Linezolid Kabi

Package Leaflet: Information for the User

Linezolid Kabi, 2 mg/mL, Solution for Infusion

Linezolid

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

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Keep this package leaflet, you may need to read it again.
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In case of any doubts, consult a doctor or nurse.
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If the patient experiences any side effects, including those not listed in this package leaflet, they should inform their doctor or nurse. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Linezolid Kabi and What is it Used For
• 2. Important Information Before Using Linezolid Kabi
• 3. How to Use Linezolid Kabi
• 4. Possible Side Effects
• 5. How to Store Linezolid Kabi
• 6. Contents of the Package and Other Information

1. What is Linezolid Kabi and What is it Used For

Linezolid Kabi is an antibiotic belonging to the group of oxazolidinones, which inhibit the growth of certain bacteria (microorganisms) that cause infections. It is used to treat pneumonia and certain skin and soft tissue infections. The doctor will decide if Linezolid Kabi is suitable for treating the infection diagnosed in the patient.

2. Important Information Before Using Linezolid Kabi

When Not to Use Linezolid Kabi

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If the patient is allergic to linezolid or any of the other ingredients of this medication (listed in section 6).
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If the patient is using or has used within the last two weeks any monoamine oxidase inhibitor (MAOI) medications (e.g., phenelzine, isocarboxazid, selegiline, moclobemide). These medications may be used to treat depression or Parkinson's disease.
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If the patient is breastfeeding. Linezolid passes into human milk and may harm the baby.

Warnings and Precautions

Consult a doctor or pharmacist before using Linezolid Kabi.
Linezolid Kabi may not be the right medication for patients who answer "yes" to any of the following questions. In such cases, inform the doctor, who will examine the patient's overall health and blood pressure before starting treatment and will monitor them during treatment or may decide to use another, more suitable treatment.
If the patient has any doubts about the following issues, they should ask their doctor.
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Does the patient have high blood pressure and is taking medication for it, or not?
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Has the patient been diagnosed with hyperthyroidism?
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Does the patient have a pheochromocytoma (a tumor of the adrenal gland) or carcinoid syndrome (a condition caused by tumors of the hormonal system, characterized by diarrhea, hot flashes, wheezing)?
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Does the patient have: manic depression, schizoaffective disorder, disorientation, or other mental disorders?
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Has the patient experienced hyponatremia (low sodium levels in the blood) or is taking medications that lower sodium levels in the blood, such as certain diuretics (also known as "water pills"), such as hydrochlorothiazide?
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Is the patient taking any opioid medications?
Taking certain medications, including antidepressants and opioids, with linezolid may lead to serotonin syndrome, a potentially life-threatening condition (see section 2 "Linezolid Kabi and Other Medications" and section 4).

When to Exercise Particular Caution When Using Linezolid Kabi

Before starting treatment with Linezolid Kabi, inform the doctor if the patient has any of the following conditions:
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Advanced age;
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Easily bruising and bleeding tendency;
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Anemia (low red blood cell count);
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Susceptibility to infections;
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History of seizures;
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Liver or kidney dysfunction, especially in patients undergoing dialysis;
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Diarrhea.
Inform the doctor immediately if the patient experiences any of the following during treatment with Linezolid Kabi:
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Vision disturbances, such as blurred vision, changes in color perception, difficulty seeing details, or narrowing of the visual field;
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Numbness or tingling in the hands or feet;
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During or after treatment with antibiotics, including Linezolid Kabi, the patient may experience diarrhea. If it is severe or persistent, or if blood or mucus is present in the stool, discontinue the use of Linezolid Kabi and consult a doctor. Do not use medications that slow down bowel movements in such cases;
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Recurring nausea or vomiting, abdominal pain, or rapid breathing;
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Muscle pain of unknown cause, tenderness, or weakness, and (or) dark urine color. These may be symptoms of a serious condition called rhabdomyolysis (muscle breakdown), which can lead to kidney damage;
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Nausea and malaise, including muscle weakness, headache, confusion, and memory disturbances, which may indicate hyponatremia (low sodium levels in the blood).

Linezolid Kabi and Other Medications

Linezolid Kabi may sometimes interact with other medications, resulting in side effects such as changes in blood pressure, body temperature, or heart rate.
Inform the doctor or pharmacist about all medications the patient is currently taking or has recently taken.
If the patient has taken or is taking the following medications within the last 2 weeks, they must inform their doctor, as they must nottake Linezolid Kabi if they are currently being treated with these medications or have taken them recently (see also section 2 "When Not to Use Linezolid Kabi"):
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Monoamine oxidase inhibitors (MAOIs, e.g., phenelzine, isocarboxazid, selegiline, moclobemide). These medications may be used to treat depression or Parkinson's disease.
If the patient is taking any of the following medications, they should also inform their doctor. The doctor may decide to continue with Linezolid Kabi, but will need to monitor the patient's overall health and blood pressure before and during treatment. In other cases, the doctor may decide to use another, more suitable treatment.
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Medications that reduce nasal congestion, used for colds and flu, containing pseudoephedrine or phenylpropanolamine.
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Certain medications used to treat asthma, such as salbutamol, terbutaline, fenoterol.
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Certain antidepressant medications, such as tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs), e.g., amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline.
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Medications used to treat migraines, such as sumatriptan, zolmitriptan.
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Medications used to treat severe allergic reactions, such as adrenaline (epinephrine).
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Medications that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, dobutamine.
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Opioids, such as pethidine, used to treat moderate to severe pain.
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Medications used to treat anxiety disorders, such as buspirone.
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Medications that prevent blood clotting, such as warfarin.
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The antibiotic rifampicin.

Linezolid Kabi with Food, Drink, and Alcohol

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Linezolid Kabi can be taken before, during, or after meals.
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Avoid consuming excessive amounts of mature cheese, yeast extracts, or soy products (e.g., soy sauce) and drinking alcohol, especially draft beer and wine, as this medication may interact with a substance called tyramine, which occurs naturally in some foods, leading to increased blood pressure.
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If the patient experiences a throbbing headache after eating or drinking, they should contact their doctor or pharmacist immediately.

Pregnancy, Breastfeeding, and Fertility

The effect of Linezolid Kabi on pregnant women is not known. Therefore, this medication should not be used during pregnancy unless prescribed by a doctor. If the patient is pregnant, breastfeeding, or thinks they may be pregnant, or is planning to have a baby, they should consult their doctor or pharmacist before using this medication.
Do not breastfeed while using Linezolid Kabi, as it passes into human milk and may affect the baby.

Driving and Using Machines

Linezolid Kabi may cause dizziness and vision disturbances. If these symptoms occur, the patient should not drive or operate any machines. Remember that feeling unwell can affect the ability to drive and use machines.

Linezolid Kabi Contains Glucose

One mL of Linezolid Kabi contains 45.7 mg of glucose (13.7 g of glucose in one bag or bottle).

This Should be Taken into Account in Patients with Diabetes.

Linezolid Kabi Contains Sodium

One mL of Linezolid Kabi contains 0.38 mg of sodium (the main component of common salt) (114 mg of sodium in one bag or bottle). This corresponds to 5.7% of the maximum recommended daily intake of sodium in the diet for adults in the case of one infusion bag/bottle.

This Should be Taken into Account in Patients Controlling Their Sodium Intake.

3. How to Use Linezolid Kabi

This medication should always be used as directed by a doctor. In case of doubts about using the medication, consult a doctor or pharmacist.

Adult Patients

The medication is administered by a doctor or medical staff as an intravenous infusion (into a vein). The recommended dose for adult patients (18 years and older) is 300 mL of solution (600 mg of linezolid) twice a day, administered directly into the bloodstream (intravenously) in an infusion, over 30 to 120 minutes.
If the patient is undergoing dialysis, they should receive Linezolid Kabi after dialysis.
The duration of treatment is usually 10 to 14 days, but may last up to 28 days. The effectiveness and safety of using this medication for more than 28 days have not been established. The doctor will decide on the duration of treatment.
During treatment with Linezolid Kabi, the doctor should order regular blood tests to monitor the patient's blood cell count.
If Linezolid Kabi is used for more than 28 days, the doctor should order an eye examination for the patient.

Use in Children and Adolescents

Linezolid Kabi is not usually used in children and adolescents (under 18 years of age).

Overdose of Linezolid Kabi

If the patient is concerned that they have received too much Linezolid Kabi, they should inform their doctor or nurse immediately.

Missing a Dose of Linezolid Kabi

The medication is administered under close supervision, so it is unlikely that a dose will be missed. If the patient thinks they have missed a dose, they should inform their doctor or nurse immediately. Do not take a double dose to make up for a missed dose.

4. Possible Side Effects

Like all medications, Linezolid Kabi can cause side effects, although not everybody gets them.
Inform the doctor, nurse, or pharmacist immediatelyif the patient experiences any of the following side effects during treatment with Linezolid Kabi.
Severe side effects of Linezolid Kabi (frequency of occurrence in parentheses):
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Severe skin reactions (uncommon), swelling, especially in the face and neck (uncommon), wheezing, and (or) difficulty breathing (rare). These may be symptoms of an allergic reaction and may require discontinuation of Linezolid Kabi. Skin reactions, such as: a purple, raised rash caused by blood vessel inflammation (rare), red ulcers, and skin peeling (skin inflammation) (uncommon), rash (common), itching (common);
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Vision disturbances (uncommon), such as blurred vision (uncommon), changes in color perception (frequency not known), difficulty seeing details (frequency not known), or narrowing of the visual field (rare);
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Severe diarrhea with blood and (or) mucus in the stool (antibiotic-associated colitis, including pseudomembranous colitis), which can rarely lead to life-threatening complications (uncommon);
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Recurring nausea or vomiting, abdominal pain, or rapid breathing (rare);
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Serotonin syndrome (frequency not known): inform the doctor if the patient is taking antidepressant medications from the SSRI group or opioids (see section 2) and experiences symptoms such as agitation, confusion, hallucinations, stiffness, tremors, coordination disturbances, seizures, rapid heartbeat, serious breathing problems, and diarrhea (suggesting serotonin syndrome) (see section 2);
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Bleeding or bruising of unknown cause, which may be due to changes in blood cell count affecting blood clotting or leading to anemia (common);
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Changes in the number of certain blood cells, which may affect the ability to fight infections (uncommon), symptoms of infection include: fever (common), sore throat (uncommon), mouth ulcers (uncommon), fatigue (uncommon);
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Rhabdomyolysis (rare): objective and subjective symptoms include muscle pain of unknown cause, tenderness, or weakness, and (or) dark urine color. These may be signs of a serious condition called rhabdomyolysis (muscle breakdown), which can lead to kidney damage;
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Pancreatitis (uncommon);
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Seizures (uncommon);
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Transient ischemic attacks (transient disturbances of blood flow to the brain, causing short-term symptoms such as loss of vision, weakness of limbs, slurred speech, loss of consciousness) (uncommon);
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"Ringing" in the ears (tinnitus).
Patient's taking Linezolid Kabi for more than 28 days have reported numbness, tingling, and blurred vision. If the patient experiences vision disturbances, they should consult their doctor as soon as possible.

Other Side Effects

Common Side Effects (May Affect up to 1 in 10 Patients):

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Fungal infections, especially vaginal or oral thrush;
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Headache;
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Metallic taste in the mouth;
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Diarrhea, nausea, or vomiting;
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Changes in the results of some blood tests, including those measuring proteins, salts, or enzymes, used to evaluate kidney or liver function and blood sugar levels;
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Sleep disturbances;
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Increased blood pressure;
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Anemia (low red blood cell count);
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Dizziness;
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Localized or generalized abdominal pain;
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Constipation;
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Indigestion;
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Localized pain;
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Decreased platelet count.

Uncommon Side Effects (May Affect up to 1 in 100 Patients):

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Vaginal or genital area inflammation in women;
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Feeling of numbness or tingling;
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Swelling, pain, or discoloration of the tongue;
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Dry mouth;
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Pain at the infusion site or surrounding area;
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Phlebitis (inflammation of the vein, including at the infusion site);
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Need to urinate more frequently;
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Chills;
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Increased thirst;
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Excessive sweating;
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Hyponatremia (low sodium levels in the blood);
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Kidney failure;
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Bloating;
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Pain at the infusion site;
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Increased creatinine levels;
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Stomach pain;
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Changes in heart rate (e.g., rapid heartbeat);
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Decreased blood cell count;
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Weakness and (or) sensory changes.

Rare Side Effects (May Affect up to 1 in 1,000 Patients):

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Surface tooth discoloration, which can be removed by a dental cleaning procedure (manual removal of tartar).

Other Side Effects (Frequency Not Known: Cannot be Estimated from Available Data):

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Hair loss.

Reporting Side Effects

If the patient experiences any side effects, including those not listed in this package leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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 gather more information on the safety of the medication.

5. How to Store Linezolid Kabi

Store the medication out of sight and reach of children.
FreeFlexBag
Do not use this medication after the expiration date stated on the carton, outer bag, and bag after "EXP:". The expiration date refers to the last day of the month stated.
Medical staff will ensure that Linezolid Kabi is not used after the expiration date stated on the bag and that the medication is administered immediately after opening the bag. The person administering the medication will inspect the solution before use, as only a clear solution free from visible particles can be used. The person administering the medication will ensure that the solution is stored properly until use, i.e., in the carton and outer bag, to protect it from light and keep it out of sight and reach of children.
KabiPac Bottle
Do not use this medication after the expiration date stated on the carton and bottle after "EXP:". The expiration date refers to the last day of the month stated.
Medical staff will ensure that Linezolid Kabi is not used after the expiration date stated on the bottle and that the medication is administered immediately after removal from the carton. The person administering the medication will inspect the solution before use, as only a clear solution free from visible particles can be used. The person administering the medication will ensure that the solution is stored properly until use, i.e., in the carton, to protect it from light and keep it out of sight and reach of children.
After Opening
Chemical and physical stability of the ready-to-use medication has been demonstrated for 24 hours at 2-8°C and 25°C.
For microbiological reasons, the medication should be used immediately, unless the opening method precludes microbial contamination. If the medication is not used immediately, the user is responsible for the storage conditions during use.
Medications should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of unused medications. This will help protect the environment.

6. Contents of the Package and Other Information

What Linezolid Kabi Contains

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The active substance is linezolid. One mL of solution contains 2 mg of linezolid.
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The other ingredients are: glucose monohydrate (a type of sugar), sodium citrate, citric acid, hydrochloric acid 1 M (for pH adjustment), sodium hydroxide 1 M (for pH adjustment), and water for injections.

What Linezolid Kabi Looks Like and Contents of the Package

FreeFlexBag
Linezolid Kabi is a clear, particle-free, colorless to yellow solution in an infusion bag (freeflex), containing 300 mL of solution (600 mg of linezolid), placed in an outer bag.
The bags are supplied in cartons containing 10, 30, or 50 bags.
KabiPac Bottle
Linezolid Kabi is a clear, particle-free, colorless to yellow or slightly brown solution in a bottle, containing 300 mL of solution (600 mg of linezolid).
Each bottle is packaged in a separate carton, and then in outer cartons containing 10, 30, or 50 bottles.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw

Manufacturer

HP Halden Pharma AS
Svinesundsveien 80
NO-1788 Halden
Norway
Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25
99-300 Kutno
To obtain more detailed information about this medication, contact the marketing authorization holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
phone: +48 22 345 67 89

This Medicinal Product is Authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland):

Under the Following Names:

Austria
Linezolid Kabi 2 mg/ml Infusionslösung
Belgium
Linezolid Fresenius Kabi 2 mg/ml, oplossing voor infusie
Bulgaria
Linezolid Kabi 2 mg/ml инфузионен разтвор
Czech Republic
Linezolid Kabi 2 mg/ml
Croatia
Linezolid Kabi 2 mg/ml otopina za infuziju
Denmark
Linezolid Fresenius Kabi
Estonia
Linezolid Fresenius Kabi
France
Linezolide Kabi 2 mg/ml, solution pour perfusion
Germany
Linezolid Kabi 2 mg/ml Infusionslösung
Greece
Linezolid Kabi
Hungary
Linezolid Fresenius Kabi, 2 mg/ml oldatos infúzió
Ireland
Linezolid 2 mg/ml solution for infusion
Italy
Linezolid Kabi
Luxembourg
Linezolid Kabi 2 mg/ml Infusionslösung
Netherlands
Linezolid Fresenius Kabi 2 mg/ml, oplossing voor infusie
Norway
Linezolid Fresenius Kabi
Poland
Linezolid Kabi
Portugal
Linezolida Kabi
Romania
Linezolid Kabi 2 mg/ml soluţie perfuzabilă
Slovenia
Linezolid Kabi 2 mg/ml raztopina za infundiranje
Slovakia
Linezolid Kabi 2 mg/ml
Spain
Linezolid Kabi 2 mg/ml solución para perfusión
United Kingdom
Linezolid 2 mg/ml solution for infusion
Date of Last Revision of the Package Leaflet:20.03.2025
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Information Intended for Healthcare Professionals Only:

Linezolid Kabi, 2 mg/mL, Solution for Infusion

Linezolid
IMPORTANT: Before prescribing this medication, read the Summary of Product Characteristics (SPC).
Linezolid is not effective against Gram-negative bacterial infections. If it is confirmed or suspected that the infection is caused by Gram-negative bacteria, appropriate treatment against these bacteria should be initiated.
Linezolid Kabi, 2 mg/mL, Solution for Infusion

Appearance

FreeFlexBag
For single use, ready to use, latex-free, infusion bag (freeflex) made of multi-layer polyolefin film, placed in an outer bag made of Polyester/Polypropylene/Aluminum. The bag contains 300 mL of solution and is placed in a carton. Each carton contains 10, 30, or 50 infusion bags.
Isotonic, clear, particle-free, colorless to yellow solution of Linezolid Kabi containing 2 mg/mL of linezolid. Other ingredients are: glucose monohydrate, sodium citrate, citric acid anhydrous, hydrochloric acid 1 M (for pH adjustment), sodium hydroxide 1 M (for pH adjustment), and water for injections.
KabiPac Bottle
For single use, ready to use, LDPE (KabiPac) bottle with a stopper containing a rubber membrane allowing needle insertion. The bottle contains 300 mL of solution and is placed in a carton to protect it from light.
Outer cartons contain 10, 30, or 50 bottles (each bottle is packaged in a separate carton).
Isotonic, clear, particle-free, colorless to yellow or slightly brown solution of Linezolid Kabi containing 2 mg/mL of linezolid. Other ingredients are: glucose monohydrate, sodium citrate, citric acid anhydrous, hydrochloric acid 1 M (for pH adjustment), sodium hydroxide 1 M (for pH adjustment), and water for injections.

Dosage and Administration

Treatment with linezolid should be initiated only in a hospital setting and after consultation with an appropriate specialist, such as a microbiologist or infectious disease specialist.
In patients who have started treatment with a parenteral form, switching to an oral form may be considered if it is clinically indicated. In such cases, no dose adjustment is necessary, as the bioavailability of linezolid after oral administration is approximately 100%.
The solution for infusion should be administered over 30 to 120 minutes.
The recommended dose of linezolid should be administered intravenously twice a day.
Recommended Dosage and Duration of Treatment in Adult Patients
The duration of treatment depends on the type of microorganism, location, and severity of the infection, as well as the patient's clinical response to treatment.
The following recommendations for the duration of treatment are based on those used in clinical trials. In some types of infections, shorter treatment may be sufficient, but there are no clinical trial data to support this.
The maximum duration of treatment is 28 days. The safety and efficacy of using this medication for more than 28 days have not been established. The doctor will decide on the duration of treatment.
In infections with concomitant bacteremia, there is no need to increase the dose or extend the duration of treatment.
The recommended doses of the solution for infusion are as follows:

Children and Adolescents
The safety and efficacy of linezolid in children and adolescents (under 18 years of age) have not been established. Available data are described in sections 4.8, 5.1, and 5.2 of the SPC, but it is not possible to determine the recommended dosage.
Elderly Patients
Dose adjustment is not necessary.
Renal Impairment
Dose adjustment is not necessary.
Severe Renal Impairment (i.e., Creatinine Clearance <30 ml min)< em>
Dose adjustment is not necessary. Due to the unknown clinical significance of increased exposure (up to 10-fold) to the two main metabolites of linezolid in patients with severe renal impairment, the medication should be used with caution in these patients and only when the expected benefit outweighs the theoretical risk.
Since approximately 30% of the linezolid dose is removed from the body during a 3-hour hemodialysis session, patients undergoing dialysis should receive Linezolid Kabi after dialysis. Hemodialysis also leads to the partial removal of linezolid's main metabolites from the body, but their levels remain significantly higher after dialysis than in patients with normal renal function or mild to moderate renal impairment. Therefore, in patients undergoing dialysis with severe renal impairment, linezolid should be used with caution and only when the expected benefit outweighs the theoretical risk.
There are no data on the use of linezolid in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or other renal replacement therapies.
Mild or Moderate Hepatic Impairment (i.e., Child-Pugh Score A or B)
Dose adjustment is not necessary.
Severe Hepatic Impairment (i.e., Child-Pugh Score C)
Due to the fact that linezolid is metabolized via non-enzymatic processes, it is expected that hepatic impairment will not significantly affect its metabolism. Therefore, dose adjustment is not recommended. However, due to limited clinical experience in patients with severe hepatic impairment, linezolid should be used with caution and only when the expected benefit outweighs the theoretical risk (see sections 4.4 and 5.2 of the SPC).

Contraindications

Hypersensitivity to the active substance or to any of the excipients.
Linezolid should not be used in patients taking any monoamine oxidase inhibitor (MAOI) type A or B (e.g., phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of stopping any of these medications.
Linezolid should not be administered to patients with the following underlying conditions or taking the following medications, unless close monitoring of blood pressure is possible:
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Patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, hyperthyroidism, manic depression, schizoaffective disorder, or acute confusional states;
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Patients taking any of the following medications: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), medications with direct or indirect sympathomimetic activity (including bronchodilators, pseudoephedrine, and phenylpropanolamine), medications that increase blood pressure (e.g., epinephrine, norepinephrine), medications with dopaminergic activity (e.g., dopamine, dobutamine), pethidine, or buspirone.
Before starting treatment, breastfeeding should be discontinued (see section 4.6 of the SPC).

Special Warnings and Precautions for Use

Myelosuppression
In patients treated with linezolid, myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been observed. In cases where a causal relationship was known, after discontinuation of linezolid, the changed hematologic indices returned to pre-treatment values. It appears that the risk of these effects is related to the duration of treatment. In elderly patients, the risk of blood disorders during linezolid treatment is higher than in younger patients.
Thrombocytopenia may occur more frequently in patients with severe renal impairment, regardless of whether they are undergoing dialysis, and in patients with moderate to severe hepatic impairment. Therefore, blood cell count should be closely monitored:
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in patients with pre-existing anemia, granulocytopenia, or thrombocytopenia;
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in patients who are taking concomitant medications that may decrease hemoglobin, blood cell count, or affect platelet count or function;
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in patients with severe renal impairment or moderate to severe hepatic impairment;
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in patients who are taking linezolid for more than 10-14 days.
Linezolid can be administered to these patients only when close monitoring of hemoglobin, blood cell count, and platelet count is possible.
If significant myelosuppression occurs during linezolid treatment, the drug should be discontinued, unless administration of the drug is absolutely necessary. In this case, careful monitoring of blood morphology parameters and implementation of appropriate measures are necessary.
In addition, in patients receiving linezolid, it is recommended to monitor the complete blood count (with hemoglobin, platelet, and white blood cell count) weekly, regardless of the initial blood morphology.
In compassionate use studies before the drug was approved, an increased frequency of severe anemia was reported in patients who received linezolid for more than the maximum recommended 28 days. In these patients, blood transfusions were more frequently required. Cases of anemia requiring blood transfusion have also been reported after the drug was approved, more often after using the drug for more than 28 days.
After the approval of linezolid, cases of sideroblastic anemia have been reported. Most patients who were first observed to have symptoms received linezolid for more than 28 days. In most patients, after discontinuation of linezolid, anemia (treated or untreated) completely or partially resolved.
Variable Mortality in Clinical Trials in Patients with Gram-Positive Bacteria-Related Bloodstream Infections Associated with Central Venous Catheter Use
In an open clinical trial in seriously ill patients with central venous catheter-related infections, higher mortality was observed in patients treated with linezolid than in patients treated with vancomycin, dicloxacillin, or oxacillin [78/363 (21.5%) vs. 58/363 (16.0%)].
The main factor influencing mortality was the presence of Gram-positive bacterial infection at the start of treatment. Mortality rates were similar in patients with exclusively Gram-positive bacterial infection (odds ratio 0.96; 95% confidence interval: 0.58-1.59), but were significantly higher (p=0.0162) in the linezolid-treated patient group with any other pathogen or without a pathogen at the start of treatment (odds ratio 2.48; 95% confidence interval: 1.38-4.46).
The greatest discrepancy occurred during treatment and within 7 days after its completion. During the study, a larger number of patients in the linezolid-treated group developed Gram-negative bacterial infections, and more of them died from Gram-negative bacterial infections and mixed infections. Therefore, in complicated skin and soft tissue infections, linezolid can be used in patients with suspected or confirmed concurrent Gram-negative bacterial infection only when other treatment options are not available. In such cases, it is necessary to start concurrent treatment against Gram-negative bacteria.
Antibiotic-Associated Diarrhea and Colitis
During treatment with almost any antibacterial agent, including linezolid, antibiotic-associated diarrhea and colitis (including pseudomembranous colitis and Clostridioides difficile-associated diarrhea) have been reported. This complication can range from mild diarrhea to life-threatening colitis. Therefore, it is essential to consider this diagnosis in patients who develop severe diarrhea during or after the completion of linezolid treatment. If antibiotic-associated diarrhea or colitis is suspected or confirmed, it is recommended to discontinue the antibacterial agent, including linezolid, and start appropriate treatment immediately. In such cases, the use of drugs that inhibit intestinal peristalsis is contraindicated.
Lactic Acidosis
During treatment with linezolid, cases of lactic acidosis have been reported. In patients who develop signs and symptoms of metabolic acidosis, including recurrent nausea or vomiting, abdominal pain, low bicarbonate levels, or hyperventilation, during linezolid treatment, immediate medical intervention is necessary. If lactic acidosis occurs, the risk-benefit ratio should be reassessed before continuing treatment.
Mitochondrial Dysfunction
Linezolid inhibits mitochondrial protein synthesis, which can lead to adverse effects such as metabolic acidosis, anemia, and neuropathy (optic and peripheral). These effects occur more frequently when the drug is used for more than 28 days.
Serotonin Syndrome
Spontaneous reports have been received of serotonin syndrome associated with the concomitant use of linezolid and serotonergic agents, including selective serotonin reuptake inhibitors (SSRIs) and opioids. Therefore, concomitant use of linezolid with serotonergic agents is contraindicated (see section 4.3), unless it is necessary. In this case, the patient should be closely monitored for signs and symptoms of serotonin syndrome, such as cognitive impairment, high fever, increased muscle tone, and lack of coordination. If these symptoms occur, the doctor should consider discontinuing one or both medications. After discontinuation of the serotonergic agent, withdrawal symptoms may occur.
Rhabdomyolysis
Cases of rhabdomyolysis have been reported in association with linezolid use. Linezolid should be used with caution in patients with risk factors for rhabdomyolysis. If signs or symptoms of rhabdomyolysis occur, linezolid should be discontinued, and appropriate treatment should be initiated.
Hyponatremia and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
In some patients treated with linezolid, cases of hyponatremia and/or SIADH have been observed. In patients at risk of hyponatremia, such as elderly patients or those taking medications that may decrease sodium levels in the blood (e.g., thiazide diuretics, such as hydrochlorothiazide), regular monitoring of serum sodium levels is recommended.
Peripheral Neuropathy and Optic Neuropathy
Cases of peripheral neuropathy and optic neuropathy have been reported in patients treated with linezolid, sometimes progressing to vision loss. These reports were mainly in patients treated for more than the maximum recommended 28 days.
It is recommended that every patient be advised to report symptoms of vision impairment, such as changes in visual acuity, color vision, blurred vision, or visual field defects. In such cases, the patient should be referred for an ophthalmological examination immediately. If the patient is taking linezolid for more than the recommended 28 days, regular monitoring of visual function is necessary.
If peripheral neuropathy or optic neuropathy occurs, further treatment with linezolid should be based on a risk assessment.
The increased risk of neuropathy during linezolid treatment may occur in patients with tuberculosis, currently or recently taking anti-mycobacterial medications.
Seizures
Seizures have been reported in patients treated with linezolid. In most of these cases, a history of seizures or risk factors for seizures were present. The doctor should ask the patient if they have a history of seizures.
Monoamine Oxidase Inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI), but at the doses used to treat infections, it does not have antidepressant effects. There are limited data available from drug interaction and safety studies of linezolid in patients with other diseases and/or taking concomitant medications that may pose a risk associated with MAO inhibition. Linezolid should not be used in these cases unless close monitoring and control of the patient's condition are possible.
Consumption of Tyramine-Rich Foods
The patient should be informed that during linezolid treatment, it is necessary to limit the consumption of tyramine-rich foods.
Superinfections
In clinical trials, the impact of linezolid on the physiological bacterial flora has not been evaluated. The use of antibiotics may sometimes lead to an overgrowth of non-susceptible microorganisms. For example, during a clinical trial, approximately 3% of patients receiving the recommended doses of linezolid developed candidiasis. If superinfection occurs during linezolid treatment, appropriate treatment should be initiated.
Special Patient Populations
In patients with severe renal impairment, linezolid should be used with caution and only when the expected benefit outweighs the theoretical risk (see sections 4.2 and 5.2).
In patients with severe hepatic impairment, linezolid should be used only when the expected benefit outweighs the theoretical risk.
Fertility Disorders
Linezolid treatment has led to transient fertility disorders and induced abnormal sperm morphology in adult male rats exposed to linezolid at levels similar to those in humans. The effect of linezolid on the male reproductive system in humans is unknown.
Clinical Trials
The safety and efficacy of linezolid have not been established for use for more than 28 days. Controlled clinical trials did not include patients with diabetic foot ulcers, decubitus ulcers, ischemic changes, severe burns, or gangrene. Therefore, experience with linezolid in these cases is limited.
Excipients
Glucose
1 mL of the solution contains 45.7 mg of glucose (i.e., 13.7 g in 300 mL of solution). This should be taken into account in patients with diabetes or other conditions associated with glucose intolerance.
Sodium
1 mL of the solution also contains 0.38 mg of sodium (i.e., 114 mg in 300 mL of solution), which corresponds to 0.02% of the WHO-recommended maximum daily intake of 2 g of sodium for adults. This should be taken into account
in patients controlling their sodium intake.
Linezolid solution for infusion may be further prepared for administration with solutions containing sodium (see sections 4.2, 6.2, and 6.6) and should be considered in relation to the total sodium content that will be administered to the patient from all sources.

Interactions

Monoamine Oxidase Inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). Data from drug interaction and safety studies of linezolid in patients taking concomitant medications that may inhibit MAO are limited. Linezolid should not be used in these cases unless close monitoring and control of the patient's condition are possible.
Interactions that May Increase Blood Pressure
In healthy volunteers, linezolid potentiated the increase in blood pressure caused by pseudoephedrine and phenylpropanolamine. Concomitant use of linezolid and pseudoephedrine or phenylpropanolamine resulted in a 30-40 mmHg increase in systolic blood pressure, compared to a 11-15 mmHg increase when linezolid was used alone, a 14-18 mmHg increase when pseudoephedrine or phenylpropanolamine was used alone, and an 8-11 mmHg increase when placebo was used. Similar studies have not been conducted in patients with hypertension. It is recommended to gradually adjust the dose of vasoconstrictor agents, including those acting on dopaminergic receptors, when used concomitantly with linezolid.
Serotoninergic Interactions
In healthy volunteers, the interaction between linezolid and dextromethorphan was studied. Dextromethorphan (2 doses of 20 mg administered 4 hours apart) was given concomitantly with linezolid or without it.
In healthy individuals receiving linezolid and dextromethorphan, no symptoms of serotonin syndrome (i.e., confusion, delirium, restlessness, tremors, flushing, high fever) were observed.
Post-marketing experience: one case of serotonin syndrome-like symptoms has been reported after concomitant administration of linezolid and dextromethorphan. The symptoms resolved after discontinuation of both medications.
During clinical use of linezolid with serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids, cases of serotonin syndrome have been reported. Therefore, concomitant use of these medications is contraindicated (see section 4.3). The management of patients who require concomitant use of linezolid and serotonergic agents has been described in the section: Special Warnings and Precautions for Use.
Consumption of Tyramine-Rich Foods
No significant increase in blood pressure was observed in patients receiving linezolid and tyramine in doses less than 100 mg. This suggests that it is only necessary to avoid consuming excessive amounts of tyramine-rich foods and beverages (e.g., mature cheeses, yeast extracts, undistilled alcoholic beverages, and products derived from fermented soybean seeds, such as soy sauce).
Drugs Metabolized by Cytochrome P450
Linezolid is not significantly metabolized by the cytochrome P450 enzyme system (CYP) and does not inhibit the activity of any human CYP isoenzymes of clinical significance (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Similarly, linezolid does not induce CYP isoenzymes in rats. Therefore, it can be expected that linezolid will not interact with other medications through the CYP450 system.
Rifampicin
The effect of rifampicin on the pharmacokinetics of linezolid has been evaluated in a study involving 16 healthy male volunteers who received 600 mg of linezolid twice daily for 2.5 days or linezolid with 600 mg of rifampicin once daily for 8 days. Rifampicin decreased linezolid Cmax and AUC values by an average of 21% [90% CI, 15, 27] and 32% [90% CI, 27, 37], respectively. The mechanism of this interaction and its clinical significance are unknown.
Warfarin
If warfarin is added to linezolid treatment after steady-state linezolid concentrations have been reached, there is a 10% decrease in mean maximum INR (International Normalized Ratio) values and a 5% decrease in the area under the INR curve. There are insufficient data from patients receiving concomitant linezolid and warfarin to assess the potential clinical significance of these results.

Effects on Fertility, Pregnancy, and Lactation

Pregnancy
There are limited data on the use of linezolid in pregnant women. Animal studies have shown toxic effects on fertility. There is a risk to humans.
Linezolid should not be used during pregnancy unless the expected benefit outweighs the theoretical risk.
Breastfeeding
Animal studies suggest that linezolid may pass into human milk, and therefore, breastfeeding should be discontinued before starting treatment with linezolid and not resumed during treatment.
Fertility
In animal studies, linezolid has caused fertility disorders.

Effects on Ability to Drive and Use Machines

Patients should be warned that during linezolid treatment, dizziness or visual disturbances may occur, and they should not drive or operate machinery.

Undesirable Effects

The following table lists undesirable effects associated with linezolid use, occurring with a frequency based on data from clinical trials involving over 6,000 adult patients who received linezolid at recommended doses for more than 28 days. The most common undesirable effects were: diarrhea (8.9%), nausea (6.9%), vomiting (4.3%), and headache (4.2%).
The most common undesirable effects leading to discontinuation of linezolid treatment were headache, diarrhea, nausea, and vomiting. Approximately 3% of patients discontinued treatment due to undesirable effects associated with linezolid use.
Additional undesirable effects reported after the drug was approved are listed in the table below and described as "frequency unknown" because their frequency cannot be determined from available data.
During linezolid treatment, the following undesirable effects have been observed with the following frequencies: very common (≥1/10), common (≥1/100 to <1>

*
See Special Warnings and Precautions for Use in the Summary of Product Characteristics.
** See Contraindications and Interactions with Other Medicinal Products and Other Forms of Interaction in the Summary of Product Characteristics.
The frequency of undesirable effects was estimated using Hanley's "Rule of Three".
†
See below.
The following undesirable effects associated with linezolid use have been considered serious in rare cases: localized abdominal pain, transient ischemic attacks, hypertension.
† In controlled clinical trials, where linezolid was used for up to 28 days, anemia was reported in 2% of patients. In compassionate use studies involving patients with life-threatening infections and comorbidities, anemia developed in 2.5% (33/1326) of patients treated with linezolid for ≤28 days and in 12.3% (53/430) of patients treated for >28 days.
Severe, drug-related anemia requiring blood transfusion occurred in 9% (3/33) of patients treated for ≤28 days and in 15% (8/53) of patients treated for >28 days.
Children and Adolescents
Data on the safety of linezolid in over 500 children and adolescents (from birth to 17 years) do not indicate that the safety profile in children and adolescents differs from that in adult patients.
Reporting of Suspected Undesirable Effects
After the product is placed on the market, it is important to report any suspected undesirable effects. This allows for continuous monitoring of the benefit-risk ratio of the product. Healthcare professionals should report any suspected undesirable effects via the Department of Adverse Reaction Monitoring of the 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
Undesirable effects can also be reported to the marketing authorization holder.

Overdose

There is no specific antidote.
No cases of linezolid overdose have been reported. However, the following information may be useful in case of overdose.
Supportive care and maintenance of renal function should be provided. Approximately 30% of the linezolid dose is removed from the body during a 3-hour hemodialysis session; however, there are no data on the removal of linezolid by peritoneal dialysis or hemoperfusion.

Instructions for Preparation of the Medicinal Product

For single use only.
FreeFlexbag
Immediately before administration, remove the outer foil, and check for any minor leaks by firmly squeezing the bag. If the bag is leaking, the product should not be used, as it may not be sterile. The solution should be inspected before administration. Only a clear solution free from particulate matter should be used. Bags should not be connected in series. Any unused product or waste material should be disposed of in accordance with local regulations. Partially used bags should not be connected.
KabiPac bottle
Immediately before administration, remove the bottle from the carton. The solution should be inspected before administration. Only a clear solution free from particulate matter should be used. Bottles should not be connected in series. Any unused product or waste material should be disposed of in accordance with local regulations. Partially used bottles should not be connected.
Linezolid Kabi, 2 mg/mL, solution for infusion is compatible with the following solutions: 50 mg/mL (5%) glucose solution for intravenous infusion; 9 mg/mL (0.9%) sodium chloride solution for intravenous infusion; Ringer's solution with lactate (Hartmann's solution) for injection.

Incompatibilities

Other substances should not be added to the solution. If linezolid is to be administered concurrently with other medications, each medication should be administered separately, according to its administration instructions. If the same intravenous line is to be used for sequential administration of several medications, the line should be flushed thoroughly with a compatible infusion solution before and after linezolid administration.
Linezolid is physically incompatible with the following medications: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, and sulfamethoxazole with trimethoprim. Additionally, it is chemically incompatible with sodium ceftriaxone.

Shelf Life

The chemical and physical stability of the prepared solution has been demonstrated for 24 hours at 2-8°C and 25°C. From a microbiological point of view, the product should be used immediately, unless the opening method precludes the risk of microbial contamination. If the product is not used immediately, the in-use storage times and conditions are the responsibility of the user.

Special Precautions for Storage

FreeFlexbag
Store in the original packaging (outer bag and carton) to protect from light.
KabiPac bottle
Until use, store in the carton to protect from light.