Dataset Information

Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial.

ABSTRACT:

Background

Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR).

Methods

We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eligible. Patients were randomized 1 : 1 to continued TAC-IR or conversion to TAC-ER. The primary outcome was change in medication adherence from baseline to 9 months, assessed using BAASIS. Secondary outcomes were tacrolimus trough levels, safety, and quality of life.

Results

Thirty-one patients were consented and randomized to either of the two groups: conversion to TAC-ER (n = 15) or continued TAC-IR (n = 16). Six patients in the TAC-ER group withdrew after randomization due to apprehension about switching medication (n = 2), unwillingness to travel (n = 2), and increased liver tests after conversion (n = 2, both were acute rejections despite therapeutic tacrolimus levels and were considered unrelated to TAC-ER). We compared the results of nine patients in the TAC-ER group that completed the study with those of sixteen in the TAC-IR group. At baseline, there was no difference in tacrolimus trough levels between groups. Improved adherence was observed in the TAC-ER group as 100% of patients reported at least one period of full adherence during the study period (100% vs. 62.6%, p = 0.035). Tacrolimus trough levels and liver tests were comparable between groups throughout the study. There were no differences in eGFR, HbA1c, or QoL between the groups.

Conclusion

TAC-ER improved medication adherence while maintaining comparable trough levels, liver function, and QoL as TAC-IR in LTR.

SUBMITTER: Verma M

PROVIDER: S-EPMC9833930 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial.

Verma Manisha M Zaki Radi R Sadeh Johnathan J Knorr John P JP Gallagher Mark M Parsikia Afshin A Navarro Victor V

Journal of transplantation 20230104

<h4>Background</h4>Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR).<h4>Methods</h4>We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eli ...[more]

PMID: 36642992

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Project description:BackgroundTacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting.AimTo obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.MethodsSingle-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.ResultsMean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.ConclusionExpression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Project description:BackgroundPrevalence of immunosuppressant nonadherence in renal transplant recipients is high despite negative clinical outcomes associated with nonadherence. Simplification of dosing has been demonstrated to improve adherence in renal transplant recipients as measured through electronic monitoring and self-report.ObjectiveThe purpose of this study was to replicate and extend previous findings by measuring adherence with multiple methods in a Canadian sample.DesignThe study design was a randomized controlled medication dosing trial in adult renal transplant patients. The trial length was 4 months.SettingThis study was conducted within the Solid Organ Transplant (SOT) Clinic at Vancouver General Hospital (VGH; Vancouver, Canada).PatientsA total of 46 adult renal recipients (at least 1 year post-transplant) were recruited through the SOT clinic. With 8 withdrawals, 38 individuals completed all phases of the study.MeasurementsMedication adherence was measured for a period of 4 months using multiple methods, including electronic monitoring (MEMS [Medication Event Monitoring System]), pharmacy refill data (medication possession ratio [MPR]), and by self-report using the Adherence subscale of the Transplant Effects Questionnaire (TEQ).MethodsParticipants were randomized to twice-daily (n = 19) or once-daily tacrolimus dosing (n = 19) and followed over a 4-month period via monthly clinic study visits. Comparisons between the treatment groups were performed using the Mann-Whitney U and chi-square tests, for continuous and categorical variables, respectively.ResultsAs outlined in Table 3, the once-daily dosing group showed significantly better MEMS Dose Adherence (P = .001), whereas MEMS Timing Adherence showed a tendency toward better adherence for this group, but was not significant (P = .052). MEMS Days Adherent (P = .418), MPR% (P = .123), and self-reported adherence (P = .284) did not differ between the once- and twice-daily dosing groups when measured as continuous variables. The MPR% was significantly better for the once-daily dosing group when measured dichotomously but not continuously (P = .044). Notably, most of those exposed to once-daily dosing (63.2%) preferred this to the twice-daily regimen.LimitationsLimitations included small sample size and short follow-up period, precluding the examination of clinical outcome differences.ConclusionsResults for dose adherence replicate the finding that dose simplification increases adherence to immunosuppressants as measured through electronic monitoring. Such an advantage for the once-daily dosing group was not seen across the 2 other electronic monitoring measurement variables (days and timing adherence). This study extends previous research by examining adherence in once versus twice-daily dosing via prescription refill data in a Canadian sample. Given the gravity of potential health outcomes associated with nonadherence, although results indicate inconsistencies in significance testing across measurement methods, the medium to large effect sizes seen in the data favoring better adherence with once-daily dosing provide an indication of the potential clinical significance of these findings.Trial registrationThis study was registered with ClinicalTrials.gov (NCT01334333) on April 11, 2011.

Dataset Information

Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial.

Background

Methods

Results

Conclusion

Publications

Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial.

Similar Datasets

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