Linezolid

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Background

  • Oxazolidinone antibiotic

Mechanism of Action

  • Inhibits the 50S ribosome of Gram-positive bacteria

Spectrum of Activity

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%)[1]
  • About 15% of patients had to permanently discontinue due to adverse effects
  • Risk of adverse reactions increases with time[2]
    • <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)
  1. Lan Z, Ahmad N, Baghaei P, Barkane L, Benedetti A, Brode SK, Brust JCM, Campbell JR, Chang VWL, Falzon D, Guglielmetti L, Isaakidis P, Kempker RR, Kipiani M, Kuksa L, Lange C, Laniado-Laborín R, Nahid P, Rodrigues D, Singla R, Udwadia ZF, Menzies D; Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment 2017. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet Respir Med. 2020 Apr;8(4):383-394. doi: 10.1016/S2213-2600(20)30047-3. Epub 2020 Mar 17. PMID: 32192585; PMCID: PMC7384398.
  2. Migliori GB, Eker B, Richardson MD, Sotgiu G, Zellweger JP, Skrahina A, Ortmann J, Girardi E, Hoffmann H, Besozzi G, Bevilacqua N, Kirsten D, Centis R, Lange C; TBNET Study Group. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J. 2009 Aug;34(2):387-93. doi: 10.1183/09031936.00009509. Epub 2009 Mar 12. PMID: 19282348.

References

  1. ^  Zhiyi Lan, Nafees Ahmad, Parvaneh Baghaei, Linda Barkane, Andrea Benedetti, Sarah K Brode, James C M Brust, Jonathon R Campbell, Vicky Wai Lai Chang, Dennis Falzon, Lorenzo Guglielmetti, Petros Isaakidis, Russell R Kempker, Maia Kipiani, Liga Kuksa, Christoph Lange, Rafael Laniado-Laborín, Payam Nahid, Denise Rodrigues, Rupak Singla, Zarir F Udwadia, Dick Menzies, N Ahmad, P Baghaei, L Barkane, A Benedetti, SK Brode, JCM Brust, JR Campbell, VWL Chang, D Falzon, L Guglielmetti, P Isaakidis, RR Kempker, M Kipiani, L Kuksa, Z Lan, C Lange, R Laniado-Laborín, P Nahid, D Rodrigues, R Singla, ZF Udwadia, D Menzies. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis. The Lancet Respiratory Medicine. 2020;8(4):383-394. doi:10.1016/s2213-2600(20)30047-3.
  2. ^  G. B. Migliori, B. Eker, M. D. Richardson, G. Sotgiu, J-P. Zellweger, A. Skrahina, J. Ortmann, E. Girardi, H. Hoffmann, G. Besozzi, N. Bevilacqua, D. Kirsten, R. Centis, C. Lange. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. European Respiratory Journal. 2009;34(2):387-393. doi:10.1183/09031936.00009509.