Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions
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 adjust...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of the Formosan Medical Association |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664620302400 |
| _version_ | 1831741720245567488 |
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| author | Chih-Ning Cheng Chien-Chih Wu Ching-Hua Kuo Chi-Chuan Wang Jann-Tay Wang Ya-Ting Lin Ren-Shiang Jhang Shu-Wen Lin |
| author_facet | Chih-Ning Cheng Chien-Chih Wu Ching-Hua Kuo Chi-Chuan Wang Jann-Tay Wang Ya-Ting Lin Ren-Shiang Jhang Shu-Wen Lin |
| author_sort | Chih-Ning Cheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T14:21:42Z |
| format | Article |
| id | doaj.art-1269d6e051e74a53be87de5ed43a7449 |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-12-21T14:21:42Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-1269d6e051e74a53be87de5ed43a74492022-12-21T19:00:45ZengElsevierJournal of the Formosan Medical Association0929-66462021-01-011201466475Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactionsChih-Ning Cheng0Chien-Chih Wu1Ching-Hua Kuo2Chi-Chuan Wang3Jann-Tay Wang4Ya-Ting Lin5Ren-Shiang Jhang6Shu-Wen Lin7Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanDivision of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanGraduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanSchool of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Corresponding author. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Room 216, No. 33, Linsen S. Rd, Taipei, 10050, Taiwan. Fax: +886 2 33668780.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.http://www.sciencedirect.com/science/article/pii/S0929664620302400LinezolidTherapeutic drug monitoringDosing adjustmentLactic acidosisThrombocytopenia |
| spellingShingle | Chih-Ning Cheng Chien-Chih Wu Ching-Hua Kuo Chi-Chuan Wang Jann-Tay Wang Ya-Ting Lin Ren-Shiang Jhang Shu-Wen Lin Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions Journal of the Formosan Medical Association Linezolid Therapeutic drug monitoring Dosing adjustment Lactic acidosis Thrombocytopenia |
| title | Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions |
| title_full | Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions |
| title_fullStr | Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions |
| title_full_unstemmed | Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions |
| title_short | Impact of high plasma concentrations of linezolid in Taiwanese adult patients— therapeutic drug monitoring in improving adverse drug reactions |
| title_sort | impact of high plasma concentrations of linezolid in taiwanese adult patients therapeutic drug monitoring in improving adverse drug reactions |
| topic | Linezolid Therapeutic drug monitoring Dosing adjustment Lactic acidosis Thrombocytopenia |
| url | http://www.sciencedirect.com/science/article/pii/S0929664620302400 |
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