scholarly journals Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients

2019 ◽  
Vol 57 (8) ◽  
pp. 937-943 ◽  
Author(s):  
Vincent J Lempers ◽  
Edmé Meuwese ◽  
Annelies M Mavinkurve-Groothuis ◽  
Stefanie Henriet ◽  
Inge M van der Sluis ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multiple Dose ◽  
Pediatric Patients ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Patient Demographics ◽  
Before And After ◽  
Intrapatient Variability ◽  
Trough Concentrations

Abstract Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2–18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1–13.5]) was obtained after 3 days (1–27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)–28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1–4 mg/l, 9.3% 4–6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1–4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.

scholarly journals Inappropriate Vancomycin Therapeutic Drug Monitoring in Hospitalized Pediatric Patients Increases Pediatric Trauma and Hospital Costs

2012 ◽  
Vol 17 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Manika Suryadevara ◽  
Kelly E. Steidl ◽  
Luke A. Probst ◽  
Jana Shaw
Keyword(s):  
Health Care ◽  
Therapeutic Drug Monitoring ◽  
Health Care Provider ◽  
Care Provider ◽  
Drug Monitoring ◽  
Hospital Cost ◽  
Pediatric Patients ◽  
Tertiary Care ◽  
Therapeutic Drug ◽  
Trough Concentrations

OBJECTIVES The objective of this study was to measure the appropriateness of vancomycin monitoring in a pediatric tertiary care center and to evaluate the effectiveness of two interventions, autonomous pharmacy therapeutic drug monitoring and health care provider education, in reducing avoidable pediatric patient trauma and hospital cost. METHODS A retrospective chart review evaluating vancomycin therapeutic drug monitoring (TDM) in pediatric inpatients was performed before and after the introduction of an autonomous pharmacy TDM program and health care provider (HCP) education. RESULTS Thirty-five patients were included in our study, prior to any intervention. Of these, 9% of patients had trough concentrations appropriately deferred. Of the total of 64 trough concentrations obtained, 94% were considered to be inappropriate. After the start of the autonomous pharmacy TDM program, of the 54 eligible patients (111 troughs), 9% had trough concentrations appropriately deferred, and 34% were inappropriate. In the 3-month period following the introduction of HCP education in combination with pharmacy TDM, we identified 27 eligible patients. Among those, 15% of the patients had trough concentrations appropriately deferred. Of the 43 trough concentrations obtained, only 9% were considered to be inappropriate. The combination of pharmacy TDM with HCP education decreased annualized hospital cost by 60%, from $13,080 to $5232. CONCLUSIONS Inappropriate vancomycin TDM occurs commonly in our institution, resulting in unnecessary hospital cost and patient trauma. The combination of pharmacy TDM and HCP education significantly improved clinical practice; however, results were short-lived. Further interventions, such as computer based order entry, will likely be needed to reinforce and improve long-term TDM practice in pediatric patients.

scholarly journals Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1991
Author(s):  
Matylda Resztak ◽  
Joanna Sobiak ◽  
Andrzej Czyrski
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Mycophenolic Acid ◽  
Drug Monitoring ◽  
Pediatric Patients ◽  
Fungal Infections ◽  
Cord Blood Transplantation ◽  
Active Form ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Acute Kidney Disease

The review includes studies dated 2011–2021 presenting the newest information on voriconazole (VCZ), mycophenolic acid (MPA), and vancomycin (VAN) therapeutic drug monitoring (TDM) in children. The need of TDM in pediatric patients has been emphasized by providing the information on the differences in the drugs pharmacokinetics. TDM of VCZ should be mandatory for all pediatric patients with invasive fungal infections (IFIs). Wide inter- and intrapatient variability in VCZ pharmacokinetics cause achieving and maintaining therapeutic concentration during therapy challenging in this population. Demonstrated studies showed, in most cases, VCZ plasma concentrations to be subtherapeutic, despite the updated dosages recommendations. Only repeated TDM can predict drug exposure and individualizing dosing in antifungal therapy in children. In children treated with mycophenolate mofetil (MMF), similarly as in adult patients, the role of TDM for MMF active form, MPA, has not been well established and is undergoing continued debate. Studies on the MPA TDM have been carried out in children after renal transplantation, other organ transplantation such as heart, liver, or intestine, in children after hematopoietic stem cell transplantation or cord blood transplantation, and in children with lupus, nephrotic syndrome, Henoch-Schönlein purpura, and other autoimmune diseases. MPA TDM is based on the area under the concentration–time curve; however, the proposed values differ according to the treatment indication, and other approaches such as pharmacodynamic and pharmacogenetic biomarkers have been proposed. VAN is a bactericidal agent that requires TDM to prevent an acute kidney disease. The particular group of patients is the pediatric one. For this group, the general recommendations of the dosing may not be valid due to the change of the elimination rate and volume of distribution between the subjects. The other factor is the variability among patients that concerns the free fraction of the drug. It may be caused by both the patients’ population and sample preconditioning. Although VCZ, MMF, and VAN have been applied in pediatric patients for many years, there are still few issues to be solve regarding TDM of these drugs to ensure safe and effective treatment. Except for pharmacokinetic approach, pharmacodynamics and pharmacogenetics have been more often proposed for TDM.

scholarly journals Therapeutic Drug Monitoring of Indinavir, Boosted with Ritonavir, in HIV Infected Pediatric Patients: TL005

2006 ◽  
Vol 60 (5) ◽  
pp. 636-636
Author(s):  
P G Cáceres ◽  
V Currás ◽  
G Bramuglia ◽  
Ch Höcht ◽  
M Rubio ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Pediatric Patients ◽  
Therapeutic Drug

scholarly journals P99 Clinical validation of published vancomycin population PK models in critically ill neonates

2019 ◽  
Vol 104 (6) ◽  
pp. e58.2-e59
Author(s):  
A van der Veen ◽  
RJ Keizer ◽  
W de Boode ◽  
A Somers ◽  
R Brüggemann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
A Priori ◽  
Predictive Performance ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Suitable Model ◽  
List Type ◽  
A Posteriori ◽  
Target Attainment

BackgroundVancomycin is commonly used for treatment of severe Gram+ neonatal infections. Currently, even with the use of optimized dosing regimens and therapeutic drug monitoring (TDM), target attainment rates are abominable, leaving patients at risk for therapeutic failure and toxicity. Model-informed precision dosing (MIPD) offers a large potential to improve therapy in the individual patient.The aim of this study was to identify a suitable model for bedside MIPD by assessing the predictive performance of published population pharmacokinetic (popPK) models.MethodsA literature search was conducted to identify parametric popPK models. PK vancomycin data were retrospectively collected from NICU patients at the Radboud University Hospital, Nijmegen, The Netherlands. The model predictive performance was assessed by comparison of predictions to observations, calculation of bias (Mean Percentage Errors, MPE) and imprecision (Normalized Root Mean Squared Errors, NRMSE). Evaluations included both a priori (model covariate input) and a posteriori (model covariate and TDM concentration input) scenarios.Results265 TDM measurements from 65 neonates (median postmenstrual age:32 weeks [range:25–45 weeks]; median weight:1281g [range:597–5360g]; median serum creatinine:0,48 mg/dL [range:0,15–1,28 mg/dL]) were used for model evaluation. Six popPK models were evaluated1–6. A posteriori predictions of all models were consistently more accurate and precise compared to the a priori (starting dose) predictions. PopPK models of Frymoyer et al. and Capparelli et al. consistently performed best through all evaluations in both the a priori and a posteriori scenario (MPE ranging from -18 to 6,4% in a priori scenario and -6,5 to -3,8% in a posteriori scenario; NRMSE ranging from 34 to 40% in a priori scenario and 23 to 24% in a posteriori scenario).ConclusionLarge differences in predictive performance of popPK models were observed. Repeated therapeutic drug monitoring remains necessary to increase target attainment rate. Best performing models for bedside MIPD were identified in our patient population.ReferencesZhao W, Lopez E, Biran V, et al. ( 2013). Vancomycin continuous infusion in neonates: Dosing optimisation and therapeutic drug monitoring. Arch Dis Child;98(6):449–453.Capparelli EV, Lane JR, Romanowski GL, et al. ( 2001). The influences of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol, 41:927–934.De Cock RFW, Allegaert K, Brussee JM, et al. ( 2014). Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration. Pharm Res;31(10):2642–2654.Frymoyer A, Hersh AL, El-Komy MH, et al. ( 2014). Association between vancomycin trough concentration and area under the concentration-time curve in neonates. Antimicrob Agents Chemother, 58(11):6454–6461.Anderson BJ, Allegaert K, Van Den Anker JN, Cossey V, Holford NHG. ( 2006). Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol;63(1):75–84.Germovsek E, Osborne L, Gunaratnam F, Lounis SA, Busquets FB, Sinha AK. ( 2019). Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data. J Antimicrob Chemother, 1–9.Disclosure(s)R. Keizer is an employee and stockholder of InsightRX.

scholarly journals Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Indy Sandaradura ◽  
Jessica Wojciechowski ◽  
Deborah J. E. Marriott ◽  
Richard O. Day ◽  
Sophie Stocker ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Dose Selection ◽  
Dose Individualization

ABSTRACT Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.

Intra-individual variability in lopinavir plasma trough concentrations supports therapeutic drug monitoring

AIDS ◽  
2003 ◽  
Vol 17 (7) ◽  
pp. 1107-1108 ◽  
Author(s):  
Marta Boffito ◽  
David J Back ◽  
Patrick G Hoggard ◽  
Annamaria Caci ◽  
Stefano Bonora ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Individual Variability ◽  
Therapeutic Drug ◽  
Trough Concentrations
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