ZIVOKS
Active material: Linezolid
When ATH: J01XX08
CCF: Oxazolidinone antibiotic group
ICD-10 codes (testimony): J15, L01, L02, L03, L08.0
When CSF: 06.18
Manufacturer: PFIZER AS (Norway)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Solution for infusion clear, colorless to yellow.
| 1 ml | |
| linezolid | 2 mg |
Excipients: sodium citrate dihydrate, lemon acid, dekstrozы Gidran, water d / and.
100 ml – disposable infusion bags, of Excel film, sealed within a laminated foil (1, 2, 5, 10 or 25) – cardboard boxes.
200 ml – disposable infusion bags, of Excel film, sealed within a laminated foil (1, 2, 5, 10 or 25) – cardboard boxes.
300 ml – disposable infusion bags, of Excel film, sealed within a laminated foil (1, 2, 5, 10 or 25) – cardboard boxes.
Pharmacological action
Antimicrobial, It refers to a class of oxazolidinone. The mechanism of action of the drug due to selective inhibition of protein synthesis in bacteria. By binding to the bacterial ribosome linezolid prevents functional 70S initiation complex, which is a component of the translation process of protein synthesis in.
Preparation active against aerobic Gram-positive bacteria: Corynebacterium jeikeium, Enterococcus faecalis (including glycopeptide-resistant strains), Enterococcus faecium (including glycopeptide-resistant strains), Enterococcus casseliflavus, Enterococcus hens, Listeria monocytogenes, Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus aureus (strains with intermediate susceptibility to glycopeptides), Staphylococcus epidermidis (including methicillin-resistant strains), Staphylococcus haemolyticus, Staphylococcus, Streptococcus agalactiae, Streptococcus intermedius, Streptococcus pneumoniae (including strains with intermediate susceptibility to penicillin and penicillin-resistant strains of), Streptococcus spp. (стрептококки групп C и G), Streptococcus pyrogenes, Streptococcus viridans; Aerobic Gram-negative bacteria: Pasteurella canis, Pasteurella multocida; anaerobic gram-positive bacteria: Clostridium perfringens, Peptostreptococcus spp. (incl. Peptostreptococcus anaerobius); anaerobic gram-negative bacteria: Bacteroides fragilis, Prevotella spp.; Chlamydia pneumoniae.
C drug moderately sensitive Legionella spp., Moraxella catarrhalis, Mycoplasma spp.
C drug resistant Haemophilus influenzae, Neisseria spp., Enterobacteriaceae, Pseudomonas spp.
There was no cross-resistance between Zyvox® and aminoglycosides, beta-lactam antibiotics, folic acid antagonists, glycopeptides, linkozamidami, xinolonami, rifamiцinami, Streptogramin, Tetracycline, chloramphenicol unnecessarily. mechanism of action is different from linezolid mechanisms of action of these antibacterials.
Resistance against the Zyvox® It develops slowly through a multi-step mutations 23S ribosomal RNA and occurs at a frequency of less than 1x10-9-1x10-11.
In vitro постантибиотический эффект Зивокса® is about 2 ч для Staphylococcus aureus, live (in animal studies) – 3.6 and h 3.9 ч для Staphylococcus aureus и Staphylococcus pneumoniae, respectively.
Pharmacokinetics
The active ingredient of the drug Zyvox® It is (s)-linezolid, which is biologically active and is metabolized in the body to inactive derivatives. Solubility of linezolid in water is about 3 mg / ml, and is not dependent on pH in the range 3-9.
The mean pharmacokinetic parameters (standard deviation) linezolid in healthy volunteers after single and repeated (until Css Linezolid blood) / in the introduction given in the tables.
Table 1
| Dosage regimen Zyvox® | Pharmacokinetic parameters | ||
| Cmax(SD) ug / ml | Cmin(SD) ug / ml | Tmax(SD) no | |
| Solution for infusion 600 mg dose | 12.9 (1.6) | – | 0.5 (0.1) |
| Solution for infusion 600 mg 2 times / day | 15.1 (2.52) | 3.68 (2.36) | 0.51 (0.03) |
Table 2
| Dosage regimen Zyvox® | Pharmacokinetic parameters | ||
| AUC(SD) mcg x h / ml | T1/2(SD) no | Cl(SD) ml / min | |
| Solution for infusion 600 mg dose | 80.2 (33.3) | 4.4 (2.4) | 138 (39) |
| Solution for infusion 600 mg 2 times / day | 89.7 (31) | 4.8 (1.7) | 123 (40) |
SD – standard deviation
Averages Withmin, achieved when dosing regimen 600 mg 2 times / day, approximately equal to the highest values of the IPC90 Least sensitive microorganisms.
Distribution
Linezolid is rapidly distributed in the tissues with good perfusion. Vd when the Css in healthy volunteers averaging 40-50 l. Binding to plasma proteins is 31% and does not depend on the concentration of linezolid in the blood.
Metabolism
Established, Cytochrome P450 isoenzymes that are not involved in the metabolism of linezolid in vitro. Linezolid also inhibits the activity of clinically important cytochrome P450 isozymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Metabolic oxidation leads to the formation 2 inactive metabolites – gidroksiэtilglicina (It is a major metabolite in humans, and is formed as a result of non-enzymatic process) and aminoetoksiuksusnoy acid (formed in smaller amounts). Also described are other inactive metabolites.
Deduction
Linezolid shows, primarily, urine as gidroksietilglitsina (40%), aminoetoksiuksusnoy acid (10%) and unchanged drug (30-35%). Since feces excreted as gidroksietilglitsina (6%) and aminoetoksiuksusnoy acid (3%). Unchanged drug is hardly excreted in the feces.
Pharmacokinetics in special clinical situations
The pharmacokinetics of linezolid was studied after a single on / in a dose 10 mg / kg or 600 mg in children from birth to 17 years (including both full-term, and preterm infants), healthy teens (12-17 years) and children between the ages of 1 weeks before 12 years.
Pharmacokinetic parameters – average value (correlation coefficient,%) [minimum; maximum]) are shown in Table.
Table 3
| Age group | Cmax ug / ml | Vd l / kg | AUC mcg x h / ml | T1/2 no | Cl ml / min / kg |
| Premature Newborns * <1 of the weekf | 12.7(30%)[9.6; 22.2] | 0.81(24%)[0.43; 1.05] | 108(47%)[41; 191] | 5.6 (46%)[2.4; 9.8] | 2.0(52%)[0.9; 4.0] |
| Full-term newborn ** <1 of the weekf | 11.5(24%)[8.0; 18.3] | 0.78(20%)[0.45; 0.96] | 55(47%)[19; 103] | 3.0(55%)[1.3; 6.1] | 3.8(55%)[1.5; 8.8] |
| Full-term newborns from ** 1 to 4 weeksf | 12.9(28%)[7.7; 21.6] | 0.66(29%)[0.35; 1.06] | 34(21%)[23; 50] | 1.5(17%)[1.2; 1.9] | 5.1(22%)[3.3; 7.2] |
| Newborns from 4 weeks before 3 monthsf | 11.0(27%)[7.2; 18.0] | 0.79(26%)[0.42; 1.08] | 33(26%)[17; 48] | 1.8(28%)[1.2; 2.8] | 5.4(32%)[3.5; 9.9] |
| Children 3 months before 11 yearsf | 15.1(30%)[6.8; 36.7] | 0.69(28%)[0.31; 1.5] | 58(54%)[19; 153] | 2.9(53%)[0.9; 8.0] | 3.8(53%)[1.0; 8.5] |
| Teens from 11 to 17 yearsJ | 16.7(24%)[9.9; 28.9] | 0.61(15%)[0.44; 0.79] | 95(44%)[32; 178] | 4.1(46%)[1.3; 8.1] | 2.1(53%)[0.9; 5.2] |
| Adult§ | 12.5(21%)[8.2; 19.3] | 0.65(16%)[0.45; 0.84] | 91(33%)[53; 155] | 4.9(35%)[1.8; 8.3] | 1.7(34%)[0.9; 3.3] |
* – pregnancy < 34 weeks (included 1 a premature baby at the age of 1 to 4 weeks.
** – pregnancy ≥ 34 weeks
f – dose of linezolid 10 mg / kg
J – dose of linezolid 600 mg or 10 mg / kg to a maximum 600 mg
§ – dose of linezolid 600 mg
Cmax and Vd Linezolid is not dependent on the patient's age, while the clearance varies with the age of linezolid. Children between the ages of 1 weeks before 11 s largest clearance, wherein the AUC and T1/2 less, than in adults. With increasing age, clearance of linezolid gradually decreases, adolescence mean clearance values are close to those in adults.
Children younger than 11 years, receiving the drug every 8 no, in adults and adolescents, receiving the drug every 12 no, marked similar average daily AUC values. Clearance linezolid higher in children and decreases with increasing age.
Pharmacokinetics of linezolid is not significantly altered in patients aged 65 and older.
Pharmacokinetic differences noted some women, expressed in a somewhat reduced Vd, reducing clearance approximately 20%, sometimes in higher concentrations in blood plasma. Since T1/2 linezolid in men and women were not significantly different, need to adjust the dose does not occur.
Patients with mild renal insufficiency, medium to severe dose adjustment is required, tk. there is no relationship between QA and elimination of the drug through the kidneys. Since 30% the dose is excreted within 3 h hemodialysis, patients, receiving similar treatment, linezolid should be given after dialysis.
Pharmacokinetics linezolid unchanged in patients with mild to moderate hepatic insufficiency, in connection with which there is no need to adjust the dose.
The pharmacokinetics in patients with severe hepatic impairment has not been studied. However, given the, linezolid is metabolized as a result of non-enzymatic process, it can be argued, liver function that does not significantly affect drug metabolism.
Testimony
Treatment of infectious and inflammatory diseases, caused by sensitive Gram-positive aerobic and anaerobic microorganisms (including infections, accompanied by bacteremia):
- Community-acquired pneumonia;
- Nosocomial pneumonia;
- Infections of the skin and soft tissues;
- Infections, вызванные Enterococcus spp. (incl. штаммами Enterococcus faecalis и Enterococcus faecium, vancomycin-resistant).
Infection, caused by Gram-negative microorganisms, confirmed or suspected (in a combination therapy).
Dosage regimen
The solution for infusion should be administered over 30-120 m.
The dosage regimen and duration of treatment depends on the pathogen, localization and severity of the infection, as well as the clinical efficacy.
The recommended dosing regimen for adults and children over 12 years listed in Table:
| Testimony (including infections, accompanied by bacteremia) | Single dose and frequency of administration | The recommended duration of treatment |
| Community-acquired pneumonia | 600 mg every 12 no | 10-14 days |
| Nosocomial pneumonia | 600 mg every 12 no | 10-14 days |
| Infections of the skin and soft tissues | 600 mg every 12 no | 10-14 days |
| Enterococcal infections | 600 mg every 12 no | 14-28 days |
The recommended dosing regimen for children aged 12 years listed in Table:
| Testimony (including infections, accompanied by bacteremia) | Single dose and frequency of administration | The recommended duration of treatment |
| Community-acquired pneumonia | 10 mg / kg every 8 no | 10-14 days |
| Nosocomial pneumonia | 10 mg / kg every 8 no | 10-14 days |
| Infections of the skin and soft tissues | 10 mg / kg every 8 no | 10-14 days |
| Enterococcal infections | 10 mg / kg every 8 no | 14-28 days |
Patients, which at the beginning of the drug therapy administered in /, You can then be translated into any dosage form for oral administration. This titration is not required, tk. oral bioavailability is nearly 100%.
Terms of administration of the solution
It should remove the protective sheath of foil immediately prior to the infusion and for approximately 1 min to compress the infusion bag, to make sure there are no leaks. If the packet flows, the solution is not sterile.
Infusion packets can not be connected in series.
The remains unused solution should be discarded. Do not use partially filled package.
Side effect
From the digestive system: often (>1%) – dysgeusia, nausea, vomiting, diarrhea, stomach ache (incl. spastic), flatulence, Changes in total bilirubin, GOLD, IS, Alkaline phosphatase.
From the hematopoietic system: often (>1%) – obratimaya anemia, thrombocytopenia, leukopenia, pancytopenia.
Other: often (>1%) – headache, candidiasis; rarely – cases of peripheral neuropathy and optic neuropathy in applying more 28 days (the link between the use of Zyvox® and the development of neuropathy has not been proven, because most of these cases the patients receiving both drugs or, that can cause neuropathy (Amitriptyline, paroxetine, Isoniazid) and / or have had disease, which can lead to neuropathic (diabetes, arterial hypertension, chronic renal failure, osteosarcoma, encephalopyosis).
Side reactions do not depend on the dose and, usually, do not require discontinuation of treatment.
Contraindications
- Hypersensitivity to linezolid and / or other ingredients.
Pregnancy and lactation
There are no adequate and well-controlled studies of the safety of the drug Zyvox® during pregnancy was conducted. The use Zyvox® Pregnancy is possible only in cases, if the expected benefit of therapy for the mother outweighs the potential risk.
Unknown, whether it is allocated linezolid with breast milk, so you should stop breast-feeding in the appointment of the mother during lactation.
Cautions
With the development of diarrhea patients, taking Zyvox®, It should take into account the risk of pseudomembranous colitis of varying severity.
Monitoring of laboratory parameters
In the course of treatment should be carried out CBC in patients with an increased risk of bleeding, myelosuppression history, as well as the concomitant use of drugs, reducing the level of hemoglobin, number of platelets or their functional properties, and in patients, receiving linezolid more 2 weeks.
Effects on ability to drive vehicles and management mechanisms
The drug Zyvox® no effect on the ability to drive vehicles and management mechanisms.
Overdose
Currently, cases of drug overdose Zyvox® not reported.
Treatment: if necessary, symptomatic therapy (incl. necessary to maintain the level of glomerular filtration rate). About 30% the dose is excreted within 3 h hemodialysis.
Drug Interactions
Linezolid is a weak reversible non-selective MAO inhibitor, however, some patients Zyvox® can cause moderate reversible enhancement of the pressor action of pseudoephedrine and phenylpropanolamine. Considering this, while the application is recommended to reduce the initial dose of adrenergic drugs (incl. Dopamine and its agonists) to continue to carry out titration titration.
Pharmacokinetic interactions
When concomitant administration of Zyvox® with aztreonam and gentamicin were observed changes in the pharmacokinetics of linezolid.
Pharmaceutical interaction
Zivoks® in the form of solution for infusion is compatible with the following solutions: 5% glucose (dextrose), 0.9% sodium chloride solution, Ringer solution for injections with lactose.
The solution for infusion pharmaceutically incompatible with amphotericin B, chlorpromazine, diazepamom, pentamidine izetionatom, phenytoin, Erythromycin, co-trimoxazole.
The solution for infusion is chemically incompatible with ceftriaxone sodium.
Do not introduce additional components into a solution for infusion. In the appointment of Zyvox® simultaneously with other drugs, each drug should be administered separately.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored at temperatures above 25 ° C. Shelf life – 3 year.
Prior to use, infusion bags should be stored in a shell from foil and in a cardboard box. After opening the contents of the package must be used immediately.
