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Inflammation is a potential risk factor of voriconazole overdose in hematological patients. | LitMetric

AI Article Synopsis

  • Voriconazole (VRC) overdoses are common among hematological patients and can lead to significant adverse effects.
  • This study analyzed data from 62 patients (31 with VRC overdoses and 31 without) to identify risk factors associated with overdoses, focusing on various genetic, biological, and demographic parameters.
  • High levels of C-reactive protein (CRP) were found to be the primary risk factor for VRC overdose, with patients having CRP levels above 96 mg/L being 27 times more likely to experience an overdose compared to those with lower levels.

Article Abstract

Voriconazole (VRC) overdoses are frequent and expose patients at high risk of adverse effects. This case-control study performed in hematological patients who benefited from VRC therapeutic drug monitoring from January 2012 to December 2015 aimed to identify risk factors of VRC overdose. Pharmacogenetic, biological, and demographic parameters at the time of VRC trough concentration (C ) were retrospectively collected from medical records. Cases (VRC overdose: defined by a VRC C ≥ 4 mg/L; n = 31) were compared to controls (no VRC overdose: defined by VRC C < 4 mg/L; n = 31) using nonparametric or chi-square tests followed by multivariable analysis. VRC overdoses were significantly associated with high CRP and bilirubin levels, intravenous administration, and age in univariable analysis. In contrast, the proportion of CYP genotypes (CYP2C19, CYP3A4, or CYP3A5, considered alone or combined in a combined genetic score) were not significantly different between patients who experienced a VRC overdose and those who did not. In multivariable analysis, the class of CRP level (defined by median CRP levels of 96 mg/L) was the sole independent risk factor of VRC overdose (P < 0.01). Patients with CRP levels > 96 mg/L) had a 27-fold (IC 95%: [6-106]) higher risk of VRC overdose than patients with CRP levels ≤ 96 mg/L. This study demonstrates that inflammatory status, assessed by CRP levels, is the main risk factor of VRC overdose in French hematological patients, whereas pharmacogenetic determinants do not appear to be involved.

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Source
http://dx.doi.org/10.1111/fcp.12422DOI Listing

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