De Novo Dosing and Trough Attainment Trends of Extended-Release Tacrolimus in the Absence of Dose Adjustments
1Department of Surgery, Lehigh Valley Health Network, Allentown, PA, 2Veloxis Pharmaceuticals, Cary, NC
Meeting: 2020 American Transplant Congress
Abstract number: D-101
Keywords: Dosage, Immunosuppression
Session Information
Session Name: Poster Session D: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Initial dosing of tacrolimus extended-release tablets (LCPT) was 0.17 mg/kg/day in the pivotal trial in de novo kidney transplant recipients. Dosing subsequent to the first dose was based on clinician assessment of troughs. Most patients’ trough concentrations were above the protocol-specific target leading to frequent dose changes, which makes interpretation of early assessment of this dosing strategy difficult. To better understand trends in early levels in the absence of dose changes, we performed a post-hoc, subgroup analysis of patients who did not receive a dose change in the first 7 days following initiation of LCPT therapy at 0.17 mg/kg/day.
*Methods: Patients randomized to receive LCPT were included in this analysis if they remained in the study and had no dosage adjustments through the first 7 days post-initiation of tacrolimus therapy. The primary outcome was median level at each timepoint through the first week. Secondary outcomes include median dose and level through the first 14 post-initiation days.
*Results: In total, 39 patients met inclusion for this analysis. Demographics and transplant characteristics are noted below.
| Full Study cohort (N=268) | No dose adjustment cohort (N=39) | |
| Age (mean) | 44.8 | 39.9 |
| Male sex (%) | 64.9 | 56.4 |
| Caucasian Race (%) | 75.7 | 82.1 |
| Weight, Kg | 74.9 | 68.0 |
| Deceased donor (%) | 49.6 | 51.3 |
| Prior transplant (%) | 4.1 | 10.3 |
| Low CD Ratio (%) | 33.3 | 50.3 |
A previous analysis of the full study population classified patients into trough concentration to dose (CD) ratio tertiles based on day 30 dose and trough; using this scheme, the majority of patients who did not require dose adjustments fell into the low CD ratio category, indicating that these patients would likely require higher doses to maintain therapeutic levels, on average. Average trough levels are shown.
Study defined goal was between 6 – 11 ng/mL for the first 30 days. Trough concentrations gradually increased over the first week. After 7 days, the LCPT dose among this cohort was reduced from the starting dose of 0.17 mg/kg to 0.15 mg/kg to maintain therapeutic levels.
*Conclusions: These results illustrate trough level attainment trends in the first week post-transplant utilizing LCPT. It appears that gradual increases in the mean tacrolimus trough occur throughout the first 7 days.
To cite this abstract in AMA style:
Moritz MJ, Stevens DR, Meier-Kriesche U, Horwedel TA. De Novo Dosing and Trough Attainment Trends of Extended-Release Tacrolimus in the Absence of Dose Adjustments [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/de-novo-dosing-and-trough-attainment-trends-of-extended-release-tacrolimus-in-the-absence-of-dose-adjustments/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress