Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Hamada, Yukihiro; Tokimatsu, Issei; Mikamo, Hiroshige; Kimura, Masao; Seki, Masafumi; Takakura, Shunji; Ohmagari, Norio; Takahashi, Yoshiko; Kasahara, Kei; Matsumoto, Kazuaki; Okada, Kenji; Igarashi, Masahiro; Kobayashi, Masahiro; Mochizuki, Takahiro; Nishi, Yoshifumi; Tanigawara, Yusuke; Kimura, Toshimi; Takesue, Yoshio

doi:10.1007/s10156-013-0607-8

Cited by 149 publications

(93 citation statements)

References 77 publications

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“…In our center, we selected 2 to 5.5 mg/liter as the reference range for total VTCs (24-26, 43, 44). However, as there is still no clear consensus about the reference range of VTCs (24-26, 43, 45-49), the same conclusions can be drawn when simulating the worst-case scenario with an upper limit of 4 mg/liter (45)(46)(47)(48), as shown in Fig. 2.…”

Section: Discussionmentioning

confidence: 76%

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

Vanstraelen

Wauters

Vercammen

et al. 2014

Antimicrob Agents Chemother

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f Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.9 mg/liter, and 9.0 mg/liter (66 samples from 22 patients). Plasma albumin concentrations ranged from 13.8 to 38.7 g/liter. Total voriconazole concentrations in adult ICU patients treated with voriconazole ranged from 0.5 to 8.7 mg/liter. Unbound and bound voriconazole concentrations were separated using high-throughput equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry (LC-MSMS). Multivariate analysis revealed a positive relationship between voriconazole plasma protein binding and plasma albumin concentrations (P < 0.001), indicating higher unbound voriconazole concentrations with decreasing albumin concentrations. The correlation is more pronounced in the presence of elevated bilirubin concentrations (P ‫؍‬ 0.05). We therefore propose to adjust the measured total voriconazole concentrations in patients with abnormal plasma albumin and total serum bilirubin plasma concentrations who show adverse events potentially related to voriconazole via a formula that we developed. Assuming 50% protein binding on average and an upper limit of 5.5 mg/liter for total voriconazole concentrations, the upper limit for unbound voriconazole concentrations is 2.75 mg/liter. Alterations in voriconazole unbound concentrations caused by hypoalbuminemia and/or elevated bilirubin plasma concentrations cannot be countered immediately, due to the adult saturated hepatic metabolism. Consequently, increased unbound voriconazole concentrations can possibly cause adverse events, even when total voriconazole concentrations are within the reference range.

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Section: Discussionmentioning

confidence: 76%

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

Vanstraelen

Wauters

Vercammen

et al. 2014

Antimicrob Agents Chemother

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“…Optimizing voriconazole dosing for an individual can be challenging as a result of considerable interpatient and intrapatient variability in plasma concentrations . Nonetheless, there have been recommendations published with respect to a possible upper limit for therapeutic drug levels in an effort to minimize the risk of other drug‐related toxicities . Further investigation is needed to determine whether therapeutic drug monitoring may help mitigate the risk of SCC.…”

Section: Discussionmentioning

confidence: 99%

Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study

Hamandi

Fegbeutel

Silveira

et al. 2018

American Journal of Transplantation

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This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.

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“…A growing number of studies have shown that VRC exhibits significant exposure–response relationships for efficacy and toxicity; the target trough concentrations (C min ) have been identified . Hence, therapeutic drug monitoring (TDM) is now widely recommended to optimize clinical outcomes . VRC is known to be metabolized principally by cytochrome P450 (CYP) 2C19 and, to a lesser extent, by CYP3A4 and CYP2C9 enzymes .…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

Lin

Yan

et al. 2018

Brit J Clinical Pharma

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Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Cited by 149 publications

References 77 publications

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

Impact of Hypoalbuminemia on Voriconazole Pharmacokinetics in Critically Ill Adult Patients

Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

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