Version July 2025
Dosage guidance:
Safety: The risk of serious hematologic and neurologic toxicity increases after >2 weeks and >4 weeks of therapy, respectively. When prolonged therapy is required, alternative agents are preferred; if benefits of linezolid outweigh risks and prolonged therapy is used, monitor closely.
General dosing (Ref):
GA <34 weeks:
PNA ≤7 days: Oral, IV: 10 mg/kg/dose every 12 hours.
PNA >7 days: Oral, IV: 10 mg/kg/dose every 8 hours.
GA ≥34 weeks: Oral, IV: 10 mg/kg/dose every 8 hours.
Enterococcus faecium (vancomycin resistant) infection: Note: The manufacturer recommends a duration of 14 to 28 days; however, shorter or longer durations may be appropriate; duration should be individualized based on source and extent of infection, response, etc.
GA <34 weeks:
PNA <7 days: Oral, IV: 10 mg/kg/dose every 12 hours; may be increased to 10 mg/kg/dose every 8 hours if clinical response is inadequate.
PNA ≥7 days: Oral, IV: 10 mg/kg/dose every 8 hours.
GA ≥34 weeks: Oral, IV: 10 mg/kg/dose every 8 hours. Note: Case reports describe the use of higher doses up to 12 to 15 mg/kg/dose every 8 hours to treat vancomycin-resistant enterococcal endocarditis and meningitis/ventriculitis in former premature neonates (n=2; GA: 26 and 35 weeks; age at treatment: Term) (Ref).
Pneumonia: Note: The manufacturer suggests treating for 10 to 14 days; however, optimal duration of therapy is unknown; shorter durations may be appropriate.
GA <34 weeks:
PNA <7 days: Oral, IV: 10 mg/kg/dose every 12 hours; may be increased to 10 mg/kg/dose every 8 hours if clinical response is inadequate.
PNA ≥7 days: Oral, IV: 10 mg/kg/dose every 8 hours.
GA ≥34 weeks: Oral, IV: 10 mg/kg/dose every 8 hours.
Skin and soft tissue infection: Note: The manufacturer recommends treatment for 10 to 14 days; however, treatment duration depends on several factors including likely pathogen and extent of infection; shorter durations may be appropriate.
GA <34 weeks:
PNA <7 days: Oral, IV: 10 mg/kg/dose every 12 hours; may be increased to 10 mg/kg/dose every 8 hours if clinical response is inadequate.
PNA ≥7 days: Oral, IV: 10 mg/kg/dose every 8 hours.
GA ≥34 weeks: Oral, IV: 10 mg/kg/dose every 8 hours.
Dosage guidance:
Safety: The risk of serious hematologic and neurologic toxicity increases after >2 weeks and >4 weeks of therapy, respectively. When prolonged therapy is required, alternative agents are preferred; if benefits of linezolid outweigh risks and prolonged therapy is used, monitor closely.
General dosing (Ref):
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours, maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours.
Bloodstream infection, resistant gram-positive infection (eg, vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus):
Note: Duration of therapy varies based on various clinical factors including causative pathogen, source of bacteremia, and response (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose (Ref).
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours OR 10 mg/kg/dose every 12 hours; maximum dose: 600 mg/dose (Ref).
Endocarditis; pathogen-directed therapy for vancomycin-resistant Enterococcus faecium:
Note: Dosing is from manufacturer labeling for vancomycin-resistant E. faecium infections; guidelines do not provide specific recommendations due to lack of pediatric data. Infectious Diseases consultation is recommended, and prolonged therapy (>4 to 6 weeks) is required; prolonged use of linezolid may be limited by toxicity (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours.
Enterococcus faecium (vancomycin-resistant) infection: Note: The manufacturer recommends a duration of 14 to 28 days; however, shorter or longer durations may be appropriate; duration should be individualized based on source and extent of infection, response, etc.
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours, maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours.
Exit-site or tunnel infection, peritoneal dialysis catheter (Ref): Note: Treat exit-site infection for ≥2 weeks (≥3 weeks for S. aureus) and at least 7 days after complete resolution; treat tunnel infection for 2 to 4 weeks.
Infants and Children <5 years: Oral: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children 5 to <12 years: Oral: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral: 600 mg every 12 hours.
Meningitis, including health care–associated ventriculitis/meningitis (eg, cerebrospinal fluid shunt infection) (alternative agent): Limited data available:
Note: Duration should be individualized based on patient characteristics and response; typical duration is 10 to 14 days; longer durations required for abscess or empyema (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose (Ref).
Children ≥12 years and Adolescents: Oral, IV: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg/dose (Ref).
Nontuberculous mycobacterial infection, pulmonary (eg, Mycobacterium abscessus): Limited data available:
Patients with cystic fibrosis (Ref): Note: Use as part of an appropriate combination regimen until patient is culture negative on therapy for ≥1 year; use caution in patients chronically coinfected with methicillin-resistant Staphylococcus aureus (MRSA) due to potential for resistance development. Prolonged use of linezolid may be limited by toxicity; guidelines suggest adding high-dose pyridoxine to reduce risk of cytopenias.
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 10 mg/kg/dose every 12 or 24 hours; maximum dose: 600 mg/dose.
Patients without cystic fibrosis (Ref): Note: Use as part of an appropriate combination regimen until patient is culture negative on therapy for ≥1 year. Prolonged use of linezolid may be limited by toxicity. Dosing in BTS guidelines for infants and children is based on WHO recommendations for drug resistant tuberculosis.
Infants and Children <10 years: Oral, IV: 10 mg/kg/dose every 12 hours; maximum dose: 300 mg/dose.
Children ≥10 years: Oral, IV: 10 mg/kg/dose every 24 hours; maximum dose: 600 mg/dose; doses of 300 mg every 24 hours have also been used.
Adolescents: Oral, IV: 600 mg every 12 or 24 hours; consider reducing to 300 mg every 24 hours if serious adverse effects develop.
Osteoarticular infection, acute (eg, septic [bacterial] arthritis, osteomyelitis]): Limited data available:
Note: Duration should be individualized based on several factors including causative pathogen, response to therapy, and normalization of inflammatory markers. Minimum total duration for septic arthritis is 2 to 3 weeks and for osteomyelitis is 3 to 4 weeks; longer duration commonly necessary, particularly for infections caused by MRSA. Prolonged use of linezolid may be limited by toxicity (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose (Ref).
Children ≥12 years and Adolescents: Oral, IV: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg/dose (Ref).
Peritonitis (peritoneal dialysis): Note: Recommended treatment duration is 2 to 3 weeks depending on pathogen (Ref):
Infants and Children <5 years: Oral: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children 5 to <12 years: Oral: 10 mg/kg/dose every 12 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral: 600 mg every 12 hours.
Pneumonia: Note: The usual duration of therapy for uncomplicated, community-acquired pneumonia is 10 days; however, shorter duration may be effective for more mild disease; complicated infection may require longer treatment (Ref). For nosocomial pneumonia (eg, hospital-acquired, ventilator-associated), optimal duration is unknown; the manufacturer recommends 10 to 14 days of treatment, but shorter durations of 7 days are recommended in adults (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours.
Skin and soft tissue infection:
Uncomplicated: Note: Typical duration is 5 days but may be extended if clinical response is inadequate (Ref).
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/dose.
Children ≥12 years and Adolescents: Oral: 600 mg every 12 hours.
Complicated: Note: Typical duration is 7 to 14 days and should be individualized based on clinical response; for necrotizing infection, continue until further debridement is not necessary and the patient has improved clinically, including being afebrile for ≥48 hours (Ref).
Infants and Children <12 years: Oral, IV: 10 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 600 mg every 12 hours.
Tuberculosis, active (drug-resistant); treatment: Limited data available: Note: Use as part of an appropriate combination regimen; duration should be individualized based on extent of disease, rapidity of culture conversion, clinical response, and toxicity; use of linezolid for >6 months is recommended for optimal effectiveness. Monitor closely for hematologic and neurologic toxicity (Ref).
Infants and Children <12 years: Note: Dosing for lower weight ranges is based on pharmacokinetic modeling (Ref).
5 to <10 kg: Oral, IV: 15 mg/kg/dose once daily.
10 to 23 kg: Oral, IV: 12 mg/kg/dose once daily.
>23 kg: Oral, IV: 10 mg/kg/dose once daily; maximum dose: 600 mg/dose.
Children ≥12 years and Adolescents: Oral, IV: 10 mg/kg/dose once daily; maximum dose: 600 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney impairment: Infants, Children, and Adolescents: IV, Oral: Any degree of kidney impairment: No adjustment is recommended. In patients with impaired kidney function, the 2 primary metabolites may accumulate and the risk of thrombocytopenia is increased. Monitor closely; dosage adjustment may be necessary, but specific recommendations are not available; utilize therapeutic drug monitoring and monitor efficacy closely (Ref).
Hemodialysis, intermittent: Dialyzable, parent drug and metabolites (~30% to 57% removed via high-flux dialyzer) (Ref).
Infants, Children, and Adolescents: IV, Oral: Administer dose after dialysis session; the risk of thrombocytopenia is increased in patients with impaired kidney function. Monitor closely; dosage adjustment may be necessary, but specific recommendations are not available; utilize therapeutic drug monitoring and monitor efficacy closely (Ref).
Peritoneal dialysis: Infants, Children, and Adolescents: IV, Oral: The risk of thrombocytopenia is increased in patients with impaired kidney function. Specific recommendations are not available; utilize therapeutic drug monitoring and monitor efficacy closely (Ref).
Continuous renal replacement therapy (CRRT): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Flow rates vary widely in pediatric patients. Appropriate dosing requires consideration of drug penetration to site of infection, minimum inhibitory concentration (MIC) of bacteria, and severity of illness. Close monitoring of response and adverse reactions due to drug accumulation (eg, hematologic toxicity) is important. Due to minimal data in pediatric patients receiving CRRT, consider monitoring serum concentrations if available.
Infants, Children, and Adolescents: IV, Oral: Based on adult data, dosage adjustment is not necessary; monitor closely (Ref). Note: While pediatric data are lacking, high variability of linezolid pharmacokinetics has been observed in critically ill adult patients and those on renal replacement therapies; monitor patient closely for efficacy and toxicities, and utilize therapeutic drug monitoring when possible (Ref).
Mild to moderate impairment: No adjustment necessary.
Severe hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Based on experience in adult patients, linezolid concentrations and risk of thrombocytopenia may be increased in patients with cirrhosis; use with caution and monitor closely; consider therapeutic drug monitoring when feasible (Ref).
(For additional information see "Linezolid: Drug information")
Dosage guidance:
Safety: 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.
Bloodstream infection:
Empiric therapy or pathogen-directed therapy for methicillin-resistant Staphylococcus aureus (MRSA) (alternative agent) (off-label use): Oral, IV: 600 mg every 12 hours (Ref); 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 (Ref).
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 (Ref). 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 (Ref).
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 (Ref). For staphylococci, usually used in combination with rifampin (eg, in the setting of retained hardware) (Ref), but conflicting data are available on the effect of rifampin on linezolid levels (Ref).
Diabetic foot infection: Empiric therapy or pathogen-directed therapy for MRSA.
Oral, IV: 600 mg every 12 hours; for empiric therapy, usually given as part of an appropriate combination regimen. Duration of therapy depends on severity and clinical response. Most patients with infection limited to skin and soft tissue respond to 1 to 2 weeks of therapy. For infections requiring surgical debridement, duration is usually 2 to 4 weeks in the absence of osteomyelitis; prolonged use of linezolid may be limited by toxicity (Ref).
Endocarditis, treatment (off-label use):
Enterococcus, penicillin-, aminoglycoside-, and vancomycin-resistant: Note: Some experts prefer other agents given limited data with linezolid for endocarditis (Ref).
IV, Oral: 600 mg every 12 hours for >6 weeks; prolonged use of linezolid may be limited by toxicity (Ref).
S. aureus, oral step-down therapy (alternative agent):
Note: Data are limited; not first-line therapy. Reserve use for methicillin-resistant S. aureus or for methicillin-susceptible S. aureus in the setting of penicillin allergy. Some experts suggest oral antibiotics as an alternative for patients who inject drugs and are not able to complete IV standard of care therapy. Prolonged use may be limited by toxicity. (Ref).
Oral: 600 mg every 12 hours in combination with rifampin for a total duration, including initial IV therapy, of 6 weeks (Ref).
Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (alternative agent) (off-label use): Empiric or pathogen-directed therapy of MRSA.
IV, Oral: 600 mg every 12 hours; when used for empiric therapy, use as part of an appropriate combination regimen. Duration generally ranges from 4 to 8 weeks for spinal epidural abscess, and 6 to 8 weeks for brain abscess and intracranial epidural abscess; prolonged use of linezolid may be limited by toxicity (Ref).
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 (Ref).
Mycobacterial (nontuberculous, rapidly growing) infection (off-label use):
Note: Patients should be under the care of a clinician with expertise in managing mycobacterial infection (Ref).
Oral, IV: 600 mg 1 or 2 times daily as part of an appropriate combination regimen (Ref); some experts prefer 600 mg once daily to minimize toxicity (Ref).
Osteomyelitis and/or discitis (alternative agent) (off-label use):
Pathogen-directed therapy for Staphylococcus spp., including MRSA: Oral, IV: 600 mg every 12 hours (Ref). Some experts combine with rifampin in the presence of retained hardware (Ref), but conflicting data are available on the effect of rifampin on linezolid levels (Ref).
Pathogen-directed therapy for Enterococcus spp.: Oral, IV: 600 mg every 12 hours (Ref).
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) (Ref).
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 (Ref).
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 (Ref).
Pathogen-directed therapy for Staphylococcus spp., including MRSA: 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 (Ref).
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 (Ref).
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 (Ref). Some experts recommend 4 weeks of therapy for patients with concomitant bacteremia (Ref).
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 (Ref). Note: For empiric therapy, give as part of an appropriate combination regimen (Ref).
Toxic shock syndrome (off-label use):
Toxin production suppression due to group A streptococci (alternative agent):
Note: Reserve for streptococcal toxic shock syndrome caused by isolates resistant to clindamycin (Ref).
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 (Ref).
Empiric therapy or pathogen-directed therapy for S. aureus, including MRSA and toxin production suppression: Oral, IV: 600 mg every 12 hours as part of an appropriate combination regimen. 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 (Ref).
Tuberculosis disease, drug resistant (off-label use): Oral, IV: 600 mg once daily as part of an appropriate combination regimen including pyridoxine (Ref); dose reduction to 300 mg once daily or 600 mg 3 to 4 times weekly may be used for certain regimens or for patients who develop toxicity (Ref). Consider serum monitoring to ensure therapeutic concentration (Ref). Note: For patients <50 kg, an initial dose of 450 mg once daily has been suggested (Ref).
Duration of therapy: Individualize based on rapidity of culture conversion, extent of disease, and patient-specific factors, including clinical response and toxicity (Ref).
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) (Ref).
Oral, IV: 600 mg every 12 hours; duration generally ranges from 7 to 10 days depending on clinical response (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (Ref). 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 (Ref).
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 (Ref).
IV: 450 mg every 8 hours. Utilize therapeutic drug monitoring when available (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable, parent drug and metabolites (~30% to 57% removed via high-flux dialyzer (Ref).
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 (Ref). 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 (Ref). More frequent monitoring of CBC should be considered due to increased risk of myelosuppression (Ref).
Peritoneal dialysis: Likely to be dialyzable (low protein binding, small volume of distribution) (Ref):
Oral, IV: No dosage adjustment necessary (Ref).
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 (Ref). More frequent monitoring of CBC should be considered due to increased risk of myelosuppression (Ref).
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 (Ref).
Note: High variability of linezolid pharmacokinetics has been observed in critically ill patients (Ref) and those on renal replacement therapies (Ref). 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 (Ref).
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 (Ref).
Note: High variability of linezolid pharmacokinetics has been observed in critically ill patients (Ref) and those on renal replacement therapies (Ref). 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 (Ref).
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 (Ref).
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 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 (including anemia, leukopenia, pancytopenia, and thrombocytopenia) have been reported with the use of linezolid (Ref). Thrombocytopenia is the most frequently observed blood dyscrasia and has been reported more often in patients with severe kidney impairment and in patients with moderate to severe hepatic impairment. 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)
• 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
• Severe kidney impairment or moderate to severe hepatic impairment
• Concurrent medications that cause bone marrow suppression
• Chronic infection (previous or concurrent antibiotic therapy)
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)
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
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, children: 12%; children, adolescents, adults: ≤2%)
1% to 10%:
Dermatologic: Pruritus (neonates, infants, children, adolescents: ≤1%; nonapplication site), skin rash (adults: 1% to 2%)
Endocrine & metabolic: Increased lactate dehydrogenase (adults: ≤2%)
Gastrointestinal: Abdominal pain (≤2%), dysgeusia (adults: 1% to 2%), increased serum amylase (neonates, infants, children, adults: ≤2%), increased serum lipase (adults: 3% to 4%; children, adolescents: <1%), 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, children: 6%; adults ≤2%) (table 1), decreased neutrophils (neonates, infants, children: 6%; children, adolescents, adults: ≤1%), eosinophilia (neonates, infants, children, adolescents: ≤2%), thrombocytopenia (table 2) (neonates, infants, children: 5%; decreased platelet count (table 3): adults: ≤10%)
|
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 |
|
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 |
|
Drug (Linezolid) |
Comparator |
Population |
|---|---|---|
|
0.3% to 10% |
0.4% to 7% |
Adults |
Hepatic: Abnormal hepatic function tests (adults: ≤2%), increased serum alanine aminotransferase (neonates, infants, children, adults: 2% to 10%), increased serum alkaline phosphatase (adults: ≤4%), increased serum aspartate aminotransferase (adults: 2% to 5%), increased serum bilirubin (neonates, infants, children: 6%; adults: <1%)
Infection: Fungal infection (adults: ≤2%)
Nervous system: Dizziness (adults: 2% to 3%), headache (children, adolescents, adults: 6% to 9%; neonates, infants, children: <1%), vertigo (children, adolescents: 1%)
Renal: Increased blood urea nitrogen (adults: ≤2%), increased serum creatinine (≤2%)
Postmarketing:
Cardiovascular: Hypertensive crisis (Ref)
Dermatologic: Bullous skin disease (Ref), purpuric rash (Ref), Stevens-Johnson syndrome, toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Hypoglycemia (Ref), hyponatremia (Ref), lactic acidosis (Ref), SIADH (Ref)
Gastrointestinal: Clostridioides difficile-associated diarrhea, hematemesis (Ref), melanoglossia (Ref), staining of tooth (Ref)
Hematologic & oncologic: Leukopenia (Ref), pancytopenia (Ref), pure red cell aplasia (Ref), sideroblastic anemia (Ref)
Hypersensitivity: Anaphylaxis, angioedema (Ref), hypersensitivity angiitis (Ref)
Nervous system: Hallucination (Ref), peripheral neuropathy (Ref), psychosis (Ref), seizure (Ref), serotonin syndrome (Ref)
Neuromuscular & skeletal: Rhabdomyolysis (Ref)
Ophthalmic: Blurred vision (Ref), optic neuropathy (Ref), vision loss (Ref)
Hypersensitivity to linezolid or any component of the formulation; concurrent use or within 2 weeks of monoamine oxidase inhibitors (MAOIs).
Note: Although linezolid is contraindicated per manufacturer labeling when used in combination with SSRIs, TCAs and buspirone, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore linezolid can be administered concomitantly with these agents when necessary. Monitor patients on these combinations; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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: serotonin 5-HT1 receptor agonists (triptans); or opioids, including meperidine.
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).
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) [contains aspartame, sodium benzoate]
Zyvox: 100 mg/5 mL (150 mL) [contains aspartame, sodium benzoate; orange flavor]
Generic: 100 mg/5 mL (150 mL)
Tablet, Oral:
Zyvox: 600 mg
Generic: 600 mg
Yes
Solution (Linezolid in Sodium Chloride Intravenous)
600MG/300ML 0.9% (per mL): $0.29
Solution (Linezolid Intravenous)
600MG/300ML (per mL): $0.05 - $0.37
Solution (Zyvox Intravenous)
200 mg/100 mL (per mL): $0.69
600MG/300ML (per mL): $0.13
Suspension (reconstituted) (Linezolid Oral)
100 mg/5 mL (per mL): $2.69 - $6.38
Suspension (reconstituted) (Zyvox Oral)
100 mg/5 mL (per mL): $1.96
Tablets (Linezolid Oral)
600 mg (per each): $183.47 - $288.00
Tablets (Zyvox Oral)
600 mg (per each): $325.21
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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:
Generic: 600 mg
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.
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.
Infusion: Store at 25°C (77°F). Protect from light and freezing. Keep infusion bags in overwrap until ready for use.
Oral suspension: Store at 25°C (77°F); following reconstitution store at room temperature and use suspension within 21 days. Protect from light.
Tablet: Store at 25°C (77°F). Protect from light and moisture.
Treatment of community-acquired pneumonia, nosocomial pneumonia (eg, hospital-acquired, ventilator-associated), uncomplicated and complicated skin and soft tissue infections, and vancomycin-resistant Enterococcus faecium infections (All indications: FDA approved in all ages). Has also been used for the treatment of bloodstream infections, osteoarticular infections, meningitis, tuberculosis, Mycobacterium abscessus pulmonary infections, and exit-site or tunnel infections and peritonitis in patients with peritoneal dialysis catheters.
Zyvox may be confused with Zosyn, Zovirax
Substrate of CYP2J2 (Minor), CYP4F2 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits Monoamine Oxidase;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Alosetron: May increase serotonergic effects 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
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amphetamines: Monoamine Oxidase Inhibitors may increase hypertensive effects 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
Antiemetics (5HT3 Antagonists): May increase serotonergic effects 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
Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Apraclonidine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Apraclonidine. Monoamine Oxidase Inhibitors may increase serum concentration of Apraclonidine. Risk X: Avoid
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: Monoamine Oxidase Inhibitors may increase neurotoxic (central) effects of Atomoxetine. Risk X: Avoid
Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may increase hypertensive effects of Atropine (Ophthalmic). Risk X: Avoid
Avocado: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benzhydrocodone: May increase serotonergic effects 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 serum concentration of Betahistine. Risk C: Monitor
Bezafibrate: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Bezafibrate. Risk X: Avoid
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor
Brimonidine (Topical): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Topical). Risk C: Monitor
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Buprenorphine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
BuPROPion: Monoamine Oxidase Inhibitors may increase hypertensive effects of BuPROPion. Risk X: Avoid
BusPIRone: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
Butorphanol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
CarBAMazepine: May increase adverse/toxic effects 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
Carbinoxamine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cerebrolysin: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Chlorphenesin Carbamate: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects 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
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Codeine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Codeine. Risk X: Avoid
COMT Inhibitors: May increase adverse/toxic effects 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 increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
CycloSPORINE (Systemic): May increase serum concentration of Linezolid. Risk C: Monitor
Cyproheptadine: May decrease serotonergic effects of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may increase anticholinergic effects of Cyproheptadine. Risk X: Avoid
Dapoxetine: May increase serotonergic effects 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
Deutetrabenazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Deutetrabenazine. Risk X: Avoid
Dexmethylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Dexmethylphenidate. Risk X: Avoid
Dextromethorphan: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid
Diamorphine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Diamorphine. Risk X: Avoid
Diethylpropion: Monoamine Oxidase Inhibitors may increase hypertensive effects of Diethylpropion. Risk X: Avoid
Difenoxin: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Dihydrocodeine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Consider avoiding use of dihydrocodeine while the patient is taking monoamine oxidase inhibitors (MAOIs) and for 2 weeks after MAOI discontinuation. Risk D: Consider Therapy Modification
Diphenoxylate: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Domperidone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Domperidone. Monoamine Oxidase Inhibitors may decrease therapeutic effects of Domperidone. Domperidone may decrease therapeutic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
DOPamine: Monoamine Oxidase Inhibitors may increase hypertensive effects 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
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Droxidopa: Monoamine Oxidase Inhibitors may increase hypertensive effects of Droxidopa. Risk X: Avoid
EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk X: Avoid
Ergot Derivatives: May increase serotonergic effects 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
Esketamine (Nasal): May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Fenfluramine: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
FentaNYL: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Gepirone: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
Guanethidine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
HYDROcodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROcodone. Management: Consider alternatives to this combination when possible. If coadministration is required, use test doses, titrate small doses frequently, and monitor patients closely for evidence of serotonergic and opioid toxicities. Risk D: Consider Therapy Modification
HYDROmorphone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROmorphone. Management: Coadministration of hydromorphone and monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) is not recommended. If required, use test doses, titrate small doses frequently, and monitor for CNS and respitatory depression. Risk D: Consider Therapy Modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Indoramin: Monoamine Oxidase Inhibitors may increase hypotensive effects of Indoramin. Risk X: Avoid
Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may decrease therapeutic effects 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
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Lasmiditan: May increase serotonergic effects 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
Levodopa-Foslevodopa: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid
Levomethadone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Levonordefrin: Monoamine Oxidase Inhibitors may increase hypertensive effects of Levonordefrin. Management: Avoid the use of levonordefrin during or within 2 weeks of treatment with a monoamine oxidase inhibitor whenever possible. If levonordefrin cannot be avoided during this period, monitor closely for enhanced or prolonged increases in blood pressure. Risk D: Consider Therapy Modification
Lithium: Linezolid may increase serotonergic effects 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
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Maprotiline: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Meptazinol: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Meptazinol. Risk X: Avoid
Mequitazine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Mequitazine. Risk X: Avoid
Metaxalone: May increase serotonergic effects 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
Methadone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methotrimeprazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methyldopa: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methyldopa. Risk X: Avoid
Methylene Blue: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
Methylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Methylphenidate. Risk X: Avoid
Metoclopramide: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Mianserin: Monoamine Oxidase Inhibitors may increase neurotoxic effects of Mianserin. Risk X: Avoid
Mivacurium: Monoamine Oxidase Inhibitors may increase serum concentration of Mivacurium. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): Linezolid may increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid
Monoamine Oxidase Inhibitors (Type B): Linezolid may increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Morphine (Systemic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Morphine (Systemic). Risk X: Avoid
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Myelosuppressive Agents: Linezolid may increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Nalbuphine: Monoamine Oxidase Inhibitors may increase CNS depressant effects of Nalbuphine. Nalbuphine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Nalbuphine may increase hypertensive effects of Monoamine Oxidase Inhibitors. Management: Use of nalbuphine is not recommended in patients taking MAOIs, or within 14 days of stopping MAOI therapy. If urgent nalbuphine use is needed, use test doses and frequent titration while monitoring blood pressure, CNS depression, and serotonergic toxicity Risk D: Consider Therapy Modification
Nefazodone: Linezolid may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid
Nefopam: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Nefopam. Risk X: Avoid
Normethadone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Normethadone. Risk X: Avoid
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Ondansetron: May increase serotonergic effects 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
Opicapone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Opioid Agonists: May increase serotonergic effects 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
Opipramol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Opium: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Opium. Risk X: Avoid
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects 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
OxyCODONE: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider Therapy Modification
OxyMORphone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Ozanimod: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pheniramine: May increase anticholinergic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Pholcodine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pizotifen: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Pizotifen. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Ramosetron: May increase serotonergic effects 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
Reboxetine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reboxetine. Risk X: Avoid
Remifentanil: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. 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 increase adverse/toxic effects 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
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: Linezolid may increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Non-Opioid CNS Depressants: Linezolid may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Opioids (High Risk): Linezolid may increase serotonergic effects of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Risk X: Avoid
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid
Serotonin/Norepinephrine Reuptake Inhibitor: Linezolid may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sevoflurane: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects 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 increase hypertensive effects of Solriamfetol. Risk X: Avoid
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease 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
SUFentanil: May increase adverse/toxic effects 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
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sympathomimetics: Linezolid may increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
Syrian Rue: May increase serotonergic effects 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
Tapentadol: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Tetrabenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tianeptine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Tilidine: May increase serotonergic effects 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
Tricyclic Antidepressants: Linezolid may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tryptophan: Linezolid may increase serotonergic effects of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid
Typhoid Vaccine: Antibiotics may decrease therapeutic effects 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
Tyrosine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Valbenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Viloxazine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Vitamin K Antagonists: Linezolid may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of Linezolid. This could result in serotonin syndrome. Risk X: Avoid
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
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.
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.
Outcome data related to linezolid use during pregnancy are limited (Navarro 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of linezolid may be altered (van Kampenhout 2017).
Weekly CBC, particularly in the following patients: Patients at increased risk for bleeding, patients with preexisting myelosuppression, patients receiving concomitant medications that cause bone marrow suppression, patients receiving >2 weeks of therapy, patients with chronic infection who have received previous or concomitant antibiotic therapy; more frequent monitoring may be warranted in certain scenarios based on clinical judgment (Jones 2015; Norris 2019; manufacturer's labeling). Weekly liver function tests with extended use (Norris 2019). Sodium (routinely in patients at risk of hyponatremia [eg, patients receiving diuretics] and/or syndrome of inappropriate antidiuretic hormone secretion [SIADH]). Periodic serum bicarbonate with extended therapy. Consider monitoring lactate in patients with renal or hepatic dysfunction or who are receiving long-term therapy (Su 2011).
Peripheral sensory and visual function with extended therapy (eg, ≥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) (Nambiar 2011; manufacturer's labeling). Monitor for signs and symptoms of lactic acidosis (eg, recurrent nausea and vomiting, unexplained acidosis, low bicarbonate levels) and signs and symptoms of hyponatremia. Monitor for signs and symptoms of serotonin syndrome or neuroleptic malignant syndrome-like reaction (especially in patients on concomitant serotonergic agents). Monitor for diarrhea.
Linezolid concentration monitoring is not routine, but may be considered in certain scenarios (eg, pathogens with minimum inhibitory concentrations [MICs] ≥2 mg/L, kidney impairment, drug-drug interactions, inadequate response to infection, patients at increased risk for adverse effects) (Cojutti 2015; Li 2019; Rao 2020; Thibault 2019).
Gram-positive bacterial infections: Efficacy targets:
AUC24/MIC: ≥80 to 120 (Li 2019; Rao 2020).
Trough concentration: 2 to 7 mg/L (Cojutti 2015; Rao 2020).
Toxicity:
Hematological toxicity may be associated with Cmin (trough) >7 to 10 mg/L (Abdul-Aziz 2020; Cattaneo 2013; Kawasuji 2021; Pea 2012) or AUC >280 to 350 mg•hour/L (Abdul-Aziz 2020; Pea 2012).
Mitochondrial toxicity (peripheral neuropathy, optic neuropathy, lactic acidosis, myelosuppression) may be associated with Cmin (trough) >2 mg/L when given for an extended duration (Song 2015).
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.
Absorption: Rapid and extensive.
Distribution:
Vd:
Neonates, GA <34 weeks:
PNA <7 days: 0.81 L/kg.
PNA >7 days: Median 0.99 L/kg; range: 0.7 to 1.45 L/kg (Thibault 2019).
Neonates, GA ≥34 weeks:
PNA <7 days: 0.78 L/kg.
PNA 7 to ≤28 days: 0.66 L/kg.
Infants <3 months of age: 0.79 L/kg.
Infants ≥3 months and Children ≤11 years of age: 0.69 L/kg.
Children ≥12 years and 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:
Neonates, GA <34 weeks:
PNA <7 days: 5.6 hours.
PNA >7 days: Median: 3.44 hours; range: 2.44 to 9.77 hours (Thibault 2019).
Neonates, GA ≥ 34 weeks:
PNA <7 days: 3 hours.
PNA 7 to ≤28 days: 1.5 hours.
Infants <3 months of age: 1.8 hours.
Infants ≥3 months and Children ≤11 years of age: 2.9 hours.
Children ≥12 years and 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:
Neonates, GA <34 weeks:
PNA <7 days: 2 mL/minute/kg.
PNA >7 days: Median ~2.8 mL/minute/kg; range: ~1.2 to 5.2 mL/minute/kg (Thibault 2019).
Neonates, GA ≥ 34 weeks:
PNA <7 days: 3.8 mL/minute/kg.
PNA 7 to ≤28 days of age: 5.1 mL/minute/kg.
Infants <3 months of age: 5.4 mL/minute/kg.
Infants ≥3 months and Children ≤11 years of age: 3.8 mL/minute/kg.
Children ≥12 years and Adolescents: 2.1 mL/minute/kg.
Adults: 1.7 mL/minute/kg.
Altered kidney function: 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).
