2026 Eastern States Conference

Title: Retrospective analysis of tacrolimus dose requirements by CYP3A5 genotype in adult heart transplantation
Authors: Meade Avery, PharmD, MPH; Sara Strout, PharmD, BCTXP; Jim Stevenson, PharmD, MS, BCPP
Learning Objective: Describe how CYP3A5 genotype affects tacrolimus dose requirement in new heart transplant recipients.
Background: Tacrolimus dose requirement is influenced by CYP3A5 genomics, but data in heart transplant is limited.
Methods: This is a single center retrospective analysis of heart transplant recipients with pharmacogenomic results transplanted between 6/1/24 and 11/30/25. Recipients of liver or bone marrow transplants were excluded. The primary endpoint was the first stably therapeutic tacrolimus dose in relation to CYP3A5 metabolizer status. Secondary endpoints included tacrolimus dose at discharge or day 30 post-transplant (whichever occurred first), concurrent use of moderate to strong CYP3A4 or P-gp inhibitors, LFT elevations, hematocrit, and time to therapeutic tacrolimus concentration. Statistical analyses, including linear regression, Kruskal-Wallis non-parametric tests, and descriptive statistics, were completed using Stata.
Results: 84 heart recipients completed CYP3A5 testing; 5 liver recipients were excluded. 47 patients were CYP3A5 non-expressers (poor metabolizers), and 32 were expressers (22 intermediate and 10 normal metabolizers). 86% of patients received genomic results before starting tacrolimus. CYP3A5 expressers required 2.3x more tacrolimus than non-expressers (p=0.0001). Tacrolimus dose requirement also increased for each functional CYP3A5 allele (p=0.0001). Dose differences were similar at discharge. Through multivariable analyses, genomics remained the primary contributor to tacrolimus dose. Poor metabolizers had the shortest mean time to stably therapeutic (8.9 days). For each functional CYP3A5 allele, time to therapeutic increased by ~1.5 days (p=0.014).
Conclusion: CYP3A5 phenotype was the main contributor to tacrolimus dose requirement and time to therapeutic, suggesting protocolization may be required to more appropriately account for CYP3A5 phenotype in initial dosing.
Self-Assessment Question: Which CYP3A5 metabolizer phenotype would likely require the highest tacrolimus dose?
a. Poor metabolizer
b. Intermediate metabolizer
c. Normal metabolizer
d. CYP3A5 phenotype does not impact tacrolimus dose