Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program.

Tacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence-based guidelines for CYP3A5 normal/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive CYP3A genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for CYP3A5 and CYP3A4 was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic-recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third-party payers. CYP3A5 normal/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only ≈66% of African Americans in our cohort were normal/intermediate metabolizers who required higher doses. Routine CYP3A5 genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.

Enoxaparin adherence for venous thromboembolism prophylaxis in hospitalized patients with sickle cell disease.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with sickle cell disease (SCD). METHODS: This retrospective study assessed adherence to prescribed enoxaparin for VTE prophylaxis in adults with SCD while hospitalized. A total of 172 encounters of 72 unique patients were evaluated between 1 January and 31 December 2019. Patients were grouped based on adherence to prescribed enoxaparin. Group 1 received 100% of doses ordered. Group 2 received between 99% and 1% of doses ordered. Group 3 received 0% of doses ordered. RESULTS: Only 45 encounters (32.3%) received 100% of ordered doses and 81 encounters (47%) did not receive any of the ordered enoxaparin doses. In total, only 37% of all prescribed enoxaparin doses were administered to patients. CONCLUSION: This low level of administered enoxaparin is concerning in a patient population at an increased risk for VTE. VTE prophylaxis adherence needs to be addressed with each admission and, if appropriate, alterative options to enoxaparin should be considered.