Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Breslin, Nadine; Hedvat, Jessica; Salerno, David M.; Jandovitz, Nicholas; Patel, Chandni; Lee, Sara; Lange, Nicholas W

doi:10.1111/ctr.14529

Cited by 4 publications

(13 citation statements)

References 10 publications

(9 reference statements)

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“…This finding was consistent across all groups 9 . Additionally, a larger proportion of patients with BMI > 30 kg/m 2 had supratherapeutic trough levels and BMI was found to be independently associated with the higher trough levels 9 . This differs from our study which showed that utilizing IBW in obese patients led to initial underdosing; however, should be noted that our obese population had a mean weight of 100.5 kg.…”

Section: Discussionsupporting

confidence: 72%

“…9 IBW led to no difference in therapeutic doses between the BMI groups on post-op day (POD) 7 with similar findings on POD 14. 9 Obesity in solid organ transplant is associated with higher incidence of DGF, acute rejection, metabolic complications, and mortality so it is crucial to ensure appropriate dosing of tacrolimus. 10 Therefore, the objectives of this study were to assess the conversion ratio from IR to LCP tacrolimus in obese kidney transplant recipients, defined as a BMI of ≥30 kg/m 2 and assess the impact of BMI and ideal body weight (IBW), total body weight (TBW), and adjusted body weight (AdjBW) on IR and LCP mg/kg dosing at steady state therapeutic goal.…”

supporting

confidence: 60%

“…A recent study published by Breslin et al evaluated de novo dosing of LCP stratified by BMI (BMI > 30 kg/m 2 , BMI 25–30 kg/m 2 , and BMI < 25 kg/m 2 ). They found that utilizing IBW had a stronger correlation with therapeutic LCP doses 9 . This finding was consistent across all groups 9 .…”

Section: Discussionmentioning

confidence: 71%

“…They found that utilizing IBW had a stronger correlation with therapeutic LCP doses 9 . This finding was consistent across all groups 9 . Additionally, a larger proportion of patients with BMI > 30 kg/m 2 had supratherapeutic trough levels and BMI was found to be independently associated with the higher trough levels 9 .…”

Section: Discussionmentioning

confidence: 79%

“…This study did not report BMI; however, the median weight was 83.3 kg 8 . Recently a retrospective study was completed by Breslin and colleagues assessing de novo dosing of LCP in obese patients 9 . They stratified patients into three groups based on BMI: >30 kg/m 2 , 25–30 kg/m 2 , and <25 kg/m 2 9 .…”

Section: Introductionmentioning

confidence: 99%

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Impact of obesity on the conversion of immediate‐release tacrolimus to extended‐release tacrolimus in kidney transplant recipients

Newman,

Patel,

Patel

et al. 2023

Clinical Transplantation

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Outcomes analyzing conversion from IR‐tacrolimus (IR) to LCP‐tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight‐based dose at a steady‐state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI < 30 and BMI ≥ 30 kg/m2, respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07 mg/kg/day for BMI < 30 and BMI ≥ 30 kg/m2, respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11 mg/kg vs.09 mg/kg and .08 mg/kg vs. .06 mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady‐state doses, and might yield more accurate steady‐state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.

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Section: Discussionsupporting

confidence: 72%

supporting

confidence: 60%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impact of obesity on the conversion of immediate‐release tacrolimus to extended‐release tacrolimus in kidney transplant recipients

Newman,

Patel,

Patel

et al. 2023

Clinical Transplantation

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Clinical Consequences of Altered Drug Disposition in Obesity: Call for Change

Bruno,

Greenblatt,

Harmatz

et al. 2023

The Journal of Clinical Pharma

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Obesity is a serious condition with many known comorbid conditions and other health risks. Despite the rising global rates of obesity, drug disposition in this population is typically understudied, which results in limited information guiding the use of drugs in patients with obesity. Presently, dosing adjustments for patients with obesity typically focus on addressing altered drug clearance with body size and are therefore limited to chronic dosing recommendations. These instructions are variable and rarely based on dedicated studies in people with obesity. This review briefly discusses the current clinical use of body measurements to guide chronic dosing instructions and highlights the need for obesity‐specific dosing instructions when the half‐life of a drug is prolonged (typically through increased volume of distribution) in people with obesity. Examples of drugs with apparent opportunities for either ramp‐up, loading, or washout instructions for patients based on body mass index are identified, specifically for vortioxetine, posaconazole, and brexpiprazole. We call for inclusion of people with obesity in clinical studies as a special subpopulation during drug development and propose the use of body mass index to guide dosing decisions among these patients.

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Incomplete Data and Potential Risks of Drugs in People with Obesity

Apovian,

Bruno,

Kyle

et al. 2023

Curr Obes Rep

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Purpose of Review To provide examples of knowledge gaps in current pharmaceutical treatments for people with obesity and call for changes to regulatory and pharmaceutical clinical research requirements during the drug discovery and development process. Recent Findings Treatment of obesity and its comorbidities often require the use of prescription drugs, many of which have not been fully evaluated in people with obesity. Despite a growing body of research on this topic, the impact of obesity on the pharmacokinetics and pharmacodynamics of drugs is often under-studied by drug sponsors and regulators, and subsequently underappreciated by clinicians and caretakers. There are currently multiple opportunities for pharmaceuticals to include dosing information specifically for patients with obesity in order to ensure safety and efficacy of drugs in this population. Additionally, there are serious gaps between what is known about the effects of obesity on drug disposition and the current use of drugs according to drug prescribing information and clinical practice. Summary There is currently no requirement to test drugs in people with obesity during the drug approval process, even when preliminary data suggests there may be altered kinetics in this population. The lack of information on the safe and effective use of drugs in people with obesity may be contributing to poorer health outcomes in this population.

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Comparing weight‐based dosing of tacrolimus XR in obese and non‐obese renal transplant recipients

Cited by 4 publications

References 10 publications

Impact of obesity on the conversion of immediate‐release tacrolimus to extended‐release tacrolimus in kidney transplant recipients

Impact of obesity on the conversion of immediate‐release tacrolimus to extended‐release tacrolimus in kidney transplant recipients

Clinical Consequences of Altered Drug Disposition in Obesity: Call for Change

Incomplete Data and Potential Risks of Drugs in People with Obesity

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