NEODOSE

INDICATIONS

Limited to treatment of infections, including endocarditis and ventriculitis, caused by gram positive organisms (eg, methicillin-resistant Staph. aureus,, penicillin-resistant Strep. pneumoniae, and vancomycin-resistant Enterococcus faecium) that are refractory to conventional therapy with vancomycin and other antibiotics. Do not use as treatment or in any patient with infections caused by gram-negative organisms.

• Anthrax: Intravenous linezolid is recommended for neonates 32 week gestational age or older for the following:

CONTRAINDICATIONS

Contraindicated in patients with carcinoid syndrome, uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or patients receiving concurrent serotonergic agents, sympathomimetic agents, vasopressive agents, or dopaminergic agents unless monitored closely.

PRECAUTIONS

Use not recommended in pediatric patients with central nervous system (CSF) infections due to variable linezolid CSF concentrations. Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported. Symptomatic hypoglycemia has been reported in patients with diabetes receiving insulin. Serotonin syndrome may occur with concurrent use of serotonergic agents. Peripheral and optic neuropathy have been reported in pediatric patients, mainly in patients treated for longer than 28 days. Convulsions have been reported. Lactic acidosis has been reported in a case series of 3 children aged 6 months, 6 months, and 16 years receiving linezolid for 53, 31 and 7 days of treatment, respectively. All 3 children had liver dysfunction and complicated medical courses while receiving linezolid therapy. Two patients developed multiple system organ failure and metabolic acidosis, and the third patient developed pressor-refractory shock and metabolic acidosis. The role of linezolid in the development of lactic acidosis in these patients is unknown. Safety and efficacy of linezolid therapy for greater than 28 days has not been evaluated in controlled clinical trials.

The FDA issued an alert regarding Zyvox (linezolid) on March 16, 2007.

Patients in an open-label, randomized trial comparing linezolid with vancomycin, oxacillin, or dicloxacillin in the treatment of seriously ill patients with intravascular catheter-related bloodstream infections had a higher chance of death than did patients treated with any comparator antibiotic, and the chance of death was related to the type of organism causing the infection. Patients with Gram positive infections had no difference in mortality according to their antibiotic treatment. In contrast, mortality was higher in patients treated with linezolid who were infected with Gram negative organisms alone, with both Gram positive and Gram negative organisms, or who had no infection when they entered the study.

ADVERSE EFFECTS

Elevated transaminases and diarrhea occur in approximately 5% of treated patients; thrombocytopenia and anemia occur in 2% to 5%. Sideroblastic anemia and severe cutaneous adverse reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported during postmarketing surveillance.

ADMINISTRATION

• Intravenous: Give as an intermittent IV infusion over 30 to 120 minutes. Supplied as ready-to-use infusion bags (2 mg/mL); no further dilution is necessary
• Oral: May administer without regard to timing of feedings. Before administering oral suspension, gently mix by inverting bottle 3 to 5 times. Do not shake.

MONITORING

Monitor CBC weekly, especially in patients receiving linezolid for longer than 2 weeks, those with myelosuppression, those receiving concurrent myelosuppressive drugs, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Monitor lactate concentrations in patients receiving extended courses of linezolid therapy or in patients with pre-existing hepatic or renal dysfunction. Patients receiving an extended course of therapy (eg, over 28 days) should be monitored for signs and symptoms of neuropathy. Monitor for signs and symptoms of serotonin syndrome (hyperpyrexia, hyperreflexia, and incoordination) in patients receiving concomitant serotonergic agents. Visual function should be assessed in patients receiving long-term linezolid (3 months or greater) and in all patients experiencing visual impairment. Monitor blood pressure in patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or in patients receiving sympathomimetic agents, vasopressive agents, or dopaminergic agents.