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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Linezolid: Drug information

Linezolid: Drug information
(For additional information see "Linezolid: Patient drug information" and see "Linezolid: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Zyvox
Brand Names: Canada
  • APO-Linezolid;
  • SANDOZ Linezolid;
  • Zyvoxam
Pharmacologic Category
  • Antibiotic, Oxazolidinone
Dosing: Adult

Note: Linezolid is not a preferred agent for the treatment of infections requiring prolonged therapy as the risk of serious hematologic and neurologic toxicity increases after >2 weeks and >4 weeks of therapy, respectively.

Anthrax, systemic infection (off-label use): Note: Consult public health officials for event-specific recommendations.

IV: 600 mg every 12 hours as part of an appropriate combination regimen. The duration for non-CNS infection is ≥2 weeks or until clinically stable, whichever is longer. The duration for meningitis is ≥2 to 3 weeks or until clinically stable, whichever is longer (CDC [Hendricks 2014]).

Note: Antitoxin should also be administered. Following the course of IV combination therapy for systemic anthrax infection (including meningitis), patients exposed to aerosolized spores require oral monotherapy with an appropriate agent to complete a total antimicrobial course of 60 days (CDC [Hendricks 2014]).

Bloodstream infection:

Empiric therapy or pathogen-directed therapy for methicillin-resistant Staphylococcus aureus (alternative agent) (off-label use): Oral, IV: 600 mg every 12 hours (Lowy 2021; Moise 2002); treat uncomplicated S. aureus bacteremia for ≥14 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]).

Empiric therapy or pathogen-directed therapy for vancomycin-resistant enterococci: Oral, IV: 600 mg every 12 hours; treat uncomplicated bacteremia for 7 to 14 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]; Zhao 2016). Some experts recommend a duration of 5 to 7 days for uncomplicated infection with rapid blood culture clearance (within 24 hours) and in the absence of metastatic infection (Murray 2021).

CNS infection, health care-associated (eg, cerebrospinal fluid shunt infection) (alternative agent) (off-label use): Pathogen-directed therapy for Staphylococcus spp., including methicillin-resistant species or Cutibacterium acnes.

Oral, IV: 600 mg every 12 hours; duration of therapy is generally 10 to 14 days (Boak 2006; Castro 2005; IDSA [Tunkel 2017]; Kanafani 2020; Nagashima 2008). For staphylococci, usually used in combination with rifampin (eg, in the setting of retained hardware) (IDSA [Tunkel 2017]), but conflicting data are available on the effect of rifampin on linezolid levels (Blassman 2016; Gómez 2011; Hoyo 2012).

Cystic fibrosis, acute pulmonary exacerbation, moderate to severe (off-label use): Empiric therapy or pathogen-directed therapy for methicillin-resistant S. aureus (MRSA) (Chmiel 2014; Simon 2019).

Oral, IV: 600 mg every 12 hours (Chmiel 2014; Keel 2011). Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).

Diabetic foot infection, moderate to severe: Empiric therapy or pathogen-directed therapy for MRSA.

Oral, IV: 600 mg every 12 hours; for empiric therapy, use as part of an appropriate combination regimen. Duration is usually 2 to 4 weeks in the absence of osteomyelitis; prolonged use of linezolid may be limited by toxicity (IDSA [Lipsky 2012]; Lipsky 2004; Weintrob 2020).

Endocarditis, treatment, native or prosthetic valve (off-label use): Pathogen-directed therapy for penicillin-, aminoglycoside-, and vancomycin-resistant enterococci.

IV, Oral: 600 mg every 12 hours for >6 weeks; prolonged use of linezolid may be limited by toxicity (AHA [Baddour 2015]).

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (alternative agent) (off-label use): Pathogen-directed therapy for MRSA.

IV, Oral: 600 mg every 12 hours; duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess, and 6 to 8 weeks for intracranial epidural abscess; prolonged use of linezolid may be limited by toxicity (Bodilsen 2018; IDSA [Liu 2011]; Ntziora 2007; Sexton 2021; Sexton 2019b; Southwick 2020).

Meningitis, bacterial (off-label use): As pathogen-directed therapy (eg, penicillin-, ampicillin-, and vancomycin-resistant enterococci; Staphylococcus spp., including MRSA [alternative agent]; C. acnes [alternative agent]).

IV: 600 mg every 12 hours. Treatment duration is usually 10 to 14 days (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Ntziora 2007; Sipahi 2013).

Osteomyelitis and/or discitis (alternative agent) (off-label use):

Pathogen-directed therapy for Staphylococcus spp., including methicillin-resistant S. aureus: Oral, IV: 600 mg every 12 hours (Birmingham 2003; IDSA [Berbari 2015]; IDSA [Liu 2011]; Rao 2004). Some experts combine with rifampin in the presence of retained hardware (IDSA [Liu 2011]), but conflicting data are available on the effect of rifampin on linezolid levels (Blassman 2016; Gómez 2011; Hoyo 2012).

Pathogen-directed therapy for Enterococcus spp.: Oral, IV: 600 mg every 12 hours (Birmingham 2003; IDSA [Berbari 2015]; IDSA [Liu 2011]; Rao 2004).

Duration of therapy: Duration is generally ≥6 weeks; prolonged use of linezolid may be limited by toxicity. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation) (IDSA [Berbari 2015]; Osmon 2019).

Pneumonia, as a component of empiric therapy or pathogen-directed therapy for methicillin-resistant S. aureus:

Oral, IV: 600 mg every 12 hours; duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days. When used for empiric therapy, give as part of an appropriate combination regimen (IDSA/ATS [Kalil 2016]; IDSA/ATS [Metlay 2019]; IDSA [Liu 2011]).

Prosthetic joint infection (alternative agent) (off-label use):

Pathogen-directed therapy for Enterococcus spp. (penicillin-susceptible or penicillin-resistant): Oral, IV: 600 mg every 12 hours for 4 to 6 weeks; prolonged use of linezolid may be limited by toxicity (IDSA [Osmon 2013]; manufacturer's labeling).

Pathogen-directed therapy for Staphylococcus spp., including methicillin-resistant S. aureus: Oral, IV: 600 mg every 12 hours. Duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors; prolonged use of linezolid may be limited by toxicity (IDSA [Osmon 2013]; manufacturer's labeling).

Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), give oral suppressive antibiotic therapy with an appropriate regimen following completion of initial treatment (Berbari 2019; IDSA [Osmon 2013]).

Septic arthritis (alternative agent) (off-label use): Pathogen-directed therapy for MRSA.

Oral, IV: 600 mg every 12 hours. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis); prolonged use of linezolid may be limited by toxicity (Goldenberg 2019; IDSA [Liu 2011]). Some experts recommend 4 weeks of therapy for patients with concomitant bacteremia (Goldenberg 2019).

Skin and soft tissue infection (alternative agent): Empiric therapy or pathogen-directed therapy for resistant gram-positive organisms (eg, MRSA).

Oral, IV: 600 mg every 12 hours. Total duration of therapy is usually 5 to 14 days; for necrotizing infection, continue until further debridement is not necessary and the patient has improved clinically, including being afebrile for ≥48 hours (IDSA [Liu 2011]; IDSA [Stevens 2014]). Note: For empiric therapy, give as part of an appropriate combination regimen (IDSA [Stevens 2014]).

Toxic shock syndrome (alternative agent) (off-label use):

Toxin production suppression due to group A streptococci: Oral, IV: 600 mg every 12 hours as part of an appropriate combination regimen. Duration is until clinically and hemodynamically stable for ≥48 to 72 hours; then discontinue linezolid and give monotherapy with an appropriate antistreptococcal agent (Rac 2017; Stevens 2021).

Empiric therapy or pathogen-directed therapy for S. aureus, including methicillin-resistant S. aureus and toxin production suppression: Oral, IV: 600 mg every 12 hours. Duration for toxin production is until clinically and hemodynamically stable for ≥48 to 72 hours; then discontinue linezolid and give monotherapy with an appropriate antistaphylococcal agent. If linezolid is given alone to complete therapy, the duration is typically 10 to 14 days in the absence of bacteremia (Chu 2021; Stevens 2006).

Tuberculosis, drug-resistant (off-label use): Oral, IV: 600 mg once daily as part of an appropriate combination regimen including pyridoxine (Ahmad 2018; ATS/CDC/ERS/IDSA [Nahid 2019]; Caminero 2017; Lee 2012; Migliori 2009; WHO 2019); dose reduction to 300 to 450 mg once daily or 600 mg 3 to 4 times weekly may be used for patients who develop toxicity (ATS/CDC/ERS/IDSA [Nahid 2019]; Caminero 2017; Drew 2020). Consider serum monitoring to ensure therapeutic concentration (ATS/CDC/ERS/IDSA [Nahid 2019]; Bolhuis 2016; Kamp 2017). Note: Other studied dosing strategies include 1.2 g orally once daily when used in combination with bedaquiline and pretomanid (Conradie 2020) or an initial dose of 600 mg twice daily for 4 to 6 weeks before reducing the dose to 300 to 600 mg once daily (Agyeman 2016; Tang 2015).

Duration of therapy: Individualize based on rapidity of culture conversion, extent of disease, and patient-specific factors, including clinical response and toxicity; use of linezolid for >6 months is recommended for optimal effectiveness (WHO 2019). Monitor closely for hematologic and neurologic toxicity (ATS/CDC/ERS/IDSA [Nahid 2019]; Lee 2012; WHO 2019).

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Reserve for use as a component of empiric therapy or pathogen-directed therapy for resistant gram-positive pathogens (eg, vancomycin-resistant enterococci) (Hooton 2021; manufacturer’s labeling).

Oral, IV: 600 mg every 12 hours; duration generally ranges from 7 to 10 days depending on clinical response (Hooton 2021; Murray 2021; Pontefract 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS

Note: Observational studies suggest an increased incidence of thrombocytopenia in patients with kidney impairment (Crass 2019; Giunio-Zorkin 2019; Lin 2006; Matsumoto 2009; Nukui 2013; Rabon 2018; Wu 2006). Use with caution; utilize therapeutic drug monitoring when available and limit duration of use when possible.

Note: Renally adjusted dose recommendations are based on doses of 600 mg every 12 hours.

Altered kidney function:

Oral, IV:

CrCl 40 to <130 mL/minute: No dosage adjustment necessary.

CrCl <40 mL/minute: No dosage adjustment necessary. Based on Monte Carlo simulations, in clinically stable patients with CrCl <30 mL/minute and an anticipated treatment course >10 days, some experts suggest reducing dose to 300 mg twice daily after 72 hours with therapeutic drug monitoring to reduce the risk of thrombocytopenia (Crass 2019; Sasaki 2011; Shi 2021; expert opinion).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):

Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).

IV: 450 mg every 8 hours. Utilize therapeutic drug monitoring when available (Cojutti 2018; Crass 2019; Pea 2017; expert opinion).

Hemodialysis, intermittent (thrice weekly): Dialyzable, parent drug and metabolites (~30% to 57% removed via high-flux dialyzer [Brier 2003; El-Assal 2014; Fiaccadori 2004; Fiaccadori 2006]).

Oral, IV: No dosage adjustment necessary; when scheduled doses fall on dialysis days, 1 of the twice-daily doses should be administered after the dialysis session (Brier 2003; Cattaneo 2016; Roger 2018; manufacturer’s labeling). Based on Monte Carlo simulations, in clinically stable patients with CrCl <30 mL/minute and an anticipated treatment course >10 days, some experts suggest reducing dose to 300 mg twice daily after 72 hours with therapeutic drug monitoring to reduce the risk of thrombocytopenia (Crass 2019; Sasaki 2011; expert opinion). More frequent monitoring of CBC should be considered due to increased risk of myelosuppression (Shi 2021).

Peritoneal dialysis: Likely to be dialyzable (low protein binding, small volume of distribution) (expert opinion):

Oral, IV: No dosage adjustment necessary (Li 2016).

Based on Monte Carlo simulations, in clinically stable patients with CrCl <30 mL/minute and an anticipated treatment course >10 days, some experts suggest reducing dose to 300 mg twice daily after 72 hours with therapeutic drug monitoring to reduce the risk of thrombocytopenia (Crass 2019; Gervasoni 2015; Ma 2016; Sasaki 2011; expert opinion). More frequent monitoring of CBC should be considered due to increased risk of myelosuppression (Gervasoni 2015; Ma 2016).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, hematological toxicity) due to drug accumulation is important.

Oral, IV: No dosage adjustment necessary (Fiaccadori 2004; Kraft 2003; Meyer 2005; Pea 2004).

Note: High variability of linezolid pharmacokinetics has been observed in critically ill patients (Dong 2011; Yagi 2013) and those on renal replacement therapies (Barrasa 2019; Soraluce 2020; Villa 2016; Zheng 2020; Zoller 2014). Standard dose may not be sufficient for bacterial infections with high MIC ≥2 mg/L. Consider an alternative agent or utilize higher doses informed by therapeutic drug monitoring in patients at risk of toxicity or treatment failure (Abdul-Aziz 2020; Barrasa 2019; Roger 2016; Soraluce 2020; Zheng 2020; Zoller 2014).

PIRRT (eg, sustained, low-efficiency diafiltration):

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, hematologic toxicity) due to drug accumulation is important.

Oral, IV: No dosage adjustment necessary. One of the twice-daily doses should be administered after PIRRT (Brown 2020; Cremaschi 2010; Fiaccadori 2004; Swoboda 2010).

Note: High variability of linezolid pharmacokinetics has been observed in critically ill patients (Dong 2011; Yagi 2013) and those on renal replacement therapies (Barrasa 2019; Soraluce 2020; Villa 2016; Zheng 2020; Zoller 2014). Standard dose may not be sufficient for bacterial infections with MIC ≥2 mg/L; consider an alternative agent or utilize higher doses informed by therapeutic drug monitoring in patients at risk of toxicity or treatment failure (Zheng 2020; expert opinion).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling. Linezolid concentrations may be increased in patients with cirrhosis and risk of thrombocytopenia may be increased. Use with caution and monitor for thrombocytopenia; consider therapeutic drug monitoring when feasible (Luque 2019; Sasaki 2011; Swoboda 2010; Zhang 2020).

Dosing: Pediatric

(For additional information see "Linezolid: Pediatric drug information")

Note: Linezolid is not a preferred agent in treatment of infections requiring prolonged therapy (ie, >2 weeks) due to the risk of serious hematologic and neurologic toxicity. Use of linezolid is generally reserved for treatment of infections due to drug-resistant organisms (eg, MRSA, VRE).

General dosing, susceptible infection (mild, moderate, or severe) (Red Book 2012): Oral, IV:

Infants and Children <12 years: 10 mg/kg/dose every 8 hours, maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Bacteremia: Oral, IV: Note: Treatment should continue for 10 to 28 days depending on the organism.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Bone and joint infection (Liu 2011):

Osteomyelitis [S. aureus (methicillin-resistant)]: Oral, IV: Note: Treatment should continue for a minimum of 4 to 6 weeks.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Septic arthritis [S. aureus (methicillin-resistant)]: Oral, IV: Note:Treatment should continue for a minimum of 3 to 4 weeks.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Catheter (peritoneal dialysis); exit-site or tunnel infection (Warady [ISPD 2012]): Oral:

Infants and Children <5 years: 10 mg/kg/dose three times daily; maximum dose: 600 mg/dose

Children ≥5 years to 11 years: 10 mg/kg/dose twice daily; maximum dose: 600 mg/dose

Children ≥12 years and Adolescents: 600 mg/dose twice daily

Catheter-related infections, Staphylococcal (methicillin-resistant) or enterococcal (resistant) (confirmed infection): Oral, IV: Note: Not recommended use for empiric treatment (Mermel 2009).

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg

CNS infection:

Brain abscess, subdural empyema, spinal epidural abscess [S. aureus (methicillin-resistant)]: Oral, IV: Note: Treatment should continue for 4 to 6 weeks (Liu 2011). Note: The manufacturer does not recommend the use of linezolid for empiric treatment of pediatric CNS infections since therapeutic linezolid concentrations are not consistently achieved or maintained in the CSF of patients with ventriculoperitoneal shunts.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Meningitis [S. aureus (methicillin-resistant)]: Oral, IV: Note: Treatment should continue for 2 weeks (Liu 2011; Tunkel 2004).

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Endocarditis, treatment [E. faecium (vancomycin-resistant)]: Oral, IV: Note: Treatment should continue for at least 8 weeks (Baddour 2005).

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Peritonitis (peritoneal dialysis) (Warady [ISPD 2012]): Oral:

Infants and Children <5 years: 10 mg/kg/dose three times daily; maximum dose: 600 mg/dose

Children 5 to 11 years: 10 mg/kg/dose twice daily; maximum dose: 600 mg/dose

Children ≥12 years and Adolescents: 600 mg/dose twice daily

Pneumonia

Community- or hospital-acquired (non-MRSA): Oral, IV: Note: Treatment should continue for 10 to 14 days.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

S. aureus (methicillin-resistant): Oral, IV: Note: Treatment should continue for 7 to 21 days depending on severity (Liu 2011).

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Septic thrombosis of cavernous or dural venous sinus [S. aureus (methicillin-resistant)]: Oral, IV: Note: Treatment should continue for 4 to 6 weeks (Liu 2011).

Infants and Children <12 years: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: 600 mg every 12 hours

Skin and skin structure infections: Note: Treatment should continue for 10 to 14 days.

Uncomplicated:

Infants and Children <5 years: Oral: 10 mg/kg/dose every 8 hours

Children 5 to 11 years: Oral: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: Oral: 600 mg every 12 hours

Complicated:

Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg

Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours

Tuberculosis, multidrug-resistant: Limited data available: Oral: Note: Experience in pediatric patients reflects extrapolation of dosing approach used in adult patients which includes a lower daily dose to decrease risk of adverse effects due to the anticipated long duration of therapy and if toxicity does occur, further dosage reductions (a 25% to 50% dose decrease or increased dosing interval have been used); reported treatment duration dependent upon clinical course; reported range: 13 to 36 months in pediatric patients. All reports describe linezolid as part of a multidrug antimycobacterial regimen; other reported agents within the combination therapy were variable, dependent upon specific organism sensitivities, and generally included 3 to 5 other agents.

Infants ≥4 months and Children: 10 to 12 mg/kg/dose twice daily; maximum dose: 600 mg; dosing based on case reports describing successful treatment in infants and a young child (n=3; ages: 4.5 months, 11 months, and 23 months) (Pinon 2010; Schaaf 2009). Use has also been reported in a 10-year old child, treatment was successfully completed with dosing of 600 mg once daily (Condos 2008).

Adolescents: 600 mg once daily was reported in a retrospective review of 30 patients (n= four adolescents) and a case report (patient age: 14 years) (Dauby 2011; Schecter 2010). In another case series, 600 mg twice daily dosing was used for the initial 2 weeks of therapy and then decreased to once daily dosing; at reduced dosage, patients seemed to have decreased hematologic toxicity while neurotoxicity remained unchanged (Park 2006).

Vancomycin-resistant Enterococcus faecium (VREF) infections: Oral, IV: Note: Treatment should continue for 14 to 28 days.

Infants and Children <12 years: 10 mg/kg/dose every 8 hours, maximum dose: 600 mg

Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

No adjustment is recommended. The two primary metabolites may accumulate in patients with renal impairment but the clinical significance is unknown. Weigh the risk of accumulation of metabolites versus the benefit of therapy.

Infants, Children, and Adolescents: The following adjustments have been recommended (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 10 mg/kg/dose every 8 hours (for ages <5 years) or every 12 hours (for ages 5 to 11 years).

Intermittent hemodialysis: 10 mg/kg/dose every 12 hours

Peritoneal dialysis (PD): 10 mg/kg/dose every 12 hours

Continuous renal replacement therapy (CRRT): No adjustment necessary

Dosing: Hepatic Impairment: Pediatric

Mild to moderate impairment (Child Pugh class A or B): No adjustment is recommended.

Severe hepatic impairment (Child Pugh Class C): Use has not been adequately evaluated.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2): Note: Consider CKD-EPI results to further determine dosing (expert opinion).

Oral, IV: No dosage adjustment necessary based on body size alone (Bhalodi 2013); however, for patients with a calculated GFRCKD-EPI of 60 to 129 mL/minute/1.73 m2 and an organism minimal inhibitory concentration (MIC) of ≤1 mg/L, consider an initial loading dose of 600 mg once, then 450 mg every 8 hours (based on Monte Carlo simulations; expert opinion). Higher doses may be needed if the MIC is ≥2 mg/L (Blackman 2021). However, in the absence of therapeutic drug monitoring (to ensure trough concentrations <8 mg/L), doses of 600 mg every 8 hours and above should be avoided due to unacceptable risks for myelosuppression (Cojutti 2018).

Rationale for recommendations: There are limited data on the effect of obesity on linezolid dosing requirements. In one study of obese patients with various infections (mostly sepsis or hospital-acquired pneumonia), linezolid trough concentrations at steady state were not influenced by weight or BMI, but more so by estimated GFR using the CKD-EPI equation (Cojutti 2018). Therefore, one should also consider CKD-EPI results to further determine dosing (expert opinion).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 600 mg/300 mL (300 mL)

Solution, Intravenous [preservative free]:

Zyvox: 200 mg/100 mL (100 mL); 600 mg/300 mL (300 mL)

Generic: 600 mg/300 mL (300 mL)

Suspension Reconstituted, Oral:

Zyvox: 100 mg/5 mL (150 mL) [orange flavor]

Generic: 100 mg/5 mL (150 mL)

Tablet, Oral:

Zyvox: 600 mg

Generic: 600 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Zyvoxam: 600 mg/300 mL (300 mL)

Generic: 600 mg/300 mL (300 mL)

Suspension Reconstituted, Oral:

Zyvoxam: 100 mg/5 mL (150 mL) [contains aspartame, sodium benzoate]

Tablet, Oral:

Zyvoxam: 600 mg [DSC] [contains alcohol, usp]

Generic: 600 mg

Administration: Adult

IV: Administer intravenous infusion over 30 to 120 minutes. When the same intravenous line is used for sequential infusion of other medications, flush line with D5W, NS, or LR before and after infusing linezolid. The yellow color of the injection may intensify over time without affecting potency.

Oral: Administer without regard to meals.

Oral suspension: Invert gently to mix prior to administration, do not shake.

Administration: Pediatric

Oral: Administer with or without food. With reconstituted suspension, gently invert bottle 3 to 5 times before use. Do not shake.

Parenteral: IV: Check infusion bag for minute leaks and solution for particulate matter prior to administration. Administer without further dilution over 30 to 120 minutes. When the same intravenous line is used for sequential infusion of other medications, flush line with D5W, NS, or LR before and after infusing linezolid. The yellow color of the injection may intensify over time without affecting potency.

Use: Labeled Indications

Enterococcal infections (vancomycin-resistant): Treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia. Note: Not a preferred agent in resistant Enterococcus faecalis infections, which are usually susceptible to beta-lactams (O’Driscoll 2015).

Pneumonia:

Treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only).

Treatment of hospital-acquired or health care-associated pneumonia caused by S. aureus (methicillin-susceptible and methicillin-resistant isolates) or S. pneumoniae.

Skin and skin structure infections:

Complicated: Treatment of complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by S. aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, or Streptococcus agalactiae.

Uncomplicated: Treatment of uncomplicated skin and skin structure infections caused by S. aureus (methicillin-susceptible isolates) or S. pyogenes.

Limitations of use: Linezolid has not been studied in the treatment of decubitus ulcers. Linezolid is not indicated for treatment of gram-negative infections; if a concomitant gram-negative pathogen is documented or suspected, initiate specific therapy immediately.

Use: Off-Label: Adult

Anthrax, systemic infection; CNS infection, health care-associated (eg, cerebrospinal fluid shunt infection); Cystic fibrosis, acute pulmonary exacerbation, moderate to severe; Endocarditis, treatment, native or prosthetic valve; Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess; Meningitis, bacterial; Osteomyelitis and/or discitis; Prosthetic joint infection; Septic arthritis; Toxic shock syndrome; Tuberculosis, drug-resistant

Medication Safety Issues
Sound-alike/look-alike issues:

Zyvox may be confused with Zosyn, Zovirax

Adverse Reactions (Significant): Considerations
Clostridioides difficile infection

Clostridioides difficile infection has occurred, including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis.

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months post-antibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Type of antibiotic (Ref); linezolid may pose significantly less risk (Ref)

• Long durations in a hospitalization or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)

• Chemotherapy (Ref)

Lactic acidosis

Lactic acidosis has been reported with the use of linezolid. Patients who develop recurrent nausea and vomiting, unexplained acidosis, or low bicarbonate levels need immediate evaluation. Overall incidence is relatively low but can be life-threatening (Ref) with one study reporting an overall 6.8% incidence (Ref). Peak lactate levels ranged between 3 and 38 mmol/L (Ref). Most reports have occurred in adults; however, there are also reports in pediatric patients (Ref). Lactic acidosis is generally reversible within 15 days of discontinuation of linezolid; however, some cases may take longer to resolve or result in death (Ref).

Mechanism: Unclear; proposed mechanism is through inhibition of mitochondrial protein synthesis resulting in limited aerobic energy production. This leads to anaerobic glycolysis and lactate generation (Ref).

Onset: Varied; may occur on first day of therapy up to 109 days on therapy (Ref)

Risk factors:

• Age ≥60 years (Ref)

• Prolonged use (≥28 days) (Ref)

• Cmin (trough) >2 mg/L when given for an extended duration (Ref)

Myelosuppression

Thrombocytopenia and anemia have been reported with the use of linezolid (Ref). Thrombocytopenia is the most frequently observed blood dyscrasia. Myelosuppression is typically reversible with discontinuation of therapy (Ref) and typically takes 1 to 2 weeks to recover (Ref).

Mechanism: Unclear; proposed mechanism for linezolid-induced thrombocytopenia may be immune-mediated platelet destruction and for linezolid-induced anemia is likely due to direct bone marrow suppression via inhibition of mitochondrial respiration (Ref).

Onset: Intermediate; typically occurs ≥14 days of therapy (Ref); although some studies have noted thrombocytopenia occurring within 7 days of therapy initiation (Ref).

Risk factors:

• Prolonged use (≥14 days) (Ref)

• CrCl <60 mL/minute (Ref)

• Hemodialysis (Ref)

• Baseline platelet count ≤200 x 109/L (Ref)

• Higher daily per kg dose (Ref)

• Cmin (trough) >2 mg/L when given for an extended duration (Ref)

• Preexisting myelosuppression

• Concurrent medications that cause bone marrow suppression

• Chronic infection (previous or concurrent antibiotic therapy)

Neuropathy, peripheral and optic

Peripheral neuropathy and optic neuropathy have been reported in both adults and pediatric patients. Symptoms reported related to peripheral neuropathy include pain, numbness, paresthesia, and weakness (Ref). Symptoms related to optic neuropathy include decreased visual acuity, color vision, and sensation of brightness (Ref). Improvement or complete recovery of optic neuropathy typically occurs with discontinuation of therapy; however, complete recovery of peripheral neuropathy may not occur with discontinuation of therapy (Ref).

Mechanism: Unclear; may be associated with mitochondrial toxicity (Ref).

Onset: Intermediate; typically occurs ≥28 days of therapy (Ref); although, there have been some reports of cases occurring before 28 days of therapy (Ref).

Risk factors:

• Prolonged use (≥28 days) (Ref)

• Cmin (trough) >2 mg/L when given for an extended duration (Ref)

Serotonin syndrome

Symptoms of agitation, confusion, hallucinations, hyperreflexia, myoclonus, shivering, and tachycardia may occur. Typically reversible within 48 hours of discontinuation of linezolid and/or serotonergic agents (Ref); however, some reported cases have resulted in death (Ref).

Mechanism: Non–dose-related; reversible, weak nonselective monoamine oxidase inhibitor, resulting in inhibition of serotonin metabolism (Ref).

Onset: Intermediate; range from 1 to 20 days, median of 4 days (Ref)

Risk factors:

• Concurrent use with serotonergic agents (eg, selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors) (Ref)

• Concurrent use with agents which reduce linezolid metabolism

• Carcinoid syndrome

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Diarrhea (8% to 11%)

Hematologic & oncologic: Decreased white blood cell count (neonates, infants, and children: 12%; children, adolescents, and adults: ≤2%)

1% to 10%:

Dermatologic: Pruritus (neonates, infants, children, and adolescents: ≤1%; nonapplication site), skin rash (adults: 1% to 2%)

Endocrine & metabolic: Increased amylase (neonates, infants, children, and adults: ≤2%), increased lactate dehydrogenase (adults: ≤2%)

Gastrointestinal: Abdominal pain (≤2%), dysgeusia (adults: 1% to 2%), increased serum lipase (adults: 3% to 4%; children and adolescents: <1%), loose stools (neonates, infants, children, and adolescents: 2%), nausea (2% to 7%), oral candidiasis (adults: ≤2%), tongue discoloration (adults: ≤1%), vomiting (2% to 9%)

Genitourinary: Vulvovaginal candidiasis (adults: 1% to 2%)

Hematologic & oncologic: Anemia (neonates, infants, and children: 6%; adults ≤2%) (table 1), decreased neutrophils (neonates, infants, and children: 6%; children, adolescents, and adults: ≤1%), decreased platelet count (adults: ≤10%) (table 2), eosinophilia (neonates, infants, children, and adolescents: ≤2%), thrombocytopenia (neonates, infants, and children: 5%) (table 3)

Linezolid: Adverse Reaction: Anemia

Drug (Linezolid)

Comparator

Population

Dose

Dosage Form

Indication

Number of Patients (Linezolid)

Number of Patients (Comparator)

Comments

6%

7%

Neonates, infants, and children

10 mg/kg every 8 hours

Oral or IV

N/A

215

101

Comparator: Vancomycin

0%

0%

Children and adolescents

Patients 5 through 11 years of age: 10 mg/kg every 12 hours; patients 12 years or older: 600 mg every 12 hours

Oral

Uncomplicated skin and skin structure infections

248

251

Comparator: Cefadroxil

2%

1%

Adults

600 mg every 12 hours

N/A

N/A

1,498

1,464

Comparator: Cefpodoxime proxetil, ceftriaxone, dicloxacillin, oxacillin, or vancomycin

0.4%

0%

Adults

400 mg every 12 hours

Oral

Uncomplicated skin and skin structure infections

548

537

Comparator: Clarithromycin

Linezolid: Adverse Reaction: Decreased Platelet Count

Drug (Linezolid)

Comparator

Population

0.3% to 10%

0.4% to 7%

Adults

Linezolid: Adverse Reaction: Thrombocytopenia

Drug (Linezolid)

Comparator

Population

Dose

Dosage Form

Indication

Number of Patients (Linezolid)

Number of Patients (Comparator)

Comments

5%

2%

Neonates, infants, and children

10 mg/kg every 8 hours

Oral or IV

N/A

215

101

Comparator: Vancomycin

0%

0%

Children and adolescents

Patients 5 through 11 years of age: 10 mg/kg every 12 hours; patients 12 years or older: 600 mg every 12 hours

Oral

Uncomplicated skin and skin structure infections

248

251

Comparator: Cefadroxil

Hepatic: Abnormal hepatic function tests (adults: ≤2%), increased serum alanine aminotransferase (neonates, infants, children, and adults: 2% to 10%), increased serum alkaline phosphatase (adults: ≤4%), increased serum aspartate aminotransferase (adults: 2% to 5%), increased serum bilirubin (neonates, infants, and children: 6%; adults: <1%)

Infection: Fungal infection (adults: ≤2%)

Nervous system: Dizziness (adults: 2% to 3%), headache (children, adolescents, and adults: 6% to 9%; neonates, infants, and children: <1%), vertigo (children and adolescents: 1%)

Renal: Increased blood urea nitrogen (adults: ≤2%), increased serum creatinine (≤2%)

Postmarketing:

Cardiovascular: Hypersensitivity angiitis (Kruzer 2018)

Dermatologic: Bullous skin disease (Chen 2020), Stevens-Johnson syndrome, toxic epidermal necrolysis (Ivic 2014)

Endocrine & metabolic: Hypoglycemia (Johannesmeyer 2017), lactic acidosis (Im 2015, Mao 2018)

Gastrointestinal: Clostridioides difficile associated diarrhea, staining of tooth (Santos 2015)

Hematologic & oncologic: Leukopenia (Bayram 2017), pancytopenia (Leader 2018), sideroblastic anemia (Willekens 2013)

Hypersensitivity: Anaphylaxis, angioedema (Yang 2012)

Nervous system: Peripheral neuropathy (Vishnu 2016), seizure (Cholongitas 2009, Shneker 2009)

Ophthalmic: Blurred vision (Lee 2003), optic neuropathy (Lee 2018), vision loss (Lee 2003)

Contraindications

Hypersensitivity to linezolid or any component of the formulation; concurrent use or within 2 weeks of MAO inhibitors

Canadian labeling: Additional contraindications (not in US labeling): Unless monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following: sympathomimetic agents (eg, pseudoephedrine, phenylpropanolamine), vasopressive agents (eg, epinephrine, norepinephrine), dopaminergic agents (eg, dopamine, dobutamine). Unless carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following: SSRIs, TCAs, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Warnings/Precautions

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Carcinoid syndrome: Use with caution and closely monitor for serotonin syndrome in patients with carcinoid syndrome.

• Hepatic impairment: Use with caution in patients with liver cirrhosis; risk of thrombocytopenia may be increased (Luque 2019; Sasaki 2011).

• Hypertension: Use with caution and closely monitor BP in patients with uncontrolled hypertension.

• Hyperthyroidism: Use with caution and closely monitor BP in patients with untreated hyperthyroidism.

• Pheochromocytoma: Use with caution and closely monitor BP in patients with pheochromocytoma.

• Renal impairment: Use with caution; risk of thrombocytopenia may be increased (Hanai 2016).

• Seizure disorder: Seizures have been reported; use with caution in patients with a history of seizures.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Phenylalanine: Some products may contain phenylalanine.

Other warnings/precautions:

• Appropriate use: Unnecessary use may lead to the development of resistance to linezolid; consider alternatives before initiating outpatient treatment.

• Catheter-related bloodstream infections (CRBSI): Linezolid should not be used in the empiric treatment of CRBSI but may be appropriate for targeted therapy (Mermel 2009).

Metabolism/Transport Effects

Inhibits Monoamine Oxidase

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Amphetamines: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid combination

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Apraclonidine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Apraclonidine. Monoamine Oxidase Inhibitors may increase the serum concentration of Apraclonidine. Risk X: Avoid combination

AtoMOXetine: Monoamine Oxidase Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Risk X: Avoid combination

Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Risk X: Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Benzhydrocodone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and frequent titration of small benzhydrocodone. Risk D: Consider therapy modification

Betahistine: Monoamine Oxidase Inhibitors may increase the serum concentration of Betahistine. Risk C: Monitor therapy

Bezafibrate: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Risk X: Avoid combination

Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor therapy

Brimonidine (Topical): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Topical). Risk C: Monitor therapy

Buprenorphine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

BuPROPion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of BuPROPion. Risk X: Avoid combination

BusPIRone: May enhance the serotonergic effect of Linezolid. This could result in serotonin syndrome. Risk X: Avoid combination

CarBAMazepine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid combination

Carbinoxamine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid combination

Cerebrolysin: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Codeine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Codeine. Risk X: Avoid combination

COMT Inhibitors: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Avoid coadministration of COMT inhibitors and nonselective monoamine oxidase inhibitors (MAOIs) (eg, isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue) whenever possible. Risk D: Consider therapy modification

Cyclobenzaprine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Cyproheptadine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Deutetrabenazine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Deutetrabenazine. Risk X: Avoid combination

Dexmethylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Risk X: Avoid combination

Dextromethorphan: Monoamine Oxidase Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination

Diethylpropion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Diethylpropion. Risk X: Avoid combination

Dihydrocodeine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Diphenoxylate: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Domperidone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Domperidone. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

DOPamine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Risk D: Consider therapy modification

Droxidopa: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Droxidopa. Risk X: Avoid combination

EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk X: Avoid combination

Epinephrine (Racemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Esketamine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Fenfluramine: May enhance the serotonergic effect of Linezolid. This could result in serotonin syndrome. Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Guanethidine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Heroin: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Heroin. Risk X: Avoid combination

HYDROcodone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Risk D: Consider therapy modification

HYDROmorphone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Risk X: Avoid combination

Indoramin: Monoamine Oxidase Inhibitors may enhance the hypotensive effect of Indoramin. Risk X: Avoid combination

Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Isometheptene: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Isometheptene. Risk X: Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Levodopa-Containing Products: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid combination

Levomethadone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Levonordefrin: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Levonordefrin. Risk X: Avoid combination

Lithium: Linezolid may enhance the serotonergic effect of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider therapy modification

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Maprotiline: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Meptazinol: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Meptazinol. Risk X: Avoid combination

Mequitazine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Mequitazine. Risk X: Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methadone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Methyldopa: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methyldopa. Risk X: Avoid combination

Methylene Blue: May enhance the serotonergic effect of Linezolid. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination

Metoclopramide: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Mianserin: Monoamine Oxidase Inhibitors may enhance the neurotoxic effect of Mianserin. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Antidepressant): Linezolid may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): Linezolid may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination

Morphine (Systemic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Risk X: Avoid combination

Nefazodone: Linezolid may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination

Nefopam: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Nefopam. Risk X: Avoid combination

Normethadone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Normethadone. Risk X: Avoid combination

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opicapone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Opioid Agonists: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opium: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Opium. Risk X: Avoid combination

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

OxyCODONE: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

OxyMORphone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Ozanimod: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Pheniramine: May enhance the anticholinergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Pholcodine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Pizotifen: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Pizotifen. Risk X: Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Reboxetine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reboxetine. Risk X: Avoid combination

Remifentanil: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider therapy modification

Reserpine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Monitor closely for paradoxical effects of reserpine (eg, excitation, hypertension). Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: Linezolid may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Serotonergic Non-Opioid CNS Depressants: Linezolid may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination

Serotonergic Opioids (High Risk): Linezolid may enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider therapy modification

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase the serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid combination

Serotonin/Norepinephrine Reuptake Inhibitors: Linezolid may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Solriamfetol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Solriamfetol. Risk X: Avoid combination

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

SUFentanil: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Risk X: Avoid combination

Sympathomimetics: Linezolid may enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Risk D: Consider therapy modification

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Tapentadol: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Tetrabenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Tetrahydrozoline (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Risk X: Avoid combination

Tianeptine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Tricyclic Antidepressants: Linezolid may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination

Tryptophan: Linezolid may enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid combination

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Valbenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Viloxazine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Food Interactions

Concurrent ingestion of foods rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). Beverages containing tyramine (eg, hearty red wine and beer) may increase toxic effects. Management: Avoid tyramine-containing foods (aged or matured cheese, air-dried or cured meats including sausages and salamis; fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments). Food’s freshness is also an important concern; improperly stored or spoiled food can create an environment in which tyramine concentrations may increase. Avoid foods containing dopamine, tyrosine, phenylalanine, tryptophan, or caffeine. Avoid beverages containing tyramine.

Pregnancy Considerations

Information related to linezolid use during pregnancy is limited (Jaspard 2017; Mercieri 2010). Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of linezolid may be altered (van Kampenhout 2017).

Breast-Feeding Considerations

Linezolid is present in breast milk.

Breast milk concentrations of linezolid are similar to maternal serum concentrations (Sagirli 2009). Case reports describe use of linezolid for mastitis unresponsive to other antibiotics in breastfeeding as well as nonbreastfeeding women (Appalaraju 2011; Rowe 2014; Yasar 2011).

Available case reports note the relative infant dose (RID) of linezolid may be >10% of the weight-adjusted maternal dose (based on a maternal dose of 600 mg twice daily); however, the RID is ~6% of a weight-adjusted neonatal dose (based on a neonatal dose of 10 mg/kg 3 times daily) (Lim 2017; Rowe 2014). In general, breastfeeding is considered acceptable when the RID of a medication is <10%; when the RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Linezolid serum concentrations were below the limit of detection in 1 exclusively breastfed infant during maternal therapy of linezolid 600 mg twice daily (Lim 2017).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea and vomiting (WHO 2002).

Dietary Considerations

Some products may contain sodium and/or phenylalanine. Avoid consuming large amounts of tyramine-containing foods/beverages. Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salami), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments.

Monitoring Parameters

Weekly CBC, particularly in patients at increased risk of bleeding, with pre-existing myelosuppression, on concomitant medications that cause bone marrow suppression, in those who require >2 weeks of therapy, or in those with chronic infection who have received previous or concomitant antibiotic therapy; more frequent monitoring may be warranted in certain scenarios based on clinical judgement (Bishop 2006; Choi 2019; Gervasoni 2015).

Peripheral sensory and visual function with extended therapy (≥3 months) or in patients with new-onset neuropathic or visual symptoms, regardless of therapy length (any symptoms of visual change or impairment warrant immediate ophthalmic evaluation); in patients with renal impairment, monitor for hematopoietic (eg, anemia, leukopenia, thrombocytopenia) and neuropathic (eg, peripheral neuropathy, optic neuritis) adverse events when administering for extended periods. Periodic serum bicarbonate with extended therapy. Consider monitoring lactic acid in patients with renal dysfunction (Mori 2018). Monitor for signs and symptoms of lactic acidosis (eg, recurrent nausea and vomiting, unexplained acidosis, low bicarbonate levels). Monitor for signs and symptoms of serotonin syndrome or neuroleptic malignant syndrome-like reaction (especially in patients on concomitant serotonergic agents or with carcinoid syndrome).

Linezolid has been found to have significant interpatient variability (Cattaneo 2016; Pea 2010; Pea 2017) and limited data suggest that monitoring linezolid trough concentrations may be used to optimize dosing, especially in patients with renal dysfunction (Cattaneo 2016; Gervasoni 2015; Pea 2017) and/or concern for thrombocytopenia (Matsumoto 2010; Nukui 2013; Tsuji 2017).

Reference Range

Proposed therapeutic trough range in adult patients: 2 to 7 mg/L (Ide 2018; Pea 2012) or 2 to 8 mg/L (Cattaneo 2016).

Mechanism of Action

Inhibits bacterial protein synthesis by binding to bacterial 23S ribosomal RNA of the 50S subunit. This prevents the formation of a functional 70S initiation complex that is essential for the bacterial translation process. Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci.

Pharmacodynamics and Pharmacokinetics

Absorption: Rapid and extensive.

Distribution:

Vd:

Preterm neonates <1 week of age: 0.81 L/kg.

Full-term neonates <1 week of age: 0.78 L/kg.

Full-term neonates ≥1 week to ≤28 days of age: 0.66 L/kg.

Infants >28 days to <3 months of age: 0.79 L/kg.

Infants and Children 3 months to 11 years of age: 0.69 L/kg.

Adolescents: 0.61 L/kg.

Adults: 0.65 L/kg.

Bone (cancellous):serum ratio, steady state, mean: 40% (range: 16% to 53%) (Rana 2002).

CSF:blood ratio: ~60% to 70% (Myrianthefs 2006; Tsona 2010).

Lung penetration:

Epithelial lining fluid:serum ratio, steady state: ≥100%; varies with time (Boselli 2005; Boselli 2012; Conte 2002; Honeybourne 2003).

Tissue:serum ratio, steady state: ~49% (range: 17% to 132%) (Kempker 2018).

Protein binding: Adults: 31%.

Metabolism: Hepatic via oxidation of the morpholine ring, resulting in two inactive metabolites (aminoethoxyacetic acid, hydroxyethyl glycine); minimally metabolized, may be mediated by cytochrome P450.

Bioavailability: Oral: ~100%.

Half-life elimination:

Preterm neonates <1 week of age: 5.6 hours.

Full-term neonates <1 week of age: 3 hours.

Full-term neonates ≥1 week to ≤28 days of age: 1.5 hours.

Infants >28 days to <3 months of age: 1.8 hours.

Infants and Children 3 months to 11 years of age: 2.9 hours.

Adolescents: 4.1 hours.

Adults: 4.9 hours.

Time to peak: Adults: Oral: 1 to 2 hours.

Excretion: Urine (~30% of total dose as parent drug, ~50% of total dose as metabolites); two metabolites of linezolid may accumulate in patients with severe renal impairment; feces (~9% of total dose as metabolites).

Nonrenal clearance: Adults: ~65%.

Clearance:

Preterm neonates <1 week of age: 2 mL/minute/kg.

Full-term neonates <1 week of age: 3.8 mL/minute/kg.

Full-term neonates ≥1 week to ≤28 days of age: 5.1 mL/minute/kg.

Infants >28 days to <3 months of age: 5.4 mL/minute/kg.

Infants and Children 3 months to 11 years of age: 3.8 mL/minute/kg.

Adolescents: 2.1 mL/minute/kg.

Adults: 1.7 mL/minute/kg.

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: Data are conflicting regarding the contribution of renal dysfunction to the elimination of linezolid. Several studies indicate that linezolid exposure is increased in patients with significant renal dysfunction (Cattaneo 2016; Gervasoni 2015; Ide 2018; Matsumoto 2010; Nukui 2013; Sasaki 2011; Tsuji 2017) although this may be reduced by a compensatory increase in non-renal elimination (Brier 2003; El-Assal 2014). Metabolites A and B accumulate in patients with renal insufficiency; the significance of this accumulation is not known.

Anti-infective considerations:

Parameters associated with efficacy:

Gram-positive bacterial infection: AUC24/minimum inhibitory concentration (MIC), goal: ≥80 to 120; %T > MIC, goal: ≥ ~85% (Abdul-Aziz 2020; Rayner 2003); lower AUC targets may be appropriate for streptococcal infections and higher targets may be needed for bone infection (Andes 2002; Rayner 2003).

Mycobacterium tuberculosis: %T > MIC, goal: 100% (1-log kill, acute phase); %T > MIC, goal: 77% (1-log kill, chronic phase); AUC24/MIC, goal: 1,000 (1-log kill, chronic phase) (Bigelow 2020).

Expected drug exposure in patients with normal renal function:

Cmax (peak) serum concentrations:

600 mg once daily: ~13 mg/L (Kempker 2018).

600 mg twice daily: 18 to 23 mg/L, steady state (Boselli 2005; Myrianthefs 2006; Rana 2002; manufacturer's labeling).

AUC:

Children 2 to 11 years of age: AUC24: ~10 mg/kg 3 times daily: ~240 mg•hour/L (IQR 174 to 395) (Cojutti 2015).

Children 12 years of age and adolescents: AUC24: ~10 mg/kg twice daily: ~300 mg•hour/L (IQR 204 to 655) (Cojutti 2015).

Adults: AUC24: 600 mg twice daily: 154 to 276 mg•hour/L (Boselli 2005; manufacturer's labeling).

Postantibiotic effect:

Methicillin-susceptible S. aureus: ~1 to 3 hours; S. pneumoniae: None (Andes 2002; Chen 2018).

Parameters associated with toxicity:

Hematological toxicity: Cmin (trough) >7 to 10 mg/L (Abdul-Aziz 2020; Cattaneo 2013; Pea 2012); AUC >280 to 350 mg•hour/L (Abdul-Aziz 2020; Pea 2012).

Mitochondrial toxicity (peripheral neuropathy, optic neuropathy, lactic acidosis, myelosuppression): Cmin (trough) >2 mg/L when given for an extended duration (Song 2015).

Pricing: US

Solution (Linezolid in Sodium Chloride Intravenous)

600MG/300ML 0.9% (per mL): $0.25

Solution (Linezolid Intravenous)

600MG/300ML (per mL): $0.08 - $0.37

Solution (Zyvox Intravenous)

200 mg/100 mL (per mL): $0.69

600MG/300ML (per mL): $0.19

Suspension (reconstituted) (Linezolid Oral)

100 mg/5 mL (per mL): $5.47 - $6.38

Suspension (reconstituted) (Zyvox Oral)

100 mg/5 mL (per mL): $5.40

Tablets (Linezolid Oral)

600 mg (per each): $2.91 - $183.67

Tablets (Zyvox Oral)

600 mg (per each): $321.99

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Anozilad (HU);
  • Arlin (BD);
  • Axazolid (LK);
  • Ezolid (BD);
  • Linelid (UA);
  • Linespan (LB);
  • Linevox (AU);
  • Linez (EG);
  • Lineza (CZ);
  • Linox (IN);
  • Linozid (DK);
  • Linxyd (NL);
  • Litrecan (AR);
  • Lizedia (GR);
  • Lizolid (LK, VN);
  • Lizomac (ZW);
  • Loxenil (PH);
  • Lynvox (NL);
  • Macdin (VN);
  • Nel (BD);
  • Nezkil (PK);
  • Nezolid (AU);
  • Nezox (BD);
  • Oxazolid (EG);
  • Yaprinca (CR, DO, GT, HN, NI, PA, SV);
  • Zetalid (GR);
  • Zolic (FI);
  • Zolid (ZW);
  • Zyvix (BD);
  • Zyvox (AE, AR, AU, BB, BH, BR, CL, CN, CY, EG, GB, HK, ID, IE, IQ, IR, JO, KR, LB, LK, LY, MT, MY, NZ, OM, PH, QA, RU, SA, SG, SY, TH, TW, UA, UY, VE, VN, YE);
  • Zyvoxam (CR, DO, GT, HN, MX, NI, PA);
  • ZYvoxam (SV);
  • Zyvoxid (AT, BE, BG, CH, CO, CY, CZ, DE, DK, EE, ES, FI, FR, GR, HR, IL, IS, IT, LT, LU, LV, NL, NO, PL, RO, SE, SI, SK, TR, ZA)


For country abbreviations used in Lexicomp (show table)

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