Linezolid

Background

• Oxazolidinone antibiotic

Mechanism of Action

• Inhibits the 50S ribosome of Gram-positive bacteria

Spectrum of Activity

• Active against Gram-positive bacteria
• Not active against Gram-negative bacteria

Dosing

• Linezolid 600 mg PO/IV q12h

Renal Dosing

• No adjustment needed

Safety

Adverse Drug Reactions

• Serotonin syndrome when taken concurrently with certain psychiatric medications
  • Ideally hold SSRIs when starting linezolid
• Cytopenias, including thrombocytopenia (most common), anemia, and leukopenia (least common)
  • More common with prolonged use, e.g. after 2 weeks
  • Likely more common with higher dose (600 mg versus 300 mg)

Long-Term Use

• The generally-recommended maximum therapy is 28 days
• However, linezolid is used in the treatment for MDR-TB in much longer courses
• The most common adverse effects were peripheral neuropathy (64%), myelosuppression (22%), optic neuritis (5%), GI effects (2%), and rash (2%)
• About 15% of patients had to permanently discontinue due to adverse effects
• Risk of adverse reactions increases with time
  • <10% at 2 weeks (for higher, standard dose)
  • 12% at 4 weeks
  • 20% at 8 weeks
  • 40% at 16 weeks
  • 55% at 32 weeks

Drug-Drug Interactions

• Coadminitration with rifampin decreases AUC and peak by 32 and 21%, respectively
• Increases warfarin INR
• Weak, reversible, nonselective MAO inhibitor, leading to a risk of serotonin syndrome if coadministered with other MAOIs (and may SSRIs)