LINEZOLID (Generic for ZYVOX)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Tuberculosis patients*
-Concomitant pyridoxine is recommended.
-Directly observed therapy (DOT) is recommended for all children as well as adolescents living with HIV.

Route-Specific Administration

Oral Administration
-Administer without regard to food.
Oral Liquid Formulations
-Before using, gently mix the constituted suspension well by turning the bottle gently upside down 3 or 5 times; do not shake the bottle before administration.
-Administer using a calibrated measuring device.

Reconstitution of the oral suspension

-Review the manufacturer's reconstitution instructions for the particular product and package size; the amount of water to be used for reconstitution may vary between manufacturers.
-Prior to reconstitution, tap the bottle several times to loosen the powder.
-Add approximately half of the total amount of water needed and shake well. Add the remaining water and shake well.
-Storage: The prepared oral suspension may be kept at controlled room temperature, protected from light, for 21 days without significant loss of potency. Discard any unused suspension after 21 days.



Injectable Administration
-Visually inspect parenteral products for leaks, particulate matter and discoloration prior to administration whenever solution and container permit. A yellow color may intensify over time but does not affect the potency of linezolid.
Intravenous Administration
-Linezolid IV infusion is available in a concentration of 2 mg/mL as a premixed sterile IV infusion in ready-to-use plastic infusion bags; no further dilution is required.

Intermittent IV Infusion
-Do not use the infusion bag in series connections. Do not introduce additives into the linezolid infusion solution.
-Linezolid is physically and chemically incompatible with several drugs during simultaneous Y-site administration. If the same intravenous line is used for the sequential infusion of several medications, the line should be flushed before and after the linezolid infusion.
-Compatible intravenous solutions for line flushing include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer's Injection.
-Keep the linezolid dose in the overwrap protected from light until ready to use.
-Infuse the ordered linezolid dosage IV over 30 to 120 minutes.

The most common gastrointestinal adverse events reported in pediatric patients treated with linezolid in controlled trials were diarrhea (7.8-10.8%), nausea (1.9-3.7%), and vomiting (2.9-9.4%). These events were usually mild to moderate in intensity and limited in duration; however, in patients who develop severe diarrhea, antibiotic-associated colitis should be considered as part of the differential diagnosis. Other GI adverse events included localized abdominal pain (0.5-2.4%), generalized abdominal pain (0.9-2.4%), and loose stools (1.6-2.3%). Taste alteration (dysgeusia) was reported in approximately 1-2% of adult patients during clinical trials. Superficial tooth discoloration and tongue discoloration have been noted in post-marketing reports in children receiving oral and IV linezolid therapy ; however, in cases with a known outcome, the discoloration was removable with professional dental cleaning (manual descaling) and resolved within 1-2 months after linezolid discontinuation.

Headache is one of the most common non-gastrointestinal adverse effects associated with linezolid therapy. In pediatric clinical trials, headache was reported by 0.9-6.5% of patients, and in adult trials, up to 8.8% experienced headache. Vertigo (0-1.2%) was also reported in pediatric trials, and dizziness was reported in approximately 2-3% of adults during clinical trials. Convulsions (seizures) have been reported in patients treated with linezolid. In some cases, a history of seizures or risk factors for seizures may have been present.

Linezolid is a nonselective inhibitor of monoamine oxidase (MAO). Although the development of new onset hypertension (outside of the setting of a drug-interaction) is not included in the FDA-approved product labeling as an adverse reaction to linezolid therapy, there is a theoretical risk for an increase in systolic blood pressure due to the presence of higher levels of circulating endogenous catecholamines (e.g., norepinephrine) caused by MAO inhibition. Hypertension was reported in phase II and phase III controlled studies of linezolid in adults (incidence not reported). However, linezolid was not studied in patients with uncontrolled hypertension or with other conditions that would make them more susceptible to the side effects of MAO inhibition. Certain medications, like adrenergic agents or sympathomimetics, when used concomitantly with linezolid, may increase the risk for clinically significant drug-induced hypertension or palpitations. Such medications should be avoided when possible. If vasopressor drugs like dopamine, dobutamine, or epinephrine must be used concomitantly with linezolid, reduced initial dosages of the pressor agents, along with careful monitoring and titration to achieve the desired response will be necessary. Also, the amount of tyramine ingested in the diet should be limited.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with linezolid. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Candidiasis may occur as oral candidiasis (0.5% to 1.7% adults) or vaginal candidiasis (1.1% to 1.8% adults). General fungal infection (0.3% to 1.5% adults) has also been reported.

Thrombocytopenia has been reported with linezolid therapy (0% to 12.9%); however, the incidence has been similar or less than that seen with comparators (i.e., vancomycin, cefadroxil) in clinical trials. Thrombocytopenia associated with linezolid appears to be more common in patients who receive therapy for more than 2 weeks and in patients with severe renal impairment (regardless of dialysis) or moderate to severe hepatic impairment; most platelet counts return to normal or baseline upon drug discontinuation. While no related clinical events were noted in controlled phase III trials, bleeding events were reported in thrombocytopenic patients receiving linezolid during compassionate use protocols. In pediatric clinical trials, anemia (0% to 5.6%), eosinophilia (0.4% to 1.9%), abnormal hemoglobin (0% to 15.7%), abnormal WBC counts (0.8% to 12.4%), and abnormal neutrophils (1.2% to 5.9%) were also reported. Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) and sideroblastic anemia have been reported in postmarketing surveillance. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward baseline levels. Vitamin B6 (pyridoxine) may be useful for preventing and reversing linezolid-induced cytopenias. Monitor complete blood counts weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than 2 weeks, those with pre-existing bone marrow suppression, those with severe renal impairment, those with moderate or severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with chronic infection who have received previous or concomitant antibacterial drug therapy. Consider discontinuing linezolid in patients who develop or have worsening myelosuppression.

Peripheral neuropathy and optic neuropathy have been reported in patients treated with linezolid, including in children. Eight cases of peripheral and/or optic neuropathy were reported in pediatric patients. In these cases, treatment duration ranged from 4 weeks to 1 year. In the cases with reported outcomes, symptom resolution occurred between 2 weeks and 6 months after linezolid discontinuation. Although these postmarketing reports have primarily been in patients who received longer than the maximum recommended duration of 28 days, these events (i.e., blurred vision) have also been reported in patients receiving shorter courses of linezolid. Optic neuritis, sometimes progressing to loss of vision, has also been reported during linezolid therapy; patients with loss of vision were treated for more than 28 days. Monitor visual function in all patients taking linezolid for extended periods (3 months or more), in all patients reporting new visual symptoms regardless of length of linezolid therapy, and in all patients receiving linezolid as part of combination therapy for tuberculosis. If patients experience symptoms of visual impairment, regardless of length of therapy, prompt ophthalmic evaluation is recommended. If peripheral or optic neuropathy occurs, the continued use of linezolid in these patients should be weighed against the potential risks. Neuropathy occurs more frequently in persons living with HIV and those with diabetes, alcoholism, malnutrition, and chronic renal failure. Concomitant administration of pyridoxine is recommended in these patients to reduce the risk of neurotoxicity.

Serotonin syndrome, including fatal cases, has been reported in patients receiving linezolid with serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs). If concurrent use is required, ensure that the patient is closely monitored for signs and/or symptoms of serotonin syndrome. Monitoring is also recommended for those patients who discontinued a serotonergic agent in order to initiate linezolid therapy; monitor for 2 weeks (5 weeks if fluoxetine was taken) or until 24 hours after the last dose of linezolid, whichever comes first. If serotonin syndrome or neuroleptic malignant syndrome-like symptoms occur, such as autonomic instability, cognitive dysfunction (extreme agitation, delirium, coma), hyperthermia, myoclonus, and rigidity, it is recommended to discontinue the offending drug(s) and provide supportive care.

Lactic acidosis has occurred with linezolid use. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate concentration while receiving linezolid should receive immediate medical evaluation. In one case series, lactic acidosis was reported in 3 pediatric patients (6 months to 16 years of age) with hepatic dysfunction. In 1 case, lactic acidosis developed after 6 days of linezolid; the other cases were receiving prolonged therapy (approximately 4 weeks or longer). Lactate concentrations ranged from 6.1 to 24 mEq/L. In these cases, repeated episodes of nausea and vomiting were not reported. Other abnormal laboratory values reported in pediatric clinical trials included elevated hepatic enzymes (ALT, 0% to 10.1%), lipase (0.4%), amylase (0.6%), total bilirubin (6.3%), and serum creatinine (0.4% to 2.4%).

Hypersensitivity or skin and soft tissue reactions have been reported with linezolid. Pruritus was reported in 0.8% to 1.4% of patients during pediatric clinical trials, and rash was reported in approximately 1% to 2% of adults during clinical trials. Anaphylaxis (anaphylactoid reactions, anaphylactic shock), angioedema, bullous skin disorders (bullous rash), including severe cutaneous adverse reactions (SCAR), such as toxic epidermal necrolysis and Stevens-Johnson syndrome, and hypersensitivity vasculitis have been reported in postmarketing surveillance.

Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid. Cases have been reported in patients with diabetes receiving therapy. If hypoglycemia occurs, a decrease in the dose of insulin or hypoglycemic agent may be necessary. Discontinuation of these agents or linezolid may be required in some patients.

Linezolid may lead to vitamin B6 deficiency. Supplementation with vitamin B6 is recommended in patients taking linezolid for tuberculosis.

Postmarketing cases of hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been observed in patients treated with linezolid. Signs and symptoms included confusion, somnolence, generalized weakness, and in severe cases led to respiratory failure and death. Discontinue linezolid with any signs or symptoms of hyponatremia and/or SIADH and instituted appropriate supportive measures.

Linezolid is contraindicated in patients who have known hypersensitivity to linezolid or any of the other product components. Linezolid oral suspension contains phenylalanine, a component of aspartame. Before prescribing linezolid oral suspension to a patient with phenylketonuria, consider the combined daily amount of phenylalanine from all sources, including linezolid oral suspension. Other linezolid formulations do not contain phenylalanine.

Myelosuppression or bone marrow suppression, including anemia, leukopenia, pancytopenia, and thrombocytopenia, has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment concentrations. Thrombocytopenia has been reported more often in patients with severe renal impairment, regardless of dialysis, and in patients with moderate to severe hepatic impairment. Monitor complete blood counts weekly in patients who receive linezolid, particularly those who receive linezolid for longer than 2 weeks, those with pre-existing bone marrow suppression, those with severe renal impairment, those with moderate or severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with chronic infection who have received previous or concomitant antibacterial drug therapy. Consider discontinuing linezolid in patients who develop or have worsening myelosuppression.

Unless patients are monitored for potential increases in blood pressure, do not administer linezolid to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or patients taking directly and indirectly acting sympathomimetic agents, vasopressive agents, or dopaminergic agents. Unless clinically appropriate and patients are carefully observed for signs and/or symptoms of serotonin syndrome or neuroleptic malignant syndrome-like (NMS-like) reactions, do not administer linezolid to patients with carcinoid syndrome and/or patients taking serotonin re-uptake inhibitors, tricyclic antidepressants, bupropion, buspirone, serotonin 5-HT1 receptor agonists (triptans), or opioids.

Linezolid is a reversible, nonselective monoamine oxidase inhibitor (MAOI) and is contraindicated in patients receiving MAOI therapy or who have received an MAOI within the previous 14 days.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including linezolid, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Monitor visual function in all patients taking linezolid for extended periods (3 months or more), in all patients reporting new visual symptoms regardless of length of linezolid therapy, and in all patients receiving linezolid as part of combination therapy for tuberculosis. Peripheral and optic neuropathies have been reported in patients treated with linezolid, primarily in those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Persons living with human immunodeficiency virus (HIV) infection, as well as those with diabetes, alcoholism, malnutrition, chronic renal failure, and advanced age, may be predisposed to developing neuropathy. Concomitant pyridoxine is recommended in any patient receiving linezolid for tuberculosis and at risk for peripheral neuropathy.

While a causal relationship between linezolid and hypoglycemia has not been established, caution patients with diabetes mellitus of potential hypoglycemic reactions when treated with linezolid. Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents when treated with linezolid, a reversible, nonselective monoamine oxidase inhibitor (MAOI). Some MAOIs have been associated with hypoglycemic episodes in diabetic patients receiving insulin or hypoglycemic agents. Patients with diabetes mellitus may be predisposed to developing neuropathy. Concomitant pyridoxine is recommended in any patient receiving linezolid for tuberculosis and at risk for peripheral neuropathy.

Convulsions have been reported in patients when treated with linezolid. In some of these cases, a history of seizure disorder or risk factors for seizures was reported.

Monitor serum sodium concentrations regularly in patients at risk for hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH), including those taking diuretics during linezolid therapy. Postmarketing cases of hyponatremia and/or SIADH have been observed in patients treated with linezolid.

Description: Linezolid is one drug in a relatively new class of synthetic antibiotics known as fluorinated oxazolidinones. Linezolid is a non-selective inhibitor of monoamine oxidase (MAO), a property that has implications for medication safety and drug interactions. Linezolid is indicated for gram-positive infections and is approved for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and skin and skin structure infections, and for vancomycin-resistant enterococcal (VRE) infections, including infections complicated by bacteremia. The drug provides an alternative to vancomycin, particularly in inpatient settings. In an open-label, randomized study in adult patients with catheter-related bloodstream infections including catheter-site infections, higher mortality was noted with linezolid-treated patients compared with other agents (vancomycin, oxacillin, and dicloxacillin). The chance of death was related to the causative organism. In the linezolid arm, mortality was higher in patients infected with gram negative bacteria alone, in patients infected with both gram positive and gram negative bacteria, and in patients who had no observed infection when enrolled in the study. No difference in mortality was noted in linezolid-treated patients with only gram positive infections. Linezolid is not approved for treating gram-negative infections, catheter-related bloodstream infections, or catheter-site infections. The significance of these findings in the pediatric population is unknown. Linezolid is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Enterococcus faecalis, Enterococcus faecium, Pasteurella multocida, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of bacteremia and sepsis due to vancomycin-resistant enterococci (VRE) or methicillin-resistant S. aureus (MRSA)*:
-for the treatment of bacteremia due to vancomycin-resistant enterococci (VRE):
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for 14 to 28 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for 14 to 28 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for 14 to 28 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 14 to 28 days.
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 14 to 28 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 14 to 28 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 14 to 28 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 14 to 28 days.
-for the treatment of sepsis due to vancomycin-resistant enterococci (VRE) or methicillin-resistant S. aureus (MRSA)*:
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. Guidelines recommend linezolid as an alternative to vancomycin for neonatal MRSA sepsis in patients with non-endovascular infections.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours. Guidelines recommend linezolid as an alternative to vancomycin for neonatal MRSA sepsis in patients with non-endovascular infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope. Guidelines recommend linezolid as an alternative to vancomycin for neonatal MRSA sepsis in patients with non-endovascular infections.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia, and nosocomial pneumonia:
-for the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response. The FDA-approved duration is 10 to 14 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response. The FDA-approved duration is 10 to 14 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
-for the treatment of nosocomial pneumonia:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response. The FDA-approved duration is 10 to 14 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response. The FDA-approved duration is 10 to 14 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for at least 7 days. The FDA-approved duration is 10 to 14 days.

For the treatment of skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, and leg ulcer:
-for the treatment of uncomplicated, nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 5 to 14 days. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 5 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 5 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 to 12 hours for 5 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 5 to 14 days.
Intravenous dosage*:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for 5 to 14 days. Consideration may be given to the use of 10 mg/kg/dose IV every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for 5 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for 5 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 to 12 hours for 5 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 5 to 14 days.
-for the treatment of unspecified complicated skin infections:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 7 to 14 days. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 7 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 7 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 7 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 7 to 14 days.
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for 7 to 14 days. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for 7 to 14 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for 7 to 14 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for 7 to 14 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 7 to 14 days.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections. Consideration may be given to the use of 10 mg/kg/dose IV every 8 hours in those with a sub-optimal clinical response.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, and infectious bursitis*:
-for the treatment of osteomyelitis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants and Children 3 months to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants and Children 3 months to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants and Children 3 months to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 10 mg/kg/dose PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants and Children 3 months to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
-for the treatment of infectious bursitis* due to methicillin-resistant S. aureus:
Intravenous dosage:
Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Oral dosage:
Children 1 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

For the treatment of central nervous system infections*, including meningitis*, ventriculitis*, brain abscess*, subdural empyema*, spinal epidural abscess*, and septic thrombosis of the cavernous or dural venous sinus*:
Intravenous dosage:
Neonates: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Infants and Children 1 to 11 years: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Children and Adolescents 12 to 17 years: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg IV every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Oral dosage:
Neonates: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Infants and Children 1 to 11 years: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.
Children and Adolescents 12 to 17 years: The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg PO every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

For the treatment of infective endocarditis*:
NOTE: Linezolid is recommended as a treatment option for endocarditis caused by E. faecium strains resistant to penicillin, aminoglycosides, and vancomycin; however, data are limited in pediatric patients.
Intravenous dosage:
Neonates: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours.
Infants and Children 1 to 11 years: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose).
Children and Adolescents 12 to 17 years: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg IV every 12 hours.
Oral dosage:
Neonates: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours.
Infants and Children 1 to 11 years: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose).
Children and Adolescents 12 to 17 years: Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg PO every 12 hours.

For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
-for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
-for the treatment of systemic anthrax* without aerosol exposure, including those with signs and symptoms of meningitis, as part of combination therapy:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Children and Adolescents 12 to 17 years: 15 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
-for the treatment of systemic anthrax* with aerosol exposure, including those with signs and symptoms of meningitis, as part of a combination therapy:
Intravenous dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Children and Adolescents 12 to 17 years: 15 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy.
Immunocompromised Children and Adolescents 12 to 7 years: 15 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for at least 14 days; may consider step-down to oral therapy. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset.
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for at least 14 days. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset. Oral therapy is not recommended with signs and symptoms of meningitis.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for at least 14 days. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset. Oral therapy is not recommended with signs and symptoms of meningitis.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for at least 14 days. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset. Oral therapy is not recommended with signs and symptoms of meningitis.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Immunocompromised Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 14 days. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset. Oral therapy is not recommended with signs and symptoms of meningitis.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 14 days; oral therapy is not recommended with signs and symptoms of meningitis.
Immunocompromised Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 14 days. Transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course from illness onset. Oral therapy is not recommended with signs and symptoms of meningitis.

For the treatment of drug-resistant tuberculosis infection*, including multidrug-resistant tuberculosis infection (MDR-TB)* and extensively drug-resistant tuberculosis infection (XDR-TB)*, as part of combination therapy:
Oral dosage:
Infants and Children 1 to 11 years weighing less than 10 kg: 15 mg/kg/dose PO once daily.
Infants and Children 1 to 11 years weighing 10 to 14 kg: 12 to 15 mg/kg/dose PO once daily.
Children 1 to 11 years weighing 15 kg or more: 10 to 12 mg/kg/dose (Max: 600 mg/dose) PO once daily.
Children and Adolescents 12 to 17 years: 10 to 12 mg/kg/dose (Max: 600 mg/dose) PO once daily.
Intravenous dosage:
Infants and Children 1 to 11 years weighing less than 10 kg: 15 mg/kg/dose IV once daily
Infants and Children 1 to 11 years weighing 10 to 14 kg: 12 to 15 mg/kg/dose IV once daily.
Children 1 to 11 years weighing 15 kg or more: 10 to 12 mg/kg/dose (Max: 600 mg/dose) IV once daily.
Children and Adolescents 12 to 17 years: 10 to 12 mg/kg/dose (Max: 600 mg/dose) IV once daily.

For the treatment of intraabdominal infections*, including peritonitis*, appendicitis, intraabdominal abscess*, peritoneal dialysis-related peritonitis*, and peritoneal dialysis catheter-related infection*:
-for the treatment of complicated healthcare-acquired or hospital-acquired intraabdominal infections* with adequate source control:
Oral dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours as part of combination therapy for 7 to 10 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 400 mg/dose) PO every 8 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Intravenous dosage:
Neonates younger than 34 weeks gestation and 0 to 6 days: 10 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days.
Neonates younger than 34 weeks gestation and 7 days and older: 10 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days.
Neonates 34 weeks gestation and older: 10 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days.
Infants and Children 1 to 11 years: 10 mg/kg/dose (Max: 400 mg/dose) IV every 8 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of peritoneal dialysis-related peritonitis*:
Oral dosage:
Infants and Children 1 month to 4 years: 10 mg/kg/dose PO every 8 hours for 14 to 21 days.
Children 5 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 14 to 21 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 14 to 21 days.
Intravenous dosage:
Infants and Children 1 month to 4 years: 10 mg/kg/dose IV every 8 hours for 14 to 21 days.
Children 5 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for 14 to 21 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 14 to 21 days.
-for the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage:
Infants and Children 1 month to 4 years: 10 mg/kg/dose PO every 8 hours for at least 14 to 28 days.
Children 5 to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for at least 14 to 28 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for at least 14 to 28 days.

For the treatment of acute exacerbations of bronchiectasis*:
Oral dosage:
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 14 days.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 14 days.
Intravenous dosage:
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for 14 days.
Children and Adolescents 12 to 17 years: 600 mg IV every 12 hours for 14 days.

For postexposure of anthrax prophylaxis*:
-for postexposure anthrax prophylaxis* after nonaerosol exposure (cutaneous or ingestion):
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 7 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 7 days after exposure.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 7 days after exposure.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 7 days after exposure.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 7 days after exposure.
-for postexposure anthrax prophylaxis* after aerosol exposure:
Oral dosage:
Neonates 32 to 33 weeks gestation and 0 to 6 days: 10 mg/kg/dose PO every 12 hours for 60 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 10 mg/kg/dose PO every 8 hours for 60 days after exposure.
Neonates 34 weeks gestation and older: 10 mg/kg/dose PO every 8 hours for 60 days after exposure.
Infants and Children 1 month to 11 years: 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 60 days after exposure.
Children and Adolescents 12 to 17 years: 600 mg PO every 12 hours for 60 days after exposure.

Maximum Dosage Limits:
-Neonates
Premature Neonates younger than 34 weeks gestation and 0 to 7 days: 20 mg/kg/day PO/IV.
Premature Neonates younger than 34 weeks gestation 8 days and older: 30 mg/kg/day PO/IV.
Neonates 34 weeks gestation and older: 30 mg/kg/day PO/IV.
-Infants
30 mg/kg/day PO/IV.
-Children
1 to 11 years: 30 mg/kg/day (Max: 1,800 mg/day) PO/IV.
12 years: 1,200 mg/day PO/IV.
-Adolescents
1,200 mg/day PO/IV.

Patients with Hepatic Impairment Dosing
No dosage adjustment is recommended in mild to moderate hepatic insufficiency (Child-Pugh class A or B). Linezolid has not been studied in severe hepatic dysfunction.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Intermittent hemodialysis
Administer linezolid after hemodialysis on dialysis days. Linezolid and its metabolites are removed by hemodialysis. About 30% of a linezolid dose is eliminated in a 3-hour hemodialysis session.

No dosage adjustment is needed in pediatric patients receiving the adult dosage. For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.

Peritoneal dialysis
No dosage adjustment is necessary in pediatric patients receiving the adult dosage. For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.

Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.

No dosage adjustment is needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Oxazolidinones exhibit a mechanism of action that is different from other antimicrobial classes. Linezolid inhibits bacterial protein synthesis by interfering with translation. Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit; this action prevents the formation of a functional 70S initiation complex, an essential step in the bacterial translation process. Without proper protein production, susceptible bacteria cannot multiply. The action of linezolid is considered to be bacteriostatic against staphylococci and enterococci. Linezolid appears to be bactericidal against the majority of streptococcal strains tested. The predominant activity of linezolid is against aerobic gram-positive organisms. Linezolid exhibits little activity against aerobic gram-negative organisms or anaerobes in vitro; combination with other antimicrobial therapies may be clinically indicated if presumptive or documented pathogens include gram-negative or anaerobic bacteria.

The susceptibility interpretive criteria for linezolid are delineated by pathogen. The MICs are defined for Staphylococcus sp. as susceptible at 4 mcg/mL or less and resistant at 8 mcg/mL or more. The MICs are defined for Enterococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL and resistant at 8 mcg/mL or more. The MICs are defined for S. pneumoniae, beta-hemolytic Streptococcus sp., S. viridans group, Aerococcus sp., and Corynebacterium sp. as susceptible at 2 mcg/mL or less. The MICs are defined for Lactobacillus sp. as susceptible at 4 mcg/mL or less.

Linezolid is also a reversible, non-selective inhibitor of monoamine oxidase (MAO).

Pharmacokinetics: Linezolid is administered by intravenous infusion or orally. Oral bioavailability is 100% resulting in the ability for the IV and tablet formulations to be used interchangeably without the need to make dose adjustments. Linezolid is widely distributed to well-perfused tissues, including skin, bones, muscles, adipose tissues, extracellular lung fluid, and cerebrospinal fluid. Plasma protein binding is low (i.e., roughly 31%). In healthy adults, the volume of distribution is 40-50 L.

Linezolid is metabolized via oxidation of the morpholine ring, which results in two inactive carboxylic acid metabolites: aminoethoxyacetic acid (metabolite A) and hydroxyethyl glycine (metabolite B). Metabolite A is presumed to be formed via an enzymatic pathway, while formation of metabolite B is mediated by a non-enzymatic chemical oxidation mechanism in vitro. Approximately 30% of the dose appears unchanged in the urine, 40% as metabolite B, and 10% as metabolite A. The net renal clearance of linezolid is low and is suggestive of net renal tubular reabsorption. Virtually no linezolid appears in the feces as unchanged drug, and the metabolites present in the feces only account for 9% of the total dose. The half-life of linezolid in children ranges from 1.5-5.6 hours compared to 4.26-5.4 hours in adults.

Affected cytochrome P450 isoenzymes: none
Linezolid is not an inducer of the CYP450 enzyme system in animals, nor does it inhibit the activities of clinically active human CYP450 isoenzymes (i.e., 1A2, 2C9, 2C19, 2D6, 2E1, 3A4). In vitro studies have demonstrated that linezolid is minimally metabolized and the metabolism may be mediated by the human CYP450 enzyme system; however, the metabolic pathway is not fully understood. A study showed decreased linezolid Cmax and AUC when administered with a strong inducer of the CYP450 enzyme system (i.e., rifampin). It is unknown whether the CYP450 induction was the reason for this decrease, but caution may be warranted when linezolid is coadministered with strong inducers.


-Route-Specific Pharmacokinetics
Oral Route
Peak concentrations are achieved 1-2 hours after oral administration. Food delays absorption slightly, but overall exposure is unaffected. The absolute bioavailability is 100%.

Intravenous Route
Peak concentrations are achieved 30 minutes after IV administration.


-Special Populations
Pediatrics
Pharmacokinetic studies of linezolid in children have revealed a similar Cmax (11-16.7 mcg/ml) and Vd (0.61-0.81 L/kg) regardless of age. However, clearance is variable and is age-dependent. Clearance is highest in children > 1 week to 11 years, leading to lower exposure (AUC) and a shorter elimination half-life in children compared with adults. Clearance decreases in adolescents and is similar to adult values.

Neonates
In pharmacokinetic studies, clearance values in preterm neonates < 34 weeks gestational age (< 1 week postnatal age), neonates >= 34 weeks gestational age (< 1 week postnatal age), and neonates >= 34 weeks gestational age (1-4 weeks postnatal age) were 2, 3.8, and 5.1 ml/min/kg, respectively. Corresponding elimination half-life values were 5.6, 3, and 1.5 hours, respectively.

Infants and Children
In pharmacokinetic studies, clearance values in infants (28 days to 3 months) and children (3 months to 11 years) were 5.4 and 3.8 ml/min/kg, respectively. Corresponding elimination half-life values were 1.8 and 2.9 hours, respectively.

Adolescents
In pharmacokinetic studies, clearance and elimination half-life in adolescents were 2.1 ml/min/kg and 4.1 hours, respectively, which are similar to values seen in adults.

Hepatic Impairment
The pharmacokinetics of linezolid in patients with mild-to-moderate hepatic impairment (Child-Pugh class A or B) are unaltered. The pharmacokinetics of linezolid have not been studied in patients with severe hepatic impairment.

Renal Impairment
The pharmacokinetics of the parent drug, linezolid, are unaltered in patients with renal impairment. The 2 primary metabolites of linezolid may accumulate in patients with renal impairment with the amount of accumulation increasing with severity of renal impairment. The clinical significance of this accumulation is unknown.