Leaflet: Information for the user

Linezolid Kabi 2 mg/ml infusion solution

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.This medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

2.What you need to know before starting to use Linezolid Kabi

3.How to use Linezolid Kabi

4.Possible side effects

5.Storage of Linezolid Kabi

6.Contents of the pack and additional information

LinezolidKabi2 mg/ml is an antibiotic from the oxazolidinones group that acts by inhibiting the growth of certain types of bacteria (germs) that cause infections.

It is used for the treatment of pneumonia and certain skin or subcutaneous tissue infections. Your doctor will decide if Linezolid Kabi 2 mg/ml is suitable for treating your infection.

Do not use Linezolid Kabi

• if you are allergic to linezolid or any of the other ingredients of this medicine (listed in section 6).
• if you are taking or have taken in the last 2 weeks any medicine belonging to the class of monoamine oxidase inhibitors (MAOIs, e.g., phenelzine, isocarboxazid, selegiline, moclobemide). You may have been prescribed these medicines to treat depression or Parkinson's disease.
• if you are breastfeeding. The reason is that linezolid passes into breast milk and may affect the baby.

Warnings and Precautions

Consult your doctor, pharmacist or nurse before starting to use Linezolid Kabi.

Linezolid Kabi 2 mg/ml may not be suitable for you, if you answer "yes" to any of the following questions. In this case, inform your doctor that you will need a general health check and blood pressure check before and during treatment or decide whether there is a better treatment for you.

Ask your doctor if you are unsure if these categories apply to you.

• Do you have high blood pressure, regardless of whether you are taking medicines for this?
• Have you been diagnosed with hyperthyroidism?
• Do you have a tumor of the adrenal glands (pheochromocytoma) or carcinoid syndrome (caused by hormonal system tumors with symptoms of diarrhea, skin flushing, wheezing)?
• Do you suffer from bipolar disorder, schizoaffective disorders, mental confusion or other mental problems?
• Do you have a history of hyponatremia (low sodium levels in the blood) or take medicines that reduce sodium levels in the blood, such as certain diuretics like hydrochlorothiazide?
• Are you taking opioids?

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

Be especially careful with Linezolid Kabi

Consult your doctor before starting to take Linezolid Kabi 2 mg/ml if:

• You are an elderly patient
• You have bruises and bleed easily
• You are anaemic (you have low red blood cells)
• You are prone to infections
• You have a history of epileptic seizures
• You have liver or kidney problems, especially if you are on dialysis
• You have diarrhea

Inform your doctor immediately if during treatment you experience:

• Visual problems such as blurred vision, changes in color vision, difficulty seeing in detail or narrowing of your field of vision.
• Loss of sensation in your arms or legs or a feeling of tingling or pins and needles in your arms or legs.
• You may have diarrhea if you are taking or have taken antibiotics, including Linezolid Kabi 2 mg/ml. If this becomes severe or persistent or you notice that your stools contain blood or mucus, stop taking Linezolid Kabi 2 mg/ml immediately and consult your doctor. In this situation, do not take medicines that inhibit or slow down intestinal movements.
• Recurring nausea or vomiting, abdominal pain or hyperventilation.
• Discomfort and dizziness with muscle weakness, headache, confusion and memory deterioration that may indicate hyponatremia (low sodium levels in the blood).

Use of Linezolid Kabi with other medicines

There is a risk that Linezolid Kabi may sometimes interact with other medicines causing adverse reactions, such as changes in blood pressure, temperature or heart rate.

Inform your doctor or pharmacist if you are taking or have taken recently any other medicine.

Inform your doctor if you are taking or have taken in the last 2 weeksthe following medicines, as Linezolid Kabi should not be taken if you are already taking these medicines or have taken them recently (see also in section 2, "Do not use Linezolid Kabi"):

• Medicines that may inhibit monoamine oxidase (MAOIs, e.g., phenelzine, isocarboxazid, selegiline, moclobemide). You may have been prescribed these medicines to treat depression or Parkinson's disease.

Inform your doctor also if you are taking any of the following medicines. Your doctor may still decide to prescribe Linezolid Kabi, but you will need a general health check and blood pressure check before and during treatment. In other cases, your doctor may decide to prescribe a better treatment for you.

• Decongestants or cold medicines containing pseudoephedrine or phenylpropanolamine.
• Some medicines for treating asthma, such as salbutamol, terbutaline, fenoterol,
• Determined antidepressants such as tricyclics or SSRIs (selective serotonin reuptake inhibitors). There are many of these, such as amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline.
• Medicines for treating migraines, such as sumatriptan and zolmitriptan.
• Medicines for treating severe and sudden allergic reactions, such as adrenaline (epinephrine).
• Medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine and dobutamine.
• Opioids (e.g., pethidine) used to treat moderate to severe pain.
• Medicines for treating anxiety disorders, such as buspirone.
• Medicines that prevent blood clotting, such as warfarin.
• An antibiotic called rifampicin.

Use of Linezolid Kabi with food and drink

• You can take Linezolid Kabi before, during or after meals.
• Avoid taking large amounts of strong cheese, yeast extracts or soya extracts (such as soy sauce) and alcoholic beverages, especially draught beer and wine. The reason is that linezolid may react with a substance called tyramine that is present in some foods. This interaction may cause an increase in your blood pressure.
• If you develop a throbbing headache after eating or drinking, inform your doctor or pharmacist immediately.

Pregnancy, breastfeeding and fertility

There are no known effects of Linezolid Kabi on pregnant women. Therefore, it should not be used during pregnancy, unless your doctor advises you to do so. If you are pregnant or breastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Do notbreatfeedif you are using Linezolid Kabi, as it passes into breast milk and may affect the baby.

Driving and operating machines

Linezolid Kabi may cause dizziness or affect your vision. If this happens, do not drive or operate machines. Remember that if you feel unwell, your ability to drive or operate machines may be impaired.

Linezolid Kabi contains glucose

This medicine contains glucose.

Patients with diabetes mellitus should note that this medicine contains 45.7 mg of glucose per ml of solution (13.7 g in a bag).

Linezolid Kabi contains sodium

Patients on low-sodium diets should note that each 1 ml of Linezolid Kabi contains 0.38 mg of sodium (main component of table salt/for cooking) (114 mg of sodium in a bag). The sodium in a bag is equivalent to 5.7% of the maximum daily sodium intake recommended for an adult.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Adults

This medication will be administered to you by a doctor or other healthcare professional through an infusion (by perfusion within a vein).

The recommended dose for adults (18 years or older) is 300 ml (600 mg of linezolid) twice a day administered directly into the bloodstream (intravenously), through an infusion over a period of 30 to 120 minutes.

If you are undergoing dialysis, Linezolid Kabi will be administered to you after each dialysis session.

A typical treatment period usually lasts 10 to 14 days, but may extend to 28 days. The safety and efficacy of this medication have not been established for periods exceeding 28 days. Your doctor will decide on the duration of treatment.

Your doctor must perform blood tests periodically during treatment with Linezolid Kabi to monitor your hemogram.

Your doctor must monitor your vision if you use Linezolid Kabi for more than 28 days.

Use in children and adolescents

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

If you use more Linezolid Kabi than you should

If you think you have been administered more Linezolid Kabi than you should, inform your doctor or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Linezolid Kabi

As this medication is administered under close supervision, it is highly unlikely that you will forget a dose. If you think you have forgotten to administer a dose of treatment, inform your doctor or nurse. Do not take a double dose to compensate for the missed dose.

Like all medicines, Linezolid Kabi may cause side effects, although not everyone will experience them.

Inform your doctor or pharmacist immediatelyif you experience any of the following side effects during treatment with Linezolid Kabi:

The most serious side effects (frequency in parentheses) of Linezolid Kabi are:

• Severe skin changes (rare), swelling, particularly around the face and neck (rare), shortness of breath and/or difficulty breathing (rare). This may be a sign of an allergic reaction and treatment with Linezolid Kabi may need to be discontinued. Skin reactions such as a raised purple rash due to inflammation of blood vessels (rare), skin with red sores and peeling (dermatitis) (rare), skin rash (frequent), itching (frequent).
• Visual problems (rare) such as blurred vision (rare), changes in color perception (unknown), difficulty seeing details (unknown) or narrowing of the visual field (rare).
• Intense diarrhea, with stools containing blood and/or mucus (antibiotic-associated colitis including pseudomembranous colitis), which in rare cases may lead to potentially life-threatening complications (rare).
• Repeated nausea or vomiting, abdominal pain or rapid breathing (rare).
• Seizures or convulsions have been reported (rare).
• Serotonin syndrome (unknown) should inform your doctor if you experience agitation, confusion, delirium, stiffness, tremors, discoordination, convulsions, rapid heart rate, severe respiratory problems, and diarrhea (suggestive of serotonin syndrome) while taking Linezolid Kabi simultaneously with antidepressants such as SSRIs or opioids (see section 2).
• Unexplained bleeding or bruising, which may be due to an alteration in the number of certain blood cells that can affect blood clotting or produce anemia (frequent).
• Changes in the number of certain blood cells that can affect the ability to fight infections (rare). Some signs of infection include: fever (frequent), sore throat (rare), mouth ulcers (rare), and fatigue (rare).
• Pancreatitis (rare).
• Convulsions (rare).
• Transient ischemic attacks. (Temporary alteration of blood flow to the brain causing short-term symptoms such as loss of vision, weakness in arms and legs, difficulty speaking, and loss of consciousness) (rare).
• Tinnitus (ringing in the ears) (rare).

Numbness, tingling, or blurred vision are other side effects reported by patients treated with Linezolid Kabi for more than 28 days. If you experience difficulty with your vision, consult your doctor as soon as possible.

Other side effects include:

Frequent (may affect up to 1 in 10 people)

• Fungal infections, especially vaginal or oral
• Headache
• Metalllic taste in the mouth
• Diarrhea, nausea, or vomiting
• Changes in some blood test results, including protein, salt, or enzyme levels that measure kidney or liver function or blood glucose concentration
• Difficulty falling asleep
• Increased blood pressure
• Anemia (low red blood cell count)
• Dizziness
• Localized or general abdominal pain
• Constipation
• Indigestion
• Localized pain
• Reduced platelet count

Rare (may affect up to 1 in 1000 people)

• Change in the surface color of the teeth, which can be removed with a professional dental cleaning (tartrectomy)

Also, the following side effects have been reported (unknown frequency: cannot be estimated from available data)

• Alopecia (hair loss)

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Freeflex Bag: Do not use this medication after the expiration date that appears on the bag, outer bag, and outer packaging after CAD. The expiration date is the last day of the month indicated.

The healthcare professional will ensure that Linezolid Kabi is not used after the "Use by" date printed on the bag and will administer it as soon as the seal is broken. They will also visually inspect the solution before using it and only administer the solution if it is transparent without particles. Store the outer bag in the original packaging to protect it from light until preparation.

KabiPac Vial: Do not use this medication after the expiration date that appears on the vial and outer packaging after CAD. The expiration date is the last day of the month indicated.

The Hospital Staff will ensure that Linezolid Kabi is not used after the "Use by" date printed on the vial and will administer it as soon as it is removed from the outer packaging. They will also visually inspect the solution before using it and only administer the solution if it is transparent without particles. They will also ensure that the solution is stored correctly in its outer packaging to protect it from light and out of the sight and reach of children until needed.

After Opening

Physical and chemical stability has been demonstrated for use for 24 hours at 2-8°C.

From a microbiological standpoint, unless the opening method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the time and conditions of use are the responsibility of the user.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Linezolid Kabi

• The active ingredient is linezolid. Each 1 ml of solution contains 2 mg of linezolid.
• The other components are glucose monohydrate (a type of sugar), sodium citrate, citric acid, hydrochloric acid or sodium hydroxide, and water for injection preparations.

Appearance of Linezolid Kabi and packaging contents

Freeflex Bag:

Linezolid Kabi is presented as a transparent, practically particle-free, colorless or yellowish solution in single-use infusion bags containing 300 ml (600 mg of linezolid) of solution.

The bags are supplied in boxes of 10, 30, or 50 bags.

KabiPac Vial:

Linezolid Kabi is presented as a transparent, practically particle-free, colorless or yellowish or light brown solution in single-use infusion vials containing 300 ml (600 mg of linezolid) of solution.

The vials are supplied in boxes of 10, 30, or 50 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

Fresenius Kabi España, S.A.U.

Marina 16-18,

08005 Barcelona

Spain

Responsible Manufacturer

HP Halden Pharma AS

Svinesundsveien 80

1788 Halden

Norway

or

Fresenius Kabi Polska Sp. z o.o.

Sienkiewicza 25

PL - 99-300 Kutno

Poland

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Last review date of this leaflet: 2023.

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information isindicated only for healthcare professionals:

Linezolid Kabi 2 mg/ml solution for infusion

IMPORTANT: Consult the summary of product characteristics before prescribing.

Linezolid lacks activity against infections caused by Gram-negative microorganisms. Specific treatment for this type of microorganism will be initiated at the same time if documentation or suspicion of a Gram-negative microorganism is documented.

Description of Freeflex bags:

Infusion bags Freeflex, made of polyolefin, multi-layer, latex-free, single-use, ready to use, sealed inside an outer aluminum laminated bag. The bag contains 300 ml of solution and packaged inside a box. Each box contains 10, 30, or 50 infusion bags.

Linezolid Kabi contains linezolid 2 mg/ml in an isotonic solution, transparent, practically particle-free, colorless to yellowish. The other ingredients are: glucose monohydrate, sodium citrate, citric acid, hydrochloric acid or sodium hydroxide, and water for injection preparations.

Description of KabiPac vials:

KabiPac vials, made of polyethylene, single-use, ready to use, closed with a stopper containing a rubber disc that allows the insertion of the needle. The vial contains 300 ml of solution and packaged inside a box. Each box contains 10, 30, or 50 infusion vials.

Linezolid Kabi contains linezolid 2 mg/ml in an isotonic solution, transparent, practically particle-free, colorless to yellowish or light brown. The other ingredients are: glucose monohydrate, sodium citrate, citric acid, hydrochloric acid or sodium hydroxide, and water for injection preparations.

Dosage and administration

Linezolid should be initiated only in a hospital setting and after consulting with a relevant specialist such as a microbiologist or an infectious diseases specialist. Patients who initiate treatment with the parenteral formulation may switch to any of the oral presentations when clinically indicated. In this case, no dose adjustment is required, as the oral bioavailability of linezolid is approximately 100%.

The solution for infusion should be administered over a period of 30 to 120 minutes.

The recommended dose of linezolid should be administered intravenously IV twice a day.

Recommended doses and treatment duration in adults:

The treatment duration depends on the pathogenic microorganism, the site of infection, and its severity, and the patient's clinical response.

The following recommendations on treatment duration are a reflection of those used in clinical trials. It is possible that for some types of infection, shorter treatment regimens may be adequate, although they have not been evaluated in clinical trials.

The maximum treatment duration is 28 days. The safety and efficacy of linezolid administered for periods longer than 28 days have not been established.

No dose adjustment is required for infections associated with concurrent bacteremia.

The recommended dosing regimens are as follows:

Pediatric population

The safety and efficacy of linezolid have not been established in children under 18 years of age. The available data are described in sections 4.8, 5.1, and 5.2 of the summary of product characteristics, however, no dosing recommendation can be made.

Geriatric population:No dose adjustment is required.

Renal impairment:No dose adjustment is required.

Severe renal impairment (i.e., creatinine clearance [ClCr] <30)

No dose adjustment is required. Since the clinical significance of increased exposure (up to 10-fold) to the two major metabolites of linezolid in patients with severe renal impairment is unknown, linezolid should be used with caution in these patients and only when the expected benefits outweigh the potential risks.

Since approximately 30% of the linezolid dose is eliminated during 3 hours of hemodialysis, linezolid should only be administered after dialysis in this type of patient. The major metabolites of linezolid are partially eliminated during hemodialysis, although their concentrations remain considerably higher after dialysis than in patients with normal renal function or mild to moderate renal impairment.

Therefore, linezolid should be used with special caution in patients with severe renal impairment undergoing dialysis and only when the expected benefits outweigh the potential risks.

There is no experience with the administration of linezolid to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal impairment (other than hemodialysis).

Liver impairment:Patients with moderate or severe liver impairment (Child-Pugh class A or B): No dose adjustment is required.

Severe liver impairment (Child-Pugh class C):Since linezolid is metabolized by a non-enzymatic process, it is not expected that liver impairment will significantly alter its metabolism, and therefore no dose adjustment is recommended. However, there are insufficient clinical data, and linezolid should be used in these patients only when the expected benefits outweigh the potential risks (see sections 4.4 and 5.2 of the summary of product characteristics).

Contraindications

Hypersensitivity to linezolid or any of the excipients.

Linezolid should not be used in patients who are being medicated with monoamine oxidase inhibitors (MAOIs) or in the two weeks following the administration of these medications. Unless facilities for strict monitoring and control of blood pressure are available, linezolid should not be administered to patients with the following underlying diseases or under the following types of concomitant treatments:

- Patients with untreated hypertension, pheochromocytoma, carcinoid syndrome, hyperthyroidism, bipolar disease, schizoaffective disorders, acute confusion states.

- Patients who are taking any of the following medications: selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), direct or indirect adrenergic sympathomimetics (including bronchodilator adrenergics, pseudoephedrine, and phenylpropanolamine), vasopressors (such as epinephrine and norepinephrine), dopaminergic agents (such as dopamine and dobutamine), meperidine, or buspirone.

Breastfeeding should be discontinued before and during treatment (see section 4.6 of the summary of product characteristics).

Special warnings and precautions for use

Myelosuppression

Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients treated with linezolid. In patients who were monitored, the affected hematological parameters returned to pre-treatment levels after discontinuation of treatment. The risk of these effects appears to be associated with the duration of treatment. Elderly patients treated with linezolid may be at a higher risk of experiencing hematological disorders than younger patients.

Thrombocytopenia may be more frequent in patients with severe renal impairment, whether or not they are undergoing dialysis. Therefore, close monitoring of the hemogram is recommended in patients who: have pre-existing anemia, granulocytopenia, or thrombocytopenia; are receiving concomitant medications that may decrease hemoglobin levels and hematocyte count or affect platelet count and function; have severe renal impairment; or are receiving more than 10-14 days of treatment.

Linezolid should only be administered to these patients if it is possible to closely monitor their hemoglobin, blood cell count, and platelet count.

If significant myelosuppression occurs during treatment with linezolid, treatment should be discontinued, unless continuation is considered absolutely necessary, in which case, close monitoring of hematological parameters and implementation of appropriate therapeutic measures should be undertaken.

It is also recommended to perform a complete blood count (including hemoglobin, platelets, absolute leukocyte count, and formula) weekly in patients receiving linezolid, regardless of their baseline hemogram.

In compassionate use studies, a higher incidence of severe anemia was reported in patients treated with linezolid for periods longer than the maximum recommended treatment duration of 28 days. These patients required more frequent blood transfusions. Cases of anemia requiring blood transfusion have also been reported during post-marketing experience, with a higher number of cases in patients who received linezolid for more than 28 days.

Reports of sideroblastic anemia have also been received during post-marketing experience. In cases where the onset is known, most patients were treated for more than 28 days. Most patients recovered partially or totally after discontinuation of linezolid treatment, with or without treatment for anemia.

Disproportionate mortality in a clinical trial in patients with Gram-positive catheter-related infections

In an open-label study in severely ill patients with catheter-related Gram-positive infections, an excess of mortality was observed in patients treated with linezolid compared to those treated with vancomycin/dicloxacillin/oxacillin [78/363 (21.5%) vs. 58/363 (16.0%)]. The main factor influencing mortality rates was the baseline state of Gram-positive infection. Mortality rates were similar in patients with infections caused exclusively by Gram-positive microorganisms (odds ratio 0.96; 95% CI: 0.58-1.59), but were significantly higher (p = 0.0162) in the linezolid arm for patients infected with any other microorganism or in whom no baseline microorganism was isolated. The greatest imbalance occurred during treatment and within 7 days following discontinuation of the study drug in the linezolid arm. In the linezolid arm, more patients acquired Gram-negative infections during the study and died from Gram-negative infections and polymicrobial infections. Therefore, linezolid should only be used in patients with complicated skin and soft tissue infections in whom there is suspicion or certainty of co-infection with Gram-negative microorganisms if there are no other treatment alternatives available. In these circumstances, concomitant treatment for Gram-negative microorganisms should be initiated.

Antibiotic-associated diarrhea and colitis

With the use of almost all antibiotics, including linezolid, cases of antibiotic-associated diarrhea and colitis, including pseudomembranous colitis and diarrhea associated with Clostridioides difficile, have been reported, with varying severity from mild diarrhea to life-threatening colitis. Therefore, this diagnosis should be considered in patients who develop severe diarrhea during or after treatment with linezolid. If antibiotic-associated diarrhea or colitis is suspected or confirmed, treatment with the antibiotic should be discontinued, and appropriate therapeutic measures should be initiated immediately. In this situation, medications that inhibit peristalsis are contraindicated.

Lactic acidosis

Reports of lactic acidosis have been received with the use of linezolid. Patients who develop signs or symptoms of metabolic acidosis, including recurrent nausea or vomiting, abdominal pain, low bicarbonate levels, or hyperventilation while being treated with linezolid should receive immediate medical attention. If lactic acidosis occurs, the benefits of continuing linezolid treatment should be weighed against the potential risks.

Mitochondrial dysfunction

Linezolid inhibits mitochondrial protein synthesis. As a result of this inhibition, adverse events such as lactic acidosis, anemia, and neuropathy (optic and peripheral) may occur, which are more frequent when treatment duration exceeds 28 days.

Serotonin syndrome

Reports of serotonin syndrome have been received with the concomitant administration of linezolid and serotoninergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids. Therefore, concomitant administration of linezolid and serotoninergic agents is contraindicated (see section 4.3 of the summary of product characteristics), except when the concomitant use is absolutely necessary. In these cases, patients should be closely monitored for signs and symptoms of serotonin syndrome, such as cognitive dysfunction, hyperpyrexia, hyperreflexia, and ataxia. If symptoms occur, one or both agents should be discontinued; if the SSRI is discontinued, symptoms may resolve.

Hypotension and SIADH

Hypotension and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been observed in some patients treated with linezolid. Regular monitoring of serum sodium levels is recommended in patients at risk of hypotension, such as elderly patients or patients taking medications that may reduce serum sodium levels (e.g., thiazide diuretics such as hydrochlorothiazide).

Optic and peripheral neuropathy

Reports of optic neuropathy and peripheral neuropathy, as well as neuritis, have been received with the use of linezolid; in some cases, vision loss has occurred. These cases have occurred primarily in patients treated for periods longer than the maximum recommended duration of 28 days.

Patients should be advised to report any visual symptoms, such as changes in visual acuity, color vision, blurred vision, or visual field defects. In such cases, visual function should be evaluated as soon as possible, and an ophthalmologist should be consulted if necessary. Regular monitoring of visual function is recommended in any patient treated with linezolid for a period longer than 28 days.

Continuation of linezolid treatment in patients who have experienced optic or peripheral neuropathy should be evaluated against potential risks.

A higher risk of neuropathy may exist when linezolid is used in patients who are currently taking or have recently taken antimycobacterial medications for tuberculosis treatment.

Seizures

Reports of seizures have been received with the use of linezolid. In most cases, a history of seizures or risk factors for seizures was reported. Patients should be advised to report any history of seizures.

MAOIs

Linezolid is a reversible and non-selective monoamine oxidase (MAO) inhibitor; however, it does not exhibit any antidepressant effect at the doses used for antibacterial treatment. Limited data are available on the pharmacological and safety interactions of linezolid in patients receiving concomitant treatments with a risk of MAO inhibition. Therefore, linezolid should not be used in these circumstances, unless close monitoring and control of the patient are possible.

Use with foods rich in tyramine

Patients should be advised not to consume large amounts of foods rich in tyramine.

Superinfection

The effects of linezolid treatment on normal flora have not been evaluated in clinical trials.

Occasionally, the use of antibacterials, including linezolid, may lead to the overgrowth of non-susceptible microorganisms. Approximately 3% of patients who received linezolid at the recommended doses during clinical trials presented with candidiasis associated with treatment. In cases of superinfection during treatment, appropriate measures should be taken.

Special populations

Linezolid should be used with caution in patients with severe renal impairment, and only when the expected benefits outweigh the potential risks (see sections 4.2 and 5.2).

Linezolid should be administered to patients with severe liver impairment only if the expected benefits outweigh the potential risks.

Effects on fertility

In studies with adult male rats, linezolid caused a reversible decrease in fertility and abnormal sperm morphology. The potential effects of linezolid on human male reproductive systems are unknown.

Clinical trials

The safety and efficacy of linezolid have not been established when administered for periods longer than 28 days.

Clinical trials did not include patients with diabetic foot lesions, pressure ulcers, ischemic lesions, severe burns, or gangrene. Therefore, there is limited experience with the use of linezolid in the treatment of these conditions.

Excipients

Glucose

This medicinal product contains 45.7 mg of glucose per ml of solution (13.7 g/300 ml), which should be taken into account in the treatment of patients with diabetes mellitus or other conditions associated with glucose intolerance.

Sodium

This medicinal product contains 0.38 mg of sodium per ml of solution (114 mg/300 ml) equivalent to 0.02 of the maximum daily recommended intake (RDI) of 2 g of sodium by the WHO for an adult, which should be taken into account in the treatment of patients with low-sodium diets.

Linezolid solution for infusion may be prepared for administration with solutions containing sodium (see sections 4.2, 6.2, and 6.6) and this should be considered in relation to the total sodium intake from all sources administered to the patient.

Interactions

MAOIs

Linezolid is a reversible and non-selective monoamine oxidase (MAO) inhibitor. Limited data are available on the pharmacological and safety interactions of linezolid in patients receiving concomitant treatments with a risk of MAO inhibition. Therefore, linezolid should not be used in these circumstances, unless close monitoring and control of the patient are possible.

Potential interactions that increase blood pressure

Linezolid increased the hypertensive effect produced by pseudoephedrine and phenylpropanolamine in healthy normotensive volunteers. Simultaneous administration of linezolid with pseudoephedrine or phenylpropanolamine produced mean increases in systolic blood pressure of approximately 30-40 mmHg, compared with the 11-15 mmHg produced by linezolid alone, the 14-18 mmHg produced by pseudoephedrine or phenylpropanolamine alone, and the 8-11 mmHg produced by placebo. No similar studies have been conducted in hypertensive patients. It is recommended that if linezolid is administered with vasopressor agents (including dopaminergic agents), the doses of these agents should be titrated carefully to achieve the desired response.

Potential serotoninergic interactions

In healthy volunteers, the potential pharmacological interaction of linezolid with dextromethorphan was studied. Two doses of 20 mg of dextromethorphan were administered with a 4-hour interval, with or without linezolid. In healthy volunteers who received linezolid and dextromethorphan, no serotonin syndrome effects (confusion, delirium, restlessness, tremor, flushing, diaphoresis, hyperpyrexia) were observed.

During post-marketing experience, a case of a patient experiencing symptoms similar to those of serotonin syndrome was reported during the use of linezolid and dextromethorphan, which resolved after discontinuation of both treatments.

Reports of serotonin syndrome have been received during the clinical use of linezolid with serotoninergic agents, including antidepressants such as SSRIs and opioids. Therefore, concomitant administration of linezolid with serotoninergic agents is contraindicated (see section 4.3 of the summary of product characteristics), except when the concomitant use is absolutely necessary.

Use with foods rich in tyramine

No significant pressor response was observed in volunteers who received linezolid and less than 100 mg of tyramine. This suggests that only excessive consumption of foods or beverages high in tyramine (e.g., aged cheese, yeast extracts, undistilled alcoholic beverages, and fermented soy products such as soy sauce) is necessary to be avoided.

Drugs metabolized through cytochrome P450

Linezolid is not metabolized detectably by the cytochrome P450 (CYP) enzyme system or inhibits any of the clinically significant human CYP isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4). Similarly, linezolid does not induce CYP enzymes in rats. Therefore, no CYP450-induced pharmacological interactions are expected with linezolid.

Rifampicin

The effect of rifampicin on the pharmacokinetics of linezolid was studied in 16 healthy male volunteers who received 600 mg of linezolid twice daily for 2.5 days, with and without 600 mg of rifampicin once daily for 8 days. Rifampicin reduced the Cmax and AUC of linezolid by a mean of 21% [90% CI: 15, 27] and 32% [90% CI: 27, 37], respectively. The mechanism of this interaction and its clinical relevance are unknown.

Warfarin

Simultaneous administration of warfarin and linezolid (in steady-state) produced a 10% mean maximum reduction in INR and a 5% mean reduction in AUC of INR. Data from patients who have received warfarin and linezolid are insufficient to evaluate the clinical relevance, if any, of these findings.

Fertility, pregnancy, and lactation

Pregnancy

There are limited data on the use of linezolid in pregnant women. Animal studies have shown reproductive toxicity. There is a potential risk in humans.

Linezolid should not be used during pregnancy, except when clearly necessary. That is, only if the potential benefit outweighs the possible risk.

Lactation

Animal data suggest that linezolid and its metabolites may pass into breast milk, and breastfeeding should be discontinued before and during treatment.

Fertility

Studies in animals have shown that linezolid caused a decrease in fertility.

Effects on the ability to drive and use machines

Patients should be advised that they may experience dizziness or visual symptoms while receiving linezolid, and they should be advised not to drive or operate machinery if either of these symptoms occurs.

Adverse reactions

The following table lists all adverse reactions reported with a frequency based on all causality data from clinical trials in which more than 2,000 adult patients received the recommended doses of linezolid up to a maximum of 28 days.

The most frequently reported adverse reactions were diarrhea (8.9%), nausea (6.9%), vomiting (4.3%), and headache (4.2%).

The adverse reactions related to the drug that led to treatment discontinuation were headache, diarrhea, nausea, and vomiting. Approximately 3% of patients discontinued treatment due to an adverse reaction related to the drug.

The additional adverse reactions reported during post-marketing experience are included in the table in the "Unknown frequency" category, as the frequency cannot be estimated from the available data.

The following adverse reactions have been observed and reported during treatment with linezolid with the following frequencies: Very common (≥1/10), common (≥1/100 to <1

System Organ Class	Common(≥1/100 to <1	Uncommon (≥1/1,000 to <1	Rare (≥1/10,000 to <1	Unknown frequency (cannot be estimated from available data)
Infections and infestations	candidiasis, oral candidiasis, vaginal candidiasis, fungal infections	antibiotic-associated colitis, including pseudomembranous colitis* vaginitis
Haematological disorders	thromboc Country of registration Spain Active substance Linezolid Prescription required Yes Manufacturer Fresenius Kabi España, S.A.U. Composition Glucosa monohidrato (50,24 mg mg), Citrato de sodio (e-331) (1,64 mg mg), Hidroxido de sodio (e 524) (C.S C.S mg) This information is for reference only and does not constitute medical advice. Always consult a licensed doctor before taking any medication. Oladoctor is not responsible for medical decisions based on this content. Talk to a doctor online Have questions about this medication or your symptoms? Connect with a licensed doctor for guidance and personalized care. 5.01 review Anna Moret Dermatology18 years of experience Dr. Anna Moret is a board-certified dermatologist and dermatovenereologist. She specialises in adult and pediatric dermatology, venereology, aesthetic skin care, and general medicine. Her consultations are evidence-based and tailored to each patient’s dermatological needs. 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