Session Time: 3:15pm-4:45pm
Presentation Time: 3:15pm-3:27pm
*Purpose: Polypharmacy, typically defined as the use of five or more medications, is a barrier to adherence, and the resulting complex medication regimens result in increased risk of adverse drug interactions and complications, as well as poorer adherence. Solid organ transplant recipients, exposed to lifelong immunosuppression regimes and a spectrum of additional medications for management of comorbidities, have higher rates of drug-drug interactions and other adverse events.
*Methods: The Clinical Pharmacogenetics Implementation Consortium (CPIC) and Pharmacogenomics Knowledgebase (PharmGKB) are open source resources that aggregate, curate and disseminate key human genetic variation knowledge for drug response(s). Their goal of clinical implementation of pharmacogenetic (PGx) tests by creating and curating peer-reviewed, evidence-based guidelines for defined variants underpinning response to clinical practice is designed to help clinicians apply genetic testing results to optimized drug dosing/therapy.
*Results: We analyzed established CPIC/PharmGKB variants in 51 genes in 3451 kidney, 2613 liver, and 1783 heart UPenn transplant patients. From these cohorts, up to 12.5 million directly genotyped or imputed (INFO score >0.7) single-nucleotide polymorphisms (SNPs) were available in 1619 kidney, 1218 liver, and 1083 heart UPenn transplant patients using the iGeneTRAIN consortium Genome-wide Genotyping array and analyses pipelines. We examined PGx risk allele variants for each patient with the spectrum of transplant medications, immunosuppressant’s, and frequently prescribed drugs including those used to treat post-transplant malignancies as well as cardiometabolic and infection complications. We observed that 85.7% of our prioritized CPIC variants were directly captured or imputed, with > 99.5% of our UPenn transplant patients had at least one CPIC ‘actionable’ PGx variant and > 31% having 3 or more actionable variants.
*Conclusions: Medication Regimen Complexity Index (MRCI), a standardized quantitative measure of regimen complexity, a logical proxy to identify patients at higher risk for drug-drug and gene-drug and interactions, was also examined in all UPenn transplant patients and ongoing analyses is correlating MRCI with drug-drug and CPIC gene-drug analyses.
To cite this abstract in AMA style:Callans L, Obayemi J, Gao H, Shaked A, Chang B, Keating B. Combining Pharmacy and Genome-Wide Genotyping Data to Examine Medication Regimen Complexity Indices (MRCI), Drug-Drug and Gene-Drug Interactions in Transplant Patients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/combining-pharmacy-and-genome-wide-genotyping-data-to-examine-medication-regimen-complexity-indices-mrci-drug-drug-and-gene-drug-interactions-in-transplant-patients/. Accessed March 8, 2021.
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