Zyvox

Generic Name: Linezolid
Class: Oxazolidinones
VA Class: AM900
Molecular Formula: C₁₆H₂₀FN₃O₄
CAS Number: 165800-03-3

Introduction

Antibacterial; synthetic oxazolidinone.^{1 2 3 4 5}

Uses for Zyvox

Vancomycin-resistant Enterococcus faecium Infections

Treatment of infections caused by susceptible vancomycin-resistant Enterococcus faecium (VRE), including infections associated with concurrent bacteremia.^{1 2 3 4}

Respiratory Tract Infections

Treatment of community-acquired pneumonia (CAP), including infections associated with concurrent bacteremia, caused by susceptible Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae [MDRSP] resistant to ≥2 of the following anti-infectives: penicillin, second-generation cephalosporins, macrolides, tetracycline, co-trimoxazole).^{1 2 3 4}

Treatment of CAP caused by susceptible Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only).^{1 2 3 4}

Treatment of nosocomial pneumonia caused by susceptible S. aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]) or susceptible S. pneumoniae (including MDRSP).^{1 2 3 4 11}

Not usually recommended for empiric outpatient or inpatient treatment of respiratory tract infections since it does not provide coverage against all potential respiratory tract pathogens.^{12 19} However, IDSA and ATS recommend that vancomycin or linezolid be included in initial empiric regimens for treatment of CAP if MRSA may be involved.¹⁹ IDSA and ATS also recommend that vancomycin or linezolid be included in initial empiric regimens used for treatment of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia in hospitals where methicillin-resistant (oxacillin-resistant) strains of Staphylococcus are common or if there are risk factors for these strains.²¹

Not indicated for treatment of respiratory tract infections caused by gram-negative bacteria.¹ It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if the documented or presumptive pathogens also include gram-negative bacteria.¹

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains only) or susceptible S. pyogenes (group A β-hemolytic streptococci).^{1 2 3 4 10}

Treatment of complicated skin and skin structure infections, including diabetic foot infections, without concurrent osteomyelitis, caused by susceptible S. aureus (including methicillin-resistant [oxacillin-resistant] strains), S. pyogenes, or S. agalactiae (group B streptococci).^{1 2 3 4 10 26}

Use in the treatment of decubitus ulcers has not been studied.^{1 3}

IDSA and other experts consider vancomycin the drug of choice for treatment of skin and soft-tissue infections caused by MRSA and recommend linezolid or daptomycin as alternatives.^{20 22} Some experts recommend linezolid for the treatment of moderate diabetic foot infections when MRSA may be involved.²⁶

Not indicated for treatment of skin and skin structure infections caused by gram-negative bacteria.¹ It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if the documented or presumptive pathogens also include gram-negative bacteria.¹

Zyvox Dosage and Administration

Administration

Administer orally or by IV infusion.^{1 2 3 4}

When clinically appropriate, IV route may be switched to oral without dosage adjustment.^{1 3}

Avoid large quantities of foods or beverages with high tyramine content during linezolid therapy.^{1 3 4} (See Monoamine Oxidase Inhibition under Cautions.)

Oral Administration

Administer orally without regard to meals.¹

Reconstitution

Reconstitute powder for oral suspension at time of dispensing by adding the amount of water specified on the bottle to provide a suspension containing 100 mg/5 mL.¹ After tapping the bottle gently to loosen the powder, add the water in 2 portions and agitate well after each addition.¹

Prior to administration of each dose, gently mix the suspension by inverting the bottle 3–5 times; do not shake.¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Single-use containers of linezolid injection for IV infusion should be administered without further dilution.¹ The containers should not be used in series connections, and additives should not be introduced into the solution.^{1 3}

Rate of Administration

Administer by IV infusion over 30–120 minutes.^{1 3}

Dosage

Manufacturer states safety and efficacy of >28 days of linezolid treatment not evaluated in controlled clinical trials.¹

Pediatric Patients

General Dosage for Neonates <7 Days of Age

Oral or IV

10 mg/kg every 12 hours initially; consider 10 mg/kg every 8 hours in neonates with an inadequate response to the lower dosage.¹ By 7 days of age, all neonates should receive 10 mg/kg every 8 hours.¹

Vancomycin-resistant Enterococcus faecium Infections

Oral or IV

Children 7 days through 11 years of age: 10 mg/kg every 8 hours for 14–28 days.¹

Adolescents ≥12 years of age: 600 mg every 12 hours for 14–28 days.¹

Respiratory Tract Infections

Community-acquired or Nosocomial Pneumonia

Oral or IV

Children 7 days through 11 years of age: 10 mg/kg every 8 hours for 10–14 days.¹

Adolescents ≥12 years of age: 600 mg every 12 hours for 10–14 days.¹

Skin and Skin Structure Infections

Uncomplicated Skin and Skin Structure Infections

Oral

Children 7 days through 4 years of age: 10 mg/kg every 8 hours for 10–14 days.¹

Children 5–11 years of age: 10 mg/kg every 12 hours for 10–14 days.¹

Adolescents ≥12 years of age: 600 mg every 12 hours for 10–14 days.¹

Complicated Skin and Skin Structure Infections

Oral or IV

Children 7 days through 11 years of age: 10 mg/kg every 8 hours for 10–14 days.¹

Adolescents ≥12 years of age: 600 mg every 12 hours for 10–14 days.¹

Adults

Vancomycin-resistant Enterococcus faecium Infections

Oral or IV

600 mg every 12 hours for 14–28 days.¹

Respiratory Tract Infections

Community-acquired or Nosocomial Pneumonia

Oral or IV

600 mg every 12 hours for 10–14 days.¹

Skin and Skin Structure Infections

Uncomplicated Skin and Skin Structure Infections

Oral

400 mg every 12 hours for 10–14 days.¹

Complicated Skin and Skin Structure Infections

Oral or IV

600 mg every 12 hours for 10–14 days.¹

Special Populations

Hepatic Impairment

Dosage adjustments not required in mild to moderate hepatic impairment (Child-Pugh class A or B).¹ Data not available regarding pharmacokinetics in severe hepatic impairment.¹

Renal Impairment

Dosage adjustments not required.¹ Use caution in severe renal impairment.⁵ (See Renal Impairment under Cautions.)

For hemodialysis patients, administer after dialysis session.^{1 4}

Geriatric Patients

Dosage adjustments not required.¹

Cautions for Zyvox

Contraindications

• 
  

  Known hypersensitivity to linezolid or any ingredient in the formulation.^{1 3}

  
  


• 
  

  Patients who are receiving (or have received within the last 2 weeks) drugs that inhibit MAO A or B (e.g., isocarboxazid, phenelzine).¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Unless patients are monitored for potential increases in BP, should not be used in patients with uncontrolled hypertension, pheochromocytoma, or thyrotoxicosis or in patients receiving directly or indirectly acting sympathomimetic agents (e.g., pseudoephedrine), vasopressive agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine).¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Unless patients are carefully monitored for signs and/or symptoms of serotonin syndrome, should not be used in patients with carcinoid syndrome.¹

  
  


• 
  

  Because of risk of serotonin syndrome, generally should not be used in patients receiving SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors, or other serotonergic drugs.¹ (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Myelosuppression (anemia, leukopenia, pancytopenia, thrombocytopenia) reported.^{1 6}

Toxicity studies in adult and juvenile dogs and rats indicate myelosuppression, reduced extramedullary hematopoiesis in spleen and liver, and lymphoid depletion of thymus, lymph nodes, and spleen.¹

Monitor CBCs weekly during linezolid therapy, especially in those receiving the drug for >2 weeks and in those who have preexisting myelosuppression, are receiving concomitant drugs associated with bone marrow suppression, or have a chronic infection that was or is being treated with concomitant anti-infective therapy.^{1 6}

Consider discontinuing linezolid if myelosuppression develops or worsens.^{1 6} Hematologic parameters generally have increased toward pretreatment values following discontinuance of the drug.^{1 6}

Mortality

In an investigational study in seriously ill patients with intravascular catheter-related infections†, mortality was higher in patients receiving linezolid than in patients receiving a comparator anti-infective (vancomycin, oxacillin, dicloxacillin); patients also could receive concomitant therapy for gram-negative infection.^{1 23} Although there was no difference in mortality between linezolid and the comparator regimens in patients with only gram-positive bacteria identified in the baseline culture, mortality was higher in linezolid-treated patients with gram-negative bacterial infections, mixed gram-positive and gram-negative infections, or no pathogen identified at baseline.^{1 23} Causality has not been established.¹

Linezolid is not approved by the FDA for treatment of catheter-related bacteremia or catheter-site infections and is not approved for treatment of gram-negative bacterial infections.²³

Monamine Oxidase Inhibition

Linezolid is a weak, nonselective, reversible inhibitor of MAO,^{1 2 3 4} and potentially may interact with MAO inhibitors and adrenergic and serotonergic agents.¹ (See Specific Drugs under Interactions.)

A significant pressor response has been reported when tyramine doses >100 mg were used in adults receiving linezolid.¹ Instruct patients to consume <100 mg of tyramine per meal during linezolid therapy.^{1 3 4} Foods high in tyramine content include those that may have undergone protein changes by aging, fermentation, pickling, or smoking to improve flavor (e.g., aged cheeses: 0–15 mg tyramine/ounce; fermented or air-dried meat: 0.1–8 mg/ounce; sauerkraut: 8 mg/8 ounces; soy sauce: 5 mg/teaspoon; tap beer: 4 mg/12 ounces; red wine: 0–6 mg/8 ounces).¹ Consider that tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated.¹

Serotonin Syndrome

Serotonin syndrome (including some fatalities) reported in patients receiving linezolid concomitantly with serotonergic drugs (e.g., SSRIs).^{1 5 15 16 17 25 28 29} Signs and symptoms of serotonin syndrome include mental changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering, shaking, diarrhea, loss of coordination, and/or fever.²⁸

FDA states that linezolid generally should not be used in patients receiving serotonergic drugs.²⁸ Certain life-threatening or urgent emergency situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug, including when the anti-infective is indicated for treatment of VRE infections, nosocomial pneumonia (including cases caused by MRSA), or complicated skin and skin structure infections (including cases caused by MRSA).²⁸ In such situations, consider availability of alternative anti-infectives and weigh benefits of linezolid against risks of serotonin syndrome.²⁸ If linezolid is initiated, immediately discontinue the serotonergic agent.²⁸ (See Specific Drugs under Interactions.)

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organisms.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of Clostridium difficile.¹ Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including linezolid, and may range in severity from mild diarrhea to fatal colitis.¹ Hypertoxin producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.¹ Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.¹

If CDAD is suspected or confirmed, may need to discontinue anti-infectives not directed against C. difficile.¹ Some mild cases may respond to discontinuance alone.¹ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, angioedema, and bullous skin disorders, such as those described as Stevens-Johnson syndrome, reported.¹

General Precautions

Lactic Acidosis

Lactic acidosis, characterized by recurrent nausea and vomiting, has been reported.^{1 14} Patients who develop recurrent nausea and vomiting, unexplained acidosis, or a low bicarbonate concentration while receiving linezolid should undergo immediate medical evaluation.^{1 14}

Neuropathy

Peripheral and optic neuropathy, sometimes progressing to loss of vision, reported; these events have occurred principally in patients receiving the drug for >28 days.^{1 24} Blurred vision reported in some patients receiving the drug for <28 days.¹

If a patient experiences symptoms of visual impairment (e.g., changes in visual acuity or color vision, blurred vision, or visual field defect), promptly perform an ophthalmic evaluation.¹ Monitor visual function in all patients receiving linezolid for extended periods of time (i.e., ≥3 months).¹ In addition, monitor visual function in all patients reporting a new visual symptom, regardless of length of therapy.¹

If peripheral or optic neuropathy occurs, weigh potential benefits versus risks of continued linezolid therapy.¹

Seizures

Seizures reported; history of seizures or risk factors for seizures noted in some cases.¹

Selection and Use of Anti-infectives

Linezolid is indicated only for treatment of certain infections caused by certain gram-positive bacteria.¹ The drug has no clinical activity against gram-negative bacteria and is not indicated for treatment of infections caused by gram-negative bacteria.¹

It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if documented or presumptive pathogens also include gram-negative bacteria.¹ (See Uses.)

Manufacturer states that safety and efficacy of linezolid given for >28 days have not been evaluated in controlled clinical trials.¹ (See Dosage under Dosage and Administration.)

To reduce development of drug-resistant bacteria and maintain effectiveness of linezolid and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Phenylketonuria

Oral suspension contains aspartame, which is metabolized in the GI tract to provide 20 mg of phenylalanine per 5 mL of suspension.^{1 5}

Other linezolid preparations do not contain aspartame;¹ these other preparations should be used in individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine.¹

Other Precautions

Linezolid has not been studied in patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism.^{1 3} (See Contraindications under Cautions.)

Superficial tooth discoloration and tongue discoloration reported.¹ In cases with known outcome, tooth discoloration was removable with professional dental cleaning (manual descaling).¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Linezolid and its metabolites are distributed into milk in rats; not known whether distributed into human milk.¹ Use caution.¹

Pediatric Use

Safety and efficacy of linezolid for the treatment of vancomycin-resistant E. faecium infections, community-acquired pneumonia (CAP), nosocomial pneumonia, and complicated skin and skin structure infections in pediatric patients are supported by adequate and well-controlled studies in adults, pharmacokinetic studies in pediatric patients, and additional data from a comparator-controlled study of gram-positive infections in neonates and children through 11 years of age.¹ Safety and efficacy of the drug for the treatment of CAP in pediatric patients also is supported by evidence from an uncontrolled study in patients 8 months through 12 years of age.¹

Safety and efficacy of linezolid for the treatment of uncomplicated skin and skin structure infections in pediatric patients have been established in a comparator-controlled study in pediatric patients 5–17 years of age.¹

In children with a suboptimal response to linezolid, especially those with infections caused by pathogens with linezolid MICs of 4 mcg/mL, consider inadequate systemic exposure, site and severity of infection, and underlying medical conditions.¹

Use of linezolid for empiric treatment of CNS infections not recommended.¹ Therapeutic concentrations of linezolid are not achieved or maintained in CNS fluid.¹

Geriatric Use

Pharmacokinetic, safety, and efficacy profiles similar to those in younger adults.^{1 2}

Hepatic Impairment

Pharmacokinetics not evaluated in patients with severe hepatic impairment.¹

Renal Impairment

Although clinical importance not determined, the 2 principal metabolites of linezolid may accumulate in patients with renal impairment, especially severe renal impairment.^{1 3} Weigh potential benefits against potential risks of accumulation of linezolid metabolites.¹ Use with caution in severe renal impairment.⁵

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, constipation, localized or generalized abdominal pain), fever, headache, insomnia, rash, dizziness, skin disorder, pharyngitis, cough, upper respiratory tract infection.¹

Interactions for Zyvox

Minimally metabolized; possibly by CYP isoenzymes.¹

Does not inhibit CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4.¹ Does not induce CYP isoenzymes.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potent inducers of hepatic enzymes: Possible reduced linezolid concentrations.¹

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	Gentamicin: Pharmacokinetics of linezolid and gentamicin not affected if the drugs are used concomitantly1 2 3 Gentamicin or streptomycin: In vitro evidence of additive or indifferent antibacterial effects1
Ampicillin	In vitro evidence of additive or indifferent antibacterial effects1
Aztreonam	Pharmacokinetics of linezolid and aztreonam not affected if the drugs are used concomitantly1 2 3 In vitro evidence of additive or indifferent antibacterial effects1
Carbamazepine	Possible decreased linezolid concentrations1
Carbapenems	Imipenem: In vitro evidence of additive or indifferent antibacterial effects1
MAO inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine)	Potential pharmacologic interaction1 Increased risk of CNS toxicity, including serotonin syndrome1 28	Do not use linezolid in patients who are receiving (or have received within the last 2 weeks) an MAO inhibitor1 If a life-threatening or urgent emergency situation necessitates immediate linezolid treatment in a patient receiving an MAO inhibitor, consider availability of alternative anti-infectives and weigh benefits of linezolid against risk of serotonin syndrome28 If emergency use of linezolid is considered necessary, immediately discontinue the MAO inhibitor; monitor closely for symptoms of CNS toxicity (e.g., mental changes, muscle twitching, excessive sweating, shivering/shaking, diarrhea, loss of coordination, fever) for 2 weeks or until 24 hours after last linezolid dose, whichever comes first28 If nonemergency use of linezolid is planned, withhold the MAO inhibitor for at least 2 weeks prior to initiating linezolid;28 MAO inhibitor may be resumed 24 hours after last linezolid dose28 Do not initiate MAO inhibitor in patient receiving linezolid; when necessary, initiate 24 hours after last linezolid dose28
Phenobarbital	Possible decreased linezolid concentrations1
Phenytoin	Effect on phenytoin pharmacokinetics unlikely;1 possible decreased linezolid concentrations1	Dosage adjustments not required1
Rifampin	Decreased peak plasma concentration and AUC of linezolid1	Mechanism of the interaction and clinical importance unknown1
Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, amoxapine, bupropion, buspirone, maprotiline, mirtazapine, nefazodone, trazodone, vilazodone)	Increased risk of serotonin syndrome1 3 4 5 15 16 17 25 28	Do not use concurrently;28 if a life-threatening or urgent emergency situation necessitates immediate linezolid treatment in a patient receiving a serotonergic drug, consider availability of alternative anti-infectives and weigh benefit of linezolid against risk of serotonin syndrome28 If emergency use of linezolid is considered necessary, immediately discontinue the serotonergic drug; monitor closely for symptoms of CNS toxicity (e.g., mental changes, muscle twitching, excessive sweating, shivering/shaking, diarrhea, loss of coordination, fever) for 2 weeks (5 weeks if the patient was receiving fluoxetine) or until 24 hours after the last linezolid dose, whichever comes first28 If nonemergency use of linezolid is planned, withhold the serotonergic drug for at least 2 weeks (5 weeks if the patient was receiving fluoxetine) prior to initiating linezolid;28 serotonergic drug may be resumed 24 hours after last linezolid dose28 Do not initiate serotonergic drug in patients receiving linezolid; when necessary, initiate 24 hours after last linezolid dose28
Sympathomimetic agents	Potential pharmacologic interaction (enhanced vasopressor effects) with sympathomimetic agents, vasopressor agents, or dopaminergic agents1	Manufacturer of linezolid states that, unless patients are monitored for potential increases in BP, do not use in patients receiving directly or indirectly acting sympathomimetic agents (e.g., pseudoephedrine), vasopressor agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine)1 If an adrenergic agent (e.g., dopamine, epinephrine) is used in a patient receiving linezolid, use lower initial doses of the adrenergic agent and titrate dosage to achieve desired response1
Vancomycin	In vitro evidence of additive or indifferent antibacterial effects1
Warfarin	No substantial effect on warfarin pharmacokinetics1	Dosage adjustments not required1

Zyvox Pharmacokinetics

Absorption

Bioavailability

Rapidly and extensively absorbed after oral administration.¹ Absolute oral bioavailability is approximately 100%.^{1 18}

Peak plasma concentrations attained within 1–2 hours following oral administration.¹

Food

Time to peak concentrations is delayed and peak concentration decreased when administered with a high-fat meal,¹ but extent of absorption is not affected.¹ Not considered clinically important.¹

Distribution

Extent

Readily distributed into well-perfused tissues.¹

Studies in pediatric patients with ventriculoperitoneal shunts indicate that therapeutic concentrations of linezolid are not achieved or maintained in CNS fluid.¹

Linezolid and its metabolites are distributed into milk in rats; not known whether distributed into human milk.¹

Plasma Protein Binding

Approximately 31%.¹

Elimination

Metabolism

Principally metabolized by oxidation of the morpholine ring to 2 inactive metabolites.¹ Minimally metabolized; possibly mediated by CYP enzyme system.¹

Elimination Route

Approximately 65% of a dose eliminated via nonrenal clearance; renal clearance is low, suggesting net tubular reabsorption.¹ Almost no linezolid is found in feces as unchanged drug.¹

Linezolid and its metabolites removed by hemodialysis.¹

Not known whether linezolid or its metabolites are removed by peritoneal dialysis.^{1 3 5}

Half-life

Adults: Mean elimination half-life is 4.3–6.4 hours.^{1 18}

Neonates: Mean elimination half-life is 5.6 hours in preterm neonates <1 week of age, 3 hours in full-term neonates <1 week of age, and 1.5 hours in neonates 1 week to 28 days of age.¹

Infants and children: Mean elimination half-life is 1.8 hours in infants >28 days through 2 months of age and 2.9 hours in children 3 months through 11 years of age.¹

Adolescents 12 through 17 years of age: Mean elimination half-life is 4.1 hours.¹

Special Populations

In pediatric patients, clearance varies with age and there is wide intraindividual variability.¹ Excluding neonates <1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as children age, clearance of linezolid decreases and clearance in adolescents is similar to that observed in adults.¹

Pharmacokinetics not affected by mild-to-moderate hepatic impairment (Child-Pugh class A or B).¹

Pharmacokinetics of linezolid not affected by renal insufficiency, but the primary metabolites may accumulate.¹ Clinical importance unclear.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹ Protect from light.¹

For Suspension

25°C (may be exposed to 15–30°C).¹ Protect from light.¹ After reconstitution, store at room temperature and use within 21 days.¹

Parenteral

Injection, for IV Infusion

25°C (may be exposed to 15–30°C); do not freeze.¹ Protect from light.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Drug Compatibility

Admixture CompatibilityHID

Compatible
Aztreonam
Cefazolin sodium
Ceftazidime
Ciprofloxacin
Gentamicin sulfate
Levofloxacin
Ofloxacin
Tobramycin sulfate
Incompatible
Ceftriaxone sodium
Co-trimoxazole
Erythromycin lactobionate

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Alfentanil HCl
Amikacin sulfate
Amino acids 4.9%, dextrose 20%
Aminophylline
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Aztreonam
Bretylium tosylate
Buprenorphine HCl
Butorphanol tartrate
Calcium gluconate
Carboplatin
Cefazolin sodium
Cefotetan disodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Cimetidine HCl
Ciprofloxacin
Cisplatin
Clindamycin phosphate
Cyclophosphamide
Cyclosporine
Cytarabine
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Dextrose 5% in sodium chloride 0.45 or 0.9%
Dextrose 5% in water
Digoxin
Diphenhydramine HCl
Dobutamine HCl
Dopamine HCl
Doxorubicin HCl
Doxycycline hyclate
Droperidol
Enalaprilat
Esmolol HCl
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Fentanyl citrate
Fluconazole
Fluorouracil
Furosemide
Ganciclovir sodium
Gemcitabine HCl
Gentamicin sulfate
Granisetron HCl
Haloperidol lactate
Heparin sodium
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Ifosfamide
Imipenem–cilastatin sodium
Labetalol HCl
Leucovorin calcium
Levofloxacin
Lidocaine HCl
Lorazepam
Magnesium sulfate
Mannitol
Meperidine HCl
Meropenem
Mesna
Methotrexate sodium
Methylprednisolone sodium succinate
Metoclopramide HCl
Metronidazole
Midazolam HCl
Mitoxantrone HCl
Morphine sulfate
Nalbuphine HCl
Naloxone HCl
Nicardipine HCl
Nitroglycerin
Ofloxacin
Ondansetron HCl
Paclitaxel
Pentobarbital sodium
Phenobarbital sodium
Piperacillin sodium–tazobactam sodium
Potassium chloride
Prochlorperazine edisylate
Promethazine HCl
Propranolol HCl
Ranitidine HCl
Remifentanil HCl
Ringer’s injection
Ringer’s injection, lactated
Sodium bicarbonate
Sodium chloride 0.9%
Sufentanil citrate
Theophylline
Tobramycin sulfate
Vancomycin HCl
Vecuronium bromide
Verapamil HCl
Vincristine sulfate
Zidovudine
Incompatible
Amphotericin B
Chlorpromazine HCl
Diazepam
Pentamidine isethionate
Phenytoin sodium

Actions and Spectrum

• 
  

  Synthetic oxazolidinone anti-infective agent structurally unrelated to other anti-infectives commercially available in the US.^{1 2 3 4 5}

  
  


• 
  

  Acts early in bacterial translation; binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents formation of a functional 70S initiation complex.^{1 2 3}

  
  


• 
  

  Bacteriostatic against enterococci and staphylococci and bactericidal against most streptococci.^{1 2 4}

  
  


• 
  

  Active in vitro against vancomycin-resistant Enterococcus faecium.^{1 3} Although clinical importance unknown, also active in vitro against E. faecium (vancomycin-susceptible strains) and E. faecalis (including vancomycin-resistant strains).¹

  
  


• 
  

  Active in vitro against Staphylococcus aureus (including methicillin-resistant [oxacillin-resistant] strains), Streptococcus agalactiae (group B streptococci), S. pneumoniae (including MDRSP), and S. pyogenes (group A β-hemolytic streptococci).¹ Although clinical importance unknown, also active in vitro against S. epidermidis (including methicillin-resistant [oxacillin-resistant] strains), S. haemolyticus, viridans group streptococci, and Pasteurella multocida.¹

  
  


• 
  

  Resistant strains of E. faecium, E. faecalis, and S. aureus have emerged during linezolid therapy.¹

  
  


• 
  

  Cross-resistance between linezolid and other anti-infectives commercially available in the US is unlikely because of the drug’s unique mechanism of action.^{1 2 3}

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including linezolid) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.¹

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with linezolid or other antibacterials in the future.¹

  
  


• 
  

  Advise patients that linezolid may be taken orally without regard to meals.¹

  
  


• 
  

  If using the oral suspension, importance of not shaking the bottle vigorously and gently inverting the bottle 3–5 times to resuspend the drug prior to administration of each dose.¹

  
  


• 
  

  Advise patients of the potential risk of serotonin syndrome, particularly if linezolid is used concomitantly with MAO inhibitors, SSRIs, SNRIs, tricyclic antidepressants, or other serotonergic drugs.²⁸ Importance of immediately contacting clinician if signs and symptoms of serotonin syndrome develop (e.g., confusion, hyperactivity, memory problems, muscle twitching, excessive sweating, shivering, shaking, diarrhea, loss of coordination, fever).²⁸ Importance of not discontinuing serotonergic drugs without first consulting clinician.²⁸

  
  


• 
  

  Importance of avoiding excessive amounts of dietary tyramine (>100 mg per meal) during linezolid therapy.^{1 4}

  
  


• 
  

  Advise individuals with phenylketonuria that the oral suspension contains aspartame, which is metabolized in the GI tract to provide 20 mg of phenylalanine per 5 mL of suspension.^{1 4}

  
  


• 
  

  Importance of notifying clinician of any history of hypertension or seizures.¹

  
  


• 
  

  Importance of notifying clinician if any change in vision occurs.¹

  
  


• 
  

  Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹

  
  


• 
  

  Importance of informing cli