active ingredient: linezolid;
1 ml of 2 mg of linezolid;
auxiliary substances: sodium citrate dihydrate, citric acid, glucose monohydrate, sodium hydroxide, hydrochloric acid divorced, water injection.
Solution for infusion.
Basic physico-chemical properties:
a clear solution practically free of any visible particles from colorless to yellow.
Antibacterial agents for systemic use. ATC code J01X X08.
Zyvox is an antibacterial drug.
During a randomized, cross-controlled by using the comparison drug and placebo careful study of the QT interval involving 40 healthy volunteers, the drug Zyvox used a single dose of 600 mg by 1-hour infusion, a single dose of 1200 mg by 1-hour infusion and were administered placebo and a single oral dose of the comparison drug. With the introduction of Zivox in doses of 600 mg and 1200 mg, there was no significant effect on The QTc interval at the maximum concentration of the drug in blood plasma and at any other time.
The average performance of pharmacokinetics of linezolid in adults after a single and repeated administration and intravenous drug presented in table 1.
The mean (standard deviation) of the pharmacokinetic parameters of linezolid in adults
dose linezolida max
ug * h/MLT 1/2
Tablets of 400 mg
One hundred forty six
One hundred ten
Tablets of 600 mg
One hundred twenty seven
600 mg, intravenous injection ‡
One hundred thirty eight
One hundred twenty three
600 mg, oral suspension
One hundred forty one
* AUC for single dose = AUC 0 - ENU; multiple dose = AUC 0-t .
† Data normalized to a dose of 375 mg.
Data, normalized dose of 625 mg, intravenous dose was administered with an infusion duration of 0.5 hours.
C max-the maximum concentration in the blood plasma C min-the minimum concentration in the blood plasma T max - the time to reach C max ; AUC - the area under the curve "concentration-time"; t 1/2 - the half - life; CL-systemic clearance.
Linezolid is intensely absorbed after oral. The maximum concentration in blood plasma is reached in 1-2 hours after administration, and the bioavailability of the drug is about 100%. Therefore, linezolid can be used orally with or without dose adjustment.
Linezolid can be used regardless of the meal. The time to reach maximum concentration increases from 1.5 to 2.2 hours and Cmax is reduced by about 17% with the use of linezolid with food high in fat. However, the total exposure, which is estimated by AUC 0-EN, is similar in both cases.
Pharmacokinetics studies have shown that linezolid is rapidly distributed in tissues with good perfusion. Approximately 31% of linezolid binds to plasma proteins, and it does not depend on the concentration of the drug. The volume of distribution of linezolid in equilibrium in healthy adult volunteers is an average of 40-50 liters.
The concentrations of linezolid were determined in various liquids with the participation of a limited number of participants in phase 1 studies after repeated administration of linezolid. The ratio of the concentration of linezolid in saliva to the concentration in blood plasma was 1,2: 1, and the ratio of the concentration of linezolid in sweat to the concentration in blood plasma - 0,55: 1.
Linezolid is mainly metabolized by oxidation morpholino ring to form two inactive carboxylic acid derivatives with an open ring metabolite aminoethoxyacetic acid (A) and metabolite to gidroksietilimino (In). It is assumed that metabolite a is formed enzymatically, whereas the formation of metabolite b is mediated by a non-enzymatic mechanism, including chemical oxidation in vitro . In vitro studies have shown that linezolid is minimally metabolized with the possible participation of the human cytochrome 450 system in this process. However, the metabolic pathways for linezolid have not been fully studied.
The non-renal clearance is approximately 65% of the total clearance of linezolid. In the equilibrium state, about 30% of the drug dose is found in the urine in the form of linezolid, 40% - in the form of metabolite B and 10% - in the form of metabolite A. the average renal clearance of linezolid is 40 ml/min, indicating kanaltsevuyu reabsorption. Linezolid in feces is practically undefined, whereas approximately 6% of the drug dose is in feces as metabolite B and 3% - as metabolite A.
Slight nonlinearity of clearance was observed when increasing the dose of linezolid, which, obviously, is a consequence of low renal and non-renal clearance of this drug at its high concentrations. However, this difference in clearance was insignificant and did not affect the imaginary half-life period.
Treatment of infections caused by sensitive strains of anaerobic or aerobic gram-positive microorganisms, including infections accompanied by bacteremia, such as:
complicated infections of the skin and its structures, in particular infection on the background of diabetic foot without concomitant osteomyelitis, caused by Staphylococcus aureus (metitillinciuvstiveny and methicillin-resistant isolates), Streptococcus pyogenes or Streptococcus agalactiae;
uncomplicated infections of the skin and its structures, caused by Staphylococcus aureus (metitillinciuvstiveny isolates only) or Streptococcus pyogenes;
infections caused by enterococci, including vancomycin-resistant strains of Enterococcus faecium and faecalis .
If the pathogens include gram-negative microorganisms, clinically indicated the appointment of combination therapy.
Hypersensitivity to linezolid or any other component of the drug.
Zyvox should not be used in patients who are taking any medications that inhibit the monoamine oxidase A and b (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks after taking such drugs.
Except when there is an opportunity for careful observation and monitoring of blood pressure, Zyvox should not be administered to patients with underlying clinical state or concomitant intake of the following drugs:
uncontrolled hypertension, pheochromocytoma, carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder, acute dizziness episodes.
serotonin reuptake inhibitors, tricyclic antidepressants, 5-NT 1 receptor serotonin agonists (tryptans), direct and indirect sympathomimetics (including adrenergic bronchodilators, pseudoephedrine, phenylpropanolamine), vasopressors (epinephrine, norepinephrine), dopaminergic compounds (dopamine, dobutamine), pethidine or buspiron.
Special security measures
Myelosuppression (including anemia, leukopenia, pancytopenia and thrombocytopenia) was reported in patients taking linezolid. After linezolid withdrawal the indicators of the changed blood parameters returned to the values observed before the start of treatment. It is likely that the risk of these effects is associated with the duration of treatment. In elderly patients, the use of linezolid may be accompanied by a higher risk of pathological changes in the blood compared with younger patients. In patients with severe renal insufficiency (regardless of whether they undergo dialysis) may increase the frequency of thrombocytopenia. Thus, careful monitoring of blood counts is