Zyvox solution for infusion 2 mg/ml 100 ml disposable infusion bag 10 pcs. in Moscow

Pharmacological properties of the drug Zyvox

Linezolid ((s)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide) is a synthetic antimicrobial agent of the oxazolidinone group. Active in vitro against aerobic gram-positive bacteria, some gram-negative bacteria and anaerobic microorganisms. Linezolid selectively inhibits protein synthesis in bacteria: it binds to bacterial ribosomes and prevents the formation of a functional 70S initiation complex (an important component of the translation process). in vitro post-antibiotic effect of linezolid for Staphylococcus aureus was approximately 2 hours. In animal models, the in vivo was 3.6 and 3.9 hours for Staphylococcus aureus and Streptococcus pneumoniae , respectively. The following microorganisms are sensitive to linezolid: gram-positive aerobes - Corynebacterium jeikeium, Enterococcus faecalis (including glycopeptide-resistant strains), Enterococcus faecium (including glycopeptide-resistant strains), Enterococcus casseliflavus, Enterococcus gallinarum, Listeria monocytogenes, Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus epidermidis, Staphylococcus ha emolyticus , Streptococcus agalactiae, Streptococcus intermedius, Streptococcus pneumoniae (including strains with moderate sensitivity to penicillin and penicillin-resistant strains); Streptococcus pyogenes, group streptococci , group C streptococci ; gram-negative aerobes - Pasteurella canis, Pasteurella multocida; gram-positive anaerobes - Clostridium perfringens, Peptostreptococcus anaerobius, Peptostreptococcus spp.; gram-negative anaerobes - Bacteroides fragilis, Prevotella spp.; others - Chlamydia pneumoniae. Moderately sensitive microorganisms: Legionella spp., Moraxella catarrhalis, Mycoplasma spp. Resistant microorganisms: Neisseria spp., Pseudomonas spp. The mechanism of action of linezolid differs from the mechanisms of action of other classes of antimicrobial drugs (for example, aminoglycosides, β-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines and chloramphenicol). Therefore, 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 through a multistep mutation of 23S ribosomal RNA and occurs with a frequency of less than 1 • 10 –9 –1 • 10 –11. Zyvox contains the biologically active (s)-linezolid, which is metabolized in the body to form inactive derivatives. The average pharmacokinetic parameters (standard deviation) of linezolid in healthy volunteers after single and repeated (until the steady-state concentration of linezolid in the blood is reached) oral administration are presented in the table. Pharmacokinetic parameters

Cmax—maximum concentration in blood plasma; Cmin—minimum concentration in blood plasma; Tmax is the time to reach Cmax;

AUC*—area under the concentration/time curve; t1/2 - half-life; CL - system clearance; SD - standard deviation.

The average pharmacokinetic parameters (standard deviation) of linezolid in healthy volunteers after single and multiple (until the steady-state concentration of linezolid in the blood is reached) intravenous administration are presented in the table. Pharmacokinetic parameters

Suction. When administered orally, linezolid is rapidly absorbed from the gastrointestinal tract. The maximum concentration of the drug in the blood plasma is achieved after 2 hours, and the absolute bioavailability is about 100%. Distribution. Linezolid is rapidly distributed into well-perfused tissues. The volume of distribution of the drug upon reaching equilibrium concentration in a healthy adult averages 40–50 l, which is approximately equal to the total water content in the body. Binding to blood proteins reaches 31% and is independent of concentration. Metabolism. It has been established that cytochrome P450 isoforms do not participate in the metabolism of linezolid in vitro, and it does not inhibit the activity of clinically important CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Metabolic oxidation of the morpholine ring primarily results in the formation of 2 inactive open-ring carboxylic acid derivatives. The metabolite hydroxyethylglycine (A) is the main metabolite in humans and is formed due to a non-enzymatic process. Another metabolite, aminoethoxyacetic acid (B), is formed in smaller quantities. Other “small” inactive metabolites have also been described. Excretion. Linezolid is primarily excreted in the urine as metabolite A (40%), unchanged drug C (30–35%), and metabolite B (10%). The unchanged drug is virtually undetectable in feces; 6% of metabolite A and 3% of metabolite B are excreted in feces. Pharmacokinetics in separate groups of patients. Linezolid clearance is higher in children and decreases with age. The pharmacokinetics of linezolid did not change significantly in patients aged 65 years and older. Some pharmacokinetic differences were noted in women, which were expressed in a slightly smaller volume of distribution, a decrease in clearance by approximately 20%, and sometimes in higher plasma concentrations. Since the half-life of linezolid does not differ significantly between women and men, there is no need for dose adjustment of the drug. In patients with moderate, moderate or severe renal insufficiency, no dose adjustment is required, since there is no relationship between creatinine clearance and renal excretion of the drug. Since 30% of the drug dose is eliminated by hemodialysis within 3 hours, linezolid should be administered to patients receiving such treatment after dialysis. The pharmacokinetics of linezolid do not change in patients with moderate or moderate hepatic impairment, and therefore there is no need to adjust the dose of the drug. The pharmacokinetics of linezolid have not been studied in patients with severe hepatic impairment, but since linezolid is metabolized by a non-enzymatic process, liver function should not have a significant effect on the metabolism of the drug.

Zyvox solution for inf. 2mg/ml 300ml 10 pcs pack.

Pharmacological group:

Antibiotic oxazolidinone.
Pharmacodynamics:
Linezolid, a synthetic antibacterial drug, belongs to a new class of antimicrobial agents, oxazolidinones, active in vitro against aerobic gram-positive bacteria, some 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 70S initiation complex, which is an important component of the translation process in protein synthesis.

The drug is active in vitro and in vivo Gram-positive aerobes: Enterococcus faecium (including strains resistant to vancomycin) Staphylococcus aureus (including methicillin-resistant strains) Streptococcus agalactiae Streptococcus pneumoniae (including multidrug-resistant strains) Streptococcus pyogenes The drug is active in vitro Gram-positive aerobes Enterococcus faecalis (including strains vancomycin-resistant) Enterococcus faecium (vancomycin-susceptible strains) Staphylococcus epidermidis (including methicillin-resistant strains) Staphylococcus haemolyticus Streptococcus spp. Viridans group Gram-negative aerobes Pasteurella multocida Linezolid-resistant microorganisms: Haemophilus influenzae Moraxella catarrhalis Neisseria spp.

Enterobacteriaceae spp.

Pseudomonas spp.

Resistance

The mechanism of action of linezolid is different from that of other classes of antimicrobials (eg, aminoglycosides, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines and chloramphenicol), and therefore cross-resistance does not exist between linezolid and these drugs. Linezolid is active against pathogenic microorganisms, both sensitive and resistant to these drugs. Resistance to linezolid develops slowly through a multistep mutation of 23S ribosomal RNA and occurs at a frequency of less than 1 x 10-9 to 1 x 10-11.

Pharmacokinetics:

Suction

The mean maximum concentration (Cmax) and mean minimum concentration (Cmin) of linezolid in plasma at steady state after intravenous administration twice daily at a dose of 600 mg were 15.1 mg/L and 3.68 mg/L, respectively.

The equilibrium concentration of linezolid in the blood is achieved on the 2nd day of drug administration.

Distribution

The volume of distribution of linezolid when equilibrium concentration is reached in a healthy adult averages 40-50 L, which is approximately equal to the total body water content. 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 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 - hydroxyethylglycine (the main metabolite in humans, 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%).

In unchanged form, linezolid is practically not excreted by the intestines.

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

Pharmacokinetics in separate groups of patients

Patients with kidney failure

After a single dose of 600 mg of the drug in patients with severe renal failure (creatinine clearance

Patients with liver failure

There is limited evidence that in patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the pharmacokinetics of linezolid and its two main metabolites are not altered. The pharmacokinetics of linezolid in patients with severe hepatic impairment (Child-Pugh class C) have not been studied. However, since linezolid is metabolized non-enzymatically, significant disruption of its metabolism is not 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 given 600 mg of linezolid every 12 hours, the drug concentration will be the same as in adults when the same dose is prescribed.

In children aged 1 week to 12 years, linezolid 10 mg/kg daily every 8 hours achieves the same exposure as adults with linezolid 600 mg twice daily.

In newborns, systemic clearance of linezolid increases rapidly during the first week of life (per kg body weight). Thus, when administered at a dose of 10 mg/kg every 8 hours, the maximum exposure of linezolid will be achieved in a child on the first day of life faster on the first day after birth. However, excess accumulation of the drug in the first week of administration with this prescription regimen will still not occur 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 volume of distribution of the drug is slightly lower than in men; they also have a 20% reduction in average clearance per body weight. The concentration of the drug in the blood plasma of women is higher than that of men, which may be partly explained by 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 the drug concentration in the blood of women to increase above the tolerated value, so no dose adjustment is required.

Use of the drug Zyvox

It is prescribed orally 2 times a day. Recommended doses for adults and adolescents (12 years and older):

Recommended doses for children (up to 11 years inclusive)*:

*Premature neonates <7 days of age (≤34 weeks of gestation) have lower systemic clearance of linezolid and greater AUC than full-term neonates and older infants. Preterm neonates older than 7 days have linezolid clearance and AUC rates similar to those of full-term and older infants.

The duration of treatment depends on the pathogen, the location and severity of the infection, as well as the clinical effect. The maximum dose for adults and children should not exceed 600 mg 2 times a day. IV is prescribed 2 times a day. The solution for infusion is administered over 30–120 minutes. IV infusion is carried out for 30–120 minutes. Do not connect infusion bags in series! It is necessary to remove the protective foil shell immediately before using the drug. The bag should be squeezed for approximately 1 minute to ensure that the integrity of the bag is not compromised. If the package leaks, the drug is unsterile and cannot be used! The remaining solution should be thrown into waste. Do not use partially filled containers! Elderly patients: no dose adjustment is required. Patients with renal failure: no dose adjustment is required. Patients with severe renal failure (creatinine clearance ≤30 ml/min): no dose adjustment is required. Due to the unknown clinical significance of high exposure (up to 10-fold) to the 2 primary metabolites of linezolid in patients with severe renal impairment, linezolid should be used with caution in such patients and only when the expected benefits of therapy outweigh the potential risks. Since approximately 30% of the administered dose of linezolid is eliminated during hemodialysis lasting 3 hours, linezolid must be administered after the hemodialysis procedure. A certain portion of the primary metabolites of linezolid are eliminated during hemodialysis, but the concentrations of these metabolites continue to be high after dialysis compared to those observed in patients with normal renal function or mild to moderate renal failure. Therefore, linezolid should be used with extreme caution in patients with severe renal impairment on dialysis and only if the expected therapeutic benefit outweighs the potential risk. There is no experience with the use of linezolid in patients who have been on peritoneal dialysis for a long time in an outpatient setting. Patients with hepatic impairment: No dose adjustment is required, however, due to limited clinical data, the use of linezolid in such patients is recommended only when the expected benefit outweighs the potential risk.

Zyvox solution for infusion 2 mg/ml 100 ml disposable infusion bag 10 pcs. in Moscow

The drug is prescribed as an intravenous infusion lasting 30–120 minutes. Do not daisy chain infusion bags or add other drugs to the infusion solution. If it is necessary to administer linezolid with other drugs, then all drugs should be prescribed separately in accordance with the recommended doses and routes of administration. Linezolid injection is pharmaceutically incompatible with the following drugs:

• amphotericin B,
• chlorpromazine,
• diazepam,
• phenytoin,
• erythromycin lactobionate,
• co-trimoxazole (trimethoprim + sulfamethoxazole),
• ceftriaxone.

Compatible infusion solutions:

• 5% dextrose solution for injection
• 0.9% sodium chloride solution for injection
• Ringer-Locke solution for injection

Patients who were prescribed the drug intravenously at the beginning of therapy can subsequently be transferred to any dosage form of the drug for oral administration, and dose selection is not required, because The bioavailability of linezolid when taken orally is almost 100%. The duration of treatment depends on the pathogen, the location and severity of the infection, as well as the clinical effect.

Adults and children (12 years and older)

600 mg IV every 12 hours for 10 - 14 days when indicated (including infections accompanied by bacteremia):

• community-acquired pneumonia caused by Streptococcus pneumoniae
  (including multidrug-resistant 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 multidrug-resistant strains);
• complicated skin and soft tissue infections, including diabetic foot infections not accompanied by osteomyelitis, caused by Staphylococcus aureus
  (including methicillin-sensitive and methicillin-resistant strains),
  Streptococcus pyogenes
  or
  Streptococcus agalactiae
  ;

600 mg IV every 12 hours for 14-28 days when indicated (including infections accompanied by bacteremia):

• infections resistant to vancomycin caused by Enterococcus faecium
  , including those accompanied by bacteremia.

Children (newborns* and children up to 11 years old)

10 mg/kg IV every 8 hours for 10 - 14 days when indicated (including infections accompanied by bacteremia):

• community-acquired pneumonia caused by Streptococcus pneumoniae
  (including multidrug-resistant 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 multidrug-resistant strains);
• complicated skin and soft tissue infections, including diabetic foot infections not accompanied by osteomyelitis, caused by Staphylococcus aureus
  (including methicillin-sensitive and methicillin-resistant strains),
  Streptococcus pyogenes
  or
  Streptococcus agalactiae
  ;

10 mg/kg IV every 8 hours for 14-28 days when indicated (including infections accompanied by bacteremia):

• infections resistant to vancomycin caused by Enterococcus faeciu
  m, including those accompanied by bacteremia.

*Premature neonates less than 7 days of age (less than 34 weeks' gestation) have lower systemic clearance of linezolid and higher AUC values ​​than most neonates and children. By 7 days after birth, linezolid clearance and AUC values ​​in preterm neonates approach those of full-term neonates and children.

Elderly patients:

no dose adjustment is required.

Patients with renal failure:

no dose adjustment is required. Because 30% of linezolid is removed by hemodialysis within 3 hours, linezolid should be administered after dialysis to patients requiring it.

Patients with liver failure:

no dose adjustment is required.

Side effects of the drug Zyvox

pain, abdominal cramps, flatulence, deviations in hematological parameters and liver function tests, diarrhea, headache, candidiasis, nausea, taste distortion, vomiting, transient anemia, thrombocytopenia, leukopenia and pancytopenia, candidiasis. Neuropathy (peripheral, optic nerve) has been observed rarely with linezolid use, especially when the maximum recommended treatment duration of 28 days is exceeded. During post-registration use of the drug, the following side effects were noted: from the blood system - reversible anemia, leukopenia, thrombocytopenia, pancytopenia; from the organ of vision - progression of optic neuropathy up to the development of blindness was sometimes reported (mainly observed when the maximum recommended duration of treatment of 28 days was exceeded); from the immune system - anaphylaxis; from the metabolic side - lactic acidosis; from the nervous system - peripheral neuropathy, seizures; from the skin and subcutaneous tissue - rash, angioedema, very rarely - Stevens-Johnson syndrome; from the gastrointestinal tract - changes in the color of the tongue, isolated cases of superficial changes in the color of teeth (plaque can be eliminated with professional dental cleaning).

Zyvox 2mg/ml 300ml 10 pcs. solution for infusion fresenius kabi norge

pharmachologic effect

Antibiotic oxazolidinone.

Composition and release form Zyvox 2 mg/ml 300 ml 10 pcs. solution for infusion fresenius kabi norge

Solution - 1 ml:

• Active ingredient: linezolid - 2 mg;
• Excipients: sodium citrate dihydrate 1.64 mg, citric acid 0.85 mg, dextrose monohydrate 50.24 mg, water for injection up to 1 ml.

100 ml and 300 ml in disposable infusion bags made of multi-layer film with two injection ports, one closed by a rubber stopper with a sleeve, the other by a removable protective cap or closed rubber stoppers and removable protective caps, sealed one at a time inside laminated foil.

1, 2, 5, 10 or 25 bags along with instructions for use are placed in a cardboard box.

Description of the dosage form

Transparent, colorless to yellow solution.

Directions for use and doses

Linezolid should only be used in a hospital setting and after consultation with an appropriate specialist, such as a microbiologist or infectious disease specialist.

The drug is prescribed as an intravenous infusion lasting 30-120 minutes.

Do not daisy chain infusion bags or add other drugs to the infusion solution. If it is necessary to administer linezolid with other drugs, then all drugs should be prescribed separately in accordance with the recommended doses and routes of administration.

Linezolid injection is pharmaceutically incompatible with the following drugs: amphotericin B, chlorpromazine, diazepam, phenytoin, erythromycin lactobionate, co-trimoxazole (trimethoprim + sulfamethoxazole), ceftriaxone.

Compatible infusion solutions:

• 5% dextrose solution for injection;
• 0.9% sodium chloride solution for injection;
• Ringer-Locke solution for injection.

Patients who were prescribed the drug intravenously at the beginning of therapy can subsequently be transferred to any dosage form of the drug for oral administration, and dose selection is not required, because The bioavailability of linezolid when taken orally is almost 100%. The duration of treatment depends on the pathogen, the location and severity of the infection, as well as the clinical effect.

Adults and children (12 years and older):

• Community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (methicillin-sensitive strains only) - Single dose 600 mg IV every 12 hours for 10-14 days;
• Hospital-acquired pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains) - Single dose 600 mg IV every 12 hours for 10-14 days;
• Complicated skin and soft tissue infections, including diabetic foot infections not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae - Single dose 600 mg IV every 12 hours for 10-14 days;
• Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only) or Streptococcus pyogenes - Single dose 400 mg IV every 12 hours (for adults) or 600 mg IV every 12 hours (for children over 12 years of age) in within 10-14 days;
• Infections caused by Enterococcus faecium resistant to vancomycin, including those accompanied by bacteremia - A single dose of 600 mg IV every 12 hours for 14-28 days.

Children (newborns* and children up to 11 years old)

• Community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (methicillin-sensitive strains only) - Single dose of 10 mg/kg IV every 8 hours for 10-14 days;
• Hospital-acquired pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains) - Single dose of 10 mg/kg IV every 8 hours for 10-14 days;
• Complicated skin and soft tissue infections, including diabetic foot infections not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae - Single dose 10 mg/kg IV every 8 hours for 10 -14 days;
• Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only) or Streptococcus pyogenes - Single dose 10 mg/kg IV every 8 hours (for children under 5 years) or 10 mg/kg IV every 12 hours ( for children from 5 to 11 years old) within 10-14 days;
• Infections caused by Enterococcus faecium resistant to vancomycin, including those accompanied by bacteremia - Single dose of 10 mg/kg IV every 8 hours for 14-28 days.

*Premature neonates less than 7 days of age (less than 34 weeks' gestation) have lower systemic clearance of linezolid and higher AUC values ​​than most neonates and children. By 7 days after birth, linezolid clearance and AUC values ​​in preterm neonates approach those of full-term neonates and children.

Elderly patients: no dose adjustment is required.

Patients with renal failure: no dose adjustment is required. Because 30% of linezolid is removed by hemodialysis within 3 hours, linezolid should be administered after dialysis to patients requiring it.

Patients with liver failure: no dose adjustment is required.

Pharmacodynamics

Linezolid, a synthetic antibacterial drug, belongs to a new class of antimicrobial agents, the oxazolidinones, that are active in vitro against aerobic gram-positive bacteria, some 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 70S initiation complex, 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 faecalis (including strains resistant to vancomycin); Staphylococcus aureus (including methicillin-resistant strains); Streptococcus agalactiae; Streptococcus pneumoniae (including multidrug-resistant strains); Streptococcus pyogenes.

The drug is active in vitro

Gram-positive aerobes: Enterococcus faecalis (including strains resistant to vancomycin); Enterococcus faecium (strains sensitive to vancomycin); Staphylococcus epidermidis (including methicillin-resistant strains); Staphylococcus haemolyticus; Streptococcus spp. Viridans group.

Gram-negative aerobes: Pasteurella multocida.

Linezolid-resistant microorganisms: Haemophilus influenzae; Moraxella catarrhalis; Neisseria spp.; Enterobacteriaceae spp.; Pseudomonas spp.

Resistance

The mechanism of action of linezolid is different from that of other classes of antimicrobials (eg, aminoglycosides, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines and chloramphenicol), and therefore cross-resistance does not exist between linezolid and these drugs.

Linezolid is active against pathogenic microorganisms, both sensitive and resistant to these drugs.

Resistance to linezolid develops slowly through a multistep mutation of 23S ribosomal RNA and occurs with a frequency of less than 1x10-9 - 1x10-11.

Pharmacokinetics

Suction

The mean maximum concentration (Cmax) and mean minimum concentration (Cmin) of linezolid in plasma at steady state after intravenous administration twice daily at a dose of 600 mg were 15.1 mg/L and 3.68 mg/L, respectively. The equilibrium concentration of linezolid in the blood is achieved on the 2nd day of drug administration.

Distribution

The volume of distribution of linezolid when equilibrium concentration is reached in a healthy adult averages 40-50 L, which is approximately equal to the total body water content. 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 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 - hydroxyethylglycine (the main metabolite in humans, 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%).

In unchanged form, linezolid is practically not excreted by the intestines.

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

Pharmacokinetics in separate groups of patients

Patients with kidney failure

After a single dose of 600 mg of the drug in patients with severe renal failure (creatinine clearance

Patients with liver failure

There is limited evidence that in patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the pharmacokinetics of linezolid and its two main metabolites are not altered.

The pharmacokinetics of linezolid in patients with severe hepatic impairment (Child-Pugh class C) have not been studied. However, since linezolid is metabolized non-enzymatically, significant disruption of its metabolism is not 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 given 600 mg of linezolid every 12 hours, the drug concentration will be the same as in adults when the same dose is prescribed.

In children aged 1 week to 12 years, linezolid 10 mg/kg daily every 8 hours achieves the same exposure as adults with linezolid 600 mg twice daily.

In newborns, systemic clearance of linezolid increases rapidly during the first week of life (per kg body weight). Thus, when administered at a dose of K) mg/kg every 8 hours, the maximum exposure of linezolid will be achieved in a child on the first day of life faster on the first day after birth. However, excess accumulation of the drug in the first week of administration with this prescription regimen will still not occur 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 volume of distribution of the drug is slightly lower than in men; they also have a 20% reduction in average clearance per body weight. The concentration of the drug in the blood plasma of women is higher than that of men, which may be partly explained by 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 the drug concentration in the blood of women to increase above the tolerated value, so no dose adjustment is required.

Indications for use Zyvox 2mg/ml 300ml 10 pcs. solution for infusion fresenius kabi norge

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 (methicillin-sensitive strains only);
• 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 or Streptococcus agalactiae;
• infections resistant to vancomycin caused by Enterococcus faecium, including those accompanied by bacteremia.

When determining whether Zyvox® is an appropriate treatment, microbiological studies or information on the prevalence of antibacterial resistance among Gram-positive bacteria should be taken into account.

Linezolid is not active against infections caused by gram-negative pathogens. If Gram-negative pathogens are suspected or confirmed, specific therapy against Gram-negative microorganisms should be initiated.

Contraindications

Hypersensitivity to linezolid and/or other components of the drug.

Concomitant use of linezolid with drugs that inhibit monoamine oxidases A or B (for example, phenelzine, isocarboxazid), as well as for 2 weeks after stopping 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: adrenergic agonists (eg, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminergic agonists (eg, dopamine), serotonin reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists (triptans), meperidine, or buspirone.

Carefully:

Patients with kidney 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. There are also no data on the use of linezolid in patients undergoing ambulatory peritoneal dialysis or other alternative treatments for renal failure.

Patients with liver failure

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

Linezolid should be used with caution in patients with systemic infections that pose a risk to life, such as infections associated with venous catheters in intensive care units.

Application of Zyvox 2mg/ml 300ml 10 pcs. solution for infusion fresenius kabi norge during pregnancy and lactation

There have been no studies of the safety of linezolid during pregnancy, therefore the use of Zyvox® during pregnancy is possible only if the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

It is unknown whether linezolid is excreted in the breast milk of lactating women, so breastfeeding should be discontinued when prescribing the drug to a mother during lactation.

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 (16.5%). 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 (odds ratio 0.96; 95% confidence interval: 0.58-1.59), but was significantly higher (p=0.0162) in the linezolid group when other microorganisms were also detected or could not be detected at the initial stage (odds ratio 2.48; 95% confidence interval: 1.38-4.46). The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. During the study, more patients in the linezolid group acquired Gram-negative organisms and subsequently 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 (see Indications). 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. Do 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 symptoms of visual impairment, 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 antimycobacterial 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 or 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, symptoms of diabetic foot syndrome, pressure ulcers or ischemic disorders, severe burns or gangrenous lesions may occur. Thus, experience with linezolid in the treatment of these conditions is limited.

Impact on the ability to drive vehicles and operate machinery

During treatment with linezolid, driving vehicles, special equipment or engaging in activities associated with increased risk is not recommended.

Overdose

No cases of linezolid overdose have been reported. Symptomatic treatment is recommended (including the need to maintain glomerular filtration rate). There are no data regarding acceleration of linezolid elimination by peritoneal dialysis or hemoperfusion.

Side effects of Zyvox 2mg/ml 300ml 10 pcs. solution for infusion fresenius kabi norge

The frequency of side effects listed below was determined according to the following (World Health Organization classification): very often (>1/10), often (>1/100 - 1/1000 - 1/10000 -

Adverse events associated with linezolid are usually mild or moderate in severity. More often than others, diarrhea, headache, nausea, and vomiting are observed.

Adult patients

Infectious and parasitic diseases: often - candidiasis (including oral candidiasis, vaginal candidiasis), fungal infections; infrequently - vaginitis; rarely - colitis caused by the use of antibiotics (including pseudomembranous colitis)*.

Disorders of the blood and lymphatic system: often - anemia; uncommon - leukopenia, neutropenia, thrombocytopenia, eosinophilia; rarely - pancytopenia; frequency unknown - myelosuppression, sideroblastic anemia.

Immune system disorders: frequency unknown - anaphylaxis.

Metabolic and nutritional disorders: infrequently - hyponatremia; frequency unknown - lactic acidosis.

Mental disorders: often - insomnia.

Nervous system disorders: often - headache, taste disturbance ("metallic" taste in the mouth), dizziness; infrequently - convulsions*, hypoesthesia, paresthesia; frequency unknown - serotonin syndrome, peripheral neuropathy*.

Visual disturbances: infrequently - 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 labyrinthine disorders: uncommon - tinnitus.

Cardiovascular system disorders: often - increased blood pressure; uncommon - arrhythmia (tachycardia), transient ischemic attack, phlebitis, thrombophlebitis.

Gastrointestinal disorders: often - diarrhea, nausea, vomiting, localized or diffuse abdominal pain, constipation, dyspepsia; uncommon - 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 (AST), alkaline phosphatase (ALP)); infrequently - increased concentration of total bilirubin.

Disorders of the skin and subcutaneous tissues: often - itching, rash; uncommon - urticaria, dermatitis, increased sweating; frequency unknown - bullous skin lesions (such as Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, alopecia.

Disorders of the kidneys and urinary tract: often - increased concentration of urea in the blood; uncommon - renal failure, increased plasma creatinine concentration, polyuria.

Disorders of the genital organs and mammary gland: infrequently - disorders of the vagina and vulva.

General disorders and disorders at the injection site: often - fever, localized pain; uncommon - chills, fatigue, thirst, pain at the injection site (for solution for infusion).

Laboratory indicators: often - an increase in the number of neutrophils, eosinophils, a decrease in hemoglobin, hematocrit or red blood cell count, an increase or decrease in the number of platelets or leukocytes, an increase in the activity of lactate dehydrogenase, creatine kinase. lipases, amylases, increased non-fasting glucose concentrations, decreased total protein, albumin, sodium or calcium, increased or decreased potassium or bicarbonates; uncommon - increased sodium or calcium levels in the blood plasma, decreased fasting glucose concentrations, increased or decreased blood chlorides, increased reticulocyte counts, decreased neutrophil counts.

The following side effects with 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. When an unapproved drug was used in early access programs for patients with life-threatening infections, 2.5% (33/1326) of patients who received linezolid ≤ 28 days developed anemia, while when linezolid was used for more than 28 days, anemia developed in 12.3% (53/430) of patients.

The incidence of anemia requiring transfusion was 9% among patients receiving linezolid ≤ 28 days (3/33) and 15% (8/53) when linezolid was used for more than 28 days.

Safety data obtained from clinical studies involving more than 500 pediatric patients (birth to 17 years of age) do not indicate that the safety profile of linezolid in children differs from that in adults.

Drug interactions

It has been established that cytochrome P450 isoenzymes are not involved 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). 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 CYP2C9 substrates, can be used concomitantly with linezolid without dose adjustment.

Monoamine oxidase inhibitors

Linezolid is a non-selective, reversible monoamine oxidase inhibitor, and some patients receiving linezolid may experience a mild 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), dopaminomimetics (for example, dopamine) and then titrate the dose.

In phase I, II and 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 antidepressants - selective serotonin reuptake inhibitors.

When used concomitantly with aztreonam and gentamicin, no changes in the pharmacokinetics of linezolid were observed.

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

Special instructions for the use of Zyvox

Pseudomembranous colitis of varying severity can develop with the use of almost all antibacterial drugs, including linezolid, and the severity can vary from moderate to life-threatening, which must be taken into account when diarrhea develops in a patient receiving antibiotic therapy. Cases of diarrhea associated with Clostridium difficile have been reported with the use of almost all antibacterial agents, including linezolid. The severity of diarrhea can range from moderate diarrhea to severe fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile . C. difficile produces toxins A and B, which cause diarrhea. strains of C. difficile cause increased morbidity and mortality because the infection they cause may be refractory to antimicrobial therapy and require colectomy. In all patients who develop diarrhea while on antibiotics, Clostridium difficile- . Some patients receiving linezolid may develop transient myelosuppression (anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. In this regard, it is necessary to monitor complete blood count indicators in patients who have an increased risk of bleeding and manifestations of myelosuppression, who are taking drugs that can reduce the amount of hemoglobin, platelets in the blood or impair their functional properties, as well as with a duration of treatment with linezolid of 2 weeks. Linezolid is inactive against gram-negative microorganisms and is ineffective in treating infections caused by them. If concomitant gram-negative infection is suspected or documented, therapy with drugs to which gram-negative bacteria are sensitive is recommended. Linezolid should be used with caution in patients with systemic infections at high risk of developing dangerous complications, such as infections due to the presence of a central venous catheter in patients in intensive care units. Linezolid is not indicated for use in patients with septic conditions due to catheter infection. Adequate and controlled studies of Zyvox in pregnant women have not been conducted. Zyvox should be used during pregnancy only for absolute indications, that is, when the potential benefit of drug therapy outweighs the potential risk. It is unknown whether linezolid passes into breast milk, so special caution should be exercised when using the drug during breastfeeding. No effect of the drug on the ability to drive vehicles or use other mechanisms was noted.

Zyvox®

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 (16.5%). 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 (odds ratio 0.96; 95% confidence interval: 0.58-1.59), but was significantly higher (p=0.0162) in the linezolid group when other microorganisms were also detected or could not be detected at the initial stage (odds ratio 2.48; 95% confidence interval: 1.38-4.46). The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. During the study, more patients in the linezolid group acquired Gram-negative organisms and subsequently 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 (see Indications). 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. Do 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 symptoms of visual impairment, 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 antimycobacterial 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 or 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, symptoms of diabetic foot syndrome, pressure ulcers or ischemic disorders, severe burns or gangrenous lesions may occur. Thus, experience with linezolid in the treatment of these conditions is limited.

Drug interactions Zyvox

Linezolid is a weak, reversible, non-selective MAO inhibitor and may cause a moderate increase in the pressor effects of pseudoephedrine hydrochloride and phenylpropanolamine hydrochloride in some patients. It is recommended to reduce the initial doses of adrenergic drugs such as dopamine (or its agonists) and subsequently titrate the dose. The pharmacokinetics of linezolid are not altered by coadministration of aztreonam and gentamicin. Zyvox solution for infusion is compatible with the following solutions: 5% dextrose solution, 0.9% sodium chloride solution, lactated Ringer's solution for injection. Additional components should not be added to linezolid solution for infusion. If linezolid is prescribed concomitantly with other drugs, each drug should be administered separately in accordance with the dosage regimen and route of administration. Zyvox in solution for infusion is chemically incompatible with the following drugs: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isothionate, phenytoin sodium, erythromycin lactobionate, trimethoprim/sulfamethoxazole. In addition, the solution is chemically incompatible with ceftriaxone sodium.

Zyvox solution for infusion 2 mg/ml bags of 300 ml 10 pcs.

The drug is prescribed as an intravenous infusion lasting 30–120 minutes. Do not daisy chain infusion bags or add other drugs to the infusion solution. If it is necessary to administer linezolid with other drugs, then all drugs should be prescribed separately in accordance with the recommended doses and routes of administration. Linezolid injection is pharmaceutically incompatible with the following drugs: amphotericin B, chlorpromazine, diazepam, phenytoin, erythromycin lactobionate, co-trimoxazole (trimethoprim + sulfamethoxazole), ceftriaxone. Compatible solutions for infusion: 5% dextrose solution for injection, 0.9% sodium chloride solution for injection, Ringer-Locke solution for injection. Patients who were prescribed the drug intravenously at the beginning of therapy can subsequently be transferred to any dosage form of the drug for oral administration, and dose selection is not required, because The bioavailability of linezolid when taken orally is almost 100%. The duration of treatment depends on the pathogen, the location and severity of the infection, as well as the clinical effect. Adults and children (12 years and older). - 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 or Streptococcus agalactiae; 600 mg IV every 12 hours for 10 - 14 days. — infections resistant to vancomycin caused by Enterococcus faecium, including those accompanied by bacteremia. 600 mg IV every 12 hours for 14–28 days. Children (newborns* and children up to 11 years old). - 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 or Streptococcus agalactiae; 10 mg/kg IV every 8 hours for 10 - 14 days. — infections resistant to vancomycin caused by Enterococcus faecium, including those accompanied by bacteremia. 10 mg/kg IV every 8 hours for 14-28 days. Elderly patients: no dose adjustment is required. Patients with renal failure: no dose adjustment is required. Because 30% of linezolid is removed by hemodialysis within 3 hours, linezolid should be administered after dialysis to patients requiring it. Patients with liver failure: no dose adjustment is required.