Linezolid is indicated for the treatment of the following infections:

• Nosocomial pneumonia
• Community-acquired pneumonia
• Complicated skin and skin structure infections, including diabetic foot infections without associated osteomyelitis
• Uncomplicated skin and skin structure infections
• Infections caused by vancomycin-resistant Enterococcus faecium

Limitations of Use: Linezolid is not indicated for the treatment of Gram-negative infections. The safety and effectiveness of Linezolid when used for longer than 28 days have not been established in controlled clinical trials.

Linezolid is a synthetic antibacterial agent belonging to the oxazolidinone class of antibiotics. It has in vitro activity against Gram-positive aerobic bacteria, some Gram-positive anaerobic bacteria, and certain Gram-negative bacteria. Linezolid works by selectively inhibiting bacterial protein synthesis through a mechanism that is different from other antibacterial agents. It binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of the functional 70S initiation complex, which is essential for bacterial protein translation. Time-kill studies have shown that Linezolid is bacteriostatic against enterococci and staphylococci. Against most strains of streptococci, it has been found to be bactericidal.

Linezolid tablets should be taken by oral route with or without food. Linezolid IV infusion should be administered by intravenous infusion over a period of 30 to 120 minutes. The recommended daily dosage for Linezolid tablets and IV infusion is described in the following table:

* Neonates less than 7 days: Most pre-term neonates less than 7 days of age (gestational age less than 34 weeks) have lower systemic linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg every 8 hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg every 8 hours by 7 days of life.

No dose adjustment is necessary when switching from intravenous to oral administration.

Intravenous administration: Linezolid IV infusion should be inspected visually against a light source for particulate matter prior to administration. Linezolid IV infusion may exhibit a yellow color that can intensify over time without adversely affecting potency. Do not use this intravenous infusion vial in series connections. Additives should not be introduced into this solution. Discard unused portion after single use.

Hepatic impairment: No dose adjustment is recommended for patients with mild-to-moderate hepatic impairment. The pharmacokinetics of Linezolid in patients with severe hepatic impairment have not been evaluated.

Use in children and adolescents: The dose of linezolid for children and adolescents have been described in dose and administration section. The use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended.

Drug interaction with medications: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase (MAO). Therefore, it may interact with adrenergic and serotonergic agents. Some patients receiving linezolid may experience a reversible increase in the pressor response to indirectly acting sympathomimetic agents, vasopressors, or dopaminergic agents. Unless patients are carefully monitored for signs and symptoms of serotonin syndrome, linezolid should not be given to patients with carcinoid syndrome or to those taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone.

Drug interaction with food and others: Patients should be advised to avoid consuming large amounts of food or beverages containing high levels of tyramine while taking linezolid.

Linezolid formulations are contraindicated in patients with known hypersensitivity to linezolid or to any of the components of the product. Linezolid should not be used in patients taking any medicinal product that inhibits monoamine oxidase A or B (for example, phenelzine or isocarboxazid), or within two weeks of taking such medications. Linezolid should also not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, or to those taking directly or indirectly acting sympathomimetic agents (such as pseudoephedrine), vasopressor agents (such as epinephrine or norepinephrine), dopaminergic agents (such as dopamine or dobutamine), serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone.

Most adverse events reported with linezolid are mild to moderate in severity. The most commonly reported adverse effects include diarrhea, headache, and nausea. Other reported adverse events include oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Pregnancy: Available data on the use of linezolid in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Linezolid is present in breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for linezolid and any potential adverse effects on the breastfed infant from linezolid or from the mother’s underlying condition. Lactating mothers should be advised to monitor the breastfed infant for diarrhea and vomiting.

Complete blood counts should be monitored weekly in patients receiving linezolid, especially in those who are treated for more than two weeks, those with pre-existing myelosuppression, those taking concomitant drugs that may cause bone marrow suppression, or those with chronic infections who have previously received or are currently receiving antibiotic therapy. If patients develop symptoms of visual impairment, such as changes in visual acuity, color vision changes, blurred vision, or visual field defects, prompt ophthalmic evaluation is recommended. Linezolid is not approved and should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections. A careful medical history is necessary because Clostridium difficile-associated diarrhea (CDAD) has been reported up to two months after antibiotic use. If CDAD is suspected or confirmed, ongoing antibiotic therapy not directed against C. difficile may need to be discontinued. Unless patients are monitored for possible increases in blood pressure, linezolid should not be given to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, or to those taking sympathomimetic agents, vasopressor agents, or dopaminergic agents. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or low bicarbonate levels while receiving linezolid should receive immediate medical evaluation. If hypoglycemia occurs, a reduction in the dose of insulin or oral hypoglycemic agents, or discontinuation of insulin, oral hypoglycemic agents, or linezolid may be required.

Overdose Effects No cases of linezolid overdose have been reported. In the event of overdose, symptomatic and supportive treatment is recommended, along with maintenance of glomerular filtration. Approximately 30% of a linezolid dose is removed خلال 3 hours of hemodialysis. There are no available data regarding the removal of linezolid by peritoneal dialysis or hemoperfusion.

Macrolides

Linezolid formulations should be stored at room temperature, between 15°C and 30°C, protected from light and moisture. Keep all medicines out of the reach of children.