Predictive score of haematological toxicity in patients treated with linezolid

Castillo, Juan González-Del; Candel, Francisco Javier; Manzano-Lorenzo, R.; Arias, Luis Fernando; García‐Lamberechts, Eric Jorge; Martín‐Sánchez, Francisco Javier

doi:10.1007/s10096-017-2960-5

Cited by 17 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have also identified the presence of moderate or severe liver diseases as a risk factor for developing hematological toxicity (20,(29)(30)(31). In the same way, lactic acidosis has proven to be more common in patients with liver impairment (32).…”

Section: Discussionmentioning

confidence: 97%

Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction

Zhang

Zhu

Chen

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Currently, pharmacokinetics data of linezolid in patients with LD are limited. This study aimed to characterize pharmacokinetics parameters of linezolid in patients with LD, identify the factors influencing the pharmacokinetics, and propose an optimal dosage regimen. We conducted a prospective study and established a population pharmacokinetics model with the Phoenix NLME software. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and prediction corrected-visual predictive check. A total of 163 concentration samples from 45 patients with LD were adequately described by a one-compartment model with first-order elimination along with prothrombin activity (PTA) and creatinine clearance as significant covariates. Linezolid clearance (CL) was 2.68 liters/h (95% confidence interval [CI], 2.34 to 3.03 liters/h); the volume of distribution (V) was 58.34 liters (95% CI, 48.00 to 68.68 liters). Model-based simulation indicated that the conventional dose was at risk for overexposure in patients with LD or severe renal dysfunction; reduced dosage (300 mg/12 h) would be appropriate to achieve safe (minimum steady-state concentration [Cmin,ss] at 2 to 8 μg/ml) and effective targets (the ratio of area under the concentration-time curve from 0 to 24 h [AUC0–24] at steady state to MIC, 80 to 100). In addition, for patients with severe LD (PTA, ≤20%), the dosage (400 mg/24 h) was sufficient at an MIC of ≤2 μg/ml. This study recommended therapeutic drug monitoring for patients with LD. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900022118.)

show abstract

Section: Discussionmentioning

confidence: 97%

Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction

Zhang

Zhu

Chen

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The way thrombocytopenia is defined may partly explain this disparity. We defined it as a reduction in platelet counts ≥ 30% from baseline and a value ≤ 150,000 cells/µL while other studies considered a decrease of 25% in platelet counts [ 25 ] or a decrease in platelet counts ≥ 50% from baseline [ 17 ]. The reasons why this prevalence is more than 20 times higher than that reported in the SmPC are possibly related to the high proportion of patients presenting associated risk factors in our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Renal failure has already been described as a risk factor in previous studies [ 14 , 15 , 16 , 17 , 37 ]. Our cut-off value for renal failure was 60 mL/min as in Hanai’s [ 15 ] and Nukui’s [ 16 ] studies, but others described lower values, between 30 and 50 mL/min [ 14 , 25 , 38 ]. The renal function is also included in the Charlson index, but based on serum creatinine levels, with a cut-off value set at 3 mg/dL.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacovigilance good practices recommend to collect and report data about possible ADR related to off-label use [ 24 ], because these conditions of usage are new and may result in toxicity issues that were not highlighted during the registration clinical trials. Current reports that examined linezolid safety in relation with its local conditions of use (including off-label indications) are scarce and concern Japanese patients [ 14 , 15 , 16 ] or, in Europe, hematological toxicity in a single hospital in Spain (see for example [ 25 , 26 ]). A meta-analysis also compiled 12 studies from 11 countries and focused on safety of linezolid in patients with TB [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Use and Adverse Drug Reactions of Linezolid: A Retrospective Study in Four Belgian Hospital Centers

et al. 2021

View full text Add to dashboard Cite

In Belgium, linezolid is indicated for pneumonia and skin and soft tissue infections, but is more broadly used, due to its oral bioavailability and activity against multiresistant organisms. This could increase the risk of adverse drug reactions (ADR), notably hematological disorders (anemia, thrombocytopenia), neuropathy, or lactic acidosis. We analyzed linezolid clinical use in relationship with occurrence of ADR in Belgian hospitals and highlighted risk factors associated with the development of thrombocytopenia. A retrospective analysis of electronic medical records and laboratory tests of adult patients treated with linezolid in four Belgian hospitals in 2016 allowed the collection of ADR for 248 linezolid treatments. Only 19.7% of indications were in-label. ADR included 43 thrombocytopenia, 17 anemia, 4 neuropathies, and 4 increases in lactatemia. In a multi-variate analysis, risk factors of thrombocytopenia were a treatment duration > 10 days, a glomerular filtration rate < 60 mL/min, and a Charlson index ≥ 4. Off-label use of linezolid is frequent in Belgium, and ADR more frequent than reported in the summary of product characteristics, but not statistically associated with any indication. This high prevalence of ADR could be related to a high proportion of patients presenting risk factors in our population, highlighting the importance of detecting them prospectively.

show abstract

“…Hepatic impairment, however, was a significant risk factor associated with thrombocytopenia in both the general population and the subgroup analysis, which warrants further investigation into the role that hepatic metabolism may play in the mechanism of LAT. 14…”

mentioning

confidence: 99%

Incidence and Risk Factors for Development of Thrombocytopenia in Patients Treated With Linezolid for 7 Days or Greater

Rabon¹,

Fisher²,

MacVane³

2018

Ann Pharmacother

View full text Add to dashboard Cite

Predictive score of haematological toxicity in patients treated with linezolid

Abstract: This score could help in the identification of patients with high risk for HT and assess the use of an antibiotic other than LZD, an important issue considering its relation with 30-day mortality observed in our study.

Cited by 17 publications

References 22 publications

Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction

Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction

Clinical Use and Adverse Drug Reactions of Linezolid: A Retrospective Study in Four Belgian Hospital Centers

Incidence and Risk Factors for Development of Thrombocytopenia in Patients Treated With Linezolid for 7 Days or Greater

Contact Info

Product

Resources

About