LINEZOLID ALTAN 2 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

LinezolidAltan2mg/ml solution for infusion EFG

linezolid

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the package leaflet

1. What is Linezolid Altan and what is it used for
2. What you need to know before you use Linezolid Altan
3. How to use Linezolid Altan
4. Possible side effects
5. Storage of Linezolid Altan
6. Contents of the pack and further information

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

Linezolid Altan is an antibiotic of the oxazolidinone group that works by preventing the growth of certain bacteria (germs) that cause infections.

It is used to treat pneumonia and certain skin or subcutaneous tissue infections. Your doctor will have decided if linezolid is suitable for treating your infection.

2. What you need to know before you use Linezolid Altan

Do not use LinezolidAltan:

• If you are allergic (hypersensitive) to linezolid or any of the other components of this medication (listed in section 6).
• If you are taking or have taken in the last 2 weeks any medication called monoamine oxidase inhibitors (MAOIs, such as phenelzine, isocarboxazid, selegiline, moclobemide). These medications are usually used to treat depression or Parkinson's disease.
• If you are breastfeeding. This medication passes into breast milk and could affect the baby.

Warnings and precautions

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

Linezolid Altan may not be suitable for you if you answer yesto any of the following questions. In that case, inform your doctor, as they will need to monitor your overall 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 medications 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 cause symptoms of diarrhea, skin flushing, and wheezing)?
• Do you suffer from bipolar disorder, schizophrenic disorder, mental confusion, or other mental problems?
• Do you have a history of hyponatremia (low sodium levels in the blood) or take medications that reduce sodium levels in the blood, such as certain diuretics (also called "water pills") like hydrochlorothiazide?
• Do you take any opioids?

The use of certain medications, including antidepressants and opioids, along with Linezolid may cause side effects such as changes in blood pressure, body temperature, or heart rate.

Inform your doctor or pharmacist if you are using, have recently used, or may need to use another medication.

Tell your doctor if you are taking or have taken in the last 2 weeksthe following medications, as you must notuse Linezolid Altan if you are still taking them or have taken them recently (see also section 2 above "Do not use Linezolid Altan").

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

Also, inform your doctor if you are taking the following medications.

Your doctor may decide to treat you with Linezolid Altan, but will need to assess your overall health and blood pressure before and during treatment. In other cases, your doctor may decide that another treatment is better for you.

• Cold remedies containing pseudoephedrine or phenylpropanolamine.
• Certain medications for asthma, such as salbutamol, terbutaline, fenoterol.

Certain antidepressants called tricyclics or SSRIs (selective serotonin reuptake inhibitors). There are many medications of this type, including amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, or sertraline; or certain medications used to treat opioid dependence, such as buprenorphine. These medications may interact with linezolid, and you may experience symptoms such as involuntary muscle contractions, agitation, hallucinations, coma, excessive sweating, tremors, increased muscle tone, and high body temperature. Contact your doctor if you experience these symptoms.

• Medications used to treat migraines, such as sumatriptan or zolmitriptan.
• Medications for treating severe allergic reactions, such as adrenaline (epinephrine).
• Medications that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine.
• Opioids, such as pethidine, used to treat moderate to severe pain.
• Medications used to treat anxiety disorders, such as buspirone.
• Medications that prevent blood clotting, such as warfarin.
• An antibiotic called rifampicin.

Using Linezolid Altan with food, drinks, and alcohol

• You can use Linezolid Altan before, during, or after meals.
• Avoid eating excessive amounts of cheese, yeast extracts, or soybean extracts (such as soy sauce) and alcoholic beverages, especially draft beer and wine. The reason is that Linezolid Altan may react with a substance called tyramine that is naturally present in some foods, causing an increase in your blood pressure.
• If you start experiencing headaches after eating or drinking, inform your doctor, pharmacist, or nurse immediately.

Pregnancy, breastfeeding, and fertility

The effect of Linezolid Altan on pregnant women is unknown. Therefore, pregnant women should not use Linezolid Altan unless advised by their doctor.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist.

You should not breastfeed while using Linezolid Altan because this medication passes into breast milk and could affect your baby.

Driving and using machines

Linezolid Altan may cause dizziness or vision problems. If this happens, do not drive or use machines. Remember that if you are not feeling well, your ability to drive or use machines may be affected.

Linezolid Altan contains glucose and sodium

Glucose

This medication contains glucose.

Patients with diabetes mellitus should note that this medication contains (13.7 g of glucose per bag). Each ml of this medication contains 45.7 mg of glucose.

Sodium

This medicine contains 114 mg of sodium (main component of table salt/kitchen salt) per 300 ml infusion bag. This amount is equivalent to 5.7% of the maximum recommended daily intake of sodium for an adult. Please inform your doctor or nurse if you are on a low-sodium diet.

3. How to use Linezolid Altan

Adults

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

This medication will be administered by a doctor or other healthcare professional through a drip (by 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 a dialysis program, you will be administered Linezolid Altan after each session.

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

While using Linezolid Altan, your doctor will perform periodic blood tests to monitor your blood count.

If you use Linezolid Altan for more than 28 days, your doctor will need to monitor your vision.

Use in children and adolescents

Linezolid Altan is not normally used in children or adolescents (under 18 years).

If you use more Linezolid Altan than you should

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

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

If you forget to use Linezolid Altan

Since this medication is administered under close supervision, it is very unlikely that a dose will be missed. If you think a dose of treatment has been missed, inform your doctor or nurse. Do not take a double dose to make up for missed doses.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Tell your doctor, nurse, or pharmacist immediatelyif you notice any of these side effects during your treatment with Linezolid:

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

• Severe skin reactions (uncommon), swelling, particularly around the face and neck (uncommon), wheezing, and/or difficulty breathing (rare). This may be a sign of an allergic reaction and may require discontinuation of treatment with Linezolid Altan. Skin reactions such as a purple rash due to inflammation of blood vessels (rare), red, painful, and scaly skin (dermatitis) (uncommon), skin rash (frequent), itching (frequent).
• Vision problems (uncommon), such as blurred vision (uncommon), changes in color perception (not known), difficulty seeing details (not known), or if you notice that your field of vision is reduced (rare).
• Severe diarrhea that contains blood and/or mucus (antibiotic-associated colitis, including pseudomembranous colitis), which in rare circumstances may lead to life-threatening complications (uncommon).
• Repeated nausea or vomiting, abdominal pain, or rapid breathing (rare).
• There have been reports of epileptic seizures or convulsions (uncommon).
• Serotonin syndrome (not known). You should inform your doctor if you experience agitation, confusion, delirium, rigidity, tremors, coordination problems, convulsions, rapid heartbeat, severe respiratory problems, and diarrhea (suggestive of serotonin syndrome) while also being treated with antidepressants called 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 cause anemia (frequent).
• Reduction in the number of blood cells that can affect the ability to fight infections (uncommon). Some signs of infection include: fever (frequent), sore throat (uncommon), mouth ulcers (uncommon), and fatigue (uncommon).
• Rhabdomyolysis (rare): Signs and symptoms include muscle pain, sensitivity, or weakness, and/or dark urine. These can be signs of a serious disease called rhabdomyolysis (muscle degradation), which can cause kidney damage.
• Pancreatitis (uncommon).
• Convulsions (uncommon).
• Transient ischemic attacks (temporary alteration of blood flow to the brain that causes short-term symptoms such as vision loss, weakness in arms and legs, difficulty speaking, and loss of consciousness) (uncommon).
• "Ringing" in the ears (tinnitus) (uncommon).

There have been reports of numbness, tingling, or blurred vision in patients who have used Linezolid Altan 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):

• Fungal infections, especially in the vagina or mouth.
• Headache.
• Metallic taste.
• Diarrhea, vomiting, nausea.
• Alteration of some blood test results, proteins, salts, or enzymes that measure liver, kidney, or blood sugar function.
• Difficulty sleeping.
• Increased blood pressure.
• Anemia (reduction in the number of red blood cells).
• Itching.
• Dizziness.
• Abdominal pain, general or localized.
• Constipation.
• Indigestion.
• Localized pain.
• Reduced platelet count.

Uncommon(may affect up to 1 in 100 people):

• Vaginal or genital inflammation in women.
• Feeling of tingling or numbness.
• Swelling, discomfort, color changes of the tongue.
• Dry mouth.
• Pain at the injection site (vein) or around it.
• Vein inflammation (including the location where the infusion is administered).
• Need to urinate more frequently.
• Chills.
• Feeling of thirst.
• Increased sweating.
• Hyponatremia (low sodium levels in the blood).
• Kidney failure.
• Abdominal swelling.
• Pain at the injection site.
• Increased creatinine.
• Stomach pain.
• Changes in heart rhythm (e.g., increased heart rate).
• Decreased blood cell count.
• Weakness and/or sensory changes.

Rare(may affect up to 1 in 1,000 people):

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

Not known (frequency cannot be estimated from available data):

• Alopecia (hair loss)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Linezolid Altan

Keepthis medicationout of sight and reach of children.

Do not use this medication after the expiration date stated on the packaging after “EXP”. The expiration date is the last day of the indicated month.

Do not freeze.

Hospital staff will ensure that Linezolid Altan is not used after the printed use-by date and that it is administered immediately after breaking the seal. They will also visually inspect the solution before use and only use it if it is transparent and particle-free. They will also ensure that the solution is stored correctly in its container and aluminum paper wrapper to protect it from light and keep it out of sight and reach of children until use.

After opening:

From a microbiological point of view, unless the opening method prevents the risk of microbial contamination, the product should be used immediately. If not used immediately, the storage time and conditions are the responsibility of the user.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Container Content and Additional Information

Linezolid CompositionAltan

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

The other components are glucose monohydrate (a type of sugar, see section 2. Linezolid Altan contains glucose), sodium citrate (E331, see section 2), anhydrous citric acid (E330), hydrochloric acid (E507) or sodium hydroxide (E524) to adjust the pH and water for injectable preparations.

Product Appearance and Container Content

Linezolid Altan is a clear solution presented in a single infusion bag containing 300 ml (600 mg of linezolid) of solution.

The bags are presented in packs of 1, 10 or 25 bags.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Altan Pharmaceuticals, S.A.

C/ Cólquide, Nº 6, Portal 2, 1ª planta, Oficina F. Edificio Prisma

Las Rozas, 28230 Madrid, Spain

Manufacturer

Infomed Fluids S.R.L

50 Theodor Pallady blvd, District 3,

032266 Bucharest, Romania

Tel: +40 21 345 02 22

Fax: +40 21 345 3185

E-mail: [email protected]

This medicinal product has been authorized in the EU Member Statesand in the United Kingdom (Northern Ireland)under the following names:

France: Linezolid Panpharma 2 mg/ml Solution for Infusion

Germany: Linezolid Panpharma 2 mg/ml Infusion Solution

Romania: Linezolid Infomed 2 mg/ml solution for infusion

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

Date of the last revision of thisleaflet:

March 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

IMPORTANT: Consult the technical data sheet before prescribing.

Linezolid is not active against infections caused by Gram-negative pathogenic microorganisms. Treatment against Gram-negative microorganisms should be initiated concomitantly if co-infection with Gram-negative pathogenic microorganisms is certain or suspected.

Description

Intravenous infusion bags for single use, latex-free, multilayer polyolefin sealed, with an outer aluminum laminate bag. Each bag contains 300 ml of solution and is presented in a pack. Each pack contains 1, 10 or 25 intravenous infusion bags.

Linezolid Altan 2 mg/ml solution for infusion contains linezolid 2 mg/ml in an isotonic, clear, colorless to yellow solution. The other components are: glucose monohydrate, sodium citrate (E331), anhydrous citric acid (E330), hydrochloric acid (E507) or sodium hydroxide (E524) and water for injectable preparations.

Posology and Method of Administration

Treatment with linezolid should only be initiated in the hospital setting and after evaluation by a specialist physician, such as a microbiologist or an infectious disease specialist.

Patients who initiate treatment with the parenteral formulation may switch to any of the oral formulations 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 (IV) twice a day.

Duration and Recommended Dosage for Treatment in Adults:

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

The recommendations on the duration of treatment indicated below reflect those used in clinical trials. For some types of infection, it may be convenient 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 when administered for periods longer than 28 days have not been established (see section 4.4).

Infections associated with bacteremia do not require increasing the recommended dose or duration of treatment. The recommended doses of linezolid are as follows:

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

Elderly Patients:No dose adjustment is required.

Renal Insufficiency:No dose adjustment is required.

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

Since approximately 30% of the linezolid dose is eliminated during 3 hours of hemodialysis, linezolid should be administered after dialysis in patients receiving such treatment. The main metabolites of linezolid are partially eliminated by hemodialysis, but their concentrations are considerably higher after dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency. Therefore, linezolid should be used with special caution in patients with severe renal insufficiency undergoing dialysis and only if the expected benefit outweighs the possible risk.

So far, there is no experience with the administration of linezolid in patients on continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal insufficiency (other than hemodialysis).

Hepatic Insufficiency:Patients with mild to moderate hepatic insufficiency (Class A or B in the Child-Pugh scale): No dose adjustment is required.

Mild to Moderate Hepatic Insufficiency (Class C in the Child-Pugh Scale):Since linezolid is metabolized through a non-enzymatic process, it is expected that impaired hepatic function will not significantly alter its metabolism, and therefore, no dose adjustment is recommended. However, there are insufficient clinical data, and it is recommended to use linezolid in these patients only if the expected benefit outweighs the theoretical risk (see sections 4.4 and 5.2 of the Technical Data Sheet).

Contraindications

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

Linezolid should not be used in patients who are taking monoamine oxidase inhibitors A or B (e.g., phenelzine, isocarboxazid, selegiline, moclobemide) or during the two weeks following the administration of such medication.

Unless the necessary means are available to perform 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, thyrotoxicosis, bipolar disorder, psychoaffective disorders, acute confusional state.

• Patients who are taking any of these medications: serotonin reuptake inhibitors (see section 4.4), tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), direct or indirect sympathomimetics (including adrenergic bronchodilators, pseudoephedrine, and phenylpropanolamine), vasopressors (e.g., epinephrine, norepinephrine), dopaminergic drugs (e.g., dopamine, dobutamine), pethidine, or buspirone.

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

Myelosuppression

Cases of myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) have been reported in patients treated with linezolid. In patients who were followed up, it has been seen that after discontinuing treatment, the affected hematological parameters have increased towards pre-treatment levels. The risk of these effects appears to be associated with the duration of treatment. Elderly patients treated with linezolid may be at greater risk of experiencing blood dyscrasias than younger patients. Thrombocytopenia may occur more frequently in patients with severe renal insufficiency, with or without dialysis, and in patients with moderate to severe hepatic insufficiency. Therefore, it is recommended to perform close monitoring of the blood count in patients who: have pre-existing anemia, granulocytopenia, or thrombocytopenia; are receiving concomitant medication that may decrease hemoglobin levels or hematocrit or affect platelet count or function; have severe renal insufficiency or moderate to severe hepatic insufficiency; or are receiving more than 10-14 days of treatment. Linezolid should only be administered to these patients if it is possible to perform close monitoring of hemoglobin levels, blood count, and platelet count.

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

Additionally, a complete blood count (including hemoglobin, platelets, absolute leukocyte count, and formula) is recommended weekly for patients receiving linezolid, regardless of their baseline blood count.

In compassionate use studies, a higher incidence of severe anemia was reported in patients who were being treated with linezolid for periods longer than the recommended maximum treatment duration of 28 days. These patients required blood transfusions more frequently. 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.

Cases of sideroblastic anemia have been reported during post-marketing experience. In the cases where the start time is known, most patients were treated for more than 28 days. Most patients recovered fully or partially after discontinuing treatment with linezolid, with or without treatment for anemia.

Mortality Imbalance in a Clinical Trial in Patients with Gram-Positive Vascular Infections Related to Catheters

In an open study in seriously ill patients with catheter-related Gram-positive vascular infections, an excess of mortality was observed in patients treated with linezolid compared to those treated with vancomycin/dicloxacillin/oxacillin [78/363 (21.5%) versus 58/363 (16.0%)]. The main factor influencing the mortality rate 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 study 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 co-infection with Gram-negative microorganisms is suspected or confirmed, if no alternative treatments are available (see section 4.1). In these circumstances, concomitant treatment against 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 Clostridium difficile-associated diarrhea, have been reported, whose severity can range from mild diarrhea to life-threatening colitis. Therefore, it is essential to consider this diagnosis in patients who develop severe diarrhea during or after treatment with linezolid. If antibiotic-associated diarrhea or colitis is suspected or confirmed, treatment with antibacterial agents, including linezolid, should be discontinued, and appropriate therapeutic measures should be initiated immediately. In this situation, medications that inhibit peristalsis are contraindicated.

Lactic Acidosis

Cases of lactic acidosis have been reported 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 treatment with linezolid 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; these events are more frequent when the duration of treatment is longer than 28 days.

Serotonin Syndrome

Spontaneous reports of serotonin syndrome, a potentially life-threatening condition, have been associated with the concomitant administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids (see section 4.5). Therefore, concomitant administration of linezolid and serotonergic agents is contraindicated (see section 4.3), unless the administration of linezolid and serotonergic 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 incoordination. If signs or symptoms appear, consideration should be given to discontinuing one or both agents; if treatment with the serotonergic agent is discontinued, symptoms may disappear.

The occurrence of serotonin syndrome has also been associated with the concomitant administration of linezolid and buprenorphine.

Rhabdomyolysis

Cases of rhabdomyolysis have been reported with the use of linezolid. Linezolid should be used with caution in patients with predisposing factors to rhabdomyolysis. If signs or symptoms of rhabdomyolysis are observed, treatment with linezolid should be discontinued, and appropriate treatment should be initiated.

Hyponatremia and SIADH

Hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been observed in some patients treated with linezolid. It is recommended to regularly monitor serum sodium levels in patients at risk of hyponatremia, such as elderly patients or those taking medications that may reduce sodium levels in the blood (e.g., thiazide diuretics such as hydrochlorothiazide).

Optic and Peripheral Neuropathy

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

All patients should be warned to report symptoms of visual disturbance, such as changes in visual acuity, changes in color vision, blurred vision, or defects in the visual field. In such cases, evaluation of visual function should be performed as soon as possible, and an ophthalmologist should be consulted if necessary. Visual function should be monitored regularly in any patient treated with Linezolid for a period longer than the recommended 28 days.

Continuation of treatment with Zyvoxid in patients who have suffered optic or peripheral neuropathy should be weighed 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

Cases of seizures have been reported in patients treated with Linezolid Altan. In most of these cases, a history of previous seizures or risk factors for seizures was reported. Patients should be advised to inform their doctor if they have a history of seizures.

Monoamine Oxidase Inhibitors

Linezolid is a reversible and non-selective monoamine oxidase inhibitor (MAOI); however, it has no antidepressant effect at the doses used for antibacterial treatment. There are limited data on pharmacological interaction and safety studies of linezolid in patients receiving linezolid and MAOIs.

and present underlying pathologies and/or receive concomitant treatment with drugs that increase this risk. Therefore, the use of linezolid is not recommended in these circumstances, unless close observation and monitoring of the patient are possible (see sections 4.3 and 4.5).

Use with tyramine-rich foods

Patients should be warned not to consume large amounts of tyramine-rich foods (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 can produce the overgrowth of non-susceptible microorganisms. Approximately 3% of patients who received linezolid at the recommended doses during clinical trials presented treatment-associated candidiasis. In cases of superinfection during treatment, appropriate measures should be taken.

Special populations

Linezolid should be used with special caution in patients with severe renal insufficiency, and only if the expected benefit is considered to outweigh the possible risk (see sections 4.2 and 5.2 of the product characteristics summary).

It is recommended that linezolid be administered to patients with severe hepatic insufficiency only if the expected benefit is considered to outweigh the possible risk (see sections 4.2 and 5.2).

Effects on fertility

In studies conducted in adult male rats with linezolid exposure levels similar to those expected in humans, a reversible decrease in fertility and abnormal sperm morphology were observed. The potential effects of linezolid on the 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.

Controlled clinical trials did not include patients with diabetic foot lesions, decubitus ulcers, ischemic lesions, severe burns, or gangrene. Consequently, there is limited experience with the use of linezolid in the treatment of these pathologies.

Excipient warnings

Glucose

Each ml of solution contains 45.7 mg of glucose (13.7 g in 300 ml), which should be taken into account in the treatment of patients with diabetes mellitus.

Sodium

This medicinal product contains 114 mg of sodium per 300 ml infusion bag (0.38 mg/ml), equivalent to 5.7% of the maximum recommended daily sodium intake by the WHO of 2 g of sodium for an adult. The sodium content should be taken into account in patients on a controlled sodium diet.

The linezolid infusion solution can be further 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 from all sources that will be administered to the patient.

Interaction with other medicinal products and other forms of interaction

Monoamine oxidase inhibitors

Linezolid is a reversible non-selective monoamine oxidase inhibitor (MAOI). The data from linezolid pharmacological interaction and safety studies administered to patients undergoing concomitant treatments with MAO inhibition risk are very limited. Therefore, the use of linezolid is not recommended in these circumstances, unless close observation and control of the patient are possible (see sections 4.3 and 4.4).

Potential interactions that produce increased blood pressure

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

Potential serotonergic 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 difference, with or without linezolid. In healthy subjects who received linezolid and dextromethorphan, no effects of the serotonin syndrome (confusion, delirium, restlessness, tremor, flushing, diaphoresis, and hyperpyrexia) were observed.

During post-marketing experience: a case of a patient experiencing symptoms similar to those of the serotonin syndrome during the intake of linezolid and dextromethorphan has been reported, which resolved with the interruption of both treatments.

Linezolid should be used with caution when administered concomitantly with buprenorphine due to the increased risk of serotonergic syndrome, a life-threatening condition (see section 4.4 of the Technical Sheet).

Cases of serotonergic syndrome have been reported during the clinical use of linezolid in combination with serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids. Therefore, as concomitant administration is contraindicated (see section 4.3), the management of patients for whom treatment with linezolid and serotonergic agents is absolutely necessary is described in section 4.4.

Use with tyramine-rich foods

No significant pressor response was observed in subjects who received linezolid and less than 100 mg of tyramine. This suggests that only excessive intake of foods or beverages with high tyramine content (e.g., mature cheese, yeast extracts, non-distilled alcoholic beverages, and fermented soy products such as soy sauce) should be avoided.

Drugs metabolized through cytochrome P450

Linezolid is not detectably metabolized by the cytochrome P450 enzyme system nor does it inhibit any of the human cytochrome P450 isoforms that are significantly involved in drug metabolism (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4). Similarly, linezolid does not induce cytochrome P450 isoenzymes in rats. Therefore, no cytochrome P450-mediated drug interactions are expected with linezolid.

Rifampicin

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

Warfarin

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

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, unless clearly necessary, i.e., only if the potential benefit outweighs the possible risk.

Breastfeeding

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

Fertility

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

Effects on ability to drive and use machines

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

Adverse reactions

In the following table, all adverse reactions of this medicinal product and their frequencies are listed based on all causality data from clinical trials in which more than 6,000 adult patients received the recommended doses of linezolid for up to 28 days. The most frequently reported adverse reactions were diarrhea (8.49%), nausea (6.9%), vomiting (4.3%), and headache (4.2%).

The adverse reactions most frequently reported that led to treatment discontinuation were headache, diarrhea, nausea, and vomiting. Approximately 3% of patients discontinued treatment due to a drug-related adverse reaction.

Additional adverse reactions reported during post-marketing experience are included in the table.

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

1 See section 4.4 Special warnings and precautions for use

2 See section 4.3 Contraindications and 4.5 Interaction with other medicinal products and other forms of interaction

3 See below

# Adverse reaction frequency estimated using the "rule of three".

The following adverse reactions to linezolid were considered serious in rare cases: localized abdominal pain, transient ischemic attacks, and hypertension.

3 In controlled clinical trials where linezolid was administered for periods of up to 28 days, 2% of patients reported anemia. In a compassionate use program for patients with life-threatening infections and underlying co-morbidities, the percentage of patients who developed anemia when receiving linezolid ≤ 28 days was 2.5% (33/1326) compared to 12.3% (53/430) when treated for > 28 days. The proportion of cases of medication-related severe anemia requiring blood transfusion was 9% (3/33) in patients treated ≤ 28 days and 15% (8/53) in those treated for more than 28 days.

Pediatric population

The safety data from clinical trials based on more than 500 pediatric patients (from birth to 17 years) do not indicate that the safety profile of linezolid for pediatric patients differs from that of adults.

Reporting of suspected adverse reactions

It is important to report any suspected adverse reactions to the medicinal product after authorization. This allows for continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Spanish Medicines Surveillance System for Human Use https://www.notificaram.es.

Overdose

No specific antidote is known.

No cases of overdose have been reported. However, the following information may be useful:

Supportive measures should be instituted, along with maintenance of glomerular filtration.

Approximately 30% of the linezolid dose is eliminated during 3 hours of hemodialysis, but no data are available on the elimination of linezolid by peritoneal dialysis or hemoperfusion. The two main metabolites of linezolid are also eliminated to some extent by hemodialysis.

The signs of toxicity in rats, after administration of 3,000 mg/kg/day of linezolid, were decreased activity and ataxia, while dogs treated with 2,000 mg/kg/day presented vomiting and tremors.

Instructions for use and handling

For single use only. Remove the outer bag only at the time of use, checking for minor leaks by firmly squeezing the bag. In case of leaks, it should not be used because it may have lost its sterility. The solution should be visually inspected before use, and only transparent and particle-free solutions should be used. These bags should not be used in serial connections with other medicinal products (see section 6.2). Unused solution should be discarded.

Do not reuse used bags.

Linezolid Altan solution for infusion is compatible with the following solutions: 5% glucose solution for intravenous infusion, 0.9% sodium chloride solution for intravenous infusion, Ringer's lactate solution for injectable preparations (Hartmann's solution).

Incompatibilities

No additives should be added to this solution. If linezolid is administered with other medicinal products simultaneously, each should be administered separately according to its instructions for use. Similarly, if the same intravenous line is used for the sequential infusion of several medicinal products, it should be flushed before and after the administration of linezolid with a compatible solution.

It is known that Linezolid solution for infusion is not physically compatible with the following compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, and sodium phenytoin. Additionally, it is not chemically compatible with sodium ceftriaxone.

Shelf life

Before opening: 24 months.

After opening: Des

From a microbiological point of view, unless the opening method excludes the risk of bacterial contamination, the product must be used immediately, otherwise the storage times and conditions will be the responsibility of the user.

Special storage precautions

Keep the outer bag in the original packaging (aluminum and cardboard bag) to protect it from light until use.