Linezolid - instructions for use, doses, side effects, contraindications

Component name	amount
Active substance:
Linezolid	2.0 mg
Excipients:
Dextrose monohydrate (corresponding to 50.0 mg of dextrose)	55.0 mg
Lemon acid	0.75 mg
Sodium citrate dihydrate	1.8 mg
Water for injections	Up to 1 ml

Description:Transparent colorless or with a brownish hue solution.

Pharmacotherapeutic group:Antibiotic-oxazolidinone.

ATX: & nbsp

J.01.X.X.08 Linezolid

J.01.X.X Other antibacterial drugs

Pharmacodynamics:Linezolid, a synthetic antibacterial drug, refers to a new class of antimicrobial agents, oxazolidinones, active in vitro against aerobic gram-positive bacteria, certain gram-negative bacteria and anaerobic microorganisms. Linezolid selectively inhibits protein synthesis in bacteria. By binding to bacterial ribosomes, it prevents the formation of a functional initiating complex 70S, which is an important component of the translation process in protein synthesis.
Sensitivity
The drug is active in vitro and in vivo.
Gram-positive aerobes:
Enterococcus faecium (including strains resistant to vaikomycin)
Staphylococcus aureus (including methyllylium-resistant strains)
Streptococcus agalactiae
Streptococcus pneumoniae (including multiresistant strains)
Streptococcus pyogenes
The drug is active in vitro.
Gram-positive aerobes:
Enterococcus faecalis (including strains resistant to vaikomycin)
Enterococcus faecium (strains sensitive to vaikomycin)
Staphylococcus epidermidis (including methyl ilylli-resistant strains)
Staphylococcus haemolyticus.
Streptococcus spp. group Viridans
Gram-negative aerobes:
Pasteurella multocida
Resistant to linezolid microorganisms:
Haemophilus influenzae
Mogaxella catarrhalis
Neisseria spp.
Enterobacteriaceae spp.
Pseudomonas spp.
Resistance
The mechanism of action of linezolid differs from the mechanisms of action of antimicrobials of other classes (for example, amyglycosides, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines and chloramphepicol), so there is no cross-resistance between linezolid and these drugs. Linezolid is active against pathogenic microorganisms, both sensitive and resistant to these drugs. Resistance to linezolid develops slowly by a multi-stage mutation of 23S ribosomal RNA and occurs at a frequency of less than 1x10^-⁹ - 1x10^-¹¹.

Pharmacokinetics:Suction
The mean maximum concentration (C_max) and the mean minimum concentration (C_min) of lyisolide in plasma in equilibrium after intravenous administration twice a day at a dose of 600 mg were 15.1 mg / L and 3.68 mg / L, respectively. The equilibrium concentration of liisolide in the blood is reached on the 2nd day of administration of the drug.
Distribution
The volume of distribution of linezolid at equilibrium concentration in a healthy adult is on the average 40-50 liters, which is approximately equal to the total water content in the body. Binding to plasma proteins is 31% and does not depend on the concentration of linezolid in the blood.
Metabolism
It has been established that cytochrome P450 isoenzymes do not participate in the metabolism of linezolid in vitro. Linezolid does not inhibit or potentiate the activity of clinically important cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).
Metabolic oxidation leads to the formation of two inactive metabolites - hydroxyethyl glycine (the main metabolite in humans, formed as a result of a non-enzymatic process) and aminoethoxyacetic acid (formed in smaller amounts). Other inactive metabolites are also described.
Excretion
The extrarenal clearance is about 65% of the linezolid clearance. With increasing dose of linezolid, a small degree of nonlinearity of clearance is noted. This can be explained by a decrease in renal and extrarenal clearance with a high dose of linezolid. However, the differences in clearance are small and do not affect the apparent half-life.
Linezolid in patients with normal renal function and with renal insufficiency of mild and moderate degree is excreted by the kidneys in the form of hydroxyethyl glycine (40%), amioethoxyacetic acid (10%) and unchanged (30-35%). The intestine is excreted in the form of hydroxyethyl glycine (6%) and amioethoxyacetic acid (3%).
Unchanged linezolid practically not excreted by the intestine. The half-life of linezolid is 5-7 hours on average.
Pharmacokinetics in selected groups of patients
Patients with renal insufficiency
After a single dose of 600 mg of the drug in patients with severe renal insufficiency (creatinine clearance <30 ml / mii), the concentration of its two main metabolites increased by 7 to 8 times. However, no increase in the area under the concentration-time curve (AUC) of the parent drug was observed.Despite the fact that some basic metabolites were removed during hemodialysis, their plasma concentration after taking 600 mg of linezolid and carrying out the dialysis procedure in patients with severe renal insufficiency remained significantly higher than the concentration in the blood in patients with normal renal function, mild or moderate renal insufficiency.
Patients with hepatic insufficiency
There is limited evidence that the pharmacokinetics of linezolid and its two major metabolites do not change in patients with mild and moderate hepatic insufficiency (A and B classes according to the Child-Pugh classification). The pharmacokinetics of linezolid in patients with severe hepatic insufficiency (class C according to the Child-Pugh classification) has not been studied. However, since linezolid it is not metabolized by a non-enzyme route, it is not expected to significantly impair its metabolism in liver failure.
Children and teens
In adolescents (12 to 17 years), the pharmacokinetics of linezolid, taken at a dose of 600 mg, did not differ from the kinetics in adults. Thus, in the appointment of adolescents with 600 mg of linezolid every 12 hours, the concentration of the drug will be the same as in adults when the same dose is given.
In children from 1 week to 12 years, the use of linezolid at a dose of 10 mg / kg every 8 hours allows achieving the same exposure as in adults with 600 mg of linezolid twice daily.
In newborns, the systemic clearance of linezolid rapidly increases during the first week of life (based on kg of body weight). Thus, with a dose of 10 mg / kg every 8 hours, the maximum exposure of linezolid will be achieved in the child of the first day of life more quickly on the first day after birth. However, excessive accumulation of the drug in the first week of admission with such an appointment scheme still will not happen due to the rapid increase in clearance.
Elderly
In elderly patients aged 65 years and older, the pharmacokinetics of linezolid do not change significantly.
Women
In women, the distribution of the drug is somewhat lower than that of men; they also reduced by 20% the average clearance in terms of body weight. The concentration of the drug in the blood plasma of women is higher than that of men, which can partly be explained by differences in body weight. However, since the half-life of linezolid in men and women is not significantly different, there is no reason to expect an increase in the concentration of the drug in the blood of women above the tolerated value, so that no dose adjustment is required.

Indications:Treatment of infectious inflammatory diseases, if known or suspected, that they are caused by aerosol and anaerobic Gram-positive microorganisms sensitive to linezolid (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 pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug resistant strains);
- complicated skin and soft tissue infections, including infections with diabetic foot syndrome not accompanied by osteomyelitis caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae;
- infections resistant to vancomycin, caused by Enterococcus faecium, including those accompanied by bacteremia.
If the pathogens of infection include gram-negative microorganisms, the purpose of combination therapy is clinically indicated.

Contraindications:Hypersensitivity to linezolid and / or other components of the drug.
The simultaneous use of linezolid with inhibitors of monoamine oxidase A or B (e.g., fenelzii, isocarboxazid) within 14 days before or after treatment with linezolid.
In the absence of careful monitoring of patients and monitoring of blood pressure, linezolid should not be prescribed:
- 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 (for example, pseudoephedrine, phenyl propanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (eg, dopamine), serotonin reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists (tryptanes), meperidine or buspirone.

Carefully:Severe renal insufficiency, myelosuppressive state, visual disturbances, ischemic injury of organs and tissues, bedsores, diabetic foot, gangrene, liver failure, the presence of a history of seizures. Linezolid use with caution in patients with systemic infections posing a risk to life, such as those associated with venous catheters in intensive care units.

Pregnancy and lactation:Pregnancy
Studies of the safety of linezolid in pregnancy have not been conducted, so the use of the drug Linezolid during pregnancy is possible only if the intended benefit of therapy for the mother exceeds the potential risk to the fetus.
Breast-feeding
Linezolid penetrates into the breast milk of nursing women, so if you need to use the drug during lactation should stop breastfeeding.

Dosing and Administration:The drug is intended for intravenous administration. The duration of the infusion is 30 - 120 minutes. The dosage regimen and duration of treatment depend on the causative agent, localization and severity of the infection, as well as on clinical efficacy.
Recommended dosing regimen for adults and children (12 years and over)

Indications (including infections, withProvingswhich are bacteremia)	Single dose and multiplicity introduction of	Recommended Duration treatment
- extra-billMr.ichMr.pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteraemia, or Staphylococcus aureus (only methicillin-sensitive strains);	600 mg IV every 12 hours	10-14 days
- hospitalized pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);	600 mg IV every 12 hours	10-14 days
- complicated skin and soft tissue infections, including infections with diabetic foot syndrome not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicilliMr.sensoryMr.th and methylcentnersillinesistentMr.th strains), Streptococcus pyogenes or Streptococcus agalactiae;	600 mg IV every 12 hours	10-14 days
resistant infectionsMr.comicin caused by Enterococcus faecium, including those accompanied by bacteremia.	600 mg IV every 12 hours	14-28 days

The recommended dosing regimen for children (newborns * and children under 12)

Indications (including infections, withProvingswhich are bacteremia)	Single dose and multiplicity introduction of	Recommended Duration treatment
- extra-billMr.ichMr.pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteraemia, or Staphylococcus aureus (only methicillin-sensitive strains);	10 mg /kg in / in every 8 h	10-14 days
- hospitalized pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);	10 mg /kg in / in every 8 h	10-14 days
- complicated skin and soft tissue infections, including infections with diabetic foot syndrome not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicilliMr.sensoryMr.th and methylcentnersillinesistentMr.th strains), Streptococcus pyogenes or Streptococcus agalactiae;	10 mg /kg in / in every 8 h	10-14 days
resistant infectionsMr.comicin caused by Enterococcus faecium, including those accompanied by bacteremia.	10 mg /kg in / in every 8 h	14-28 days

* In preterm infants less than 7 days of age (pregnancy less than 34 pedules), the systemic clearance of linezolid is lower, and the AUC is higher than most newborns and children. By the 7th day after birth, linezolid clearance and AUC values in premature newborns are close to those of full-term newborns and children.
The maximum dose for adults and children is 1.2 g / day.
Dose adjustment for elderly patients is not required.
Patients with renal insufficiency do not need dose adjustment.Patients who are on hemodialysis, the drug should be administered after the end of the procedure for hemodialysis.
Patients with hepatic insufficiency do not need dose adjustment.

Side effects:The incidence of adverse reactions is represented by the following classification recommended by the World Health Organization:
Very often: ≥ 10%
Frequently: ≥ 1% and <10%
Uncommon:> 0.1% and <1%
Rarely: ≥0.01% and <0.1%
Very rarely: <0.01%
Adult patients
The undesirable phenomena associated with the use of linezolid are usually of mild or moderate severity. Most often, diarrhea, headache and nausea are noted.
On the part of the digestive system:
Often: diarrhea, nausea, vomiting, candidiasis of the oral mucosa, indigestion.
Infrequent: change in staining of the tongue, pancreatitis, gastritis, bloating, dry mouth, glossitis, loose stool, stomatitis.
Rarely: pseudomembranous colitis, discoloration of tooth enamel.
Laboratory indicators:
Often: anemia, increased activity of creatine kinase, increased fasting glucose concentration; decrease in total protein, albumin, sodium or calcium; increase or decrease of potassium or bicarbonate; neutrophilia, eosinophilia; reduction of hemoglobin, hematocrit or the number of red blood cells.
Uncommon: increase in the concentration of triglycerides in the blood, increased activity of "liver" enzymes (including alanipamiiotraisferazy (ALT), aspartataminotraisferazy (the ACT), alkaline phosphatase (AP)), lactate dehydrogenase (LDH), lipase, amylase, increased total bilirubin concentration and creatinine, increased prolactin concentration; increase in the content of sodium or calcium; decreased fasting glucose; increase or decrease in chloride, leukopenia, neutropenia, thrombocytopenia.
Rarely: pancytopenia.
From the cardiovascular system:
Often: increased blood pressure.
Infrequently: tachycardia, transient ischemic attack, phlebitis, thrombophlebitis.
From the sense organs:
Infrequent: blurred vision, tinnitus.
Rarely: a defect in the fields of vision.
From the nervous system:
Often: perversion of taste ("metallic" taste), headache, dizziness.
Infrequently: paresthesia, hypesthesia, convulsions (see section "Special instructions").
From the central nervous system:
Often: insomnia.
From the genitourinary system:
Often: increased blood urea nitrogen, vaginal candidiasis.
Infrequent: renal failure, vulvovaginal disorders, vaginitis, polyuria
From the skin:
Often: rash, itching.
Infrequent: dermatitis, increased sweating, urticaria.
Other:
Often: fever, local pain.
Infrequent: chills, fatigue, pain at the injection site, thirst, hypopatremia, opportunistic fungal infection.
Children and teens
On the part of the digestive system:
Often: diarrhea, nausea, vomiting, abdominal pain (local and generalized), gastrointestinal bleeding, candidiasis of the oral mucosa, loose stools.
Laboratory indicators:
Often: thrombocytopenia, anemia, hypokalemia, thrombocythemia.
Infrequently: eosinophilia, an increase in the concentration of triglycerides in the blood, increased activity of ALT, lipase, amylase, the concentration of total bilirubin and creatinine.
From the nervous system:
Often: headache, convulsions (see section "Special instructions"), vertigo.
From the skin:
Often: rash.
Infrequent: itching (not at the injection site).
From the respiratory system:
Often: respiratory failure, apnea, upper respiratory tract infection, pharyngitis, pneumonia, cough.
Other:
Often: fever, sepsis, generalized edema, reactions at the injection site.
Spontaneous (post-registration) data
Laboratory indicators:
sideroblastic anemia.
From the sense organs: change in visual acuity, optic neuritis, optic neuropathy, loss of vision, change in color vision (see. section "Special instructions").
Allergic reactions: anaphylaxis.
From the skin: alopecia, angioedema; Bullous skin lesions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the side of metabolism: lactic acidosis.
From the nervous system: peripheral neuropathy.
Other: serotonin syndrome (see. Forums "Interaction with other medicinal products" and "Cautions").

Overdose:No cases of overdose of linezolid have been reported. Recommended symptomatic treatment (including the need to maintain the speed of glomerular filtration). Pet data on the acceleration of deducing linezolid for peritoneal dialysis or hemoperfusion.

Interaction:Do not add other drugs to the infusion solution.If necessary, enter linezolid with other drugs, then all medications should be administered separately in accordance with recommended doses and routes of administration.
Linezolid for injection is pharmaceutically incompatible with the following drugs: amphotericin B, chlorpromazine, diazepam, pentamides, phenytoin, erythromycin, co-trimoxazole (trimethoprim + sulfamethoxazole), ceftriaxone.
Compatible solutions for infusion:
- 5% dextrose solution for injection;
- 0.9% solution of sodium chloride for injection;
- Ringer-Lock solution for injections.
Patients who at the beginning of therapy received the drug intravenously, then can be transferred to any dosage form of the drug for oral administration, with the selection of a dose is not required, g. the bioavailability of lipesolid upon ingestion is almost 100%.
Potential interactions leading to increased blood pressure (BP)
If it is not possible to carry out careful monitoring of patients and monitor blood pressure, simultaneous use of lipesolide with adrenomimetics (for example, pseudoephedrine, phenylpropanolamine, epipryphry, norepinephrine, dobutamine) and dopaminomimetics (for example, dopamine) is contraindicated (see the section "Contraindications").
Potential serotonergic interactions
The simultaneous use of lipizolide and serotonergic drugs is contraindicated. If simultaneous therapy is required, careful monitoring of the patient is required in order to detect symptoms of serotonin syndrome in a timely manner (see the sections "Contraindications", "Special instructions").
Inhibitors of monoamine oxidase
Linezolid is a non-selective, reversible monoamine oxidase inhibitor. The simultaneous use of linezolid and monoamine oxidase inhibitors is contraindicated, but at least 14 days before or after the end of therapy with lyisolide (see the sections "Contraindications" and "Special instructions").
Drugs metabolized by the cytochrome P450 system It is established that cytochrome P450 isoenzymes do not participate in the metabolism of linezolid in vitro. Linezolid does not inhibit or potentiate the activity of clinically important cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Thus, no CYP450-induced interaction is expected when taking linezolid.With the simultaneous use of linezolid and (S) -varmarin, which is largely metabolized by the isoenzyme CYP2C9, the pharmacokinetic characteristics of warfarin do not change. Such drugs as warfarin and phenytoin, which are substrates of the CYP2C9 isoenzyme, can be used concomitantly with linezolid without dose adjustment. Rifampicin C caused a decrease in C_max and AUC of linezolid on average by 21% and 32%, respectively.

Special instructions:With the established infection (if there is a suspicion of infection) caused by concomitant gram-negative microorganisms, additional application of the agents acting on the gram-negative microflora is shown.
Myelopression
The occurrence of myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients taking linezolid. After cancellation of linezolid, the parameters of the changed blood parameters returned to the values that were observed before the start of treatment. Probably, the risk of these effects is associated with the duration of treatment. In elderly patients, the use of linezolid may be associated with a higher risk of pathological changes in the blood compared to younger individuals.In patients with severe renal failure (regardless of whether they undergo dialysis), an increase in the incidence of thrombocytopenia is possible.
Thus, careful monitoring of hematological indicators is recommended in the following categories of patients:
- Patients with pre-existing anemia, granulocytopenia or thrombocytopenia;
- patients receiving concomitant therapy with drugs that can reduce hemoglobin levels, reduce the number of blood cells or negatively affect the number or functional activity of platelets;
- Patients with severe renal failure;
- patients receiving linezolid therapy for more than 10-14 days. Use linezolid for the treatment of such patients it is desirable only in combination with a careful control of the level of hemoglobin, a general blood test and, if possible, the number of platelets.
If clinically significant myelosuppression develops during linezolid treatment, therapy should be discontinued. Exceptions are cases where continued treatment is absolutely necessary.In such situations, it is necessary to carefully monitor the indicators of the general blood test and implement appropriate treatment strategies.
In addition, it is recommended to monitor the parameters of the total blood test weekly (including determination of hemoglobin levels, platelet count, total white blood cell count and expanded leukocyte formula) in patients undergoing linezolid treatment, regardless of baseline blood count.
In the group of patients who received linezolid for> 28 days (maximum recommended duration of treatment), an increase in the incidence of serious anemia was observed. Such patients more often needed a blood transfusion. About cases of anemia with the need for blood transfusion were also reported in the postmarketing period. Such anemia often occurred in patients who received linezolid for> 28 days.
Also in the postmarketing period reported cases of sideroblastic anemia. Among the cases for which the time of initiation of treatment was known, the majority of patients received linezolid for> 28 days.After cancellation of linezolid, the majority of patients recovered completely or partially as a result of treatment of anemia or even without treatment. Mortality mismatch in a clinical trial involving patients with bloodstream infections associated with the use of catheters and caused by Gram-positive pathogens
In an open trial involving patients with severe intravascular infections caused by the use of catheters, there was an increase in mortality in the group of patients who used linezolid, compared with vancomycin / dicloxacilin / oxacillin treatment groups (78/363 (21.5%) versus 58/363 (16.0%)). The main factor influencing the mortality rate was the state of Gram-positive infection at baseline.
The mortality rate in patients with infections caused exclusively by Gram-positive organisms was comparable (mismatch coefficient 0.96, 95% confidence interval 0.58-1.59), but in the linezolid treatment group, the mortality rate was significantly higher in patients with any other causative agent or lack of pathogens at the baseline level (mismatch ratio 2.48, 95% confidence interval 1.38-4.46).11 and the discrepancy was observed during treatment and within 7 days from the time of withdrawal of the study drug. In the course of the study, the linezolid group had a larger number of individuals who developed gram-negative infections during the study, as well as patients who died from infections caused by gram-negative pathogens and from polymicrobial infections. Thus, with complicated infections of the skin and soft tissues in patients with an established or suspected associated infection, Gram-negative pathogens linezolid should be used only in the absence of other treatment options. In such circumstances, it is necessary to begin parallel treatment of gram-negative infection.
Pseudomembranous colitis
With almost all antibiotics, including linezolid, reported the occurrence of diarrhea and colitis associated with the use of antibiotics, including pseudomembranous colitis, and Clostridium difficile diarrhea, the severity of which may vary from mild diarrhea to colitis with fatal outcome. Thus, it is important to consider the possibility of this diagnosis in patients who develop diarrhea during or after the application of linezolid.If there is a suspicion of diarrhea or colitis associated with the use of antibiotics, or confirmation of this diagnosis, it is necessary to stop the current treatment with antibacterial drugs (including linezolid) and immediately begin appropriate therapeutic measures. The use of drugs that inhibit intestinal peristalsis is contraindicated.
Lactic acidosis
With the use of linezolid, the development of lactic acidosis was reported. Patients who experience symptoms and manifestations of lactic acidosis, including recurrent nausea or vomiting, abdominal pain, low bicarbonate levels, or hyperventilation, should immediately seek medical help. In case of development of lactic acidosis it is necessary to weigh the benefit of further treatment with linezolid and potential risks.
Mitochondrial dysfunction
Linezolid inhibits the synthesis of mitochondrial proteins. As a result of this depression, adverse reactions such as lactic acidosis, anemia and neuropathy (peripheral and optic nerve) can develop. These phenomena are more often observed with lenesolide for> 28 days.
Peripheral neuropathy and optic nerve neuropathy The development of peripheral neuropathy as well as neuropathy of the optic nerve has been reported, which sometimes progressed to loss of vision in patients receiving linezolid. Such reports, in the first place, concerned patients who received treatment for> 28 days (maximum recommended duration of treatment). All patients should be advised to report symptoms of visual impairment, such as changes in visual acuity, changes in color perception, blurred vision or loss of part of the field of vision. In such cases it is recommended to urgently conduct an examination with a referral to the ophthalmologist - if necessary. If the patient takes linezolid more recommended 28 days, you need to regularly monitor your vision. In the case of peripheral neuropathy or optic nerve neuropathy, the risk / benefit ratio of continuance of linezolid therapy in these patients should be assessed.
An increased risk of developing neuropathy is possible with linezolid in patients receiving or recently received antibiotic therapy for the treatment of tuberculosis.
Convulsions
Cases of seizures have been reported in patients receiving linezolid therapy.In most cases, a risk factor has been reported, such as a history of seizures. Patients should be reported to the doctor if they have previously had seizures.
Hypoglycaemia
There have been reports of hypoglycemia in the treatment of linezolid in patients with diabetes mellitus receiving insulin or oral hypoglycemic drugs. Despite the fact that a causal relationship between the use of linezolid and hypoglycemia is not established, patients with diabetes should be warned about the possibility of developing hypoglycemic conditions in the treatment with linezolid.
Inhibitors of monoamine oxidase
Linezolid is a non-selective inhibitor of reversible monoamine oxidase. In studies of drug interactions and safety studies of linezolid, a very limited amount of data on the use of linezolid in patients with underlying diseases and / or concomitant medications has been obtained in which there are certain risks due to the inhibition of monoamine oxidase. Therefore, the use of linezolid simultaneously with monoamine oxidase A or B inhibitors (eg, phenelzine, isocarboxazide) is contraindicated within 14 days before or after termination of linezolid therapy.sections "Contraindications" and "Interaction with other medicinal products").
Serotonin syndrome
There have been spontaneous reports of the development of serotonin syndrome associated with simultaneous use of linezolid and serogonimergic drugs, including antidepressants (such as selective serotonin reuptake inhibitors). Thus, simultaneous use of linezolid and serotonergic drugs is contraindicated. If concomitant use is required, the patient should be carefully monitored to identify symptoms of serotonin syndrome, such as cognitive impairment, hyperpyrexia, hyperreflexia, and impaired coordination of movements. In case of such symptoms, the doctor should consider the possibility of canceling a particular drug. After the withdrawal of a serotonergic drug, symptoms of the "withdrawal" syndrome can be observed.
Application in conjunction with saturated thiam other products In patients who received linezolid and tyramine in an amount of <100 mg, did not observe a significant vasopressor effect.This indicates the need to avoid only excessive consumption of foods and beverages with a high content of tyramine (namely, mature cheeses, yeast extracts, undistilled alcoholic beverages and fermented products from soybeans, such as soy sauce). Superinfection
The effect of linezolid on normal microflora was not studied during clinical trials. The use of antibiotics can sometimes lead to excessive growth of insensitive microorganisms. For example,^≈ 3% of patients who received linezolid in recommended doses, during the clinical studies observed the emergence of candidiasis, associated with the use of the drug. If superinfections occur during treatment, appropriate measures should be taken.
Special patient groups
Use linezolid for the treatment of patients with severe renal failure should be cautious and only in situations where the expected benefit exceeds the risk.
Use linezolid for the treatment of patients with severe hepatic insufficiency is recommended only in situations where the expected benefit exceeds the risk.
Controlled clinical trials did not include patients with diabetic foot injury, pressure ulcers, ischemic lesions, severe burns or gangrene. Therefore, the experience of using linezolid for the treatment of these conditions is limited.
Changes in dyeing of tooth enamel
There have been reports of reversible surface changes in tooth enamel staining with linezolid. These changes in staining were removed by professional dental cleaning.
Excipients
1 ml of the solution contains 55.5 mg of dextrose monohydrate (corresponding to 50.0 mg of dextrose). This should be considered when treating patients with diabetes mellitus or other conditions associated with glucose intolerance.
1 ml of the solution also contains 1.8 mg of sodium citrate dihydrate. The sodium content should be taken into account for patients who adhere to a diet with reduced sodium intake.

Effect on the ability to drive transp. cf. and fur:During the treatment with linezolid, to drive vehicles, special equipment or engage in activities associated with increased risk, and activities requiring increased concentration and speed of psychomotor reactions,It is not recommended in connection with the possibility of developing dizziness or symptoms of visual impairment.

Form release / dosage:Solution for infusions 2 mg / ml.

Packaging:For 100 ml, 200 ml, 300 ml in polyethylene bottles without a cap or with a welded euro bag or plastic cap or infusion plug.
For 1 bottle in a hermetically sealed bag of polymer film or without a package, in a pack of cardboard along with instructions for use.

Storage conditions:Store in a dark place at a temperature of 2 to 25 ° C. Freezing of the drug is not allowed.
Keep out of the reach of children.

Shelf life:2 years.
Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003229

Date of registration:29.09.2015

Expiration Date:29.09.2020

The owner of the registration certificate:EAST-FARM, CJSC EAST-FARM, CJSC Russia

Manufacturer: & nbsp

EAST-FARM, CJSC Russia

Information update date: & nbsp2016-10-20

Illustrated instructions

Instructions

Linezolid (Linezolid)