Linezolid kabi

Patient Information Leaflet

Linezolid Kabi, 2 mg/mL, infusion solution
Linezolidum
Please read all of this leaflet carefully before using this medicine, as it contains
important information for you.
­ Keep this leaflet, as you may need to read it again.
­ If you have any further questions, please consult your doctor or nurse.
­ If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of the leaflet

1. What Linezolid Kabi is and what it is 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 pack and other information

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

Linezolid Kabi is an antibiotic belonging to the oxazolidinone group, which inhibits the growth of certain bacteria (microorganisms) that cause infections. It is used to treat pneumonia and certain skin and soft tissue infections. Your doctor will decide whether Linezolid Kabi is appropriate for treating the infection diagnosed in you.

2. Important information before using Linezolid Kabi

When not to use Linezolid Kabi
­ Do not use if the patient is allergic to linezolid or any of the other ingredients of this medicine
(listed in section 6).
­ Do not use if the patient is currently taking or has taken within the last two weeks any medicines from
a group called monoamine oxidase inhibitors (MAO inhibitors, e.g. phenelzine, isocarboxazid, selegiline,
moclobemide). These medicines may be used to treat depression or Parkinson's disease.
­ Do not use if the patient is breastfeeding. Linezolid passes into human milk and may harm the infant.

Warnings and precautions
Consult a doctor or pharmacist before using Linezolid Kabi.
Linezolid Kabi may not be the right medicine for a patient who answers "Yes" to any of the following
questions. In such cases, inform the doctor, who will examine the patient's general health and blood
pressure before starting treatment and monitor them during treatment, or may decide to use another,
more suitable treatment.
If the patient is unsure whether any of the following apply, they should consult their doctor.
­ Does the patient have high blood pressure and take medication for it?
­ Has the patient been diagnosed with hyperthyroidism?
­ Does the patient have a tumour of the adrenal gland (pheochromocytoma) or carcinoid syndrome
(caused by tumours of the hormonal system, presenting with diarrhoea, hot flushes, and wheezing)?
­ Does the patient have manic depression, schizoaffective disorders, disorientation, or other
psychiatric disorders?
­ Has the patient previously experienced hyponatraemia (low sodium levels in the blood), or is the
patient taking medicines that reduce sodium levels in the blood, such as certain diuretics (also known
as "water tablets"), e.g. hydrochlorothiazide?
­ Is the patient taking any opioid medicines?

The use of certain medicines, including antidepressants and opioids, together with linezolid may lead
to serotonin syndrome—a potentially life-threatening condition (see section 2 "Linezolid Kabi with other
medicines" and section 4).

When to take special care with Linezolid Kabi
Before starting treatment with Linezolid Kabi, inform the doctor if the patient has any of the following
conditions:
­ advanced age;
­ tendency to bruise easily or to bleed;
­ anaemia (low number of red blood cells);
­ susceptibility to infections;
­ history of seizures;
­ impaired liver or kidney function, particularly in dialysed patients;
­ diarrhoea.

Immediately inform the doctor if any of the following occur during treatment with Linezolid Kabi:
­ visual disturbances such as blurred vision, changes in colour perception, difficulty seeing details, or
narrowing of the visual field;
­ loss of sensation in the hands or feet, or tingling or prickling sensations in the hands or feet;
­ diarrhoea may occur during or after treatment with antibiotics, including Linezolid Kabi. If it is
severe or persistent, or if blood or mucus is observed in the stool, stop using Linezolid Kabi
immediately and contact the doctor. In such cases, do not use medicines that inhibit or slow down
intestinal motility;
­ recurring nausea or vomiting, abdominal pain, or rapid breathing;
­ unexplained muscle pain, tenderness, weakness, and/or darkening of the urine. These may be
symptoms of a serious condition called rhabdomyolysis (muscle breakdown), which may lead to
kidney damage;
­ nausea and malaise, including muscle weakness, headache, confusion, and memory disturbances,
which may indicate hyponatraemia (low sodium levels in the blood).

Linezolid Kabi with other medicines
Linezolid Kabi may sometimes interact with certain other medicines, potentially causing adverse effects
such as changes in blood pressure, body temperature, or heart rhythm.
Inform the doctor or pharmacist about all medicines currently or recently taken by the patient.
If the patient has taken or is currently taking any of the following medicines within the last 2 weeks,
inform the doctor, as Linezolid Kabi must not be used in patients currently or recently treated with
these medicines (see also section 2 "When not to use Linezolid Kabi"):
­ monoamine oxidase inhibitors (MAO inhibitors, e.g. phenelzine, isocarboxazid, selegiline,
moclobemide). These medicines may be used to treat depression or Parkinson's disease.

If the patient is taking any of the following medicines, inform the doctor. The doctor may decide to
continue treatment with Linezolid Kabi but will need to monitor the patient's general health and blood
pressure before and during treatment. In other cases, the doctor may decide to use a different, more
appropriate treatment.
­ Medicines that reduce mucosal congestion used in colds and flu, containing pseudoephedrine or
phenylpropanolamine.
­ Certain medicines used to treat asthma, e.g. salbutamol, terbutaline, fenoterol.
­ Certain antidepressants such as tricyclic antidepressants or selective serotonin reuptake inhibitors
(SSRIs), e.g. amitriptyline, citalopram, clomipramine, doxepin, dosulepin, fluoxetine, fluvoxamine,
imipramine, lofepramine, paroxetine, sertraline.
­ Medicines used to treat migraine, e.g. sumatriptan, zolmitriptan.
­ Medicines used to treat severe allergic reactions, e.g. adrenaline (epinephrine).
­ Medicines that increase blood pressure, e.g. noradrenaline (norepinephrine), dopamine, dobutamine.
­ Opioids, e.g. pethidine, used to treat moderate to severe pain.
­ Medicines used to treat anxiety disorders, e.g. buspirone.
­ Medicines that inhibit blood clotting, e.g. warfarin.
­ An antibiotic called rifampicin.

Linezolid Kabi with food, drink, and alcohol
­ Linezolid Kabi may be taken before, during, or after meals.
­ Avoid consuming large amounts of mature cheeses, yeast extracts, or soybean products (e.g. soy
sauce), and avoid drinking alcohol, particularly cask beer and wine, because this medicine may
interact with a substance called tyramine, naturally present in certain foods, leading to increased
blood pressure.
­ If the patient experiences a throbbing headache after eating or drinking, contact the doctor or
pharmacist immediately.

Pregnancy, breastfeeding, and fertility
The effect of Linezolid Kabi in pregnant women is unknown. Therefore, this medicine should not be used
during pregnancy unless prescribed by a doctor. If the patient is pregnant, breastfeeding, suspects she may
be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this
medicine.
Breastfeeding should be avoided during treatment with Linezolid Kabi, as it passes into human milk and
may affect the infant.

Driving and using machines
Linezolid Kabi may cause dizziness and visual disturbances. If these symptoms occur, the patient should
not drive or operate machinery. Remember that general malaise may impair the ability to drive or use
machinery.

Linezolid Kabi contains glucose
One mL of Linezolid Kabi contains 45.7 mg of glucose (13.7 g glucose in one bag or bottle).
This should be considered in patients with diabetes.

Linezolid Kabi contains sodium
One mL of Linezolid Kabi contains 0.38 mg of sodium (main component of table salt) (114 mg sodium
in one bag or bottle). This corresponds to 5.7% of the maximum recommended daily dietary sodium
intake for adults per infusion bag/bottle.
This should be considered in patients monitoring their dietary sodium intake.

3. How to use Linezolid Kabi

This medicine should always be used exactly as your doctor has told you. If you are unsure about how to use the medicine, please consult your doctor or pharmacist.
Adult patients
This medicine is administered as an intravenous infusion by a doctor or qualified medical personnel.
The recommended dose for adult patients (aged 18 years and older) is 300 mL of solution (600 mg linezolid) given twice daily as an intravenous infusion over 30 to 120 minutes.
If the patient is undergoing dialysis, Linezolid Kabi should be administered after completion of dialysis.
The usual duration of treatment is 10 to 14 days, but may last up to 28 days. The efficacy and safety of using this medicine for longer than 28 days have not been established. The decision on the duration of treatment will be made by the doctor.
While receiving Linezolid Kabi, your doctor should arrange for regular blood tests to monitor blood cell counts.
If Linezolid Kabi is used for longer than 28 days, your doctor should arrange for regular eye examinations.
Use in children and adolescents
Linezolid Kabi is generally not used in children and adolescents (under 18 years of age).
Accidental overdose of Linezolid Kabi
If you are concerned that you may have received too high a dose of Linezolid Kabi, inform your doctor or nurse immediately.
Missed dose of Linezolid Kabi
As this medicine is administered under strict medical supervision, it is unlikely that a dose will be missed. However, if you think a dose has been missed, inform your doctor or nurse immediately. Do not double the dose to make up for a missed dose.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should inform your doctor, nurse or pharmacist immediately if the patient notices any of the following adverse reactions while using
Linezolid Kabi.
Severe adverse reactions (frequency stated in parentheses) of Linezolid Kabi:

• severe skin reactions (not common), swelling, particularly in the face and neck area (not common), 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: raised, purple rash caused by inflammation of blood vessels (vasculitis) (rare), red lesions and peeling of the skin (dermatitis) (not common), rash (common), itching (common);
• visual disturbances (not common), such as blurred vision (not common), changes in colour perception (frequency not known), difficulty in seeing details (frequency not known), or narrowing of the field of vision (rare);
• severe diarrhoea with blood and (or) mucus in the stool (antibiotic-associated colitis, including pseudomembranous colitis), very rarely leading to life-threatening complications (not common);
• recurrent nausea or vomiting, abdominal pain or rapid breathing (rare);
• serotonin syndrome (frequency not known): inform your doctor if symptoms such as agitation, confusion, hallucinations, rigidity, tremor, coordination disorders, seizures, rapid heartbeat, severe breathing problems and diarrhoea occur when Linezolid Kabi is used together with antidepressants of the SSRI group or opioids (see section 2) (suggesting serotonin syndrome) (see section 2);
• bleeding or unexplained bruising, possibly due to changes in blood cell counts affecting blood clotting processes or leading to anaemia (common);
• changes in the number of certain blood cells, possibly affecting the ability to fight infections (not common); symptoms of infection include: fever (common), sore throat (not common), mouth ulcers (not common), fatigue (not common);
• rhabdomyolysis (rare): objective and subjective symptoms include muscle pain of unknown cause, tenderness or weakness of muscles and (or) dark discolouration of urine. These may be signs of a serious condition called rhabdomyolysis (muscle breakdown), which may lead to kidney damage;
• pancreatitis (not common);
• seizures (not common);
• transient ischaemic attacks (transient disturbances in blood supply to the brain causing temporary symptoms such as loss of vision, limb weakness, slurred speech, loss of consciousness) (not common);
• "ringing" in the ears (tinnitus).

In patients treated with Linezolid Kabi for longer than 28 days, numbness, tingling and blurred vision have been reported. If visual disturbances occur, medical advice should be sought as soon as possible.

Other adverse reactions
Common adverse reactions (may affect less than 1 in 10 patients):

• fungal infections, particularly of the vagina or oral thrush;
• headache;
• metallic taste in the mouth;
• diarrhoea, nausea or vomiting;
• changes in results of certain blood tests, including measurements of proteins, salts or enzymes used to assess kidney or liver function and blood sugar levels;
• sleep disturbances;
• elevated blood pressure;
• anaemia (low number of red blood cells);
• dizziness;
• localized or generalized abdominal pain;
• constipation;
• indigestion;
• localized pain;
• decreased platelet count.

Uncommon adverse reactions (may affect less than 1 in 100 patients):

• inflammation of the vagina and genital area in women;
• sensation of numbness or tingling;
• swelling, pain or discolouration of the tongue;
• dryness in the mouth;
• pain at or near the site of infusion;
• phlebitis (including at the infusion site);
• need to urinate more frequently;
• chills;
• increased thirst;
• excessive sweating;
• hyponatraemia (low sodium levels in the blood);
• kidney failure;
• bloating;
• pain at the injection site;
• increased creatinine levels;
• stomach pain;
• changes in heart rate rhythm (e.g. rapid heartbeat);
• decreased number of blood cells;
• weakness and (or) sensory changes.

Rare adverse reactions (may affect less than 1 in 1,000 patients):

• superficial discolouration of teeth, reversible after dental cleaning (manual removal of tartar).

The following adverse reactions have also been reported (frequency not known: cannot be estimated from available data):

• alopecia (hair loss).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Linezolid Kabi

Keep the medicine out of sight and reach of children.
Free flex bag
Do not use this medicine after the expiry date stated on the carton, outer bag, and bag after "EXP:". The expiry date refers to the last day of the stated month.
Medical personnel must ensure that Linezolid Kabi is not used after the expiry date indicated on the bag and that the medicine is administered promptly after opening the bag. The person administering the medicine should inspect the solution before use, as only a clear solution free from visible solid particles should be used. The person administering the medicine must ensure that the solution is stored properly until use—i.e., in the carton and outer bag—to protect it from light and to keep it out of sight and reach of children.

KabiPac bottle
Do not use this medicine after the expiry date stated on the carton and bottle after "EXP:". The expiry date refers to the last day of the stated month.
Medical personnel must ensure that Linezolid Kabi is not used after the expiry date indicated on the bottle and that the medicine is administered promptly after removal from the cardboard carton. The person administering the medicine should inspect the solution before use, as only a clear solution free from visible solid particles should be used. The person administering the medicine must ensure that the solution is stored properly until use—i.e., in the cardboard carton—to protect it from light and to keep it out of sight and reach of children.

After opening
The medicinal product has been shown to be chemically and physically stable for 24 hours at temperatures of 2–8°C and 25°C.
From a microbiological standpoint, the medicine should be used immediately, unless the method of opening excludes the risk of microbiological contamination. If the medicine is not used immediately, the user is responsible for the duration and conditions of storage during use.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Linezolid Kabi contains
- The active substance is linezolid. One mL of solution contains 2 mg of linezolid.
- The other ingredients are: monohydrate glucose (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 pack
free flex bag
Linezolid Kabi is a clear, particle-free, colourless to yellow solution in an infusion bag (free flex), containing 300 mL of solution (600 mg linezolid), placed in an outer bag.
The bags are supplied in cardboard boxes containing 10, 30 or 50 bags.

KabiPac bottle
Linezolid Kabi is a clear, particle-free, colourless to yellow or slightly brownish solution in a bottle, containing 300 mL of solution (600 mg linezolid).
Each bottle is individually packed in a cardboard box, then placed in outer cardboard boxes containing 10, 30 or 50 bottles.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Poland

Manufacturer
HP Halden Pharma AS
Svinesundsveien 80
NO-1788 Halden
Norway
Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25
99-300 Kutno
Poland

For further information about this medicinal product, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Poland
Tel.: +48 22 345 67 89

This medicinal product is authorised in the European Economic Area and 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

Information intended exclusively for medical professionals:

Linezolid Kabi, 2 mg/mL, infusion solution
Linezolidum
IMPORTANT: Before prescribing this medicinal product, read the Summary of Product Characteristics (SmPC).
Linezolid is not effective in the treatment of infections caused by Gram-negative bacteria. If infection caused by Gram-negative bacteria is confirmed or suspected, appropriate additional therapy directed against these bacteria should be initiated.

Appearance
free flex bag
Single-use, ready-to-administer, latex-free infusion bag made of multilayer polyolefin film, placed in an outer bag of polyester/polypropylene/aluminum foil. The bag contains 300 mL of solution and is packed in a cardboard box. Each cardboard box contains 10, 30, or 50 infusion bags.
Linezolid Kabi is an isotonic, clear, particle-free, colorless to yellow solution containing 2 mg/mL of linezolid. Other ingredients are: monohydrate glucose, sodium citrate, anhydrous citric acid, hydrochloric acid 1 M (for pH adjustment), sodium hydroxide 1 M (for pH adjustment), and water for injections.

KabiPac bottle
Single-use, ready-to-administer LDPE bottle (KabiPac) with a cap containing a rubber membrane suitable for needle puncture. The bottle contains 300 mL of solution and is packed in a cardboard box for protection from light.
Outer cardboard boxes contain 10, 30, or 50 bottles (each bottle individually packed in a separate cardboard box).
Linezolid Kabi is an isotonic, clear, particle-free, colorless to yellow or slightly brownish solution containing 2 mg/mL of linezolid. Other ingredients are: monohydrate glucose, sodium citrate, anhydrous citric acid, 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 hospital settings and after consultation with an appropriate specialist, e.g., a microbiologist or infectious disease specialist.
In patients who have started treatment with parenteral administration, a switch to one of the oral formulations may be made if clinically indicated. In such cases, dose adjustment is not necessary, as the oral bioavailability of linezolid is approximately 100%.
The infusion solution should be administered as an infusion lasting between 30 and 120 minutes.
The recommended doses of linezolid should be administered intravenously twice daily.

Recommended dosage and duration of treatment in adult patients
The duration of treatment depends on the type of microorganism, site and severity of infection, and the patient's clinical response to therapy.
The treatment durations recommended below are consistent with those used in clinical trials. In certain types of infections, shorter treatment durations may be sufficient; however, clinical trial data on this are lacking.
The maximum duration of treatment is 28 days. The safety and efficacy of linezolid administered for longer than 28 days have not been established.
In infections with concomitant bacteremia, there is no need to increase the dose or extend the duration of treatment.
Recommended doses of the infusion solution are as follows:

Children and adolescents
The safety and efficacy of linezolid in children and adolescents (aged <18 years) have not been established.
Available data are described in sections 4.8, 5.1 and 5.2 of the SmPC, but recommended dosing cannot be determined.
Elderly patients
Dose adjustment is not necessary.
Renal impairment
Dose adjustment is not necessary.
Severe renal impairment (i.e. creatinine clearance <30 mL/min)
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 failure, the drug should be used with particular
caution in these patients and only when the anticipated benefit outweighs the theoretical risk.
Since approximately 30% of the dose of linezolid is removed from the body during a 3-hour hemodialysis session,
the drug should be administered after dialysis in dialysis patients. Hemodialysis also leads to partial removal of
the main metabolites of linezolid, but their concentrations remain significantly higher after dialysis than those
observed in patients with normal renal function or mild to moderate renal impairment. Therefore, linezolid should
be used with particular caution in dialysis patients with severe renal failure and only when the anticipated benefit
outweighs the theoretical risk.
There are currently no data on the use of linezolid in patients undergoing continuous ambulatory peritoneal dialysis
(CAPD) or other non-hemodialysis renal replacement therapies.
Mild or moderate hepatic impairment (i.e. Child-Pugh class A or B)
Dose adjustment is not necessary.
Severe hepatic impairment (i.e. Child-Pugh class C)
Since linezolid is metabolized via non-enzymatic processes, it can be 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
anticipated benefit outweighs the theoretical risk (see sections 4.4 and 5.2 of the SmPC).
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Linezolid must not be used in patients receiving any monoamine oxidase inhibitor (MAOI) of type A or B (e.g.
phenelzine, isocarboxazid, selegiline, moclobemide), or within two weeks of discontinuing any drug from this group.
Linezolid must not be administered to patients with the underlying conditions listed below or who are concurrently
receiving any of the following types of medications, unless close observation and monitoring of the patient's blood
pressure is possible:
­ patients with untreated hypertension, pheochromocytoma, carcinoid syndrome, hyperthyroidism, depression in
bipolar affective disorder, schizoaffective disorders, acute states of disorientation;
­ patients receiving any of the following drugs: serotonin reuptake inhibitors, tricyclic antidepressants, 5-HT receptor
agonists (triptans), drugs with direct or indirect sympathomimetic activity (including bronchodilators, pseudoephedrine
and phenylpropanolamine), vasoconstrictive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g.
dopamine, dobutamine), meperidine or buspirone.
Breastfeeding must be discontinued prior to starting treatment and not resumed during treatment (see section 4.6
of the SmPC).
Special warnings and precautions for use
Bone marrow suppression
Bone marrow suppression (including anemia, leukopenia, pancytopenia and thrombocytopenia) has been observed
in patients treated with linezolid. In cases where a causal relationship was known, hematological parameters returned
to pre-treatment values after discontinuation of linezolid. The risk of these events appears to be related to the duration
of treatment. The risk of blood count abnormalities during treatment with linezolid is greater in elderly patients 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 counts
should be closely monitored:
­ in patients with pre-existing anemia, granulocytopenia or thrombocytopenia;
­ in patients receiving concomitant medications that may reduce hemoglobin levels, blood cell counts or affect platelet
count or function;
­ in patients with severe renal impairment or moderate to severe hepatic impairment;
­ in patients receiving linezolid for longer than 10–14 days.
Linezolid may be administered to these patients only if close monitoring of hemoglobin concentration, blood cell and
platelet counts is possible.
If significant bone marrow suppression occurs during treatment with linezolid, the drug should be discontinued unless
its administration is absolutely necessary. Hematological parameters should then be carefully monitored and appropriate
management initiated.
Furthermore, in patients receiving linezolid, weekly monitoring of the complete blood count (including hemoglobin
concentration, platelet count and leukocyte count with smear) is recommended, regardless of the initial blood count.
In studies involving humanitarian use of the drug prior to marketing authorization, an increased incidence of severe
anemia was reported in patients who received linezolid for longer than the maximum recommended 28 days. Blood
transfusions were more frequently required in these patients. Cases of anemia requiring blood transfusion have also
been reported post-marketing, more frequently after treatment with this drug for longer than 28 days.
Post-marketing, cases of sideroblastic anemia have been reported. Most patients in whom initial symptoms were
observed had received linezolid for longer than 28 days. In most patients, anemia (treated or untreated) resolved
completely or partially after discontinuation of linezolid.
Variable mortality in a clinical trial in patients with Gram-positive catheter-related bloodstream infections
In an open clinical trial in critically ill patients with catheter-related infections treated with linezolid, higher mortality
was observed compared to 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 infection caused solely by Gram-positive bacteria (odds ratio 0.96; 95% CI:
0.58–1.59), but were significantly higher (p=0.0162) in the linezolid group among patients with any other pathogen or
no pathogen at baseline (odds ratio 2.48; 95% CI: 1.38–4.46).
The greatest divergence occurred during treatment and within 7 days after its completion. During the study, a greater
number of patients in the linezolid group developed Gram-negative microorganism infections and a higher number died
due to infections caused by Gram-negative bacteria or mixed infections. Therefore, in complicated skin and soft tissue
infections, linezolid may be used in patients with confirmed or suspected concomitant Gram-negative bacterial infection
only when no other treatment options are available. In such cases, concomitant anti-Gram-negative therapy should be
initiated immediately.
Diarrhea and antibiotic-associated colitis
Diarrhea and colitis, including pseudomembranous colitis and Clostridioides difficile-associated diarrhea, have been
reported during treatment with nearly every antibacterial agent, including linezolid. This complication may range from
mild diarrhea to fatal colitis. It is therefore important to consider this diagnosis in patients who develop acute diarrhea
during or after treatment with linezolid. If antibiotic-associated diarrhea or colitis is suspected or confirmed,
discontinuation of the antibacterial agent, including linezolid, is recommended, along with prompt initiation of appropriate
treatment. In such situations, the use of drugs that inhibit intestinal peristalsis is contraindicated.
Lactic acidosis
Cases of lactic acidosis have occurred during treatment with linezolid. In patients who develop objective and subjective
signs of metabolic acidosis during treatment with linezolid, including recurrent nausea or vomiting, abdominal pain, low
bicarbonate levels or hyperventilation, immediate medical intervention is required. If lactic acidosis occurs, the benefit-risk
ratio should be evaluated before continuing treatment.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis, which may lead to adverse effects such as metabolic acidosis, anemia
and neuropathy (optic and peripheral). These effects occur more frequently when the drug is administered for longer
than 28 days.
Serotonin syndrome
Cases of serotonin syndrome associated with concomitant administration of linezolid and serotonergic drugs, including
selective serotonin reuptake inhibitors (SSRIs) and opioids, have been reported in spontaneous reports (see section 4.5
of the SmPC). Therefore, concomitant administration of linezolid with serotonergic drugs is contraindicated (see section
4.3 of the SmPC), except when absolutely necessary. In such cases, patients should be closely observed for subjective
and objective signs of serotonin syndrome, such as cognitive disturbances, very high fever, hyperreflexia and lack of
coordination. If such signs occur, the physician should consider discontinuing one or both drugs. Symptoms of withdrawal
may occur after discontinuation of the serotonergic drug.
Rhabdomyolysis
Cases of rhabdomyolysis associated with the use of linezolid have been reported. Linezolid should be used with caution
in patients with risk factors predisposing to rhabdomyolysis. If objective or subjective signs of rhabdomyolysis are observed,
administration of linezolid should be discontinued and appropriate treatment initiated.
Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Cases of hyponatremia and (or) syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been observed
in some patients treated with linezolid. In patients at risk of hyponatremia, for example elderly patients or those receiving
drugs that may reduce serum sodium concentration (e.g. thiazide diuretics such as hydrochlorothiazide), regular monitoring
of serum sodium concentration is recommended.
Peripheral neuropathy and optic neuropathy
Cases of peripheral neuropathy and optic neuropathy, sometimes progressing to vision loss, have been reported in patients
treated with linezolid. These reports primarily involved patients treated for longer than the maximum recommended 28 days.
Patients should be advised to report symptoms of visual deterioration, such as changes in visual acuity, color vision, blurred
vision or visual field defects. In such cases, prompt ophthalmological evaluation is recommended. If a patient receives
linezolid for longer than the recommended 28 days, regular monitoring of visual function should be performed.
If peripheral neuropathy or optic neuropathy occurs, further treatment with linezolid should be based on a risk assessment.
Increased risk of neuropathy during linezolid administration may occur in patients with tuberculosis who are currently or
recently receiving anti-mycobacterial drugs.
Seizures
Seizures have been reported in patients treated with linezolid. In most of these cases, a history of seizures or risk factors
predisposing to seizures was noted. The physician should inquire whether the patient has a history of seizures.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective monoamine oxidase inhibitor (MAOI), but has no antidepressant effect at doses
used for the treatment of infections. Data from drug interaction and safety studies in patients with other diseases and/or
receiving concomitant medications that may pose a risk related to MAO inhibition are limited. Linezolid should not be used
in such cases unless close monitoring and observation of the patient's condition are possible.
Consumption of tyramine-rich foods
Patients should be informed that consumption of tyramine-rich foods should be limited during treatment with linezolid.
Superinfections
The effect of linezolid on normal bacterial flora has not been evaluated in clinical trials. Antibiotic use may occasionally
lead to overgrowth of non-susceptible microorganisms. For example, during a clinical trial, approximately 3% of patients
receiving recommended doses of linezolid developed drug-related candidiasis. If superinfection occurs during treatment
with linezolid, appropriate treatment should be initiated.
Special patient groups
Linezolid should be used with particular caution in patients with severe renal impairment and only when the anticipated
benefit outweighs the theoretical risk (see sections 4.2 and 5.2 of the SmPC).
Linezolid should be used in patients with severe hepatic impairment only when the anticipated benefit outweighs the
theoretical risk.
Fertility
Administration of linezolid led to reversible reduction in fertility 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 administered for longer than 28 days have not been established. Controlled clinical
trials did not include patients with diabetic foot, pressure ulcers, ischemic lesions, severe burns or gangrene. Therefore,
experience with the use of linezolid in such cases is limited.
Excipients
Glucose
1 mL of solution contains 45.7 mg glucose (i.e. 13.7 g in 300 mL solution). This should be taken into account in patients
with diabetes or other conditions associated with glucose intolerance.
Sodium
1 mL of solution also contains 0.38 mg sodium (i.e. 114 mg in 300 mL solution), equivalent to 0.02% of the WHO
recommended maximum daily intake of 2 g sodium for adults. This should be taken into account in patients
controlling dietary sodium intake.
Linezolid for infusion solution may be further prepared for administration with sodium-containing solutions (see sections
4.2, 6.2 and 6.6), and this should be considered in relation to the total sodium content administered to the patient from
all sources.
Interactions
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective monoamine oxidase inhibitor (MAOI). Data from drug interaction and safety
studies in patients receiving concomitant medications that may inhibit monoamine oxidase (MAO) are limited. Linezolid
should not be used in such cases unless close monitoring and observation of the patient's condition are possible.
Interactions increasing blood pressure
In healthy volunteers, linezolid potentiated the increase in blood pressure caused by pseudoephedrine and phenylpropanolamine
hydrochloride. Concomitant administration of linezolid with pseudoephedrine or phenylpropanolamine resulted in an increase
in systolic blood pressure of 30–40 mmHg, compared to an increase of 11–15 mmHg with linezolid alone, 14–18 mmHg with
pseudoephedrine or phenylpropanolamine alone, and 8–11 mmHg with placebo. Similar studies have not been conducted in
patients with hypertension. Gradual dose adjustment of vasoactive agents, including those acting on dopaminergic receptors,
is recommended when used concomitantly with linezolid.
Serotonergic interactions
Interactions between linezolid and dextromethorphan were studied in healthy volunteers. Dextromethorphan (2 doses of
20 mg given 4 hours apart) was administered with or without linezolid. No symptoms of serotonin syndrome (e.g. confusion,
delirium, agitation, tremor, facial flushing, increased sweating, high fever) were observed in healthy subjects receiving both
linezolid and dextromethorphan.
Post-marketing experience: one case of symptoms suggestive of serotonin syndrome was reported after concomitant
administration of linezolid and dextromethorphan. Symptoms resolved after discontinuation of both drugs.
During clinical use of linezolid with serotonergic drugs, including antidepressants such as selective serotonin reuptake
inhibitors (SSRIs) and opioids, cases of serotonin syndrome have been reported. Therefore, concomitant use of these drugs
is contraindicated (see section 4.3 of the SmPC). Management of patients requiring concomitant use of linezolid and
serotonergic drugs is 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 at doses below 100 mg.
This indicates that only excessive consumption of foods and beverages high in tyramine (e.g. aged cheeses, yeast extracts,
non-distilled alcoholic beverages and fermented soy products such as soy sauce) should be avoided.
Drugs metabolized by cytochrome P450
Linezolid is not significantly metabolized by the cytochrome P450 (CYP) enzyme system 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
cytochrome P450 isoenzymes in rats. Therefore, CYP450-related drug interactions are not expected during treatment with
linezolid.
Rifampicin
The effect of rifampicin on the pharmacokinetics of linezolid was evaluated in a study involving volunteers, 16 healthy
men who received 600 mg linezolid twice daily for 2.5 days or linezolid with 600 mg rifampicin once daily for 8 days.
Rifampicin reduced C and AUC values of linezolid 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 during linezolid treatment after steady-state concentrations are achieved, a 10% reduction in mean
maximum INR (International Normalized Ratio) values and a 5% reduction in INR AUC are observed. There are insufficient
data from patients receiving concomitant linezolid and warfarin to assess the potential clinical significance of these findings.
Effects on fertility, pregnancy and lactation
Pregnancy
Data on the use of linezolid in pregnant women are limited. Animal studies have shown toxic effects of linezolid on
reproduction. There is a risk when using the drug in humans.
Linezolid must not be used during pregnancy unless the expected benefit outweighs the theoretical risk.
Breastfeeding
Animal studies indicate that linezolid may pass into human milk and therefore breastfeeding should be discontinued prior
to starting linezolid treatment and not resumed during treatment.
Fertility
Animal studies showed that linezolid caused reduced fertility.
Effects on ability to drive and use machines
Patients should be warned that dizziness or visual disturbances may occur during treatment with linezolid and that they
should not drive or operate machinery under such conditions.
Undesirable effects
The table below lists adverse reactions associated with the use of linezolid, occurring at frequencies determined based
on data from clinical trials involving over 6,000 adult patients who received linezolid at recommended doses for longer
than 28 days. The most commonly reported adverse reactions were: diarrhea (8.9%), nausea (6.9%), vomiting (4.3%) and
headache (4.2%).
The most commonly reported adverse reactions leading to discontinuation of treatment were: headache, diarrhea, nausea
and vomiting. Approximately 3% of patients discontinued treatment due to adverse reactions related to the drug.
Additional adverse reactions reported post-marketing are listed in the table below and described as "frequency not known"
because their frequency cannot be determined from available data.
The following adverse reactions have been observed and reported during treatment with linezolid, with the following
frequency of occurrence: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare
(≥1/10,000 to <1/1,000), very rare (≥1/10,000), frequency not known (frequency cannot be determined from available data).

* See Special warnings and precautions for use in SmPC.
** See Contraindications and Interactions with other medicinal products and other forms of interaction in SmPC.
The frequency of adverse reactions was estimated using Hanley's "Rule of Three".
† See below.
The following adverse reactions associated with linezolid use have been considered severe in rare cases: localized abdominal pain, transient ischaemic attacks, hypertension.
† In controlled clinical trials where linezolid was administered for up to 28 days, anaemia was observed in 2% of patients. In studies involving compassionate use of linezolid prior to marketing authorisation in patients with life-threatening infections and concomitant illnesses, anaemia 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 anaemia 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
Safety data from clinical trials involving over 500 children and adolescents (from birth to 17 years of age) do not indicate that the safety profile in children and adolescents differs from that in adult patients.

Reporting of suspected adverse reactions
It is important to report suspected adverse reactions after a medicinal product has been authorised. This enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Suspected adverse reactions may also be reported to the marketing authorisation holder.

Overdose
There is no specific antidote.
No cases of linezolid overdose have been reported. However, the following information may be useful in managing overdose.
Supportive treatment maintaining vital functions and glomerular filtration should be administered. Approximately 30% of a dose of linezolid is removed during a 3-hour haemodialysis session; however, there are no data available on the removal of linezolid by peritoneal dialysis or haemoperfusion.

Instructions for preparation of the medicinal product for administration
For single use only.

Free flex bag
Immediately before administration, remove the outer foil and check for small leaks by firmly squeezing the bag. If leakage occurs, do not use the product, as it may not be sterile. Inspect the solution before administration. Only use clear, particle-free solutions. Do not use bags in series connection. Any unused portions or waste material should be disposed of in accordance with local regulations. Do not connect bags with partially used contents.

KabiPac bottle
Immediately before administration, remove the bottle from the cardboard box. Inspect the solution before administration. Only use clear, particle-free solutions. Do not use bottles in series connection. Any unused portions or waste material should be disposed of in accordance with local regulations. Do not connect bottles with partially used contents.

Linezolid Kabi, 2 mg/mL, infusion solution is compatible with the following solutions: 50 mg/mL (5%) glucose infusion solution for intravenous use; 9 mg/mL (0.9%) sodium chloride infusion solution for intravenous use; Ringer's lactate injection solution (Hartmann's injection solution).

Pharmaceutical incompatibilities
Do not add other substances to the solution. If linezolid is to be administered simultaneously with other medicinal products, each product should be administered separately according to its recommended administration guidelines. If the same infusion line is to be used for sequential administration of several drugs, the line must be thoroughly flushed with a compatible infusion solution before and after administration of linezolid.
Linezolid is physically incompatible with the following medicinal products: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, sodium phenytoin and sulfamethoxazole with trimethoprim. Additionally, it is chemically incompatible with sodium ceftriaxone.

Shelf life
Chemical and physical stability of the ready-to-use solution has been demonstrated for 24 hours at 2-8°C and at 25°C. From a microbiological standpoint, the product should be used immediately unless the method of opening excludes the risk of microbiological contamination. If not used immediately, responsibility for storage conditions and duration during use lies with the user.

Special precautions for storage

Free flex bag
Store in the original packaging (outer bag and cardboard box) to protect from light.

KabiPac bottle
Store in the cardboard box until the time of use to protect from light.