Weight‐based tacrolimus trough concentrations post liver transplant

Liu, Zheng; Cheng, Jeffrey; Powell, Elizabeth E.; Macdonald, Graeme A.; Fawcett, Jonathan; Lynch, Stephen V.; Martin, Jennifer

doi:10.1111/imj.14043

Cited by 5 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with a previous study conducted in adult liver transplant recipients. 38 However, it must be noted that some transplant recipients in this study had an extended post-transplant hospital stay (up to 137 days). In these transplant recipients, post-operative complications or infections often occur, in response to which prescribers may prefer to dose tacrolimus more cautiously (personal communication).…”

Section: Discussionmentioning

confidence: 75%

Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software

Kirubakaran

Stocker

Carlos

et al. 2021

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Background: Therapeutic drug monitoring is recommended to guide tacrolimus dosing because of its narrow therapeutic window and considerable pharmacokinetic variability. This study assessed tacrolimus dosing and monitoring practices in heart transplant recipients and evaluated the predictive performance of a Bayesian forecasting software using a renal transplant-derived tacrolimus model to predict tacrolimus concentrations.Methods: A retrospective audit of heart transplant recipients (n = 87) treated with tacrolimus was performed. Relevant data were collected from the time of transplant to discharge. The concordance of tacrolimus dosing and monitoring according to hospital guidelines was assessed. The observed and software-predicted tacrolimus concentrations (n = 931) were compared for the first 3 weeks of oral immediate-release tacrolimus (Prograf) therapy, and the predictive performance (bias and imprecision) of the software was evaluated. Results:The majority (96%) of initial oral tacrolimus doses were guideline concordant. Most initial intravenous doses (93%) were lower than the guideline recommendations. Overall, 36% of initial tacrolimus doses were administered to transplant recipients with an estimated glomerular filtration rate of ,60 mL/min/1.73 m despite recommendations to delay the commencement of therapy. Of the tacrolimus concentrations collected during oral therapy (n = 1498), 25% were trough concentrations obtained at steady-state. The software displayed acceptable predictions of tacrolimus concentration from day 12 (bias: 26%; 95%confidence interval, 211.8 to 2.5; imprecision: 16%; 95% confidence interval, 8.7-24.3) of therapy.Conclusions: Tacrolimus dosing and monitoring were discordant with the guidelines. The Bayesian forecasting software was suitable for guiding tacrolimus dosing after 11 days of therapy in heart transplant recipients. Understanding the factors contributing to the variability in tacrolimus pharmacokinetics immediately after transplant may help improve software predictions.

show abstract

Section: Discussionmentioning

confidence: 75%

Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software

Kirubakaran

Stocker

Carlos

et al. 2021

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

show abstract

“…Reduced expression of P‐gp is attributed to the increase in proinflammatory mediators such as tumour necrosis factor‐α, IL‐6 and inducible nitric oxide synthase in the adipose tissue of patients who are obese (Engeli et al, 2004; Fried et al, 1998; Kern et al, 2001). Conversely, other studies have shown that there was no difference in the tacrolimus trough levels between patients who are obese versus not obese, after weight‐based dosing in the immediate posttransplant phase (Liu et al , 2019). In addition, retrospective analysis of the Australian and New‐Zealand dialysis and transplant registry data ( n = 7919) has shown that underdosing of patients who are obese could be associated with unfavourable outcomes, that is, graft rejections (Flabouris et al, 2019).…”

Section: Discussionmentioning

confidence: 92%

“…It has been postulated that the activity of the hepatic cytochrome P450 metabolising enzyme (CYP3A4) and intestinal transporters are altered in individuals who are obese which can lead to higher trough levels (Sawamoto et al, 2014). Conversely, some smaller studies examining tacrolimus dosing post‐liver transplant have shown that such dose modification would not be warranted (Liu et al, 2019). There is a need for further clinical studies in renal transplant recipients to clarify this association and guide in tacrolimus dosing practice.…”

Section: Literature Reviewmentioning

confidence: 99%

Body weight‐based initial dosing of tacrolimus in renal transplantation: Is this an ideal approach?

Chinnadurai

Ibrahim

Tay

et al. 2020

Journal of Renal Care

View full text Add to dashboard Cite

Background Tacrolimus dosing immediately posttransplant is based on body weight. Recent studies have highlighted that the dosing of tacrolimus purely based on weight may not be appropriate, particularly in individuals who are obese. Objectives This study aimed to estimate the effect of body mass index (BMI) and the weight‐based dosing on tacrolimus trough levels in recipients of renal transplants. Design and Participants This study was conducted on 400 of the 863 patients registered in the Salford, UK, renal transplant database between 2012 and 2019 who had complete and analysable datasets. Data were collected at baseline (first tacrolimus trough level after transplantation), after 1 month and 6 months posttransplantation. The cohort was split into three groups based on BMI (kg/m2; Group 1 ≤ 25, Group 2 > 25–30 and Group 3 > 30) which were compared with respect to tacrolimus dose, plasma levels and concentration/dose (C/D) ratio at the three‐time points. Results Patients in the higher BMI group (Group 3) had significantly higher baseline tacrolimus trough levels despite receiving a lower initiation dose per kilogram of body weight. After 1 and 6‐months posttransplant, the higher BMI group were receiving a significantly lower tacrolimus dose relative to their body weight, with a significant negative correlation between body weight and tacrolimus/kg body weight. There was no adverse relationship evident between tacrolimus dosing or concentration and graft function. Conclusions Our study showed that standard dosing of tacrolimus based on body weight in individuals who were obese did not adversely affect their tacrolimus concentrations or transplant function.

show abstract

“…Obesity does not influence target TAC trough levels. 23 Although there are two TAC formulations available-one that permits once-daily dosing (extended release) and one that depends on twice-per-day dosing (immediate-release)- only immediate-release capsules are currently officially approved in the United States for use among liver transplant recipients. A post-hoc analysis showed that mortality was 10% higher among female recipients receiving extendedrelease versus immediate-release TAC.…”

Section: Tacrolimusmentioning

confidence: 99%

Immunosuppressive Drug Levels in Liver Transplant Recipients: Impact in Decision Making

Kourkoumpetis

Levitsky

2019

Semin Liver Dis

View full text Add to dashboard Cite

To prevent rejection, liver transplant providers largely base their management decisions on their clinical impression and pharmacokinetics. Clinical impression relies on assessing graft function, liver enzymes, and biopsy. High immunosuppressive drug levels, although minimizing rejection, are related to significant side effects such as nephrotoxicity and metabolic syndrome, contributing to long-term morbidity and mortality. Similarly, levels that are lower than necessary can decrease the rate of side effects with a potential toll on rejection and graft survival. Herein, the authors present an update on immunosuppressive drug level monitoring and manipulation strategies according to different scenarios and time from transplant. They also provide a brief overview of next level immunosuppression monitoring strategies that aim to properly balance rejection rates with drug side effect profiles.

show abstract

Weight‐based tacrolimus trough concentrations post liver transplant

Cited by 5 publications

References 14 publications

Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software

Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software

Body weight‐based initial dosing of tacrolimus in renal transplantation: Is this an ideal approach?

Immunosuppressive Drug Levels in Liver Transplant Recipients: Impact in Decision Making

Contact Info

Product

Resources

About