(li NE zoh lid)
Enterococcal infections, vancomycin-resistant: Treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia.
Pneumonia:
Community-acquired: Treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only).
Hospital-acquired or healthcare-associated: Treatment of hospital-acquired or healthcare-associated pneumonia caused by S. aureus (methicillin-susceptible and -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 -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.
Hypersensitivity to linezolid or any component of the formulation; concurrent use or within 2 weeks of MAO inhibitors
Enterococcal infections, vancomycin-resistant, including concurrent bacteremia: Oral, IV: 600 mg every 12 hours for 14 to 28 days
Pneumonia:
Community-acquired (CAP):
Manufacturers labeling (includes concurrent bacteremia): Oral, IV: 600 mg every 12 hours for 10 to 14 days.
Alternate dosing (Liu 2011): Oral, IV: S. aureus (methicillin-resistant): 600 mg every 12 hours for 7 to 21 days
Hospital-acquired or healthcare-associated:
Manufacturer's labeling: Oral, IV: 600 mg every 12 hours for 10 to 14 days.
Note: May consider 7-day treatment course (versus manufacturer recommended 10 to 14 days) in patients with healthcare-, hospital-, and ventilator- associated pneumonia who have demonstrated good clinical response (ATS/IDSA 2005).
Alternate dosing (Liu 2011): Oral, IV: S. aureus (methicillin-resistant): 600 mg every 12 hours for 7 to 21 days
Skin and skin structure infections, complicated: Oral, IV: 600 mg every 12 hours for 10 to 14 days. Note: For diabetic foot infections, initial treatment duration is up to 4 weeks depending on severity of infection and response to therapy (Lipsky 2012).
Skin and skin structure infections, uncomplicated: Oral: 400 mg every 12 hours for 10 to 14 days. Note: 400 mg dose is recommended in the product labeling; however, 600 mg dose is commonly employed clinically; consider 5- to 10-day treatment course as opposed to the manufacturer recommended 10 to 14 days (Liu 2011; Stevens 2014). For diabetic foot infections, may extend treatment duration up to 4 weeks if slow to resolve (Lipsky 2012).
Brain abscess, subdural empyema, spinal epidural abscess (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 600 mg every 12 hours for 4 to 6 weeks
Infective endocarditis, treatment (off-label use; AHA [Baddour 2015]): IV, Oral: Enterococcus (native or prosthetic valve; resistant to penicillin, aminoglycosides, and vancomycin): 600 mg every 12 hours for a minimum of 6 weeks
Meningitis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 600 mg every 12 hours for 2 weeks
Osteomyelitis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 600 mg every 12 hours for a minimum of 8 weeks (some experts combine with rifampin)
Prosthetic joint infection (off-label use):
Enterococcus spp (penicillin-susceptible or -resistant) (alternative treatment): Oral, IV: 600 mg every 12 hours for 4 to 6 weeks (consider adding an aminoglycoside) followed by an oral antibiotic suppressive regimen (Osmon 2013)
Staphylococci (oxacillin-sensitive or -resistant) (alternative treatment): Oral, IV: 600 mg every 12 hours for 2 to 6 weeks used in combination with rifampin followed by oral antibiotic treatment and suppressive regimens (Osmon 2013)
Septic arthritis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 600 mg every 12 hours for 3 to 4 weeks
Septic thrombosis of cavernous or dural venous sinus (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 600 mg every 12 hours for 4 to 6 weeks
Refer to adult dosing.
Usual dosage: Oral, IV:
Children ≤11 years: 10 mg/kg (maximum: 600 mg/dose) every 8 hours
Children ≥12 years and Adolescents: Refer to adult dosing.
Indication-specific dosing:
Enterococcal infections, vancomycin-resistant, including concurrent bacteremia: Oral, IV:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for 14 to 28 days
Children ≥12 years and Adolescents: Refer to adult dosing.
Pneumonia:
Community-acquired (CAP):
Manufacturers labeling (includes concurrent bacteremia): Oral, IV:
Infants and Children ≤11 years: 10 mg/kg/dose every 8 hours for 10 to 14 days
Children ≥12 years and Adolescents: Refer to adult dosing.
Alternate dosing:
Infants >3 months and Children ≤11 years (IDSA/PIDS 2011):
S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), mild infection or step-down therapy (alternative to amoxicillin): Oral: 10 mg/kg/dose every 8 hours
S. pneumoniae (MICs to penicillin ≥4.0 mcg/mL):
Severe infection (alternative to ceftriaxone): IV: 10 mg/kg/dose every 8 hours
Mild infection, step-down therapy (preferred): Oral: 10 mg/kg/dose every 8 hours
S. aureus (methicillin-resistant/clindamycin-susceptible):
Severe infection (alternative to vancomycin or clindamycin): IV: 10 mg/kg/dose every 8 hours
Mild infection, step-down therapy (alternative to clindamycin): Oral: 10 mg/kg/dose every 8 hours
S. aureus (methicillin- and clindamycin-resistant):
Severe infection (alternative to vancomycin): IV: 10 mg/kg/dose every 8 hours
Mild infection, step-down therapy (preferred): Oral: 10 mg/kg/dose every 8 hours
Children ≤11 years (Liu 2011): Oral, IV: S. aureus (methicillin-resistant): 10 mg/kg/dose every 8 hours for 7 to 21 days (maximum: 600 mg/dose)
Children ≥12 years and Adolescents (IDSA/PIDS 2011):
S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), mild infection or step-down therapy (alternative to amoxicillin): Oral: 10 mg/kg/dose every 12 hours
S. pneumoniae (MICs to penicillin ≥4.0 mcg/mL)
Severe infection (alternative to ceftriaxone): IV: 10 mg/kg/dose every 12 hours
Mild infection, step-down therapy (preferred): Oral: 10 mg/kg/dose every 12 hours
S. aureus (methicillin-resistant/clindamycin-susceptible):
Severe infection (alternative to vancomycin/clindamycin): IV: 10 mg/kg/dose every 12 hours
Mild infection, step-down therapy (alternative to clindamycin): Oral: 10 mg/kg/dose every 12 hours
S. aureus (methicillin- and clindamycin-resistant):
Severe infection (alternative to vancomycin): IV: 10 mg/kg/dose every 12 hours
Mild infection, step-down therapy (preferred): Oral: 10 mg/kg/dose every 12 hours
Children ≥12 years and Adolescents (Liu 2011): S. aureus (methicillin-resistant): Refer to adult dosing.
Hospital-acquired or healthcare-associated: Oral, IV:
Manufacturer's labeling:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for 10 to 14 days
Children ≥12 years and Adolescents: Refer to adult dosing.
Note: May consider 7-day treatment course (versus manufacturer recommended 10 to 14 days) in patients with healthcare-, hospital-, and ventilator-associated pneumonia who have demonstrated good clinical response (ATS/IDSA 2005).
Alternate dosing (Liu 2011): S. aureus (methicillin-resistant):
Infants and Children ≤11 years: 10 mg/kg/dose every 8 hours for 7 to 21 days (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Skin and skin structure infections, complicated: Oral, IV:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for 10 to 14 days
Children ≥12 years and Adolescents: Refer to adult dosing.
Skin and skin structure infections, uncomplicated: Oral:
Infants and Children <5 years: 10 mg/kg every 8 hours for 10 to 14 days
Children 5 to 11 years: 10 mg/kg every 12 hours for 10 to 14 days
Children ≥12 years and Adolescents: 600 mg every 12 hours for 10 to 14 days
Brain abscess, subdural empyema, spinal epidural abscess (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV: 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.
Children ≤ 11 years: 10 mg/kg every 8 hours for 4 to 6 weeks (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Meningitis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for 2 weeks (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Osteomyelitis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for a minimum of 4 to 6 weeks (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Septic arthritis (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV:
Infants and Children ≤11 years: 10 mg/kg every 8 hours for 3 to 4 weeks (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Septic thrombosis of cavernous or dural venous sinus (S. aureus [methicillin-resistant]) (off-label use) (Liu 2011): Oral, IV:
Children ≤11 years: 10 mg/kg every 8 hours for 4 to 6 weeks (maximum: 600 mg/dose)
Children ≥12 years and Adolescents: Refer to adult dosing.
Mild to severe impairment: No dosage adjustment necessary. The two primary metabolites may accumulate in patients with renal impairment but the clinical significance is unknown; use with caution.
End-stage renal disease (ESRD)on intermittent hemodialysis (IHD):
Manufacturers labeling: Dialyzable (~30% removed during 3-hour dialysis session): Administer after hemodialysis on dialysis days.
Alternate dosing: If administration time is not immediately after dialysis session, may consider administration of a supplemental dose especially early in the treatment course to maintain levels above the MIC (Brier 2003). However, others have recommended no supplemental dose or dosage adjustment for patients on IHD (Heintz 2009; Trotman 2005)
Peritoneal dialysis: No supplemental dose or dosage adjustment needed (Heintz 2009; Trotman 2005)
Continuous renal replacement therapy (CVVH, CVVHD, CVVHDF): Some have suggested no supplemental dose or dosage adjustment needed (Heintz 2009; Trotman 2005). Others have postulated that achievement of MIC 2 mg/L may be suboptimal in ~30% of patients undergoing CVVHD or CVVHDF given 600 mg every 12 hours; however, no alternative dosing recommendations suggested (Roger 2016).
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 (has not been studied).
Oral suspension: Refer to manufacturer 's product labeling for reconstitution instructions. Prior to administration mix gently by inverting bottle; do not shake.
IV: Administer intravenous infusion over 30 to 120 minutes. Do not mix or infuse with other medications. 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.
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 salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Zyvox: 600 mg/300 mL (300 mL); 200 mg/100 mL (100 mL)
Generic: 2 mg/mL (300 mL); 600 mg/300 mL (300 mL); 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
Stable in D51/2 NS, D5W, LR, NS
Y-site administration: Incompatible with amphotericin B, chlorpromazine, diazepam, pentamidine, phenytoin
Alcohol (Ethyl): May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Apraclonidine: MAO Inhibitors may enhance the adverse/toxic effect of Apraclonidine. MAO Inhibitors may increase the serum concentration of Apraclonidine. Avoid combination
AtoMOXetine: MAO Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination
Atropine (Ophthalmic): MAO Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Betahistine: MAO Inhibitors may increase the serum concentration of Betahistine. Monitor therapy
Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid combination
Blood Glucose Lowering Agents: MAO Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Brimonidine (Ophthalmic): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). MAO Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy
Brimonidine (Topical): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). MAO Inhibitors may increase the serum concentration of Brimonidine (Topical). Monitor therapy
Buprenorphine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
BuPROPion: MAO Inhibitors may enhance the hypertensive effect of BuPROPion. Avoid combination
BusPIRone: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, blood pressure elevations been reported. Avoid combination
CarBAMazepine: May enhance the adverse/toxic effect of MAO Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Avoid combination
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Codeine: MAO Inhibitors may enhance the adverse/toxic effect of Codeine. Monitor therapy
COMT Inhibitors: May enhance the adverse/toxic effect of MAO Inhibitors. Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Cyproheptadine: MAO Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of MAO Inhibitors. Avoid combination
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Dexmethylphenidate: MAO Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Avoid combination
Dextromethorphan: MAO Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Diethylpropion: MAO Inhibitors may enhance the hypertensive effect of Diethylpropion. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Domperidone: MAO Inhibitors may enhance the adverse/toxic effect of Domperidone. MAO Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of MAO Inhibitors. Monitor therapy
EPINEPHrine (Oral Inhalation): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination
Epinephrine (Racemic): MAO Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
FentaNYL: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
HYDROcodone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification
HYDROmorphone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Avoid combination
Isometheptene: MAO Inhibitors may enhance the adverse/toxic effect of Isometheptene. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Levodopa: May enhance the adverse/toxic effect of MAO Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Management: The concomitant use of nonselective monoamine oxidase inhibitors (MAOIs) and levodopa is contraindicated. Discontinue the nonselective MAOI at least two weeks prior to initiating levodopa. Monitor patients taking a selective MAOIs and levodopa. Consider therapy modification
Levonordefrin: MAO Inhibitors may enhance the hypertensive effect of Levonordefrin. Avoid combination
Lithium: MAO Inhibitors may enhance the adverse/toxic effect of Lithium. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification
MAO Inhibitors: May enhance the adverse/toxic effect of Linezolid. Avoid combination
Maprotiline: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Meperidine: MAO Inhibitors may enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Avoid combination
Mequitazine: MAO Inhibitors may enhance the anticholinergic effect of Mequitazine. Avoid combination
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methyldopa: MAO Inhibitors may enhance the adverse/toxic effect of Methyldopa. Avoid combination
Methylene Blue: MAO Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Methylphenidate: MAO Inhibitors may enhance the hypertensive effect of Methylphenidate. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
Mianserin: MAO Inhibitors may enhance the neurotoxic effect of Mianserin. Avoid combination
Mirtazapine: Linezolid may enhance the serotonergic effect of Mirtazapine. This could result in serotonin syndrome. Avoid combination
Moclobemide: MAO Inhibitors may enhance the adverse/toxic effect of Moclobemide. Avoid combination
Morphine (Liposomal): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Liposomal). Avoid combination
Morphine (Systemic): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination
Nefazodone: Linezolid may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Avoid combination
Nefopam: MAO Inhibitors may enhance the adverse/toxic effect of Nefopam. Avoid combination
OxyCODONE: MAO Inhibitors may enhance the adverse/toxic effect of OxyCODONE. Management: Per Canadian labeling, use of oxycodone is contraindicated in patients who either are receiving MAO inhibitors or have used them within 14 days. Though not contraindicated in U.S. prescribing information, consider alternatives when possible. Consider therapy modification
OxyMORphone: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Pheniramine: May enhance the anticholinergic effect of MAO Inhibitors. Avoid combination
Pholcodine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Pindolol: MAO Inhibitors may enhance the hypotensive effect of Pindolol. Management: Canadian labeling for pindolol states that concurrent use with a monoamine oxidase inhibitor is not recommended. Consider therapy modification
Pizotifen: MAO Inhibitors may enhance the anticholinergic effect of Pizotifen. Avoid combination
Reboxetine: MAO Inhibitors may enhance the adverse/toxic effect of Reboxetine. Avoid combination
Reserpine: MAO 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. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Linezolid may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination
Serotonin 5-HT1D Receptor Agonists: MAO Inhibitors may decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Exceptions: Eletriptan; Frovatriptan; Naratriptan. Avoid combination
Serotonin Modulators: Linezolid may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Exceptions: Nicergoline. Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: Linezolid may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. 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. Consider therapy modification
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. Consider therapy modification
Tapentadol: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tetrahydrozoline (Nasal): MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Avoid combination
Tianeptine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
TraZODone: Linezolid may enhance the serotonergic effect of TraZODone. This could result in serotonin syndrome. Avoid combination
Tricyclic Antidepressants: Linezolid may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Avoid combination
Tryptophan: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
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; visual function with extended therapy ( ≥3 months) or in patients with new onset visual symptoms, regardless of therapy length; in patients with renal impairment, monitor for hematopoietic (eg, anemia, leukopenia, thrombocytopenia) and neuropathic (eg, peripheral neuropathy) adverse events when administering for extended periods.
Percentages as reported in adults; frequency similar in pediatric patients unless otherwise noted.
>10%:
Central nervous system: Headache (<1% to 11%)
Gastrointestinal: Diarrhea (3% to 11%)
Hematologic & oncologic: Decreased hemoglobin (1% to 16%), thrombocytopenia (<1% to 13%), leukopenia (children 1% to 12%; adults <1% to 2%)
1% to 10%:
Central nervous system: Insomnia (3%), dizziness ( ≤3%), vertigo (children 1%)
Dermatologic: Skin rash (1% to 2%), pruritus (children 1%)
Endocrine & metabolic: Increased amylase (<1% to 2%), increased lactate dehydrogenase (<1% to 2%)
Gastrointestinal: Nausea (1% to 10%), vomiting (1% to 9%), increased serum lipase (3% to 4%), constipation (2%), dysgeusia (1% to 2%), loose stools (children 1% to 2%), oral candidiasis (1% to 2%), abdominal pain ( ≤2%), tongue discoloration ( ≤1%), pancreatitis
Genitourinary: Vulvovaginal candidiasis (1% to 2%)
Hematologic & oncologic: Neutropenia (children 1% to 6%; adults ≤1%), anemia (children ≤6%; adults ≤2%), eosinophilia (children ≤2%)
Hepatic: Increased serum ALT ( ≤10%), increased serum bilirubin (children ≤6%; adults ≤1%), increased serum AST (adults 2% to 5%), increased serum alkaline phosphatase (<1% to 4%), abnormal hepatic function tests ( ≤2%)
Infection: Fungal infection ( ≤1% to 2%)
Renal: Increased blood urea nitrogen ( ≤2%), increased serum creatinine (<1% to 2%)
Miscellaneous: Fever (2%)
<1% (Limited to important or life-threatening): Anaphylaxis, angioedema, bullous skin disease, Clostridium difficile-associated diarrhea, convulsions, hypertension, hypoglycemia, lactic acidosis, optic neuropathy, pancytopenia, peripheral neuropathy, rhabdomyolysis, seizures, serotonin syndrome (with concurrent use of other serotonergic agents), Stevens-Johnson syndrome, vision loss
Pharmacokinetics of linezolid are not altered in patients with renal insufficiency. Metabolites A and B may accumulate in patients with renal insufficiency; the significance of this accumulation is not known. Approximately 30% of a dose is eliminated in a 3-hour dialysis session.
Concerns related to adverse effects:
- Lactic acidosis: Has been reported with use. Patients who develop recurrent nausea and vomiting, unexplained acidosis, or low bicarbonate levels need immediate evaluation.
- Myelosuppression: Has been reported and may be dependent on duration of therapy (generally >2 weeks of treatment); use with caution in patients with preexisting myelosuppression, in patients receiving other drugs which may cause bone marrow suppression, or in chronic infection (previous or concurrent antibiotic therapy). Weekly CBC monitoring is recommended; consider discontinuation in patients developing myelosuppression (or in whom myelosuppression worsens during treatment).
- Peripheral and optic neuropathy (with vision loss): Has been reported in adults and children and may occur primarily with extended courses of therapy >28 days; any symptoms of visual change or impairment warrant immediate ophthalmic evaluation and possible discontinuation of therapy.
- Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs, agents which reduce linezolids metabolism, or in patients with carcinoid syndrome. Avoid use in such patients unless clinically appropriate and under close monitoring for signs/symptoms of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
- Carcinoid syndrome: Use with caution and closely monitor for serotonin syndrome in patients with carcinoid syndrome; linezolid has not been studied in patients with this condition. Do not use in the absence of close monitoring.
- Diabetes mellitus: Hypoglycemic episodes have been reported; use with caution and closely monitor glucose in diabetic patients. Dose reductions/discontinuation of concurrent hypoglycemic agents or discontinuation of linezolid may be required.
- Hypertension: Use with caution and closely monitor blood pressure in patients with uncontrolled hypertension; linezolid has not been studied in patients with this condition. Do not use in the absence of close monitoring.
- Hyperthyroidism: Use with caution and closely monitor blood pressure in patients with untreated hyperthyroidism; linezolid has not been studied in patients with this condition. Do not use in the absence of close monitoring.
- Pheochromocytoma: Use with caution and closely monitor blood pressure in patients with pheochromocytoma; linezolid has not been studied in patients with this condition. Do not use in the absence of close monitoring.
- Seizure disorder: Seizures have been reported; use with caution in patients with a history of seizures.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: 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. However, limited data in the form of case reports in pediatric and adult patients suggest that linezolid may be useful in treating gram-positive CNS infections that have failed to respond to other treatment options describing successful treatment of documented VRE and Staphylococcus aureus CNS and shunt infections in the literature (Cook 2005; da Silva 2007; Milstone 2007; Shaikh 2001; Villani 2002).
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).
C
Adverse effects were observed in some animal reproduction studies at doses that were also maternally toxic. Information related to linezolid use during pregnancy is limited.
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.
Rapid and extensive
Vd:
Preterm neonates <1 week: 0.81 L/kg
Full-term neonates <1 week: 0.78 L/kg
Full-term neonates ≥1 week to ≤28 days: 0.66 L/kg
Infants >28 days to <3 months: 0.79 L/kg
Infants and Children 3 months to 11 years: 0.69 L/kg
Adolescents: 0.61 L/kg
Adults: 0.65 L/kg
Hepatic via oxidation of the morpholine ring, resulting in two inactive metabolites (aminoethoxyacetic acid, hydroxyethyl glycine); minimally metabolized, may be mediated by cytochrome P450
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: 2 mL/minute/kg
Full-term neonates <1 week: 3.8 mL/minute/kg
Full-term neonates ≥1 week to ≤28 days: 5.1 mL/minute/kg
Infants >28 days to <3 months: 5.4 mL/minute/kg
Infants and Children 3 months to 11 years: 3.8 mL/minute/kg
Adolescents: 2.1 mL/minute/kg
Adults: 1.7 mL/minute/kg
Adults: Oral: 1 to 2 hours
Preterm neonates <1 week: 5.6 hours
Full-term neonates <1 week: 3 hours
Full-term neonates ≥1 week to ≤28 days: 1.5 hours
Infants >28 days to <3 months: 1.8 hours
Infants and Children 3 months to 11 years: 2.9 hours
Adolescents: 4.1 hours
Adults: 4.9 hours
Adults: 31%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of lactic acidosis (fast breathing, fast heartbeat, abnormal heartbeat, vomiting, drowsiness, shortness of breath, feeling very tired or weak, severe dizziness, feeling cold, or muscle pain or cramps), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), vision changes, severe headache, seizures, vision changes, burning or numbness feeling, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.