scholarly journals Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients: factors affecting trough plasma concentrations

2017 ◽  
Vol 73 (3) ◽  
pp. 748-756 ◽  
Author(s):  
Wirawan Jeong ◽  
Gregory I Snell ◽  
Bronwyn J Levvey ◽  
Glen P Westall ◽  
C Orla Morrissey ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplant ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Single Centre ◽  
Factors Affecting ◽  
Single Centre Study ◽  
Lung Transplant Recipients ◽  
Trough Plasma

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

scholarly journals 1737. Impact of Therapeutic Drug Monitoring (TDM) of Azole Prophylaxis in Lung Transplant Recipients on the Development of Positive Fungal Events

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Anooj Shah ◽  
Carly D’Agostino ◽  
Kathleen Cunningham ◽  
Clare Kane ◽  
Michael G Ison ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Study Groups ◽  
Fungal Species ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Lung Transplant Recipients ◽  
Index Value ◽  
The Impact

Abstract Background The utility and clinical impact of therapeutic drug monitoring (TDM) of prophylactic azole antifungals in lung transplant recipients is not well described. The objective of this study was to investigate the impact of TDM of azole prophylaxis in lung transplant recipients on the development of positive fungal events. Methods A retrospective analysis was performed on 47 lung transplant recipients between 2013 and 2018 at Northwestern Memorial Hospital. A positive fungal event was defined as fungal species on BAL culture and/or positive BAL Aspergillus galactomannan (GM) with an index value ≥1.0. Study groups were defined based on attainment of therapeutic trough levels after initiation of oral therapy (therapeutic if posaconazole level ≥0.7 μg/mL or voriconazole ≥1–5.5 μg/mL, subtherapeutic if ≥2 consecutive levels of posaconazole <0.7 μg/mL or voriconazole <1 μg/mL after initial dose increase). Results There were no differences in baseline characteristics (Figure 1). There were a total of 11 fungal events with 3 (12.0%) occurring in the therapeutic cohort and 8 (36.4%) in those subtherapeutic (P = 0.08). In the 5 patients with a positive GM, the mean index was 2.02 ± 0.95. 7/30 (23.3%) of patients on posaconazole had a fungal event, with 2/7 (28.6%) requiring treatment at the time of event. For patients on voriconazole, 4/17 (23.5%) had a fungal event, with 1/4 (25.0%) requiring treatment. Mean time to fungal event was 164.5 ± 8.9 days vs. 135.9 ± 13.7 days in the therapeutic and subtherapeutic group, respectively (P = 0.05). All patients on posaconazole suspension who experienced a fungal event were subtherapeutic (3/3, 100%) compared with the majority of patients on posaconazole delayed release (DR) tablets who achieved therapeutic levels (17/22, 77.3%). Mean posaconazole trough level observed in the patients receiving DR tablet was 2.15 ± 0.95 μg/mL. Conclusion There was an association between two consecutive subtherapeutic azole prophylaxis levels and positive fungal events indicating a role for TDM in lung transplant recipients. Time to fungal event post-transplant was shorter in subtherapeutic patients. As anticipated, the use of posaconazole suspension resulted in subtherapeutic levels. This study presents an opportunity for further research of the impact of TDM on clinical outcomes to optimize patient care. Disclosures All authors: No reported disclosures.

scholarly journals Review of Pharmacologic Considerations in the Use of Azole Antifungals in Lung Transplant Recipients

2021 ◽  
Vol 7 (2) ◽  
pp. 76 ◽  
Author(s):  
Megan E. Klatt ◽  
Gregory A. Eschenauer
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Drug Reactions ◽  
Azole Antifungals ◽  
Lung Transplant Recipients ◽  
Pharmacologic Profile

Mold-active azole antifungals are commonly prescribed for the prevention of invasive fungal infections in lung transplant recipients. Each agent exhibits a unique pharmacologic profile, an understanding of which is crucial for therapy selection and optimization. This article reviews pharmacologic considerations for three frequently-used azole antifungals in lung transplant recipients: voriconazole, posaconazole, and isavuconazole. Focus is drawn to analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population.

scholarly journals Voriconazole Therapeutic Drug Monitoring Among Lung Transplant Recipients Receiving Targeted Therapy for Invasive Aspergillosis

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Guillaume Butler-Laporte ◽  
Charles Poirier ◽  
Pasquale Ferraro ◽  
Marie-Claude Langevin ◽  
Claude Lemieux ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Therapeutic Drug Monitoring ◽  
Invasive Aspergillosis ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Lung Transplant Recipients

scholarly journals Prospective, Observational Study of Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis: Factors Impacting Levels of and Associations between Serum Troughs, Efficacy, and Toxicity

2012 ◽  
Vol 56 (5) ◽  
pp. 2371-2377 ◽  
Author(s):  
Dimitra Mitsani ◽  
M. Hong Nguyen ◽  
Ryan K. Shields ◽  
Yoshiya Toyoda ◽  
Eun J. Kwak ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Observational Study ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Prospective Observational Study ◽  
Target Range ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Lung Transplant Recipients ◽  
The Times

ABSTRACTVoriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n= 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n= 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (P= 0.005). Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (P= 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml (P= 0.01) and among patients with no trough of >1.5 μg/ml (P= 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P= 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.

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