Expiration date: 08/2025

Composition

1 film-coated tablet, 600 mg contains:

Active substance: linezolid 600 mg,

Excipients: corn starch 40 mg, sodium croscarmellose 38 mg, mannitol 54 mg, magnesium stearate 8 mg,

povidone K-30 20 mg, microcrystalline cellulose 100 mg,

Film cover: Opadry white 26 mg, including: 

hypromellose (hydroxypropyl methylcellulose) 8,775 mg hyprolose (hydroxypropyl cellulose) 8,775 mg, 5.2 mg talc, titanium dioxide, and 3.25 mg.

Indications

Treatment of infectious and inflammatory diseases if it is known or suspected that they are caused by linezolid-sensitive aerobic and anaerobic gram-positive microorganisms (including infections accompanied by bacteremia):

• community-acquired pneumonia caused by Streptococcus pneumoniae (including multiresistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (methicillin-sensitive strains only),
• hospital-acquired pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including polyresistant strains),
• complicated skin and soft tissue infections, including infections in diabetic foot syndrome, not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes and Streptococcus agalactiae,
• uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only) or Streptococcus pyogenes,
• infections caused by Enterococcus faecalis (strains resistant to vancomycin), including those associated with bacteremia.

Contraindications

• hypersensitivity to linezolid and/or other components of the drug,
• children up to 12 years (due to the inability of adequate dose selection),
• concomitant administration with drugs, inhibiting monoamine oxidase A or B (eg, phenelzine, isocarboxazide), as well as within two weeks after discontinuation of these drugs,

In the absence of careful monitoring of patients and blood pressure monitoring should not be prescribed linezolid:

• patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, schizoaffective disorder and acute state of confusion,
• patients receiving the following types of drugs: adrenomimetics (eg, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (eg, dopamine), serotonin reuptake inhibitors, tricyclic antidepressants, agonists 5NT1-receptors (tryptans), meperidine or buspiron.

Side effect

Infectious / parasitic diseases

Often – candidiasis (incl. oral candidiasis, vaginal candidiasis), fungal infections, infrequently – vaginitis, rarely – colitis caused by antibiotics (incl. pseudomembranous colitis).

Disorders of the blood and lymphatic system

Often – anemia, infrequently – leukopenia, neutropenia, thrombocytopenia, eosinophilia, rarely – pancytopenia, the frequency is unknown – myelosuppression, sideroblastic anemia.

Immune system disorders

The frequency is unknown – anaphylaxis.

Metabolic and nutritional disorders

Infrequently – hyponatremia, the frequency is unknown – lactic acidosis.

Mental disorders

Often insomnia.

Disorders of the nervous system

Often – headache, taste perversion (metallic taste), dizziness, rarely – seizures, gipostezii, paresthesia, frequency unknown – serotonin syndrome, peripheral neuropathy.

Violations of the organ of vision

Infrequently – blurred vision, rarely – the appearance of visual field defects, the frequency is unknown – optic neuropathy, optic neuritis, vision loss, change in visual acuity, change in color vision.

Violations of the organ of hearing and labyrinth disorders

Rarely, ringing in the ears.

Disorders of the cardiovascular system

Often – increased blood pressure, infrequently: arrhythmia (tachycardia), transient ischemic attack, phlebitis, thrombophlebitis.

Disorders of the gastrointestinal tract

Often – diarrhea, nausea, vomiting, localized or diffuse pain in the abdomen, constipation, dyspepsia, infrequently – pancreatitis, gastritis, bloating, dry mouth, glossitis, loose stools, stomatitis, changes in the color of the mucous membrane of the tongue and other disorders of the tongue, rarely – a superficial change in the color of tooth enamel.

Disorders of the liver and biliary tract

Often – a change in the results of functional tests of the liver, increased activity of "liver enzymes" (including alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (alkaline phosphatase)), infrequently – an increase in the concentration of total bilirubin.

Violations of the skin

Often – rash, itching, infrequently – urticaria, dermatitis, excessive sweating, the frequency is unknown – bullous skin lesions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, alopecia.

Kidney and urinary tract disorders

Often – an increase in the concentration of blood urea, infrequent renal failure, an increase in the concentration of creatinine in blood plasma, polyuria.

Violations of the genital organs and breast cancer

Rarely – violations of the vagina and vulva.

General disorders and disorders at the site of administration

Often – fever, localized pain, infrequently – chills, weakness, thirst, pain at the injection site (for infusion solution).

How to take, course of administration and dosage

The drug can be taken both during meals and between meals. Patients who at the beginning of therapy linezolid appointed intravenously, in the future can be transferred to the dosage forms of linezolid for oral administration, while dose selection is not required, because the bioavailability of linezolid when administered is almost 100%. The duration of treatment depends on the pathogen, the location and severity of the infection, as well as the clinical effect.

Overdose

There are no reports of overdoses.

If necessary, symptomatic therapy (including the need to maintain the level of glomerular filtration). Approximately 30% of the dose is excreted within 3 hours with hemodialysis. There is no data on the acceleration of linezolid excretion in peritoneal dialysis or hemoperfusion.

Special instruction

In an open study among seriously ill patients with intravascular catheter-associated infections, there was an excess of mortality in patients receiving linezolid compared with patients receiving vancomycin/dicloxacillin/oxacillin [78/363 (21.5%) versus 58/363 (16.0%)]. The main factor affecting mortality was the gram-positive causative agent of infection at the initial stage. The mortality rate was similar among patients whose infections were caused only by gram-positive microorganisms, but was significantly higher in the linezolid group when other microorganisms were detected, or could not be detected at the initial stage. The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. In many patients of the linezolid group, gram-negative microorganisms were detected during the study, and they died from infection caused by gram-negative microorganisms or polymicrobial infections. Thus, in the case of complicated infections of the skin and soft tissues, linezolid should be used in patients with known or possible co-infection with gram-negative microorganisms, only if there are no alternative treatment options. In these cases, additional use of drugs acting on gram-negative microflora is shown simultaneously. Some patients taking linezolid may develop reversible myelosuppression (with anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. Elderly patients also have an increased risk of developing this condition. Thrombocytopenia often occurred in patients with severe renal failure, regardless of the use of patient hemodialysis. In this regard, during treatment, it is necessary to monitor blood counts in patients with an increased risk of bleeding, myelosuppression in history, as well as with the simultaneous use of drugs that reduce hemoglobin or platelet count and/or their functional properties, with severe renal failure, as well as in patients taking linezolid more than 2 weeks. Linezolid in these patients applies only in the case when possible, careful monitoring of hemoglobin, number of white blood cells and platelets. If during therapy with linezolid develops pronounced myelosuppression, treatment should be discontinued, unless the continuation of therapy is considered absolutely necessary. In this case, intensive monitoring of blood parameters and appropriate treatment are required. In addition, it is recommended that a blood test (including the determination of hemoglobin, platelet count and white blood cells (with the calculation of the leukocyte formula) is carried out weekly in patients receiving linezolid regardless of the parameters of the initial blood test. A higher incidence of severe anemia was observed in patients receiving linezolid longer than the maximum recommended duration of 28 days. These patients often required blood transfusions. Cases of sideroblastic anemia were recorded in the post-registration period. In most cases, the duration of linezolid therapy exceeded 28 days. In most patients, the manifestations were completely or partially reversible after discontinuation of treatment with/without linezolid specific treatment of anemia.

Patients taking antibacterial drugs, including linezolid, should take into account the risk of pseudomembranous colitis of varying severity. Cases of diarrhea associated with Clostridium difficile have been reported in connection with the use of virtually all antibacterial drugs, including linezolid. The severity of diarrhea can range from mild to severe. Treatment with antibacterial drugs violates the normal intestinal microflora, which leads to excessive growth of Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to the development of diarrhea associated with Clostridium difficile. Excessive amounts of toxins produced by Clostridium difficile strains can cause increased mortality among patients, as such infections can be resistant to antimicrobial therapy and may also require a colonectomy. You can not use drugs that inhibit intestinal peristalsis. The possibility of developing diarrhea associated with Clostridium difficile should be considered in all patients with diarrhea following antibiotic use. Careful medical supervision for 2 months is necessary for patients who have undergone diarrhea associated with Clostridium difficile after administration of antibacterial drugs.

In case of symptoms of deterioration of visual function, such as changes in visual acuity, changes in color perception, blurred, visual field defects, it is recommended to consult an ophthalmologist immediately. Visual function should be monitored in all patients taking linezolid for a long time (more than 28 days), as well as in all patients with newly developed symptoms of visual impairment, regardless of the duration of therapy.

In the case of peripheral neuropathy and optic neuropathy, the risk/benefit ratio of continued linezolid therapy in these patients should be assessed. The risk of developing neuropathy is higher if linezolid is used in patients who are currently using or who have recently taken antibacterial drugs to treat tuberculosis.

In connection with the use of linezolid reported lactic acidosis. Patients who receive linezolid on the background of repeated nausea or vomiting, abdominal pain, unexplained acidosis or there is a decrease in the concentration of bicarbonate anions, require careful supervision by a doctor.

Linezolid inhibits mitochondrial protein synthesis. Side effects such as lactic acidosis, anemia and neuropathy (peripheral and optic nerve) can result from this inhibition, these effects are more common when the drug is used for more than 28 days.

Convulsions have been reported in patients taking linezolid, and in most cases there was an indication of seizures or the presence of risk factors for their development. Patients need to collect a detailed history of previous episodes of seizures.

If it is necessary to use the drug in combination with selective serotonin reuptake inhibitors, patients should be constantly monitored to identify signs and symptoms of serotonin syndrome, such as cognitive impairment, hyperpyrexia, hyperreflexia and impaired coordination of movements. In the case of the appearance of these symptoms, you should cancel one or both of the drug received. When you stop taking serotonergic drugs, symptoms of "withdrawal"syndrome may occur.

Reported cases of reversible surface changes the staining of the tooth enamel with the use of linezolid. These changes in staining were removed by professional teeth cleaning.

Cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus who received linezolid simultaneously with insulin or hypoglycemic drugs. Although the causal relationship between the administration of linezolid and the development of hypoglycemia has not been established, patients with diabetes should be warned about the possibility of hypoglycemia. In case of hypoglycemia correction of insulin/hypoglycemic drugs dose or linezolid cancellation is necessary.

Patients should be advised not to eat large amounts of food containing tyramine (such as red wine, old cheese, some alcoholic beverages, smoked meat).

Clinical studies examining the effect of linezolid on the normal microflora of the human body have not been conducted.

The use of antibacterial drugs can sometimes lead to increased growth of microorganisms immune to it. Clinical studies have shown that approximately 3% of patients receiving recommended doses of linezolid developed candidiasis associated with antibiotics. In the event of superinfection against the background of taking linezolid, appropriate medical measures should be taken.

Clinical study.

Safety and efficacy of linezolid longer than 28 days have not been established.

Patients with diabetic foot syndrome, bedsores or ischemic disorders, severe burns or gangrenous lesions did not participate in controlled clinical trials. Thus, the experience of using linezolid in the treatment of these conditions is limited.

Influence on the ability to drive vehicles, mechanisms

During treatment, driving and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions are not recommended.