LINEZOLID 600 600MG TABLET

Indications

• Bacterial pneumonia
• Complicated skin and soft-tissue infections
• Diabetic foot infections
• Cellulitis (specialist use only)
• Erysipelas (specialist use only)
• Leg ulcer infection (specialist use only)

Dosage

Children: Refer to BNF for Children; close monitoring is recommended in patients receiving treatment for more than 10

Adults: 600 mg every 12 hours, usually for 10–14 days (maximum duration of treatment is 28 days).

Mechanism of action

Linezolid exerts its antibacterial effects by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit, preventing the formation of the functional 70S initiation complex necessary for bacterial reproduction. This interference with the translation process inhibits protein synthesis, effectively stopping bacterial growth.

Pharmacodynamics

Linezolid demonstrates bacteriostatic activity against staphylococci and enterococci while being bactericidal against most streptococci. It shows some activity against Gram-negative and anaerobic bacteria but is generally not effective against them. Additionally, Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO), which can pose a risk for serotonin syndrome when taken with serotonergic medications.

Pharmacokinetics

Linezolid is well absorbed orally, with a bioavailability of approximately 100%. It is extensively distributed in body tissues and fluids, achieving therapeutic concentrations in the lungs, skin, and soft tissues. The drug is primarily metabolized by oxidation, with negligible renal clearance, making it suitable for patients with renal impairment but necessitating caution in those with severe hepatic impairment. Linezolid's half-life is about 4 to 5 hours, allowing for twice-daily dosing.

Contra-indications

• uncontrolled hypertension
• phaeochromocytoma
• carcinoid tumour
• thyrotoxicosis
• bipolar depression
• schizophrenia
• acute confusional states

Adverse effects

• anaemia
• constipation
• diarrhoea
• dizziness
• gastrointestinal discomfort
• headache
• hypertension
• increased risk of infection
• insomnia
• localised pain
• nausea
• skin reactions
• taste alteration
• vomiting
• arrhythmia
• chills
• dry mouth
• eosinophilia
• fatigue
• gastritis
• hyperhidrosis
• hyponatraemia
• leucopenia
• neutropenia
• oral disorders
• pancreatitis
• polyuria
• renal failure
• seizures
• sensation abnormal
• thirst
• thrombocytopenia
• thrombophlebitis
• tinnitus
• tooth discolouration
• antibiotic-associated colitis
• bone marrow disorders
• visual disorders
• vulvovaginal disorder
• alopecia
• angioedema
• lactic acidosis
• nerve disorders
• serotonin syndrome
• severe cutaneous adverse reactions

Interactions

• beta 2 agonists
• buspirone
• levodopa
• methylphenidate
• ozanimod
• reboxetine
• sympathomimetics
• vasoconstrictors (e.g., adrenaline, ephedrine, isometheptene, noradrenaline, phenylephrine)
• pseudoephedrine
• bupropion
• MAO inhibitors

Precautions

• Close observation of blood pressure required in certain conditions
• Monitor full blood count weekly during treatment
• Caution in renal impairment

Mechanism of action

Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It 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 essential for bacterial reproduction, thereby preventing bacteria from dividing. Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant _Enterococcus faecium_ and _Staphylococcus aureus_ have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use. Linezolid is a synthetic oxazolidinone anti-infective agent that is structurally unrelated to other anti-infectives commercially available in the US. In contrast to other anti-infectives that inhibit bacterial protein synthesis, linezolid acts early in translation by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit and preventing the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. Linezolid acts via inhibition of protein synthesis. It bind to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex. This step is essential for the bacterial translation process. Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled. Mitochondrial ultrastructure, mitochondrial respiratory chain enzyme activity /were studied/, and mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic acidosis, and renal failure after prolonged use of linezolid. In addition, mtDNA, respiratory chain enzyme activity, and protein amount in muscle and liver samples obtained from experimental animals that received linezolid or placebo /were evaluated/. In the patient, mitochondrial respiratory chain enzyme activity was decreased in affected tissues, without ultrastructural mitochondrial abnormalities and without mutations or depletion of mtDNA. In the experimental animals, linezolid induced a dose- and time-dependent decrease of the activity of respiratory chain complexes containing mtDNA-encoded subunits and a decreased amount of protein of these complexes, whereas the amount of mtDNA was normal. These results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences.

Pharmacodynamics

Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci. Linezolid has shown some _in vitro_ activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms. Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes and can therefore contribute to the development of serotonin syndrome when administered alongside serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections, as the risk of therapy appears to outweigh its benefits under these circumstances.