*Purpose: The purpose of this study is to evaluate compliance and efficacy of The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype guided tacrolimus dosing.

*Methods: At our institution, tacrolimus dosing is protocolized at 2 mg orally twice daily to achieve a goal trough concentration (7-9ng/mL). Pharmacogenomic testing for CYP3A5 was implemented, yet clinicians are hesitant to deviate from a long-standing protocol. The CPIC guidelines recommend normal starting doses for poor metabolizers and starting doses of 1.5-2 times normal dose for intermediate and normal metabolizers. To evaluate guideline compliance, a retrospective, single center study of kidney transplant recipients between 7/1/19- 6/30/21 was conducted. Patients were excluded if they did not receive a kidney transplant or did not have CYP3A5 results. Continuous and categorical variables were compared using T-tests and Chi-squared.

*Results: After IRB approval, 29 kidney transplant patients with CYP3A5 genotyping were identified. Of these patients, there were 9 (31%) African American, 15 (52%) Caucasian, 3 (10%) Asian, and 2 (7%) Hispanic/Latino. Eighteen (62%), were poor metabolizers, 8 (28%) intermediate metabolizers and 3 (10%) normal metabolizers. Starting doses of tacrolimus (mg/kg/day) were 0.05±0.01, 0.06±0.02, and 0.06±0.01 for poor, intermediate, and normal metabolizers, respectively (p=0.564). Doses (mg/kg/day) that achieved a therapeutic tacrolimus concentration were 0.08±0.04, 0.11±0.04, and 0.27±0.24 for poor, intermediate, and normal metabolizers, respectively (p=0.002). Days to therapeutic tacrolimus trough concentration was 3.2±1.9, 4.8±3.7, and 6.0±1.0 for poor, intermediate, and normal metabolizers, respectively (p=0.117). The number of tacrolimus dose changes to achieve a therapeutic trough was 2.7±1.0, 3.0±0.8, and 4.0±1.0 for poor, intermediate, and normal CYP3A5 metabolizers, respectively (p=0.116).

*Conclusions: All patients were started on the same protocolized starting dose. Normal metabolizers had a significantly higher tacrolimus therapeutic doses compared to poor and intermediate metabolizers. Time to achieve a therapeutic trough concentration, dose changes and percent of concentrations in range were all higher for normal metabolizers, yet did not reach significance. Although a small pilot study, these data support the CPIC recommendation that CYP3A5 normal metabolizers require higher doses to achieve therapeutic concentrations.

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