Establishing a CYP3A5 genotype-guided tacrolimus dosing protocol in adult kidney transplant recipients

Despite a well-established association of CYP3A5 genotype with tacrolimus dose requirements and clinical practice guidelines for personalized dosing, integration of genotype-guided tacrolimus dosing is limited. Herein we describe the process for implementing a CYP3A5 genotype-guided tacrolimus dosing protocol in adult kidney transplant recipients at an academic medical center.

We evaluated existing primary literature and clinical practice guidelines, as well as internal data, to determine the target population for implementation. Adult kidney transplant recipients were selected given the routine use of oral tacrolimus and limited drug-drug interactions. These data were also used to gain prescriber buy-in for and determine genotype-guided tacrolimus dose recommendations. Selecting a testing laboratory involved assessment of variant coverage, turnaround time, cost, and the return process for results. Obtaining testing before transplantation required development of multiple workflows to capture patients at listing or on the waitlist and for in-person and virtual care. Clinical decision support to automatically select initial post-transplantation tacrolimus doses per the genotype-guided protocol was developed. Clinician education was tailored to the role the individual had in the implementation process, and patient education was developed. Genotype-guided dosing was implemented in October 2023, approximately 1 year after conceptualization. The majority (61%) of adult kidney transplant recipients since implementation have received genotype-guided dosing.

Implementation of CYP3A5 genotype-guided tacrolimus dosing requires unique considerations associated with route of administration and transplant population, but integrating pharmacogenetics into a tacrolimus dosing protocol is feasible with multidisciplinary support. Future studies will evaluate the impact of this dosing strategy on clinical and healthcare utilization outcomes.