Pharmacy Resident University of Minnesota Medical Center Woodbury, Minnesota, United States
Poster Abstract: Tacrolimus is a medication commonly used in Hematopoietic Stem Cell Transplant (HSCT) to prevent Graft Versus Host Disease (GVHD). GVHD is a serious, systemic complication that involves graft cells recognizing and attacking the recipient’s cells. Management and prevention are an important part of improving patient outcomes and quality of life. Prevention is typically site and protocol-specific, but typically involves a calcineurin inhibitor such as tacrolimus or cyclosporine. In the pediatric and adult population, IV (intravenous) tacrolimus is utilized extensively.
Tacrolimus is metabolized by demethylation and hydroxylation by CYP3A4 and CYP3A5 enzymes in both the intestines and the liver. Strong evidence supports that CYP3A4 and CYP3A5 phenotypes influence tacrolimus pharmacokinetics, especially with oral administration. Due to this evidence, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has released guidelines for oral tacrolimus dosing based on the CYP3A5 genotype. These recommendations include increasing the starting dose by 1.5 to 2 times the recommended starting dose for extensive metabolizers of CYP3A5, only. Although there is much published on the effects of genetic polymorphisms in CYP3A4 and CYP3A5 on the pharmacokinetics of IV tacrolimus, there are no established clinical practice guidelines for IV tacrolimus based on CYP3A4 or CYP3A5 genotype.
Prior to HSCT, patients at our institution meet with a pharmacist. Pharmacogenomic testing is offered to patients, and results are utilized to guide dosing of other medications such as voriconazole. This guidance allows the care team to minimize time to therapeutic levels while minimizing toxicities and sub-therapeutic levels.
This study aims to review pharmacogenomic test results and subsequent tacrolimus testing and levels to develop an appropriate dosing schema for IV tacrolimus. The primary endpoint will be days to target tacrolimus trough levels. Secondary endpoints will include therapeutic failure, tacrolimus-associated adverse drug reactions, and GVHD-associated adverse reactions.
We will conduct a single-center, retrospective chart review of pediatric patients aged 0 to 25 years old, who underwent Hematopoietic Stem Cell Transplant or cellular therapy between February 2021 and June 2023. All patients with PGx data, initial IV tacrolimus prescription, and at least 1 tacrolimus level will be included in this study.
Data collection will include demographic data, CYP3A5/3A5 PGx results, initial IV tacrolimus dosing, number of dose adjustments, tacrolimus drug levels, time to a therapeutic level, relevant drug interactions, tacrolimus adverse drug reactions, and GVHD-associated reactions. Results are in process currently.
References (must also be included in final poster): Will be included in final poster
