Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data

Matsumoto, Kazuaki; Abematsu, Kazuko; Shigemi, Akari; Kanazawa, Naoko; Watanabe, Erika; Yokoyama, Yuta; Ikawa, Kazuro; Morikawa, Norifumi; Takeda, Yasuo

doi:10.1179/1973947815y.0000000057

Cited by 15 publications

(13 citation statements)

References 20 publications

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“…In this study, non-therapeutic voriconazole levels were associated with adverse drug events (ADEs) requiring discontinuation. Other studies have described how TDM can reduce the rate of voriconazole discontinuation due to ADEs [ 23 , 39 ]. Unfortunately for this study, it was difficult to accurately assess the total number of adverse drug events requiring discontinuation due to the lack of ADEs reported in patient charts and inability to verify if an ADE was related to voriconazole.…”

Section: Discussionmentioning

confidence: 99%

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Schoeppler

Jaeger

et al. 2017

Ann Clin Microbiol Antimicrob

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BackgroundTherapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability. However, its benefits on clinical outcomes are still being defined. Additionally, TDM data are limited for posaconazole IV and delayed-release tablet formulations among specific patient populations, including critically ill. The aim of this study was to determine the percentage of therapeutic posaconazole and voriconazole drug levels across all formulations in a real-world clinical setting and elucidate factors affecting attainment of target concentrations.MethodsThis study was a retrospective cohort study conducted at the University of Colorado Hospital between September 2006 and June 2015 that evaluated patients who received posaconazole or voriconazole TDM as part of routine care.ResultsVoriconazole (n = 250) and posaconazole (n = 100) levels were analyzed from 151 patients. Of these, 54% of voriconazole and 69% of posaconazole levels were therapeutic. For posaconazole, 14/38 (37%), 28/29 (97%) and 27/33 (82%) levels were therapeutic for the oral suspension, IV, and delayed-release tablet, respectively. Intravenous and delayed-release tablet posaconazole were 20 fold (p < 0.01) and sevenfold (p = 0.002) more likely than the oral suspension to achieve a therapeutic level. Subsequent levels were more likely to be therapeutic after dose adjustments (OR 3.31; 95% CI 1.3–8.6; p = 0.02), regardless of timing of initial non-therapeutic level. In a multivariable logistic regression analysis, no characteristics were independently predictive of therapeutic voriconazole levels and only absence of H2RA/PPI use was independently predictive of therapeutic posaconazole levels. There was no correlation between survival and therapeutic drug levels for either voriconazole (p = 0.67) or posaconazole (p = 0.50).ConclusionsA high percentage of drug levels did not achieve TDM targets for voriconazole and posaconazole oral suspension, supporting the need for routine TDM for those formulations. The utility of TDM for the IV and delayed-release tablet formulations of posaconazole is less apparent.

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Section: Discussionmentioning

confidence: 99%

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Schoeppler

Jaeger

et al. 2017

Ann Clin Microbiol Antimicrob

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“…18,19, Two RCTs 19,42 were found, and the remaining citations were retrospective or prospective cohort and case series studies. 18,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][43][44][45][46][47] Efficacy Relationship. A total of 22 studies investigated the effect of TDM on efficacy outcomes of voriconazole therapy.…”

Section: Impact Of Tdm On Efficacy And/or Toxicitymentioning

confidence: 99%

“…A total of 22 studies investigated the effect of TDM on efficacy outcomes of voriconazole therapy. 18,19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]46,47 Two RCTs studied the relationship between TDM and voriconazole efficacy. In a South Korean RCT, 110 patients were randomized 1:1 to TDM or control arms, receiving a standard weight-based loading dose of 6 mg/kg and 4-mg/kg maintenance dose thereafter.…”

Section: Impact Of Tdm On Efficacy And/or Toxicitymentioning

confidence: 99%

“…Twelve of the studies reported significant associations between VTCs and voriconazole-related AEs. 18,[28][29][30][31][36][37][38]40,[44][45][46] The most frequently reported AEs were hepatotoxicity and neurotoxicity. Hepatotoxicity was most frequently defined as liver enzymes elevated above grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), or >3 to 5 times the upper limit of normal.…”

Section: Impact Of Tdm On Efficacy And/or Toxicitymentioning

confidence: 99%

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Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review

Lee

Hamandi

et al. 2020

Ann Pharmacother

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Objectives To examine current knowledge on the clinical utility of therapeutic drug monitoring (TDM) in voriconazole therapy, the impact of CYP2C19 genotype on voriconazole plasma concentrations, and the role of CYP2C19 genotyping in voriconazole therapy. Data Sources Three literature searches were conducted for original reports on (1) TDM and voriconazole outcomes and (2) voriconazole and CYP2C19 polymorphisms. Searches were conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to June 2020. Study Selection and Data Extraction Randomized controlled trials, cohort studies, and case series with ≥10 patients were included. Only full-text references in English were eligible. Data Synthesis A total of 63 studies were reviewed. TDM was recommended because of established concentration and efficacy/toxicity relationships. Voriconazole trough concentrations ≥1.0 mg/L were associated with treatment success; supratherapeutic concentrations were associated with increased neurotoxicity; and hepatotoxicity associations were more prevalent in Asian populations. CYP2C19 polymorphisms significantly affect voriconazole metabolism, but no relationship with efficacy/safety were found. Genotype-guided dosing with TDM was reported to increase chances of achieving therapeutic range. Relevance to Patient Care and Clinical Practice Genotype-guided dosing with TDM is a potential solution to optimizing voriconazole efficacy while avoiding treatment failures and common toxicities. Conclusions Voriconazole plasma concentrations and TDM are treatment outcome predictors, but research is needed to form a consensus target therapeutic range and dosage adjustment guidelines based on plasma concentrations. CYP2C19 polymorphisms are a predictor of voriconazole concentrations and metabolism, but clinical implications are not established. Large-scale, high-methodological-quality trials are required to investigate the role for prospective genotyping and establish CYP2C19-guided voriconazole dosing recommendations.

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“…For example, in Japan, sustained high trough levels of voriconazole (>4–5 ug/ml) have been associated with an increased risk of liver injury, and decreasing the dose to remain below this threshold is part of the therapeutic drug monitoring that is recommended. [163, 164]…”

Section: Strategies For the Prevention Of Dilimentioning

confidence: 99%

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

Stine¹,

Lewis²

2015

Expert Review of Gastroenterology & Hepatology

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While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for lefluonomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including HLA genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.

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Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data

Cited by 15 publications

References 20 publications

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

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