Colistin Tzf

Leaflet accompanying the packaging: patient information

COLISTIN TZF, 1,000,000 IU, lyophilisate for solution for injection, infusion, and inhalation
Colistimethate sodium

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Colistin TZF and what is it used for
• 2. Important information before using Colistin TZF
• 3. How to use Colistin TZF
• 4. Possible side effects
• 5. How to store Colistin TZF
• 6. Contents of the packaging and other information

1. What is Colistin TZF and what is it used for

Colistin TZF contains the active substance colistimethate sodium (colistin), which belongs to the group of polymyxin antibiotics.

• Colistin TZF is administered by injection to treat certain types of severe infections caused by specific bacteria. Colistin TZF is used when other antibiotics are not suitable.
• Colistin TZF is administered by inhalation to treat chronic lung infections in patients with cystic fibrosis. Colistin TZF is used when these infections are caused by bacteria called Pseudomonas aeruginosa(blue pus bacteria).

2. Important information before using Colistin TZF

When not to use Colistin TZF

• If the patient is allergic (hypersensitive) to colistimethate sodium, colistin, or other polymyxins, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before starting treatment with Colistin TZF, the patient should discuss with their doctor if they have or have had kidney problems - the doctor will adjust the dose accordingly to the degree of kidney impairment;
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if the patient has myasthenia gravis;
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if the patient has porphyria (a rare, usually inherited, metabolic disorder);
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if the patient has asthma.
If the patient experiences muscle spasms, fatigue, or increased urine production, they should inform their doctor immediately, as these events may be related to a condition known as pseudo-Bartter syndrome.
During treatment with Colistin TZF by inhalation, the patient may experience a feeling of chest tightness, breathing difficulties. The doctor usually recommends monitoring blood counts and non-protein nitrogen levels in the blood, especially in patients with kidney impairment, cystic fibrosis, newborns, and patients receiving high doses of the medicine.
Particular caution should be exercised when administering colistimethate sodium to premature infants and newborns, as their kidneys are not yet fully developed.

Colistin TZF and other medicines

The patient should inform their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
In particular, the patient should inform their doctor if they are taking any of the following medicines.

• Medicines that may affect kidney function (e.g., aminoglycoside antibiotics, such as gentamicin, amikacin, tobramycin). Taking such medicines and Colistin TZF at the same time may increase the risk of kidney damage.
• Medicines that may affect the nervous system. Taking such medicines and Colistin TZF at the same time may increase the risk of side effects related to the nervous system.
• Medicines called muscle relaxants, often used during general anesthesia. Colistin TZF may enhance the effect of these medicines. If the patient is to undergo general anesthesia, they should inform the anesthesiologist that they are taking Colistin TZF.

If the patient is taking any of these medicines, the doctor may decide to stop their use during treatment with Colistin TZF, reduce the dose of one of the medicines, or recommend frequent monitoring of colistin levels in the blood.
If the patient has myasthenia gravis 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 Colistin TZF may further increase the risk of muscle weakness and breathing difficulties.
Taking Colistin TZF by infusion at the same time as taking Colistin TZF by inhalation may increase the risk of side effects.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
Colistin TZF should not be used during pregnancy, unless the doctor considers it absolutely necessary.
The medicine is excreted in human milk. In breastfeeding women, it should be used with great caution, only if absolutely necessary.

Driving and using machines

Colistin may cause a decrease in physical and mental performance. If the patient experiences side effects such as dizziness or vision disturbances, they should not drive or operate machines (see section 4, "Possible side effects").

3. How to use Colistin TZF

The dose of the medicine and the duration of treatment will be determined by the doctor, depending on the severity of the infection, the sensitivity of the microorganism causing the infection, the patient's health status, age, and weight.
The patient should not use this medicine on their own.
The medicine will be administered to the patient by a healthcare professional (doctor or nurse), in accordance with the doctor's instructions.

Colistin TZF should not be administered intrathecally or intracardially.

Intravenous and intramuscular administration

Colistin TZF is administered by the doctor, usually intravenously in injections or infusions.
If intravenous administration is not possible, colistimethate sodium can be administered intramuscularly.
The method of administration and preparation of solutions is given at the end of the leaflet in the section intended for healthcare professionals only.
The dose is expressed in international units (IU) of colistimethate sodium. The information intended for healthcare professionals only includes a table for converting the dose of colistimethate sodium, expressed in IU, to colistimethate sodium in mg and to mg of colistin base activity (CBA).
Adults and adolescents
The usual daily dose for adults is 9 million units, divided into two or three doses. If the patient is very ill (critically ill patients), they will be given a larger dose of 9 million units at the start of treatment.
In some cases, the doctor may decide to administer a higher daily dose of up to 12 million units.
Use in children
The usual daily dose for children with a body weight of up to 40 kg is 75,000 to 150,000 units per kilogram of body weight, divided into three doses.
In cystic fibrosis, higher doses have been used.
For children with a body weight over 40 kg, the doctor will consider using the recommendations for adults.
Special patient groups
In patients with impaired kidney function, newborns, and patients with cystic fibrosis, the doctor will recommend frequent monitoring of colistin levels in the blood.
Children and adults with impaired kidney function, including those undergoing dialysis, usually receive lower doses - the dosing recommendations are given at the end of the leaflet in the section intended for healthcare professionals only.
The doctor will regularly monitor kidney function while the patient is receiving Colistin TZF.
Caution should be exercised when administering colistimethate sodium to patients with impaired liver function.

Inhalation administration

The usual dose for adults, adolescents, and children over 2 years of age is 1 to 2 million units, two to three times a day (up to 6 million units per day).
The usual dose for children under 2 years of age is 0.5 to 1 million units, two times a day (up to 2 million units per day).
The doctor may decide to modify the dose, depending on the patient's health status. If the patient is taking other inhaled medicines, the doctor will inform them of the order in which they should be taken.

Method of administration and preparation of solutions

Detailed information is given at the end of the leaflet in the section intended for healthcare professionals - "Information intended for healthcare professionals only".

Use of a higher than recommended dose of Colistin TZF

If the patient thinks they have taken a dose higher than recommended, they should inform their doctor, pharmacist, or nurse as soon as possible.
Overdose of the medicine may lead to an increase in side effects and may be life-threatening. It may be necessary to stop taking the medicine and apply appropriate treatment.

Missing a dose of Colistin TZF

If a dose is missed, the medicine should be administered as soon as possible, if the time to the next dose is long enough, or continue with the regular administration of the medicine.

Do not take a double dose to make up for a missed dose.

Stopping treatment with Colistin TZF

It is important to use the medicine according to the recommended treatment cycle. Do not stop treatment because the patient feels better. If the treatment cycle is stopped too early, the infection may return.

4. Possible side effects

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

• transient sensory disturbances (manifested as facial numbness), dizziness, speech disturbances, vision disturbances, feeling of disorientation, psychoses may occur in patients receiving high doses of the medicine, in patients with kidney impairment, who have not had their dose reduced properly, and in patients receiving muscle relaxants (curare-type) or medicines toxic to the nervous system; reducing the dose of the medicine alleviates the above-mentioned disturbances;
• apnea;
• allergic skin rashes; if a rash appears, the patient should stop taking the medicine and inform their doctor;
• kidney problems; these disturbances usually disappear after stopping the medicine;
• irritation at the injection site, fever.

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.

Side effects that may occur after inhalation:

• bronchospasm;
• throat or mouth pain, caused by hypersensitivity or fungal infection;
• skin rashes caused by hypersensitivity.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 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.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Colistin TZF

The medicine should be stored out of sight and reach of children.
Store in a temperature below 25°C. Protect from light.
Do not use this medicine after the expiry date (EXP) stated on the packaging. The expiry date refers to the last day of the month.
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 Colistin TZF contains

The active substance of the medicine is colistimethate sodium (colistin).
One vial contains 1,000,000 IU (approximately 80 mg) of colistimethate sodium.
The product does not contain other ingredients.

What Colistin TZF looks like and contents of the packaging

Lyophilisate of white or cream color, in the form of a disk or fragments of different sizes.
Packaging:1 vial or 20 vials in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder
Tarchomińskie Zakłady Farmaceutyczne "Polfa" S.A.
ul. A. Fleminga 2,
03-176 Warsaw
Phone number: 22 811 18 14
To obtain more detailed information about this medicine, the patient should contact the marketing authorization holder.
Manufacturer
Tarchomińskie Zakłady Farmaceutyczne "Polfa" S.A.
ul. A. Fleminga 2,
03-176 Warsaw
Manufacturer
LYOCONTRACT GmbH
Pulverwiese 1
38871 Ilsenburg
Germany

Date of last revision of the leaflet:

Information intended for healthcare professionals only

To obtain additional information, see the Summary of Product Characteristics.

Dosing in adult patients with impaired kidney function

No dosing recommendations have been established for children with impaired kidney function.
In adult patients with impaired kidney function, it is necessary to adjust the dose, but the available pharmacokinetic data on patients with impaired kidney function are very limited.
The following method of adjusting the dose is proposed as a guideline.
In patients with creatinine clearance <50 ml min, it is recommended to reduce the dose.
It is recommended to administer the dose twice a day.

million IU = million IU
Hemodialysis and continuous hemofiltration or hemodiafiltration
It appears that colistin is dialyzable by conventional hemodialysis and continuous venovenous hemofiltration or hemodiafiltration (CVVHF, CVVHDF). The available data from population pharmacokinetic studies with a very small number of patients undergoing renal replacement therapy are extremely limited. No exact dosing recommendations can be given. The following schemes can be considered.
Hemodialysis
Days without HD: 2.25 million IU/day (2.2 to 2.3 million IU/day).
Days with HD: 3 million IU on days with hemodialysis, to be administered after the HD session.
It is recommended to administer the dose twice a day.
CVVHF or CVVHDF
As in patients with normal kidney function. It is recommended to administer the dose three times a day.

Method of administration and preparation of solutions

Colistin TZF should not be administered intrathecally or intracardially

Intravenous administration

Colistimethate sodium is usually administered in an intravenous infusion of 50 mL solution over approximately 30 minutes or in an intravenous injection (dose up to 2 million IU) in 10 mL solution over at least 5 minutes.
Infusion solution
The contents of the vial should be dissolved in approximately 2 mL of water for injections, gently shaking - do not allow the solution to foam. This solution should be diluted with 0.9% sodium chloride solution to approximately 50 mL to 100 mL and administered in an intravenous infusion.
Solution for injection
The contents of the vial should be dissolved in approximately 2 mL of water for injections, gently shaking - do not allow the solution to foam. This solution should be diluted with 0.9% sodium chloride solution to approximately 10 mL and administered in a slow intravenous injection.

Intramuscular administration

If intravenous administration is not possible, colistimethate sodium can be administered intramuscularly (injected slowly into large muscles).
Solution for intramuscular injection
The contents of the vial should be dissolved in approximately 2 mL of water for injections, gently shaking - do not allow the solution to foam. This solution should be diluted with water or 0.9% sodium chloride solution to approximately 5 mL.

Inhalation administration

The solution for inhalation should be prepared in an appropriate inhalator (available in pharmacies).
Preparation of the solution for inhalation
The appropriate dose of colistimethate sodium should be dissolved in 2 to 4 mL of water for injections or 0.9% sodium chloride solution. Administer in an inhalator.

Dose conversion table

In the EU, the dose of colistimethate sodium must be prescribed and administered only in international units (IU). The number of IU in the vial is indicated on the product labeling.
Due to different ways of expressing the dose in relation to potency, confusion and errors in treatment have occurred. In the United States and other parts of the world, the dose is expressed in milligrams of colistin base activity (mg CBA).
The following conversion table is prepared for informational purposes, and the values should be treated only as nominal and approximate.

Colistimethate sodium conversion table

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

Special precautions for storage

In accordance with the principles of proper handling, the solution should be administered immediately after preparation.

The solution for injectionprepared as described above remains stable for 24 hours at a temperature of 2°C to 8°C (refrigerator).
The prepared infusionsolution should be used within 24 hours.
The prepared inhalationsolution should be administered immediately after preparation.
The solution can only be used if it is clear and free of contaminants.

Special precautions for disposal of the medicinal product

Any unused product or waste material should be disposed of in accordance with local regulations.

Incompatibilities

Colistimethate sodium is physically and chemically incompatible with erythromycin, hydrocortisone, carbenicillin, cefalotin, cefaloridine, kanamycin, and lincomycin hydrochloride. Solutions of colistimethate sodium should not be mixed with other medicines.