Pronunciation:

(li NE zoh lid)

U.S. Brand Names:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Lactic acidosis has been reported with use. Patients who develop recurrent nausea and vomiting, unexplained acidosis, or low bicarbonate levels need immediate evaluation.

Linezolid has mild MAO inhibitor properties and has the potential to have the same interactions as other MAO inhibitors; use with caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism; avoid use with serotonergic agents such as TCAs, venlafaxine, trazodone, sibutramine, meperidine, dextromethorphan, and SSRIs; consider alternatives before initiating outpatient treatment (unnecessary use may lead the development of resistance to linezolid)

Adverse Reactions:

1% to 10%:

Cardiovascular: Hypertension (1% to 3%)

Central nervous system: Headache (0.5% to 11%), insomnia (3%), dizziness (0.4% to 2%), fever (2%)

Dermatologic: Rash (2%)

Gastrointestinal: Nausea (3% to 10%), diarrhea (3% to 11%), vomiting (1% to 4%), constipation (2%), taste alteration (1% to 2%), tongue discoloration (0.2% to 1%), oral moniliasis (0.4% to 1%), pancreatitis

Genitourinary: Vaginal moniliasis (1% to 2%)

Hematologic: Thrombocytopenia (0.3% to 10%), anemia, leukopenia, neutropenia; Note: Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia; may be more common in patients receiving linezolid for >2 weeks)

Hepatic: Abnormal LFTs (0.4% to 1%)

Miscellaneous: Fungal infection (0.1% to 2%)

<1%: C. difficile-related complications, increase in creatinine, dyspepsia, localized abdominal pain, pruritus

Postmarketing and/or case reports: Lactic acidosis, peripheral neuropathy, optic neuropathy

Overdosage/Toxicology:

Drug Interactions:

Adrenergic agents (eg, phenylpropanolamine, pseudoephedrine, sympathomimetic agents, vasopressor or dopaminergic agents) may cause hypertension.

Myelosuppressive medications: Concurrent use may increase risk of myelosuppression with linezolid.

Serotonergic agents (eg, TCAs, venlafaxine, trazodone, sibutramine, meperidine, dextromethorphan, and SSRIs) may cause a serotonin syndrome (eg, hyperpyrexia, cognitive dysfunction) when used concomitantly.

Tramadol: Concurrent use may increase risk of seizures.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may contain tyramine, hypertensive crisis may result).

Food: Avoid foods (eg, cheese) and beverages containing tyramine in patients receiving linezolid (hypertensive crisis may result).

Stability:

Infusion: Store at 25°C (77°F). Protect from light. Keep infusion bags in overwrap until ready for use. Protect infusion bags from freezing.

Oral suspension: Following reconstitution, store at room temperature; use reconstituted suspension within 21 days

Compatibility:

Compatibility when admixed: Incompatible: Ceftriaxone

Y-site administration: Compatible: Amikacin, ampicillin, cytarabine, D5NS, D5W, heparin, LR, NS, ranitidine. Incompatible: Amphotericin B, chlorpromazine, diazepam, erythromycin, pentamidine, phenytoin, sulfamethoxazole/trimethoprim

Mechanism of Action:

Pharmacodynamics/Kinetics:

Absorption: Rapid and extensive

Distribution: Vdss: Adults: 40-50 L

Protein binding: Adults: 31%

Metabolism: Hepatic via oxidation of the morpholine ring, resulting in two inactive metabolites (aminoethoxyacetic acid, hydroxyethyl glycine); does not involve CYP

Bioavailability: 100%

Half-life elimination: Children 1 week (full-term) to 11 years: 1.5-3 hours; Adults: 4-5 hours

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

Excretion: Urine (30% as parent drug, 50% as metabolites); feces (9% as metabolites)

Nonrenal clearance: 65%; increased in children 1 week to 11 years

Dosage:

VRE infections: Oral, I.V.:

Preterm neonates (<34 weeks gestational age): 10 mg/kg every 12 hours; neonates with a suboptimal clinical response can be advanced to 10 mg/kg every 8 hours. By day 7 of life, all neonates should receive 10 mg/kg every 8 hours.

Infants (excluding preterm neonates <1 week) and Children 11 years: 10 mg/kg every 8 hours for 14-28 days

Children 12 years and Adults: 600 mg every 12 hours for 14-28 days

Nosocomial pneumonia, complicated skin and skin structure infections, community acquired pneumonia including concurrent bacteremia: Oral, I.V.:

Infants (excluding preterm neonates <1 week) and Children 11 years: 10 mg/kg every 8 hours for 10-14 days

Children 12 years and Adults: 600 mg every 12 hours for 10-14 days

Uncomplicated skin and skin structure infections: Oral:

Infants (excluding preterm neonates <1 week) and Children <5 years: 10 mg/kg every 8 hours for 10-14 days

Children 5-11 years: 10 mg/kg every 12 hours for 10-14 days

Children 12-18 years: 600 mg every 12 hours for 10-14 days

Adults: 400 mg every 12 hours for 10-14 days

Elderly: No dosage adjustment required

Dosage adjustment in renal impairment: No adjustment is recommended. The two primary metabolites may accumulate in patients with renal impairment but the clinical significance is unknown. Weigh the risk of accumulation of metabolites versus the benefit of therapy. Both linezolid and the two metabolites are eliminated by dialysis. Linezolid should be given after hemodialysis.

Dosage adjustment in hepatic impairment: No dosage adjustment required for mild to moderate hepatic insufficiency (Child-Pugh Class A or B). Use in severe hepatic insufficiency has not been adequately evaluated.

Administration:

I.V.: Administer intravenous infusion over 30-120 minutes. Do not mix or infuse with other medications. When the same intravenous line is used for sequential infusion of other medications, flush line with D5W, NS, or LR before and after infusing linezolid. The yellow color of the injection may intensify over time without affecting potency.

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

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Oral/I.V.: You may experience GI discomfort, nausea, vomiting, taste alteration (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); mild headache (analgesic may help); or constipation (increase exercise, fluids, fruit, or fiber may help). Report immediately unresolved, liquid diarrhea; white plaques in mouth; skin rash or irritation; acute headache, dizziness, blurred vision; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Anesthesia and Critical Care Concerns/Other Considerations:

Cardiovascular Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Infusion [premixed]: 200 mg (100 mL) [contains sodium 1.7 mEq]; 400 mg (200 mL) [contains sodium 3.3 mEq]; 600 mg (300 mL) [contains sodium 5 mEq]

Powder for oral suspension: 20 mg/mL (150 mL) [contains phenylalanine 20 mg/5 mL, sodium benzoate, and sodium 0.4 mEq/5 mL; orange flavor]

Tablet: 400 mg, 600 mg [each strength contains sodium 0.1 mEq/tablet]

International Brand Names: