Selezolid (Solution) Instructions for Use

Marketing Authorization Holder

Kraspharma, PJSC (Russia)

ATC Code

J01XX08 (Linezolid)

Active Substance

Linezolid (Rec.INN registered by WHO)

Dosage Form

Selezolid

Solution for infusion 2 mg/1 ml: bot. 100 ml, 200 ml or 300 ml

Dosage Form, Packaging, and Composition

Solution for infusion is a transparent, colorless or with a brownish tint liquid.

Excipients: sodium citrate dihydrate – 1.64 mg, anhydrous citric acid – 0.85 mg, dextrose monohydrate – 50.24 mg, water for injection – up to 1 ml.

Theoretical osmolarity 291 mOsm/l.

100 ml – glass bottles (1) – cardboard packs.
200 ml – glass bottles (1) – cardboard packs.
300 ml – glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the oxazolidinone group

Pharmacotherapeutic Group

Systemic antibacterial agents; other antibacterial agents

Pharmacological Action

Antimicrobial agent, belongs to the class of oxazolidinones. The mechanism of action is due to the selective inhibition of protein synthesis in bacteria. By binding to bacterial ribosomes, Linezolid prevents the formation of a functional 70S initiation complex, which is a component of the translation process in protein synthesis.

Active against aerobic gram-positive bacteria 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 aureus (strains with intermediate susceptibility to glycopeptides), Staphylococcus epidermidis (including methicillin-resistant strains), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus intermedius, Streptococcus pneumoniae (including strains with intermediate susceptibility to penicillin and penicillin-resistant strains), Streptococcus spp. (streptococci of groups C and G), Streptococcus pyogenes, Streptococcus viridans; aerobic gram-negative bacteria Pasteurella canis, Pasteurella multocida; anaerobic gram-positive bacteria Clostridium perfringens, Peptostreptococcus spp. (including Peptostreptococcus anaerobius); anaerobic gram-negative bacteria Bacteroides fragilis, Prevotella spp.; Chlamydia pneumoniae.

Less active against Legionella spp., Moraxella catarrhalis, Mycoplasma spp.

Not active against Haemophilus influenzae, Neisseria spp., Enterobacteriaceae, Pseudomonas spp.

No cross-resistance has been noted between linezolid and aminoglycosides, beta-lactam antibiotics, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines, chloramphenicol because the mechanism of action of linezolid differs from the mechanisms of action of the indicated antibacterial drugs.

Resistance to linezolid develops slowly through multi-step mutation of 23S ribosomal RNA and occurs at a frequency of less than 1×10^-9-1×10^-11.

Pharmacokinetics

Linezolid is rapidly distributed in tissues with good perfusion. The V_d at steady-state C_ss in healthy volunteers averages 40-50 L. Plasma protein binding is 31% and does not depend on the concentration of linezolid in the blood.

It has been established that cytochrome P450 isoenzymes are not involved in the metabolism of linezolid in vitro. Linezolid also does not inhibit the activity of clinically important cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Metabolic oxidation leads to the formation of 2 inactive metabolites – hydroxyethyl glycine (is the main metabolite in humans and is formed as a result of a non-enzymatic process) and aminoethoxyacetic acid (formed in smaller quantities). Other inactive metabolites have also been described.

Linezolid is excreted mainly in the urine as hydroxyethyl glycine (40%), aminoethoxyacetic acid (10%) and unchanged drug (30-35%). It is excreted in feces as hydroxyethyl glycine (6%) and aminoethoxyacetic acid (3%). The unchanged drug is practically not excreted in feces.

Indications

Treatment of infectious and inflammatory diseases caused by susceptible anaerobic and aerobic gram-positive microorganisms (including infections accompanied by bacteremia): community-acquired pneumonia; hospital-acquired pneumonia; skin and soft tissue infections; infections caused by Enterococcus spp. (including strains of Enterococcus faecalis and Enterococcus faecium resistant to vancomycin).

Infections caused by gram-negative microorganisms, confirmed or suspected (as part of combination therapy).

ICD codes

Dosage Regimen

The dosage regimen and duration of treatment depend on the pathogen, location and severity of the infection, as well as on clinical effectiveness.

Administer intravenously as infusions at a dose of 600 mg at 12-hour intervals. Duration of treatment is 14-28 days.

Patients who were initially prescribed the drug intravenously can subsequently be switched to any oral dosage form. In this case, dose selection is not required, because bioavailability when taken orally is almost 100%.

Adverse Reactions

From the digestive system frequently (>1%) – taste perversion, nausea, vomiting, diarrhea, abdominal pain (including spasmodic), flatulence, changes in total bilirubin, ALT, AST, ALP.

From the hematopoietic system frequently (>1%) – reversible anemia, thrombocytopenia, leukopenia, pancytopenia.

Other frequently (>1%) – headache, candidiasis; rarely – cases of peripheral neuropathy and optic neuropathy when used for more than 28 days (the relationship between the use of linezolid and the development of neuropathy has not been proven).

Adverse reactions are not dose-dependent and, as a rule, do not require discontinuation of treatment.

Contraindications

Hypersensitivity to linezolid.

Use in Pregnancy and Lactation

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

It is unknown whether Linezolid is excreted in breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Special Precautions

If diarrhea develops during the use of linezolid, the risk of developing pseudomembranous colitis of varying severity should be considered.

During treatment, it is necessary to conduct a clinical blood test in patients with an increased risk of bleeding, a history of myelosuppression, as well as with the simultaneous use of drugs that reduce hemoglobin levels, platelet count or their functional properties, and in patients receiving Linezolid for more than 2 weeks.

Drug Interactions

Linezolid is a weak reversible non-selective MAO inhibitor, therefore in some cases Linezolid can cause a moderate reversible enhancement of the pressor effect of pseudoephedrine and phenylpropanolamine. Taking this into account, when used simultaneously, it is recommended to reduce the initial doses of adrenergic drugs (including dopamine and its agonists) and subsequently select the dose by titration.

Concomitant use with buprenorphine (separately or in combination with naloxone) may lead to the development of serotonin syndrome.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.