Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions

Abstract

Background: Previous studies have shown that the development of thrombocytopenia was associated with the elevated plasma concentration of linezolid, but little is known about the relationship between other uncommon adverse drug reactions (ADRs) and plasma concentration. The appropriate dosing adjustment has remained controversial. This prospective observational study was conducted to investigate the association between the plasma concentration of linezolid, ADRs, and clinical outcomes. Methods: Adult patients on linezolid treatment undergoing at least one therapeutic drug monitoring (TDM) were enrolled. The association between linezolid concentrations and ADRs was examined by multivariate Cox regression model. Predictors of linezolid concentrations was determined by linear regression model. The cut-off point of linezolid concentration and the effect of dosing adjustments based on TDM was also explored. Results: Of 50 patients enrolled in the study, plasma concentrations were 1.5–3 times higher than what was described in the prescribing information. The median minimum concentration (Cmin) was significantly higher in patients with thrombocytopenia compared to patients without thrombocytopenia (13.0 vs. 7.2 μg/mL, P = 0.0273), and a higher median maximum concentration was also observed in patients with lactic acidosis (33.0 vs. 27.5 μg/mL, P = 0.0420). The Cmin was elevated in patients with advanced age and severely impaired renal function. Dosing adjustment tailored by early TDM with the upper limit of Cmin 9 μg/mL may improve platelet counts. Conclusion: Elevated linezolid concentrations were associated with thrombocytopenia and lactic acidosis. TDM-guided dosing adjustment could be considered as a pragmatic way to mitigate thrombocytopenia.

Keywords

• Linezolid
• Therapeutic drug monitoring
• Dosing adjustment
• Lactic acidosis
• Thrombocytopenia