Linezolid Polpharma

Leaflet attached to the packaging: information for the user

Linezolid Polpharma, 2 mg/ml, solution for infusion

Linezolidum

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• -You should keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or nurse.
• This medicine has been prescribed specifically for you. 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 side effects not listed in this leaflet, they should tell their doctor or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Linezolid Polpharma and what is it used for

Linezolid Polpharma is an antibiotic belonging to the group of oxazolidinones. Its action is based on inhibiting the growth of certain bacteria (microorganisms) that cause infections.
The medicine is used in adults to treat pneumonia and certain skin or soft tissue infections.
The doctor will decide whether the use of linezolid is appropriate to treat a specific infection in the patient.

2. Important information before using Linezolid Polpharma

When not to use Linezolid Polpharma

• If the patient is allergic to linezolid or any of the other ingredients of this medicine (listed in section 6).
• If the patient is currently taking or has taken within the last 2 weeks any of the medicines called monoamine oxidase inhibitors (MAOIs, e.g. phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are used to treat depression or Parkinson's disease.
• If the patient is breastfeeding. Linezolid passes into breast milk and may harm the baby.

If the patient answers “yes”to any of the following questions, it means that Linezolid Polpharma may not be suitable for them.
In such a situation, the patient should tell their doctor, who may recommend that tests be performed before and during treatment, or decide to use a different, more suitable treatment.
In case of any doubts as to whether the patient is affected by the situations described below, the patient should ask their doctor.

• Does the patient have high blood pressure and is taking medication for it, or not?
• Has the patient been diagnosed with hyperthyroidism?
• Does the patient have a pheochromocytoma (a tumor of the adrenal gland) or a carcinoid syndrome (caused by a tumor of the hormonal system, with symptoms such as diarrhea, hot flashes, wheezing)?
• Does the patient have: bipolar depression, schizoaffective disorders, states of disorientation or other mental disorders?
• Is the patient taking any opioid medications?
• Is the patient taking any of the following medications:
• medicines that reduce nasal congestion, used for colds or flu, containing pseudoephedrine or phenylpropanolamine,
• medicines used to treat asthma, such as salbutamol, terbutaline, fenoterol,
• certain antidepressants, known as tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs), e.g. amitriptyline, cypramil, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline,
• medicines used to treat migraines, such as sumatriptan and zolmitriptan,
• medicines used to treat sudden, severe allergic reactions, such as adrenaline (epinephrine),
• medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine,
• opioids, such as pethidine - used to treat moderate or severe pain,
• medicines used to treat anxiety disorders, such as buspirone,
• antibiotics called rifampicin.

Concomitant use of certain medications, including antidepressants and opioids, with Linezolid Polpharma may lead to the occurrence of serotonin syndrome - a potentially life-threatening condition (see section 2 "Linezolid Polpharma and other medicines" and section 4).

Warnings and precautions

If the patient has any of the following disorders, they should inform their doctor before starting to take the medicine:

• tendency to bruise and bleed,
• anemia,
• prone to infections,
• history of seizures,
• liver or kidney dysfunction, especially if the patient is on dialysis,
• diarrhea.

The patient should immediately inform their doctor if any of the following occur during treatment:

• vision disturbances, such as blurred vision, changes in color vision, difficulty seeing details, or narrowing of the field of vision; loss of sensation in hands or feet or a feeling of tingling or prickling;
• diarrhea, which may occur during or after the use of antibiotics, including Linezolid Polpharma; if the diarrhea is severe or persistent or if there is blood or mucus in the stool, the patient should stop taking Linezolid Polpharma and contact their doctor; in such a situation, the patient should not take medications that slow down or stop bowel movements;
• recurring nausea or vomiting, abdominal pain, or rapid breathing.

Linezolid Polpharma and other medicines

Linezolid Polpharma may sometimes interact with certain other medicines, which can cause side effects, such as changes in blood pressure, temperature, or heart rate.
If within the last 2 weeksthe patient has taken any of the following medicines, they should tell their doctor, as it is contraindicatedto use Linezolid Polpharma at that time (see also section 2 "When not to use Linezolid Polpharma"):

• monoamine oxidase inhibitors (MAOIs, e.g. phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are used to treat depression or Parkinson's disease.

The patient should also inform their doctor if they are taking any of the following medications. The doctor may decide to continue the use of Linezolid Polpharma, but it will be necessary to monitor the patient's overall health and blood pressure before and during treatment.
Otherwise, the doctor may decide that a different treatment will be best for the patient.

• Medicines that reduce nasal congestion, used for colds or flu, containing pseudoephedrine or phenylpropanolamine.
• Certain medicines used to treat asthma, such as salbutamol, terbutaline, fenoterol.
• Certain antidepressants, known as tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs).
• Medicines used to treat migraines, such as sumatriptan and zolmitriptan.
• Medicines used to treat sudden, severe allergic reactions, such as adrenaline (epinephrine).
• Medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine.
• Opioids, such as pethidine - used to treat moderate or severe pain.
• Medicines used to treat anxiety disorders, such as buspirone.
• Anticoagulants, such as warfarin.

The patient should tell their doctor about all the medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

Linezolid Polpharma with food, drink, and alcohol

• The patient should avoid consuming large amounts of mature cheeses, yeast extracts, or soy products (e.g. soy sauce) and drinking alcohol, especially beer and wine. The medicine may react with a substance called tyramine, which occurs naturally in some foods, causing an increase in blood pressure.
• If the patient experiences a throbbing headache after eating or drinking, they should immediately tell their doctor or pharmacist.

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.
The effect of Linezolid Polpharma on pregnant women is not known. Therefore, this medicine should not be used during pregnancy, unless prescribed by a doctor.
The patient should not breastfeed while taking Linezolid Polpharma, as it passes into breast milk and may affect the baby.

Driving and using machines

Linezolid Polpharma may cause dizziness or vision disturbances. If such symptoms occur, the patient should not drive vehicles or operate any machines. The patient should remember that feeling unwell can affect their ability to drive and use machines.

What Linezolid Polpharma contains

Glucose

The medicine contains 13.7 g of glucose in 300 ml of solution (45.7 mg/ml). This should be taken into account in patients with diabetes.

Sodium

The medicine contains 113 mg of sodium (the main component of common salt) in 300 ml of solution. This corresponds to 5.65% of the maximum recommended daily intake of sodium in the diet for adults. This should be taken into account in patients who control their sodium intake. The sodium content from the diluent should be considered when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used to dilute the medicine, the patient should consult the Summary of Product Characteristics.

3. How to use Linezolid Polpharma

Linezolid can be taken before, during, or after a meal.

Adults

The medicine will be administered by a doctor or healthcare professional as an intravenous infusion. The usual 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 on dialysis, they should receive Linezolid Polpharma after the dialysis session.
Treatment usually lasts from 10 to 14 days, but may last up to 28 days. The effectiveness and safety of using this medicine for a period longer than 28 days have not been established. The doctor will decide how long the treatment should last.
During treatment with Linezolid Polpharma, the doctor will recommend regular blood tests to monitor the patient's blood count.
If the patient is taking Linezolid Polpharma for more than 28 days, the doctor should recommend an eye examination.

Use in children and adolescents

Linezolid Polpharma is not usually recommended for use in children and adolescents (under 18 years of age).

Overdose of Linezolid Polpharma

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

Missed dose of Linezolid Polpharma

The medicine is administered under close supervision, so it is unlikely that a dose will be missed. If the patient thinks that a dose has been missed, they should immediately inform their doctor or nurse.
In case of any further doubts about the use of this medicine, the patient should consult their doctor or nurse.

4. Possible side effects

Like all medicines, Linezolid Polpharma can cause side effects, although not everybody gets them.
If any of the following side effects occur, the patient should immediatelytell their doctor, nurse, or pharmacist:

• skin reactions, such as redness, pain, or peeling of the skin (dermatitis), rash, itching, or swelling, especially on the face and neck; these may be symptoms of an allergic reaction and may require discontinuation of Linezolid Polpharma;
• vision problems, such as changes in visual acuity, changes in color vision, difficulty seeing details, or narrowing of the field of vision;
• severe diarrhea with blood and/or mucus (colitis, including antibiotic-associated pseudomembranous colitis), which can rarely lead to life-threatening complications;
• recurring nausea or vomiting, abdominal pain, or rapid breathing;
• seizures or convulsions have been reported during the use of the medicine;
• serotonin syndrome (frequency not known) - if the patient experiences excessive stimulation, confusion, hallucinations, stiffness, tremors, lack of coordination, seizures, rapid heartbeat, serious breathing problems, and diarrhea (suggesting serotonin syndrome), also during concomitant use of antidepressants, known as SSRIs or opioids, the patient should tell their doctor (see section 2).

In patients taking the medicine for more than 28 days, numbness, tingling, or blurred vision have been reported. If the patient experiences vision disturbances, they should contact their doctor as soon as possible.

Other side effects

Frequent(occurring in no more than 1 in 10 patients):

• fungal infections, especially vaginal or oral "thrush"
• headache
• metallic taste in the mouth
• diarrhea, nausea, or vomiting
• changes in blood test results, including kidney or liver function tests or increased blood sugar levels
• bleeding or bruising of unknown cause, which may be due to changes in the number of a certain type of blood cell, affecting blood clotting and leading to anemia
• sleep disturbances
• increased blood pressure
• anemia (low red blood cell count)
• changes in the number of certain blood cells, affecting the ability to fight infections
• skin rash
• itching
• dizziness
• local or generalized abdominal pain
• constipation
• nausea
• localized pain
• fever.

Uncommon(occurring in no more than 1 in 100 patients):

• vaginal or genital infections in women
• sensory disturbances, such as tingling or numbness
• blurred vision
• "ringing" in the ears (tinnitus)
• phlebitis
• dryness or pain in the mouth, swelling, irritation, or discoloration of the tongue
• pain at the infusion site or in the area of the infusion site
• phlebitis (including the vein into which the infusion is inserted)
• need to urinate more frequently
• chills
• feeling tired or thirsty
• pancreatitis
• increased sweating
• changes in blood levels of proteins and salts or enzyme activity indicating kidney or liver function
• seizures
• hyponatremia (low sodium levels in the blood)
• kidney dysfunction
• decreased platelet count
• bloating
• transient ischemic attacks (temporary disturbances of blood flow to the brain, causing short-term symptoms such as loss of vision, weakness of the lower and upper limbs, slurred speech, and loss of consciousness)
• pain at the injection site
• skin inflammation
• increased creatinine levels
• abdominal pain
• changes in heart rhythm (e.g. increased heart rate).

Rare(occurring in no more than 1 in 1000 patients):

• narrowing of the field of vision
• superficial tooth discoloration, which can be removed by a dental cleaning procedure.

Also reported

Frequency not known(cannot be estimated from the available data):

• serotonin syndrome (symptoms include rapid heartbeat, disorientation, excessive sweating, hallucinations, involuntary movements, seizures, rapid breathing, and diarrhea)
• lactic acidosis (symptoms include recurring nausea and vomiting, abdominal pain, rapid breathing)
• severe skin reactions
• sideroblastic anemia (a type of anemia)
• hair loss
• color vision disturbances, difficulty seeing details
• decreased blood cell count
• weakness and/or sensory disturbances.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Medical Devices, and Biocides
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 Linezolid Polpharma

Hospital staff will ensure that the expiration date on the Linezolid Polpharma label has not been exceeded and that the medicine is administered to the patient immediately after opening. Before administration, it will be checked that the solution is clear, as it can only be administered if it does not contain sediment particles. It will also be checked that the solution has been stored properly, in the outer packaging, to protect it from light.
The entry on the packaging after the abbreviation EXP means the expiration date, and after the abbreviation Lot means the batch number.
The medicine should be stored out of sight and reach of children.

6. Contents of the packaging and other information

What Linezolid Polpharma contains

• The active substance of the medicine is linezolid. One milliliter of solution contains 2 mg of linezolid.
• The other ingredients are: glucose monohydrate (a type of sugar), sodium citrate (E331), anhydrous citric acid (E330), 0.1 N hydrochloric acid (for pH adjustment), 0.1 N sodium hydroxide (for pH adjustment), and water for injections.

What Linezolid Polpharma looks like and what the pack contains

Linezolid Polpharma is a clear, colorless to yellow solution.
The medicine is packaged in single-dose bags made of low-density polyethylene (LDPE), formed with an Insocap adapter, containing 300 ml of solution (600 mg of linezolid).
Each carton contains 1 or 10 polyethylene bags.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Polpharma S.A.
Pelplińska 19, 83-200 Starogard Gdański
Phone: +48 22 364 61 01
Date of last revision of the leaflet:December 2024

Information intended for healthcare professionals only

IMPORTANT. Before prescribing the product, the Summary of Product Characteristics should be consulted.
Linezolid Polpharma, 2 mg/ml, solution for infusion is an isotonic, clear, colorless to yellow solution. One milliliter contains 2 mg of linezolid. Other ingredients: glucose monohydrate, sodium citrate (E331), anhydrous citric acid (E330), 0.1 N hydrochloric acid (for pH adjustment), 0.1 N sodium hydroxide (for pH adjustment), water for injections.
Linezolid is not effective in treating infections caused by Gram-negative bacteria. If it is established or suspected that the infection is caused by Gram-negative bacteria, it is necessary to initiate concurrent treatment against these bacteria.

Dosage and administration

Treatment with linezolid should only be started in a hospital setting and after consultation with a specialist in microbiology or infectious diseases.
In patients who started treatment with the intravenous form of the product, it may be possible to switch to the oral form of the product if it is clinically indicated. In this case, there is no need to modify the dosage, as the bioavailability of linezolid after oral administration is approximately 100%.
The infusion solution is administered over 30 to 120 minutes.
The recommended dose of linezolid should be administered intravenously or orally twice a day.
Recommended dosage and duration of treatment in adults
The duration of treatment depends on the type of microorganism, the location and severity of the infection, and the patient's clinical response to treatment.
The recommendations for the duration of treatment are based on those used in clinical trials. In some types of infections, a shorter treatment duration may be sufficient, but there is no data from clinical trials to support this.
The maximum treatment duration is 28 days. The safety and efficacy of using linezolid for more than 28 days have not been established. The doctor will decide how long the treatment should last.
In bloodstream infections caused by Gram-positive bacteria, there is no need to increase the dose or extend the treatment duration.
The recommendations for intravenous infusion and tablet dosing are the same and are as follows:

Children and adolescents
There are insufficient data on the safety and efficacy of linezolid in children and adolescents (under 18 years of age) to determine the recommended dosage. Therefore, linezolid is not recommended for use in this age group until further data are available.
Elderly patients
No dose adjustment is necessary.
Patients with renal impairment
No dose adjustment is necessary.
Patient with severe renal impairment (i.e. creatinine clearance <30 ml min)
No dose adjustment is necessary. However, due to the unknown clinical significance of the increased exposure (up to 10-fold) to the two main metabolites of linezolid in patients with severe renal impairment, linezolid 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 3 hours of hemodialysis, linezolid should be administered to dialysis patients 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 or mildly to moderately impaired renal function.
Therefore, in patients with severe renal impairment undergoing dialysis, linezolid should be used with caution and only when the expected benefit outweighs the theoretical risk.
Patients with hepatic impairment
In patients with mild or moderate hepatic impairment (Child-Pugh score A or B), no dose adjustment is necessary.
Patient with severe hepatic impairment (i.e. Child-Pugh score C)
Linezolid is metabolized by non-enzymatic processes, and it is expected that liver dysfunction will not significantly affect the metabolism of this medicine. However, there are limited pharmacokinetic data and clinical data on the use of linezolid in patients with severe hepatic impairment. Linezolid should be used with caution in these patients and only when the expected benefit outweighs the theoretical risk.

Contraindications

Hypersensitivity to linezolid or any of the excipients of this product.
Linezolid should not be used in patients who are currently taking or have taken within the last 2 weeks any monoamine oxidase inhibitors of type A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide).
Linezolid should not be administered to patients with the following underlying conditions or taking the following types of medications, unless close monitoring of the patient and blood pressure monitoring are possible:

• Patient with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, hyperthyroidism, bipolar depression, schizoaffective disorders, acute disorientation.
• Patient taking any of the following medications: selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin receptor agonists (triptans), medications with direct or indirect sympathomimetic activity (including bronchodilators, pseudoephedrine, and phenylpropanolamine), pressor amines (e.g. adrenaline, noradrenaline), medications with dopaminergic activity (e.g. dopamine, dobutamine), pethidine, or buspirone.

Breastfeeding should be discontinued before starting and during treatment with the medicine.

Special warnings and precautions for use

Myelosuppression
Myelosuppression has been observed in patients treated with linezolid (including anemia, leukopenia, pancytopenia, and thrombocytopenia). In cases where treatment outcomes were known, after discontinuation of linezolid, the changed blood test results returned to pre-treatment values. The risk of such effects appears to be related to the duration of therapy. In elderly patients treated with linezolid, there is a higher risk of blood disorders than in younger patients. Thrombocytopenia may occur more frequently in patients with severe renal impairment, regardless of dialysis. Therefore, the blood cell count should be closely monitored: in patients with pre-existing anemia, granulocytopenia, or thrombocytopenia, in patients taking medications that may decrease hemoglobin, blood cell count, or affect platelet count or function, in patients with severe renal impairment, and in patients taking linezolid for more than 10 to 14 days. Linezolid can be administered to these patients only if close monitoring of hemoglobin, blood cell count, and platelet count is possible.
If significant myelosuppression occurs during treatment with linezolid, treatment should be discontinued, unless continuation of therapy is absolutely necessary. In this case, the patient's blood count should be closely monitored, and appropriate action should be taken.
Additionally, in patients receiving linezolid, it is recommended to monitor the peripheral blood count weekly (with hemoglobin, platelet count, and white blood cell count with smear), regardless of the initial blood count.
In studies involving the use of linezolid for compassionate reasons before its marketing authorization, an increased incidence of severe anemia was observed in patients who received linezolid for more than the maximum recommended 28 days. In these patients, more frequent blood transfusions were necessary. Cases of anemia requiring blood transfusion have also been reported after the marketing authorization of linezolid, more frequently after the use of this medicine for more than 28 days.
After the marketing authorization of linezolid, cases of sideroblastic anemia have been reported. Most patients who experienced the first symptoms were treated with linezolid for more than 28 days. After discontinuation of linezolid, anemia resolved completely or partially in most patients.
Variable mortality in clinical trials in patients with Gram-positive bloodstream infections related to central venous catheters
In an open-label clinical trial, in seriously ill patients with central venous catheter-related bloodstream infections, higher mortality was observed in patients receiving linezolid than in patients treated with vancomycin, dicloxacillin, or oxacillin [78/363 (21.5%) versus 58/363 (16.0%)]. The main factor influencing mortality was the presence of Gram-positive bacteremia at the start of treatment. Mortality rates were similar in patients with Gram-positive bacteremia only [odds ratio 0.96; 95% confidence interval: 0.58-1.59], but were significantly higher [p=0.0162] in the group of patients receiving linezolid in patients 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 largest difference occurred during treatment and within 7 days after its completion. During the study, more patients in the linezolid group acquired Gram-negative bacterial infections and 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 initiate concurrent treatment against Gram-negative bacteria.
Antibiotic-associated diarrhea and colitis
The occurrence of pseudomembranous colitis has been reported during the use of almost all antibacterial agents, including linezolid. Therefore, it is important to consider this diagnosis in any patient who develops diarrhea after the use of any antibacterial agent. If antibiotic-associated pseudomembranous colitis is suspected or confirmed, it may be necessary to discontinue treatment with linezolid. Appropriate action should be taken.
During the use of almost all antibacterial agents, including linezolid, antibiotic-associated diarrhea and colitis have been reported, including Clostridium difficile-associated diarrhea. It can range from mild diarrhea to life-threatening colitis. Therefore, it is essential to consider this diagnosis in patients who develop acute diarrhea after the use of linezolid. If diarrhea or colitis is suspected or confirmed to be associated with antibiotic use, it is recommended to discontinue the use of the antibacterial agent, including linezolid, and to start appropriate treatment immediately. In such a situation, the use of medications that slow down or stop bowel movements is contraindicated.
Lactic acidosis
Lactic acidosis has been reported during the use of linezolid. If the patient develops symptoms of lactic acidosis, such as recurring nausea or vomiting, abdominal pain, or rapid breathing, immediate medical attention is necessary. If lactic acidosis occurs, the risk-benefit ratio should be reassessed before continuing treatment with linezolid.
Mitochondrial disorders
Linezolid inhibits mitochondrial protein synthesis. As a result, side effects such as lactic acidosis, anemia, and neuropathy (optic or peripheral) may occur; these side effects occur more frequently if the product is used for more than 28 days.
Serotonin syndrome
Serotonin syndrome has been reported in spontaneous reports, associated with the concomitant use of linezolid and serotonergic medications, including antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), and opioids. Therefore, the concomitant use of linezolid with serotonergic medications is contraindicated, unless the concomitant administration of linezolid and a serotonergic medication is necessary. In this case, the patient should be closely monitored for symptoms of serotonin syndrome, such as cognitive impairment, high fever, hyperreflexia, and lack of coordination. If symptoms occur, the doctor should consider discontinuing treatment with one or both medications; after discontinuation of serotonergic medications, withdrawal symptoms may occur.
Peripheral neuropathy and optic neuropathy
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.
The patient should be advised to report any symptoms of vision disturbances, such as changes in visual acuity, changes in color vision, blurred vision, or field defects.
In such cases, the patient should be referred for an ophthalmological examination immediately. If the patient is taking Linezolid Polpharma for more than 28 days, their visual function should be regularly monitored.
If peripheral neuropathy or optic neuropathy occurs, the possibility of continuing treatment with Linezolid Polpharma should be weighed against the risk.
The risk of neuropathy may be increased during the administration of linezolid to patients who are currently or have recently been treated for tuberculosis with antitubercular medications.
Seizures
Seizures have been reported in patients treated with linezolid. In most cases, the patients had a history of seizures or risk factors. The doctor should ask the patient if they have had seizures in the past.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the doses used to treat infections, it does not have an antidepressant effect. There are very limited data on drug interactions and the safety of using linezolid in patients with other diseases and/or taking other medications that may inhibit MAO. Therefore, in such situations, linezolid should not be used unless close monitoring and control of the patient are possible.
Use with tyramine-rich foods
The patient should be advised to limit their consumption of tyramine-rich foods while taking linezolid.
Superinfections
In clinical trials, the effect of linezolid on the physiological bacterial flora has not been evaluated.
The use of antibiotics may sometimes lead to the overgrowth of non-susceptible microorganisms.
For example, during a clinical trial, approximately 3% of patients receiving the recommended doses of linezolid developed drug-dependent candidiasis. If superinfection occurs during the use of linezolid, 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.
In patients with severe hepatic impairment, linezolid should be used only when the expected benefit outweighs the theoretical risk.
Clinical trials
The safety and efficacy of using linezolid for more than 28 days have not been established.
No controlled clinical trials have been conducted in patients with diabetic foot, decubitus ulcers, ischemic changes, severe burns, or gangrene. Therefore, experience with the use of linezolid in such cases is limited.
Excipients

Glucose

This medicine contains 45.67 mg of glucose in 1 ml (i.e. 13.702 g in 300 ml of solution). This should be taken into account in patients with diabetes.

Sodium

This medicine contains 113 mg of sodium in 300 ml of solution, which corresponds to 5.65% of the maximum recommended daily intake of sodium in the diet for adults, as recommended by the WHO. This should be taken into account in patients who control their sodium intake.
The sodium content from the diluent should be considered when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used to dilute the medicine, the patient should consult the Summary of Product Characteristics.

Interactions

Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). There are only limited data from drug interaction and safety studies of linezolid in patients taking concomitant medications that may inhibit monoamine oxidase (MAO). Therefore, linezolid should not be used unless close observation and monitoring of the patient are possible.
Interactions that may increase blood pressure
It has been shown that in healthy volunteers with normal blood pressure, linezolid potentiates the increase in blood pressure caused by pseudoephedrine and phenylpropanolamine. Co-administration of linezolid and pseudoephedrine or phenylpropanolamine resulted in an increase in systolic blood pressure of 30-40 mmHg, compared to an increase of 11-15 mmHg when linezolid was administered alone, 14-18 mmHg when pseudoephedrine or phenylpropanolamine was administered alone, and 8-11 mmHg when placebo was administered. Similar studies have not been conducted in patients with hypertension. It is recommended that the dose of vasopressor agents, including dopamine agonists, be adjusted gradually during their concomitant use with linezolid.
Serotoninergic interactions
Interactions between linezolid and dextromethorphan have been studied in healthy volunteers. Dextromethorphan (2 doses of 20 mg given 4 hours apart) was administered to patients receiving either linezolid or placebo. No symptoms of serotonin syndrome (disorientation, hallucinations, agitation, tremor, flushing, sweating, high fever) were observed in patients receiving linezolid and dextromethorphan.
Post-marketing: one case of serotonin syndrome-like symptoms (confusion, hallucinations, agitation, tremor, flushing, sweating, high fever) has been reported after concomitant administration of linezolid and dextromethorphan; the symptoms resolved after discontinuation of both drugs.
During clinical studies, cases of serotonin syndrome have been reported in patients taking linezolid and serotonergic agents, including antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), and opioids. Therefore, their concomitant use is not recommended.
Use with tyramine-rich foods
No significant increase in blood pressure has been observed in patients receiving linezolid and a dose of tyramine less than 100 mg. This suggests that it is only necessary to avoid excessive consumption of foods and beverages with high tyramine content (e.g., mature cheeses, yeast extracts, undistilled alcoholic beverages, and fermented soybean products, such as soy sauce).
Drugs metabolized by cytochrome P450
Linezolid is not significantly metabolized by the cytochrome P450 enzyme system (CYP450) and does not inhibit the activity of any of the human CYP isoforms at clinically relevant concentrations (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Similarly, linezolid does not induce CYP450 isoenzymes in rats. Therefore, it is expected that linezolid will not interact with other agents metabolized by CYP450.
Rifampicin
The effect of rifampicin on the pharmacokinetics of linezolid was studied in sixteen healthy male volunteers who received 600 mg linezolid twice daily for 2.5 days or linezolid plus 600 mg rifampicin once daily for 8 days. Rifampicin decreased the C and AUC of linezolid by 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 therapy after the steady-state linezolid concentrations are achieved, there is a 10% decrease in mean maximum INR (International Normalized Ratio) values and a 5% decrease in the area under the INR-time curve. There are insufficient data to determine the clinical significance of the concomitant use of linezolid and warfarin.

Fertility, Pregnancy, and Lactation

Pregnancy
There are insufficient data on the use of linezolid in pregnant women. Animal studies have shown toxic effects of linezolid on fertility. There is a risk during human use.
Linezolid should not be used during pregnancy unless it is absolutely necessary, i.e., only when the expected benefit outweighs the theoretical risk.
Breast-feeding
Animal studies suggest that linezolid and its metabolites may pass into breast milk, and therefore, breast-feeding should be discontinued before starting linezolid treatment and should not be resumed during treatment.
Fertility
Animal studies have shown that linezolid reduces fertility. It is not known whether linezolid affects fertility in humans.

Effects on Ability to Drive and Use Machines

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

Overdose

No specific antidote is known.
No cases of linezolid overdose have been reported. However, the following information may be useful in managing overdoses.
Supportive care, including monitoring of vital signs and maintenance of renal function, is recommended. Approximately 30% of the linezolid dose is removed by hemodialysis over a 3-hour period; however, there are no data on the removal of linezolid by peritoneal dialysis or hemoperfusion.

Instructions for Use

The packaging is for single use only. Before administration, the polyethylene bag should be checked for leaks by firmly squeezing it for one minute. If the bag leaks, the product should not be used, as it may not be sterile. Before administration, the solution should be inspected; it can only be administered if it is clear and free of particles.
The polyethylene bag should be connected to a two-channel set after checking its integrity and removing the protective foil.
Polyethylene bags should not be used in series. Unused portions of the solution should be discarded. Partially used bags should not be connected.

Compatibility

Linezolid Polpharma, solution for infusion, is compatible with the following solutions: 5% glucose solution for infusion, 0.9% sodium chloride solution for infusion, Ringer's solution with lactate for injection.

Incompatibilities

No other substances should 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 recommendations. If the same intravenous line is to be used for sequential administration of linezolid and other medications, the line should be flushed with a compatible solution before and after linezolid administration.
The solution for infusion Linezolid Polpharma is physically incompatible with the following medications: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium, and sulfamethoxazole with trimethoprim. Additionally, it is chemically incompatible with ceftriaxone sodium.

Shelf Life

Unopened: 30 months.
After opening: chemical and physical stability has been demonstrated for 2 hours at 25°C. For microbiological reasons, the product should be used immediately. If the product is not used immediately, the user is solely responsible for the duration and conditions of use.

Special Precautions for Storage

No special temperature storage recommendations.
The polyethylene bag should be stored in the outer packaging to protect it from light.
Any unused portions of this product or waste materials should be disposed of in accordance with local regulations.