Evaluation of Weight-Based Dose During Transition From Immediate-Release to Extended-Release Tacrolimus in Kidney Transplant Recipients.

BACKGROUND: Manufacturer recommendations for conversion from immediate-release to extended-release tacrolimus, Envarsus XR®, suggests 80% of the total daily dose of the immediate-release formulation. This conversion has not consistently achieved therapeutic levels in the kidney transplant population. OBJECTIVES: To determine if a reliable weight-based dosing strategy could be utilized to transition kidney transplant patients from immediate-release to extended-release tacrolimus. This may help establish a safe protocol to guide transition between formulations. METHODS: Retrospective, single-center study of adult kidney transplant recipients between July 2015 and December 2018. Excluded patients received dual organs, lacked appropriately drawn tacrolimus levels, or were prescribed interacting medications. Patients were identified by querying prescriptions for extended-release tacrolimus and chart review was performed to exclude any patients without sufficient follow-up after transition. RESULTS: 30 patients who transitioned from immediate-release tacrolimus to tacrolimus XR were included in the final analysis. The median weight-based dose of tacrolimus XR that achieved a therapeutic level among the cohort was 0.158 mg/kg/day (Q1-Q3: 0.0587-0.221), which was about 80% of the original median weight-based immediate-release tacrolimus dose. Therapeutic dosing strategies were widely variable, represented by an R2 of 0.33 on linear regression. There was a statistically significant difference in median weight-based dosing strategies among patients of various racial backgrounds (p = 0.0148). CONCLUSIONS: A weight-based dose of tacrolimus XR could not reliably predict a therapeutic level among the total cohort due to the wide inter-patient variability. The median weight-based rate of conversion from immediate-release to extended-release tacrolimus was 80%.

Early versus delayed initiation of cytomegalovirus prophylaxis after liver transplant.

OBJECTIVES: Delaying cytomegalovirus (CMV) prophylaxis after liver transplantation may limit medication side effects and reduce inpatient drug costs. The primary objective of this study was to determine the incidence of CMV DNAemia in liver transplant recipients who initiated prophylaxis immediately after transplant (early prophylaxis) and those who initiated prophylaxis on postoperative day 7 or at discharge, whichever came first (delayed prophylaxis). STUDY DESIGN: This was a retrospective, single-center study of adult liver transplant recipients between February 2017 and February 2019. Patients who were at low risk for CMV (D-/R-), received dual organs, had a history of invasive CMV disease, or received prophylaxis with an agent other than ganciclovir/valganciclovir were excluded. Chart review of patient profiles was completed 9 months following the transplant, and the primary end point was the first positive CMV PCR within that timeframe. Cumulative incidence of CMV DNAemia was estimated by adjusting for competing events for early and delayed prophylaxis groups. The subdistribution hazard model was utilized to examine the effect of the timing of prophylaxis on CMV DNAemia while accounting for CMV serostatus. Secondary end points included peak quantifiable viral load, time to detection, and incidence of tissue-invasive disease. RESULTS: A total of 119 patients (60 early prophylaxis and 59 delayed prophylaxis) were included, and baseline demographics were similar except for sex. Twenty patients in the early group and 17 in the delayed group developed CMV DNAemia within 9 months of transplant with a cumulative incidence of 31.7% (95% confidence interval (CI) 20%, 44%) and 28.8% (95% CI 18%, 41%), respectively. After controlling for CMV serostatus, the relative incidence of DNAemia was similar between prophylaxis groups (subdistribution hazard ratio: 1.01, 95% CI 0.53, 1.90). CONCLUSIONS: No significant difference in CMV DNAemia within 9 months of liver transplant was observed between patients who received early and delayed prophylaxis. Future studies are warranted to conclude that delaying prophylaxis can be considered a safe alternative to initiating prophylaxis immediately after transplant.