The Effect of Therapeutic Drug Monitoring on Safety and Efficacy of Voriconazole in Invasive Fungal Infections: A Randomized Controlled Trial

Park, Wan Beom; Kim, Nak Hyun; Kim, Kye-Hyung; Lee, Seung Hwan; Nam, Won Seok; Yoon, Seo Hyun; Song, Kyoung Ho; Choe, Pyoeng Gyun; Kim, Nam Joong; Jang, In Jin; Oh, Myoung Don; Yu, Kyung‐Sang

doi:10.1093/cid/cis599

Cited by 335 publications

(282 citation statements)

References 23 publications

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“…Voriconazole clearance averages 932 ml/min in ultrarapid metabolizers, 522 ml/min in extensive metabolizers, and 147 ml/min in poor metabolizers (194). Both CYP-2C19 genotyping and therapeutic drug monitoring have been suggested as approaches to guide therapy and control pharmacokinetic variability (195)(196)(197). The voriconazole half-life averages 7 to 14 h, depending on the genotype.…”

Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 99%

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii . This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.

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Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 99%

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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“…to medically important molds have been engineered at a cost of less-predictable pharmacokinetics (17). Voriconazole is an ideal candidate for therapeutic drug monitoring for the following reasons: (i) there are well-established drug exposure-effect and drug exposure-toxicity relationships (7,8,10); (ii) there is evidence that therapeutic drug monitoring may lead to improved therapeutic outcomes (8,18); and (iii) voriconazole exhibits significant interpatient variability with classical nonlinear pharmacokinetics (12). While therapeutic drug monitoring may be a desirable adjunct to the routine use of voriconazole, at this time there are no algorithms that can be used to adjust the regimen to attain predefined serum concentration targets in an optimally precise manner.…”

Section: Discussionmentioning

confidence: 99%

Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

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VanGuilder

Donnelly

et al. 2013

Antimicrob Agents Chemother

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eThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

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“…Recent literature has reported mixed results concerning the association of voriconazole therapeutic drug monitoring. Park et al demonstrated that therapeutic drug monitoring reduces drug discontinuation due to adverse events and improves treatment response [28]; while Racil et al failed to establish improved outcomes with measured voriconazole concentrations [29]. The true magnitude of the utility of a standardized protocol for monitoring serum concentrations of nonweight based dosing for voriconazole as primary antifungal prophylaxis has yet to occur in a prospective, randomized trial and remains controversial.…”

Section: Discussionmentioning

confidence: 99%

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

et al. 2013

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The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n = 2 Aspergillus spp., n = 2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n = 24), fever of unknown origin (n = 19), adverse events (n = 23), and other causes (n = 17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy. Am. J. Hematol. 88:283–288, 2013. © 2013 Wiley Periodicals, Inc.

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The Effect of Therapeutic Drug Monitoring on Safety and Efficacy of Voriconazole in Invasive Fungal Infections: A Randomized Controlled Trial

Abstract: NCT00890708.

Cited by 335 publications

References 23 publications

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

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