Linezolid (linezolid)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Linezolid is an oxazolidinone anti-infective agent.
Linezolid is an oxazolidinone anti-infective agent. The mechanism of action of linezolid involves binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevention of formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process.
In vitro, linezolid is bacteriostatic against susceptible enterococci and staphylococci and bactericidal against susceptible streptococci. Linezolid is active in vitro against most strains of Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA)), Streptococcus agalactiae (group B streptococci, GBS), S. pneumoniae, S. pyogenes (group A beta-hemolytic streptococci, GAS), and vancomycin-resistant Enterococcus faecium. Linezolid also has in vitro activity against E. faecalis (including vancomycin-resistant strains), E. faecium (vancomycin-susceptible strains), S. epidermidis (including methicillin-resistant strains (oxacillin-resistant strains)), S. haemolyticus, viridans group streptococci, group G streptococci, Corynebacterium, and Pasteurella multocida; however, safety and efficacy of linezolid in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled clinical studies to date.
Linezolid is active in vitro against Mycobacterium tuberculosis, including some multiple-drug resistant (MDR) and extensively drug-resistant (XDR) strains. Linezolid also has activity in vitro against some strains of M. chelonaei, M. fortuitum, M. gilvum, M. gordonae, M. kansasii, M. mucgenicum, and M. simiae.
Resistance to linezolid has been produced in vitro by serial passage of MRSA or enterococci (i.e., E. faecalis, E. faecium) in the presence of increasing concentrations of the drug, and resistance to linezolid has emerged in patients receiving the drug for the treatment of infections caused by MRSA or enterococci. Linezolid resistance generally is associated with point mutations in the 23S rRNA gene. However, linezolid resistance in staphylococci mediated by the chloramphenicol-florfenicol (cfr) gene located on a plasmid has been reported and such resistance is transferable between staphylococci.
Cross-resistance between linezolid and other oxazolidinones (e.g., tedizolid) has been reported. Bacteria resistant to linezolid because of mutations in chromosomal genes encoding the 23S rRNA or ribosomal proteins (L3 and L4) usually are cross-resistant to other oxazolidinones (e.g., tedizolid) and vice versa. However, in vitro data indicate that the presence of the cfr gene in S. aureus that results in resistance to linezolid does not necessarily result in cross-resistance to tedizolid in the absence of chromosomal mutations.
Cross-resistance between linezolid and non-oxazolidinone anti-infectives is unlikely.
Linezolid is well absorbed following oral administration (absolute bioavailability approximately 100%) and is readily distributed to well-perfused tissues. Peak plasma concentrations are attained within 1-2 hours following oral administration. The time to peak concentrations is delayed and peak concentrations are decreased when linezolid is administered with a high-fat meal, but the extent of absorption is not affected.
This effect is not considered clinically important. In adults with CNS infections, IV administration of linezolid (600 mg twice daily) resulted in steady-state mean peak CSF concentrations that were 36-58% of mean peak plasma concentrations; the time to peak CSF concentrations was approximately 3-4 hours after a dose. In pediatric patients with ventriculoperitoneal shunts receiving single or multiple doses of linezolid, therapeutic concentrations of the drug were not consistently achieved or maintained in CSF.
Linezolid is approximately 31% bound to plasma proteins. The drug is metabolized principally via oxidation to 2 inactive metabolites: an aminoethoxyacetic acid metabolite and a hydroxyethyl glycine metabolite. Linezolid is minimally metabolized and metabolism may be mediated by the cytochrome P-450 (CYP) enzyme system.
Approximately 65% of a linezolid dose is eliminated via nonrenal clearance. Under steady-state conditions, approximately 30% of a linezolid dose is eliminated in urine as unchanged drug. Mean renal clearance of linezolid is 40 mL/minute, suggesting net tubular reabsorption.
Almost no linezolid is found in feces as unchanged drug; approximately 3 and 6% of a dose is eliminated in feces as metabolite A and metabolite B, respectively. Linezolid and its metabolites are removed by hemodialysis. Approximately 30% of a linezolid dose is removed by a 3-hour hemodialysis session started 3 hours after the dose.
It is not known whether linezolid and its metabolites are removed by peritoneal dialysis. The mean elimination half-life of linezolid is 4.3-6.4 hours in adults. In neonates, the mean elimination half-life of linezolid is 5.6 hours in preterm neonates younger than 1 week of age, 3 hours in full-term neonates younger than 1 week of age, and 1.5 hours in neonates 1 week to 28 days of age.
In infants and children, the mean elimination half-life of linezolid is 1.8 hours in infants older than 28 days through 2 months of age and 2.9 hours in infants and children 3 months through 11 years of age. In adolescents 12 through 17 years of age, the mean elimination half-life of linezolid is 4.1 hours.
Linezolid is used for the treatment of community-acquired pneumonia, nosocomial pneumonia, and uncomplicated or complicated skin and skin structure infections caused by certain susceptible staphylococci or streptococci. Linezolid also is used for the treatment of infections caused by vancomycin-resistant Enterococcus faecium.
Generic name: linezolid
Pronunciation: (lin-AYZ-oh-lid)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Linezolid
Indications
The following indications are listed for Linezolid:
- Complicated Skin And Skin Structure Staphylococcus Aureus Infection
- Complicated Skin And Skin Structure Streptococcus Agalactiae Infection
- Complicated Skin And Skin Structure Streptococcus Pyogenes Infection
- Diabetic Foot Infection Due To Gram-Positive Bacteria
- Nosocomial Pneumonia Due To Streptococcus Pneumoniae
- Skin And Skin Structure Streptococcus Pyogenes Infection
- Staphylococcal Pneumonia
- Staphylococcus Aureus Skin And Skin Structure Infection
- Staphylococcus Nosocomial Pneumonia
- Streptococcal Pneumonia
- Vancomycin Resistant Enterococcus Faecium Bacteremia
- Vancomycin-Resistant Enterococcus Faecium Infection
Also known as: Bacteremia Due To Vref, Complicated Skin And Skin Soft Tissue Infection Due To Streptococcus Pyogenes, Complicated Staphylococcus Aureus Skin And Skin Soft Tissue Infection, Complicated Streptococcus Pyogenes Skin And Skin Structure Infection, Nosocomial Pneumococcal Pneumonia, Nosocomial Pneumonia Due To Staphylococcus Species, Pneumonia Due To Staphylococcus Species, Pneumonia Due To Staphylococcus Spp., Pneumonia Due To Streptococcus Species, Pneumonia Due To Streptococcus Spp., Skin & Skin Soft Tissue Streptococcus Pyogenes Infection, Skin And Skin Soft Tissue Staphylococcus Aureus Infection, Vancomycin-Resistant Enterococcus Faecium Bacteremia, Vancomycin-Resistant Streptococcus Faecium Bacteremia, Vref Infection.
Dosing
When clinically appropriate, patients treated initially with IV linezolid may be switched to oral linezolid without dosage adjustment.
The manufacturer states that safety and efficacy of >28 days of linezolid treatment have not been evaluated in controlled clinical trials. Linezolid is administered for longer durations when used in multiple-drug regimens for the treatment of multidrug-resistant (MDR) tuberculosis+.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to linezolid or any ingredient in the formulation.
*Current or recent (within the last 2 weeks) treatment with drugs that inhibit MAO A or B (e.g., isocarboxazid, phenelzine).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in >=5% of adults and/or pediatric patients receiving linezolid include diarrhea, nausea, vomiting, headache, and anemia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of linezolid for the treatment of community-acquired pneumonia (CAP), nosocomial pneumonia, complicated skin and skin structure infections, and vancomycin-resistant Enterococcus faecium infections in pediatric patients are supported by adequate and well-controlled studies in adults, pharmacokinetic studies in pediatric patients, and additional data from a comparator-controlled study of gram-positive infections in neonates and children through 11 years of age. Safety and efficacy of the drug for the treatment of CAP in pediatric patients also are supported by evidence from an uncontrolled study in patients 8 months through 12 years of age.
Safety and efficacy of linezolid for the treatment of uncomplicated skin and skin structure infections in pediatric patients have been established in a comparator-controlled study in pediatric patients 5-17 years of age.
While some pharmacokinetic parameters (i.e., peak plasma concentration, volume of distribution) are similar in pediatric patients of all ages, linezolid clearance varies with age. Excluding neonates <1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as pediatric patients age, the clearance of linezolid decreases and clearance values in adolescents approach those observed in adults. Systemic exposure (mean daily AUC) in pediatric patients <12 years of age receiving linezolid every 8 hours generally is similar to that in adults and adolescents receiving the drug every 12 hours. There is wider intraindividual variability in linezolid clearance and systemic drug exposure in all pediatric age groups relative to adults.
The manufacturer states that linezolid is not recommended for empiric treatment of CNS infections in pediatric patients; therapeutic concentrations of the drug were not consistently achieved or maintained in the CSF of pediatric patients with ventriculoperitoneal shunts.
Inadequate systemic exposure, site and severity of infection, and underlying medical conditions should be considered in pediatric patients with a suboptimal response to linezolid, especially those with infections caused by gram-positive bacteria that have minimum inhibitory concentrations (MICs) of 4 mcg/mL.
Available data from published and postmarketing case reports regarding use of linezolid in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
In studies in mice, rats, and rabbits, linezolid was not teratogenic; however, embryofetal toxicities were reported. These nonteratogenic effects included increased post-implantational embryo death, decreased fetal body weights, and increased incidence of costal cartilage fusion in mice; decreased fetal body weights, reduced ossification of sternebrae, and decreased survival of pups in rats; and reduced fetal body weight in rabbits.
Linezolid is distributed into human milk. It is not known whether the drug affects the breast-fed infant or milk production. Available data suggest that a breast-fed infant would receive approximately 6-9% of the recommended daily therapeutic infant dose (10 mg/kg every 8 hours).
The benefits of breast-feeding and the importance of linezolid to the woman should be considered along with the potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.
If linezolid is used in a nursing woman, the manufacturer recommends that the breast-fed infant be monitored for diarrhea and vomiting since these are the most common adverse reactions reported in infants being treated with linezolid.
Dosage adjustments are not necessary in geriatric patients.
No overall differences in safety, efficacy, or pharmacokinetics have been observed in geriatric patients >=65 years of age compared with younger adults. Other clinical experience has not revealed age-related differences in response, but the possibility of greater sensitivity in some older patients cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.