Antibacterial drug, a new class of antimicrobial agents, oxazolidinones, active in vitro against aerobic gram-positive bacteria, some gram-negative bacteria and anaerobes. The mechanism of action is due to selective inhibition of protein synthesis in bacteria. By binding to the bacterial ribosome linezolid primobolan depot dosage prevents the formation of a functional 70S initiation complex, which is an essential component of the translation process of protein synthesis.
Is active in vitro and in vivo against primobolan depot dosage 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.
Is active in vitro against 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.
Resistance to linezolid bacteria: Haemophilus influenzae, Moraxella catarrhalis, Neisseria spp, Enterobacteriaceae spp, Pseudomonas spp…
He mentioned cross-resistance between linezolid and antimicrobial agents of the following classes: primobolan depot dosage aminoglycosides, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracycline and chloramphenicol, because of the action of linezolid and differences of these classes of drugs mechanisms. Linezolid is active against pathogenic microorganisms both sensitive and resistant to these drugs. Resistance towards linezolid develops slowly by the multistep mutation 23S ribosomal RNA occurs c frequency of less than 1×10 -9 -1 × 10 11 .
After oral linezolid is rapidly and extensively absorbed from the gastrointestinal tract. The maximum concentration of linezolid in the blood plasma (Cmax) -21.2 mg / l, the median time to reach maximum concentration in the blood of linezolid (TSmah) – 2 hours, the absolute bioavailability of approximately 100%. Food intake does not affect absorption of linezolid. The equilibrium concentration of linezolid in the blood is reached on the second day of admission.
The volume of distribution of primobolan depot dosage linezolid when the equilibrium concentration in a healthy adult is an average of 40-50 liters. Binding to plasma proteins is 31% and is independent of the concentration of linezolid in the blood.
was established that P450 isoenzymes are not involved in the metabolism of linezolid in vitro. Linezolid does not inhibit or potentiate the activity of a clinically significant cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, ZA4).
Metabolic oxidation leads to the formation of two inactive metabolites -gidroksietilglitsina (the major metabolite in humans, formed as a result of non-enzymatic process) and aminoetoksiuksusnoy acid (produced in smaller quantities). other inactive metabolites are also described.
Pharmacokinetics in specific patient populations Patients with renal insufficiency. After a single dose of 600 mg of linezolid in patients with severe renal insufficiency (creatinine clearance <30 mL / min), the concentration of its two main metabolites increased 7-8 times. However, larger AUC (area under “concentration-time” curve) of the initial preparation was not observed. Although the hemodialysis deduced that a number of major metabolites, their concentration in the blood plasma after administration of 600 mg of linezolid and dialysis procedures remained significantly higher blood concentrations in patients with normal renal function, renal failure with mild or moderate.
Patients with hepatic insufficiency. There is limited evidence that in patients with hepatic insufficiency, mild or moderate (Class A and B for the classification of Child-Pugh), the pharmacokinetics of linezolid and its two main metabolites does not change. The pharmacokinetics of linezolid in patients with severe hepatic insufficiency (class C Child-Pugh classification) has not been studied. However, as linezolid is metabolised by non-enzymatic, it is not expected to significant violations of its metabolism in liver failure.
Children. Children (12 years and older) the pharmacokinetics of linezolid, taken at a dose of 600 mg did not differ from adult kinetics. When assigning adolescents linezolid 600 mg every 12 hours, the concentration will be the same as in adults with assignment of the same dose.
Elderly patients. In elderly patients aged 65 years and older pharmacokinetics of linezolid are not significantly altered.
. Women In women, the amount of linezolid slightly lower allocation than in men; they also reduced by 20% when the average clearance per body weight. The half-life of linezolid is not significantly different in men and women, a dose adjustment is required.
Indications for use:
Treatment of infectious and inflammatory diseases caused by susceptible to linezolid aerobic and anaerobic Gram-positive organisms (including infection, accompanied by bacteremia):
– Community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (only metitsillinchuvstvitelnye strains);
– nosocomial pneumonia caused by Staphylococcus aureus (including metitsillinchuvstvitelnye and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains) ;
– complicated skin and soft tissue infections, including infections in diabetic foot syndrome is not accompanied by osteomyelitis, caused by Staphylococcus aureus (including metitsillinchuvstvitelnye and methicillin-resistant strains), Streptococcus pyogenes, or of Streptococcus agalactiae;
– uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only metitsillinchuvstvitelnye strains) pyogenes or Streptococcus;
– infections caused by vancomycin-resistant strains of Enterococcus faecium, including accompanied by bacteremia.
Hypersensitivity to linezolid or any other components of the preparation. Children age under 12 years (due to the impossibility of an adequate selection of the dose). The simultaneous use of inhibitors of monoamine oxidase (MAO) A and B (e.g., phenelzine, isocarboxazid), and two weeks after discontinuation of these drugs.
In the absence of blood pressure monitoring should not be administered linezolid in patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and / or patients receiving agonists (eg, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), Dofaminomimetiki (eg, dopamine).
In the absence of close monitoring of patients with possible development of serotonin syndrome should not be administered linezolid people with carcinoid syndrome and / or patients receiving these medications: serotonin reuptake inhibitors, tricyclic antidepressants, agonists of 5-HT1 receptors (triptans), meperidine or buspirone.
Hepatic failure, severe renal failure (if the expected benefit outweighs the potential risk). Systemic infections, pose a risk to life, such as infection associated with venous catheters in intensive care units.
Application of pregnancy and during breastfeeding
Safety trials of linezolid during pregnancy was conducted. The use of Linezolid-Acre drug ® during pregnancy is possible only when the intended benefits of the therapy for the mother outweighs the potential risk to the fetus.
The appointment Linezolid drug-acre ® during lactation should stop breastfeeding.
Dosing and Administration
Inside. The drug can be taken during meals or between meals. The duration of therapy depends on the pathogen, location and severity of the infection and the clinical effect.
Community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (only metitsillinchuvstvitelnye strains)
Adults and children (12 years and older.): 600 mg every 12 hours, the recommended duration of treatment – 10-14 days.
Hospital pneumonia _vyzvannaya Staphylococcus aureus (including methicillin-resistant strains and metiiillinchuvstvitelnye) or Streptococcus pneumoniae (including multidrug-resistant strains)
Adults and children (12 years and older): 600 mg every 12 hours, the recommended duration of treatment – 10-14 days..
Complicated skin and soft tissue infections, including infections in diabetic foot syndrome is not accompanied by osteomyelitis, caused by Staphylococcus aureus (including metitsillinchuvstvitelnye and methicillin-resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae
Adults and children (12 years and older): 600 mg every 12 hours. The recommended duration of treatment – 10-14 days.
Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only metitsillinchuvstvitelnye strains) or Streptococcus pyogenes
Adults and children over 12 years old. 600 mg every 12 hours, the recommended duration of treatment – 10-14 days.
Infections caused by resistant to Vancomycin Enterococcus faecium, including bacteremia accompanied by
adults and children (12 years and older.): 600 mg every 12 hours, the recommended duration of treatment – 14-28 days.
Elderly patients: dose adjustment is required.
Patients with renal impairment: dose adjustment is required. Due to the fact that 30% of linezolid removed by hemodialysis for 3 hours, linezolid be taken after dialysis patients in need of it.
Patients with hepatic impairment: dose adjustment is required.
The frequency of side effects is classified in accordance with the recommendations of the World Health Organization (WHO): very often ‘(≥ 10%); often (≥ 1%, <10%); infrequently (≥0,1%, <1%); rare (≥ 0,01%, <0,1%); very rare (<0.01%), including isolated cases. Adverse events associated with taking linezolid, are usually mild or moderate severity. Most others are marked headache, diarrhea and nausea.
Adult patients From the digestive system: often – diarrhea, nausea, vomiting, constipation, abdominal pain (including spastic), flatulence, candidiasis of the oral mucosa; infrequently – to change the language of staining. Laboratory tests: often – thrombocytopenia; infrequently – increasing the concentration of triglycerides in the blood, the increase in “liver” enzymes (including alaninaminotranoferazy (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lipase, amylase, the concentration of total bilirubin and creatinine) increased concentration of prolactin. From the nervous system: often – headache, dizziness, convulsions; infrequently – dysgeusia. On the part of the central nervous system: often – insomnia. With the genitourinary system: often – vaginal candidiasis.For the skin: often – a rash. Other: . often – fever, rarely – opportunistic fungal infections have also been marked by an increase blood pressure, indigestion, itching.
Children (12 years and older) From the digestive system: often – diarrhea, nausea, vomiting, abdominal pain (local or generalized), loose stools. Laboratory findings: infrequently – eosinophilia, an increased concentration of triglycerides in the blood, increased ALT, lipase , creatinine concentration. From the nervous system: often – headache, vertigo. For the skin: often – a rash, rarely – itching. The respiratory system: often – upper respiratory tract infection, pharyngitis, cough. Other: often – fever , unspecified pain.
Post-marketing data (the frequency is unknown) Laboratory findings: reversible myelosuppression (thrombocytopenia, anemia, leukopenia, pancytopenia). From the senses: . Cases of optic neuropathy, sometimes leading to loss of vision Allergic reactions: anaphylaxis. For the skin: rash, angioedema edema, bullous skin lesions similar to Stevens-Johnson syndrome. On the part of metabolism: lactic acidosis. From the nervous system: peripheral neuropathy, seizures. From the digestive system: discoloration of tooth enamel. Other: chills, fatigue, serotonin syndrome.
Cases of overdose of linezolid have not been reported.
Recommended symptomatic treatment (including the need to maintain the glomerular filtration rate). About 30% of the dose is excreted within three hours in hemodialysis.
The specific antidote is unknown.
Interaction with other drugs
Linezolid is a reversible non-selective MAO inhibitor, so some patients can cause moderate reversible increase in the pressor action of pseudoephedrine and phenylpropanolamine. In a joint application is recommended to reduce the initial dose of agonists (eg, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopamine receptor agonists (eg, dopamine) in the future to carry out the titration of the dose.
There was no development of serotonin syndrome in patients receiving linezolid in conjunction with serotonergic drugs. However, there are few reports about the development of serotonin syndrome during treatment with linezolid and antidepressants -selective reuptake inhibitors serototonina.
While the use of aztreonam and gentamicin pharmacokinetics of linezolid changes were noted.
Rifampicin caused decrease Cmax and AUC linezolid an average of 21% and 32%, respectively.
In established infection (or suspected infection) caused by a concomitant Gram-negative organisms, shows the use of additional funds, acting on Gram-negative flora.
Some patients receiving linezolid may develop reversible myelosuppression (anemia, thrombocytopenia, leukopenia, and pancytopenia), depending on the duration of therapy. In this regard, in the treatment necessary to monitor blood parameters in patients with increased bleeding risk, myelosuppression history, and while the use of drugs that reduce hemoglobin or platelet count and / or their functional properties, as well as in patients receiving linezolid for more than 2 weeks.
Patients taking antibiotics, including linezolid, should take into account the risk of pseudomembranous colitis of varying severity.
Cases of diarrhea associated with Clostridium difficile, reported in association with use of nearly all antibacterial agents, including linezolid. The severity of the diarrhea may range from mild to severe.Treatment of antibacterial drugs disrupts the normal intestinal flora, which leads to overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to the development of diarrhea.Excessive amounts of the toxins produced by strains of Clostridium difficile, can cause high mortality among patients, such as the infection may be resistant to antimicrobial therapy, and may need kolonektomiya. The possibility of diarrhea associated with Clostridium difficile, should be considered in all patients with diarrhea following the use of antibiotics. Patients who have had diarrhea associated with Clostridium difficile after the administration of antibacterial agents need careful medical observation for 2 months.
If you have symptoms of deterioration of visual function, such as changes in visual acuity, changes in color vision, blurred, visual field defects, it is recommended to address urgently to the ophthalmologist for consultation. Should monitor visual function in all patients receiving linezolid for a long time (more than 28 days), and all patients with newly emerging vision impairment symptoms, regardless of the duration of therapy. In the case of peripheral neuropathy and optic neuropathy, should evaluate the risk / benefit of continuing therapy with linezolid in these patients.
In connection with the use of linezolid reported lactic acidosis. Patients in patients receiving linezolid appears repeated nausea or vomiting, unexplained acidosis, or a marked reduction in the concentration of carbonate anions, require careful medical supervision.
Convulsions have been reported in patients treated with linezolid, and in most cases had a history of seizures or an indication of the presence of risk factors for their development. If necessary, use of the drug in combination with the selective serotonin reuptake inhibitors should continuously monitor patients for signs and symptoms of serotonin syndrome such as cognitive impairment, hyperpyrexia, hyperreflexia and incoordination. In the case of the appearance of these symptoms should be discontinued one or both of taking the drug. Symptoms “cancellation” syndrome may occur when you stopped taking serotonergic agents.