indication

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.

toxicity

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

biotransformation

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

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%.

half life

4.5-5.5 hours

drug interactions

Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like linezolid.

Brimonidine: MAO Inhibitors like linezolid may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like linezolid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Citalopram: Combination associated with possible serotoninergic syndrome

Desvenlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Dobutamine: Possible increase of arterial pressure

Dopamine: Possible increase of arterial pressure

Ephedra: Possible increase of arterial pressure

Ephedrine: Possible increase of arterial pressure

Epinephrine: Possible increase of arterial pressure

Escitalopram: Combination associated with possible serotoninergic syndrome

Fenoterol: Possible increase of arterial pressure

Fluoxetine: Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.

Fluvoxamine: Combination associated with possible serotoninergic syndrome

Isoproterenol: Possible increase of arterial pressure

Mephentermine: Possible increase of arterial pressure

Metaraminol: Possible increase of arterial pressure

Methoxamine: Possible increase of arterial pressure

Nefazodone: Combination associated with possible serotoninergic syndrome

Norepinephrine: Possible increase of arterial pressure

Orciprenaline: Possible increase of arterial pressure

Paroxetine: Combination associated with possible serotoninergic syndrome

Phenylephrine: Possible increase of arterial pressure

Phenylpropanolamine: Possible increase of arterial pressure

Pirbuterol: Possible increase of arterial pressure

Procaterol: Possible increase of arterial pressure

Pseudoephedrine: Possible increase of arterial pressure

Salbutamol: Possible increase of arterial pressure

Sertraline: Combination associated with possible serotoninergic syndrome

Terbutaline: Possible increase of arterial pressure

Tetrabenazine: Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.

Tolcapone: Tolcapone and Linezolid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.

Tramadol: Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Linezolid. These agents should not be administered within 14 days of each other.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Venlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Vilazodone: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Zolmitriptan: The MAO inhibitor, linezolid, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing linezolid are contraindicated.