Tacrolimus, an immunosuppressant agent indicated for organ transplants, is commonly administered to reduce the risk of renal graft rejection in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD). Due to its narrow therapeutic index and high inter-patient variability, studies have suggested that CYP3A5-based dosing provides specialized regimens which may significantly improve the chances of achieving therapeutic concentrations. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations, extensive (CYP3A5*1/*1) and intermediate metabolizers (CYP3A5*1/*3) require a higher initial dose while poor metabolizers (CYP3A5*3/*3) require a lower initial dose in order to achieve target tacrolimus concentrations. Studies concluded that CYP3A5 expressers present a greater risk for chronic nephrotoxicity and acute transplant rejection, supporting the need to closely monitor patients for severe adverse events. Further trials considering CYP3AS polymorphisms are needed to determine whether this genotype dosing improves clinical outcomes, which includes reducing rejection and toxicity, before testing can be recommended.
Alam S, Johns S, Norman H, Heilbronner B, Rojeab Y. The Effect of CYP3A5 Polymorphism on Kidney Transplant Recipients Given Tacrolimus. PAW Review. 2016 Jan 01; 7(1):Article 5 23-27 . Available from: https://digitalcommons.onu.edu/paw_review/vol7/iss1/5. Free full text article.