Linezolid Canon, 600 mg 10 pcs

Pharmacotherapeutic group

An antibiotic – oxazolidinone

ATX code: J01XX08

The antimicrobial agent belongs to the class of oxazolidinones. The mechanism of action of the drug is due to the inhibition of protein synthesis in bacteria. Linezolid binds to site 23S of bacterial ribosomal RNA 50S subunit and prevents formation of functional initiating complex 70S which is an important component of translation process at protein synthesis. Linezolid is active in-vitro against aerobic gram-positive bacteria of some gram-negative bacteria and anaerobic microorganisms.

Sensitivity

The drug is active invitro and invivo:

Gram-positive aerobes

Enterococcusfaecium (including vancomycin-resistant strains)

Staphylococcusaureus (including methicillin-resistant strains)

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Streptococcusagalactiae

Streptococcuspneumoniae (including multidrug-resistant strains)

Streptococcuspyogenes

The drug is active invitro:

Gram-positive aerobes

Enterococcusfaecalis (including vancomycin-resistant strains)

Enterococcusfaecium (vancomycin-sensitive strains)

Staphylococcusepidermidis (including methicillin-resistant strains)

Staphylococcushaemolyticus

Streptococcus viridans

Gram-negative aerobes: Pasteurellamultocida

Linezolid-resistant microorganisms:

Haemophilusinfluenzae

Mogachella catarrhalis

Neisseria spp.

Enterobacteriaceae spp

Pseudomonas spp.

There is no cross-resistance of microorganisms between linezolid and antimicrobials of other classes (aminoglycosides beta-lactam antibiotics folic acid antagonists glycopeptides lincosamides quinolones rifampicin tetracyclines and chloramphenicol). Linezolid is active against both sensitive and resistant microorganisms to these drugs. Resistance to linezolid develops very slowly through a multistep mutation of 23S -ribosomal RNA. In addition to its main antimicrobial action, it has the properties of a weak non-selective inhibitor of monoamine oxidase (MAO) types A and B.

Pharmacokinetics:

Intake

Linezolid is rapidly and intensively absorbed from the gastrointestinal tract after oral administration. Maximal concentration of linezolid in blood plasma (Cmax) is 212 mg/l Mean time period before reaching maximal concentration of linezolid in blood (TSmax) – 2 hours Absolute bioavailability is about 100%.

Eating does not affect absorption of linezolid. Equilibrium concentration of linezolid in blood is reached on the 2nd day of use.

Distribution

The volume of distribution of linezolid at equilibrium concentration in a healthy adult averages 40-50 liters, which is approximately equal to the total body water content. Binding to plasma proteins is 31% and does not depend on the concentration of linezolid in the blood.

Metabolism

It was found that cytochrome P450 isoenzymes are not involved in the metabolism of linezolid. 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 – hydroxyethylglycine (the main metabolite in humans is formed by a non-enzymatic process) and aminoethoxyacetic acid (formed in smaller amounts). Other inactive metabolites have also been described.

Extrarenal clearance is about 65% of linezolid clearance. As the dose of linezolid increases, a slight degree of nonlinearity in clearance is noted. This may be due to decreased renal and extrarenal clearance at high dose of linezolid. However, the differences in clearance are small and do not affect the apparent elimination half-life.

Linesolid in patients with normal renal function and in mild to moderate renal failure is excreted by the kidneys as hydroxyethylglycine (40%) aminoethoxyacetic acid (10%) and unchanged (30-35%). The intestine excreted as hydroxyethylglycine (6%) and aminoethoxyacetic acid (3%). Linezolid in unchanged form is practically not excreted by the intestine.

The half-life of linezolid is on average 5-7 hours.

Pharmacokinetics in selected patient groups

Patients with renal impairment

After a single administration of linezolid at a dose of 600 mg in patients with severe renal impairment (creatine clearance <30 ml/min), concentrations of its two major metabolites increased 7-8-fold.

Patients with hepatic impairment

There is limited evidence that in patients with mild to moderate hepatic impairment (Child-Pugh class A and B) the pharmacokinetics of linezolid and its two major metabolites are not altered. Pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C) have not been studied. However, since linezolid is metabolized by a non-enzymatic pathway, no significant impairment of its metabolism in hepatic insufficiency is expected.

Children and adolescents

In adolescents (12-17 years), the pharmacokinetics of linezolid taken at a dose of 600 mg was not different from that of adults. Thus, when adolescents are prescribed linezolid 600 mg every 12 hours, its concentration will be the same as in adults at the same dose.

Patients in the elderly

In patients aged 65 years and older, the pharmacokinetics of linezolid do not change significantly.

Patients who are female

Women have slightly lower volume of distribution of linezolid than men; they also have a 20% lower average clearance per body weight. Plasma concentration of linezolid in women is higher than in men which may be partially 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 elevated plasma concentrations of linezolid in women above the tolerated level, so no dose adjustment is required.

Indications

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

– community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia or Staphylococcus aureus (only methicillin-sensitive strains);

– hospital-acquired pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);

– complicated infections of the skin and soft tissues, 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 infections of the skin and soft tissues caused by Staphylococcus aureus (only methicillin-sensitive strains) or Streptococcus pyogenes;

– infections caused by Enterococcus faecalis (strains resistant to vancomycin), including those accompanied by bacteremia.

Pharmacological effect

Pharmacotherapeutic group

Antibiotic – oxazolidinone

ATX code: J01XX08

The antimicrobial agent belongs to the oxazolidinone class. The mechanism of action of the drug is due to the inhibition of protein synthesis in bacteria. Linezolid binds to the 23S site on the bacterial ribosomal RNA 50S subunit and prevents the formation of a functional 70S initiation complex, an important component of the translation process during protein synthesis. Linezolid is active in vitro against aerobic gram-positive bacteria, some gram-negative bacteria and anaerobic microorganisms.

Sensitivity

The drug is active invitro and invivo:

Gram-positive aerobes

Enterococcusfaecium (including vancomycin-resistant strains)

Staphylococcus aureus (including methicillin-resistant strains)

Streptococcusagalactiae

Streptococcus pneumoniae (including multidrug-resistant strains)

Streptococcus pyogenes

The drug is active in vitro:

Gram-positive aerobes

Enterococcus faecalis (including vancomycin-resistant strains)

Enterococcusfaecium (strains sensitive to vancomycin)

Staphylococcus epidermidis (including methicillin-resistant strains)

Staphylococcushaemolyticus

Streptococci of the viridans group

Gram-negative aerobes: Pasteurellamultocida

Linezolid-resistant microorganisms:

Haemophilusinfluenzae

Moraxella catarrhalis

Neisseria spp.

Enterobacteriaceae spp.

Pseudomonas spp.

There is no cross-resistance of microorganisms between linezolid and antimicrobial drugs of other classes (aminoglycosides, beta-lactam antibiotics, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifampicins, tetracyclines and chloramphenicol). Linezolid is active against both sensitive and resistant microorganisms to these drugs. Resistance to linezolid develops very slowly through a multistep mutation of the 23S ribosomal RNA. In addition to the main antimicrobial effect, it exhibits the properties of a weak, non-selective inhibitor of monoamine oxidase (MAO) types A and B.

Pharmacokinetics:

Suction

After oral administration, linezolid is rapidly and intensively absorbed from the gastrointestinal tract. The maximum concentration of linezolid in the blood plasma (Cmax) is 212 mg/l; the average period of time until the maximum concentration of linezolid in the blood (TCmax) is reached is 2 hours; the absolute bioavailability is about 100%.

Food intake does not affect the absorption of linezolid. The equilibrium concentration of linezolid in the blood is achieved on the 2nd day of administration.

Distribution

The volume of distribution of linezolid upon reaching equilibrium concentration in a healthy adult averages 40-50 L, which is approximately equal to the total water content in the body. Plasma protein binding is 31% and is independent of the concentration of linezolid in the blood.

Metabolism

It has been established that cytochrome P450 isoenzymes are not involved in the in vitro metabolism of linezolid. 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 – hydroxyethylglycine (the main metabolite in humans is formed as a result of a non-enzymatic process) and aminoethoxyacetic acid (formed in smaller quantities). Other inactive metabolites have also been described.

Removal

Extrarenal clearance accounts for approximately 65% ​​of linezolid clearance. As the dose of linezolid increases, a slight degree of nonlinearity in clearance is observed. This may be explained by decreased renal and extrarenal clearance with high doses of linezolid. However, differences in clearance are small and do not affect the apparent half-life.

Linezolid in patients with normal renal function and with mild to moderate renal failure is excreted by the kidneys in the form of hydroxyethylglycine (40%), aminoethoxyacetic acid (10%) and unchanged (30-35%). The intestines are excreted in the form of hydroxyethylglycine (6%) and aminoethoxyacetic acid (3%). Linezolid is practically not excreted unchanged by the intestines.

The half-life of linezolid averages 5-7 hours.

Pharmacokinetics in selected patient groups

Patients with renal failure

After a single dose of linezolid 600 mg in patients with severe renal failure (creatine clearance <30 ml/min), the concentration of its two main metabolites increased 7-8 times.

However, there was no increase in the AUC (area under the concentration-time curve) of the parent drug. Despite the fact that some major metabolites were removed by hemodialysis, their plasma concentrations after taking 600 mg of linezolid and undergoing dialysis remained significantly higher than the blood concentrations in patients with normal renal function and mild to moderate renal failure.

Patients with liver failure

There is limited data that in patients with mild to moderate hepatic impairment (Child-Pugh class A and B), the pharmacokinetics of linezolid and its two main metabolites do not change. Pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C) has not been studied. However, since linezolid is metabolized non-enzymatically, no significant disruption of its metabolism is expected in liver failure.

Children and teenagers

In adolescents (12-17 years), the pharmacokinetics of linezolid taken at a dose of 600 mg did not differ from the kinetics in adults. Thus, when adolescents are prescribed 600 mg of linezolid every 12 hours, its concentration will be the same as in adults when prescribed the same dose.

Elderly patients

In patients aged 65 years and older, the pharmacokinetics of linezolid do not change significantly.

Female patients

In women, the volume of distribution of linezolid is slightly lower than in men; they also have a 20% reduction in average clearance per body weight. Plasma concentrations of linezolid in women are higher than in men, which may be partly due to differences in body weight. However, since the half-life of linezolid does not differ significantly between men and women, there is no reason to expect an increase in the concentration of linezolid in the blood plasma of women above the tolerable level, so no dose adjustment is required.

Special instructions

In an open-label study of critically 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%) vs. 58/363 (16.0%)]. The main factor influencing mortality was the gram-positive pathogen at the initial stage.

The mortality rate was similar among patients whose infections were caused only by gram-positive organisms, but was significantly higher in the linezolid group when other organisms were also detected or were not initially detected. The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. Many patients in the linezolid group developed Gram-negative organisms during the study and died from Gram-negative or polymicrobial infections.

Therefore, for complicated skin and soft tissue infections, linezolid should be used in patients with known or possible co-infection with Gram-negative organisms only if no alternative treatment options are available. In these cases, additional use of drugs acting on gram-negative microflora is simultaneously indicated. Some patients taking linezolid may develop reversible myelosuppression (with anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. Older patients are also at increased risk of developing this condition.

Thrombocytopenia occurred more often in patients with severe renal failure, regardless of the patient’s use of hemodialysis. In this regard, during treatment it is necessary to monitor blood counts in patients with an increased risk of bleeding, a history of myelosuppression, as well as with 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 for more than 2 weeks.

Linezolid is used in such patients only when close monitoring of hemoglobin, white blood cell and platelet counts is possible. If significant myelosuppression develops during linezolid therapy, treatment should be discontinued unless continued therapy is considered absolutely necessary. In this case, intensive monitoring of blood counts and appropriate treatment are necessary.

In addition, it is recommended that blood tests (including hemoglobin, platelet count, and white blood cell count (with leukocyte count calculation)) be performed weekly in patients receiving linezolid, regardless of baseline blood test values. A higher incidence of severe anemia was observed in patients receiving linezolid for more than the maximum recommended duration of 28 days. These patients were more likely to require blood transfusions. Cases of sideroblastic anemia have been reported in the post-marketing period. In most cases, the duration of linezolid therapy exceeded 28 days. In most patients, manifestations were completely or partially reversible after discontinuation of linezolid treatment with or without specific anemia treatment.

In patients taking antibacterial drugs, including linezolid, the risk of developing pseudomembranous colitis of varying severity should be considered. Cases of Clostridium difficile-associated diarrhea have been reported in association with the use of virtually all antibacterial drugs, including linezolid. The severity of diarrhea can vary from mild to severe. Treatment with antibacterial drugs disrupts the normal intestinal microflora, which leads to excessive growth of Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to Clostridium difficile-associated diarrhea. Excessive amounts of toxins produced by Clostridium difficile strains may cause increased mortality in patients, as such infections may be resistant to antimicrobial therapy and may require colonectomy. You should not use medications that inhibit intestinal motility. The possibility of developing Clostridium difficile-associated diarrhea should be considered in all patients with diarrhea following antibiotic use. Close medical observation for 2 months is necessary for patients who experience diarrhea associated with Clostridium difficile after administration of antibacterial drugs.

If symptoms of deterioration in visual function appear, such as changes in visual acuity, changes in color perception, blurred vision, visual field defects, it is recommended to immediately consult an ophthalmologist for consultation. Visual function should be monitored in all patients taking linezolid long-term (more than 28 days) and in all patients with new-onset visual symptoms, regardless of the duration of therapy.

In the event of development of peripheral neuropathy and optic neuropathy, the risk/benefit ratio of continuing 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.
Lactic acidosis has been reported in association with linezolid use. Patients who experience repeated nausea or vomiting, abdominal pain, unexplained acidosis, or a decrease in bicarbonate anion concentrations while taking linezolid require careful monitoring by a physician.

Linezolid inhibits mitochondrial protein synthesis. Side effects such as lactic acidosis, anemia and neuropathy (peripheral and optic) may 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, with most cases having a history of convulsions or risk factors for their development. Patients should obtain a detailed history regarding 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 impaired cognitive function, hyperpyrexia, hyperreflexia and impaired motor coordination. If these symptoms appear, one or both medications should be discontinued. When you stop taking a serotonergic drug, withdrawal symptoms may occur.

Cases of reversible superficial discoloration of tooth enamel have been reported with the use of linezolid. These discolorations were removed by professional teeth cleaning.

Cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving linezolid concomitantly with insulin or hypoglycemic agents. Although a cause-and-effect relationship between the use of linezolid and the development of hypoglycemia has not been established, patients with diabetes mellitus should be warned about the possibility of developing hypoglycemia. If hypoglycemia occurs, dose adjustment of insulin/hypoglycemic drugs or discontinuation of linezolid is necessary.
Patients should be advised not to consume large quantities of foods containing tyramine (such as red wine, old cheese, some alcoholic beverages, smoked meats).

There have been no clinical studies examining the effect of linezolid on the normal microflora of the human body.

The use of antibacterial drugs can sometimes lead to increased growth of microorganisms that are resistant to it. Clinical studies have shown that approximately 3% of patients receiving recommended doses of linezolid developed antibiotic-associated candidiasis. If superinfection occurs while taking linezolid, appropriate medical measures should be taken.

Clinical studies.

The safety and effectiveness of linezolid for more than 28 days have not been established.
Controlled clinical trials did not include patients with diabetic foot syndrome, pressure ulcers or ischemic disorders, severe burns or gangrenous lesions. Thus, experience with linezolid in the treatment of these conditions is limited.

Impact on the ability to drive vehicles and machinery

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

Active ingredient

Linezolid

Composition

1 film-coated tablet, 600 mg contains:

Active substance: linezolid 600 mg;

Excipients: corn starch 40 mg, croscarmellose sodium 38 mg, mannitol 54 mg, magnesium stearate 8 mg, povidone K-30 20 mg, microcrystalline cellulose 100 mg;

Film coating: opadry white 26 mg, including: hypromellose (hydroxypropyl methylcellulose) 8.775 mg, hyprolose (hydroxypropylcellulose) 8.775 mg, talc 5.2 mg, titanium dioxide 3.25 mg.

Pregnancy

The use of linezolid during pregnancy is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus. It is unknown whether linezolid is excreted in breast milk; therefore, it is recommended to avoid breastfeeding during linezolid therapy.

Contraindications

– Hypersensitivity to linezolid and/or other components of the drug;

– children under 12 years of age (due to the impossibility of adequate dose selection;

– simultaneous use with drugs that inhibit monoamine oxidase A or B (for example, phenelzine isocarboxazid) and also within two weeks after stopping taking these drugs;

Unless patients are closely monitored and blood pressure monitored, linezolid should not be prescribed:

– patients with uncontrolled arterial hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, schizoaffective disorder and acute confusion;

– patients receiving the following types of drugs: adrenomimetics (for example pseudoephedrine phenylpropanolamine epinephrine norepinephrine dobutamine) dopaminomimetics (for example dopamine) serotonin reuptake inhibitors tricyclic antidepressants 5HT1 receptor agonists (triptans) meperidine or buspirone.

With caution:

Patients with renal failure

Due to the unknown clinical significance of linezolid’s two primary metabolites in patients with severe renal impairment, linezolid should be used with caution in such patients and only if the expected benefit outweighs the potential risk.

Patients with liver failure

There is limited clinical data to recommend the use of linezolid in such patients only if the expected benefit outweighs the potential risk.

Linezolid should be used with caution in patients with life-threatening systemic infections such as infections associated with venous catheters in intensive care units.

Side Effects

The frequency of side effects presented below was determined according to the following (World Health Organization classification):

“very often” (≥1/10)
“often” (≥1/100 < 1/10)
“infrequently” (≥1/1000 < 1/100)
“rarely” (≥1/10000 < 1/1000)
“very rare” (< 1/10000)
frequency is unknown (it is impossible to estimate the frequency of development from the available data).

Adverse events associated with linezolid are usually mild or moderate in severity. The most common symptoms are diarrhea, headache and nausea, vomiting.

Adult patients

Infectious and parasitic diseases

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

Blood and lymphatic system disorders

Often – anemia; uncommon – leukopenia, neutropenia, thrombocytopenia, eosinophilia; rarely – pancytopenia; frequency unknown – myelosuppression, sideroblastic anemia.

Immune system disorders

Frequency unknown – anaphylaxis.

Metabolic and nutritional disorders

Uncommon: hyponatremia; frequency unknown – lactic acidosis.

Mental disorders

Often – insomnia.

Nervous system disorders

Often – headache, perversion of taste (“metallic” taste in the mouth), dizziness; infrequently – convulsions, hypoesthesia, paraesthesia; frequency unknown – serotonin syndrome peripheral neuropathy.

Visual disorders

Uncommon: blurred vision; rarely – the appearance of visual field defects; frequency unknown – optic neuropathy optic neuritis loss of vision changes in visual acuity changes in color vision.

Hearing and labyrinth disorders

Uncommon: ringing in the ears.

Cardiovascular disorders

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

Gastrointestinal disorders

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

Disorders of the liver and biliary tract

Often – changes in the results of liver function tests, increased activity of “liver enzymes” (including alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (ALP)) infrequently – increased concentration of total bilirubin.

Skin disorders

Often – rash itching; uncommon – urticaria, dermatitis, increased sweating; frequency unknown – bullous skin lesions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, alopecia.

Renal and urinary tract disorders

Often – increased blood urea concentration; infrequently – renal failure, increased concentration of creatinine in the blood plasma, polyuria.

Disorders of the genital organs and breast

Uncommon: disorders of the vagina and vulva.

General and administration site disorders

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

Laboratory indicators

Often – an increase or decrease in potassium or bicarbonates, an increase in the number of neutrophils, eosinophils, a decrease in hematocrit hemoglobin or the number of red blood cells, an increase or decrease in the number of platelets or leukocytes, an increase in the activity of lactate dehydrogenase, creatine kinase lipase amylase, an increase in the concentration of glucose not on an empty stomach, a decrease in total protein albumin, a decrease in sodium or calcium in the blood plasma; infrequently – an increase in sodium or calcium in the blood plasma; a decrease in fasting glucose concentration; an increase or decrease in blood chlorides; an increase in the number of reticulocytes; a decrease in the number of neutrophils.

The following side effects with the use of linezolid in rare cases were classified as serious: localized abdominal pain, transient ischemic attack, arterial hypertension.

In controlled clinical studies in which linezolid was used for a maximum of 28 days, only 2% of patients developed anemia. In another study of patients with life-threatening infections, 25% (33/1326) of patients treated with linezolid for less than 28 days developed anemia, while 123% (53/430) of patients treated with linezolid for more than 28 days developed anemia.

The incidence of anemia requiring transfusion was 9% among patients receiving linezolid for less than 28 days (3/33) and 15% (8/53) in those receiving linezolid for more than 28 days. Side effects in children do not differ from those in adult patients.

Interaction

It has been established that cytochrome P450 isoenzymes are not involved in the in vitro metabolism of linezolid. Linezolid does not inhibit or potentiate the activity of clinically important cytochrome P450 isoenzymes (1A2 2C9 2C19 2D6 2E1 3A4). Therefore, a CYP450-induced interaction is not expected with linezolid. With simultaneous use of linezolid and (S)-warfarin, which is largely metabolized by the CYP2C9 isoenzyme, the pharmacokinetic characteristics of warfarin do not change. Drugs such as warfarin and phenytoin, which are substrates of the CYP2C9 isoenzyme, can be used simultaneously with linezolid without dose adjustment.

Monoamine oxidase inhibitors

Linezolid is a non-selective, reversible monoamine oxidase inhibitor; therefore, some patients receiving linezolid may experience a moderate, reversible increase in the pressor effects of pseudoephedrine and phenylpropanolamine. In this regard, it is recommended to reduce the initial doses of the following groups of drugs: adrenergic agonists (for example, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine) and dopaminergic agonists (for example, dopamine) and then titrate the dose.

In phase I II III studies, the development of serotonin syndrome was not observed in patients receiving linezolid in combination with serotonergic drugs. However, there have been several reports of the development of serotonin syndrome during the use of linezolid and selective serotonin reuptake inhibitor antidepressants. When used concomitantly with aztreonam and gentamicin, no changes in the pharmacokinetics of linezolid were observed.

Rifampicin caused a decrease in Cmax and AUC of linezolid by an average of 21% and 32%, respectively.

Overdose

There are no reports of cases of overdose.

If necessary, symptomatic therapy is carried out (including the need to maintain the level of glomerular filtration). Approximately 30% of the dose is eliminated within 3 hours during hemodialysis.

There is no evidence that linezolid elimination is accelerated by peritoneal dialysis or hemoperfusion.

Storage conditions

At a temperature not exceeding 25 °C in the manufacturer’s packaging.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after expiration date.

Manufacturer

Kanonpharma production CJSC, Russia