Linezolid - instructions for use, doses, side effects, contraindications

Selectively suppresses protein synthesis in bacteria by binding to bacterial ribosomes and preventing the formation of a functional initiating complex 70S, an important translation component in protein synthesis.

Pharmacokinetics:

Absorption is high; the degree of absorption when administered orally in the form of suspension and tablets coated with a coating is the same; food intake does not affect the degree of absorption, the intake of fatty foods leads to an increase in TCmax to 1.5-2.2 h and a decrease in Cmax by 17%. Absorption - 100%. Rapidly distributed in tissues with good perfusion; VD when reaching Css in a healthy adult - 0.57-0.71 l / kg (Css of the drug in the blood is reached on the 2-3rd day of application); women have a lower volume of distribution than men. Relationship with plasma proteins 31%; does not depend on concentration. The half-life of linezolid in women and men does not differ significantly, there is no need to correct the dosage regimen; taking 400 mg tablets coated with a film, once and twice a day, respectively: the half-life is 5.2 and 4.69 hours; TCmax - 1.52 and 1.12 h; Cmax 8.1 and 11 μg / ml; AUC was 55.1 and 73.4 μg×h / ml; clearance 146 and 110 ml / min.Receiving tablets of 600 mg, coated film, once and twice a day, respectively: the half-life - 4.26 and 5.4 hours; TCmax = 1.28 and 1.03 h; Cmax = 12.7 and 21.2 μg / ml; AUC was 91.4 and 138 μg×h / ml; clearance - 127 and 80 ml / min. Suspension for oral administration - a single dose of 600 mg: half-life - 4.6 hours; TCmax - 0.97 h; Cmax 11 μg / ml; AUC - 80.8 μg×h / ml; clearance - 141 ml / m. Solution for infusion, administered 600 mg once and twice a day, respectively: the half-life is 4.4 and 4.8 hours; TCmax - 0.5 and 0.51 h; Cmax = 12.9 and 15.1 μg / ml; AUC was 80.2 and 89.7 μg×h / ml; clearance is 138 and 123 ml / min. Clearance - 0.57 ml / min / kg; the clearance of linezolid is higher in children and decreases with age; in women the clearance of linezolid is less by 20% and the higher concentration of the drug in plasma than in men. Elimination: about 65% - extrarenal excretion; 30% is excreted by the kidneys (30-35% in the form of unchanged drug, 40% in the form of metabolite A and 10% in the form of metabolite B); with feces, 6% of metabolite A and 3% of metabolite B. In patients with chronic renal failure, correction of the dosing regimen is not required, since there is no correlation between creatinine clearance and excretion through the kidneys; since 30% of the dose is excreted within 3 hours of hemodialysis, in patients receiving similar treatment, linezolid prescribe after dialysis; The pharmacokinetics of linezolid does not change in patients with mild or moderate severity of liver failure, so the correct dosing regimen is required.

Indications:

Treatment of infections caused by sensitive Gram-positive microorganisms.

Infections caused by vancomycin-resistant strains Enterococcus faecium, including those accompanied by bacteremia.

Hospital pneumonia caused by Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug resistant strains - MDRSP).

Community-acquired pneumonia caused by Streptococcus pneumoniae (Including multidrug-resistant strains - MDRSP), including cases accompanied by bacteremia, or Staphylococcus aureus (only methicillin-sensitive strains).

Complicated skin and soft tissue infections, including infections with diabetic foot syndrome, not accompanied by osteomyelitis, caused by Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae.

Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only methicillin-sensitive strains) or Streptococcus pyogenes.

ICD-10

X.J10-J18.J15 Bacterial pneumonia, not elsewhere classified

XII.L00-L08.L01 Impetigo

XII.L00-L08.L02 Abscess of skin, boil and carbuncle

XII.L00-L08.L03 Phlegmon

XII.L00-L08.L08.0 Pyoderma

Contraindications:

Hypersensitivity to linezolid.

Carefully:No data.

Pregnancy and lactation:

Adequate and strictly controlled studies of the safety of linezolid in pregnancy have not been conducted. The use of linezolid during pregnancy is only possible if the intended benefit of therapy for the mother exceeds the potential risk to the fetus

It is not known whether linezolid with breast milk, so if you need to use the drug during lactation breastfeeding should be discontinued.

Category FDA - C.

Dosing and Administration:

The dosage regimen and duration of treatment depends on the pathogen, the location and severity of the infection, and also on clinical effectiveness.

Enter intravenously in the form of infusions in a dose of 600 mg with an interval of 12 hours. Duration of treatment is 14-28 days.

Patients who at the beginning of therapy were prescribed intravenously, can later be transferred to any form of oral administration.At the same time, selection of the dose is not required, since the bioavailability with oral administration is almost 100%.

Side effects:

Allergic reactions.

GIT: generalized or localized abdominal pain, flatulence, diarrhea (11%), constipation, nausea (6%), taste distortion, metallic taste in the mouth (2%), vomiting (9%), gastrointestinal bleeding, discoloration of the tongue , candidiasis of the oral cavity (1%); hyperbilirubinemia, increased activity of ALT, ACT, alkaline phosphatase.

CNS: headache (7%); dizziness (2%); sleep disorders, seizures (3%); neuropathy (the risk of peripheral neuropathy is higher when using the drug for more than 28 days).

Hematological: anemia (6%), thrombocytopenia (5%), eosinophilia (1%), reversible myelosuppression - anemia, leukopenia, pancytopenia (the risk of myelosuppression is higher with the drug for more than 10-14 days, in patients with episodes of myelosuppression in history and in serious diseases kidney).

Dermatological: rash (7%), changes from the skin (2%).

Metabolic disorders: hypokalemia (3%), generalized edema (2%), lactic acidosis.

Respiratory system: upper respiratory tract infection (4%), pharyngitis (3%), pneumonia, dyspnea (3%), cough, apnea (2%).

Other: fever (14%), sepsis (8%); injuries, reactions at the injection site (3%); fungal infections; localized pain (2%); candidiasis of the vagina.

Overdose:

Not described.

Treatment is symptomatic.

Interaction:

Pharmaceutically incompatible with amphotericin B, diazepam, co-trimoxazole, pentamidine isethionate, phenytoin, chlorpromazine, ceftriaxone, erythromycin.

It is pharmaceutically compatible with 5% dextrose solution, 0.9% sodium chloride solution, Ringer's injection solution with lactose.

At simultaneous appointment it is recommended to reduce initial doses of adrenomimetic agents (dopamine or agonists of its receptors) and further titrate the dose.

MAO inhibitors, sympathomimetic agents of direct and indirect action (amphetamines, phenylephrine, ephedrine), tricyclic antidepressants, products containing tyramine and vasoconstrictive amines (cheese, beer, alcohol-poor wines or non-alcoholic liqueurs, beans, smoked meats, poultry, fish, sausages, fermented, overripe fruit) - the risk of severe hypertension, simultaneous the use is contraindicated, it is necessary to follow a diet with the exception of the listed products within 2 weeks after the end of treatment.

The drug may cause a reversible increase in the pressor action of pseudoephedrine and phenylpropanolamine (a reversible nonselective MAO inhibitor).

Simultaneous reception of selective serotonin reuptake inhibitors increases the risk of developing serotonin syndrome; should refrain from using selective serotonin reuptake inhibitors for 14 days prior to the appointment of linezolid.

With simultaneous use of broad-spectrum antibiotics can reduce the contraceptive effect of estrogens (the risk is probably minimal). When hormone replacement therapy (low doses), the interaction is unlikely.

Special instructions:

Oxazolidinones - antibacterial agents with bacteriostatic action, inhibit protein synthesis in ribosomes.

Cross-resistance with other classes of antibacterial drugs is unlikely.

Distinctive characteristics

Linezolid is a bacteriostatic agent of the oxazolidinone group, is active against gram-positive aerobic bacteria, including vancomycin-resistant enterococci and methicillin-resistant staphylococci.Less active against gram-negative bacteria [in vitro active against Haemophilus influenzae, Legionella spp., Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae and Pasteurella spp.]. Inactive for Acinetobacter spp., Enterobacteriaceae and Pseudomonas spp.

There are reports of the emergence of linezolid-resistant strains of enterococci (E. faecium and E. faecalis) and methicillin-resistant S. aureus and S. epidermidis, S. oralis.

During the treatment period, it is necessary to control the number of platelets and hemoglobin in the blood in patients with a high risk of bleeding, anemia or thrombocytopenia in the anamnesis, as well as in patients who simultaneously receive drugs that lower hemoglobin or platelet count in the blood or receive linezolid more than 2 weeks.

With the development of diarrhea in the patient, its cause may be pseudomembranous colitis.

In patients with severe renal failure, use very carefully. Despite the fact that correction of the dosing regimen is not required, in these patients the peak plasma concentrations of the two main metabolites of linezolid after several days of treatment can be 10 times higher.

The efficacy and safety of linezolid and vancomycin in neutropenic fever in cancer patients are comparable to B18.

It is necessary to take into account the limitations for the use of linezolid, due to the ability to inhibit MAO and the bacteriostatic nature of the action.

Instructions

Linezolid (Linezolidum)