Risk factors for linezolid-induced thrombocytopenia in adult inpatients

Han, Xiaonian; Wang, Jinping; Zan, Xin; Peng, Lirong; Nie, Xin

doi:10.1007/s11096-021-01342-y

Cited by 20 publications

(20 citation statements)

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“…This may be attributed to the low rate of cirrhosis (9.1%) among patients. The duration of LZD therapy has been reported as a risk factor for thrombocytopenia, 25,31,[34][35][36] which is consistent with the present study.…”

Section: Discussionsupporting

confidence: 93%

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Onita

Ishihara

Ikebuchi

et al. 2022

Clinical Pharmacy Therapeu

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What Is Known and Objective Linezolid (LZD) may cause thrombocytopenia, which can result in discontinuation of treatment. In this study, the blood LZD trough concentration was estimated based on population pharmacokinetic (PK) parameters derived from two previously published models in the Japanese population to determine the rate of achieving the target trough value when the risk of thrombocytopenia is low and to clarify its relationship with the onset of thrombocytopenia. Methods This study included adult patients hospitalized at Shimane University Hospital, who received LZD treatment for at least 4 days from January 2010 to December 2017. Patients whose platelet count fell below 70% before LZD administration were categorized as the thrombocytopenic group. Patient PK parameters were calculated based on the population PK models described by Matsumoto et al. and Sasaki et al., and these parameters were designated A and B, respectively. Based on these parameters, the rate of achieving an LZD trough concentration of less than 8 μg/ml, which is the safety target achievement rate, was calculated using a random simulation for each patient. We further analysed the association between the incidence of thrombocytopenia and patient factors, including safety target achievement rate, through univariate, multivariate, and receiver operating characteristic (ROC) analyses. Results and Discussion Patients (n = 77) aged 72 ± 11 years and weighing 56.7 ± 10.9 kg, with a creatinine clearance (CLcr) of 60.5 ± 47.2 ml/min and a cirrhosis prevalence of 9.1%, were analysed. All patients received LZD at a dose of 600 mg twice daily for a total of 10.9 ± 8.9 days. Univariate analyses revealed significant differences (p < 0.05) in the duration of LZD therapy, serum creatinine, creatinine clearance, LZD clearance, and the safety target achievement rate for parameters A and B between the thrombocytopenic and non‐thrombocytopenic groups. A multivariate analysis of these factors stratified with the cutoff values obtained by ROC analysis revealed that the duration of LZD therapy and the safety target achievement rates for parameters A and B were significant factors (odds ratios for duration of LZD therapy: 7.436 [95% confidence interval (CI): 1.918–28.831] and 4.712 [95% CI: 1.567–14.163]; odds ratio for safety target achievement rate: 0.060 [95% CI: 0.016–0.232] and 0.167 [95% CI: 0.056–0.498] for parameters A and B, respectively). When the safety target achievement rates for patients treated with LZD were compared between the thrombocytopenic and non‐thrombocytopenic groups, the safety target achievement rate was higher in the non‐thrombocytopenic group in both the patients treated with LZD for less than 10 days and those for 10 days or more. Therefore, the safety target achievement rate estimated by the PK/PD simulation may represent to be an important index for risk assessment of LZD‐induced thrombocytopenia. What Is New and Conclusion The risk of LZD‐induced thrombocytopenia, which increased with the duration of LZD therapy, may ...

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Section: Discussionsupporting

confidence: 93%

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Onita

Ishihara

Ikebuchi

et al. 2022

Clinical Pharmacy Therapeu

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“…Thrombocytopenia, as the main reason for the dose adjustment of selinexor, can lead to life-threatening hemorrhage in patients. 21 Approximately half of the research samples had reversible thrombocytopenia of any grade, and symptoms can be alleviated by dose modification or interruption. 1 There has only been one study on the precise mechanism of selinexor-induced thrombocytopenia.…”

Section: Resultsmentioning

confidence: 99%

The development and validation of a liquid chromatography tandem mass spectrometry method for the quantification of selinexor and its application in Chinese multiple myeloma patients

Yan,

He,

Yang

et al. 2024

Anal. Methods

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“…A meta-analysis showed that approximately one out of every two patients experienced adverse events due to LZD (4), but the incidence of LZD-related adverse reactions in Chinese children has rarely been reported. Hematological toxicity, hyperlacticaemia, and optic neuropathy are the main adverse reactions to LZD (3, 4, 5), and thrombocytopaenia is a significant adverse drug reaction with the highest risk in the clinic ( Han et al, 2021 ). The incidence of LZD-induced thrombocytopaenia varies from 3.8% to 15.7% in children worldwide ( Meissner et al, 2003 ; Garazzino et al, 2011 ; Garazzino and Tovo, 2011 ), which is lower than that in adults (range 16.7–60.5%) but higher than the drug label reported (2.4% in children) ( Natsumoto et al, 2014 ; Hirano et al, 2014 ; U.S. Department of Health and Human Services, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Linezolid Exposure and the Typical Clinical Laboratory Safety and Bacterial Clearance in Chinese Pediatric Patients

Huo

Wu²,

Shu³

et al. 2022

Front. Pharmacol.

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Objectives: There have been limited studies concerning the safety and efficacy of linezolid (LZD) in children. This study aimed to evaluate the association between LZD exposure and clinical safety and efficacy in Chinese pediatric patients.Methods: This retrospective cross-sectional study included patients ≤18 years of age who received ≥3 days of LZD treatment between 31 January 2015, and 31 December 2020. Demographic characteristics, medication information, laboratory test information, and bacterial culture results were collected from the Hospital Information System (HIS). Exposure was defined as AUC24 and calculated by the non-linear mixed-effects modeling program (NONMEM), version 7.2, based on two validated population pharmacokinetic models. Binary logistic regression analyses were performed to analyze the associations between AUC24 and laboratory adverse events, and receiver operating characteristic curves were used to calculate the cut-off values. Efficacy was evaluated by bacterial clearance.Results: A total of 413 paediatric patients were included, with an LZD median (interquartile range) dose, duration, clearance and AUC24 of 30.0 (28.1-31.6) mg/kg/day, 8 (4‒15) days,1.31 (1.29-1.32) L/h and 81.1 (60.6-108.7) mg/L·h, respectively. Adverse events associated with TBil, AST, ALT, PLT, hemoglobin, WBC, and neutrophil count increased during and after LZD treatment when compared with before medication (p < 0.05), and the most common adverse events were thrombocytopaenia (71/399, 17.8%) and low hemoglobin (61/401, 15.2%) during the LZD treatment. Patients with AUC24 higher than 120.69 mg/L h might be associated with low hemoglobin 1–7 days after the end of the LZD treatment, and those with an AUC24 higher than 92.88 mg/L∙h might be associated with thrombocytopaenia 8–15 days after the end of the LZD treatment. A total of 136 patients underwent bacterial culture both before and after LZD treatment, and the infection was cleared in 92.6% (126/136) of the patients, of whom 69.8% (88/126) had AUC24/MIC values greater than 80.Conclusion: Hematological indicators should be carefully monitored during LZD treatment, especially thrombocytopaenia and low hemoglobin, and a continuous period of monitoring after LZD withdrawal is also necessary. Since the AUC24 cut-off values for laboratory adverse events were relatively low, a trade-off is necessary between the level of drug exposure required for treatment and safety, and the exposure target (AUC24/MIC) in pediatric patients should be further studied, especially for patients with complications and concomitant medications.

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Risk factors for linezolid-induced thrombocytopenia in adult inpatients

Cited by 20 publications

References 25 publications

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

The development and validation of a liquid chromatography tandem mass spectrometry method for the quantification of selinexor and its application in Chinese multiple myeloma patients

Relationship Between Linezolid Exposure and the Typical Clinical Laboratory Safety and Bacterial Clearance in Chinese Pediatric Patients

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