg/day has been reported in children with cystic fibrosis.
There are no data regarding the use or initial dose amount in critically ill children.
Dosage recommendations have not been established in children with renal impairment.

Intrathecal and intracerebroventricular administration
Based on limited data, the following dose is recommended in adults:
Intracerebroventricular route

• 125,000 IU/day

Doses administered via the intrathecal route should not exceed those recommended for intracerebroventricular use.
Specific dosage recommendations cannot be provided for children for the intrathecal and intracerebroventricular routes of administration.
Method of administration
Colistimetato sodico Noridem Ltd is administered intravenously as a slow infusion over 30 - 60
minutes.
Patients with a totally implanted venous access device (TIVAD) in place may
tolerate bolus injections of up to 2 million units in 10 ml administered over a minimum period of 5
minutes.
Colistimate undergoes hydrolysis forming the active substance colistin in aqueous solution. For preparation of the dose, in particular when combining more vials, the reconstitution of the required dose must be carried out using strictly aseptic techniques.

Dosage conversion table:
In the EU, the dose of sodium colistimate (CMS) must be prescribed and administered
exclusively as IU. The product label indicates the number of IU per vial.
Confusion and medical errors have occurred due to the different expression of dosage in
terms of potency. The dose is expressed in the USA, and other parts of the world, in milligrams of colistin base activity (mg CBA).
The following conversion table has been prepared for informational purposes and the values should be
considered exclusively nominal and approximate.

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

Overdosage

Symptoms
Overdosage may result in neuromuscular blockade which may lead to muscle weakness,
apnea and possible respiratory arrest. Overdosage may also cause acute renal failure
characterised by decreased urine output and increased serum BUN and creatinine concentration.

Treatment
There is no specific antidote, manage with supportive treatment. Measures to
increase the elimination rate of colistin, e.g. mannitol for diuresis, prolonged hemodialysis or peritoneal dialysis, can be attempted, but the effectiveness is unknown.