Label: information for the user

Linezolid Normon 2 mg/ml infusion solution

Linezolid

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

6. Contents of the pack and additional information

Linezolid Normon 2 mg/ml is an antibiotic belonging to the oxazolidinones group that acts by preventing the growth of certain bacteria (germs) that cause infections.

Antibiotics are used to treat bacterial infections and do not serve to treat viral infections such as the flu or the common cold.

It is essential that you follow the instructions regarding the dose, administration, and duration of treatment indicated by your doctor.

Do not store or reuse this medication. If once the treatment is completed you have leftover antibiotic, return it to the pharmacy for proper disposal. Do not dispose of the medication through the drain or in the trash.

It is used for the treatment of pneumonia and certain skin or subcutaneous tissue infections.

Your doctor will have decided if linezolid is suitable for treating your infection.

Do not use Linezolid Normon 2 mg/ml if:

• You are allergic to linezolid or any of the other components of this medicine (listed in section 6).
• You are taking or have taken in the last 2 weeks any medicine called monoamine oxidase inhibitors (MAOIs such as phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are usually used to treat depression or Parkinson's disease.
• You are breastfeeding. Linezolid Normon 2 mg/ml passes into the milk and could affect the baby.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Linezolid Normon 2 mg/ml.

Linezolid Normon 2 mg/ml may not be suitable for you if you respondyesto any of the following questions. In that case, inform your doctor, as he/she will need to monitor your general health and blood pressure before and during treatment or may decide that another treatment is better for you.

Ask your doctor if you are unsure whether any of these categories apply to your case.

• Do you have high blood pressure, whether or not you are taking medicines to treat it?
• Have you been diagnosed with hyperthyroidism?
• Do you have a tumor of the adrenal glands (pheochromocytoma) or carcinoid syndrome (caused by tumors in the hormonal system that present with symptoms of diarrhea, skin flushing, wheezing)?
• Do you suffer from bipolar disorder, schizophrenia, confusion or other mental problems?
• Have you had a history of hyponatremia (low sodium levels in the blood) or are you taking 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 and 4).

Be especially careful with Linezolid Normon2 mg/ml:

Inform your doctor before using this medicine if:

• You are an elderly patient.
• You bleed easily and bruise easily.
• You have anemia (low red blood cell count).
• You are prone to infections.
• You have a history of 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 clearly, or if you notice that your field of vision is reduced.
• Loss of sensation in the arms or legs or a feeling of tingling or burning in the arms or legs.
• Dysentery may occur while taking or after taking antibiotics, including linezolid. If diarrhea becomes intense, lasts a long time, or if you notice that your stools contain blood or mucus, stop taking Linezolid Normon 2 mg/ml immediately and consult your doctor. In this situation, do not take medicines that stop or reduce intestinal movements.
• Recurring nausea or vomiting, abdominal pain, or rapid breathing.
• Discomfort and dizziness with muscle weakness, headache, confusion, and memory deterioration that may indicate hyponatremia (low sodium levels in the blood).

Use of Linezolid Normon 2 mg/ml with other medicines

Linezolid Normon 2 mg/ml may interact with certain medicines and produce adverse effects such as changes in blood pressure, body temperature, or heart rate.

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

Inform your doctor if you are taking or have been taking in the last 2 weeksthe following medicines, asyou must notuse Linezolid Normon 2 mg/ml if you are still taking them or if you have recently taken them (see also section 2, "Do not use Linezolid Normon 2 mg/ml"):

• Monoamine oxidase inhibitors (MAOIs, such as phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are usually used to treat Parkinson's disease.

Inform your doctor also if you are taking the following medicines. Your doctor may decide to treat you with Linezolid Normon 2 mg/ml, but will need to assess your general health and blood pressure before and during treatment. In other cases, your doctor may decide that another treatment is better for you.

Use of Linezolid Normon 2 mg/mlwith food, drinks, and alcohol

Pregnancy, breastfeeding, and fertility

The effect of Linezolid Normon2 mg/mlon pregnant women is unknown. Therefore, pregnant women should not use Linezolid Normon2 mg/ml, unless advised by their doctor.If you are pregnant or breastfeeding, or think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

You should not breastfeed while taking Linezolid Normon2 mg/mlbecause this medicine passes into the milk and could affect your baby.

Driving and operating machines

Linezolid Normon 2 mg/ml may cause dizziness or visual problems. If this happens, do not drive or operate machines. Remember that if you do not feel well, you may be affected in your ability to drive or operate machines.

Linezolid Normon 2 mg/ml contains

Glucose

Patients with diabetes mellitus should note that this medicine contains 13.7 g of glucose per dose.

Sodium

This medicine contains 114 mg of sodium (main component of table salt/for cooking) in each dose. This is equivalent to 5.7% of the maximum daily sodium intake recommended for an adult.

Adults

Follow exactly the administration instructions of the medication contained in this leaflet or those indicated by your doctor, pharmacist or nurse.If in doubt, ask your doctor, pharmacist or nurse.

This medication will be administered to you by a doctor or other healthcare professional through a drip (infusion into 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 a drip over a period of 30 to 120 minutes.

If you are on dialysis, use Linezolid Normon 2 mg/ml after each session.

The normal duration of treatment is 10-14 days, but it may be extended up to 28 days. The safety and efficacy of this medication have not been established in treatment periods exceeding 28 days. Your doctor will decide the duration of your treatment.

While using Linezolid Normon 2 mg/ml, your doctor will perform periodic blood tests to monitor your blood count.

If you take Linezolid Normon 2 mg/ml for more than 28 days, your doctor should monitor your vision.

Use in children and adolescents

Linezolid Normon 2 mg/ml is not normally used in children or adolescents (under 18 years).

If you use more Linezolid Normon 2 mg/mlthan you should

If you think you may have been given more Linezolid Normon 2 mg/ml than you should, inform your doctor or nurse.

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

If you forgot to use Linezolid Normon 2 mg/ml

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The most serious side effects of Linezolid 2 mg/ml (frequency in parentheses) are:

• Severe skin changes (rare), swelling, particularly around the face and neck (rare), shortness of breath or difficulty breathing (rare).
• This may be a sign of an allergic reaction and may require discontinuation of Linezolid Normon 2 mg/ml treatment. Skin reactions such as purple elevated rash due to inflammation of blood vessels (rare), red, painful, and scaly skin (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 if you notice a reduction in your visual field (rare).
• Severe diarrhea containing blood and/or mucus (antibiotic-associated colitis, including pseudomembranous colitis), which in rare cases may lead to complications that can be life-threatening (rare).
• Recurring nausea or vomiting, abdominal pain, or rapid breathing (rare).
• There have been reported cases of seizures or convulsions (rare).
• Serotonin syndrome (unknown) should inform your doctor if you experience agitation, confusion, delirium, rigidity, tremors, discoordination, convulsions, rapid heart rate, severe respiratory problems, and diarrhea (suggestive of serotonin syndrome) while also being treated with antidepressants called ISRSs 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).
• Reduction in the number of white 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 symptoms such as loss of vision, weakness in arms and legs, difficulty speaking, and loss of consciousness) (rare).
• Tinnitus (ringing in the ears) (rare).

There have been reported cases of numbness, tingling, or blurred vision in patients who have taken linezolid for more than 28 days. If you experience vision difficulties, consult your doctor as soon as possible.

Other side effects include:

Frequent (may affect up to 1 in 10 people):

• Infections caused by fungi, especially in the vagina or mouth.
• Headache.
• Metalllic taste.
• Diarrhea, vomiting, nausea.
• Alteration of some blood test results, including protein, salt, or enzyme tests that measure liver, kidney function, or blood sugar levels.
• Difficulty sleeping.
• Increased blood pressure.
• Anemia (reduction in the number of red blood cells).
• Itching.
• Dizziness.
• Abdominal pain localized or generalized.
• Constipation.
• Indigestion.
• Pain localized.
• Reduction in the number of platelets.

Rare (may affect up to 1 in 1000 people):

• Change in the color of the tooth surface, which disappears with professional dental cleaning procedures.

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

• Alopecia (hair loss).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: 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.

Do not use this medication after the expiration date that appears on the packaging afterCad. The expiration date is the last day of the month indicated.

The hospital staff will ensure that Linezolid 2 mg/ml solution for infusion is not used after the 'CAD' date printed on the bag and that it is administered immediately upon breaking the seal. They will also visually inspect the solution before use and only use it if it is a transparent solution without particles. They will also ensure that the solution is properly stored in its box and packaging to protect it from light and out of the sight and reach of children until use.

Special storage conditions:

Before opening:Do not store at a temperature above 86°F (30°C). Do not refrigerate or freeze. Store in the original packaging (overbag and bag) to protect it from light until ready for use.

After the first opening:Linezolid Normon 2 mg/ml is physically and chemically stable for at least four hours at room temperature after the first opening. From a microbiological standpoint, unless the opening method excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, the time and storage conditions are the responsibility of the user.

For single use only. Dispose of any remaining solution.

Do not use this medication if you observe any particles or if the solution is not transparent.

Do not dispose of medications through wastewater or household waste. Ask your pharmacist how to dispose of unused medications. These measures will help protect the environment.

Composition of Linezolid Normon 2 mg/ml

The active ingredient is linezolid. Each milliliter of solution contains 2 mg of linezolid. Each bag of 300 ml contains 600 mg of linezolid.

The other components are glucose monohydrate (a type of sugar, see section 2 “Linezolid Normon 2 mg/ml contains glucose”), sodium citrate (E331, see section 2 “Linezolid Normon 2 mg/ml contains sodium”), citric acid (E330), diluted hydrochloric acid (E507), sodium hydroxide (E524), and water for injection preparations.

Appearance of the product and contents of the package

Linezolid Normon 2 mg/ml is a transparent solution that is presented in individual infusion bags containing 300 ml of solution.It is presented in packs of 10 bags.

Holder of the marketing authorization and responsible for manufacturing

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

This medicinal product is authorized in the member states of the European Economic Area under the following names:

Spain: Linezolid Normon 2 mg/ml solution for infusion EFG

Portugal: Linezolida Normon

Last revision date of this leaflet:February 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/

The following information is intended only for healthcare professionals:

Linezolid Normon 2 mg/ml solution for infusion EFG

Linezolid

IMPORTANT: Consult the technical data sheet before prescribing.

Linezolid is not active against infections caused by Gram-negative pathogenic microorganisms. Concomitant treatment should be initiated against Gram-negative microorganisms if there is certainty or suspicion of co-infection with Gram-negative pathogenic microorganisms.

Description

It is presented in carton boxes containing a overbag with a polyolefin bag containing the infusion solution inside.

Linezolid Normon 2 mg/ml is available in packs containing 10 bags of 300 ml of infusion solution.

Linezolid Normon 2 mg/ml solution for infusion contains linezolid 2mg/ml in a transparent solution. Other components are: glucose monohydrate (a type of sugar), sodium citrate (E331), anhydrous citric acid (E330), diluted hydrochloric acid 1N (E507), sodium hydroxide 1N (E524), and water for injection preparations.

Dosage and administration

Linezolid treatment should only be initiated in a hospital setting and after evaluation by a specialist doctor, such as a microbiologist or an infectious diseases specialist.

Patients who initiate treatment with the parenteral formulation can switch to oral presentation when clinically indicated. In this case, no dose adjustment is required, as the oral bioavailability of linezolid is approximately 100%.

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

The recommended dose of linezolid should be administered intravenously (I.V.) twice a day.

Duration and recommended dosage for treatment in adults:

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

The recommendations for the duration of treatment listed below reflect those used in clinical trials. For some types of infection, it may be advisable to prescribe shorter treatments, although this has not been evaluated in clinical trials.

The maximum duration of treatment is 28 days. The safety and efficacy of linezolid have not been established when administered for periods longer than 28 days (see section 4.4).

Infections associated with bacteremia do not require an increase in the recommended dose or the duration of treatment.

The recommended doses are identical for the infusion solution and the tablets and are as follows:

Pediatric population:No safety and efficacy have 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, but no dosage recommendation can be made.

Geriatric population:No dose adjustment is required.

Renal impairment:No dose adjustment is required.

Severe renal impairment (i.e. CLCR<30>No dose adjustment is required in these patients. Since the clinical relevance of the exposure of these patients to high concentrations (up to 10 times) of the two main metabolites of linezolid is unknown, this medicinal product will be used with special caution in patients with severe renal impairment and will only be administered if the expected benefit outweighs the potential risk.

Since approximately 30% of the linezolid dose is eliminated during 3 hours of hemodialysis, linezolid will be administered after dialysis in patients who receive this treatment. The main metabolites of linezolid are eliminated in part by hemodialysis, but their concentrations are considerably higher after dialysis than in patients with normal renal function or mild to moderate renal impairment. Therefore, linezolid will be used with special caution in patients with severe renal impairment undergoing dialysis and only if the expected benefit outweighs the potential risk.

Until now, no experience has been gained in 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 mild to moderate liver impairment (Class A or B in the Child-Pugh scale):No dose adjustment is required.

Patients with moderate liver impairment (Class C in the Child-Pugh scale):Since linezolid is metabolized by a non-enzymatic process, it is expected that impairment of liver function will not significantly alter its metabolism, and therefore no dose adjustment is recommended. However, there are insufficient clinical data, and linezolid should only be used in these patients if the expected benefit outweighs the theoretical risk.

Contraindications

Hypersensitivity to linezolid or to any of the excipients listed in section 6.1.

Linezolid should not be used in patients taking medications that inhibit monoamine oxidases A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or during the two weeks following the administration of such medication.

Unless there are means available for close monitoring and control of blood pressure, linezolid should not be administered to patients with the following underlying clinical conditions or who are being treated with the following medications:

• Patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, hyperthyroidism, bipolar disorder, affective disorders, acute confusional state.
• Patients taking any of the following medications: selective serotonin reuptake inhibitors (see section 4.4), tricyclic antidepressants, 5-HT1 receptor agonists (triptans), direct or indirect sympathomimetics (including bronchodilators, pseudoephedrine, and phenylpropanolamine), vasopressors (e.g. epinephrine, norepinephrine), dopaminergic drugs (e.g. dopamine, dobutamine), meperidine, or buspirone.

The data from animal studies suggest that linezolid and its metabolites may pass into breast milk, so breastfeeding should be interrupted before and during treatment (see section 4.6).

Special warnings and precautions for use

Mielosuppression

There have been reports of myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) in patients treated with linezolid. In patients who were monitored, it was seen that after discontinuing treatment, the affected hematological parameters returned to their pre-treatment levels. The risk of these effects appears to be associated with the duration of treatment. Elderly patients treated with linezolid may have a higher risk of experiencing hematological disorders than younger patients. Thrombocytopenia may occur more frequently in patients with severe renal impairment, whether or not they are undergoing dialysis. Therefore, it is recommended to closely monitor the hemogram in patients who: have pre-existing anemia, granulocytopenia, or thrombocytopenia; are receiving concomitant medication that may decrease hemoglobin levels and hematocrit or reduce the count or affect the count or function of platelets; have severe renal impairment; or who 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 levels, 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 should be implemented and appropriate therapeutic measures taken.

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 recommended maximum treatment duration of 28 days. These patients required blood transfusions more frequently. Cases of severe anemia requiring blood transfusions have also been reported during post-marketing experience, with a higher number of cases in patients who received linezolid for more than 28 days.

There have been reports of sideroblastic anemia 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 discontinuing linezolid treatment, with or without treatment for anemia.

Unbalanced 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 was the baseline status 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 (odds ratio 2.48; 95% CI: 1.38-4.46). The greatest imbalance occurred during treatment and within 7 days after discontinuation of the drug. In the linezolid arm, there were more patients who acquired Gram-negative infections during the study and who 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 available treatments (see section 4.1). In these circumstances, concomitant treatment should be initiated against Gram-negative microorganisms.

Diarhea and antibiotic-associated colitis

With the use of almost all antibiotics, including linezolid, cases of antibiotic-associated diarrhea and antibiotic-associated colitis, including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been reported, ranging from mild diarrhea to fatal colitis. Therefore, it is essential to consider this diagnosis in patients who develop severe diarrhea during or after treatment with linezolid. If diarrhea-associated antibiotic or antibiotic-associated colitis is suspected or confirmed, treatment with the antibacterial agents, including linezolid, should be discontinued and appropriate therapeutic measures should be taken immediately. In this situation, medications that inhibit peristalsis are contraindicated.

Acidosis

There have been reports of lactic acidosis 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

There have been spontaneous reports of serotonin syndrome associated with the concomitant administration of linezolid and serotoninergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids (see section 4.5 of the technical data sheet). Therefore, concomitant administration of linezolid and serotoninergic agents is contraindicated (see section 4.3 of the technical data sheet), except if the concomitant administration of linezolid and serotoninergic agents 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 signs or symptoms occur, one or both agents should be discontinued; if the antidepressant is discontinued, symptoms may resolve.

Hypontremia and SIADH

There have been reports of hypontremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) in some patients treated with linezolid. It is recommended to regularly monitor serum sodium levels in patients at risk of hypontremia, 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

There have been reports of peripheral neuropathy, as well as optic neuropathy and optic neuritis, which may progress to loss of vision in patients treated with linezolid; these cases have occurred mainly in patients treated for periods longer than the recommended maximum duration of 28 days.

Patients should be advised to report any visual symptoms, such as changes in visual acuity, changes in color vision, blurred vision, or defects in the visual field. In such cases, visual function should be evaluated as soon as possible, and an ophthalmologist should be consulted if necessary. Visual function should be regularly monitored in any patient treated with Linezolid Normon 2 mg/ml for a period longer than the recommended 28 days.

The continuation of treatment with Linezolid Normon 2 mg/ml in patients who have suffered optic or peripheral neuropathy should be evaluated against the potential risks.

There may be a higher risk of neuropathies when linezolid is used in patients who are currently taking or have recently taken antimycobacterial medication for the treatment of tuberculosis.

Seizures

There have been reports of seizures in patients treated with 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.

Inhibitors of monoamine oxidase

Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO); however, it does not exert any antidepressant effect at the doses used for antibacterial treatment. There is limited data on the interaction and safety of linezolid in patients receiving concomitant treatment with medications that increase the risk of MAO inhibition. Therefore, linezolid should not be used in these circumstances, except if close monitoring and control of the patient can be performed (see sections 4.3 and 4.4).

Use with foods rich in tyramine

Patients should be advised not to consume large amounts of foods rich in tyramine (see section 4.5).

Superinfection

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

Occasionally, the use of antibiotics 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 if the expected benefit outweighs the potential risk (see sections 4.2 and 5.2 of the summary of product characteristics).

Linezolid should only be used in patients with severe liver impairment if the expected benefit outweighs the potential risk (see sections 4.2 and 5.2).

Effects on fertility

In studies in adult male rats, linezolid caused a reversible decrease in fertility and abnormal sperm morphology; the potential effects of linezolid on human male reproductive system are unknown (see section 5.3).

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, decubitus ulcers, ischemic lesions, severe burns, or gangrene. Therefore, there is limited experience with the use of linezolid in the treatment of these conditions.

Warnings about excipients

Glucose

This medicinal product contains glucose. If your doctor has told you that you have a certain type of sugar intolerance, consult with them before taking this medicinal product.

Patients with diabetes mellitus should be aware that this medicinal product contains 13.7 g of glucose per dose.

Sodium

This medicinal product contains 114 mg of sodium (the main component of table salt/for cooking) per dose. This is equivalent to 5.7% of the maximum recommended daily intake for an adult. Linezolid Normon 2 mg/ml 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 taken into account in relation to the total sodium intake from all sources administered to the patient.

Interactions with other medicinal products and other forms of interaction

Inhibitors of monoamine oxidase

Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO). The data from interaction and safety studies of linezolid administered to patients receiving concomitant treatment with medications that increase the risk of MAO inhibition are very limited. Therefore, linezolid should not be used in these circumstances, except if close monitoring and control of the patient can be performed (see sections 4.3 and 4.4).

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 30-40 mmHg, compared with 11-15 mmHg produced by linezolid alone, 14-18 mmHg produced by pseudoephedrine or phenylpropanolamine alone, and 8-11 mmHg produced by placebo. No similar studies have been performed in hypertensive patients. It is recommended that if linezolid is administered with medications with vasopressor effects (including dopaminergic agents), the doses of these medications should be carefully titrated to achieve the desired response.

Potential serotoninergic interactions

The potential pharmacological interaction of linezolid with dextromethorphan was studied in healthy volunteers. 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 effects of serotonin syndrome were observed (confusion, delirium, restlessness, tremor, flushing, diaphoresis, hyperpyrexia).

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.

There have been reports of serotonin syndrome during the concomitant clinical use of linezolid with serotoninergic agents, including antidepressants such as SSRIs and opioids (see section 4.3 of the technical data sheet). Therefore, concomitant administration is contraindicated (see section 4.3 of the technical data sheet), except if the concomitant administration of linezolid and serotoninergic agents 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 signs or symptoms occur, one or both agents should be discontinued; if the antidepressant is discontinued, symptoms may resolve.

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 large amounts of foods or beverages high in tyramine (e.g. aged cheese, yeast extracts, undistilled alcoholic beverages, and fermented soy products such as soy sauce) need to be avoided.

Medicaments metabolized through the cytochrome P450

Linezolid is not metabolized to a detectable extent by the cytochrome P450 (CYP) enzyme system or inhibits any of the clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4). Similarly, linezolid does not induce CYP450 isoenzymes in rats. Therefore, no pharmacological interactions induced by CYP450 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

The simultaneous administration of warfarin and linezolid (in steady-state) produced a 10% mean reduction in the maximum INR (International Normalized Ratio) and a 5% reduction in the AUC of INR. The 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

The data on the use of linezolid in pregnant women are limited. Animal studies have shown reproductive toxicity (see section 5.3). There is a potential risk in humans.

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

Lactation

The data from animal studies suggest that linezolid and its metabolites may pass into breast milk, so breastfeeding should be interrupted before and during treatment.

Fertility

In animal studies, linezolid caused a decrease in fertility (see section 5.3).

Effects on the ability to drive and use machines

Patients should be advised that they may experience dizziness or visual disturbances (as described in sections 4.4 and 4.8) while receiving linezolid and should be advised not to drive or operate machinery if any of these symptoms occur.

Adverse reactions

The following table lists all adverse reactions of this medicinal product and their frequencies based on all causality data from clinical trials in which more than 6,000 adult patients received the recommended doses of linezolid for 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 most frequently reported adverse reactions that required discontinuation of treatment were headache, diarrhea, nausea, and vomiting. Approximately 3% of patients discontinued treatment due to an adverse reaction related to the medicinal product.

The following adverse reactions have been reported during post-marketing experience and are included in the table in the category of “Frequency not known”, 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 <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000), and frequency not known (cannot be estimated from the available data).

System Organ Class	Common (≥1/100 to <1)	Uncommon (≥1/1.000 to <1)	Rare (≥1/10.000 to <1)	Very rare (<1)	Frequency not known (cannot be estimated from the available data)
Infecions and infestations	candidiasis, oral candidiasis, vaginal candidiasis, fungal infections	antibiotic-associated colitis, pseudomembranous colitis*, vaginitis
Haematological disorders	thrombocytopenia*, anemia*†	pancytopenia*, leucopenia*, neutropenia, thrombocytopenia*, eosinophilia	sideroblastic anemia*		myelosuppression*
Immune system disorders			anaphylaxis
Metabolism and nutrition disorders		hypontremia	lactic acidosis*
Mental disorders	insomnia
Nervous system disorders	headache, metallic taste perception error, dizziness	seizures*, peripheral neuropathy*, hypoesthesia, paresthesia			serotonin syndrome**
Eye disorders		optic neuropathy*, blurred vision*	abnormal visual field changes*		optic neuritis*, loss of vision*, changes in visual acuity*, changes in color vision*
Ear and labyrinth disorders		tinnitus
Cardiac disorders		arrhythmia (tachycardia)
Vascular disorders	hypertension	transient ischemic attacks, phlebitis, thrombophlebitis
Gastrointestinal disorders	diarrhea, nausea, vomiting, abdominal pain localized or generalized, constipation, dyspepsia	pancreatitis, gastritis, abdominal distension, dry mouth, glossitis, soft stools, stomatitis, changes in tongue color	tooth discoloration
Hepatobiliary disorders	abnormal liver function tests; elevated AST, ALT, and alkaline phosphatase	elevated total bilirubin
Skin and subcutaneous tissue disorders	pruritus, skin rash	angioedema, urticaria, dermatitis herpetiformis, dermatitis, diaphoresis	toxic epidermal necrolysis#, Stevens-Johnson syndrome#, hypersensitivity vasculitis		< Країна реєстрації Іспанія Активна речовина Linezolid Потрібен рецепт Так Виробник Laboratorios Normon S.A. Склад Citrato de sodio (e-331) (492 mg mg), Glucosa (15.06 g mg), Hidroxido de sodio (e 524) (C.S.PH=4.0-6.0 mg mg) Информация носит справочный характер и не является медицинской рекомендацией. Перед приёмом любых препаратов проконсультируйтесь с врачом. Oladoctor не несёт ответственности за медицинские решения, принятые на основе этого контента. Поговоріть з лікарем онлайн Маєте питання щодо цього лікування або ваших симптомів? Зв'яжіться з ліцензованим лікарем для отримання допомоги та персонального догляду. 5.01 відгук Анна Морет Дерматологія18 років досвіду Анна Морет — лікарка-дерматолог і дерматовенеролог із міжнародною сертифікацією. Спеціалізується на дерматології дорослих і дітей, венерології, естетичному догляді за шкірою та загальній медицині. Проводить онлайн-консультації, базуючись на доказовій медицині та індивідуальних потребах кожного пацієнта. Сфера допомоги охоплює: • захворювання шкіри: екзема, акне, розацеа, дерматити, псоріаз • проблеми з волоссям і шкірою голови: випадіння волосся, лупа, себорейний дерматит • дитяча дерматологія — від новонароджених до підлітків • венерологія та інфекції, що передаються статевим шляхом (ІПСШ) • естетичні запити: вікові зміни шкіри, неінвазивні косметологічні процедури • алергічні реакції та підвищена чутливість шкіри • перевірка родимок, оцінка новоутворень, скринінг раку шкіри • поради щодо догляду за шкірою та підбір індивідуальної космецевтики Поєднуючи дерматологію із загальноклінічним досвідом, Анна Морет надає всебічну допомогу, що охоплює як стан шкіри, так і супутні захворювання. Має сертифікацію Канадської ради естетичної медицини, що підтверджує міжнародний підхід до естетичної дерматології. Записатися на онлайн-консультацію Більше часу 5.01 відгук Аліна Цуркан Сімейна медицина12 років досвіду Аліна Цуркан — ліцензована лікарка сімейної медицини в Португалії. Проводить онлайн-консультації для дорослих і дітей, допомагаючи пацієнтам у вирішенні широкого спектра щоденних медичних запитів з професійним підходом і увагою до деталей. Звернутися можна з такими станами: • респіраторні інфекції: застуда, грип, бронхіт, пневмонія • Захворювання очей: кон’юнктивіт (інфекційний і алергічний) • ЛОР-захворювання: синусит, отит, тонзиліт • проблеми з травленням: гастрит, кислотний рефлюкс, синдром подразненого кишківника (СПК) • інфекції сечових шляхів та інші поширені інфекції • хронічні захворювання: артеріальна гіпертензія, діабет, порушення функції щитоподібної залози • головний біль і мігрень Окрім лікування симптомів, Аліна Цуркан приділяє особливу увагу профілактиці та ранньому виявленню захворювань. Проводить планові огляди, надає медичні рекомендації, здійснює повторні консультації та виписує рецепти — з урахуванням індивідуальних потреб кожного пацієнта. Її підхід — комплексний, уважний і адаптований до кожного етапу життя пацієнта: від гострих станів до довготривалого контролю здоров’я. Записатися на онлайн-консультацію Більше часу 5.09 відгуків Андрій Попов Терапія6 років досвіду Андрій Попов — ліцензований в Іспанії терапевт і фахівець із лікування болю. Проводить онлайн-консультації для дорослих, допомагаючи впоратися з хронічним і гострим болем, а також із широким спектром загальних медичних запитів. Спеціалізується на діагностиці та лікуванні болю, що триває понад 3 місяці або суттєво знижує якість життя. Працює з такими станами, як: • хронічний біль будь-якого походження • мігрень і повторювані головні болі • біль у шиї, спині, попереку та суглобах • посттравматичний біль після травм, розтягнень або операцій • невропатичний біль, фіброміалгія, невралгії Окрім знеболення, Андрій Попов допомагає пацієнтам у веденні загальних медичних станів, зокрема: • респіраторні інфекції (застуда, бронхіт, пневмонія) • артеріальна гіпертензія, порушення обміну речовин, цукровий діабет • профілактичні огляди та контроль загального стану здоров’я Онлайн-консультація триває до 30 хвилин і включає детальний аналіз симптомів, рекомендації щодо обстежень, формування індивідуального плану лікування та подальший супровід за потреби. Андрій Попов дотримується принципів доказової медицини, поєднуючи клінічний досвід із уважним і персоналізованим підходом до кожного пацієнта. Записатися на онлайн-консультацію Більше часу 5.01 відгук Євген Яковенко Загальна хірургія11 років досвіду Євген Яковенко — ліцензований лікар-хірург і терапевт в Іспанії. Спеціалізується на загальній і дитячій хірургії, внутрішній медицині та лікуванні болю. Проводить онлайн-консультації для дорослих і дітей, поєднуючи хірургічну практику з терапевтичним супроводом. Сфера медичної допомоги охоплює: • діагностику та лікування гострого й хронічного болю • перед- і післяопераційний супровід, оцінку ризиків, контроль стану • хірургічні захворювання: грижі, жовчнокам’яна хвороба, апендицит • консультації з дитячої хірургії: вроджені стани, дрібні втручання • травми: переломи, ушкодження м’яких тканин, обробка ран • онкохірургія: консультації, планування, супровід після лікування • внутрішні захворювання: патології серцево-судинної та дихальної систем • ортопедичні стани, реабілітація після травм • інтерпретація результатів візуалізації для хірургічного планування Євген Яковенко активно займається науковою діяльністю та міжнародною співпрацею. Член Асоціації хірургів Німеччини (BDC), співпрацює з Асоціацією сімейних лікарів Лас-Пальмаса та Німецьким консульством на Канарських островах. Регулярно бере участь у міжнародних медичних конференціях і публікує наукові статті. Поєднуючи багатопрофільний досвід із доказовою медициною, він надає точну та індивідуалізовану допомогу для пацієнтів із різними медичними запитами. Записатися на онлайн-консультацію Більше часу Переглянути всіх лікарів Слідкуйте за новинами та заощаджуйте на послугах Поради лікарів, оновлення платформи та знижки для підписників. Підписатися Слідкуйте за нами в соцмережах ПослугиЛікаріДопомога Пошук