Linezolid

Antibiotic Class:

Oxazolidinone  

Antimicrobial Activitity:

Mainly active against gram-positive organisms.

Mechanism of Action:

Inhibition of bacterial ribosomal protein synthesis by binding to the 23S portion of the 50S ribosomal subunit.

Pharmacodynamics:

The percentage of time the concentration of the drug is greater than the MIC of the organism (%T>MIC) and area under the plasma concentration-time curve to MIC ratio (AUC/MIC) have shown to be correlated with outcomes.

Pharmacokinetics: (600mg I.V. dose)

Cmax: 15.1mg/L; Half-life: 4.8 hours; Clearance (total): 123ml/min

Adverse Effects:

Hematologic: myelosuppression (reversible) thrombocytopenia (most common), anemia, leukopenia

Lactic acidosis

Peripheral neuropath, optic neuropathy

Serotonin syndrome from interaction with SSRI antidepressants

GI: Nausea

Other: Headache

Dosage:

Intravenous:

Premixed bags with latex free ports as 600mg/300ml, 400mg/200ml, and 200mg/100ml

Oral:

Tablets as 400 and 600mg strengths.

Powder for reconstitution oral suspension as100mg/5ml, total volume 150ml. Orange flavored.

Adults:

VRE and MRSA infections, nosocomial or community acquired pneumonia, complicated skin and skin structure infections: 600mg IV or PO every 12 hours

Uncomplicated skin and skin structure infections: 400mg IV or PO every 12 hours

Pediatrics:

Pediatric dosing regimen that provide a pharmacokinetic profile similar to adults have not been determined. However, 10mg/kg three times daily may be effective based on previous studies in patients aged 3 months to 16 years of age.

Disease state based dosing:

Hepatic failure: No dosage adjustment for patients with mild to moderate hepatic insufficiency is necessary. In patients with severe hepatic insufficiency (Childs-Pugh class C) the pharmacokinetics have not been evaluated.

Renal failure: No dosage adjustment necessary.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 600mg q12h

CVVHD (Continuous venovenous hemodialysis): 600mg q12h

CVVHDF (Continuous venovenous hemodiafiltration) 600mg q12h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Linezolid is a weak, non-selective, reversible inhibitor of monoamine oxidase. Therefore linezolid has the potential to interact with adrenergic and serotonergic agents. Also, an exaggerated pressor response may be seen with the ingestion of foods high in tyramine content. Ingestion of more than 100mg of tyramine at a single meal should be avoided.

Drug Interactions:

Linezolid does not interact with cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. No drug interactions with the CYP450 system are expected.

Pregnancy:

Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements:

In patients receiving linezolid, weekly complete blood counts with differential are recommended to monitor for myelosuppression related adverse events, particularly in those that receive the drug for greater than 2 weeks.

Brand names/Manufacturer:

Zyvox/Pfizer pharmaceuticals

Zyvoxam

Zyvoxid