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Active ingredient: Linezolid - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Anti-Infective Agents
  • Antibacterial Agents
  • Protein Synthesis Inhibitors

Dosage Forms

  • Solution
  • Tablets

Brands / Synonyms

Linezlid; Zyvox; Zyvoxid

Indications

For the treatment of bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.

Pharmacology

Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, which has clinical utility in the treatment of infections caused by aerobic Gram-positive bacteria. The in vitro spectrum of activity of linezolid also includes certain Gram-negative bacteria and anaerobic bacteria. Susceptible organisms include methicillin- and vancomycin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant pneumococci and anaerobes. Oxazolidinones inhibit protein synthesis by binding at the P site at the ribosomal 50S subunit. Resistance to other protein synthesis inhibitors does not affect oxazolidinone activity, however rare development of oxazolidinone resistance cases, associated with 23S rRNA alterations during treatment have been reported. Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.

Mechanism of Action

Linezolid is a synthetic antibacterial agent of the oxazolidinone class of antibiotics. It has in vitro activity against aerobic Gram positive bacteria, certain Gram negative bacteria and anaerobic microorganisms. It selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. Specifically, linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. The results of time-kill studies have shown linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, linezolid was found to be bactericidal for the majority of strains. Linezolid is also a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

Absorption

Linezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.

Toxicity

Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.

Biotrnasformation / Drug Metabolism

Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite

Contraindications

ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.

Drug Interactions

Monoamine Oxidase Inhibition: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents:Some individuals receiving ZYVOX may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Co-administration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase 1, 2 or 3 studies. Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed for signs and symptoms of serotonin syndrome (e.g., cognitive dysfunction, hyperpyrexia, hyperreflexia, incoordination). If any signs or symptoms occur physicians should consider discontinuation of either one or both agents (ZYVOX or concomitant serotonergic agents).

Drug-Laboratory Test Interactions

There are no reported drug-laboratory test interactions.

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