Analysis of the risk factors of linezolid-related haematological toxicity in Chinese patients

J Clin Pharm Ther. 2021 Jun;46(3):807-813. doi: 10.1111/jcpt.13359. Epub 2021 Feb 8.

Abstract

What is known and objectives: Haematological toxicity including thrombocytopenia, anaemia and leucopenia is the main adverse events of linezolid (LZD) therapy. This study aimed to investigate the risk factors for LZD-induced haematological toxicity and define the threshold of plasma trough concentration to minimize the haematological toxicity.

Methods: 145 patients who received LZD for more than 10 days were retrospectively reviewed to determine the incidence of LZD-induced haematological toxicity. Meanwhile, the risk factors of haematological toxicity were confirmed by univariate and multivariate logistic regression analysis.

Results and discussion: 9 (6.2%) patients developed leucopenia, while 52 (35.9%) and 26 (17.9%) patients developed thrombocytopenia and anaemia, respectively. The estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 (OR, 2.744; 95% CI, 1.117-6.734; p = 0.028) and baseline platelet count <200 × 109 /L (OR, 6.817; 95% CI, 2.870-16.193; p < 0.0001) were found to be significant risk factors for LZD-related thrombocytopenia. Aspartate aminotransferase (AST) >80 U/L (OR, 4.844; 95% CI, 1.207-19.451; p = 0.026) and eGFR <90 ml/min/1.73 m2 (OR, 7.132; 95% CI, 2.088-24.357; p = 0.002) were the risk factors for LZD-related anaemia. However, no significant risk factors were identified for LZD-related leucopenia. Moreover, LZD plasma trough concentration >8 mg/L [OR, 3.047; 95% CI, 1.233-7.539; p = 0.016] could be a predictor for the development of thrombocytopenia and anaemia.

What is new and conclusion: Hepatic and/or renal dysfunction are the risk factors for LZD-related haematological toxicity, while the target plasma trough concentration within 8 mg/L via dose reduction could minimize the haematological toxicity induced by LZD.

Keywords: haematological toxicity; linezolid; therapeutic drug monitoring.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / blood
  • China
  • Drug Monitoring
  • Female
  • Hematologic Diseases / chemically induced*
  • Humans
  • Kidney Function Tests
  • Linezolid / adverse effects*
  • Linezolid / blood
  • Liver Function Tests
  • Male
  • Middle Aged
  • Platelet Count
  • Retrospective Studies
  • Thrombocytopenia / chemically induced
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Linezolid